Medicine and Marijuana

For those who are still concerned about ‘evidence based science’ and ‘best medical and pharmaceutical practice’…the following ‘open letter’ with attachments was sent to all Federal Senators, NSW and Victorian Premiers last week. 

Dear Senator,
 
In the coming weeks/months, you will no doubt be presented with a Bill to consider changing both law and process to permit a new version of ‘medical marijuana’. On behalf of our Institute and a concerned public I would like you to carefully consider the following.

Firstly I write with some concerns about the consultation conducted on behalf of Victorian State government by the VLRC in Melbourne on May 6th this year and the now subsequent recommendations that have emerged from this very small Melbourne meeting (Less than 60 people in attendance! – This issue was directly raised with Victorian Health Minister earlier this year).

Whilst we gleaned from radio interviews with VLRC representatives prior to the consultation that the public discussions on the potential introduction of a new form ‘medical marijuana’ (different to existing medicinal forms of cannabis derived pharmaceuticals already in the Australian market) were not for changing laws to suit a particular agenda. It was instead implied that the purpose was to look at potential redundancies that might hinder best practice.  It was to be, for all intents and purposes an unbiased mechanism to: glean evidence, perspectives, opinions and ideas from the general public for consideration in the higher and more important discussion of wise, evidence based, best healthcare practice before making any move on the release of another version of therapeutic cannabis.

Conversely, our affiliate/colleagues experience of the very small Melbourne consultation did not reflect any of the above expectation. Rather those of our affiliates who attended observed the following:

  1. A seemingly deliberately emotively charged atmosphere, in favour of getting cannabis legalised for medical purposes. The tone seemed to be set to that end from the outset.
  2. The meeting was facilitated by representatives of the VLRC who appeared to have a bias toward the legalisation of ‘medical marijuana’ in manner that suited the self-medicating option, regardless of evidence based science.
  3. When attempts were made to present evidence contrary to the seemingly predetermined agenda of these facilitators, they were either quickly shut down (if they dared to speak in the first place) or continually ignored; apparently, dissenting opinions were not welcome. Whilst at the same time, proponents for ‘self-medication’ use of cannabis were given complete and unfettered access to the floor, producing statements such as:“Many, many people have been cured – from just about anything and everything.”
    “What would you rather have – infertility or 35 seizures a day?”
    “Random workplace drug testing is wrong.”Not only are these statements (now on record) outrageous, they are also utterly unsubstantiated by any legitimate clinical trial. This very small contingent of pro-cannabis lobbyists were permitted to simply spruik anecdotes with no evidence based presentation yet also had their evidenced-deprived opinions affirmed and validated by the facilitators.
  4. The facilitators appeared to infer that the Government (of Victoria, at least) already has legislation in place with this current ‘consultation’ process simply in play to validate those changes and therefore it is in essence a forgone conclusion. There was also a strong indication that either the A.M.A. or T.G.A. recommendations or processes would be ignored and negated wherever possible by simple legal changes.

Senator, it is a concern that if this particular experience of ours was repeated in other consultations with the same consensus manufacturing agenda, then this consultative process is a travesty.

If a government negates not only good evidence based science, but also established protective, best practice medical processes to enable a legal rite of passage for self-medication, it is placing itself at an extremely high risk of litigation. Future law-suits are likely, from the ‘victims’ of self-medicating regimes who will cite the changes in law that were NOT based on proper clinical trial or TGA and AMA recommendations and protocols.  When emotionally charged vitriol combines with vote chasing and misguided sympathies, it is the recipients of these untested substances that will be the final casualties – especially children! Compassion and wisdom dictate that all fair and democratic processes be engaged to maximise help and minimise harm, especially to children who will be the ones at greatest risk of an ill-advised self-medicating regime.

Senator, for purposes of clarification about the possible national legalisation of ‘another’ route/process/protocol for medicines are you able to confirm or deny that:

  1. The representations by the facilitators at the Melbourne consultation are in fact reflective of the pre-ordained intent of the public consultation documented above in not only Victoria, but other States and Territories?
  2. If not, will a review of the practice/method/behaviours be made into this particular process and subsequently the clearly questionable recommendations that have emerged from such narrow, non-evidence based and seemingly biased processes?
  3. A fair and proper representation of all views on this matter be gleaned from these meetings/consultations and interpreted and represented fairly without prejudice?
  4. A.M.A. and T.G.A. processes and protocols for best practice on medicines will be upheld and engaged, or simply ignored and by-passed?

Finally Senator, it is of grave concern that a pattern seems to be emerging from this ‘populist’ process, that best practice, evidence based protocols may simply be ignored and by passed.  If this is indeed the plan and the use of VLRC type agencies is the vehicle to do so, then the following must be raised.

The Dalgarno Institute ask:

  • Do you want your government and your ministerial role to be linked with a poorly considered and non-evidenced based process that enables a self-medicating policy – particularly for the ones the State has greatest responsibility to protect – the children?
  • Will your government and ministerial role be the ones who in so ignoring proper clinical processes facilitate a quasi-health regime that will precipitate immediate and long term unwanted side effects that can then be later subject to litigation and class-actions?
  • If an unqualified and unproven self-medicating mechanism is sanctioned and approved by government, and the inevitable damage (particularly to children) emerges, will the taxpayers of Australia have to fund the damages of an ill-conceived and non-TGA/AMA approved medical practice? Or will there be iron-clad caveats in place that ensure those who chose to use their own version of ‘medicine’ be the only ones liable for the outcomes of it, and not place further healthcare and monetary burden on the vast majority of tax-payers who have sought to follow best evidence-based and prescriptive practices?
  • If proper clinical trials and T.G.A and A.M.A. processes and protocols are negated or circumvented and a ‘new’ or ‘alternative’ process for registering, manufacturing, prescribing and dispensing marijuana as medicine be put in place, then how will you/your government  address the following important questions.
    • Who will be ‘growing’ and preparing this ‘medicine’?
    • Who will monitor content and quality of ‘medicine’?
    • Who will determine dosage rates and quantities?
    • What mechanisms will be in place to ensure quality control is followed?
    • What mechanisms will be in place to ensure, movement, dispensing and use of this ‘medicine’ is done without risk to non-patients?
    • Who will be able to prescribe this ‘medicine’ – Doctors, pharmacists, naturopaths, nurses, and counsellors? Who will monitor this process and ensure total safety?
    • What community safe-guards will be in place to ensure this new ‘medicine’ will not be misused?
    • Will the ‘medicine’ come in edible or smoked form and what safeguards will be in play around such a ‘medicine delivery’ system?
    • Will there be advertising and public promotion of this new form of ‘medicine’? Will that be strictly monitored to ensure no misinformation will mislead the public?
    • Which government department will oversee this process and how many more new protocols, processes, staff and finance will be required to set up this new vehicle for ‘medicine’ identification and management?
    • Who will be paying for this new and added cost?

We at Dalgarno Institute and its growing coalition remain very concerned for the overwhelming majority of Australians who are being kept in the dark about this new and illegitimate push to change evidence based processes and the laws that ensure those processes are protected. We are looking to you, in your role, to ensure that there is a genuine and robust pursuit of best medical and health practice outcomes for all Australians, particularly the most vulnerable – the young, very sick and disadvantaged – and that any mechanism that seeks to undermine that platform not be permitted to emerge under any circumstance.  Science and best health practice, NOT lawyers should determine pharmaceutical best practice.

I have also attached just a very small sample of the volumes of evidence-based data currently in the scientific space that raise clear warnings about a ‘new’ and untested version of cannabis as medicine. Please avail yourself of them and consult the people who do know better, compassion and good government demands it.
We look forward to receiving your response.

Sincerely Yours, 

Shane Varcoe
Executive Director
Dalgarno Institute

You can read our compassionate policy stance on M.M titled ‘CANNABIS AS MEDICINE? CAUTION NEEDED’!

https://dalgarnoinstitute.org.au/index.php/advocacy/dalgarno-aod-policy/86-open-letter-to-all-australian-politicians-regarding-new-version-of-medicinal-cannabis

Source: Email from Dalgarno Institute

September 2017

Thomas M. Nappe, DO* and Christopher O. Hoyte, MD

Abstract

Since marijuana legalization, pediatric exposures to cannabis have increased. To date, pediatric deaths from cannabis exposure have not been reported. The authors report an 11-month-old male who, following cannabis exposure, presented with central nervous system depression after seizure, and progressed to cardiac arrest and died. Myocarditis was diagnosed post-mortem and cannabis exposure was confirmed.

Given the temporal relationship of these two rare occurrences – cannabis exposure and sudden death secondary to myocarditis in an 11-month-old – as well as histological consistency with drug-induced myocarditis without confirmed alternate causes, and prior reported cases of cannabis-associated myocarditis, a possible relationship exists between cannabis exposure in this child and myocarditis leading to death. In areas where marijuana is commercially available or decriminalized, the authors urge clinicians to preventively counsel parents and to include cannabis exposure in the differential diagnosis of patients presenting with myocarditis.

INTRODUCTION

Since marijuana legalization, pediatric exposures to cannabis have increased, resulting in increased pediatric emergency department (ED) visits. Neurologic toxicity is most common after pediatric exposure; however, gastrointestinal and cardiopulmonary toxicity are reported. According to a retrospective review of 986 pediatric cannabis ingestions from 2005 to 2011, pediatric exposure has been specifically linked to a multitude of symptoms including, but not limited to, drowsiness, lethargy, irritability, seizures, nausea and vomiting, respiratory depression, bradycardia and hypotension.Prognosis is often reassuring. 

Specific myocardial complications related to cannabis toxicity that are well documented in adolescence through older adulthood include acute coronary syndrome, cardiomyopathy, myocarditis, pericarditis, dysrhythmias and cardiac arrest. To date, there are no reported pediatric deaths from myocarditis after confirmed, recent cannabis exposure. The authors report an 11-month-old male who, following cannabis exposure, presented in cardiac arrest after seizure and died. Myocarditis was diagnosed post-mortem and cannabis exposure was confirmed. Analyses of serum cannabis metabolites, post-mortem infectious testing, cardiac histopathology, as well as clinical course, support a potential link between the cannabis exposure and myocarditis that would justify preventive parental counseling and consideration of urine drug screening in this reported setting.

CASE REPORT

An 11-month-old male with no known past medical history presented to the ED with central nervous system (CNS) depression and then went into cardiac arrest. The patient was lethargic for two hours after awakening that morning and then had a seizure. During the prior 24–48 hours, he was irritable with decreased activity and was later retching. He was noted to be healthy before developing these symptoms. Upon arrival in the ED, he was unresponsive with no gag reflex. Vital signs were temperature 36.1° Celsius, heart rate 156 beats per minute, respiratory rate 8 breaths per minute, oxygen saturation 80% on room air.

Physical exam revealed a well-nourished, 20.5 lb., 11-month-old male, with normal development, no trauma, normal oropharynx, normal tympanic membranes, no lymphadenopathy, tachycardia, clear lungs, normal abdomen and Glasgow Coma Scale rating of 4. He was intubated for significant CNS depression and required no medications for induction or paralysis. Post-intubation chest radiograph is shown in Image 2. He subsequently became bradycardic with a heart rate in the 40s with a wide complex rhythm. Initial electrocardiogram (ECG) was performed and is shown in Image 1.

He then became pulseless, and cardiopulmonary resuscitation was initiated. Laboratory analysis revealed sodium 136 mmol/L, potassium 7.7 mmol/L, chloride 115 mmol/L, bicarbonate 8.0 mmol/L, blood urea nitrogen 24 mg/dL, creatinine 0.9 mg/dL, and glucose 175 mg/dL Venous blood gas pH was 6.77. An ECG was repeated (Image 3). He received intravenous fluid resuscitation, sodium bicarbonate infusion, calcium chloride, insulin, glucose, ceftriaxone and four doses of epinephrine. Resuscitation continued for approximately one hour but the patient ultimately died.

Initial electrocardiogram demonstrating wide-complex tachycardia.

Post-intubation chest radiograph. Measurement indicates distance of endotracheal tube tip above carina.

Repeat electrocardiogram showing disorganized rhythm, peri-arrest.

Further laboratory findings in the ED included a complete blood count (CBC) with differential, liver function tests (LFTs), one blood culture and toxicology screen. CBC demonstrated white blood cell count 13.8 K/mcL with absolute neutrophil count of 2.5 K/mcL and absolute lymphocyte count of 10.7 K/mcL, hemoglobin 10.0 gm/dL, hematocrit 34.7%, and platelet count 321 K/mcL. LFTs showed total bilirubin 0.6 mg/dL, aspartate aminotransferase 77 IU/L, and alanine transferase 97 IU/U. A single blood culture from the right external jugular vein revealed aerobic gram-positive rods that were reported two days later as Bacillus species (not Bacillus anthracis). Toxicology screening revealed urine enzyme-linked immunosorbent assay positive for tetrahydrocannabinol-carboxylic acid (THC-COOH) and undetectable serum acetaminophen and salicylate concentrations. Route and timing of exposure to cannabis were unknown.

Autopsy revealed a non-dilated heart with normal coronary arteries. Microscopic examination showed a severe, diffuse, primarily lymphocytic myocarditis, with a mixed cellular infiltrate in some areas consisting of histiocytes, plasma cells, and eosinophils. Myocyte necrosis was also observed. There was no evidence of concomitant bacterial or viral infection based on post-mortem cultures obtained from cardiac and peripheral blood, lung pleura, nasopharynx and cerebrospinal fluid. Post-mortem cardiac blood analysis confirmed the presence of Δ-9-carboxy-tetrahydrocannabinol (Δ-9-carboxy-THC) at a concentration of 7.8 ng/mL. Additional history disclosed an unstable motel-living situation and parental admission of drug possession, including cannabis.

DISCUSSION

As of this writing, this is the first reported pediatric death associated with cannabis exposure. Given the existing relationship between cannabis and cardiovascular (CV) toxicity, as well as the temporal progression of events, post-mortem analysis, and previously reported cases of cannabis-induced myocarditis, the authors propose a relationship between cannabis exposure in this patient and myocarditis, leading to cardiac arrest and ultimately death. This occurrence should justify consideration of urine drug screening for cannabis in pediatric patients presenting with myocarditis of unknown etiology in areas where cannabis is widely used. In addition, parents should be counseled regarding measures to prevent such exposures.

The progressive clinical presentation of this patient during the prior 24–48 hours, including symptoms of somnolence, lethargy, irritability, nausea, seizure and respiratory depression are consistent with previously documented, known complications of recent cannabis exposure in the pediatric population. It is well known that common CV effects of cannabis exposure include tachycardia and decreased vascular resistance with acute use and bradycardia in more chronic use. These effects are believed to be multifactorial, and evidence suggests that cannabinoid effect on the autonomic nervous system, peripheral vasculature, cardiac microvasculature, and myocardial tissue and Purkinje fibers are all likely contributory. The pathogenesis of myocarditis is not fully understood. In general, myocarditis results from direct damage to myocytes from an offending agent such as a virus, or in this case, potentially a toxin. The resulting cellular injury leads to a local inflammatory response. Destruction of cardiac tissue may result in myocyte necrosis and arrhythmogenic activity, or cellular remodeling in chronic myocarditis.

Autopsy findings in this patient were consistent with noninfectious myocarditis as a cause of death. The histological findings of myocyte necrosis with mature lymphocytic mixed cellular infiltrate are consistent with drug-induced, toxic myocarditis.The presence of THC metabolites in the patient’s urine and serum, most likely secondary to ingestion, is the only uncovered risk factor in the etiology for his myocarditis. This is highly unlikely attributable to passive exposure.

It is difficult to extrapolate a specific time of cannabis ingestion given the unknown dose of THC, the individual variability of metabolism and excretion, as well as the lack of data on this topic in the pediatric population and post-mortem redistribution (PMR) kinetics. However, the THC metabolite detected in the patient’s blood, Δ-9-carboxy-THC, is known to peak in less than six hours and be detectable for at least a day, while the parent compound, tetrahydrocannabinol (THC), is expected to rapidly metabolize and distribute much more quickly, being potentially undetectable six hours after exposure in an infrequent user. 

The parent compound was below threshold for detection in this patient’s blood. In addition, if cannabis ingestion occurred the day of presentation, it would have been more likely that THC would have been detected with its metabolite after PMR. Given this information, the authors deduce that cannabis consumption occurred within the recent two to six days, assuming this was a single, acute high-potency ingestion. This time frame would overlap with the patient’s symptomatology and allow time for the development of myocarditis, thus supporting cannabis as the etiology.

The link between cannabis use and myocarditis has been documented in multiple teenagers and young adults. In 2008 Leontiadis reported a 16-year-old with severe heart failure requiring a left ventricular assist device, associated with biopsy-diagnosed myocarditis.The authors attributed the heart failure to cannabis use of unknown chronicity. In 2014 Rodríguez-Castro reported a 29-year-old male who had two episodes of myopericarditis several months apart.Each episode occurred within two days of smoking cannabis.In 2016, Tournebize reported a 15-year-old male diagnosed with myocarditis, clinically and by cardiac magnetic resonance imaging, after initiating regular cannabis use eight months earlier. There were no other causes for myocarditis, including infectious, uncovered by these authors, and no adulterants were identified in these patients’ consumed marijuana.Unlike our patient, all three of these previously reported patients recovered.

In the age of legalized marijuana, children are at increased risk of exposure, mainly through ingestion of food products, or “edibles.”These products are attractive in appearance and have very high concentrations of THC, which can make small exposures exceptionally more toxic in small children.

Limitations in this report include the case study design, the limitations on interpreting an exact time, dose and route of cannabis exposure, the specificity of histopathology being used to classify etiology of myocarditis, and inconsistent blood culture results. The inconsistency in blood culture results also raises concern of a contributing bacterial etiology in the development of myocarditis, lending to the possibility that cannabis may have potentially induced the fatal symptomatology in an already-developing silent myocarditis. However, due to high contaminant rates associated with bacillus species and negative subsequent blood cultures, the authors believe this was more likely a contaminant. In addition, the patient had no source of infection on exam or recent history and was afebrile without leukocytosis. All of his subsequent cultures from multiple sites were negative.

CONCLUSION

Of all the previously reported cases of cannabis-induced myocarditis, patients were previously healthy and no evidence was found for other etiologies. All of the prior reported cases were associated with full recovery. In this reported case, however, the patient died after myocarditis-associated cardiac arrest. Given two rare occurrences with a clear temporal relationship – the recent exposure to cannabis and the myocarditis-associated cardiac arrest – we believe there exists a plausible relationship that justifies further research into cannabis-associated cardiotoxicity and related practice adjustments. In states where cannabis is legalized, it is important that physicians not only counsel parents on preventing exposure to cannabis, but to also consider cannabis toxicity in unexplained pediatric myocarditis and cardiac deaths as a basis for urine drug screening in this setting.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5965161/ March 2017

The medical marijuana market is in a downward spiral as businesses, lured by big money, shift to recreational

At the height of the medical marijuana industry there were 420 dispensaries in Oregon. Now there are only eight.

In 2015, Erich Berkovitz opened his medical marijuana processing company, PharmEx, with the intention of getting sick people their medicine. His passion stemmed from his own illness. Berkovitz has Tourette syndrome, which triggers ticks in his shoulder that causes chronic pain. Cannabis takes that away.

Yet in the rapidly changing marijuana landscape, PharmEx is now one of three medical-only processors left in the entire state of Oregon.

On the retail end, it’s also grim. At the height of the medical marijuana industry in 2016, there were 420 dispensaries in Oregon available to medical cardholders. Today, only eight are left standing and only one of these medical dispensaries carries Berkovitz’s products.

Ironically, Oregon’s medical marijuana market has been on a downward spiral since the state legalized cannabis for recreational use in 2014. The option of making big money inspired many medical businesses to go recreational, dramatically shifting the focus away from patients to consumers. In 2015, the Oregon Liquor Control Commission (OLCC) took over the recreational industry. Between 2016 and 2018, nine bills were passed that expanded consumer access to marijuana while changing regulatory procedures on growing, processing and packaging.

In the shuffle, recreational marijuana turned into a million-dollar industry in Oregon, while the personalized patient-grower network of the medical program quietly dried up.

Now, sick people are suffering.

“For those patients that would need their medicine in an area that’s opted out of recreational sales, and they don’t have a grower or they’re not growing on their own, it does present a real access issue for those individuals,” said André Ourso, an administrator for the Center for Health Protection at the Oregon Health Authority. The woes of the Oregon Medical Marijuana Program (OMMP) were outlined in a recently published report by the Oregon Health Authority. The analysis found the program suffers from “insufficient and inaccurate reporting and tracking,” “inspections that did not keep pace with applications”, and “insufficient funding and staffing”.

Operating outside of Salem, Oregon, PharmEx primarily makes extracts – a solid or liquid form of concentrated cannabinoids. Through his OMMP-licensed supply chain, he gets his high dose medicine to people who suffer from cancer, Crohn’s, HIV and other autoimmune diseases. Many are end-of-life patients.

These days, most recreational dispensaries sell both consumer and medical products, which are tax-free for cardholders. The problem for Berkovitz is that he’s only medically licensed. This means recreational dispensaries can’t carry his exacts. Legally, they can

only sell products from companies with an OLCC license. Since issuing almost 1,900 licenses, the OLCC has paused on accepting new applications until further notice.

Limits on THC – a powerful active ingredient in cannabis products – are also an issue, according to Berkovitz. With the dawn of recreational dispensaries, the Oregon Health Authority began regulating THC content. A medical edible, typically in the form of a sweet treat, is now capped at 100mg THC, which Berkovitz says is not enough for a really sick person.

“If you need two 3000mg a day orally and you’re capped at a 100mg candy bar, that means you need 20 candy bars, which cost $20 a pop,” he said. “So you’re spending $400 a day to eat 20 candy bars.”

“The dispensaries never worked for high dose patients, even in the medical program,” continued Berkovitz. “What worked was people who grew their own and were able to legally process it themselves, or go to a processor who did it at a reasonable rate.”

But with increased processing and testing costs, and a decrease on the number of plants a medical grower can produce, patients are likely to seek cannabis products in a more shadowy place – the black market.

“All the people that we made these laws for – the ones who are desperately ill – are being screwed right now and are directed to the black market,” said Karla Kay, the chief of operations at PharmEx.

Kay, who also holds a medical marijuana card for her kidney disease, said some patients she knows have resorted to buying high dose medical marijuana products illegally from local farmers markets – in a state that was one of the first to legally establish a medical cannabis industry back in 1998.

Moreover, the networks between medical patients, growers and processors have diminished.

The OMMP maintains a record of processors and the few remaining dispensaries, but no published list of patients or grow sites – a privacy right protected under Oregon law, much to the chagrin of law enforcement.

According to the Oregon Health Authority’s report, just 58 of more than 20,000 medical growers were inspected last year.

In eastern Oregon’s Deschutes county, the sheriff’s office and the district attorney have repeatedly requested the location of each medical marijuana grower in their county. They’ve been consistently denied by the Oregon Health Authority.

Recently, the sheriff has gone as far as hiring a detective to focus solely on enforcing marijuana operations.

“There is an overproduction of marijuana in Oregon and the state doesn’t have adequate resources to enforce the laws when it comes to recreational marijuana, medical marijuana, as well as ensuring the growth of hemp is within the THC guidelines,” said the Deschutes sheriff, Shane Nelson. As of last February, the state database logged 1.1m pounds of cannabis flower, as reported by the Willamette Week in April. That’s three times what residents buy in a year, which means the excess is slipping out of the regulated market. To help curb the trend, senate bill 1544 was passed this year to funnel part of the state’s marijuana tax revenues into the Criminal Justice Commission and provide the funding needed to go after the black market, especially when it comes to illicit Oregon weed being smuggled to other states. The program’s priority is “placed on rural areas with lots of production and diversion, and little law enforcement”, said Rob Bovett, the legal counsel with the Association of Oregon Counties, who crafted the bill.

In a May 2018 memo on his marijuana enforcement priorities, Billy J Williams, a US attorney for the district of Oregon, noted that “since broader legalization took effect in 2015, large quantities of marijuana from Oregon have been seized in 30 states, most of which continue to prohibit marijuana.”

As of 1 July, however, all medical growers that produce plants for three or more patients – about 2,000 growers in Oregon – must track their marijuana from seed-to-sale using the OLCC’s Cannabis Tracking System.

Berkovitz, however, is looking to cut out the middle man (namely dispensaries) to keep PharmEx afloat. “The only way the patients are going to have large, high doses of medicine is if we revive the patient-grower networks. They need to communicate with each other. No one’s going to get rich, but everybody involved will get clean medicine from the people they trust at a more affordable rate.”

Source: https://www.theguardian.com/society/2018/jul/31/oregon-cannabis-medical-marijuana-problems-sick-people

Eleonora Patsenker, Ph.D. and Felix Stickel, M.D., Ph.D.

Mounting evidence indicates that the endocannabinoid (EC) system (ECS) plays an important role in various liver diseases including viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, hepatic encephalopathy, and autoimmune hepatitis. The ECS also impacts on involved processes such as hepatic hemodynamics, nutrient intake and turnover, and ischemia/reperfusion (I/R) after liver transplantation. Although this involvement is undisputed, therapeutic implications regarding the ECS are just beginning to emerge; so far, no approved drug
acting specifically on the ECS is available.

Source: https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/cld.527 2016

 

Authors: Mücke M, Weier M, Carter C, Copeland J, Degenhardt L, Cuhls H, Radbruch L, Häuser W, Conrad R.

Abstract

We provide a systematic review and meta-analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017.

     Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias.

     In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD]:

0.2 95% confidence interval [CI]: [-0.66, 1.06] P = 0.65),

appetite (SMD: 0.81 95% CI: [-1.14, 2.75]; P = 0.42),

nausea/vomiting (SMD: 0.21 [-0.10, 0.52] P = 0.19),

>30% decrease in pain (risk differences [RD]: 0.07 95% CI: [-0.01, 0.16]; P = 0.07),

or sleep problems (SMD: -0.09 95% CI: [-0.62, 0.43] P = 0.72).

     In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD: 0.20 [-0.15, 0.54]; P = 0.26).

     Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [-0.02; 0.08]; P = 0.23) or poor mental health (RD: -0.01 [-0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05).

     Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer-associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability.

     In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.

Source: https://www.ncbi.nlm.nih.gov/pubmed/29400010  February 2018

Cannabis’ effects on diabetes unclear – by Dr. Elizabeth Ko & Dr. Eve Glazier – Ask the Doctors  column, August 4, 2018 –  Ask the Doctors, c/0 Media Relations, UCLA Health, 924 Westwood Blvd. Suite 350, Los Angeles, CA  90095

Question:  I have Type 1 diabetes and have used marijuana for years to control my blood sugar.  I’ve seen my blood sugar drop 100 points in five minutes with marijuana, faster than my Humalog insulin can manage.  Why is that?  Will medical marijuana ever go mainstream?

Answer:  Marijuana, or cannabis, contains more than 100 active chemical compounds.  Known as cannabinoids, each behaves differently in the body.  As the number of states that allow the use of cannabis for medical purposes continues to grow, so does the body of evidence that many of the compounds found within the plant have therapeutic potential.

     The challenge to investigate medical claims regarding cannabis is that it remains illegal at the federal level.  Research is subject to numerous restrictions.  Even so, various studies and clinical trials are moving forward.

     We found that you’re not alone in noticing its effect on blood sugar.  However, much of what we found is anecdotal evidence, which lacks scientific rigor.  The study of cannabis and its potential effects on diabetes is in the early stages, which much of the work done in mice and on donated tissue samples.

     Until researchers are able to work extensively with human populations, the how and why of the effects of cannabis on the complex physiologic processes encompassed by diabetes will remain educated guesses.

     Preliminary research suggests that certain cannabinoids may help with glucose control.  Some studies have found that cannabis can have a positive effect on insulin resistance.  A study published in 2016 in a journal of the American Diabetes Association found that THCV, one of the cannabinoids that are not psychoactive, improved glycemic control in some individuals with Type 2 diabetes.  Another study that same year drew a link between cannabidiol, a compound in cannabis, and a decrease in inflammation of the pancreas.  In an observational study using data from the federal Centers for Disease Control and Prevention, researchers found the incidence of diabetes among regular cannabis users to be measurably lower than that of the population at large.

     The results of several other recent studies contradict a number of these pro-cannabis findings.  So, basically, the jury is still out.

     Although cannabis shows promise in the area of diabetes, science has yet to catch up with the claims being made.  In the research that has been done, the reason for the effects of cannabis is not yet fully understood.  Interest in the subject is strong, though, and continues to grow.

From “Ask the Doctors” – typed-copied from printed Erie Times-News (Erie, Pa.), August 4, 2018 (www.GoErie.com

Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs.

Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients’ compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam’s side effects.

Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.

Keywords: : cannabidiol, cannabinoids, medical uses, safety, side effects, toxicity

Introduction

Since several years, other pharmacologically relevant constituents of the Cannabis plant, apart from Δ9-THC, have come into the focus of research and legislation. The most prominent of those is cannabidiol (CBD). In contrast to Δ9-THC, it is nonintoxicating, but exerts a number of beneficial pharmacological effects. For instance, it is anxiolytic, anti-inflammatory, antiemetic, and antipsychotic. Moreover, neuroprotective properties have been shown.1,2 Consequently, it could be used at high doses for the treatment of a variety of conditions ranging in psychiatric disorders such as schizophrenia and dementia, as well as diabetes and nausea.1,2

At lower doses, it has physiological effects that promote and maintain health, including antioxidative, anti-inflammatory, and neuroprotection effects. For instance, CBD is more effective than vitamin C and E as a neuroprotective antioxidant and can ameliorate skin conditions such as acne.3,4

The comprehensive review of 132 original studies by Bergamaschi et al. describes the safety profile of CBD, mentioning several properties: catalepsy is not induced and physiological parameters are not altered (heart rate, blood pressure, and body temperature). Moreover, psychological and psychomotor functions are not adversely affected. The same holds true for gastrointestinal transit, food intake, and absence of toxicity for nontransformed cells. Chronic use and high doses of up to 1500 mg per day have been repeatedly shown to be well tolerated by humans.1

Nonetheless, some side effects have been reported for CBD, but mainly in vitro or in animal studies. They include alterations of cell viability, reduced fertilization capacity, and inhibition of hepatic drug metabolism and drug transporters (e.g., p-glycoprotein).1Consequently, more human studies have to be conducted to see if these effects also occur in humans. In these studies, a large enough number of subjects have to be enrolled to analyze long-term safety aspects and CBD possible interactions with other substances.

This review will build on the clinical studies mentioned by Bergamaschi et al. and will update their survey with new studies published until September 2016.

Relevant Preclinical Studies

Before we discuss relevant animal research on CBD possible effects on various parameters, several important differences between route of administration and pharmacokinetics between human and animal studies have to be mentioned. First, CBD has been studied in humans using oral administration or inhalation. Administration in rodents often occures either via intraperitoneal injection or via the oral route. Second, the plasma levels reached via oral administration in rodents and humans can differ. Both these observations can lead to differing active blood concentrations of CBD.1,5,6

In addition, it is possible that CBD targets differ between humans and animals. Therefore, the same blood concentration might still lead to different effects. Even if the targets, to which CBD binds, are the same in both studied animals and humans, for example, the affinity or duration of CBD binding to its targets might differ and consequently alter its effects.

The following study, which showed a positive effect of CBD on obsessive compulsive behavior in mice and reported no side effects, exemplifies the existing pharmacokinetic differences.5 When mice and humans are given the same CBD dose, more of the compound becomes available in the mouse organism. This higher bioavailability, in turn, can cause larger CBD effects.

Deiana et al. administered 120 mg/kg CBD either orally or intraperitoneally and measured peak plasma levels.5 The group of mice, which received oral CBD, had plasma levels of 2.2 μg/ml CBD. In contrast, i.p. injections resulted in peak plasma levels of 14.3 μg/ml. Administering 10 mg/kg oral CBD to humans leads to blood levels of 0.01 μg/ml.6 This corresponds to human blood levels of 0.12 μg/ml, when 120 mg/kg CBD was given to humans. This calculation was performed assuming the pharmacokinetics of a hydrophilic compound, for simplicity’s sake. We are aware that the actual levels of the lipophilic CBD will vary.

A second caveat of preclinical studies is that supraphysiological concentrations of compounds are often used. This means that the observed effects, for instance, are not caused by a specific binding of CBD to one of its receptors but are due to unspecific binding following the high compound concentration, which can inactivate the receptor or transporter.

The following example and calculations will demonstrate this. In vitro studies have shown that CBD inhibits the ABC transporters P-gp (P glycoprotein also referred to as ATP-binding cassette subfamily B member 1=ABCB1; 3–100 μM CBD) and Bcrp (Breast Cancer Resistance Protein; also referred to as ABCG2=ATP-binding cassette subfamily G member 2).7 After 3 days, the P-gp protein expression was altered in leukemia cells. This can have several implications because various anticancer drugs also bind to these membrane-bound, energy-dependent efflux transporters.1 The used CBD concentrations are supraphysiological, however, 3 μM CBD approximately corresponds to plasma concentrations of 1 μg/ml. On the contrary, a 700 mg CBD oral dose reached a plasma level of 10 ng/ml.6 This means that to reach a 1 μg/ml plasma concentration, one would need to administer considerably higher doses of oral CBD. The highest ever applied CBD dose was 1500 mg.1Consequently, more research is warranted, where the CBD effect on ABC transporters is analyzed using CBD concentrations of, for example, 0.03–0.06 μM. The rationale behind suggesting these concentrations is that studies summarized by Bih et al. on CBD effect on ABCC1 and ABCG2 in SF9 human cells showed that a CBD concentration of 0.08 μM elicited the first effect.7

Using the pharmacokinetic relationships mentioned above, one would need to administer an oral CBD dose of 2100 mg CBD to affect ABCC1 and ABCG2. We used 10 ng/ml for these calculations and the ones in Table 1,6,8 based on a 6-week trial using a daily oral administration of 700 mg CBD, leading to mean plasma levels of 6–11 ng/ml, which reflects the most realistic scenario of CBD administration in patients.6 That these levels seem to be reproducible, and that chronic CBD administration does not lead to elevated mean blood concentrations, was shown by another study. A single dose of 600 mg led to reduced anxiety and mean CBD blood concentrations of 4.7–17 ng/ml.9

Table 1.

Inhibition of Human Metabolic Enzymes by Exogenous Cannabinoids In Vitro and the Extrapolated Levels of Oral Daily CBD Administration in Humans Needed to Reach These In Vitro Concentrations (Adapted)6,8

CYP-450 isoform 1A1 1A2 1B1 2A6 2B6 2C9 2D6 3A4 3A5 3A7
CBD (in μM) 0.2 2.7 3.6 55.0 0.7 0.9–9.9 1.2–2.7 1.0 0.2 12.3
aExtrapolated oral daily CBD doses to reach the levels above (in mg) 4900 63,000 84,000 1.28 Mio. Ca. 16,000 21,000–231,000 28,000–63,000 Ca. 23,000 4900 0.29 Mio.
aThe calculations made here are based on the assumption that the CBD distribution in the blood follows the pharmacokinetics of a hydrophilic substance such as alcohol. The reality is more complex, because CBD is lipophilic and, for example, will consequently accumulate in fat tissue. These calculations were made with the intention to give the reader an impression and an approximation of the supraphysiological levels used in in vitro studies.

It also seems warranted to assume that the mean plasma concentration exerts the total of observed CBD effects, compared to using peak plasma levels, which only prevail for a short amount of time. This is not withstanding, that a recent study measured Cmax values for CBD of 221 ng/ml, 3 h after administration of 1 mg/kg fentanyl concomitantly with a single oral dose of 800 mg CBD.10

CBD-drug interactions

Cytochrome P450-complex enzymes

This paragraph describes CBD interaction with general (drug)-metabolizing enzymes, such as those belonging to the cytochrome P450 family. This might have an effect for coadministration of CBD with other drugs.7 For instance, CBD is metabolized, among others, via the CYP3A4 enzyme. Various drugs such as ketoconazol, itraconazol, ritonavir, and clarithromycin inhibit this enzyme.11 This leads to slower CBD degradation and can consequently lead to higher CBD doses that are longer pharmaceutically active. In contrast, phenobarbital, rifampicin, carbamazepine, and phenytoin induce CYP3A4, causing reduced CBD bioavailability.11 Approximately 60% of clinically prescribed drugs are metabolized via CYP3A4.1 Table 1 shows an overview of the cytochrome inhibiting potential of CBD. It has to be pointed out though, that the in vitro studies used supraphysiological CBD concentrations.

Studies in mice have shown that CBD inactivates cytochrome P450 isozymes in the short term, but can induce them after repeated administration. This is similar to their induction by phenobarbital, thereby implying the 2b subfamily of isozymes.1 Another study showed this effect to be mediated by upregulation of mRNA for CYP3A, 2C, and 2B10, after repeated CBD administration.1

Hexobarbital is a CYP2C19 substrate, which is an enzyme that can be inhibited by CBD and can consequently increase hexobarbital availability in the organism.12,13 Studies also propose that this effect might be caused in vivo by one of CBD metabolites.14,15Generally, the metabolite 6a-OH-CBD was already demonstrated to be an inducer of CYP2B10. Recorcinol was also found to be involved in CYP450 induction. The enzymes CYP3A and CYP2B10 were induced after prolonged CBD administration in mice livers, as well as for human CYP1A1 in vitro.14,15 On the contrary, CBD induces CYP1A1, which is responsible for degradation of cancerogenic substances such as benzopyrene. CYP1A1 can be found in the intestine and CBD-induced higher activity could therefore prevent absorption of cancerogenic substances into the bloodstream and thereby help to protect DNA.2

Effects on P-glycoprotein activity and other drug transporters

A recent study with P-gp, Bcrp, and P-gp/Bcrp knockout mice, where 10 mg/kg was injected subcutaneously, showed that CBD is not a substrate of these transporters itself. This means that they do not reduce CBD transport to the brain.16 This phenomenon also occurs with paracetamol and haloperidol, which both inhibit P-gp, but are not actively transported substrates. The same goes for gefitinib inhibition of Bcrp.

These proteins are also expressed at the blood–brain barrier, where they can pump out drugs such as risperidone. This is hypothesized to be a cause of treatment resistance.16 In addition, polymorphisms in these genes, making transport more efficient, have been implied in interindividual differences in pharmacoresistance.10 Moreover, the CBD metabolite 7-COOH CBD might be a potent anticonvulsant itself.14 It will be interesting to see whether it is a P-gp substrate and alters pharmacokinetics of coadministered P-gp-substrate drugs.

An in vitro study using three types of trophoblast cell lines and ex vivo placenta, perfused with 15 μM CBD, found BCRP inhibition leading to accumulation of xenobiotics in the fetal compartment.17BCRP is expressed at the apical side of the syncytiotrophoblast and removes a wide variety of compounds forming a part of the placental barrier. Seventy-two hours of chronic incubation with 25 μM CBD also led to morphological changes in the cell lines, but not to a direct cytotoxic effect. In contrast, 1 μM CBD did not affect cell and placenta viability.17 The authors consider this effect cytostatic. Nicardipine was used as the BCRP substrate in the in vitro studies, where the Jar cell line showed the largest increase in BCRP expression correlating with the highest level of transport.17,and references therein

The ex vivo study used the antidiabetic drug and BCRP substrate glyburide.17 After 2 h of CBD perfusion, the largest difference between the CBD and the placebo placentas (n=8 each) was observed. CBD inhibition of the BCRP efflux function in the placental cotyledon warrants further research of coadministration of CBD with known BCRP substrates such as nitrofurantoin, cimetidine, and sulfasalazine. In this study, a dose–response curve should be established in male and female subjects (CBD absorption was shown to be higher in women) because the concentrations used here are usually not reached by oral or inhaled CBD administration. Nonetheless, CBD could accumulate in organs physiologically restricted via a blood barrier.17

Physiological effects

CBD treatment of up to 14 days (3–30 mg/kg b.w. i.p.) did not affect blood pressure, heart rate, body temperature, glucose levels, pH, pCO2, pO2, hematocrit, K+ or Na+ levels, gastrointestinal transit, emesis, or rectal temperature in a study with rodents.1

Mice treated with 60 mg/kg b.w. CBD i.p. for 12 weeks (three times per week) did not show ataxia, kyphosis, generalized tremor, swaying gait, tail stiffness, changes in vocalization behavior or open-field physiological activity (urination, defecation).1

Neurological and neurospychiatric effects

Anxiety and depression

Some studies indicate that under certain circumstances, CBD acute anxiolytic effects in rats were reversed after repeated 14-day administration of CBD.2 However, this finding might depend on the used animal model of anxiety or depression. This is supported by a study, where CBD was administered in an acute and “chronic” (2 weeks) regimen, which measured anxiolytic/antidepressant effects, using behavioral and operative models (OBX=olfactory bulbectomy as model for depression).18 The only observed side effects were reduced sucrose preference, reduced food consumption and body weight in the nonoperated animals treated with CBD (50 mg/kg). Nonetheless, the behavioral tests (for OBX-induced hyperactivity and anhedonia related to depression and open field test for anxiety) in the CBD-treated OBX animals showed an improved emotional response. Using microdialysis, the researchers could also show elevated 5-HT and glutamate levels in the prefrontal cortex of OBX animals only. This area was previously described to be involved in maladaptive behavioral regulation in depressed patients and is a feature of the OBX animal model of depression. The fact that serotonin levels were only elevated in the OBX mice is similar to CBD differential action under physiological and pathological conditions.

A similar effect was previously described in anxiety experiments, where CBD proved to be only anxiolytic in subjects where stress had been induced before CBD administration. Elevated glutamate levels have been proposed to be responsible for ketamine’s fast antidepressant function and its dysregulation has been described in OBX mice and depressed patients. Chronic CBD treatment did not elicit behavioral changes in the nonoperated mice. In contrast, CBD was able to alleviate the affected functionality of 5HT1A receptors in limbic brain areas of OBX mice.18 and references therein

Schiavon et al. cite three studies that used chronic CBD administration to demonstrate its anxiolytic effects in chronically stressed rats, which were mostly mediated via hippocampal neurogenesis.19 and references therein For instance, animals received daily i.p. injections of 5 mg/kg CBD. Applying a 5HT1A receptor antagonist in the DPAG (dorsal periaqueductal gray area), it was implied that CBD exerts its antipanic effects via these serotonin receptors. No adverse effects were reported in this study.

Psychosis and bipolar disorder

Various studies on CBD and psychosis have been conducted.20 For instance, an animal model of psychosis can be created in mice by using the NMDAR antagonist MK-801. The behavioral changes (tested with the prepulse inhibition [PPI] test) were concomitant with decreased mRNA expression of the NMDAR GluN1 subunit gene (GRN1) in the hippocampus, decreased parvalbumin expression (=a calcium-binding protein expressed in a subclass of GABAergic interneurons), and higher FosB/ΔFosB expression (=markers for neuronal activity). After 6 days of MK-801 treatment, various CBD doses were injected intraperitoneally (15, 30, 60 mg/kg) for 22 days. The two higher CBD doses had beneficial effects comparable to the atypical antipsychotic drug clozapine and also attenuated the MK-801 effects on the three markers mentioned above. The publication did not record any side effects.21

One of the theories trying to explain the etiology of bipolar disorder (BD) is that oxidative stress is crucial in its development. Valvassori et al. therefore used an animal model of amphetamine-induced hyperactivity to model one of the symptoms of mania. Rats were treated for 14 days with various CBD concentrations (15, 30, 60 mg/kg daily i.p.). Whereas CBD did not have an effect on locomotion, it did increase brain-derived neurotrophic factor (BDNF) levels and could protect against amphetamine-induced oxidative damage in proteins of the hippocampus and striatum. No adverse effects were recorded in this study.22

Another model for BD and schizophrenia is PPI of the startle reflex both in humans and animals, which is disrupted in these diseases. Peres et al., list five animal studies, where mostly 30 mg/kg CBD was administered and had a positive effect on PPI.20 Nonetheless, some inconsistencies in explaining CBD effects on PPI as model for BD exist. For example, CBD sometimes did not alter MK-801-induced PPI disruption, but disrupted PPI on its own.20 If this effect can be observed in future experiments, it could be considered to be a possible side effect.

Addiction

CBD, which is nonhedonic, can reduce heroin-seeking behavior after, for example, cue-induced reinstatement. This was shown in an animal heroin self-administration study, where mice received 5 mg/kg CBD i.p. injections. The observed effect lasted for 2 weeks after CBD administration and could normalize the changes seen after stimulus cue-induced heroin seeking (expression of AMPA, GluR1, and CB1R). In addition, the described study was able to replicate previous findings showing no CBD side effects on locomotor behavior.23

Neuroprotection and neurogenesis

There are various mechanisms underlying neuroprotection, for example, energy metabolism (whose alteration has been implied in several psychiatric disorders) and proper mitochondrial functioning.24 An early study from 1976 found no side effects and no effect of 0.3–300 μg/mg protein CBD after 1 h of incubation on mitochondrial monoamine oxidase activity in porcine brains.25 In hypoischemic newborn pigs, CBD elicited a neuroprotective effect, caused no side effects, and even led to beneficial effects on ventilatory, cardiac, and hemodynamic functions.26

A study comparing acute and chronic CBD administration in rats suggests an additional mechanism of CBD neuroprotection: Animals received i.p. CBD (15, 30, 60 mg/kg b.w.) or vehicle daily, for 14 days. Mitochondrial activity was measured in the striatum, hippocampus, and the prefrontal cortex.27 Acute and chronic CBD injections led to increased mitochondrial activity (complexes I-V) and creatine kinase, whereas no side effects were documented. Chronic CBD treatment and the higher CBD doses tended to affect more brain regions. The authors hypothesized that CBD changed the intracellular Ca2+ flux to cause these effects. Since the mitochondrial complexes I and II have been implied in various neurodegenerative diseases and also altered ROS (reactive oxygen species) levels, which have also been shown to be altered by CBD, this might be an additional mechanism of CBD-mediated neuroprotection.1,27

Interestingly, it has recently been shown that the higher ROS levels observed after CBD treatment were concomitant with higher mRNA and protein levels of heat shock proteins (HSPs). In healthy cells, this can be interpreted as a way to protect against the higher ROS levels resulting from more mitochondrial activity. In addition, it was shown that HSP inhibitors increase the CBD anticancer effect in vitro.28 This is in line with the studies described by Bergamaschi et al., which also imply ROS in CBD effect on (cancer) cell viability in addition to, for example, proapoptotic pathways such as via caspase-8/9 and inhibition of the procarcinogenic lipoxygenase pathway.1

Another publication studied the difference of acute and chronic administration of two doses of CBD in nonstressed mice on anxiety. Already an acute i.p. administration of 3 mg/kg was anxiolytic to a degree comparable to 20 mg/kg imipramine (an selective serotonin reuptake inhibitor [SSRI] commonly prescribed for anxiety and depression). Fifteen days of repeated i.p. administration of 3 mg/kg CBD also increased cell proliferation and neurogenesis (using three different markers) in the subventricular zone and the hippocampal dentate gyrus. Interestingly, the repeated administration of 30 mg/kg also led to anxiolytic effects. However, the higher dose caused a decrease in neurogenesis and cell proliferation, indicating dissociation of behavioral and proliferative effects of chronic CBD treatment. The study does not mention adverse effects.19

Immune system

Numerous studies show the CBD immunomodulatory role in various diseases such as multiple sclerosis, arthritis, and diabetes. These animal and human ex vivo studies have been reviewed extensively elsewhere, but studies with pure CBD are still lacking. Often combinations of THC and CBD were used. It would be especially interesting to study when CBD is proinflammatory and under which circumstances it is anti-inflammatory and whether this leads to side effects (Burstein, 2015: Table 1 shows a summary of its anti-inflammatory actions; McAllister et al. give an extensive overview in Table 1 of the interplay between CBD anticancer effects and inflammation signaling).29,30

In case of Alzheimer’s disease (AD), studies in mice and rats showed reduced amyloid beta neuroinflammation (linked to reduced interleukin [IL]-6 and microglial activation) after CBD treatment. This led to amelioration of learning effects in a pharmacological model of AD. The chronic study we want to describe in more detail here used a transgenic mouse model of AD, where 2.5-month-old mice were treated with either placebo or daily oral CBD doses of 20 mg/kg for 8 months (mice are relatively old at this point). CBD was able to prevent the development of a social recognition deficit in the AD transgenic mice.

Moreover, the elevated IL-1 beta and TNF alpha levels observed in the transgenic mice could be reduced to WT (wild-type) levels with CBD treatment. Using statistical analysis by analysis of variance, this was shown to be only a trend. This might have been caused by the high variation in the transgenic mouse group, though. Also, CBD increased cholesterol levels in WT mice but not in CBD-treated transgenic mice. This was probably due to already elevated cholesterol in the transgenic mice. The study observed no side effects.31 and references within

In nonobese diabetes-prone female mice (NOD), CBD was administered i.p. for 4 weeks (5 days a week) at a dose of 5 mg/kg per day. After CBD treatment was stopped, observation continued until the mice were 24 weeks old. CBD treatment lead to considerable reduction of diabetes development (32% developed glucosuria in the CBD group compared to 100% in untreated controls) and to more intact islet of Langerhans cells. CBD increased IL-10 levels, which is thought to act as an anti-inflammatory cytokine in this context. The IL-12 production of splenocytes was reduced in the CBD group and no side effects were recorded.32

After inducing arthritis in rats using Freund’s adjuvant, various CBD doses (0.6, 3.1, 6.2, or 62.3 mg/day) were applied daily in a gel for transdermal administration for 4 days. CBD reduced joint swelling, immune cell infiltration. thickening of the synovial membrane, and nociceptive sensitization/spontaneous pain in a dose-dependent manner, after four consecutive days of CBD treatment. Proinflammatory biomarkers were also reduced in a dose-dependent manner in the dorsal root ganglia (TNF alpha) and spinal cord (CGRP, OX42). No side effects were evident and exploratory behavior was not altered (in contrast to Δ9-THC, which caused hypolocomotion).33

Cell migration

Embryogenesis

CBD was shown to be able to influence migratory behavior in cancer, which is also an important aspect of embryogenesis.1 For instance, it was recently shown that CBD inhibits Id-1. Helix-loop-helix Id proteins play a role in embryogenesis and normal development via regulation of cell differentiation. High Id1-levels were also found in breast, prostate, brain, and head and neck tumor cells, which were highly aggressive. In contrast, Id1 expression was low in noninvasive tumor cells. Id1 seems to influence the tumor cell phenotype by regulation of invasion, epithelial to mesenchymal transition, angiogenesis, and cell proliferation.34

There only seems to exist one study that could not show an adverse CBD effect on embryogenesis. An in vitro study could show that the development of two-cell embryos was not arrested at CBD concentrations of 6.4, 32, and 160 nM.35

Cancer

Various studies have been performed to study CBD anticancer effects. CBD anti-invasive actions seem to be mediated by its TRPV1 stimulation and its action on the CB receptors. Intraperitoneal application of 5 mg/kg b.w. CBD every 3 days for a total of 28 weeks, almost completely reduced the development of metastatic nodules caused by injection of human lung carcinoma cells (A549) in nude mice.36 This effect was mediated by upregulation of ICAM1 and TIMP1. This, in turn, was caused by upstream regulation of p38 and p42/44 MAPK pathways. The typical side effects of traditional anticancer medication, emesis, and collateral toxicity were not described in these studies. Consequently, CBD could be an alternative to other MMP1 inhibitors such as marimastat and prinomastat, which have shown disappointing clinical results due to these drugs’ adverse muscoskeletal effects.37,38

Two studies showed in various cell lines and in tumor-bearing mice that CBD was able to reduce tumor metastasis.34,39 Unfortunately, the in vivo study was only described in a conference abstract and no route of administration or CBD doses were mentioned.36 However, an earlier study used 0.1, 1.0, or 1.5 μmol/L CBD for 3 days in the aggressive breast cancer cells MDA-MB231. CBD downregulated Id1 at promoter level and reduced tumor aggressiveness.40

Another study used xenografts to study the proapoptotic effect of CBD, this time in LNCaP prostate carcinoma cells.36 In this 5-week study, 100 mg/kg CBD was administered daily i.p. Tumor volume was reduced by 60% and no adverse effects of treatment were described in the study. The authors assumed that the observed antitumor effects were mediated via TRPM8 together with ROS release and p53 activation.41 It has to be pointed out though, that xenograft studies only have limited predictive validity to results with humans. Moreover, to carry out these experiments, animals are often immunologically compromised, to avoid immunogenic reactions as a result to implantation of human cells into the animals, which in turn can also affect the results.42

Another approach was chosen by Aviello et al.43 They used the carcinogen azoxymethane to induce colon cancer in mice. Treatment occurred using IP injections of 1 or 5 mg/kg CBD, three times a week for 3 weeks (including 1 week before carcinogen administration). After 3 months, the number of aberrant crypt foci, polyps, and tumors was analyzed. The high CBD concentration led to a significant decrease in polyps and a return to near-normal levels of phosphorylated Akt (elevation caused by the carcinogen).42 No adverse effects were mentioned in the described study.43

Food intake and glycemic effects

Animal studies summarized by Bergamaschi et al. showed inconclusive effects of CBD on food intake1: i.p. administration of 3–100 mg/kg b.w. had no effect on food intake in mice and rats. On the contrary, the induction of hyperphagia by CB1 and 5HT1A agonists in rats could be decreased with CBD (20 mg/kg b.w. i.p.). Chronic administration (14 days, 2.5 or 5 mg/kg i.p.) reduced the weight gain in rats. This effect could be inhibited by coadministration of a CB2R antagonist.1

The positive effects of CBD on hyperglycemia seem to be mainly mediated via CBD anti-inflammatory and antioxidant effects. For instance, in ob/ob mice (an animal model of obesity), 4-week treatment with 3 mg/kg (route of administration was not mentioned) increased the HDL-C concentration by 55% and reduced total cholesterol levels by more than 25%. In addition, treatment increased adiponectin and liver glycogen concentrations.44 and references therein

Endocrine effects

High CBD concentrations (1 mM) inhibited progesterone 17-hydroxylase, which creates precursors for sex steroid and glucocorticoid synthesis, whereas 100 μM CBD did not in an in vitro experiment with primary testis microsomes.45 Rats treated with 10 mg/kg i.p. b.w. CBD showed inhibition of testosterone oxidation in the liver.46

Genotoxicity and mutagenicity

Jones et al. mention that 120 mg/kg CBD delivered intraperetonially to Wistar Kyoto rats showed no mutagenicity and genotoxicity based on personal communication with GW Pharmaceuticals47,48These data are yet to be published. The 2012 study with an epilepsy mouse model could also show that CBD did not influence grip strength, which the study describes as a “putative test for functional neurotoxicity.”48

Motor function was also tested on a rotarod, which was also not affected by CBD administration. Static beam performance, as an indicator of sensorimotor coordination, showed more footslips in the CBD group, but CBD treatment did not interfere with the animals’ speed and ability to complete the test. Compared to other anticonvulsant drugs, this effect was minimal.48 Unfortunately, we could not find more studies solely focusing on genotoxicity by other research groups neither in animals nor in humans.

Acute Clinical Data

Bergamaschi et al. list an impressive number of acute and chronic studies in humans, showing CBD safety for a wide array of side effects.1 They also conclude from their survey, that none of the studies reported tolerance to CBD. Already in the 1970s, it was shown that oral CBD (15–160 mg), iv injection (5–30 mg), and inhalation of 0.15 mg/kg b.w. CBD did not lead to adverse effects. In addition, psychomotor function and psychological functions were not disturbed. Treatment with up to 600 mg CBD neither influenced physiological parameters (blood pressure, heart rate) nor performance on a verbal paired-associate learning test.1

Fasinu et al. created a table with an overview of clinical studies currently underway, registered in Clinical Trials. gov.49 In the following chapter, we highlight recent, acute clinical studies with CBD.

CBD-drug interactions

CBD can inhibit CYP2D6, which is also targeted by omeprazole and risperidone.2,14 There are also indications that CBD inhibits the hepatic enzyme CYP2C9, reducing the metabolization of warfarin and diclofenac.2,14 More clinical studies are needed, to check whether this interaction warrants an adaption of the used doses of the coadministered drugs.

The antibiotic rifampicin induces CYP3A4, leading to reduced CBD peak plasma concentrations.14 In contrast, the CYP3A4 inhibitor ketoconazole, an antifungal drug, almost doubles CBD peak plasma concentration. Interestingly, the CYP2C19 inhibitor omeprazole, used to treat gastroesophageal reflux, could not significantly affect the pharmacokinetics of CBD.14

A study, where a regimen of 6×100 mg CBD daily was coadministered with hexobarbital in 10 subjects, found that CBD increased the bioavailability and elimination half-time of the latter. Unfortunately, it was not mentioned whether this effect was mediated via the cytochrome P450 complex.16

Another aspect, which has not been thoroughly looked at, to our knowledge, is that several cytochrome isozymes are not only expressed in the liver but also in the brain. It might be interesting to research organ-specific differences in the level of CBD inhibition of various isozymes. Apart from altering the bioavailability in the overall plasma of the patient, this interaction might alter therapeutic outcomes on another level. Dopamine and tyramine are metabolized by CYP2D6, and neurosteroid metabolism also occurs via the isozymes of the CYP3A subgroup.50,51 Studying CBD interaction with neurovascular cytochrome P450 enzymes might also offer new mechanisms of action. It could be possible that CBD-mediated CYP2D6 inhibition increases dopamine levels in the brain, which could help to explain the positive CBD effects in addiction/withdrawal scenarios and might support its 5HT (=serotonin) elevating effect in depression.

Also, CBD can be a substrate of UDP glucuronosyltransferase.14Whether this enzyme is indeed involved in the glucuronidation of CBD and also causes clinically relevant drug interactions in humans is yet to be determined in clinical studies. Generally, more human studies, which monitor CBD-drug interactions, are needed.

Physiological effects

In a double-blind, placebo-controlled crossover study, CBD was coadministered with intravenous fentanyl to a total of 17 subjects.10Blood samples were obtained before and after 400 mg CBD (previously demonstrated to decrease blood flow to (para)limbic areas related to drug craving) or 800 mg CBD pretreatment. This was followed by a single 0.5 (Session 1) or 1.0μg/kg (Session 2, after 1 week of first administration to allow for sufficient drug washout) intravenous fentanyl dose. Adverse effects and safety were evaluated with both forms of the Systematic Assessment for Treatment Emergent Events (SAFTEE). This extensive tool tests, for example, 78 adverse effects divided into 23 categories corresponding to organ systems or body parts. The SAFTEE outcomes were similar between groups. No respiratory depression or cardiovascular complications were recorded during any test session.

The results of the evaluation of pharmacokinetics, to see if interaction between the drugs occurred, were as follows. Peak CBD plasma concentrations of the 400 and 800 mg group were measured after 4 h in the first session (CBD administration 2 h after light breakfast). Peak urinary CBD and its metabolite concentrations occurred after 6 h in the low CBD group and after 4 h in the high CBD group. No effect was evident for urinary CBD and metabolite excretion except at the higher fentanyl dose, in which CBD clearance was reduced. Importantly, fentanyl coadministration did not produce respiratory depression or cardiovascular complications during the test sessions and CBD did not potentiate fentanyl’s effects. No correlation was found between CBD dose and plasma cortisol levels.

Various vital signs were also measured (blood pressure, respiratory/heart rate, oxygen saturation, EKG, respiratory function): CBD did not worsen the adverse effects (e.g., cardiovascular compromise, respiratory depression) of iv fentanyl. Coadministration was safe and well tolerated, paving the way to use CBD as a potential treatment for opioid addiction. The validated subjective measures scales Anxiety (visual analog scale [VAS]), PANAS (positive and negative subscores), and OVAS (specific opiate VAS) were administered across eight time points for each session without any significant main effects for CBD for any of the subjective effects on mood.10

A Dutch study compared subjective adverse effects of three different strains of medicinal cannabis, distributed via pharmacies, using VAS. “Visual analog scale is one of the most frequently used psychometric instruments to measure the extent and nature of subjective effects and adverse effects. The 12 adjectives used for this study were as follows: alertness, tranquility, confidence, dejection, dizziness, confusion/disorientation, fatigue, anxiety, irritability, appetite, creative stimulation, and sociability.” The high CBD strain contained the following concentrations: 6% Δ9-THC/7.5% CBD (n=25). This strain showed significantly lower levels of anxiety and dejection. Moreover, appetite increased less in the high CBD strain. The biggest observed adverse effect was “fatigue” with a score of 7 (out of 10), which did not differ between the three strains.52

Neurological and neurospychiatric effects

Anxiety

Forty-eight participants received subanxiolytic levels (32 mg) of CBD, either before or after the extinction phase in a double-blind, placebo-controlled design of a Pavlovian fear-conditioning experiment (recall with conditioned stimulus and context after 48 h and exposure to unconditioned stimulus after reinstatement). Skin conductance (=autonomic response to conditioning) and shock expectancy measures (=explicit aspects) of conditioned responding were recorded throughout. Among other scales, the Mood Rating Scale (MRS) and the Bond and Bodily Symptoms Scale were used to assess anxiety, current mood, and physical symptoms. “CBD given postextinction (active after consolidation phase) enhanced consolidation of extinction learning as assessed by shock expectancy.” Apart from the extinction-enhancing effects of CBD in human aversive conditioned memory, CBD showed a trend toward some protection against reinstatement of contextual memory. No side/adverse effects were reported.53

Psychosis

The review by Bergamaschi et al. mentions three acute human studies that have demonstrated the CBD antipsychotic effect without any adverse effects being observed. This holds especially true for the extrapyramidal motor side effects elicited by classical antipsychotic medication.1

Fifteen male, healthy subjects with minimal prior Δ9-THC exposure (<15 times) were tested for CBD affecting Δ9-THC propsychotic effects using functional magnetic resonance imaging (fMRI) and various questionnaires on three occasions, at 1-month intervals, following administration of 10 mg delta-9-Δ9-THC, 600 mg CBD, or placebo. Order of drug administration was pseudorandomized across subjects, so that an equal number of subjects received any of the drugs during the first, second, or third session in a double-blind, repeated-measures, within-subject design.54 No CBD effect on psychotic symptoms as measured with PANSS positive symptoms subscale, anxiety as indexed by the State Trait Anxiety Inventory (STAI) state, and Visual Analogue Mood Scale (VAMS) tranquilization or calming subscale, compared to the placebo group, was observed. The same is true for a verbal learning task (=behavioral performance of the verbal memory).

Moreover, pretreatment with CBD and subsequent Δ9-THC administration could reduce the latter’s psychotic and anxiety symptoms, as measured using a standardized scale. This effect was caused by opposite neural activation of relevant brain areas. In addition, no effects on peripheral cardiovascular measures such as heart rate and blood pressure were measured.54

A randomized, double-blind, crossover, placebo-controlled trial was conducted in 16 healthy nonanxious subjects using a within-subject design. Oral Δ9-THC=10 mg, CBD=600 mg, or placebo was administered in three consecutive sessions at 1-month intervals. The doses were selected to only evoke neurocognitive effects without causing severe toxic, physical, or psychiatric reactions. The 600 mg CBD corresponded to mean (standard deviation) whole blood levels of 0.36 (0.64), 1.62 (2.98), and 3.4 (6.42) ng/mL, 1, 2, and 3 h after administration, respectively.

Physiological measures and symptomatic effects were assessed before, and at 1, 2, and 3 h postdrug administration using PANSS (a 30-item rating instrument used to assess psychotic symptoms, with ratings based on a semistructured clinical interview yielding subscores for positive, negative, and general psychopathology domains), the self-administered VAMS with 16 items (e.g., mental sedation or intellectual impairment, physical sedation or bodily impairments, anxiety effects and other types of feelings or attitudes), the ARCI (Addiction Research Center Inventory; containing empirically derived drug-induced euphoria; stimulant-like effects; intellectual efficiency and energy; sedation; dysphoria; and somatic effects) to assess drug effects and the STAI-T/S, where subjects were evaluated on their current mood and their feelings in general.

There were no significant differences between the effects of CBD and placebo on positive and negative psychotic symptoms, general psychopathology (PANSS), anxiety (STAI-S), dysphoria (ARCI), sedation (VAMS, ARCI), and the level of subjective intoxication (ASI, ARCI), where Δ9-THC did have a pronounced effect. The physiological parameters, heart rate and blood pressure, were also monitored and no significant difference between the placebo and the CBD group was observed.55

Addiction

A case study describes a patient treated for cannabis withdrawal according to the following CBD regimen: “treated with oral 300 mg on Day 1; CBD 600 mg on Days 2–10 (divided into two doses of 300 mg), and CBD 300 mg on Day 11.” CBD treatment resulted in a fast and progressive reduction in withdrawal, dissociative and anxiety symptoms, as measured with the Withdrawal Discomfort Score, the Marijuana Withdrawal Symptom Checklist, Beck Anxiety Inventory, and Beck Depression Inventory (BDI). Hepatic enzymes were also measured daily, but no effect was reported.56

Naturalistic studies with smokers inhaling cannabis with varying amounts of CBD showed that the CBD levels were not altering psychomimetic symptoms.1 Interestingly, CBD was able to reduce the “wanting/liking”=implicit attentional bias caused by exposure to cannabis and food-related stimuli. CBD might work to alleviate disorders of addiction, by altering the attentive salience of drug cues. The study did not further measure side effects.57

CBD can also reduce heroin-seeking behaviors (e.g., induced by a conditioned cue). This was shown in the preclinical data mentioned earlier and was also replicated in a small double-blind pilot study with individuals addicted to opioids, who have been abstinent for 7 days.52,53 They either received placebo or 400 or 800 mg oral CBD on three consecutive days. Craving was induced with a cue-induced reinstatement paradigm (1 h after CBD administration). One hour after the video session, subjective craving was already reduced after a single CBD administration. The effect persisted for 7 days after the last CBD treatment. Interestingly, anxiety measures were also reduced after treatment, whereas no adverse effects were described.23,58

A pilot study with 24 subjects was conducted in a randomized, double-blind, placebo-controlled design to evaluate the impact of the ad hoc use of CBD in smokers, who wished to stop smoking. Pre- and post-testing for mood and craving of the participants was executed. These tests included the Behaviour Impulsivity Scale, BDI, STAI, and the Severity of Dependence Scale. During the week of CBD inhalator use, subjects used a diary to log their craving (on a scale from 1 to 100=VAS measuring momentary subjective craving), the cigarettes smoked, and the number of times they used the inhaler. Craving was assessed using the Tiffany Craving Questionnaire (11). On day 1 and 7, exhaled CO was measured to test smoking status. Sedation, depression, and anxiety were evaluated with the MRS.

Over the course of 1 week, participants used the inhaler when they felt the urge to smoke and received a dose of 400 μg CBD via the inhaler (leading to >65% bioavailability); this significantly reduced the number of cigarettes smoked by ca. 40%, while craving was not significantly different in the groups post-test. At day 7, the anxiety levels for placebo and CBD group did not differ. CBD did not increase depression (in contract to the selective CB1 antagonist rimonabant). CBD might weaken the attentional bias to smoking cues or could have disrupted reconsolidation, thereby destabilizing drug-related memories.59

Cell migration

According to our literature survey, there currently are no studies about CBD role in embryogenesis/cell migration in humans, even though cell migration does play a role in embryogenesis and CBD was shown to be able to at least influence migratory behavior in cancer.1

Endocrine effects and glycemic (including appetite) effects

To the best of our knowledge, no acute studies were performed that solely concentrated on CBD glycemic effects. Moreover, the only acute study that also measured CBD effect on appetite was the study we described above, comparing different cannabis strains. In this study, the strain high in CBD elicited less appetite increase compared to the THC-only strain.52

Eleven healthy volunteers were treated with 300 mg (seven patients) and 600 mg (four patients) oral CBD in a double-blind, placebo-controlled study. Growth hormone and prolactin levels were unchanged. In contrast, the normal decrease of cortisol levels in the morning (basal measurement=11.0±3.7 μg/dl; 120 min after placebo=7.1±3.9 μg/dl) was inhibited by CBD treatment (basal measurement=10.5±4.9 μg/dl; 120 min after 300 mg CBD=9.9±6.2 μg/dl; 120 min after 600 mg CBD=11.6±11.6 μg/dl).60

A more recent study also used 600 mg oral CBD for a week and compared 24 healthy subjects to people at risk for psychosis (n=32; 16 received placebo and 16 CBD). Serum cortisol levels were taken before the TSST (Trier Social Stress Test), immediately after, as well as 10 and 20 min after the test. Compared to the healthy individuals, the cortisol levels increased less after TSST in the 32 at-risk individuals. The CBD group showed less reduced cortisol levels but differences were not significant.61 It has to be mentioned that these data were presented at a conference and are not yet published (to our knowledge) in a peer-reviewed journal.

Chronic CBD Studies in Humans

Truly chronic studies with CBD are still scarce. One can often argue that what the studies call “chronic” CBD administration only differs to acute treatment, because of repeated administration of CBD. Nonetheless, we also included these studies with repeated CBD treatment, because we think that compared to a one-time dose of CBD, repeated CBD regimens add value and knowledge to the field and therefore should be mentioned here.

CBD-drug interactions

An 8-week-long clinical study, including 13 children who were treated for epilepsy with clobazam (initial average dose of 1 mg/kg b.w.) and CBD (oral; starting dose of 5 mg/kg b.w. raised to maximum of 25 mg/kg b.w.), showed the following. The CBD interaction with isozymes CYP3A4 and CYP2C19 caused increased clobazam bioavailability, making it possible to reduce the dose of the antiepileptic drug, which in turn reduced its side effects.62

These results are supported by another study described in the review by Grotenhermen et al.63 In this study, 33 children were treated with a daily dose of 5 mg/kg CBD, which was increased every week by 5 mg/kg increments, up to a maximum level of 25 mg/kg. CBD was administered on average with three other drugs, including clobazam (54.5%), valproic acid (36.4%), levetiracetam (30.3%), felbamate (21.2%), lamotrigine (18.2%), and zonisamide (18.2%). The coadministration led to an alteration of blood levels of several antiepileptic drugs. In the case of clobazam this led to sedation, and its levels were subsequently lowered in the course of the study.

Physiological effects

A first pilot study in healthy volunteers in 1973 by Mincis et al. administering 10 mg oral CBD for 21 days did not find any neurological and clinical changes (EEG; EKG).64 The same holds true for psychiatry and blood and urine examinations. A similar testing battery was performed in 1980, at weekly intervals for 30 days with daily oral CBD administration of 3 mg/kg b.w., which had the same result.65

Neurological and neuropsychiatric effects

Anxiety

Clinical chronic (lasting longer than a couple of weeks) studies in humans are crucial here but were mostly still lacking at the time of writing this review. They hopefully will shed light on the inconsistencies observerd in animal studies. Chronic studies in humans may, for instance, help to test whether, for example, an anxiolytic effect always prevails after chronic CBD treatment or whether this was an artifact of using different animal models of anxiety or depression.2,18

Psychosis and bipolar disorder

In a 4-week open trial, CBD was tested on Parkinson’s patients with psychotic symptoms. Oral doses of 150–400 mg/day CBD (in the last week) were administered. This led to a reduction of their psychotic symptoms. Moreover, no serious side effects or cognitive and motor symptoms were reported.66

Bergamaschi et al. describe a chronic study, where a teenager with severe side effects of traditional antipsychotics was treated with up to 1500 mg/day of CBD for 4 weeks. No adverse effects were observed and her symptoms improved. The same positive outcome was registered in another study described by Bergamaschi et al., where three patients were treated with a starting dose of CBD of 40 mg, which was ramped up to 1280 mg/day for 4 weeks.1 A double-blind, randomized clinical trial of CBD versus amisulpride, a potent antipsychotic in acute schizophrenia, was performed on a total of 42 subjects, who were treated for 28 days starting with 200 mg CBD per day each.67 The dose was increased stepwise by 200 mg per day to 4×200 mg CBD daily (total 800 mg per day) within the first week. The respective treatment was maintained for three additional weeks. A reduction of each treatment to 600 mg per day was allowed for clinical reasons, such as unwanted side effects after week 2. This was the case for three patients in the CBD group and five patients in the amisulpride group. While both treatments were effective (no significant difference in PANSS total score), CBD showed the better side effect profile. Amisulpride, working as a dopamine D2/D3-receptor antagonist, is one of the most effective treatment options for schizophrenia. CBD treatment was accompanied by a substantial increase in serum anandamide levels, which was significantly associated with clinical improvement, suggesting inhibition of anandamide deactivation via reduced FAAH activity.

In addition, the FAAH substrates palmitoylethanolamide and linoleoyl-ethanolamide (both lipid mediators) were also elevated in the CBD group. CBD showed less serum prolactin increase (predictor of galactorrhoea and sexual dysfunction), fewer extrapyramidal symptoms measured with the Extrapyramidal Symptom Scale, and less weight gain. Moreover, electrocardiograms as well as routine blood parameters were other parameters whose effects were measured but not reported in the study. CBD better safety profile might improve acute compliance and long-term treatment adherence.67,68

A press release by GW Pharmaceuticals of September 15th, 2015, described 88 patients with treatment-resistant schizophrenic psychosis, treated either with CBD (in addition to their regular medication) or placebo. Important clinical parameters improved in the CBD group and the number of mild side effects was comparable to the placebo group.2 Table 2 shows an overview of studies with CBD for the treatment of psychotic symptoms and its positive effect on symptomatology and the absence of side effects.69

Table 2.

Studies with CBD with Patients with Psychotic Symptoms (Adapted)69

Assessment Oral CBD administration Total number of study participants Main findings
BPRS (brief psychiatric rating scale) Up to 1500 mg/day for 26 days 1 Improvement of symptomatology, no side effects
BPRS Up to 1280 mg/day for 4 weeks 3 Mild improvement of symptomatology of 1 patient, no side effects
BPRS, Parkinson Psychosis Questionnaire (PPQ) Up to 600 mg/day for 4 weeks 6 Improvement of symptomatology, no side effects
Stroop Color Word Test, BPRS, PANSS (positive and negative symptom scale) Single doses of 300 or 600 mg 28 Performance after placebo and CBD 300 mg compared to CBD 600 mg; no effects on symptomatology
BPRS, PANSS Up to 800 mg/day for 4 weeks 39 CBD as effective as amisulpride in terms of improvement of symptomatology; CBD displayed superior side effect profile

Treatment of two patients for 24 days with 600–1200 mg/day CBD, who were suffering from BD, did not lead to side effects.70 Apart from the study with two patients mentioned above, CBD has not been tested systematically in acute or chronic administration scenarios in humans for BD according to our own literature search.71

Epilepsy

Epileptic patients were treated for 135 days with 200–300 mg oral CBD daily and evaluated every week for changes in urine and blood. Moreover, neurological and physiological examinations were performed, which neither showed signs of CBD toxicity nor severe side effects. The study also illustrated that CBD was well tolerated.65

A review by Grotenhermen and Müller-Vahl describes several clinical studies with CBD2: 23 patients with therapy-resistant epilepsy (e.g., Dravet syndrome) were treated for 3 months with increasing doses of up to 25 mg/kg b.w. CBD in addition to their regular epilepsy medication. Apart from reducing the seizure frequency in 39% of the patients, the side effects were only mild to moderate and included reduced/increased appetite, weight gain/loss, and tiredness.

Another clinical study lasting at least 3 months with 137 children and young adults with various forms of epilepsy, who were treated with the CBD drug Epidiolex, was presented at the American Academy for Neurology in 2015. The patients were suffering from Dravet syndrome (16%), Lennox–Gastaut syndrome (16%), and 10 other forms of epilepsy (some among them were very rare conditions). In this study, almost 50% of the patients experienced a reduction of seizure frequency. The reported side effects were 21% experienced tiredness, 17% diarrhea, and 16% reduced appetite. In a few cases, severe side effects occurred, but it is not clear, if these were caused by Epidiolex. These were status epilepticus (n=10), diarrhea (n=3), weight loss (n=2), and liver damage in one case.

The largest CBD study conducted thus far was an open-label study with Epidiolex in 261 patients (mainly children, the average age of the participants was 11) suffering from severe epilepsy, who could not be treated sufficiently with standard medication. After 3 months of treatment, where patients received CBD together with their regular medication, a median reduction of seizure frequency of 45% was observed. Ten percent of the patients reported side effects (tiredness, diarrhea, and exhaustion).2

After extensive literature study of the available trials performed until September 2016, CBD side effects were generally mild and infrequent. The only exception seems to be a multicenter open-label study with a total of 162 patients aged 1–30 years, with treatment-resistant epilepsy. Subjects were treated for 1 year with a maximum of 25 mg/kg (in some clinics 50 mg/kg) oral CBD, in addition to their standard medication.

This led to a reduction in seizure frequency. In this study, 79% of the cohort experienced side effects. The three most common adverse effects were somnolence (n=41 [25%]), decreased appetite (n=31 [19%]), and diarrhea (n=31 [19%]).72 It has to be pointed out that no control group existed in this study (e.g., placebo or another drug). It is therefore difficult to put the side effect frequency into perspective. Attributing the side effects to CBD is also not straightforward in severely sick patients. Thus, it is not possible to draw reliable conclusions on the causation of the observed side effects in this study.

Parkinson’s disease

In a study with a total of 21 Parkinson’s patients (without comorbid psychiatric conditions or dementia) who were treated with either placebo, 75 mg/day CBD or 300 mg/day CBD in an exploratory double-blind trial for 6 weeks, the higher CBD dose showed significant improvement of quality of life, as measured with PDQ-39. This rating instrument comprised the following factors: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. For the factor, “activities of daily living,” a possible dose-dependent relationship could exist between the low and high CBD group—the two CBD groups scored significantly different here. Side effects were evaluated with the UKU (Udvalg for Kliniske Undersøgelser). This assessment instrument analyzes adverse medication effects, including psychic, neurologic, autonomic, and other manifestations. Using the UKU and verbal reports, no significant side effects were recognized in any of the CBD groups.73

Huntington’s disease

Fifteen neuroleptic-free patients with Huntington’s disease were treated with either placebo or oral CBD (10 mg/kg b.w. per day) for 6 weeks in a double-blind, randomized, crossover study design. Using various safety outcome variables, clinical tests, and the cannabis side effect inventory, it was shown that there were no differences between the placebo group and the CBD group in the observed side effects.6

Immune system

Forty-eight patients were treated with 300 mg/kg oral CBD, 7 days before and until 30 days after the transplantation of allogeneic hematopoietic cells from an unrelated donor to treat acute leukemia or myelodysplastic syndrome in combination with standard measures to avoid GVHD (graft vs. host disease; cyclosporine and short course of MTX). The occurrence of various degrees of GVHD was compared with historical data from 108 patients, who had only received the standard treatment. Patients treated with CBD did not develop acute GVHD. In the 16 months after transplantation, the incidence of GHVD was significantly reduced in the CBD group. Side effects were graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0) classification, which did not detect severe adverse effects.74

Endocrine and glycemic (including appetite, weight gain) effects

In a placebo-controlled, randomized, double-blind study with 62 subjects with noninsulin-treated type 2 diabetes, 13 patients were treated with twice-daily oral doses of 100 mg CBD for 13 weeks. This resulted in lower resistin levels compared to baseline. The hormone resistin is associated with obesity and insulin resistance. Compared to baseline, glucose-dependent insulinotropic peptide levels were elevated after CBD treatment. This incretin hormone is produced in the proximal duodenum by K cells and has insulinotropic and pancreatic b cell preserving effects. CBD was well tolerated in the patients. However, with the comparatively low CBD concentrations used in this phase-2-trial, no overall improvement of glycemic control was observed.40

When weight and appetite were measured as part of a measurement battery for side effects, results were inconclusive. For instance, the study mentioned above, where 23 children with Dravet syndrome were treated, increases as well as decreases in appetite and weight were observed as side effects.2 An open-label trial with 214 patients suffering from treatment-resistant epilepsy showed decreased appetite in 32 cases. However, in the safety analysis group, consisting of 162 subjects, 10 showed decreased weight and 12 had gained weight.52 This could be either due to the fact that CBD only has a small effect on these factors, or appetite and weight are complex endpoints influenced by multiple factors such as diet and genetic predisposition. Both these factors were not controlled for in the reviewed studies.

Conclusion

This review could substantiate and expand the findings of Bergamaschi et al. about CBD favorable safety profile.1Nonetheless, various areas of CBD research should be extended. First, more studies researching CBD side effects after real chronic administration need to be conducted. Many so-called chronic administration studies, cited here were only a couple of weeks long. Second, many trials were conducted with a small number of individuals only. To perform a throrough general safety evaluation, more individuals have to be recruited into future clinical trials. Third, several aspects of a toxicological evaluation of a compound such as genotoxicity studies and research evaluating CBD effect on hormones are still scarce. Especially, chronic studies on CBD effect on, for example, genotoxicity and the immune system are still missing. Last, studies that evaluate whether CBD-drug interactions occur in clinical trials have to be performed.

In conclusion, CBD safety profile is already established in a plethora of ways. However, some knowledge gaps detailed above should be closed by additional clinical trials to have a completely well-tested pharmaceutical compound.

Abbreviations Used

AD Alzheimer’s disease
ARCI Addiction Research Center Inventory
BD bipolar disorder
BDI Beck Depression Inventory
CBD cannabidiol
HSP heat shock protein
IL interleukin
MRS Mood Rating Scale
PPI prepulse inhibition
ROS reactive oxygen species
SAFTEE Systematic Assessment for Treatment Emergent Events
STAI State Trait Anxiety Inventory
TSST Trier Social Stress Test
UKU Udvalg for Kliniske Undersøgelser
VAMS Visual Analogue Mood Scale
VAS Visual Analog Scales

Acknowledgments

The study was commissioned by the European Industrial Hemp Association. The authors thank Michal Carus, Executive Director of the EIHA, for making this review possible, for his encouragement, and helpful hints.

Author Disclosure Statement

EIHA paid nova-Institute for the review. F.G. is Executive Director of IACM.#

References

1. Bergamaschi MM, Queiroz RH, Zuardi AW, et al. Safety and side effects of cannabidiol, a Cannabis sativa constituentCurr Drug Saf. 2011;6:237–249 [PubMed]
2. Grotenhermen F, Müller-Vahl K. Cannabis und Cannabinoide in der Medizin: Fakten und AusblickSuchttherapie. 2016;17:71–76
3. Hampson AJ, Grimaldi M, Axelrod J, et al. Cannabidiol and Δ9-tetrahydrocannabinol are neuroprotective antioxidantsPNAS. 1998;95:8268–8273 [PMC free article] [PubMed]
4. Oláh A, Tóth BI, Borbíró I, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytesJ Clin Invest. 2014:124:3713. [PMC free article] [PubMed]
5. Deiana S, Watanabe A, Yamasaki Y, et al. Plasma and brain pharmacokinetic profile of Cannabidiol (CBD), cannabidivarine (CBDV), Delta (9)-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive compulsive behaviourPsychopharmacology. 2012;219:859–873[PubMed]
6. Consroe P, Laguna J, Allender J, et al. Controlled clinical trial of cannabidiol in Huntington’s diseasePharmacol Biochem Beh. 1991;40:701–708 [PubMed]
7. Bih CI, Chen T, Nunn AV, et al. Molecular targets of cannabidiol in neurological disordersNeurotherapeutics. 2015;12:699–730 [PMC free article] [PubMed]
8. Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic reviewDrug Metab Rev. 2014;46:86–95 [PubMed]
9. Fusar-Poli P, Crippa JA, Bhattacharyya S, et al. Distinct effects of D9-tetrahydro-cannabinoland cannabidiol on neural activation during emotional processingArch Gen Psychiat. 2009;66:9–5.[PubMed]
10. Manini AF, Yiannoulos G, Bergamaschi MM, et al. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humansJ Addict Med. 2014;9:204–210 [PMC free article] [PubMed]
11. Monographie NN. Cannabidiol. Deutscher Arzneimittel-Codex (DAC) inkl. Neues Rezeptur-Formularium (NRF). DAC/NRF October 22, 2015
12. Pelkonen O, Mäeenpäeä J, Taavitsainen P, et al. Inhibition and induction of human cytochrome P450 (CYP) enzymesXenobiotica. 1998;28:1203–1253 [PubMed]
13. Karlgren M, Bergström CA. How physicochemical properties of drugs affect their metabolism and clearance. In: New horizons in predictive drug metabolism and pharmacokinetics. Royal Society of Chemistry: Cambridge, UK, 2015
14. Ujváry I, Hanuš L. Human metabolites of cannabidiol: a review on their formation, biological activity, and relevance in therapyCannabis Cannabinoid Res. 2016;1:90–101
15. Bornheim LM, Everhart ET, Li J, et al. Induction and genetic regulation of mouse hepatic cytochrome P450 by cannabidiolBiochem Pharmacol. 1994;48:161–171 [PubMed]
16. Brzozowska N, Li KM, Wang XS, et al. ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in micePeer J. 2016;4:e208–1. [PMC free article] [PubMed]
17. Feinshtein V, Erez O, Ben-Zvi Z, et al. Cannabidiol enhances xenobiotic permeability through the human placental barrier by direct inhibition of breast cancer resistance protein: an ex vivo studyAm J Obstet Gynecol. 2013;209:573-e1 [PubMed]
18. Linge R, Jiménez-Sánchez L, Campa L, et al. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT 1A receptorsNeuropharmacology. 2016;103:16–26 [PubMed]
19. Schiavon AP, Bonato JM, Milani H, et al. Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed miceProg Neuropsychopharmacol. 2016;64:27–34 [PubMed]
20. Peres FF, Levin R, Almeida V, et al. Cannabidiol, among other cannabinoid drugs, modulates prepulse inhibition of startle in the SHR animal model: implications for schizophrenia pharmacotherapyFront Pharmacol. 2016;7:30–3. [PMC free article] [PubMed]
21. Gomes FV, Issy AC, Ferreira FR, et al. Cannabidiol attenuates sensorimotor gating disruption and molecular changes induced by chronic antagonism of NMDA receptors in miceJ Neuropsychopharmacol. 2015;18:pyu04–1. [PMC free article][PubMed]
22. Valvassori SS, Elias G, de Souza B, et al. Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of maniaJ Psychopharmacol. 2011;25:274–280 [PubMed]
23. Ren Y, Whittard J, Higuera-Matas A, et al. Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbancesJ Neurosci. 2009;29:14764–14769 [PMC free article][PubMed]
24. Sun S, Hu F, Wu J, Zhang S. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neuronsRedox Biol. 2017;11:577–585 [PMC free article] [PubMed]
25. Schurr A, Livne A. Differential inhibition of mitochondrial monoamine oxidase from brain by hashish componentsBiochem Pharmacol. 1976;25:1201–1203 [PubMed]
26. Alvarez FJ, Lafuente H, Rey-Santano MC. Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxicischemic newborn pigletsPediatr Res. 2008;64:653–658[PubMed]
27. Valvassori SS, Bavaresco DV, Scaini G. Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brainRev Bras Psiquiatr. 2013;35:380–386 [PubMed]
28. Scott KA, Dennis JL, Dalgleish AG, et al. Inhibiting heat shock proteins can potentiate the cytotoxic effect of cannabidiol in human glioma cellsAnticancer Res. 2015;35:5827–5837 [PubMed]
29. Burstein S. Cannabidiol (CBD) and its analogs: a review of their effects on inflammationBioorg Med Chem. 2015;23:1377–1385[PubMed]
30. McAllister SD, Soroceanu L, Desprez PY. The antitumor activity of plant-derived non-psychoactive cannabinoidsJ Neuroimmune Pharmacol. 2015;10:255–267 [PMC free article][PubMed]
31. Cheng D, Spiro AS, Jenner AM, et al. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic miceJ Alzheimers Dis. 2014;42:1383–1396 [PubMed]
32. Weiss L, Zeira M, Reich S, et al. Cannabidiol arrests onset of autoimmune diabetes in NOD miceNeuropharmacology. 2008;54:244–249 [PMC free article] [PubMed]
33. Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritisEur J Pain. 2015;20:936–948 [PMC free article] [PubMed]
34. Murase R, Limbad C, Murase R. Id-1 gene and protein as novel therapeutic targets for metastatic cancerCancer Res. 2012;72:530–8.
35. Paria BC, Das SK, Dey SK. The preimplantation mouse embryo is a target for cannabinoid ligand-receptor signalingPNAS. 1995;92:9460–9464 [PMC free article] [PubMed]
36. Leanza L, Managò A, Zoratti M, et al. Pharmacological targeting of ion channels for cancer therapy: in vivo evidencesBiochim Biophys Acta. 2016;1863:1385–1397 [PubMed]
37. Ramer R, Merkord J, Rohde H, et al. Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1Biochem Pharmacol. 2010;79:955–966[PubMed]
38. Ramer R, Bublitz K, Freimuth N. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1FASEB J. 2012;26:1535–1548 [PubMed]
39. Benhamou Y. Gene and protein as novel therapeutic targets for metastatic cancer. Available at www.marschallplan.at (accessed on October1, 2016)
40. McAllister SD, Christian RT, Horowitz MP. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cellsMol Cancer Ther. 2007;6:2921–2927 [PubMed]
41. De Petrocellis L, Ligresti A, Schiano Moriello A, et al. Non-Δ9-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanismsBr J Pharmacol. 2013;168:79–102 [PMC free article] [PubMed]
42. Fowler CJ. Delta9-tetrahydrocannabinol and cannabidiol as potential curative agents for cancer: a critical examination of the preclinical literaturePharmacol Ther. 2015;97:587–596 [PubMed]
43. Aviello G, Romano B, Borrelli F, et al. Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancerJ Mol Med. 2012;90:925–934 [PubMed]
44. Jadoon KA, Ratcliffe SH, Barrett DA. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot studyDiabetes Care. 2016;39:1777–1786 [PubMed]
45. Watanabe K, Motoya E, Matsuzawa N, et al. Marijuana extracts possess the effects like the endocrine disrupting chemicalsToxicology. 2005;206:471–478 [PubMed]
46. Narimatsu S, Watanabe K, Yamamoto I. Inhibition of hepatic microsomal cytochrome P450 by cannabidiol in adult male ratsChem Pharm Bull. 1990;38:1365–1368 [PubMed]
47. Jones NA, Hill AJ, Smith I, et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivoJ Pharm Ex Ther. 2010;332:569–577 [PMC free article] [PubMed]
48. Jones NA, Glyn SE, Akiyama S, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizuresSeizure. 2012;21:344–352 [PubMed]
49. Fasinu PS, Phillips S, ElSohly MA, et al. Current status and prospects for cannabidiol preparations as new therapeutic agentsPharmacotherapy. 2016;36:781–796 [PubMed]
50. Persson A, Ingelman-Sundberg M. Pharmacogenomics of cytochrome P450 dependent metabolism of endogenous compounds: implications for behavior, psychopathology and treatmentJ Pharmacogenomics Pharmacoproteomics 2014;5:12–7.
51. Ghosh C, Hossain M, Solanki J, et al. Pathophysiological implications of neurovascular P450 in brain disordersDrug Discov Today. 2016;21:1609–1619 [PMC free article] [PubMed]
52. Brunt TM, van Genugten M, Höner-Snoeken K, et al.Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabisJ Clin Psychopharmacol. 2014;34:344–349 [PubMed]
53. Das RK, Kamboj SK, Ramadas M, et al. Cannabidiol enhances consolidation of explicit fear extinction in humansPsychopharmacology. 2013;226:781–792 [PubMed]
54. Bhattacharyya S, Morrison PD, Fusar-Poli P, et al. Opposite effects of Δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathologyNeuropsychopharmacology. 2010;35:764–774 [PMC free article] [PubMed]
55. Martin-Santos R, Crippa J, Batalla A. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) administration in healthy volunteersCurr Pharm Des. 2012;18:4966–4979 [PubMed]
56. Crippa JAS, Hallak JEC, Machado-de-Sousa JP, et al.Cannabidiol for the treatment of cannabis withdrawal syndrome: a case reportJ Clin Pharm Ther. 2013;38:162–164 [PubMed]
57. Morgan CJ, Freeman TP, Schafer GL. Cannabidiol attenuates the appetitive effects of Δ9-tetrahydrocannabinol in humans smoking their chosen cannabisNeuropsychopharmacology. 2010;35:1879–1885 [PMC free article] [PubMed]
58. Hurd YL, Yoon M, Manini AF. Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stageNeurotherapeutics. 2015;12:807–815 [PMC free article] [PubMed]
59. Morgan CJ, Das RK, Joye A, et al. Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findingsAddictive Behav. 2013;38:2433–2436 [PubMed]
60. Zuardi AW, Guimaraes FS, Moreira AC. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteersBraz J Med Biol Res. 1993;26:213–217 [PubMed]
61. Appiah-Kusi E, Mondelli V, McGuire P, et al. Effects of cannabidiol treatment on cortisol response to social stress in subjects at high risk of developing psychosisPsychoneuroendocrinology. 2016;7(Supplement):23–24
62. Geffrey AL, Pollack SF, Bruno PL, et al. Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsyEpilepsia. 2015;56:1246–1251 [PubMed]
63. Grotenhermen F, Gebhardt K, Berger M. Cannabidiol. Nachtschatten Verlag: Solothurn, Switzerland, 2016
64. Mincis M, Pfeferman A, Guimarães RX. Chronic administration of cannabidiol in man. Pilot studyAMB Rev Assoc Med Bras.1973;19:185–190 [PubMed]
65. Cunha J, Carlini EA, Pereira AE, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patientsPharmacology. 1980;21:175–185 [PubMed]
66. Zuardi AW, Crippa JAS, Hallak JEC, et al. Cannabidiol for the treatment of psychosis in Parkinson’s diseaseJ Psychopharmacol. 2009;3:979–983 [PubMed]
67. Leweke FM, Piomelli D, Pahlisch F. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophreniaTransl psychiatry. 2012;2:e9–4. [PMC free article][PubMed]
68. Leweke F, Koethe D, Gerth C. Cannabidiol as an antipsychotic: a double-blind, controlled clinical trial of cannabidiol versus amisulpiride in acute schizophrenia. In: 15th annual symposium on cannabinoids Cannabinoid Research Society: Clearwater Beach, FL, 2005
69. Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humansSchizophr Res. 2015;162:153–161 [PubMed]
70. Zuardi AW, Crippa JAS, Dursun SM, et al. Cannabidiol was ineffective for manic episode of bipolar affective disorderJ Psychopharmacol. 2010;24:135–137 [PubMed]
71. Braga RJ, Abdelmessih S, Tseng J, et al. Cannabinoids and bipolar disorder. Cannabinoids in neurologic and mental disease. Elsevier, Amsterdam, 2015, p. 205
72. Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trialLancet Neurol. 2016;15:270–278 [PubMed]
73. Chagas MHN, Zuardi AW, Tumas V, et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trialJ Psychopharmacol. 2014;28:1088–1098 [PubMed]
74. Yeshurun M, Shpilberg O, Herscovici C, et al. Cannabidiol for the prevention of graft-versus- host-disease after allogeneic hematopoietic cell transplantation: results of a phase II studyBiol Blood Marrow Transplant. 2015;21:1770–1775 [PubMed]
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/
June 2017

MS Society says there is sufficient evidence of drug’s effectiveness to relax ban for patients with no other options

Ten thousand people with multiple sclerosis in the UK should be allowed to use cannabis legally in order to relieve their “relentless and exhausting” symptoms, experts in the disease have told ministers.

The MS Society claims the one in 10 sufferers of the condition whose pain and spasticity cannot be treated by medication available on the NHS should be able to take the drug without fear of prosecution.

The evidence on cannabis’s effectiveness, while not conclusive, is now strong enough that the government should relax the ban on the drug for MS patients who have no other treatment options, the society says in a report.

Doctors who treat MS patients have backed the society’s call, as have the Liberal Democrats and the Green party. Legalisation would ease “the extremely difficult situation in which many people with MS find themselves”, the charity said.

The society is calling for the first time for the 10,000 patients – one in 10 of the 100,000 people in Britain with MS – to be able to access cannabis without fear of arrest. It has changed its position after reviewing the evidence, consulting its medical advisers and seeking the views of 3,994 people who have the condition.

“We think cannabis should be legalised for medicinal use for people with MS to relieve their pain and muscle spasms when other treatments haven’t worked,” said Genevieve Edwards, the MS Society’s director of external affairs.

“The level of clinical evidence to support cannabis’s use for medicinal purposes is not conclusive. But there is sufficient evidence for our medical advisers to say that on the balance of probability, cannabis could benefit many people with MS experiencing pain and muscle spasms.” The charity is also urging NHS bosses to make Sativex, a cannabis-based drug used by some people with MS, available on prescription across the UK so that patients who can afford it no longer have to acquire it privately, at a cost of about £2,000 a year. Wales is the only home nation to provide the mouth spray through the NHS.

Patients’ inability to access Sativex on the NHS in England, Scotland and Northern Ireland “has resulted in many people with MS turning to illegal forms of cannabis as an alternative. It’s simply not right that some people are being driven to break the law to relieve their pain and spasticity. It’s also really risky when you’re not sure about the quality or dosage of what you’re buying,” Edwards said.

Norman Lamb, the Lib Dem health spokesman, said: “This is the strongest proof yet that the existing law on cannabis is a huge injustice that makes criminals of people whose only crime is to be in acute pain. This draconian law is potentially opening anything up to 10,000 MS sufferers to prosecution, and underlines why the Liberal Democrats have braved a tabloid backlash to campaign for the legalisation of cannabis. It is about time the government listened to the science.”

One in five (22%) MS patients who took part in a survey by the society said they had used cannabis to help manage their symptoms, but only 7% were still doing so. A quarter (26%) of those who had stopped taking it said they had done so out of fear of

prosecution. Another 26% of respondents had considered trying cannabis but had not done so for the same reason and also because they were concerned about the drug’s safety.

Doctors are divided over cannabis’s potential role in treating MS. Some are supportive while others are anxious about endorsing the use of a drug that can cause psychiatric problems. The Royal College of GPs said it was currently drawing up policy on the issue and could not comment. The Royal College of Physicians, which represents hospital doctors, said it had no policy on the issue.

Dr Willy Notcutt, a pain management specialist at the James Paget hospital in Norfolk, who has been treating MS patients for more than 20 years, said: “Every week I come across patients wishing to use cannabis to control their symptoms but who are unable to get proven drugs like Sativex from the NHS. Many patients seek illegal cannabis to get help. They can’t be sure of its origin but are being forced to commit a criminal act in order to obtain relief.”

Dr Waqar Rashid, a consultant neurologist at Brighton and Sussex University Hospitals NHS trust, said: “[Cannabis is] not a cure-all, and there are other treatments that should be tried first. But it makes sense for criminality not be a barrier to a treatment which could reduce the debilitating impact of symptoms and transform someone’s quality of life.”

Caroline Lucas, the Green party co-leader and its sole MP, said: “The MS Society’s new position is a big step forward, and recognises the fact that thousands of people with MS could benefit from the the use of medicinal cannabis. By rigidly sticking to criminalising cannabis the government drives MS sufferers to illegally acquire the drugs, thus putting themselves as risk of prosecution simply for searching for pain relief.” The National Institute for Health and Clinical Excellence (Nice), which advises the government, has told the NHS not to prescribe Sativex for spasticity because it is not cost-effective. The Home Office said: “This government has no plans to legalise cannabis. Cannabis is controlled as a Class B drug under the Misuse of Drugs Act 1971 and, in its raw form, currently has no recognised medicinal benefits in the UK.”

Case study: Steven Colborn, 55, from Seaham, County Durham

Imagine running a marathon while sharp pain darts up and down your legs. This is what multiple sclerosis feel like for me. When muscle spasticity kicks in my legs just twist and turn and bend back on themselves and it’s excruciatingly painful.

But three years ago I was offered a treatment that could help. During a regular appointment, a specialist nurse said they had managed to get a month’s supply of Sativex, a drug derived from cannabis, from the manufacturer.

The results were incredible. My muscle tension eased and I started to feel my legs moving better. I was able to get a good night’s sleep. I could exercise without getting as tired as quickly. For the first time in a long time I felt that I was managing my condition.

My month’s supply ran out and the drug wasn’t available free on the NHS. I was offered a muscle relaxer called Baclofen which hadn’t worked for me in the past.

I have been forced to pay for this drug myself. I can’t work any more so I rely on disability benefits. I have to save up a lot of money to be able to afford it – it costs £412 a month. Over the past four years I’ve only managed to buy about seven months’ worth.

I take Sativex but other people get similar relief from cannabis in its pure form. I don’t like taking this myself because of the narcotic effect, which you don’t get with Sativex. But for those it helps, it should be made legal.

I have had this illness for 36 years and every day I wake up and think ‘maybe there has been a breakthrough’. I know there will never be a cure, but I am just looking for a way to make things easier. Now I have been presented with something that offers me hope and the NHS say they cannot afford it. My question is: can you afford people like me getting worse?

Source:  https://www.theguardian.com/society/2017/jul/27/legalise-cannabis-as-treatment-of-last-resort-for-multiple-sclerosis-says-charity

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Comments by  NDPA:

UK  is 1st world nation with 1st world medicine approval system, even then we get things wrong e.g Thalidomide.

Cannabis based medicine is no problem if it goes through that system.

Sadly, ill people have been and are being exploited by the drug legalisation lobby, in furtherance of their nirvana of recreational cannabis for all.

Cannabis is a very harmful psychoactive drug, it induces dependency in around 1 in 9 or 10 users. It has numerous bad effects.

Smoking is obviously not a sensible delivery system for medication, yet a lot of those complaining want to smoke cannabis.

Cannabis based drugs like Sativex are in the pharmacopeia thanks to the wise licensing of the research on them by successive UK governments.

The mechanisms by which those cannabis based drugs are made available to  specific MS sufferers are a matter for the relevant authorities who deal with all pharmaceutical drugs. They must show efficacy and they must satisfy NICE.

There are no grounds at all for making cannabis any sort of special case, in fact the recreational user base and the legalisation lobby distort the arguments and would be better remaining silent.

SAN FRANCISCO – Visits by teens to a Colorado children’s hospital emergency department and its satellite urgent care centers increased rapidly after legalization of marijuana for commercialized medical and recreational use, according to new research being presented at the 2017 Paediatric Academic Societies Meeting in San Francisco.

The study abstract, “Impact of Marijuana Legalization in Colorado on Adolescent Emergency Visits” on Monday, May 8 at the Moscone West Convention Center in San Francisco.

Colorado legalized the commercialization of medical marijuana in 2010 and recreational marijuana use in 2014. For the study, researchers reviewed the hospital system’s emergency department and urgent care records for 13- to 21-year-olds seen between January 2005 and June 2015.

They found that the annual number of visits with a cannabis related diagnostic code or positive for marijuana from a urine drug screen more than quadrupled during the decade, from 146 in 2005 to 639 in 2014.

Adolescents with symptoms of mental illness accounted for a large proportion (66%) of the 3,443 marijuana-related visits during the study period, said lead author George Sam Wang, M.D., FAAP, with psychiatry consultations increasing from 65 to 442. More than half also had positive urine drug screen tests for other drugs. Ethanol, amphetamines, benzodiazepines, opiates and cocaine were the most commonly detected.

Dr. Wang, an assistant professor of paediatrics at the University of Colorado Anschutz Medical Campus, said national data on teen marijuana use suggest rates remained roughly the same (about 7%) in 2015 as they’d been for a decade prior, with many concluding no significant impact from legalization. Based on the findings of his study, however, he said he suspects these national surveys do not entirely reflect the effect legalization may be having on teen usage.

“The state-level effect of marijuana legalization on adolescent use has only begun to be evaluated,” he said. “As our results suggest, targeted marijuana education and prevention strategies are necessary to reduce the significant public health impact of the drug can have on adolescent populations, particularly on mental health.”

Dr. Wang will present the abstract, “Impact of Marijuana Legalization in Colorado on Adolescent Emergency Department (ED) Visits,” from 8 a.m. to 10 a.m. Numbers in this news release reflect updated information provided by the researchers. The abstract is available at https://registration.pas-meeting.org/2017/reports/rptPAS17_abstract.asp?abstract_final_id=3160.11.

The Paediatric Academic Societies (PAS) Meeting brings together thousands of individuals united by a common mission: to improve child health and well-being worldwide. This international gathering includes paediatric researchers, leaders in academic paediatrics, experts in child health, and practitioners. The PAS Meeting is produced through a partnership of four organizations leading the advancement of paediatric research and child advocacy: Academic Paediatric Association, American Academy of Paediatrics, American Paediatric Society, and Society for Paediatric Research. For more information, visit the PAS Meeting online at www.pas-meeting.org, follow us on Twitter @PASMeeting and #pasm17, or like us on Facebook. For additional AAP News coverage, visit http://www.aappublications.org/collection/pas-meeting-updates.

Source:   http://www.aappublications.org/news/2017/05/04/PASMarijuana050417

How do you know when you are being softened up for something? One sure sign is when what you are being asked to give your support to is sold to you as entirely unproblematic or as a panacea to a host of problems. Never believe it.

My antennae began twitching when the latest round in the campaign for legalised ‘medical cannabis’ began back last autumn. The instigator was the All Party Parliamentary Group for Drugs Policy Reform chaired by one Baroness Molly Meacher and its ammunition a misleading and derivative report: Accessing Medicinal Cannabis: Meeting Patients’ Needs.

With a general election under way it seems the good Baroness and her backers have decided to give their ‘medipot’ campaign another crack of the whip, ever hopeful of a change of government heart over legalising so-called medicinal cannabis.

What could be wrong with that, I hear you ask. Well, if I was sceptical about the stated purpose of this report when it was first published, I am even more so this time. Why? First, because the case for medicinal cannabis is based on a false premise, which the recent licensing of cannabidiol demonstrates again. Second, the scientific research on its efficacy doesn’t stack up too well. And third, there no safe way of using the unprocessed plant for recreational let alone medical purposes.

To recap, contrary to received wisdom, no one has stopped or is stopping  the scientific study of the chemicals in cannabis for medicinal purposes. Two approved cannabis-derived medications, Marinol and Sativex, exist already and a third, Epidiolex is undergoing clinical trials at the moment. In addition to this, the non psycho-active CBD or cannabidiol has been approved by Britain’s medicines regulatory authority, the MHRA, and the compound is now to be licensed and regulated as a medicine. Evidence of the efficacy of the derived compounds of cannabis for the wide range of symptoms they have been tested on is at best weak. This is what a dispassionate systematic research review conducted by the American Academy of Neurology and endorsed by the American Autonomic Society, the American Epilepsy Society, the Consortium of Multiple Sclerosis Centers, the International Organization of Multiple Sclerosis Nurses, and the International Rett Syndrome Foundation, shows.

There are indisputable  scientific and safety reasons for why the whole unprocessed cannabis plant is not and will never be approved as a medicine; that’s unless we chose to revert to medieval quackery and throw all scientific and safety advances  out of the window. It is not just that cannabis risks (addiction, psychosis, cancer, impaired cognitive functioning, to name but some) outweigh any possible benefits, but that as a natural ‘herb’ it is untested for pathogens and bacteria. Who is their right mind would chose mould over an approved antibiotic? And where is the luminary who thinks smoking is a sensible medication delivery system? – which how most cannabis users chose to ingest the weed.

But rational science hasn’t stopped the medipot activists in their tracks. Over the last few months they’ve been relentlessly pressing their victimhood status on the media and the inequity they suffer of not having a free and easy access to their preferred untested drug, i.e. dope.  They have really been doing rather well at convincing the media of their non-existent problem. The Daily Mail even fell for it this week, reiterating the campaigners’ victim meme of being sick people unjustly prosecuted by harsh and uncompromising authorities for the crime of tending to their pain when, in fact, it is the regulatory authorities who are protecting people from poisoning themselves. No wonder Baroness Meacher, chair of the aforesaid APPG, sounded so triumphant on the airwaves yesterday as she pushed the case for medipot to an all believing radio host. Even the Mail (all that has stood between us and drugs legalisation, she as much as said) had finally written a balanced article on the topic, she crowed.

She herself certainly was not balanced. I cannot make up my mind, given her ‘economy with truth’ regarding drug statistics on previous occasions that I have taken her up on, here, and here whether the Baroness is just daft and deluded, genuinely ingenuous, or, more worryingly, actively disingenuous. Running true to form, Baroness Meacher failed in her interview (go to circa one hour, 6 minutes into the programme) to either mention the medicines approval system or the recent licensing of cannabidiol as a medicine.  She also misled the public, deliberately it seemed, by giving the impression that the UK government has actively frustrated cannabis-based research when it hasn’t. In fact, the opposite is the case, as drugs policy analyst David Raynes made clear on the same programme.  The UK government broke ground when it licensed research into cannabis in 1998.

In the  absence of research, her spurious argument went, there remains a medical need for public access to the raw cannabis plant and therefore an end to its classification as a harmful recreational drug. There we had it.

The truth is that the APPG on Drugs Policy Reform she chairs is hardly an independent or dispassionate body. It is funded by The Open Society, which is in turn is a George Soros front. According to the Washington Times (Source: www.washingtontimes.com 2nd April 2014) this is the billionaire philanthropist who, with a cadre of like-minded, wealthy donors, has dominated the pro-legalisation side of the marijuana debate in the US by funding grass-roots movements in every state. No wonder so many capitulated.  Through a network of nonprofit groups,  Mr. Soros has spent at least $80 million on these drugs legalisation efforts since 1994. And more in the last three years. I fear the APPG’s effort (ably backed by Nick Clegg who also seems oblivious to the relationship between cannabis and mental illness) is but the latest in a line of such campaigns whose objective is effectively to legalise recreational cannabis. These go back to 1979 when Keith Stroup of NORML, the group “that speaks for pot users’ originally admitted that medipot was  a red herring to get pot a good name.  More recently he revealed that he was not too keen on cannabis compounds being subjected to scientific drug research trials. He said that the “pharmaceuticalisation” of cannabis was a battleground to be fought in order to protect ‘the options of patients’ – to smoke dope as it is.

I wonder if this too is why Meacher is so reluctant to give a full account of cannabis research and medical regulation? It rather pulls her medi-pot carpet from under her feet.

Source:  http://www.conservativewoman.co.uk/kathy-gyngell-the-push-for-medipot-remains-a-push-for-pot/   May 2017

As part of the ongoing efforts of the International Narcotics Control Board (INCB) to raise awareness of key issues relevant to international drug control, I have the pleasure to share with you three short texts:

* Application of principle of proportionality for drug-related offences

* Ensuring availability of narcotic drugs for medical purposes

* Carrying by international travellers of small quantities of preparations containing controlled substances

Application of principle of proportionality for drug-related offences

  1. The application of the principle of proportionality in the context of drug offences is a key aspect of a sound and effective drug policy. Some States have made extensive use of incarceration of low-level drug offenders, despite the fact that this approach is not mandated by the international drug control treaties, and some have even applied extrajudicial responses to drug-related offences, notwithstanding the fact that such actions are contrary to the treaties. It is essential to distinguish between the criminal justice provisions contained within the Conventions1,2,3, and the criminal justice policy measures which have been taken by some Governments.
  2. Implementation of the international treaties is subject to the internationally recognized principle of proportionality, which requires that a State’s treatment of illegal behaviour to be proportionate and that a punishment in response to criminal offences should be proportionate to the seriousness of the crime.
  3. The INCB has repeatedly called upon States to give due regard to the principle of proportionality in the elaboration and implementation of criminal justice policy in their efforts to address drug-related crime.
  4. While the choice of legislative or policy measures to address drug-related crime, including the determination of sanctions is the prerogative of States, the international drug control treaties require that these sanctions should be adequate and proportionate, taking into account the gravity of the offence and the degree of responsibility of the alleged offender.
  5. The international drug control treaties do not automatically require the imposition of conviction and punishment for drug-related offences, including those involving the possession, purchase or cultivation of illicit drugs, in appropriate cases of minor nature or when committed by drug users. While “serious offences shall be liable to adequate punishment, particularly by imprisonment or other penalties of deprivation of liberty”, offences of a minor or lesser gravity need not necessarily be subject to harsh criminal sanctions, such as incarceration. The Conventions afford discretion for Parties to provide, either as an alternative to conviction and punishment or in addition to conviction and punishment, that drug users undergo measures of treatment, education, after-care, rehabilitation and social reintegration.

*

Ensuring availability of narcotic drugs for medical purposes

  1. Some decades ago the international community made a solemn commitment with the SingleConvention on Narcotic Drugs of 1961 and the Convention on Psychotropic Substances of 1971: to ensure the availability, to make adequate provision and not to unduly restrict the availability of drugs that were considered indispensable for medical and scientific purposes. Over the past decades that promise has not been fully met. . Too many people suffer or die in pain or do not have access to the medications they need. Unnecessary suffering because of the lack of appropriate medication due to the inaction, lack of know-how or unnecessary administrative requirements is a scandal that shames us all.
  2. Around 5.5 billion people still have limited or no access to medicines containing narcotic drugs such as codeine or morphine, leaving 75 per cent of the world population without access to proper pain relief treatment. Around 92 per cent of morphine used worldwide is consumed by only 17 per cent of the world population, primarily living in the United States, Canada, Western Europe, Australia and New Zealand. Inadequate access violates the notion of article 25 of the Universal Declaration of Human Rights, including the Right to medical care, which also encompasses palliative care.
    1. This situation is caused by a variety of factors, including health care professionals, that meansThe imbalance in the availability of opioid analgesics is particularly worrying as the latest data show that many of the conditions requiring pain management, particularly cancer, are prevalent and increasing in low- and middle-income countries.doctors and nurses, not receiving adequate education and training as part of their professional education, lack of know-how and capacity of government authorities, concerns about overprescribing and addiction and overly onerous regulatory and administrative requirements. Many patients in most of the countries in Africa, Central America and the Caribbean, and South Asia are affected, but patients in other parts of the world are also affected.
    2. Concrete steps and rapid action by Member States, the international community and the pharmaceutical industry can go a long way to remedy the situation. The most important and urgent actions would involve providing specialised training for health care professionals enabling them to prescribe and administer pain medication as well as training for the competent national authorities.
    3. Governments must bring about partnerships with the pharmaceutical industry, which has a duty to act in a socially responsible manner, to ensure access to and availability of affordable medications, placing emphasis on generics.
    4. Governments need also ensure that the training curricula of doctors and nurses contain, ab initio, content on the prescribing and rational use of medicines containing controlled substances.
    5. At the same time, where necessary, legislation and regulations should be revised, prescribing practices brought up to day and the capacity of national agencies involved strengthened.
    6. If Governments, together with the relevant international agencies, were to put together a sufficiently well-resourced plan of action, Member States would be on their way to significantly contributing towards achieving a major element of Sustainable Development Goal 3 on Ensuring healthy lives and promote wellbeing for all at all ages.

 

Carrying by international travellers of small quantities of preparations containing narcotic drugs and psychotropic substances for personal medical use

  1. The Board’s continuing endeavour to assist travellers carrying small quantities of controlled substances for personal medical use across international borders gained, both, high visibility and prominent usefulness.
  2. An ever increasing inflow of queries from individual travellers and organizations on the aforementioned subject has been observed. The secretariat regularly receives requests for assistance and/or clarification of the applicable national rules and regulations. The requests come from organizations and individual travellers residing in various countries. In 2016, requests came from Australia, France, Italy, United Kingdom, and the United States; their countries of interest included Cambodia, Canada, Colombia, France, Germany, Guinea Bissau, Malaysia, Saudi Arabia, Thailand, Turkey and the USA.
  3. Several requests relate to common rules and regulations of the European Union and the Schengen area. The substances referenced in the queries included psychotropic substances listed in Schedules II, III and IV such as amfetamine, alprazolam, buprenorphine, dextroamphetamine, diazepam, methylphenidate, nitrazepam, tramadol, zolpidem and others that are not under international control.
  4. Since 2013, the information furnished by Governments on national requirements for travellers under medical treatment carrying preparations containing narcotic drugs or psychotropic substances under international control has been summarized in a standardized table format and made available in six official UN languages on INCB website.
  5. To date, such information is available for 109 Governments (up from 79 in May 2014)and is uploaded to the Board’s webpage, more than half are already available in the form of standardized tables translated into six official UN languages:http://www.incb.org/incb/en/psychotropic-substances/travellers_country_regulations.html
  6. In September 2016, given the increasing interest in this pertinent information, inparticular the international guidelines for national regulations concerning travellers under treatment with internationally controlled drugs, and the compilation of standardized summary tables of regulations by country, the secretariat sent out a reminder letter to all countries and territories, requesting all Governments to visit the above website and to inform the Board if the information pertaining to their countries accurately reflects current provisions of their national laws and regulations.
    1. The Governments that have not yet furnished any information were requested to

    provide the requisite description of all relevant legal/regulatory or administrative measures

    adopted to allow travellers entering/leaving the country to carry medical preparations

    containing controlled substances for personal medical use. In addition to full texts of relevant

    pieces of information, these Governments were also requested to fill in and to submit to the

    Board the standardized summary tables that were attached to the circular letter.

    1. The secretariat will continue to augment the list of national rules and regulations

    pertaining to travellers carrying internationally controlled substances for personal medical use,

    provide requisite assistance and attend to all inquiries in this regard.

    Source:  http://www.incb.org/incb/en/news/alerts.html

    INCB is the independent, quasi-judicial body charged with promoting and monitoring Government compliance with the three international drug control conventions: the 1961 Single Convention on Narcotic Drugs, the 1971 Convention on Psychotropic Substances, and the 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

 

 

 

 

 

I totally agree that we all need to let Attorney General Jeff Sessions know that the majority of Americans suffer because of marijuana …. whether they choose to use it or not.  It is a factor in crime, physical and mental health, academic failure, lost productivity, et al.  American cannot be great again if we continue to allow poison to be grown and distributed to the masses.

The President has taken a position that “medical marijuana” should be a State’s right, because he is not yet enlightened on the reality of what that means.  If asked to define “medical marijuana” that has helped his friends, I doubt that he would say gummy bears, Heavenly brownies and other edibles with 60 to 80% potency, sold in quantities that are potentially lethal; smoked pot at 25% THC content; or waxes and oils used for dabbing and vaping that are as high as 98% potency that cause psychotic breaks, mental illness, suicides, traffic deaths and more.

Further, if states are to have a right to offer “medical marijuana”, it has to be done under tightly controlled conditions and the profit motive eliminated.  Privately owned cultivation and dispensaries must be banned … including one’s ability to grow 6 plants at home.  6 plants grown hydroponically with 4 harvests a year could generate 24 lbs of pot, the equivalent of about 24,000 joints. That obviously would not be for personal use.  We would just have thousands of new drug dealers, with more crime, more child endangerment, more BHO labs blowing up, more traffic deaths, et al.

Source:   Letter from Roger Morgan to DrugWatch International  Feb. 2017

GW intends to advance oncology research and development efforts

GW Pharmaceuticals plc (Nasdaq:GWPH) (“GW,” “the Company” or “the Group”), a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, today announced positive top-line results from an exploratory Phase 2 placebo-controlled clinical study of a proprietary combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) in 21 patients with recurrent glioblastoma multiforme, or GBM. GBM is a particularly aggressive brain tumour, with a poor prognosis. GW has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for THC:CBD in the treatment of glioma.

The study showed that patients with documented recurrent GBM treated with THC:CBD had an 83 percent one year survival rate compared with 53 percent for patients in the placebo cohort (p=0.042). Median survival for the THC:CBD group was greater than 550 days compared with 369 days in the placebo group. THC:CBD was generally well tolerated with treatment emergent adverse events leading to discontinuation in two patients in each group. The most common adverse events (three patients or more and greater than placebo) were vomiting (75%), dizziness (67%), nausea (58%), headache (33%), and constipation (33%). The results of some biomarker analyses are still awaited.

“The findings from this well-designed controlled study suggest that the addition of a combination of THC and CBD to patients on dose-intensive temozolomide produced relevant improvements in survival compared with placebo and this is a good signal of potential efficacy,” said Professor Susan Short, PhD, Professor of Clinical Oncology and Neuro-Oncology at Leeds Institute of Cancer and Pathology at St James’s University Hospital and principal investigator of the study. “Moreover, the cannabinoid medicine was generally well tolerated. These promising results are of particular interest as the pharmacology of the THC:CBD product appears to be distinct from existing oncology medications and may offer a unique and possibly synergistic option for future glioma treatment.”

We believe that the signals of efficacy demonstrated in this study further reinforce the potential role of cannabinoids in the field of oncology and provide GW with the prospect of a new and distinct cannabinoid product candidate in the treatment of glioma.

These data are a catalyst for the acceleration of GW’s oncology research interests and over the coming months, we expect to consult with external experts and regulatory agencies on a pivotal clinical development program for THC:CBD in GBM and to expand our research interests in other forms of cancer.

The study, designed to evaluate a number of safety and efficacy endpoints, comprised an initial phase where the safety of THC:CBD in combination with dose-intense temozolomide (an oral alkylating agent that is a standard first-line treatment for GBM) was assessed in 2 cohorts of 3 patients each.  Following a satisfactory independent safety evaluation, the study then entered a randomized placebo-controlled phase where 12 patients were randomized to THC:CBD as add-on therapy compared with 9 patients randomized to placebo (plus standard of care).

Beginning in 2007 and prior to initiating this study, GW conducted substantial pre-clinical oncologic research on several cannabinoids in various forms of cancer including brain,

lung, breast, pancreatic, melanoma, ovarian, gastric, renal, prostate and bladder. These studies have resulted in approximately 15 publications and show the multi-modal effects of cannabinoids on a number of the key pathways associated with tumour growth and progression. Cannabinoids have been shown to promote autophagy (the process of regulated self-degradation by cells) via several distinct mechanisms, including acting on the AKT/mTOR pathway, an important intracellular signalling pathway that is overactive in many cancers.

In glioma, THC and CBD appear to act via distinct signalling pathways. The combination of THC and CBD showed good efficacy in various animal models of glioma, particularly when used in combination with temozolomide. Initial in vitro studies showed that the combined administration of THC and CBD led to a synergistic reduction in the viability of U87MG glioma cells when compared to the administration of each cannabinoid individually. The co-administration of temozolomide with THC and CBD had further synergistic effects, causing a significant reduction in cell viability. These pre-clinical studies justified the initiation of the Phase 2 clinical study.

GW’s portfolio of intellectual property related to the use of cannabinoids in oncology includes a number of issued patents and pending applications in both the U.S. and Europe. This portfolio is designed to protect the use of various cannabinoids individually or in combination, in the treatment of a variety of oncology-specific disorders and product formulations.

About GBM

Gliomas are tumours that arise from glial cells mainly in the brain but can also be found within the spinal cord. Within the category of Glioma there are multiple different tumor types. GBM is the most common Glioma and is one of the most common primary brain tumors, accounting for 15.6% of all primary brain tumors (Ostrom et al. 2013). They are also the most aggressive with only 28.4% of patients surviving one year and only 3.4% surviving to year five (Brodbelt et al. 2015). Studies of patients with high-grade gliomas showed that headache was the most common initial presenting symptom. These headaches can be persistent lasting more than six months and are often associated with other symptoms, including seizures, visual disturbances, cognitive impairment and nausea and vomiting depending on the location and growth rate of the tumor.

About GW Pharmaceuticals plc

Founded in 1998, GW is a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform in a broad range of disease areas. GW is advancing an orphan drug program in the field of childhood epilepsy with a focus on Epidiolex® (cannabidiol), which is in Phase 3 clinical development for the treatment of Dravet syndrome, Lennox-Gastaut syndrome, Tuberous Sclerosis Complex and Infantile Spasms. GW commercialized the world’s first plant-derived cannabinoid prescription drug, Sativex® (nabiximols), which is approved for the treatment of spasticity due to multiple sclerosis in 31 countries outside the United States. The Company has a deep pipeline of additional cannabinoid product candidates which includes compounds in Phase 1 and 2 trials for glioma, schizophrenia and epilepsy. For further information, please visit www.gwpharm.com.

Original press release: http://ir.gwpharm.com/releasedetail.cfm?ReleaseID=1010672

Source:  https://www.newcannabisventures.com/gw-pharma  17th Feb. 2017

Currently, 29 states and Washington, DC, have passed laws to legalize medical marijuana. Although evidence for the effectiveness of marijuana or its extracts for most medical indications is limited and in many cases completely lacking, there are a handful of exceptions. For example, there is increasing evidence for the efficacy of marijuana in treating some forms of pain and spasticity, and 2 cannabinoid medications (dronabinol and nabilone) are approved by the US Food and Drug Administration for alleviating nausea induced by cancer chemotherapy.

A systematic review and meta-analysis by Whiting et al1 found evidence, although of low quality, for the effectiveness of cannabinoid drugs in the latter indication. The anti -nausea effects of tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, are mediated by the interactions of THC with type cannabinoid (CB1) receptors in the dorsal vagal complex. Cannabidiol, another cannabinoid in marijuana, exerts antiemetic properties through other mechanisms. Nausea is a medically approved indication for marijuana in all states where medical use of this drug has been legalized. However, some sources on the internet are touting marijuana as a solution for the nausea that commonly accompanies pregnancy, including the severe condition hyperemesis gravidarum.

Although research on the prevalence of marijuana use by pregnant women is limited, some data suggest that this population is turning to marijuana for its antiemetic properties, particularly during the first trimester of pregnancy, which is the period of greatest risk for the deleterious effects of drug exposure to the foetus. Marijuana is the most widely used illicit drug during pregnancy, and its use is increasing. Using data from the National Survey of Drug Use and Health, Brown et al report in this issue of JAMA that 3.85%of pregnant women between the ages of 18 and 44 years reported past-month marijuana use in 2014, compared with 2.37%in 2002. In addition, an analysis of pregnancy data from Hawaii reported that women with severe nausea during pregnancy, compared with other pregnant women, were significantly more likely to use marijuana (3.7%vs 2.3%, respectively).

Although the evidence for the effects of marijuana on human prenatal development is limited at this point, research does suggest that there is cause for concern. A recent review and a meta-analysis found that infants of women who used marijuana during pregnancy were more likely to be anaemic, have lower birth weight, and require placement in neonatal intensive care than infants of mothers who did not use marijuana. Studies have also shown links between prenatal marijuana exposure and impaired higher-order executive functions such as impulse control, visual memory, and attention during the school years.

The potential for marijuana to interfere with neurodevelopment has substantial theoretical justification. The endocannabinoid system is present from the beginning of central nervous system development, around day 16 of human gestation, and is increasingly thought to play a significant role in the proper formation of neural circuitry early in brain development, including the genesis and migration of neurons, the outgrowth of their axons and dendrites, and axonal pathfinding. Substances that interfere with this system could affect foetal brain growth and structural and functional neurodevelopment.

An ongoing prospective study, for example, found an association between prenatal cannabis exposure and foetal growth restriction during pregnancy and increased frontal cortical thickness among school-aged children. Some synthetic cannabinoids, such as those found in “K2/Spice” products, interact with cannabinoid receptors even more strongly than THC and have been shown to be teratogenic in animals.

A recent study in mice found brain abnormalities, eye deformations, and facial disfigurement (cleft palate) in mouse foetuses exposed at day 8 of gestation to a potent full cannabinoid agonist, CP-55,940. The percentage of mouse foetuses with birth defects increased in a linear fashion with dose. (The eighth day of mouse gestation is roughly equivalent to the third or fourth week of embryonic development in humans, which is before many mothers know they are pregnant.) It is unknown whether these kinds of effects translate to humans; thus far, use of synthetic cannabinoids has not been linked to human birth defects, although use of these substances is still relatively new.

THC is only a partial agonist at the CB1 receptor, but the marijuana being used both medicinally and recreationally today has much higher THC content than in previous generations (12% in 2014 vs 4% in 1995), when many of the existing studies of the teratogenicity of marijuana were performed. Marijuana is also being used in new ways that have the potential to expose the user to much higher THC concentrations—such as the practice of using concentrated extracts (eg, hash oil). More research is needed to clarify the neurodevelopmental effects of prenatal exposure to marijuana, especially high-potency formulations, and synthetic cannabinoids.

One challenge is separating these effects from those of alcohol, tobacco, and other drugs, because many users of marijuana or K2/Spice also use other substances. In women who use drugs during pregnancy, there are often other confounding variables related to nutrition, prenatal care, and failure to disclose substance use because of concerns about adverse legal consequences.    Even with the current level of uncertainty about the influence of marijuana on human neurodevelopment, physicians and other health care providers in a position to recommend medical marijuana must be mindful of the possible risks and err on the side of caution by not recommending this drug for patients who are pregnant. Although no states specifically list pregnancy-related conditions among the allowed recommendations for medical marijuana, neither do any states currently prohibit or include warnings about the possible harms of marijuana to the foetus when the drug is used during pregnancy. (Only 1 state, Connecticut, currently includes an exception to the medical marijuana exemption in cases in which medical marijuana use could harm another individual, although potential harm to a foetus is not specifically listed.)

In 2015, the American College of Obstetricians and Gynecologists issued a committee opinion discouraging physicians from suggesting use of marijuana during preconception, pregnancy, and lactation. Pregnant women and those considering becoming pregnant should be advised to avoid using marijuana or other cannabinoids either recreationally or to treat their nausea.

Source:  http://jamanetwork.com/ on 12/21/2016

A recognized deficiency: Inadequate protective protocols

An evaluation of risk applied to marijuana products for medical purposes concludes that advanced mitigation strategies and new protective delivery protocols are necessary to adequately protect the public from harm. The Risk Evaluation and Mitigation Strategies (REMS) program is already an approved protocol in the United States (US) by the US Food and Drug Administration and in Canada a similar controlled distribution program is in place including RevAid®.1,2    These programs are intended to assure patients are monitored to prevent or minimize major side effects and or reactions.   There are a number of medications that fall into existing REMS restrictions include thalidomide, clozapine, isotretinoin, and lenilidomide.  In both of these programs only prescribers and pharmacists who are registered or patients who are enrolled and who have agreed to meet all the conditions of the program are given access to these drugs.1,2

Current Government-approved Cannabinoid Products

Dronabinol (Marinol®, generic), nabilone (Cesamet®, generic) are synthetic cannabinoids to mimic delta-9-THC and nabiximols (Sativex®) is a combination of delta-9-THC and cannabidiol. They all lack the pesticides, herbicides and fungicides placed on marijuana plants during growth.

The longest approved agents, dronabinol and nabilone are indicated for short term use in nausea and vomiting due to chemotherapy and appetite stimulation.3,4  Nabiximols is used as a buccal spray for multiple sclerosis and as an adjunct for cancer pain.5  The maximum delta-9-THC strengths available are 10 mg for dronabinol and 2.7 mg/spray of nabiximols.3,5  Cannabidiol (CBD), a non-psychoactive compound, is one of many cannabinoids found in marijuana.   CBD is currently available for free from the U.S. National Institute of Health in government-sponsored clinical trials as potential treatment of resistant seizures (Dravet’s Syndrome and Lennox-Gastaut Syndrome).6

‘Medical’ Marijuana products

All marijuana products, including marijuana for medical purposes, fit the prerequisites for a REMS program. The average potency of marijuana more than doubled between 1998 and 2009.7 In 2015 common leaf marijuana averaged 17.1% THC in Colorado.8  Examples of oral marijuana products contain 80 mg of THC in chocolates, cookies and drinks and even 420 mg of THC in a “Dank Grasshopper” bar.9  Butane hash oil (BHO) is a concentrated THC product used in water bongs and/or e- cigarettes and contains upwards of 50 – 90% THC with a Colorado average of 71.7 % THC.8   One “dab” (280 mg) of 62.1% BHO is equal to 1 gram of 17% THC in marijuana leaf form.8  These extremely elevated levels of THC make true scientific research with these products incapable of passing Patient Safety Committee standards.10

The Thalidomide Parallel

The risks are so severe for thalidomide, in terms of use in pregnancy that a special protocol that educates, evaluates, mitigates and monitors has been made obligatory.11

Thalidomide (Contergan®) was developed by a German company, Chemie Gruenenthal, in 1954 and approved for the consumer market in 1957.12 It was available as an over-the-counter drug for the relief of “anxiety, insomnia, gastritis, and tension” and later it was used to alleviate nausea and to help with morning sickness by pregnant women. Thalidomide was present in at least 46 countries under a variety of brand names and was available in “sample tablet form” in Canada by 1959 and licensed for prescription on December 2, 1961. Although thalidomide was withdrawn from the market in West Germany and the UK by December 2, 1961, it remained legally available in Canada until March of 1962. It was still available in some Canadian pharmacies until mid-May of 1962.12

Canada had permitted the drug onto the Canadian market when many warnings were already available

An association was being made in 1958 of phocomelia (limb malformation) in babies of mother’s using thalidomide.  A trial conducted in Germany against Gruenenthal, for causing intentional and negligent bodily injury and death, began in 1968 ending in 1970 with a claim of insufficient evidence.  Later, the victims and Gruenenthal settled the case for 100 million dollars.11

In 1962 the American pharmaceutical laws were increased by the Kefauver-Harris Drug Amendment of 1962 and proof for the therapeutic efficiency through suitable and controlled studies would be required for any government approved medication.13 According to paragraph 25 of the Contergan foundation law, every 2 years a new report is required to determine if further development of these regulations are necessary.13

In 1987 the War Amputations of Canada established The Thalidomide Task Force, to seek compensation for Canadian-born thalidomide victims from the government of Canada.12

In 1991, the Ministry of National Health and Welfare (the current Health Canada) awarded Canadian-born thalidomide survivors a small lump-sum payment.12

In 2015 the Canadian government agreed on a settlement of $180 million dollars to 100 survivors of thalidomide drug exposure and damage.14 Through Rona Ambrose, in her capacity as the Health Minister for the government of Canada at the time of the negotiations, an attempt was made to involve the drug companies related to the thalidomide issue in the survivor’s settlement agreement. Negotiations with the drug companies failed.  The Canadian taxpayer alone paid to amend the survivors by way of monetary award.

Thalidomide continues to be sold under the brand name of Immunoprin®, among others in a REMS program. It is an immunomodulatory drug and today, it is used mainly as a treatment of certain cancers (multiple myeloma) and leprosy.11

Question: If the drug thalidomide included psychotropic properties and offered the “high” of marijuana would it be prudent or responsible to allow it to be legally sold and marketed for non-medical purposes – acknowledging thalidomide’s record for toxicity in pregnancy?

Marijuana Risk Assessment and Government Acknowledgement

Risks demonstrated in the scientific literature include genetic and chromosomal damage.15, 16

When exposure occurs in utero, there is an association with many congenital abnormalities including cardiac septal defects, anotia, anophthalmos, and gastroschisis. Marijuana use can disrupt foetal growth and the development of organs and limbs and may result in mutagenic alterations in DNA. Cannabis has also been associated with foetal abnormalities in many studies including low birth weight, foetal growth restriction, preterm birth spontaneous miscarriage, spina bifida and others.15

Phocomelia has been shown in testing in a similar preclinical model (hamster) to that which revealed the teratogenicity of thalidomide.15

THC has the ability to interfere with the first stages in the formation of the brain of the fetus; this event occurs two weeks after conception.  Exposure to today’s high potency marijuana in early pregnancy is associated with anencephaly, a devastating birth defect in which infants are born with large parts of the brain or skull missing.15

The existence of specific health risks associated with marijuana products are acknowledged by national and various local governments and a plethora of elected officials in both Canada and the United States.16, 17, 18

Warnings and the contraindications for use by specific populations and in association with identified conditions, have been publicized by the Federal Government of Canada and the Federal Government of the United States of America through their respective health agencies.16, 17, 18

A government of Canada leaflet produced by Health Canada and updated in December 2015: Consumer Information – Cannabis (Marihuana, marijuana) reads19:

“The use of this product involves risks to health, some of which may not be known or fully understood. Studies supporting the safety and efficacy of cannabis for therapeutic purposes are limited and do not meet the standard required by the Food and Drug Regulations for marketed drugs in Canada.”19

“Using cannabis or any cannabis product can impair your concentration, your ability to think and make decisions, and your reaction time and coordination. This can affect your motor skills, including your ability to drive. It can also increase anxiety and cause panic attacks, and in some cases cause paranoia and hallucinations.”19

“When the product should not be used: under the age of 25, are allergic to any cannabinoid or to smoke, have serious liver, kidney, heart or lung disease, have a personal or family history of serious mental disorders such as schizophrenia, psychosis, depression, or bipolar disorder, are pregnant, are planning to get pregnant, or are breast-feeding, are a man who wishes to start a family, have a history of alcohol or drug abuse or substance dependence.”19

“A list of health outcomes related to long term use includes the following:

Increased risk of triggering or aggravating psychiatric and/or mood disorders (schizophrenia, psychosis, anxiety, depression, bipolar disorder), decrease sperm count, concentration and motility, and increase abnormal sperm morphology. Negatively impact the behavioural and cognitive development of children born to mothers who used cannabis during pregnancy.”19

In Canada, the College of Family Physicians has issued guidelines for issuing marijuana prescriptions.20

“Dried cannabis is not appropriate for patients who: a) Are under the age of 25 (Level II) b) Have a personal history or strong family history of psychosis (Level II) c) Have a current or past cannabis use disorder (Level III) d) Have an active substance use disorder (Level III) e) Have cardiovascular disease (angina, peripheral vascular disease, cerebrovascular disease, arrhythmias) (Level III) f) Have respiratory disease (Level III) or g) Are pregnant, planning to become pregnant, or breastfeeding (Level II)”20

“Dried cannabis should be authorized with caution in those patients who: a) Have a concurrent active mood or anxiety disorder (Level II) b) Smoke tobacco (Level II) c) Have risk factors for cardiovascular disease (Level III) or d) Are heavy users of alcohol or taking high doses of opioids or benzodiazepines or other sedating medications prescribed or available over the counter (Level III)”20

In February 2013 The College of Family Physicians of Canada issued a statement advancing the position that physicians should sign a declaration rather than write a prescription as the potential liability, as well as the ethical obligations, for health professionals prescribing marijuana for medical purposes appears not to have been adequately addressed by Health Canada. 21

“In our view, Health Canada places physicians in an unfair, untenable and to a certain extent unethical position by requiring them to prescribe cannabis in order for patients to obtain it legally. If the patient suffers a cannabis-related harm, physicians can be held liable, just as they are with other prescribed medications. Physicians cannot be expected to prescribe a drug without the safeguards in place as for other medications – solid evidence supporting the effectiveness and safety of the medication, and a clear set of indications, dosing guidelines and precautions.”21

Representatives of the government of the United States held a press conference at the Office of National Drug Policy (ONDCP) in 2005. Mental health experts and scientists joined high-ranking government officials to discuss an emerging body of research that identified clear links between marijuana use and mental health disorders, including depression, suicidal thoughts and schizophrenia.22

The US Substance Abuse and Mental Health Service Administration (SAMHSA) report about the correlation between age of first marijuana use and serious mental illness; and an open letter to parents on “Marijuana and Your Teen’s Mental Health,” signed by twelve of the Nation’s leading mental health organizations, ran in major newspapers and newsweeklies across the country.23

Included were the following announcements:

“Regular use of the drug has appeared to double the risk of developing a psychotic episode or long-term schizophrenia.”23

“Research has strongly suggested that there is a clear link between early cannabis use and later mental health problems in those with a genetic vulnerability – and that there is a particular issue with the use of cannabis by adolescents.” 23

“Adolescents who used cannabis daily were five times more likely to develop depression and anxiety in later life.” 23

In 2016 the Obama Administration steadfastly opposes legalization of marijuana and other drugs because legalization would increase the availability and use of illicit drugs, and pose significant health and safety risks to all Americans, particularly young people.24 The US government still maintains marijuana is classified as a Schedule I drug, meaning it has a high potential for abuse and no currently accepted medical use in treatment in the United States.17, 18

Risk Evaluation and Mitigation Strategy for Marijuana Products

The dispensing of marijuana for medical purposes must follow a strict dispensing and monitoring protocol; no less arduous than that used for the delivery of drugs such as thalidomide.

Recommendation – The implementation of a REMS for marijuana products (REMSMP).

1. The first order for a government is to protect the public. As such, it befits a government approving marijuana for medical purposes to implement a REMS program.

2. Medical cannabis/marijuana dispensaries/stores/delivery systems will be       required to comply with all necessary components of a rigorous REMS program prior to selling and dispensing marijuana products.

3. Governmental regulatory organizations must be responsible for the cannabis/marijuana for medical purposes programs and obtain the required evaluations [(i.e. laboratory tests (pregnancy, HCG, etc.), physical and mental health examination documentation], signed patient consent, provider contract and education forms – performed in the required time frames both before initiation, during and after continued usage of marijuana products for medical purposes.

4. Quarterly audits will be performed, by the government regulatory organization, on each medical marijuana/cannabis dispensary for compliance.  Failure to comply with the REMSMP program will result in fines and other appropriate penalties to the marijuana dispensaries.

A REMS for Marijuana Product Potential Framework:

EMBRYO-FETAL TOXICITY & BREASTFEEDING

* Marijuana causes DNA damage in male and female patients.15  If marijuana is used during conception or during pregnancy, it may cause birth defects, cancer formation in the offspring, Downs Syndrome or embryo-fetal death.15, 16, 18

* Pregnancy must be ruled out before the start of marijuana treatment.  Pregnancy must be prevented by both the male and female patients during marijuana treatment by the use of two reliable methods of contraception.

* When there is no satisfactory alternative treatment, females of reproductive potential may be treated with marijuana provided adequate precautions are taken to avoid pregnancy.

* Females of Reproductive Potential: Must avoid pregnancy for at least 4 weeks before beginning marijuana therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy.  Females must commit to either abstain continuously from heterosexual intercourse or use two methods or reliable birth control as mentioned.  They must have two negative pregnancy tests prior to initiating marijuana therapy and monthly pregnancy test with normal menses or two months with abnormal menses and for at least 1 month after stopping marijuana therapy.

* Males (all ages): DNA damage from marijuana is present in the semen of patients receiving marijuana.15 Therefore, males must always use a latex or synthetic condom during any sexual contacts with females of reproductive potential while using marijuana and for up to at least 28 days after discontinuing marijuana therapy, even if they have undergone a successful vasectomy.  Male patients using marijuana may not donate sperm.

* Blood Donation: Patients must not donate blood during treatment with marijuana and for at least 1 month following discontinuation of marijuana because the blood might be given to a pregnant female patient whose fetus should not be exposed to marijuana.

* Marijuana taken by any route of administration may result in drug-associated DNA damage resulting in embryo-fetal toxicity. Females of reproductive potential should avoid contact with marijuana through cutaneous absorption, smoke inhalation or orally.

* If there is contact with marijuana products topically, the exposed area should be washed with soap and water.

* If healthcare providers or other care givers are exposed to body fluids of a person on marijuana, the exposed area should be washed with soap and water.  Appropriate universal precautions should be utilized, such as wearing gloves to prevent the potential cutaneous exposure to marijuana.

* Several psychoactive cannabinoids in marijuana are fat soluble and are found to concentrate in breast milk.  Nursing mothers must not be receiving marijuana.16 Consult the primary care provider about how long to be off of marijuana before considering breast feeding.

NON-SEMINOMA TESTICULAR GERM CELL CARCINOMA

* Marijuana use is a known risk factor in the development of non-seminoma testicular germ cell carcinoma in males.25 – 28

* The presence of non-seminoma testicular germ cell carcinoma must be excluded before the start of marijuana treatment.  The patient’s primary care provider must perform a testicular examination and review the patient’s human chorionic gonadotropin (HCG) blood test before starting marijuana.  Male patients must perform weekly testicular self-evaluations while receiving marijuana.  They are also required to have their primary care provider perform a testicular evaluation and a HCG blood test performed every 4 months while receiving marijuana.29, 30

MENTAL HEALTH:

* Short term high dose and chronic marijuana usage is a known risk factor for the development of multiple mental health disorders.16, 18, 20, 31 – 34  Depression, paranoia, mental confusion, anxiety, addiction and suicide potential are all associated with acute and chronic exposure to marijuana.16, 18   Decline in intelligence is a potential risk of adolescent-onset marijuana exposure. 16, 18, 35

The presence of these mental health disorders must be evaluated by a licensed psychiatrist or psychologist by use of the Mini International Neuropsychiatric Interview or equivalent validated diagnostic instrument before marijuana is started.  The diagnostic mental health evaluation tool will be completed every 1month by an independent licensed psychiatrist or psychologist for a minimum of 6 months until unchanging and then every 4 months thereafter while receiving marijuana ending 4 months after the last exposure to marijuana.36

PSYCHIATRIC EVALUATIONS:

History of Substance Abuse Disorder: As the prevalence of substance use disorders amongst those patients requesting medical authorization of marijuana products is known to be extremely high the patient population must be screened prior to dispensing marijuana products for risk of a substance use disorder.  Substance use must be monitored prior to onset of marijuana with the World Health Organization, Smoking and Substance Involvement Screening Test (WHO-ASSIST, V3.0), and repeated at monthly intervals until unchanging and every 3 months thereafter while receiving marijuana, ending 6 months after the last exposure to marijuana.37

Conclusion

The evidence that thalidomide and tobacco products were harmful was known to the manufacturers/distributors before government and the populous acknowledged these dangers.

To date, there continue to be legal repercussions to said manufacturers/distributors/government for knowingly placing the public at risk.  We believe that the same will happen for marijuana products and that it is our responsibility to assist the Canadian government to protect the public from a similar outcome.

Since the government is fully aware of the marijuana harms, the  government must not be complicit in risking Canadian health/lives, but rather must mitigate any and all such risk to current and future generations.38, 39

The REMSMP program described assists in providing patient education, provider education and required patient monitoring before any marijuana products are allowed to be dispensed.  The program also requires on-going data collection and analysis, to determine the actual hazards from marijuana use and whether the program should even continue.  As the stewards of the country’s human and financial resources, it is critical that government protect the public from potential irreversible harm and itself from litigation risk by harmed individuals knowing that, in the context of marijuana use, harm is not only possible but probable.

Source:  Pamela McColl,  National Director,  Smart Approaches to Marijuana Canada and The Marijuana Victims’ Association,    Vancouver BC Canada    August  2016

Endorsements

Philip Seeman, M.D. Ph.D., O.C. Departments of Pharmacology and Psychiatry University of Toronto,   Nobel Prize nominee (Science)

Elizabeth Osuch, M.D. Associate Professor Rea Chair of Affective Disorders, University of Western Ontario Schulich School of Medicine and Denistry,  London, Ontario

Ray Baker, M.D., FCFP, FASAM, Associate Clinical Professor, University of British Columbia Faculty of Medicine,  Vancouver, British Columbia

Pamela McColl, Smart Approaches to Marijuana – Canada.  Board Member Campaign for Justice Against Tobacco Fraud

Robert L. DuPont, MD,  President, Institute for Behavior and Health, Inc. Clinical Professor of Psychiatry, Georgetown University School of Medicine,  First Director, National Institute on Drug Abuse,  Second US White House Drug Chief

Bertha K Madras, PhD Professor of Psychobiology, Department of Psychiatry,Harvard Medical School

Phillip A. Drum Pharm. D., FCSHP.    Smart Approaches to Marijuana – USA

Professor Gary Hulse, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Australia

Grainne Kenny, Dublin, Ireland Co-founder and Hon. President of EURAD ,Brussels, Belgium

Peter Stoker Director, National Drug Prevention Alliance, United Kingdom

Mary Brett, BSc (Hons), Chair of Charity Cannabis Skunk Sense (CanSS) www.cannabisskunksense.co.uk ,United Kingdom

Deidre Boyd, CEO: DB Recovery Resources, Editor: Recovery Plus UK

References  1. Accessed on 7/28/16:http://www.fda.gov/Drugs/DrugSafety/Postmarket DrugSafetyInformationforPatients andProviders/ucm2008016.htm#rems  2. Accessed on 7/28/16: https://www.revaid.ca  3. Accessed on 7/31/16: http://www.fda.gov/ohrms/dockets/dockets/05n0479/05N-0479-emc0004-04.pdf

4. Accessed on 7/31/16: https://www.cesamet.com/pdf/Cesamet_PI_50_count.pdf

5. Accessed on 7/31/16: http://www.ukcia.org/research/SativexMonograph.pdf

6. Accessed on 7/28/16:https://clinicaltrials.gov/ct2/results?term=CBD+and+ epilepsy&Search=Search

7. National Center for Natural Products Research (NCNPR), Research Institute of Pharmaceutical Sciences. Quarterly Report, Potency Monitoring Project, Report 107, September 16, 2009 thru December 15, 2009. University, MS: NCNPR, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi (January 12, 2010).

8. Orens A, et al. Marijuana Equivalency in Portion and Dosage. An assessment of physical and pharmacokinetic relationships in marijuana production and consumption in Colorado. Prepared for the Colorado Department of Revenue. August 10, 2015.

9. Accessed on7/30/16: https://weedmaps.com/dispensaries/tree-house-collective-dispensary-san-marcos

10.  Personal conversation with Marilyn Huestis, NIH researcher, June 2015.

11. Accessed on 8/4/16:http://www.contergan.grunenthal.info/grt-ctg/GRT-CTG/Die_Fakten/Chronologie/152700079.jsp

12. Accessed on 7/28/16: http://www.thalidomide.ca/the-canadian-tragedy/ 13. Accessed on 7/28/16:  http://www.fda.gov/Drugs/NewsEvents/ucm320924.htm 14. Accessed on 7/29/16: http://news.gc.ca/web/article-en.do?nid=945369&tp=1

15. Reece AS, Hulse GK. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Mutat Res. 2016;789:15-25. 16. Accessed on 7/28/16: http://www.hc-sc.gc.ca/dhp-mps/marihuana/med/ infoprof-eng.php 17. Accessed on 1/8/16:  https://www.whitehouse.gov/ondcp/frequently-asked-questions-and-facts-about-marijuana#harmless 18. Accessed on 1/8/16:  https://www.whitehouse.gov/ondcp/marijuana  19. Accessed on 7/20/16: http://www.hc-sc.gc.ca/dhp-mps/marihuana/info/cons-eng.php

20. College of Family Physicians of Canada. Authorizing Dried Cannabis for Chronic Pain or Anxiety: Preliminary Guidance from the College of Family Physicians of Canada. Mississauga, ON: College of Family Physicians of Canada; 2014.

21. Accessed on 3/8/16:http://www.cfpc.ca/uploadedFiles/Health_Policy/CFPC _Policy_Papers_and_Endorsements/CFPC_Policy_Papers/Medical%20Marijuana%20Position%20Statement%20CFPC.pdf 22. Accessed on 6/31/16 http://www.ovguide.com/john-p-walters-9202a8c040 00641f8000000 0003d9c0b

23. Accessed 8/1/2016: http://www.prnewswire.com/news-releases/white-house-drug-czar-research-and-mental-health-communities-warn-parents-that-marijuana-use-can-lead-to-depression-suicidal-thoughts-and-schizophrenia-54240132.html

24. Accessed on 2/8/2016. https://www.whitehouse.gov/ondcp/marijuana

25. Accessed on 8/1/2016: https://www.drugabuse.gov/news-events/nida-notes/2010/12/marijuana-linked-testicular-cancer

26. Lacson JCA, et al. Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer. 2012;118(21):5374-5383.

27. Daling JR, et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer. 2009;115(6):1215-1223.

28. Gurney J, et al. Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis. BMC Cancer 2015;15:1-10.  29. Accessed on 7/30/16:http://www.cancer.org/cancer/testicularcancer/ detailedguide/testicular-cancer-diagnosis

30. Takizawa A, et al. Clinical Significance of Low Level Human Chorionic Gonadotropin in the Management of Testicular Germ Cell Tumor. J Urology. 2008;179(3):930-935.

31. Moore TH, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370:319-328.

32. Large M, et al., Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen Psychiatry. 2011;68(6):555-61.

33. Ashton CH and Moore PB. Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr Scand, 2011;124: 250-261.

34. Ranganathan M and D’Souza DC. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology. 2006;188: 425-444, 2006.

35. Accessed on 8/1/2016:https://www.drugabuse.gov/publications/drug facts/marijuana

36. Sheehan D, et al. Mini International Neuropsychiatric Interview, DSM-IV English Version 5.0.0 2006.

37.  Accessed on 8/1/2016: http://www.who.int/substance_abuse/activities/assist/ en/

38. Accessed on 8/1/16: http://news.gc.ca/web/article-en.do?nid=844329 39. Accessed on 8/3/16: http://www.healthlinkbc.ca/healthtopics/content.asp? hwid=abl2153

October 19, 2016 2.02am BST

Currently 25 states and the District of Columbia have medical cannabis programs. On Nov. 8, Arkansas, Florida and North Dakota will vote on medical cannabis ballot initiatives, while Montana will vote on repealing limitations in its existing law.

We have no political position on cannabis legalization. We study the cannabis plant, also known as marijuana, and its related chemical compounds. Despite claims that cannabis or its extracts relieve all sorts of maladies, the research has been sparse and the results mixed. At the moment, we just don’t know enough about cannabis or its elements to judge how effective it is as a medicine.

What does the available research suggest about medical cannabis, and why do we know so little about it?

What are researchers studying?

While some researchers are investigating smoked or vaporized cannabis most are looking at specific cannabis compounds, called cannabinoids.

From a research standpoint, cannabis is considered a “dirty” drug because it contains hundreds of compounds with poorly understood effects. That’s why researchers tend to focus on just one cannabinoid at a time. Only two plant-based cannabinoids, THC and cannabidiol, have been studied extensively, but there could be others with medical benefits that we don’t know about yet. THC is the main active component of cannabis. It activates cannabinoid receptors in the brain, causing the “high” associated with cannabis, as well as in the liver, and other parts of the body. The only FDA-approved cannabinoids that doctors can legally prescribe are both lab produced drugs similar to THC. They are prescribed to increase appetite and prevent wasting caused by cancer or AIDS.

Cannabidiol (also called CBD), on the other hand, doesn’t interact with cannabinoid receptors. It doesn’t cause a high. Seventeen states have passed laws allowing access to CBD for people with certain medical conditions.

Our bodies also produce cannabinoids, called endocannabinoids. Researchers are creating new drugs that alter their function, to better understand how cannabinoid receptors work. The goal of these studies is to discover treatments that can use the body’s own cannabinoids to treat conditions such as chronic pain and epilepsy, instead of using cannabis itself.

Cannabis is promoted as a treatment for many medical conditions. We’ll take a look at two, chronic pain and epilepsy, to illustrate what we actually know about its medical benefits.

Is it a chronic pain treatment? Research suggests that some people with chronic pain self-medicate with cannabis. However, there is limited human research on whether cannabis or cannabinoids effectively reduce chronic pain. Research in people suggest that certain conditions, such as chronic pain caused by nerve injury, may respond to smoked or vaporized cannabis, as well as an FDA-approved THC drug. But, most of these studies rely on subjective self-reported pain ratings, a significant limitation. Only a few controlled clinical trials have been run, so we can’t yet conclude whether cannabis is an effective pain treatment.

An alternative research approach focuses on drug combination therapies, where an experimental cannabinoid drug is combined with an existing drug. For instance, a recent study in mice combined a low dose of a THC-like drug with an aspirin-like drug. The combination blocked nerve-related pain better than either drug alone.

In theory, the advantage to combination drug therapies is that less of each drug is needed, and side effects are reduced. In addition, some people may respond better to one drug ingredient than the other, so the drug combination may work for more people. Similar studies have not yet been run in people.

Well-designed epilepsy studies are badly needed Despite some sensational news stories and widespread speculation on the internet, the use of cannabis to reduce epileptic seizures is supported more by research in rodents than in people. In people the evidence is much less clear. There are many anecdotes and surveys about the positive effects of cannabis flowers or extracts for treating epilepsy. But these aren’t the same thing as well-controlled clinical trials, which can tell us which types of seizure, if any, respond positively to cannabinoids and give us stronger predictions about how most people respond.

While CBD has gained interest as a potential treatment for seizures in people, the physiological link between the two is unknown. As with chronic pain, the few clinical studies have been done included very few patients. Studies of larger groups of people can tell us whether only some patients respond positively to CBD.

We also need to know more about the cannabinoid receptors in the brain and body, what systems they regulate, and how they could be influenced by CBD. For instance, CBD may interact with anti-epileptic drugs in ways we are still learning about. It may also have different effects in a developing brain than

in an adult brain. Caution is particularly urged when seeking to medicate children with CBD or cannabis products.

Cannabis research is hard

Well-designed studies are the most effective way for us to understand what medical benefits cannabis may have. But research on cannabis or cannabinoids is particularly difficult. Cannabis and its related compounds, THC and CBD, are on Schedule I of the Controlled Substances Act, which is for drugs with “no currently accepted medical use and a high potential for abuse” and includes Ecstasy and heroin.

In order to study cannabis, a researcher must first request permission at the state and federal level. This is followed by a lengthy federal review process involving inspections to ensure high security and detailed record-keeping.

In our labs, even the very small amounts of cannabinoids we need to conduct research in mice are highly scrutinized. This regulatory burden discourages many researchers.

Designing studies can also be a challenge. Many are based on users’ memories of their symptoms and how much cannabis they use. Bias is a limitation of any study that includes self-reports. Furthermore, laboratory-based studies usually include only moderate to heavy users, who are likely to have formed some tolerance to marijuana’s effects and may not reflect the general population. These studies are also limited by using whole cannabis, which contains many cannabinoids, most of which are poorly understood.

Placebo trials can be a challenge because the euphoria associated with cannabis makes it easy to identify, especially at high THC doses. People know when they are high. Another type of bias, called expectancy bias, is a particular issue with cannabis research. This is the idea that we tend to experience what we expect, based on our previous knowledge. For example, people report feeling more alert after drinking what they are told is regular coffee, even if it is actually decaffeinated. Similarly, research participants may report pain relief after ingesting cannabis, because they believe that cannabis relieves pain. The best way to overcome expectancy effects is with a balanced placebo design, in which participants are told that they are taking a placebo or varying cannabis dose, regardless of what they actually receive.

Studies should also include objective, biological measures, such as blood levels of THC or CBD, or physiological and sensory measures routinely used in other areas of biomedical research. At the moment, few do this, prioritizing self-reported measures instead.

Cannabis isn’t without risks

Abuse potential is a concern with any drug that affects the brain, and cannabinoids are no exception. Cannabis is somewhat similar to tobacco, in that some people have great difficulty quitting. And like tobacco, cannabis is a natural product that has been selectively bred to have strong effects on the brain and is not without risk. Although many cannabis users are able to stop using the drug without problem, 2-6 percent of users have difficulty quitting. Repeated use, despite the desire to decrease or stop using, is known as cannabis use disorder.

As more states more states pass medical cannabis or recreational cannabis laws, the number of people with some degree of cannabis use disorder is also likely to increase.

It is too soon to say for certain that the potential benefits of cannabis outweigh the risks. But with restrictions to cannabis (and cannabidiol) loosening at the state level, research is badly needed to get the facts in order.

Source: https://theconversation.com/what-do-we-know-about-marijuanas-medical-benefits-two-experts-explain-the-evidence-64200   Oct.2016

Abstract

The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer’s disease, Parkinson’s disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, it is critical that societal passions not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure.

This critical review focuses on evidence-based research designed to assess both therapeutic benefits and harmful effects of cannabis exposure, and is combined with an illustration of the neuropathological findings in a fatal case of cannabis-induced psychosis.

The literature and reported case provide strong evidence that chronic cannabis abuse causes cognitive impairment and damages the brain, particularly white matter, where cannabinoid 1 receptors abound. Contrary to popular perception, there is little objective data supporting preferential use of cannabis over conventional therapy for restoration of central nervous system structure and function in disease states such as multiple sclerosis, epilepsy, or schizophrenia. Additional research is needed to determine if sub-sets of individuals with various neurological and psychiatric diseases derive therapeutic benefits from cannabis. David E. Mandelbaum, MD, PhD Suzanne M. de la Monte, MD MPH

Departments of Neurology, Pediatrics, Neuropathology and Neurosurgery, Hasbro Children’s Hospital and Rhode Island Hospital, and the Alpert Medical School of Brown University, Providence, RI 02903

Source:    http://dx.doi.org/10.1016/j.pediatrneurol.2016.09.004

If medical marijuana is a step toward legalization, just make it legal — or at least decriminalize it — and don’t dump it all on doctors. Making physicians the gatekeepers of legal marijuana is not fair to doctors and is not conducive to public health.

The problem is that marijuana has been prescribed by the courts, not by health-care professionals.

“Dried marijuana is not an approved drug or medicine in Canada,” says the Health Canada website. “The Government of Canada does not endorse the use of marijuana, but the courts have required reasonable access to a legal source of marijuana when authorized by a physician.” Many physicians are reluctant to take on that responsibility.

“We have Health Canada telling us that marijuana is not a medicine, we have our malpractice insurance company telling us to be very cautious because nobody is taking responsibility for the safety of it,” says Dr. Chris Simpson, a Queen’s University cardiologist and incoming president of the Canadian Medical Association.

Simpson doesn’t dismiss marijuana — he says “many compelling anecdotes” indicate that marijuana can help patients with HIV, hard-to-treat seizures and other conditions. But, he adds, “we have people out there saying marijuana can cure cancer, which seems quite improbable.”

“Somewhere in between those two extremes is the truth, and I think we need to find the truth, and the way to do that is with the appropriate research.” Testifying before a parliamentary health committee in May, Dr. Meldon Kahan, medical director of the substance-use service at Women’s College Hospital in Toronto, detailed a long list of harmful effects from cannabis use. They included impairments in attention, increased anxieties, psychosis and cancer.

“Widespread cannabis prescribing by physicians will increase the social and psychiatric harms of cannabis,” Kahan said, calling for the development of evidence-based guidelines for prescribing smoked marijuana.

“Guidelines will give physicians solid grounds on which to make prescribing decisions. Physicians are facing a deluge of requests to prescribe cannabis, and guidelines will give them the support they need to refuse to prescribe cannabis when medically unnecessary or unsafe.”

Because Health Canada allows marijuana to be prescribed by physicians, that enhances the public perception that marijuana is not only harmless, but therapeutic.

“The evidence suggests otherwise,” Kahan said. “Smoked cannabis has negligible therapeutic benefits.” Would marijuana pass the scrutiny of the University of B.C.’s Therapeutics Initiative, established to examine the effectiveness of prescription drugs? It uses solid evidence and rigorous scientific research, and it has saved lives. Marijuana should undergo the same scrutiny as to its potential benefits and harms.

But medical marijuana is not treated the same as other drugs. Science has little to do with it.

“The current means of ‘prescribing’ violates all of the usual practices of medicine,” wrote Maryland psychiatrists Dinah Miller and Anette Hanson in a 2012 Baltimore Sun commentary. “What other medication do we authorize for a year, with no stipulation as to frequency, dose or certainty that there has been a positive response without side effects?”

If marijuana can relieve the agony of someone with severe chronic pain or terminal cancer, who would withhold it? But let’s face it, the biggest demand for pot is as a recreational drug, like alcohol and tobacco. It should be handled the same, with regulations as to its production and distribution. We should not clog our courts and jails with pot-smokers.

By all means, investigate its potential for good, but let’s not pretend it does no harm.

Source: http://www.timescolonist.com/opinion/editorials/editorial-don-t-pretend-pot-is-harmless-1.1304417#sthash.8ubjqn0w.dpuf 9th August 2014

Many of the Op-Eds on the subject of the legalisation or otherwise of cannabis are written by journalists or protagonists of one or other point of view. The following links give scientific evidence from scientist and medics in the USA, and do not support the use of cannabis.

 

Medical organisations in the USA do not support smoked pot or edibles

   
   

Authoritative organisations which do not support smoked pot or edibles as a legitimate form of medication, listed by:

Rethinkpot.org:

American Medical Association,

American Cancer Society,

National Multiple Sclerosis Society, 

American Glaucoma Society,

American Academy of Pediatrics, 

National Institute of Drug Abuse (NIDA),

Substance Abuse and Mental Health Service Association (SAMHSA),

Food and Drug Association  (FDA),

American Academy of Ophthalmology,

Drug Enforcement Agency (DEA),

American Society of Addiction Medicine,

Epilepsy Foundation.

 

 

Addiction Science & Clinical Practice

Katherine A Belendiuk1, Lisa L Baldini2 and Marcel O Bonn-Miller345*

Author Affiliations

1Institute of Human Development, University of California, 1121 Tolman Hall #1690, Berkeley 94720, CA, USA

2Palo Alto University, 1791 Arastradero Road, Palo Alto 94304, CA, USA

3Center of Excellence in Substance Abuse Treatment and Education, Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia 19104, PA, USA

4Center for Innovation to Implementation and National Center for PTSD, VA Palo Alto Health Care System, 795 Willow Road (152-MPD), Menlo Park 94025, CA, USA

5Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, 3440 Market Street, Philadelphia 19104, PA, USA

For all author emails, please log on.

Addiction Science & Clinical Practice 2015, 10:10 doi:10.1186/s13722-015-0032-7

The electronic version of this article is the complete one and can be found online at:http://www.ascpjournal.org/content/10/1/10

Received:

29 August 2014

Accepted:

15 April 2015

Published:

21 April 2015

© 2015 Belendiuk et al.; licensee BioMed Central.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

The present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: Alzheimer’s disease, amyotrophic lateral sclerosis, cachexia/wasting syndrome, cancer, Crohn’s disease, epilepsy and seizures, glaucoma, hepatitis C virus, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis and muscle spasticity, severe and chronic pain, and severe nausea. Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Studies for this narrative review were included based on a literature search in PsycINFO, MEDLINE, and Google Scholar. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions. It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments.

Keywords:

Cannabis; Medical marijuana; Marijuana; Medicine; Treatment; Alzheimer’s disease; ALS; Cachexia; Cancer, Crohn’s disease; Epilepsy; Seizures; Glaucoma; Hepatitis C virus; HCV; HIV; AIDS; Multiple sclerosis; MS; Pain; Nausea; Vomiting; Post-traumatic stress disorder; PTSD

Introduction

National estimates suggest that 5.4 million people in the United States above the age of 12 have used marijuana daily or regularly within the past year [1]. This represents an increase of approximately 74.2 percent since 2006 [1]. Similar increases have also been noted among vulnerable populations in the U.S. (e.g., veterans and adolescents) [2],[3].

Marijuana is currently illegal in every country in the world. In 2012, Uruguay voted to legalize state-controlled marijuana sales but implementation of the law has been postponed until 2015. The policy in the Netherlands is mixed, with permissible retail sale of marijuana at coffee shops, but restrictions on production and possession. Notably, as the concentration of THC in marijuana has increased, Dutch coffee shops have begun to close, as perception of marijuana as a “soft” drug transitions to perceptions of marijuana as a “hard” drug.

Like the Netherlands, the United States currently has a mixed drug policy; marijuana is an illegalSchedule I drug under U.S. Federal law. However, marijuana policies vary by state, with some states (e.g., Colorado and Washington) legalizing the use of recreational marijuana (i.e., allowing the legal possession and use of marijuana under state law), and other states decriminalizing marijuana (i.e., reducing the penalties for possession and/or use of small amounts of marijuana to fines or civil penalties). Furthermore, as of this review, 23 states and the District of Columbia have passed legislation allowing medical marijuana (i.e., individuals can defend themselves against criminal charges related to marijuana possession if a medical need is documented) for the treatment of a variety of medical and psychological conditions. Though the list of conditions for which medical marijuana has been allowed varies at the state level, the majority of states agree on its use for Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), cachexia/wasting syndrome, cancer, Crohn’s disease (CD), epilepsy and seizures, glaucoma, hepatitis C virus (HCV), human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), multiple sclerosis (MS) and muscle spasticity, severe and chronic pain, severe nausea, and post-traumatic stress disorder (PTSD).

The aim of the present review is to provide a summary of the existing empirical literature regarding the effects of marijuana/cannabinoids on each of the above-noted conditions. Though some recent work has reviewed the adverse effects of marijuana [4] or the efficacy of marijuana for certain conditions (e.g., neurologic) [5], there has yet to be a comprehensive review of the effects of marijuana for each of the medical and psychiatric conditions for which it is currently used.

Methods

The list of all conditions for which medical marijuana is allowed, according to the legislation of each U.S. state for which medical marijuana has been approved, was obtained and examined [6]. From this list, common conditions for which medical marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: AD, ALS, cachexia/wasting syndrome, cancer, CD, epilepsy and seizures, glaucoma, HCV, HIV/AIDS, MS and muscle spasticity, severe and chronic pain, and severe nausea. Though not presently a qualifying condition in at least 80 percent of states with medical marijuana laws, PTSD was also included in the review, as it is rapidly gaining attention and recognition as the sole psychological disorder for which medical marijuana is allowed.

Studies for this narrative review were included based on a literature search in the following databases: PsycINFO, MEDLINE, and Google Scholar. Within each database, each combination of the following key marijuana terms and the above-listed conditions were used to conduct a search: cannabis, marijuana, marihuana, cannabinoid, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, cannabinol, cannabigerol, Marinol, dronabinol, Sativex, Nabilone, and Nabiximols. References within each obtained article were also examined to assure that no studies were overlooked. Only published, English-language studies were included in this review.

Though the primary focus of this review is on studies of marijuana plant effects, as these are most relevant to recent medical marijuana legislation, synthetic or plant-derived cannabinoids (e.g., dronabinol, Nabilone) were also included due to the general dearth of marijuana plant studies for a number of conditions. Indeed, for purposes of the review, references to oral administrations of marijuana constitute a pharmaceutical grade extraction administered in tablet or liquid form (e.g., dronabinol, Nabilone, Nabiximols), while references to smoked administration of marijuana constitute the inhalation of smoke from burned marijuana leaves and flowers. Finally, the present review is organized alphabetically by condition for which marijuana is allowed, rather than in order of disorder for which it is most to least commonly recommended, or strength of the evidence. We chose this approach as there is currently only state-level data [7]-[9], rather than national, representative data on the primary conditions for which medical marijuana is used or recommended, and the existing literature and state of the evidence for many conditions remains relatively poor.

Results

Alzheimer’s disease

AD, the leading form of dementia in the elderly, is a progressive, age-related disorder characterized by cognitive and memory deterioration [10]. AD has several neuropathological markers, including neuritic plaques and neurofibrillary tangles [11]. Although several researchers have suggested dronabinol and Nabilone may act on these mechanisms to confer therapeutic effects for patients with AD [12],[13], a recent Cochrane systematic review found no evidence that dronabinol was effective in reducing symptoms of dementia [14]. The authors of a placebo-controlled crossover study of 15 patients with AD who were refusing to eat suggest that dronabinol increases weight gain and decreases disturbed behavior [15], but there is insufficient quantitative data to support this conclusion [14], and one study participant had a grand mal seizure following dronabinol administration [15]. Another pilot study of two patients with dementia found that dronabinol reduced nocturnal motor activity [16]. No studies have examined the effects of smoked marijuana in patients with AD. In sum, there is insufficient evidence to recommend marijuana for the treatment of AD. Future directions should include conducting randomized controlled trials (RCTs) comparing both smoked and oral marijuana to placebo and existing treatments, with sample sizes large enough to detect treatment effects and the safety and tolerability of marijuana.

Amyotrophic lateral sclerosis

ALS is a fatal neurological disease with symptoms that include weakness, spasticity, and respiratory difficulties. Cannabinoids are hypothesized to act in the regions of established pathophysiology for ALS [17] and could be used for symptom management (e.g., pain, spasticity, wasting, respiratory failure, dysphagia, negative mood, and dysautonomia) [18]. Although there is limited evidence from a survey of patients with ALS that marijuana consumed in a variety of forms (i.e., oral, smoked, vaporized, and eaten) improves speech and swallowing [19], the anti-salivatory components of marijuana may reduce the risk of aspiration pneumonia, while also increasing patient comfort [18],[19]. These survey findings indicate that up to 10 percent of patients use marijuana for symptom management, and these self-reports suggest efficacy in increasing appetite and mood and decreasing pain, spasticity, and drooling. However, as is consistent with the half-life of smoked marijuana, the beneficial effects of marijuana on symptoms of ALS were fewer than 3 hours in duration [19]. The only randomized, double-blind, placebo-controlled crossover trial of marijuana in patients with ALS has a small sample size (N = 27) and indicates that while 5 mg of dronabinol is well-tolerated, there was no effect on number or intensity of cramps, quality of life, appetite, sleep, or mood [20]. There is currently insufficient clinical evidence in humans with ALS to recommend cannabinoids as primary or adjunctive therapy.

Cachexia/wasting syndrome

Cachexia is the general wasting and malnutrition that occurs in the context of chronic diseases such as HIV/AIDS and cancer. In patients with HIV or cancer, smoked marijuana and dronabinol have been shown to increase weight gain [21],[22] and food intake [22],[23] compared to placebo. In a within-subject, double-blind, staggered, double-dummy study of nine individuals with muscle mass loss, dronabinol resulted in significantly greater calorie consumption than smoked marijuana [24]. A within-subject, double-blind, placebo-controlled trial with seven HIV-positive marijuana smokers taking antiretroviral medications found that compared to placebo, dronabinol increased caloric intake [25]. Additional studies indicate that dronabinol administration increases appetite, decreases nausea, and protects against weight loss [26], with effects on appetite and weight stability enduring in long-term follow-up [27].

Both dronabinol and smoked marijuana increase the number of eating occasions [22],[25], and smoked marijuana may also affect weight gain and calorie intake by modulating appetite hormones [28]. Importantly, weight gain in one study was greater than would have been expected based on increased calorie consumption alone [23], which may be particularly relevant for those who have impaired food intake and/or nausea. These studies demonstrate that marijuana has positive effects on cachexia resulting from a medical condition, but are largely limited by small sample sizes. Additionally, studies comparing THC to FDA-approved medication (i.e., megestrol) indicate that THC is less effective in promoting appetite and weight gain [29]. In sum, there is moderate support for the use of cannabinoids for cachexia/wasting, and dronabinol has been FDA-approved for anorexia associated with weight loss in individuals with AIDS. Additional studies with larger sample sizes that examine the efficacy of marijuana compared to nutritional support/calorie augmentation in the treatment of cachexia are indicated.

Cancer

Cancer is a qualifying medical condition in every state that has approved marijuana for medical use [30]. The majority of clinical research examining the relation between THC and cancer has evaluated the effect of smoked THC on the risk for cancer, or the palliative effects of THC on chemotherapy-related nausea and emesis, chronic pain, and wasting (reviewed in respective sections); few studies have studied the effect of marijuana in any form on the treatment of primary cancer pathology. In vitro and in vivo research suggests that cannabinoids inhibit tumor growth [30] via several proposed mechanisms (e.g., suppression of cell proliferation, reduced cell migration, increased apoptosis) [31]; however, in vitro and in vivo studies also have shown that THC increases tumor growth due to reduced immune response to cancer [32]. The only clinical trial of THC on cancer examined intracranial administration of THC to nine patients with recurrent glioblastoma multiforme who had failed surgical- and radiotherapy, and results indicated that THC decreased tumor growth, while being well-tolerated with few psychotropic effects [33]. This study is limited by lack of generalizability, and clinical trials with larger representative samples that examine oral or smoked administration of THC are essential to elucidate the effects on cancer pathology. There is currently insufficient evidence to recommend marijuana for the treatment of cancer, but there may be secondary treatment effects on appetite and pain.

Crohn’s disease

CD is an inflammatory bowel disease (IBD) that has no cure; treatment targets include reducing inflammation and secondary symptoms. Between 16 percent and 50 percent of patients use marijuana to relieve symptoms of IBD [34]-[36], and patients using marijuana for 6 months or longer are five times more likely to have had surgery for their IBD [34]; whether marijuana exacerbates disease progression or more severe disease results in self-medication is unclear. Only one placebo-controlled study of the effects of marijuana in patients with CD has been conducted[37]. This study found that there was no difference between placebo and smoked marijuana on CD remission (defined as a CD Activity Index (CDAI) of less than 100), and that marijuana was superior to placebo in promoting clinical response (a decrease in CDAI score greater than 100), reducing steroid use, and improving sleep and appetite [37]. Importantly, this study did not include objective measurement of inflammatory activity, and there was no significant difference in placebo and treatment groups 2 weeks after treatment cessation [37]. Until clinical trials with objective measurement of treatment effects over an extended period of time are conducted to examine the safety and efficacy of marijuana for the treatment of IBD, there is insufficient evidence for the use of marijuana for the treatment of IBD.

Epilepsy and seizures

The known effects of cannabinoids on epilepsy and seizures are largely from animal studies, surveys, and case studies. Several animal studies indicate that marijuana and its constituents exhibit anticonvulsant effects [38]-[41] and reduce seizure-related mortality [39], but there is also evidence that cannabinoids can lower the threshold for seizures [42], and THC withdrawal increases susceptibility for convulsions [42]. Cross-sectional surveys indicate that 16–21 percent of patients with epilepsy smoke marijuana [43],[44], with some reporting positive effects (e.g., spasm reduction) and a belief that marijuana is an effective therapy [44], and others reporting increased seizure frequency and intensity [43]. Based on a Cochrane review, the few RCTs that have been conducted in humans include a total of 48 participants [45] and only examine treatment with cannabidiol. These trials exhibited heterogeneity of effects: some indicated a reduction in seizure frequency [46],[47], while others demonstrated no effect compared to placebo [48]. In addition, none of the studies examined response at greater than 6-month follow-up [45]. Systematic reviews of the literature have concluded that there is insufficient clinical data to support or refute the use of cannabinoids for the treatment of epilepsy and seizures [5],[45].

Glaucoma

Glaucoma is a neurodegenerative eye disease that can cause blindness by damaging retinal ganglion cells and axons of the optic nerve. Intraocular pressure (IOP) can influence both onset and progression of glaucoma and is often a target for intervention. Small samples have demonstrated reduced IOP following smoked marijuana [49],[50], but the effect is only present in 60–65 percent of individuals [51] and lasts for 3–4 hours, requiring repeated dosing throughout the day [52]. Furthermore, patients discontinue marijuana use due to side effects (e.g., dizziness, anxiety, dry mouth, sedation, depression, confusion, weight gain, and distortion of perception[53]), and this treatment discontinuity may exacerbate optic nerve damage and obviate the benefits of reduced IOP [54]. Limited research and documented toxicity have resulted in the American Glaucoma Society [54], Canadian Opthalmological Society [55], and the American Academy of Ophthalmology’s Complementary Therapies Task Force [52] determining that there is insufficient evidence to indicate that marijuana is safer or more effective than existing pharmacotherapy or surgery for the reduction of IOP. Development of eye drops for topical application of THC would minimize psychoactive and other side effects but is complicated by the high lipophilicity and low water solubility of cannabinoids [52],[56]. Additionally, the distance from the application site to the retina may be too great to afford neuroprotective benefits [52], given that only 5 percent of an applied dose penetrates the cornea to the intraocular space [56].

Hepatitis C virus

There have been no RCTs examining the use of cannabinoids on HCV infection. Of the studies that have been conducted, one longitudinal study demonstrates that smoked marijuana has no effect on HCV progression in individuals with HIV [57]. In contrast, individuals with HCV who smoke marijuana have a higher fibrosis progression rate [58] and more severe steatosis [59], with daily smokers having a more rapid rate of progression and greater severity [60] than occasional marijuana users [58],[59]. Marijuana may have independent negative effects on steatosis [59], but because none of these findings were in the context of a clinical trial, these correlations are not causal and it is possible that individuals who use marijuana do so to manage greater symptom severity [60].

There may be secondary effects of cannabinoids on HCV treatment side effects: dronabinol and Nabilone stabilized treatment-induced weight-loss [61]; and dronabinol, Nabilone, and marijuana procured from a marijuana club (dose and method of administration unspecified) increased HCV treatment duration and reduced post-treatment virological relapse [61],[62]. However, there is also a potential drug-drug interaction between ribavirin, a traditional HCV treatment, and marijuana due to shared cytochrome 450 metabolism [63]. Because 90 percent of HCV infections are the result of injection drug use [64], treatment of symptoms with marijuana may be contraindicated for this subpopulation, particularly because marijuana use in the context of other substance use (i.e., alcohol) has multiplicative effects on the odds of fibrosis severity [60]. Given that newer treatments for HCV (e.g., sofosbuvir) are replacing ribavirin, there will likely be less need for use of marijuana in management of treatment-related side effects. In sum, there is currently insufficient empirical support to recommend marijuana for the treatment of HCV.

HIV/AIDS

Marijuana use in HIV-infected patients is typically for the management of side effects (e.g., nausea) of older antiretroviral treatments and AIDS-related symptoms, including weight-loss and HIV-associated neuropathy (covered in cachexia and pain sections, respectively). Survey studies indicate that 23 percent of patients with HIV/AIDS smoked marijuana in the past month and do so largely to improve mood and appetite and reduce pain [65]; these patients may exhibit tolerance and need higher doses of THC than are currently approved by the FDA for use in clinical trials [25] to experience treatment effects. The few RCTs that have been conducted in a small number of patients with HIV/AIDS largely examined the effects of marijuana (synthetic or natural marijuana that is smoked or ingested) on symptoms (e.g., nausea and appetite) over a short treatment window (21–84 days; see [66] for systematic review). Studies examining the effects of marijuana on the pharmacokinetics of antiretroviral medication demonstrated that neither smoked marijuana nor dronabinol affects short-term clinical outcomes (e.g., viral load, CD4 and CD8 counts [67]), influences the efficacy of antiretroviral medication [68], or indicates that dose adjustments for protease inhibitors are necessary [21]. However, individuals who are dependent on marijuana have demonstrated poorer medication adherence and greater HIV symptoms and side effects than nonusers and nondependent users [69]. Furthermore, while some studies have no participant withdrawal due to adverse events [21],[70],[71], others reported treatment-limiting adverse events [26],[72],[73]. Finally, because drug use is a risk factor for HIV infection [74], treatment of symptoms with marijuana may be contraindicated for this subpopulation. In sum, there is variability in short-term outcomes and insufficient long-term data addressing the safety and efficacy of marijuana when used to manage symptoms of HIV/AIDS and its role in those also using newer, better-tolerated antiretroviral agents.

Multiple sclerosis and muscle spasticity

Muscle spasticity, a common feature of MS, is disordered sensorimotor control that leads to involuntary muscle activation [75] that results in pain, sleep disturbance, and increased morbidity[76]. The majority of studies examining spasticity have compared oral or sublingual forms of cannabinoids to placebo and found reduced spasm severity [77]-[84], with symptom improvement enduring at long-term follow-up [85]-[87], and also reduced spasm frequency and spasm-related pain and sleep disturbances [77],[88],[89]. With regard to smoked marijuana, one study found reductions in muscle spasticity [90]; however, another study showed that smoking marijuana impaired posture and balance in individuals with spasticity [91], so there is currently insufficient evidence to determine the efficacy of smoked marijuana on spasticity [5].

Surveys of patient populations show that between 14 and 16 percent of patients with MS report using marijuana for symptom management [92],[93] and that compared to non-marijuana-using individuals with MS, marijuana-using individuals with MS have decreased cognitive functioning[90],[94],[95]. Because cognitive dysfunction is present in 40–60 percent of individuals with MS before marijuana administration [96], marijuana use may further compromise impaired cerebral functioning in a neurologically vulnerable population. Additionally, future studies should carefully consider outcome assessment. The primary methods of measuring spasticity, the Ashworth Scale and patient self-report, may not be appropriate measures because antispastic drugs do not decrease Ashworth ratings, and patient-reported spasticity severity may be poorly correlated with patient functioning (i.e., a patient whose spasticity compensated for motor weakness may be unable to ambulate with reduced spasticity) [97]. Importantly for both MS and other neurological disorders, the American Academy of Neurology does not advocate the use of marijuana for the treatment of neurological disorders, due to insufficient evidence regarding treatment efficacy [98].

Post-traumatic stress disorder

There has been a recent emergence of empirical studies of the effects of marijuana on symptoms of PTSD, borne primarily out of the observation that individuals with PTSD report using marijuana to cope with PTSD symptoms; specifically, hyperarousal, negative affect, and sleep disturbances[99]-[101]. Empirical work has consistently demonstrated that the endocannabinoid system plays a significant role in the etiology of PTSD, with greater availability of cannabinoid type 1 receptors documented among those with PTSD than in trauma-exposed or healthy controls [102],[103]. Though the use of marijuana and oral THC [104],[105] have been implicated as a potential mechanism for the mitigation of many PTSD symptoms by way of their effects on the endocannabinoid system, some researchers caution that endocannabinoid activation with plant-based extracts over extended periods may lead to a number of deleterious consequences, including receptor downregulation and addiction [102].

There have been no RCTs of marijuana for the treatment of PTSD, though there has been one small RCT of Nabilone that showed promise for reducing nightmares associated with PTSD [106]. One unpublished pilot study of 29 Israeli combat veterans showed reductions in PTSD symptoms following the administration of smoked marijuana, with effects seen up to one year post-treatment[107]. Remaining studies have been primarily observational in nature, documenting that PTSD is associated with greater odds of a cannabis use disorder diagnosis [108] and greater marijuana craving and withdrawal immediately prior to a marijuana cessation attempt [109]. Indeed, sleep difficulties (a hallmark of PTSD) have been associated with poor marijuana cessation outcomes[110],[111], while cannabis use disorders have been associated with poorer PTSD treatment outcomes [112]. Given the lack of RCTs studying marijuana as a treatment for PTSD, there is insufficient scientific evidence for its use at this time.

Severe and chronic pain

Clinical trials have examined smoked and oral administration of cannabinoids on different types of pain (e.g., neuropathic, post-operative, experimentally induced) in multiple patient populations (e.g., HIV, cancer, and fibromyalgia). Two meta-analyses have been conducted examining the association between marijuana and pain. In the first, 18 RCTs demonstrated that any marijuana preparation containing THC, applied by any route of administration, significantly decreased pain scores from baseline compared to placebo [113]. The second examined 19 RCTs of smoked marijuana in individuals with HIV, which also indicated greater efficacy in reducing pain (i.e., sensory neuropathy) compared to placebo [114]. Importantly, the first meta-analysis showed that marijuana increased the odds of altered perception, motor function, and cognition by 4 to 5 times[113], and the second study did not recommend marijuana as routine therapy [114]. Dosage is an important factor to consider for administration of cannabinoids for pain management, as some studies have found that higher doses of smoked marijuana are associated with improved analgesia[115], whereas other studies show that higher doses of smoked marijuana increase pain response[116]. Because the analgesic effects of marijuana are comparable to those of traditional pain medications [117], future research should aim to identify which analgesics provide the lowest risk profile for the management of severe and chronic pain. Although there is preliminary support to suggest that marijuana may have analgesic effects, there is insufficient research on dosing and side effect profile, which precludes recommending marijuana for the management of severe and chronic pain.

Severe nausea

The majority of research related to the effects of marijuana on severe nausea has involved oral administration of marijuana to individuals with chemotherapy-induced nausea and vomiting (CINV). Oral marijuana (i.e., THC suspension in sesame oil and gelatin) has been shown to be more effective in reducing CINV than placebo [118], including the number and volume of vomiting episodes, and the severity and duration of nausea [119]. When compared to traditional anti-emetics, some meta-analytic reviews indicate that oral THC is more effective in reducing CINV[120]-[123], others find no significant difference [122],[124]-[126], and another suggests that combining both is the most effective at reducing the duration and severity of CINV than either alone [127]. Recent advances in both anti-emetic agents and the mechanisms of cannabinoid administration (i.e., sublingual application) warrant future research.

Importantly, patients receiving cannabinoids for severe nausea reported toxicities, including paranoid delusions (5%), hallucinations (6%), and dysphoria (13%) [122]. Additionally, cannabinoid hyperemesis syndrome has been documented, in which persistent and regular marijuana use (i.e., daily or weekly use for more than 1 year) is associated with cyclic vomiting (i.e., episodic nausea and vomiting) [128] and nonresponse to treatment for cyclic vomiting [129]. Dronabinol has been FDA-approved for CINV in individuals who have not shown a treatment response to traditional anti-emetics, but in line with recommendations from the American Society of Clinical Oncology [130] and the European Society for Medical Oncology [131], cannabinoids should not be utilized as a first-line treatment for nausea and vomiting.

Conclusions

The reviewed literature highlights the dearth of rigorous research on the effects of marijuana for the most common conditions for which it is currently recommended. It is paramount that well-designed RCTs with larger sample sizes be conducted to determine the actual medical benefits and adverse effects of marijuana for each of the above conditions. Indeed, recent reviews [4],[132] comprehensively discuss adverse events associated with marijuana use, and while it is beyond the scope of the current paper to review these effects in-depth, they are important to consider when evaluating whether or not to recommend marijuana for a medical or psychiatric disorder in place of other existing treatment options.

Given the extensive literature speaking to the harms associated with marijuana use, research on the comparative safety, tolerability, efficacy, and risk of marijuana compared to existing pharmacological agents is needed. The present literature also illuminates the need for research into the effects of isolated cannabinoids (e.g., THC, CBD) as well as species of smoked marijuana (e.g., indica and sativa), as the majority of medical marijuana users ingest marijuana by smoking the marijuana plant [133],[134], which contains a wide variety of phytocannabinoids at varying potencies [135],[136]. Furthermore, improved and objective measurement of clinical outcomes should be implemented in clinical trials to determine treatment efficacy. Finally, little research has considered the issues of dose, duration, and potency. If research identifies a therapeutic effect of marijuana for medical or psychiatric conditions, there will need to be revisions in marijuana policy to increase quality control so that dose and potency are valid and reliable. Additionally, risk of abuse and diversion can be decreased by developing prescribing practices with continued supervision of a medical professional, creating prescription monitoring programs to reduce the risk of “doctor shopping”, and identifying provisions for the safe disposal of unused cannabinoids. In sum, the current literature does not adequately support the widespread adoption and use of marijuana for medical and psychiatric conditions at this time.

Source: :http://www.ascpjournal.org/content/10/1/10 21st April 2015

Abbreviations

THC: Δ9-tetrahydrocannabinol

HIV: Human immunodeficiency virus

AIDS: Acquired immunodeficiency syndrome

RCTs: Randomized controlled trials

IOP: Intraocular pressure

MS: Multiple sclerosis

CINV: Chemotherapy-induced nausea and vomiting

HCV: Hepatitis C virus

ALS: Amyotrophic lateral sclerosis

CD: Crohn’s disease

IBD: Inflammatory bowel disease

AD: Alzheimer’s disease

PTSD: Post-traumatic stress disorder

CB1: Cannabinoid type 1

CBD: Cannabidiol

Competing interests

Dr. Belendiuk holds stock in Shire Pharmaceuticals.

Authors’ contributions

Dr. KAB synthesized the literature and authored sections of the manuscript. Ms. LLB assisted with the literature search and synthesis. Dr. MOB-M conceived the review, assisted in the search and synthesis of existing literature, and authored sections of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

Dr. Belendiuk’s salary was supported by National Institute of Mental Health R01 MH40564.

Dr. Bonn-Miller’s salary was supported by the VA Center of Excellence for Substance Abuse Treatment and Education.

Literature review and synthesis was supported by a grant from the VA Substance Use Disorder Quality Enhancement Research Initiative (SUDQ-LIP1410).

The above funding agencies played no role in the writing of the manuscript or decision to submit the manuscript for publication. The expressed views do not necessarily represent those of the Department of Veterans Affairs.

References

    1. Substance Abuse and Mental Health Services Administration: Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. Department of Health and Human Services, Rockville, MD. U.S; 2013.
    2. Bonn-Miller MO, Harris AH, Trafton JA: Prevalence of cannabis use disorder diagnoses among veterans in 2002, 2008, and 2009. Psycholog Serv 2012, 9:404-16.

     

    1. Johnston LD, O’Malley PM, Miech RA, Bachman JG, Schulenberg JE: Monitoring the Future national results on drug use: 1975–2013: Overview, Key Findings on Adolescent Drug Use. Institute for Social Research, The University of Michigan, Ann Arbor; 2014.
    2. Volkow ND, Baler RD, Compton WM, Weiss SR: Adverse health effects of marijuana use.

    N Engl J Med 2014, 370:2219-27. PubMed Abstract | Publisher Full Text

    1. Koppel BS, Brust JC, Fife T, Bronstein J, Youssof S, Gronseth G, et al.: Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the guideline development subcommittee of the American academy of neurology.

    Neurology 2014, 82:1556-63. PubMed Abstract | Publisher Full Text

    1. Procon.org. 23 legal medical marijuana states and DC: Laws, fees, and possession limits. Retrieved April 9, 2015, from [http://medicalmarijuana.procon.org/view.resource.php?resourceID=000881]
    2. Bonn-Miller MO, Boden MT, Bucossi MM, Babson KA: Self-reported cannabis use characteristics, patterns and helpfulness among medical cannabis users.

    Am J Drug Alcohol Abuse 2014, 40:23-30. PubMed Abstract | Publisher Full Text

    1. Ilgen MA, Bohnert K, Kleinberg F, Jannausch M, Bohnert ASB, Walton MA, et al.:Characteristics of adults seeking medical marijuana certification.

    Drug Alcohol Depend 2013, 132:654-9. PubMed Abstract | Publisher Full Text

    1. Nunberg H, Kilmer B, Pacula RL, Burgdorf J: An analysis of applicants presenting to a medical marijuana specialty practice in California.

    J Drug Policy Anal. 2011, 4:1. PubMed Abstract | Publisher Full Text

    1. Minati L, Edginton T, Bruzzone MG, Giaccone G: Reviews: current concepts in Alzheimer’s disease: a multidisciplinary review.

    Am J Alzheimers Dis Other Demen 2009, 24:95-121. PubMed Abstract | Publisher Full Text

    1. Fagan SG, Campbell VA: The influence of cannabinoids on generic traits of neurodegeneration.

    Br J Pharmacol 2014, 171:1347-60. PubMed Abstract | Publisher Full Text

    1. Gowran A, Noonan J, Campbell VA: The multiplicity of action of cannabinoids: implications for treating neurodegeneration.

    CNS Neurosci Ther 2011, 17:637-44. PubMed Abstract | Publisher Full Text

    1. Aso E, Ferrer I: Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.

    Front Pharmacol 2014, 5:37. PubMed Abstract | Publisher Full Text

    1. Krishnan S, Cairns R, Howard R: Cannabinoids for the treatment of dementia.

    Cochrane Database Syst Rev 2009, 2:CD007204. PubMed Abstract | Publisher Full Text

    1. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ: Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease.

    Int J Geriatr Psychiatry 1997, 12:913-9. PubMed Abstract | Publisher Full Text

    1. Walther S, Schüpbach B, Seifritz E, Homan P, Strik W: Randomized, controlled crossover trial of dronabinol, 2.5 mg, for agitation in 2 patients with dementia.

    J Clin Psychopharmacol 2011, 31:256-8. PubMed Abstract | Publisher Full Text

    1. Carter GT, Abood ME, Aggarwal SK, Weiss MD: Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials.

    Am J Hosp Palliat Care 2010, 27:347-56. PubMed Abstract | Publisher Full Text

    1. Carter GT, Rosen BS: Marijuana in the management of amyotrophic lateral sclerosis.

    Am J Hosp Palliat Care 2001, 18:264-70. PubMed Abstract | Publisher Full Text

    1. Amtmann D, Weydt P, Johnson KL, Jensen MP, Carter GT: Survey of cannabis use in patients with amyotrophic lateral sclerosis.

    Am J Hosp Palliat Care 2004, 21:95-104. PubMed Abstract | Publisher Full Text

    1. Weber M, Goldman B, Truniger S: Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial.

    J Neurol Neurosurg Psychiatry 2010, 81:1135-40. PubMed Abstract | Publisher Full Text

    1. Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, et al.: Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial.

    Ann Intern Med 2003, 139:258-66. PubMed Abstract | Publisher Full Text

    1. Haney M, Gunderson EW, Rabkin J, Hart CL, Vosburg SK, Comer SD, et al.: Dronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep.

    J Acquir Immune Defic Syndr 2007, 45:545-54. PubMed Abstract | Publisher Full Text

    1. Foltin RW, Fischman MW, Byrne MF: Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory.

    Appetite 1988, 11:1-14. PubMed Abstract | Publisher Full Text

    1. Haney M: Effects of smoked marijuana in healthy and HIV+ marijuana smokers.

    J Clin Pharmacol 2002, 42:34S-40. PubMed Abstract | Publisher Full Text

    1. Bedi G, Foltin RW, Gunderson EW, Rabkin J, Hart CL, Comer SD, et al.: Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study.

    Psychopharmacol (Berl) 2010, 212:675-86.

    1. Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, et al.: Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.

    J Pain Symptom Manage 1995, 10:89-97. PubMed Abstract | Publisher Full Text

    1. Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B, et al.: Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia.

    J Pain Symptom Manage 1997, 14:7-14. PubMed Abstract | Publisher Full Text

    1. Riggs PK, Vaida F, Rossi SS, Sorkin LS, Gouaux B, Grant I, et al.: A pilot study of the effects of cannabis on appetite hormones in HIV-infected adult men.

    Brain Res 2012, 1431:46-52. PubMed Abstract | Publisher Full Text

    1. Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, et al.: Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a north central cancer treatment group study.

    J Clin Oncol 2002, 20:567-73. PubMed Abstract | Publisher Full Text

    1. Bowles DW, O’Bryant CL, Camidge DR, Jimeno A: The intersection between cannabis and cancer in the United States.

    Crit Rev Oncol Hematol 2012, 83:1-10. PubMed Abstract | Publisher Full Text

    1. Pisanti S, Malfitano AM, Grimaldi C, Santoro A, Gazzerro P, Laezza C, et al.: Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents.

    Best Prac Res Clin Endocrinol Metab 2009, 23:117-31.

    1. McKallip RJ, Nagarkatti M, Nagarkatti PS: Δ-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response.

    J Immunol 2005, 174:3281-9. PubMed Abstract | Publisher Full Text

    1. Guzman M, Duarte MJ, Blazquez C, Ravina J, Rosa MC, Galve-Roperh I, et al.: A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme.

    Br J Cancer 2006, 95:197-203. PubMed Abstract | Publisher Full Text

    1. Storr M, Devlin S, Kaplan GG, Panaccione R, Andrews CN: Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn’s disease.

    Inflamm Bowel Dis 2014, 20:472-80. PubMed Abstract | Publisher Full Text

    1. Lal S, Prasad N, Ryan M, Tangri S, Silverberg MS, Gordon A, et al.: Cannabis use amongst patients with inflammatory bowel disease.

    Eur J Gastroenterol Hepatol 2011, 23:891-6. PubMed Abstract | Publisher Full Text

    1. Allegretti JR, Courtwright A, Lucci M, Korzenik JR, Levine J: Marijuana use patterns among patients with inflammatory bowel disease.

    Inflamm Bowel Dis 2013, 19:2809-14.

    1. Naftali T, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM:Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study.

    Clin Gastroenterol Hepatol 2013, 11:1276-80. PubMed Abstract | Publisher Full Text

    1. Hill TD, Cascio MG, Romano B, Duncan M, Pertwee RG, Williams CM, et al.: Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.

    Br J Pharmacol 2013, 170:679-92. PubMed Abstract | Publisher Full Text

    1. Jones NA, Glyn SE, Akiyama S, Hill TD, Hill AJ, Weston SE, et al.: Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

    Seizure 2012, 21:344-52. PubMed Abstract | Publisher Full Text

    1. Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ: The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy.

    J Pharmacol Exp Ther 2003, 307:129-37. PubMed Abstract | Publisher Full Text

    1. Jones NA, Hill AJ, Smith I, Bevan SA, Williams CM, Whalley BJ, et al.: Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo.

    J Pharmacol Exp Ther 2010, 332:569-77. PubMed Abstract | Publisher Full Text

    1. Gordon E, Devinsky O: Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy.

    Epilepsia 2001, 42:1266-72. PubMed Abstract | Publisher Full Text

    1. Hamerle M, Ghaeni L, Kowski A, Weissinger F, Holtkamp M: Cannabis and other illicit drug use in epilepsy patients.

    Eur J Neurol 2014, 21:167-70. PubMed Abstract | Publisher Full Text

    1. Gross DW, Hamm J, Ashworth NL, Quigley D: Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center.

    Neurology 2004, 62:2095-7. PubMed Abstract | Publisher Full Text

    1. Gloss D, Vickrey B: Cannabinoids for epilepsy.

    Cochrane Database Syst Rev 2014, 3:CD009270. PubMed Abstract | Publisher Full Text

    1. Mechoulam R, Carlini EA: Toward drugs derived from cannabis.

    Naturwissenschaften 1978, 65:174-9. PubMed Abstract | Publisher Full Text

    1. Cunha JM, Carlini EA, Pereira AE, Ramos OL, Pimentel C, Gagliardi R, et al.: Chronic administration of cannabidiol to healthy volunteers and epileptic patients.

    Pharmacology 1980, 21:175-85. PubMed Abstract | Publisher Full Text

    1. Ames FR, Cridland S: Anticonvulsant effect of cannabidiol.

    S Afr Med J 1986, 69:14. PubMed Abstract | Publisher Full Text

    1. Merritt JC, Crawford WJ, Alexander PC, Anduze AL, Gelbart SS: Effect of marihuana on intraocular and blood pressure in glaucoma.

    Ophthalmology 1980, 87:222-8. PubMed Abstract | Publisher Full Text

    1. Hepler RS, Frank IR: Marihuana smoking and intraocular pressure.

    JAMA 1971, 217:1392. PubMed Abstract | Publisher Full Text

    1. Green K: Marijuana smoking vs cannabinoids for glaucoma therapy.

    Arch Ophthalmol 1998, 116:1433-7. PubMed Abstract | Publisher Full Text

    1. Nucci C, Bari M, Spanò A, Corasaniti M, Bagetta G, Maccarrone M, et al.: Potential roles of (endo) cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection.

    Prog Brain Res 2008, 173:451-64. PubMed Abstract | Publisher Full Text

    1. Flach AJ: Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma.

    Trans Am Ophthalmol Soc 2002, 100:215-22. PubMed Abstract | Publisher Full Text

    1. Jampel H: American glaucoma society position statement: marijuana and the treatment of glaucoma.

    J Glaucoma 2010, 19:75-6. PubMed Abstract | Publisher Full Text

    1. Buys YM, Rafuse PE: Canadian ophthalmological society policy statement on the medical use of marijuana for glaucoma.

    Can J Ophthalmol 2010, 45:324-6. PubMed Abstract | Publisher Full Text

    1. Tomida I, Pertwee RG, Azuara-Blanco A: Cannabinoids and glaucoma.

    Br J Ophthalmol 2004, 88:708-13. PubMed Abstract | Publisher Full Text

    1. Brunet L, Moodie EE, Rollet K, Cooper C, Walmsley S, Potter M, et al.: Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis.

    Clin Infect Dis 2013, 57:663-70. PubMed Abstract | Publisher Full Text

    1. Hézode C, Roudot-Thoraval F, Nguyen S, Grenard P, Julien B, Zafrani E-S, et al.: Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C.

    Hepatology 2005, 42:63-71. PubMed Abstract | Publisher Full Text

    1. Hézode C, Zafrani ES, Roudot-Thoraval F, Costentin C, Hessami A, Bouvier–Alias M, et al.:Daily cannabis use: a novel risk factor of steatosis severity in patients with chronic hepatitis C.

    Gastroenterology 2008, 134:432-9. PubMed Abstract | Publisher Full Text

    1. Ishida JH, Peters MG, Jin C, Louie K, Tan V, Bacchetti P, et al.: Influence of cannabis use on severity of hepatitis C disease.

    Clin Gastroenterol Hepatol 2008, 6:69-75. PubMed Abstract | Publisher Full Text

    1. Costiniuk CT, Mills E, Cooper CL: Evaluation of oral cannabinoid-containing medications for the management of interferon and ribavirin-induced anorexia, nausea and weight loss in patients treated for chronic hepatitis C virus.

    Can J Gastroenterol 2008, 22:376-80. PubMed Abstract | Publisher Full Text

    1. Sylvestre DL, Clements BJ, Malibu Y: Cannabis use improves retention and virological outcomes in patients treated for hepatitis C.

    Eur J Gastroenterol Hepatol 2006, 18:1057-63. PubMed Abstract | Publisher Full Text

    1. Glue P: The clinical pharmacology of ribavirin.

    Semin Liver Dis 1998, 19S:17-24.

    1. Wasley A, Grytdal S, Gallagher K: Centers for Disease Control and Prevention (CDC):Surveillance for acute viral hepatitis — United States, 2006.

    MMWR Surveill Summ 2008, 57:1-24. PubMed Abstract | Publisher Full Text

    1. Prentiss D, Power R, Balmas G, Tzuang G, Israelski DM: Patterns of marijuana use among patients with HIV/AIDS followed in a public health care setting.

    J Acquir Immune Defic Syndr 2004, 35:38-45. PubMed Abstract | Publisher Full Text

    1. Lutge EE, Gray A, Siegfried N: The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS.

    Cochrane Database Syst Rev 2013, 4:CD005175. PubMed Abstract | Publisher Full Text

    1. Bredt BM, Higuera-Alhino D, Shade SB, Hebert SJ, McCune JM, Abrams DI: Short-term effects of cannabinoids on immune phenotype and function in HIV-1-infected patients.

    J Clin Pharmacol 2002, 42:82S-9. PubMed Abstract | Publisher Full Text

    1. Kosel BW, Aweeka FT, Benowitz NL, Shade SB, Hilton JF, Lizak PS, et al.: The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir.

    AIDS 2002, 16:543-50. PubMed Abstract | Publisher Full Text

    1. Bonn-Miller MO, Oser ML, Bucossi MM, Trafton JA: Cannabis use and HIV antiretroviral therapy adherence and HIV-related symptoms.

    J Behav Med 2014, 37:1-10. PubMed Abstract | Publisher Full Text

    1. Haney M, Rabkin J, Gunderson E, Foltin RW: Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood.

    Psychopharmacology (Berl) 2005, 181:170-8.

    1. Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, et al.: Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial.

    Neurology 2007, 68:515-21. PubMed Abstract | Publisher Full Text

    1. Ellis RJ, Toperoff W, Vaida F, van den Brande G, Gonzales J, Gouaux B, et al.: Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial.

    Neuropsychopharmacology 2009, 34:672-80. PubMed Abstract | Publisher Full Text

    1. Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV, et al.: Effect of dronabinol on nutritional status in HIV infection.

    Ann Pharmacother 1993, 27:827-31. PubMed Abstract | Publisher Full Text

    1. Centers for Disease Control and Prevention (CDC). HIV and substance use in the United States. Retrieved April 9, 2015, from [http://www.cdc.gov/hiv/risk/behavior/substanceuse.html]
    2. Pandyan AD, Gregoric M, Barnes MP, Wood D, van Wijck F, Burridge J, et al.: Spasticity: clinical perceptions, neurological realities and meaningful measurement.

    Disabil Rehabil 2005, 27:2-6. PubMed Abstract | Publisher Full Text

    1. Beard S, Hunn A, Wight J: Treatments for spasticity and pain in multiple sclerosis: a systematic review.

    Health Technol Assess 2003, 7(40):1-111.

    1. Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, et al.: A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols*(Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis.

    Eur J Neurol 2011, 18:1122-31. PubMed Abstract | Publisher Full Text

    1. Wade DT, Makela P, Robson P, House H, Bateman C: Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.

    Mult Scler 2004, 10:434-41. PubMed Abstract | Publisher Full Text

    1. Collin C, Davies P, Mutiboko IK, Ratcliffe S: Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.

    Eur J Neurol 2007, 14:290-6. PubMed Abstract | Publisher Full Text

    1. Wade DT, Collin C, Stott C, Duncombe P: Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis.

    Mult Scler 2010, 16:707-14. PubMed Abstract | Publisher Full Text

    1. Wade DT, Robson P, House H, Makela P, Aram J: A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.

    Clin Rehabil 2003, 17:21-9. PubMed Abstract | Publisher Full Text

    1. Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, et al.: Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up.

    J Neurol Neurosurg Psychiatry 2005, 76:1664-9. PubMed Abstract | Publisher Full Text

    1. Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, et al.: Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.

    Lancet 2003, 362:1517-26. PubMed Abstract | Publisher Full Text

    1. Pooyania S, Ethans K, Szturm T, Casey A, Perry D: A randomized, double-blinded, crossover pilot study assessing the effect of nabilone on spasticity in persons with spinal cord injury.

    Arch Phys Med Rehabil 2010, 91:703-7. PubMed Abstract | Publisher Full Text

    1. Wade DT, Makela PM, House H, Bateman C, Robson P: Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis.

    Mult Scler 2006, 12:639-45. PubMed Abstract | Publisher Full Text

    1. Serpell MG, Notcutt W, Collin C: Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.

    J Neurol 2013, 260:285-95. PubMed Abstract | Publisher Full Text

    1. Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R: A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex®(nabiximols).

    Mult Scler 2012, 18:219-28. PubMed Abstract | Publisher Full Text

    1. Flachenecker P, Henze T, Zettl UK: Nabiximols (THC/CBD oromucosal spray, Sativex®) in clinical practice—results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity.

    Eur Neurol 2014, 71:271-9. PubMed Abstract | Publisher Full Text

    1. Rog DJ, Nurmikko TJ, Friede T, Young CA: Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.

    Neurology 2005, 65:812-9. PubMed Abstract | Publisher Full Text

    1. Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte TD, Bentley H, et al.: Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

    CMAJ 2012, 184:1143-50. PubMed Abstract | Publisher Full Text

    1. Greenberg HS, Werness SA, Pugh JE, Andrus RO, Anderson DJ, Domino EF: Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers.

    Clin Pharmacol Ther 1994, 55:324-8. PubMed Abstract | Publisher Full Text

    1. Clark AJ, Ware MA, Yazer E, Murray TJ, Lynch ME: Patterns of cannabis use among patients with multiple sclerosis.

    Neurology 2004, 62:2098-100. PubMed Abstract | Publisher Full Text

    1. Page SA, Verhoef MJ, Stebbins RA, Metz LM, Levy JC: Cannabis use as described by people with multiple sclerosis.

    Can J Neurol Sci 2003, 30:201-5. PubMed Abstract | Publisher Full Text

    1. Pavisian B, MacIntosh BJ, Szilagyi G, Staines RW, O’Connor P, Feinstein A: Effects of cannabis on cognition in patients with MS: a psychometric and MRI study.

    Neurology 2014, 82:1879-87. PubMed Abstract | Publisher Full Text

    1. Honarmand K, Tierney MC, O’Connor P, Feinstein A: Effects of cannabis on cognitive function in patients with multiple sclerosis.

    Neurology 2011, 76:1153-60. PubMed Abstract | Publisher Full Text

    1. Rao SM, Leo GJ, Bernardin L, Unverzagt F: Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction.

    Neurology 1991, 41:685-91. PubMed Abstract | Publisher Full Text

    1. Leussink VI, Husseini L, Warnke C, Broussalis E, Hartung HP, Kieseier BC: Symptomatic therapy in multiple sclerosis: the role of cannabinoids in treating spasticity.

    Ther Adv Neurol Disord 2012, 5:255-66. PubMed Abstract | Publisher Full Text

    1. American Academy of Neurology. Position statement: Use of medical marijuana for neurologic disorders. Retrieved April 9, 2015, from [https://www.aan.com/uploadedFiles/Website_Library_Assets/Documents/6.Public_Policy/1.Stay_Informed/2.Position_Statements/3.PDFs_of_all_Position_Statements/Final%20Medical%20Marijuana%20Position%20Statement.pdf]
    2. Bonn-Miller MO, Vujanovic AA, Feldner MT, Bernstein A, Zvolensky MJ: Posttraumatic stress symptom severity predicts marijuana use coping motives among traumatic event-exposed marijuana users.

    J Trauma Stress 2007, 20:577-86. PubMed Abstract | Publisher Full Text

    1. Bremner JD, Southwick SM, Darnell A, Charney DS: Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse.

    Amer J Psychiatry 1996, 153:369-75.

    1. Vandrey R, Babson KA, Herrmann ES, Bonn-Miller MO: Interactions between disordered sleep, post-traumatic stress disorder, and substance use disorders.

    Int Rev Psychiatry 2014, 26:237-47. PubMed Abstract | Publisher Full Text

    1. Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, et al.:Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study.

    Mol Psychiatry 2013, 18:1034-40. PubMed Abstract | Publisher Full Text

    1. Passie T, Emrich HM, Karst M, Brandt SD, Halpern JH: Mitigation of post-traumatic stress symptoms by cannabis resin: a review of the clinical and neurobiological evidence.

    Drug Test Anal 2012, 4:649-59. PubMed Abstract | Publisher Full Text

    1. Roitman P, Mechoulam R, Cooper-Kazaz R, Shalev A: Preliminary, open-label, pilot study of add-on oral Δ-tetrahydrocannabinol in chronic post-traumatic stress disorder.

    Clin Drug Investig 2014, 34:587-91. PubMed Abstract | Publisher Full Text

    1. Fraser GA: The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD).

    CNS Neurosci Ther 2009, 15:84-8. PubMed Abstract | Publisher Full Text

    1. Jetly R, Heber A, Fraser G, Boisvert D: The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: a preliminary randomized, double-blind, placebo-controlled cross-over design study.

    Psychoneuroendocrinology 2015, 51:585-8. PubMed Abstract | Publisher Full Text

    1. Mashiah M. Medical cannabis as treatment for chronic combat PTSD: Promising results in an open pilot study [presentation]. Patients Out of Time Conference; Tuscon, Arizona; 2012.
    2. Cougle JR, Bonn-Miller MO, Vujanovic AA, Zvolensky MJ, Hawkins KA: Posttraumatic stress disorder and cannabis use in a nationally representative sample.

    Psychol Addict Behav 2011, 25:554-8. PubMed Abstract | Publisher Full Text

    1. Boden MT, Babson KA, Vujanovic AA, Short NA, Bonn-Miller MO: Posttraumatic stress disorder and cannabis use characteristics among military veterans with cannabis dependence.

    Am J Addict 2013, 22:277-84. PubMed Abstract | Publisher Full Text

    1. Babson KA, Boden MT, Harris AH, Stickle TR, Bonn-Miller MO: Poor sleep quality as a risk factor for lapse following a cannabis quit attempt.

    J Subst Abuse Treat 2013, 44:438-43. PubMed Abstract | Publisher Full Text

    1. Babson KA, Boden MT, Bonn-Miller MO: The impact of perceived sleep quality and sleep efficiency/duration on cannabis use during a self-guided quit attempt.

    Addict Behav 2013, 38:2707-13. PubMed Abstract | Publisher Full Text

    1. Bonn-Miller MO, Boden MT, Vujanovic AA, Drescher KD: Prospective investigation of the impact of cannabis use disorders on posttraumatic stress disorder symptoms among veterans in residential treatment.

    Psychological Trauma: Theory, Research, Practice, and Policy 2013, 5:193-200.

    1. Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL: Systematic review and meta-analysis of cannabis treatment for chronic pain.

    Pain Med 2009, 10:1353-68. PubMed Abstract | Publisher Full Text

    1. Phillips TJC, Cherry CL, Cox S, Marshall SJ, Rice ASC: Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials.

    PLoS One 2010, 5:e14433. PubMed Abstract | Publisher Full Text

    1. Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, et al.: Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.

    CMAJ 2010, 182:E694-701. PubMed Abstract | Publisher Full Text

    1. Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, et al.: Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers.

    Anesthesiology 2007, 107:785-96. PubMed Abstract | Publisher Full Text

    1. Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H: Low-dose vaporized cannabis significantly improves neuropathic pain.

    J Pain 2013, 14:136-48. PubMed Abstract | Publisher Full Text

    1. Sallan SE, Zinberg NE, Frei E 3rd: Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy.

    N Engl J Med 1975, 293:795-7. PubMed Abstract | Publisher Full Text

    1. Chang AE, Shiling DJ, Stillman RC, Goldberg NH, Seipp CA, Barofsky I, et al.: Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate: a prospective, randomized evaluation.

    Ann Intern Med 1979, 91:819-24. PubMed Abstract | Publisher Full Text

    1. Orr LE, McKernan JF, Bloome B: Antiemetic effect of tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis.

    Arch Intern Med 1980, 140:1431-3. PubMed Abstract | Publisher Full Text

    1. Ben Amar M: Cannabinoids in medicine: a review of their therapeutic potential.

    J Ethnopharmacol 2006, 105:1-25. PubMed Abstract | Publisher Full Text

    1. Machado Rocha FC, Stefano SC, De Cassia HR, Rosa Oliveira LM, Da Silveira DX:Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis.

    Eur J Cancer Care (Engl) 2008, 17:431-43.

    1. Tramèr MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ: Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.

    BMJ 2001, 323:16-21. PubMed Abstract | Publisher Full Text

    1. Frytak S, Moertel CG, O’Fallon JR, Rubin J, Creagan ET, O’Connell MJ, et al.: Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo.

    Ann Intern Med 1979, 91:825-30. PubMed Abstract | Publisher Full Text

    1. Ungerleider JT, Andrysiak T, Fairbanks L, Goodnight J, Sarna G, Jamison K: Cannabis and cancer chemotherapy: a comparison of oral delta-9-THC and prochlorperazine.

    Cancer 1982, 50:636-45. PubMed Abstract | Publisher Full Text

    1. Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang HM, et al.: Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting.

    Curr Med Res Opin 2007, 23:533-43. PubMed Abstract | Publisher Full Text

    1. Lane M, Vogel CL, Ferguson J, Krasnow S, Saiers JL, Hamm J, et al.: Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting.

    J Pain Symptom Manage 1991, 6:352-9. PubMed Abstract | Publisher Full Text

    1. Sun S, Zimmermann AE: Cannabinoid hyperemesis syndrome.

    Hosp Pharm 2013, 48:650-5. PubMed Abstract | Publisher Full Text

    1. Hejazi RA, McCallum RW: Review article: cyclic vomiting syndrome in adults–rediscovering and redefining an old entity.

    Aliment Pharmacol Ther 2011, 34:263-73. PubMed Abstract | Publisher Full Text

    1. Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, et al.: Antiemetics: American society of clinical oncology clinical practice guideline update.

    J Clin Oncol 2011, 29:4189-98. PubMed Abstract | Publisher Full Text

    1. Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, et al.: Guideline update for MASCC and ESMO in the prevention of chemotherapy-and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference.

    Ann Onco 2010, 21(5):232-43.

    1. Gordon AJ, Conley JW, Gordon JM: Medical consequences of marijuana use: a review of current literature.

    Curr Psychiatry Rep 2013, 15:419. PubMed Abstract | Publisher Full Text

    1. Reinarman C, Nunberg H, Lanthier F, Heddleston T: Who are medical marijuana patients? Population characteristics from nine California assessment clinics.

    J Psychoactive Drugs 2011, 43:128-35. PubMed Abstract | Publisher Full Text

    1. Walsh Z, Callaway R, Belle-Isle L, Capler R, Kay R, Lucas P, et al.: Cannabis for therapeutic purposes: patient characteristics, access, and reasons for use.

    Int J Drug Policy 2013, 24:511-6. PubMed Abstract | Publisher Full Text

    1. Potter DJ, Clark P, Brown MB: Potency of delta 9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology.

    J Forensic Sci 2008, 53:90-4. PubMed Abstract | Publisher Full Text

    1. Hillig KW, Mahlberg PG: A chemotaxonomic analysis of cannabinoid variation in cannabis (Cannabaceae).

    Am J Bot 2004, 91:966-75. PubMed Abstract | Publisher Full Text

 

 

Marijuana use for medical conditions is an issue of growing concern. Some Veterans use marijuana to relieve symptoms of PTSD and several states specifically approve the use of medical marijuana for PTSD. However, controlled studies have not been conducted to evaluate the safety or effectiveness of medical marijuana for PTSD. Thus, there is no evidence at this time that marijuana is an effective treatment for PTSD. In fact, research suggests that marijuana can be harmful to individuals with PTSD.

Epidemiology

Marijuana use has increased over the past decade. In 2013, a study found that 19.8 million people reported using marijuana in the past month, with 8.1 million using almost every day (1). Daily use has increased 60% in the prior decade (1). A number of factors are associated with increased risk of marijuana use, including diagnosis of PTSD (2), social anxiety disorder (3), other substance use, particularly during youth (4), and peer substance use (5).

Cannabis Use Disorder among Veterans Using VA Health Care

There has been no study of marijuana use in the overall Veteran population. What we do know comes from looking at data of Veterans using VA health care, who may not be representative of Veterans overall. When considering the subset of Veterans seen in VA health care with co-occurring PTSD and substance use disorders (SUD), cannabis use disorder has been the most diagnosed SUD since 2009. The percentage of Veterans in VA with PTSD and SUD who were diagnosed with cannabis use disorder increased from 13.0% in fiscal year (FY) 2002 to 22.7% in FY 2014. As of FY 2014, there are more than 40,000 Veterans with PTSD and SUD seen in VA diagnosed with cannabis use disorder (6).

trends-inptsd

 

Problems Associated with Marijuana Use

Marijuana use is associated with medical and psychiatric problems. These problems may be caused by using, but they also may reflect the characteristics of the people who use marijuana. Medical problems include chronic bronchitis, abnormal brain development among early adolescent initiators, and impairment in short-term memory, motor coordination and the ability to perform complex psychomotor tasks such as driving. Psychiatric problems include psychosis and impairment in cognitive ability. Quality of life can also be affected through poor life satisfaction, decreased educational attainment, and increased sexual risk-taking behavior (7). Chronic marijuana use also can lead to addiction, with an established and clinically significant withdrawal syndrome (8).

Active Ingredients and Route of Administration

Marijuana contains a variety of components (cannabinoids), most notably delta-9-tetrahydrocannabinol (THC) the primary psychoactive compound in the marijuana plant. There are a number of other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), and cannabigerol (CBG). Marijuana can vary in cannabinoid concentration, such as in the ratio of THC to other cannabinoids (CBD in particular). Therefore, the effects of marijuana use (e.g., experience of a high, anxiety, sleep) vary as a function of the concentration of cannabinoids (e.g., THC/CBD). In addition, the potency of cannabinoids can vary. For example, the concentration of THC in the marijuana plant can range in strength from less than 1% to 30% based upon strain and cultivation methods. In general, the potency of THC in the marijuana plant has increased as much as 10-fold over the past 40 years (9,10). Recently, cannabis extract products, such as waxes and oils, have been produced and sold in which the concentration of THC can be as high as 90%. Thus, an individual could unknowingly consume a very high dose of THC in one administration, which increases the risk of an adverse reaction.

Marijuana can be consumed in many different forms (e.g., flower, hash, oil, wax, food products, tinctures). Administration of these forms also can take different routes: inhalation (smoking or vaporizing), ingestion, and topical application. Given the same concentration/ratio of marijuana, smoking or vaporizing marijuana produces similar effects (11); however, ingesting the same dose results in a delayed onset and longer duration of effect (12). Not all marijuana users may be aware of the delayed effect caused by ingestion, which may result in greater consumption and a stronger effect than intended.

Neurobiology

Research has consistently demonstrated that the human endocannabinoid system plays a significant role in PTSD. People with PTSD have greater availability of cannabinoid type 1 (CB1) receptors as compared to trauma-exposed or healthy controls (13,14). As a result, marijuana use by individuals with PTSD may result in short-term reduction of PTSD symptoms. However, data suggest that continued use of marijuana among individuals with PTSD may lead to a number of negative consequences, including marijuana tolerance (via reductions in CB1 receptor density and/or efficiency) and addiction (15). Though recent work has shown that CB1 receptors may return after periods of marijuana abstinence (16), individuals with PTSD may have particular difficulty quitting (17).

Marijuana as a Treatment for PTSD

The belief that marijuana can be used to treat PTSD is limited to anecdotal reports from individuals with PTSD who say that the drug helps with their symptoms. There have been no randomized controlled trials, a necessary “gold standard” for determining efficacy. Administration of oral CBD has been shown to decrease anxiety in those with and without clinical anxiety (18). This work has led to the development and testing of CBD treatments for individuals with social anxiety (19), but not yet among individuals with PTSD. With respect to THC, one open trial of 10 participants with PTSD showed THC was safe and well tolerated and resulted in decreases in hyperarousal symptoms (20).

Treatment for Marijuana Addiction

People with PTSD have particular difficulty stopping their use of marijuana and responding to treatment for marijuana addiction. They have greater craving and withdrawal than those without PTSD (21), and greater likelihood of marijuana use during the six months following a quit attempt (17). However, these individuals can benefit from the many evidence-based treatments for marijuana addiction, including cognitive behavioral therapy, motivational enhancement, and contingency management (22). Thus, providers should still utilize these options to support reduction/abstinence.

Clinical Recommendations

Treatment providers should not ignore marijuana use in their PTSD patients. The VA/DoD PTSD Clinical Practice Guideline(2010) recommends providing evidence-based treatments for the individual disorders concurrently. PTSD providers should offer education about problems associated with long-term marijuana use and make a referral to a substance use disorder (SUD) specialist if they do not feel they have expertise in treating substance use.

Individuals with comorbid PTSD and SUD do not need to wait for a period of abstinence before addressing their PTSD. A growing number of studies demonstrate that that these patients can tolerate trauma-focused treatment and that these treatments do not worsen substance use outcomes. Therefore, providers have a range of options to help improve the lives of patients with the co-occurring disorders.

Marcel O. Bonn-Miller, Ph.D. and Glenna S. Rousseau, Ph.D.

For more information, see PTSD and Substance Use Disorders in Veterans.

References

  1. (2014). Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings.(Vol. NSDUH Series H-48, HHS Publication No. (SMA) 13-4795). Rockville, MD: Substance Abuse and Mental Health Services Administration.
  2. Cougle, J.R., Bonn-Miller, M. O., Vujanovic, A. A., Zvolensky, M. J., & Hawkins, K. A. (2011). Posttraumatic stress disorder and cannabis use in a nationally representative sample. Psychology of Addictive Behaviors, 25,554-558. doi: 10.1037/a0023076
  3. Buckner, J.D., Schmidt, N. B., Lang, A. R., Small, J. W., Schluach, R. C., & Lewinsohn, P. M. (2008). Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. Journal of Psychiatric Research, 42,230-239. doi: 10.1016/j.jpsychires.2007.01.002
  4. Butterworth, P., Slade, T. & Degenhardt, L. (2014). Factors associated with the timing and onset of cannabis use and cannabis use disorder: Results from the 2007 Australian National Survey of Mental Health and Well-Being. Drug and Alcohol Review, 33,555-564. doi: 10.1111/dar.12183
  5. von Sydow, K., Lieb, R., Pfister, H., Höefler, M., & Wittchen, H. U. (2002). What predicts incident use of cannabis and progression to abuse and dependence? A 4-year prospective examination of risk factors in a community sample of adolescents and young adults. Drug and Alcohol Dependence, 68,49-64.
  6. Program Evaluation and Resource Center, V.A., 2015.
  7. Volkow, N. D., Baler, R. D., Compton, W. M., & Weiss, S. R. B. (2014). Adverse health effects of marijuana use. New England Journal of Medicine, 370,2219-2227. doi: 10.1056/NEJMra1402309
  8. Budney, A. J., Hughes, J. R., Moore, B. A., & Vandrey, R. (2004). Review of the validity and significance of cannabis withdrawal syndrome. American Journal of Psychiatry, 161,1967-1977.
  9. Mehmedic, Z., Chandra, S., Slade, D., Denham, H., Foster, S., Patel, A. S., Ross, S. A., Khan, I. A., & ElSohly, M. A. (2010). Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008.Journal of Forensic Sciences, 55,1209-1217. doi: 10.1111/j.1556-4029.2010.01441.x
  10. Sevigny, E. L., Pacula, R. L., & Heaton, P. (2014) The effects of medical marijuana laws on potency. International Journal of Drug Policy, 25,308-319. doi: 10.1016/j.drugpo.2014.01.003
  11. Abrams, D. I., Vizoso, H. P., Shade, S. B., Jay, C., Kelly, M. E., & Benowitz, N. L. (2007). Vaporization as a smokeless cannabis delivery system: A pilot study. Clinical Pharmacology & Therapeutics, 82,572-578.
  12. Grotenhermen, F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics, 42,327-360.
  13. Neumeister, A., Normandin, M. D., Pietrzak, R. H., Piomelli, D., Zheng, M. Q., Gujarro-Anton, A., Potenza, M. N., Bailey, C. R., Lin, S. F., Najafzaden, S., Ropchan, J., Henry, S., Corsi-Travali, S., Carson, R. E., & Huang, Y. (2013). Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study. Molecular Psychiatry, 18,1034-1040. doi: 10.1038/mp.2013.61
  14. Passie, T., Emrich, H. M., Brandt, S. D., & Halpern, J. H. (2012). Mitigation of post-traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence. Drug Testing and Analysis, 4,649-659. doi: 10.1002/dta.1377
  15. Kendall, D.A. & Alexander, S.P. H. (2009). Behavioral neurobiology of the endocannabinoid system.Current topics in behavioral neurosciences. Heidelberg: Springer-Verlag.
  16. Hirvonen, J., Goodwin, R. S., Li, C-T., Terry, G. E., Zoghbi, S. S., Morse, C., Pike, V. W., Volkow, N. D., Huestis, M. A., & Innis, R. B. (2012). Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Molecular Psychiatry, 17,642-649. doi: 10.1038/mp.2011.82
  17. Bonn-Miller, M. O., Moos, R. H., Boden, M. T., Long, W. R., Kimerling, R., & Trafton, J. A. (in press). The impact of posttraumatic stress disorder on cannabis quit success. The American Journal of Drug and Alcohol Abuse.
  18. Crippa, J. A., Zuardi, A. W., Martín-Santos, R., Bhattacharyya, S., Atakan, Z., McGuire, P., & Fusar-Poli, P. (2009). Cannabis and anxiety: a critical review of the evidence. Human Psychopharmacology, 24,515-523. doi: 10.1002/hup.1048
  19. Bergamaschi, M. M., Queiroz, R. H. C., Hortes, M., Chagas, N., de Oliveira, C. G., De Martinis, B. S., Kapczinski, F., Quevedo, J., Roesler, R., Schröder, N., Nardi, A. E., Martín-Santos, R., Hallak, J. E. C., Zuardi, A. W., & Crippa, J. A. S. (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology, 36,1219-1226. doi: 10.1038/npp.2011.6
  20. Roitman, P., Mechoulam, R., Cooper-Kazaz, R., & Shalev, A. (2014). Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clinical Drug Investigation, 34,587-591. doi: 10.1007/s40261-014-0212-3
  21. Boden, M. T., Babson, K. A., Vujanovic, A. A., Short, N. A., & Bonn-Miller, M. (2013). Posttraumatic stress disorder and cannabis use characteristics among military Veterans with cannabis dependence. The American Journal on Addictions, 22,277-284. doi: 10.1111/j.1521-0391.2012.12018.x
  22. Roffman, R. A. & Stephens, R. S. (2006). Cannabis dependence: its nature, consequences, and treatment.International research monographs in the addictions. Cambridge, UK; New York: Cambridge University Pres

Source:  http://www.ptsd.va.gov/   May 2015

Two years ago, the Georgia Legislature tried but failed to legalize artisanal cannabidiol (CBD) oils for children suffering from epilepsy. Artisanal CBD oils are products marijuana growers are making in states that have legalized marijuana for medical use. No grower in these states has submitted its CBD product to FDA for approval as a safe or effective medicine.

In contrast, two pharmaceutical companies, GW Pharmaceuticals of Great Britain and Insys Therapeutics of the US, are developing pharmaceutical-grade CBD oils. GW’s version, Epidiolex, is in FDA Phase III clinical trials and Insys Therapeutics is about to undergo FDA testing. The Insys drug is 100% synthesized CBD, meaning it is an exact chemical duplicate of cannabidiol found in the marijuana plant but is made of pure chemicals to eliminate impurities and contaminants. Epidiolex is an extract of marijuana that has been purified to remove impurities and contaminants and is 98% CBD with trace amounts of THC and other cannabinoids. Both drugs must be tested in animals to ensure safety before companies can apply to FDA for permission to test their drugs in humans.

Artisanal CBD oils offer no such protections to patients. Random tests have shown that many contain THC, which can cause seizures, contaminants, and in some cases little to no CBD.

When the Georgia bill failed last year, Governor Nathan Deal formed a partnership with GW to conduct clinical trials of Epidiolex in Georgia as well as a statewide FDA expanded access program for children not able to enroll in the clinical trials. Both programs are up and running.

Despite this, the legislature came back with a bill this year to legalize artisanal CBD oils not only for childhood epilepsy but also for seven other diseases. Moreover, this bill permits possession of up to 20 ounces of CBD oil containing up to 5% THC. The bill passed and the governor signed it in April. It provides immunity from prosecution to those who possess CBD and calls for a special commission to recommend how best to grow marijuana, process it into CBD oils, and distribute it to patients.

Like the researchers whose work is published in JAMA today, specialists who treat epilepsy also are beginning to speak out. The NBC-TV affiliate in Atlanta interviewed several this week. Dr. Yong Park, who is helping run the clinical trials in Georgia, says doctors don’t know what the drug interactions are or what the side effects might be because they don’t have the evidence yet. Nor do they know how many pesticides artisanal CBD oils may contain nor what the long-term effects of daily exposure on the brain might be.

Under the new state law, when doctors sign a letter approving patients for the state registry that allows them to possess CBD oils, says Atlanta pediatrician Cynthia Wetmore, M.D., Ph.D., “they are required to keep track of the patients. But how do we know what dose to recommend? The oil patients have access to is not standardized. Each batch can be different. There’s a lot of variability in each batch. What side effects is it causing, if any? We have to report to the state on each patient, quarterly. It will be hard to know if it’s helping or hurting.”

Perhaps the most haunting concerns come from Dr. Amy Brooks-Kayal, a Colorado pediatric neurologist and president of the American Epilepsy Society. The Atlanta NBC-TV affiliate published her letter to a Pennsylvania representative who held hearings a few months ago on a similar bill in his state. In part, she writes:

The families and children coming to Colorado are receiving unregulated, highly variable artisanal preparations of cannabis oil prescribed, in most cases, by physicians with no training in pediatrics, neurology, or epilepsy. As a result, the epilepsy specialists in Colorado have been at the bedside of children having severe dystonic reactions and other movement disorders, developmental regression, intractable vomiting, and worsening seizures that can be so severe they have to put the child into a coma to get the seizures to stop. Because these products are unregulated, it is impossible to know if these dangerous adverse reactions are due to the CBD or because of contaminants found in these artisanal preparations. The Colorado team has also seen families who have gone into significant debt, paying hundreds of dollars a month for oils that do not appear to work for the vast majority. For all these reasons not a single pediatric neurologist in Colorado recommends the use of artisanal cannabis preparations. Possibly of most concern is that some families are now opting out of proven treatments, such as surgery or the ketogenic diet, or newer antiseizure medications because they have put all their hope in CBD oils.

All three epilepsy specialists want parents to know that giving artisanal CBD oils to children exposes them to risks that cannot be defined. They urge parents instead to enroll their children in clinical trials or expanded access programs that are testing pharmaceutical-grade CBD where doctors can monitor the children closely.

Read Atlanta story and full text of Dr. Brooks-Kayal’s letter here

Source:

http://us2.campaign-archive2.com/?u=2138d91b74dd79cbf58e302bf&id=71df2f126e&e=7ee41d6c49

Evidence does not support medical marijuana use for most of the diseases and conditions states are permitting, says an editorial in this week’s issue of the Journal of the American Medical Association (JAMA).

“First, for most qualifying conditions, approval has relied on low-quality scientific evidence, anecdotal reports, individual testimonials, legislative initiatives, and public opinion,” say the editorial’s authors. “The US Food and Drug Administration (FDA) requires evidence from at least two adequately powered randomized clinical trials before approving a drug for any specific indication,” and evidence for most conditions fails to meet FDA standards.

Second, there are inconsistencies between states about which conditions qualify for medical marijuana. Some states legalize medical marijuana for PTSD or sickle cell anemia, for example, while others do not. Such differences reflect inconsistencies in applying current evidence to legislative decision-making.

Third, most FDA-approved  drugs have just one or two active ingredients. Marijuana contains more than 400 compounds whose interactions with each other are poorly understood. In addition, the amounts of some marijuana compounds in various strains vary so widely that precise dosing is difficult, which means doctors cannot give patients proper guidance.

Fourth, some individual marijuana components are available commercially (dronabinol and nabilone) and published data exists to guide dosing. Few data exist to guide dosing of smoked [or eaten] marijuana for medical use.

Fifth, while short-term adverse effects of marijuana are quite well known, the effects of long-term use need further study. Tolerance and dependence occur with repeated exposure to marijuana, meaning that dosages will have to be increased when the drug is used medically to be effective, increasing the risk of addiction and other problems.

Finally, “there is also a small but definite risk of psychotic disorder associated with marijuana use, as well as a significant risk of symptom exacerbations and relapse in patients with an established psychotic disorder,” say the authors. Those with schizophrenia, bipolar disorder, or substance dependence must be identified and measures must be taken to protect them from medical marijuana.

“Perhaps US states should establish clinical follow-up programs to monitor long-term outcomes prospectively, especially negative outcomes (e.g. new cases of psychosis) in patients with contraindications.”

In addition to this editorial, JAMA also publishes several research articles concerning medical marijuana this week.

Read editorial here.
Read “Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems, A Clinical Review” here.
Read “Cannabinoids for Medical Use, A Systematic Review and Meta-Analysis” here.
Read “Cannabinoid Dose and Label Accuracy in Edible Medical Cannabis Products” here.

Source:  The MarijuanaReport.org.   June 24th 2015

Marijuana Use: Detrimental to Youth

ABSTRACT: Although increasing legalization of marijuana has contributed to the growing belief that marijuana is harmless, research documents the risks of its use by youth are grave. Marijuana is addicting, has adverse effects upon the adolescent brain, is a risk for both cardio-respiratory disease and testicular cancer, and is associated with both psychiatric illness and negative social outcomes. Evidence indicates limited legalization of marijuana has already raised rates of unintended marijuana exposure among young children, and may increase adolescent use. Therefore, the American College of Pediatricians supports legislation that continues to restrict the availability of marijuana except in the context of well controlled scientific studies which demonstrate medicinal benefit together with evidence-based guidelines for optimal routes of delivery and dosing for specific medical conditions.

Introduction

Federal Law has prohibited the manufacture, sale, and distribution of marijuana for more than 70 years. However, with the discovery of potential medicinal properties of marijuana and the increasing misperception that the drug is harmless, there have arisen increased efforts to achieve its broad legalization despite persistent problems of abuse. Medical use of marijuana has prompted many states to establish programs for sale of medically-prescribed marijuana. As public perception of marijuana’s safety has grown, some states have also passed voter-approved referenda legalizing recreational use of marijuana by adults. The result has been the same: limited legalization has led to greater availability of marijuana to youth.

How is Marijuana Used?

Whether used licitly or illicitly, marijuana is smoked or ingested. It may be smoked in hand-rolled cigarettes (joints), pipes or water pipes (bongs), and cigars that have been refilled with a mixture of marijuana and tobacco (blunts). Marijuana emits a distinctive pungent usually sweet-and-sour odour when it is smoked. Marijuana is not so easily detectable, however, when ingested in candy, other foods or as a tea.

 

Has Legalization Escalated Youth Exposure to Marijuana?

There is evidence legalization of marijuana limited to medical dispensaries and/or adult recreational use has led to increased unintended exposure to marijuana among young children. By 2011, rates of poison center calls for accidental paediatric marijuana ingestion more than tripled in states that decriminalized marijuana before 2005. In states which passed legislation between 2005 and 2011 call rates increased nearly 11.5% per year. There was no similar increase in states that had not decriminalized marijuana as of December 31, 2011. Additionally, exposures in decriminalized states where marijuana use was legalized were more likely than those in non-legal states to present with moderate to severe symptoms requiring admission to a paediatric intensive care unit. The median age of children involved was 18-24 months.1

Marijuana use by adolescents has grown steadily as more states enact various decriminalization laws.2 According to CDC data, more teens now smoke marijuana than cigarettes.3 It is unclear, however, whether this trend indicates a causal relationship or mere correlation. There is some evidence legalization may encourage more youth to experiment with the drug. A national study of 6116 high school seniors, prior to legalization of recreational use in any state, found 10% of nonusers said they would try marijuana if the drug were legal in their state. Significantly, this included large subgroups of students normally at low risk for drug experimentation, including non-cigarette smokers, those with strong religious affiliation, and those with peers who frown upon drug use. Among high school seniors already using marijuana, 18% said they would use more under legalization.

There is also evidence of medical marijuana diversion having a significant impact upon adolescents. For example, researchers in Colorado found that approximately 74% of adolescents in substance abuse treatment had used someone else’s medical marijuana. After adjusting for sex, race and ethnicity, those who used medical marijuana had an earlier age of regular marijuana use, and more marijuana abuse and dependence symptoms than those who did not use medical marijuana.4-5 Conclusions from this study may not apply to adolescents as a whole due to the select population surveyed. There are broader adolescent population studies suggesting no significant increase in use due to enactment of medical marijuana laws.6-10 These authors, however, caution that their results may not be definitive for five reasons: not all states with medical marijuana laws are represented in the various studies; the studies rely upon survey data from a voluntary survey (the Youth Risk Behavior Survey) which has the potential for reporting bias; there are gaps in the annual youth risk behavior data; the primary outcome measure was obtained from a single survey item; and the research is not long-term relative to when medical marijuana laws were implemented. Consequently, while all reported their data did not find medical marijuana laws to significantly increase teen use, they also advised continued long-term observation and research.

 

Is Marijuana Medicine?

A recent article in the Journal of the American Medical Association noted there is very little scientific evidence to support the use of medical marijuana. Authors Samuel Wilkinson and Deepak D’Souza explain that medical marijuana is considerably different from all other prescription medications in that “evidence supporting its efficacy varies substantially and in general falls short of the standards required for approval of other drugs by the US Food and Drug Administration (FDA).”11 The FDA requires carefully conducted studies consisting of hundreds to thousands of patients in order to accurately assess the benefits and risks of a potential medication.

Although some studies suggest marijuana may palliate chemotherapy-induced vomiting, cachexia in HIV/AIDS patients, spasticity associated with multiple sclerosis, and neuropathic pain, there is no significant evidence marijuana is superior to FDA approved medications currently available to treat these conditions. Additionally, support for use of marijuana in other conditions, including post-traumatic stress disorder, Crohn’s disease and Alzheimer’s, is not scientific, relying on emotion-laden anecdotes instead of adequately powered, double-blind, placebo-controlled randomized clinical trials.11

Also, to be considered a legitimate medicine, a substance must have well-defined and measurable ingredients that are consistent from one unit (such as a pill or injection) to the next. This consistency allows researchers to determine optimal dosing and frequency. Drs. Samuel Wilkinson and Deepak D’Souza state:

Prescription drugs are produced according to exacting standards to ensure uniformity and purity of active constituents … Because regulatory standards of the production process vary by state, the composition, purity, and concentration of the active constituents of marijuana are also likely to vary. This is especially problematic because unlike most other prescription medications that are single active compounds, marijuana contains more than 100 cannabinoids, terpenoids, and flavonoids that produce individual, interactive, and entourage effects.”11

 As a consequence, there are no dosing guidelines for marijuana for any of the conditions it has been approved to treat. And finally, there is no scientific evidence that the potential healthful effects of marijuana outweigh its documented adverse effects.11 Sound ethics demands that physicians “First do no harm.” This is why a dozen national health organizations, including the College, presently oppose further legalization of marijuana for medicinal purposes.12 If and when rigorous research delineates marijuana’s true benefits relative to its hazards, compares its efficacy with current medications on the market, determines its optimal routes of delivery and dosing, and standardizes its production and dispensing (to match that of schedule II medications like narcotics and opioids), then medical opposition will dissipate.

 

The Extent of Marijuana Abuse

In the United States, marijuana is the most frequently used illicit drug,13-14 with 23.9 million of those at least 12 years old having used an illegal drug within the past month in 2012.15 The National Institute on Drug Abuse (NIDA)-funded 2013 Monitoring the Future study of the year 2012 showed that 12.7 percent of 8th graders, 29.8 percent of 10th graders, and 36.4 percent of 12th graders had used marijuana at least once in the year prior to being surveyed. They also found that 7, 18 and 22.7 percent respectively for these groups used marijuana in the past month.13

Figure 1. Long-Term Trends in Annual Marijuana Use by Grade14

After a period of decline in the last decade, marijuana use has generally increased among young people since 2007, corresponding with both its increased availability through limited legalization and a diminishing perception of the drug’s risks. The number of current (past month) users aged 12 and up increased from 14.5 to 18.9 million.15

In 2010, 7.3 percent of all persons admitted to publicly funded treatment facilities were aged 12-17. Marijuana is the leading illicit substance mentioned in adolescent emergency department admissions and autopsy reports, and is considered one of the major contributing factors leading to violent deaths and accidents among adolescents.16

Figure 2.  Emergency Department Visits by Type of Substance Abuse16

 

Such data indicate that marijuana use in adolescents is a major and growing problem. Given the widespread availability and abuse of marijuana, and its increasing decriminalization, it is important to examine the adverse clinical consequences of marijuana use.

Marijuana and Addiction

Marijuana is addictive. While approximately 9 percent of users overall become addicted to marijuana, about 17 percent of those who start during adolescence and 25-50 percent of daily users become addicted. Thus, many of the nearly 6.5 percent of high school seniors who report smoking marijuana daily or almost daily are well on their way to addiction, if not already addicted.13 In fact, between 70-72% of 12-17 year olds who enter drug treatment programs, do so primarily because of marijuana addiction.18,13

Long-term marijuana users trying to quit report various withdrawal symptoms including irritability, sleeplessness, decreased appetite, anxiety, and drug craving, all of which can make it difficult to remain abstinent.  These withdrawal symptoms can begin within the first 24 hours following cessation, peak at two to three days, and subside within one or two weeks follow drug cessation. Behavioral interventions, including cognitive-behavioral therapy and motivational incentives (i.e., providing vouchers for goods or services to patients who remain abstinent) have proven to be effective in treating marijuana addiction.19 Although no medications are currently available, recent discoveries about the workings of the endocannabinoid system offer promise for the development of medications to ease withdrawal, block the intoxicating effects of marijuana, and prevent relapse.20

Is Marijuana a Gateway Leading to the Abuse of Other Illicit Drugs?

An additional danger associated with marijuana use observed in adolescents is a sequential pattern of involvement in other legal and illegal drugs. Marijuana is frequently a stepping stone that bridges the gap between cigarette and alcohol use and the use of other more powerful and dangerous substances like cocaine and heroin. This stage-like progression of substance abuse, known as the gateway phenomenon, is common among youth from all socioeconomic and racial backgrounds.19, 21 Additionally, marijuana is often intentionally used with other substances, including alcohol or crack cocaine, to magnify its effects. Phencyclidine (PCP), formaldehyde, crack cocaine, and codeine cough syrup are also often mixed with marijuana without the user’s knowledge.21

 

Other Effects of Marijuana on the Brain

The main active chemical in marijuana is delta-9-tetrahydrocannabinol (THC). When marijuana is smoked, THC rapidly passes from the lungs into the bloodstream, which carries the chemical to the brain and other organs throughout the body. It is absorbed more slowly when ingested in food or drink.13 In all cases, however, THC acts upon specific molecular targets on brain cells, called cannabinoid receptors. These receptors are ordinarily activated by chemicals similar to THC called endocannabinoids, such as anandamide. These receptors are naturally occurring in the body and are part of a neural communication network (the endocannabinoid system) that plays an important role in normal brain development and function. The highest density of cannabinoid receptors is found in parts of the brain that influence pleasure, memory, thinking, concentration, sensory and time perception, and coordinated movement. Marijuana over activates the endocannabinoid system, causing the high and other effects that users experience. These effects include distorted perceptions, psychotic symptoms, difficulty with thinking and problem solving, disrupted learning and memory, and impaired reaction time, attention span, judgment, balance and coordination.21 Chronic exposure to THC may also hasten the age-related loss of nerve cells.22

 Numerous mechanisms have been postulated to link cannabis use, attentional deficits, psychotic symptoms, and neural desynchronization.23 The hippocampus, a component of the brain’s limbic system, is necessary for memory, learning, and integrating sensory experiences with emotions and motivations. THC suppresses neurons in the information-processing system of the hippocampus, thus learned behaviors, dependent on the hippocampus, also deteriorate.24 Brain MRI studies now report that in young recreational marijuana users, structural abnormalities in gray matter density, volume, and shape occur in areas of the brain associated with drug craving and dependence. There also was significant abnormality measures associated with increasing drug use behavior. In addition to the regions of the nucleus accumbens and amygdala, the whole-brain gray matter density analysis revealed other brain regions that showed reduced density in marijuana users compared with control participants, including several regions in the prefrontal cortex: right/left frontal pole, right dorsolateral prefrontal cortex, and right middle frontal gyrus (although another small region in the right middle frontal gyrus showed higher gray matter density in marijuana users). Countless studies have also shown that prefrontal cortex dysfunction is involved with decision-making abnormalities and functional MRI and magnetic resonance spectroscopy studies have shown that cannabis use may affect the function of this region.25 Brain imaging with MRI was used to map areas of working memory in the brain and showed similar findings in normal and schizophrenic subjects who did not use marijuana, but decreases in the size of the working memory areas of the striatum and thalamus for those who had a history of cannabis use, that was more marked in those who used marijuana at a younger age and in users with schizophrenia.26

 In chronic adolescent users, marijuana’s adverse impact on learning and memory persists long after the acute effects of the drug wear off. A major study published in 2012 in Proceedings of the National Academy of Sciences provides objective evidence that marijuana is harmful to the adolescent brain. As part of this large-scale study of health and development, researchers in New Zealand administered IQ tests to over 1,000 individuals at age 13 (born in 1972 and 1973) and assessed their patterns of cannabis use at several points as they aged. Participants were again IQ tested at age 38, and their two scores were compared as a function of their marijuana use.

The results were striking: Participants who used cannabis heavily in their teens and continued through adulthood showed a significant drop in IQ between the ages of 13 and 38—an average of eight points for those who met criteria for cannabis dependence. Those who started using marijuana regularly or heavily after age 18 showed minor declines. By comparison, those who never used marijuana showed no declines in IQ.27 This is the first prospective study to test young people before their first use of marijuana and again after long-term use (as much as 20+ years later) thereby ruling out a pre-existing difference in IQ. This means the finding of a significant mental decline among those who used marijuana heavily before age 18, even after they quit taking the drug, is consistent with the theory that drug use during adolescence—when the brain is still rewiring, pruning, and organizing itself—has long-lasting negative effects on the brain.

Other studies have also shown a link between prolonged marijuana use and cognitive or neural impairment. A recent report in Brain, for example, reveals neural-connectivity impairment in some brain regions following prolonged cannabis use initiated in adolescence or young adulthood.28

 

Effects on Activities of Daily Living

Consistent with marijuana’s impact upon the brain, research demonstrates marijuana has the potential to cause difficulties in daily life and/or worsen a person’s existing problems. Heavy marijuana users generally report lower life satisfaction, reduced mental and physical health, more relationship problems, and less academic and career success compared to their peers who come from similar backgrounds. Marijuana use is also associated with a higher likelihood of dropping out of school, workplace tardiness and absence, more accidents on the job with concomitant workman compensation claims, and increased job turnover.29-30

A 2014 study combined the data of 3 investigations from Australia and New Zealand which compared a series of outcome measures of young adults according to their marijuana use at age 17. The researchers found a significant dose-response effect for each of these.  After adjusting for co-variables, compared to those who never used cannabis prior to age 17 (OR 1.0), the odds of graduating from high school by age 25 dropped to 0.78 (95% CI,0.67-0.90) for those who used cannabis less than monthly to 0.61 (95% CI,0.45-0.81) for those using it monthly or more to 0.47 (95% CI,0.30-0.73) for those using it weekly or more to 0.37 (95% CI,0.20-0.66) for daily users.  The decrease in attaining a university degree was almost identical.  The odds of dependence on cannabis between the ages of 17 and 25 rose progressively from 2.06 (95% CI,1.75-2.42) for less than monthly users to 17.95 (95% CI,9.44-34.12) for daily users, and the odds of other illicit drug use between the ages of 23-25 rose from 1.67 (95% CI,1.45-1.92) for less than monthly users to 7.80 (95% CI,4.46-13.63) for those who were daily users prior to age 17.  The odds of a making a suicide attempt between the ages of 17 and 25 were increased from 1.62 (95% CI,1.19-2.19) for less than monthly users to 6.83 (95% CI,2.04-22.9) for daily users.  While unadjusted odds ratios were progressively higher for progressively higher amounts of cannabis used before age 17 for both depression (between ages 17-25) and for welfare dependence (at ages 27-30 depending on the study), these differences were no longer significant after adjusting for co-variables.31Although the greatest harm was among heavier users, it is most concerning that even less than monthly usage prior to age 17 was associated with a significantly lower educational achievement, and significantly higher rates of drug dependence and suicide attempts.

 Marijuana and Mental Illness

Figure 3.  Mood and Anxiety Disorders Among Users and Non-Users of Marijuana32

 A number of studies have shown an association between chronic marijuana use and mental illness. People who are dependent on marijuana frequently have other comorbid mental disorders including but not limited to anxiety, depression, suicidal ideation, and personality disturbances, including amotivation and failure to engage in activities that are typically rewarding (see figure 3).13 Marijuana use is associated with a 7-fold increased risk of depression (OR 7.10, 95% CI,4.39-11.73) and a 5-fold increased risk of suicidal ideation (OR 5.38, 95% CI,3.31-8.73) when used alone, and with a 9-fold increased risk of depression (OR 9.15, 95% CI,4.58-18.29) and nearly 9 fold increased risk of suicidal ideation when marijuana plus other drugs are involved (OR 8.74, 95% CI 4.29-17.79).17 Daily marijuana use in young women has been associated with a five-fold increase in depression and anxiety.33

Population studies also reveal an association between cannabis use and increased risk of schizophrenia. In the short term, high doses of marijuana can produce a temporary psychotic reaction involving hallucinations and paranoia. There is also sufficient data indicating that chronic marijuana use may trigger the onset or relapse of schizophrenia in people predisposed to it, perhaps also intensifying their symptoms .13,34,32A series of large prospective studies showed a link between marijuana use and the later development of psychosis with genetic variables, the amount of drug used, and the younger the age at which use began increasing the risk of occurrence.13 Although it is possible that pre-existing mental illness may lead some individuals to self-medicate with (abuse) marijuana and other illicit drugs, further prospective studies similar to those examining psychosis, will more firmly establish marijuana as a causative factor for other forms of mental illness.

 Marijuana and Driving

Marijuana contributes to accidents while driving due to its significant impairment of judgment and motor coordination. Data from several studies was analyzed and documented that use of marijuana more than doubles a driver’s risk of involvement in an accident.13 Because they impede different driving functions, the combination of even low levels of marijuana and alcohol is worse than either substance alone.35 Studies have shown a statistically significant increase in non-alcohol drugs detected in fatally injured drivers in the past decade. The most commonly detected non-alcohol drug was cannabinol, the prevalence of which increased from 4.2% in 1999 to 12.2% in 2010 (Z = -13.63, P < 0.0001).  The increase in the prevalence of non-alcohol drugs was observed in all age groups and in both sexes. In this study, increases in the prevalence of narcotics and cannabinol detected in fatally injured drivers were particularly apparent.36

 Other Health Effects of Marijuana

Since marijuana contains many of the same compounds as tobacco, it has the same adverse effects on the respiratory system when smoked as tobacco. These include chronic cough, respiratory infections, and bronchitis.19 In the longer term emphysema and lung cancer are also among its effects.21In fact, smoking marijuana is more harmful than tobacco for two reasons: first, because it contains more tar and carcinogens than tobacco, and secondly, because marijuana smokers tend to inhale more deeply and for a longer period of time as compared to tobacco smokers.

Marijuana use also has a variety of adverse, short- and long-term effects, especially on the cardiopulmonary system. Marijuana raises the heart rate by 20-100 percent shortly after smoking; this effect can last up to three hours. In one study, it was estimated that marijuana users had a 4.8-fold increase in the risk of heart attack in the first hour after smoking the drug. This elevated risk may be due to increased heart rate as well as the effects of marijuana on heart rhythms, causing palpitations and arrhythmias. This risk may be greater in older individuals or in those with cardiac vulnerabilities. Marijuana use has been found to increase blood pressure and heart rate and to decrease the oxygen-carrying capacity of the blood.37

 Chronic smoking of marijuana and its active chemical THC has consistently been shown to increase the risk of developing testicular cancer, in particular a more aggressive form of the disease. One study compared 369 Seattle-area men aged 18-44 with testicular cancer, to 979 men in the same age bracket without the disease. The researchers found that current marijuana users were 1.7 times more likely to develop testicular cancer than nonusers, and that the younger the age of initiation (below 18) and the heavier the use, the greater the risk of developing testicular cancer.38,39,40 A similar study of 455 men in Los Angeles found that men with testicular germ cell tumors were twice as likely to have used marijuana as men without these tumors.41 THC can also cause endocrine disruption resulting in gynecomastia, decreased sperm count, and impotence.42

 

Effects of prenatal exposure to marijuana

The risk of using marijuana during pregnancy is unrecognized by the general public, but infants and children exposed prenatally to marijuana have a higher incidence of neurobehavioral problems. THC and other compounds in marijuana mimic the human brain’s cannabinoid-like chemicals, thus prenatal marijuana exposure may alter the developing endocannabinoid system in the fetal brain, which may result in attention deficit, difficulty with problem solving, and poorer memory.13 Evidence especially suggests an association between prenatal marijuana exposure and impaired executive functioning skills beyond the age of three. Specifically, children with a history of exposure are found to have an increased rate of impulsivity, attention deficits, and difficulty solving problems requiring the integration and manipulation of basic visuoperceptual skills.43

 

Rising Potency and Contaminants

The potency of marijuana has been increasing for decades, with THC concentrations rising from 4% in the 1980s to 14.5% in 2012 in samples confiscated by police.  Some strains now contain as much as 30% THC.19 For a new user, this may mean exposure to higher concentrations of THC, with a greater chance of an adverse or unpredictable reaction. Increases in potency may account for the rise in emergency department visits involving marijuana use. For experienced users, it may mean a greater risk for addiction if they are exposing themselves to high doses on a regular basis. However, the full range of consequences associated with marijuana’s higher potency is not well understood, nor is it known whether experienced marijuana users adjust for the increase in potency by using less. Since the legalization in Colorado, one certified lab there has reported that much of the marijuana they have studied and tested has been found to be laced with heavy metals, pesticides, fungus and bacteria.44

 

Health Risks Underestimated

 Health risks associated with marijuana use are often underestimated by adolescents, their parents, and health professionals. As explained above, there are newer, stronger forms of marijuana available than that which existed in 1960; current forms of marijuana are known to be three to five times more potent. Parents underestimate the availability of marijuana to teens, the extent of their use of the drug, and the risks associated with its use. In a 1995 survey, the Hazelden Foundation found that only 40 percent of parents advised their teenagers not to use marijuana, 20 percent emphasized its illegal status, and 19 percent communicated to their teenagers that it is addictive.45

 

Parental Monitoring Important

 Research shows that appropriate parental monitoring can reduce drug use, even among those adolescents who may be prone to marijuana use, such as those with conduct, anxiety, or affective mood disorders.45

Columbia University’s National Center on Addiction and Substance Abuse (CASA) found that adolescents were much less likely to use marijuana if their parents stated their disapproval. “Parents who do not want their kids getting drunk and using drugs should begin by sending a strong message to their kids about the importance of avoiding alcohol. Our survey results this year show how important it is for teens to get a clear anti-use message from their parents, especially from Dad. Teens who get drunk monthly are 18 times more likely to report marijuana use than teens who do not drink; those who believe their father is okay with them drinking are two and a half times more likely to get drunk in a typical month.  Therefore, parents who do not want their kids getting drunk and using drugs should begin by sending a strong message to their children about the importance of avoiding alcohol.”45

 

In 2011, past month use of illicit drugs, cigarettes, and binge alcohol use were lower among youth aged 12 to 17 who reported that their parents always or sometimes engaged in monitoring behaviors compared to youths whose parents seldom or never engaged in monitoring behaviors. The rate of past month use of any illicit drug was 8.2 percent for youths whose parents always or sometimes helped with homework compared with 18.7 percent among youth who indicated that their parents seldom or never helped.

Columbia Center for Alcohol and Substance Abuse found that teens who have frequent family dinners (five to seven per week) were less likely to have used marijuana.46

Compared to teens who had infrequent family dinners (2 or fewer per week), teens who had frequent family dinners were almost 1.5 times likelier to have said they had an excellent relationship with their mother and their father. The report also found that compared to teens who said they had an excellent relationship with their fathers, teens that had a less than very good relationship with their father were:

o    Almost 4 times likelier to have used marijuana

o    Twice as likely to have used alcohol

o    2.5 times as likely to have used tobacco

 

Compared to teens who said they had an excellent relationship with their mothers, teens who had a less than very good relationship with their mother were:

o    Almost 3 times likelier to have used marijuana

o    2.5 times as likely to have used alcohol

o    2.5 times likelier to have used tobacco

 

Consequently, the College encourages parents to take advantage of the “family table,” and to become involved in drug abuse prevention programs in the community or in the child’s school in order to minimize the risk of their children experimenting with drug use.

In Conclusion

In summary, marijuana use is harmful to children and adolescents.  For this reason, the American College of Pediatricians opposes its legalization for recreational use and urges extreme caution in legalizing it for medicinal use.  Likewise, the American Academy of Child and Adolescent Psychiatry (AACAP) recently offered their own policy statement opposing efforts to legalize marijuana. They similarly pointed out that “marijuana’s deleterious effects on adolescent brain development, cognition, and social functioning may have immediate and long-term implications, including increased risk of motor vehicle accidents, sexual victimization, academic failure, lasting decline in intelligence measures, psychopathology, addiction, and psychosocial and occupational impairment.”

Thus the AACAP (a) opposes efforts to legalize marijuana, (b) supports initiatives to increase awareness of marijuana’s harmful effects on adolescents, (c) supports improved access to evidence-based treatment, rather than emphasis on criminal charges, for adolescents with cannabis use disorder, and (d) supports careful monitoring of the effects of marijuana-related policy changes on child and adolescent mental health.47  The College agrees with this position on marijuana.

 

The College urges parents to do all they can to oppose the legalization of marijuana, such as working with elected officials against the drug’s legalization and scrutinizing a candidate’s positions on this important children’s issue when making voting decisions. The College encourages legislators to consider the establishment and generous funding of more facilities to treat marijuana addiction. Children look to their parents for help and guidance in working out problems and in making decisions, including the decision to not use drugs. Therefore, parents should be role models, and not use marijuana or other illicit drugs. Finally, these reports strikingly emphasize the need for parents to recognize and discuss these serious health consequences of marijuana use with their children and adolescents. They also point to the requirement for medical experts and legislators to seriously discuss and review these observations prior to promoting any state or federal effort considering legalization.

For more information on this topic, the National Clearinghouse for Alcohol and Drug Information (NCADI) offers an extensive collection of publications, videotapes, and educational materials to help parents talk to their children about drug use. For more information on marijuana and other drugs, contact: National Clearinghouse for Alcohol and Drug Information, P. O. Box 2345, Rockville, MD 20847; 1-800-729-6686. Additional helpful information is provided at the following websites: www.drugabuse.gov, www.marijuana-info.org, and www.teens.drugabuse.gov.

Primary Author: Donald Hagler, MD, FCP

Original: January 2007

Revised March 2015

Revised September 2015

 

ADDENDUM added September 2015:

The Legalization of Marijuana in Colorado: The Impact”48 is a compilation of data by the Rocky Mountain High Intensity Drug Trafficking Area that analyzes the effects of marijuana legalization in the state. This third volume allows readers to compare and contrast statistics observed from 2006 – 2009 during Colorado’s early medical marijuana era with those from 2009 to 2013 as medical marijuana commercialization grew, and also with those from the current legalized recreational marijuana era from 2013 to the present. The statistics reveal that between 2013 and 2014 there was a 45% increase in marijuana-associated impaired driving, a 32% increase in marijuana-related motor vehicle deaths (with a 92% increase from 2010 to 2014), as well as 29% and 38% increases in emergency room visits and hospital admissions secondary to marijuana use. By 2013, marijuana use in Colorado was 55% above the national average among teens and young adults, and 86% higher among those over age 25. Diversion of marijuana from Colorado to other states has also increased several fold. This new data further supports the College Position Statement above emphasizing concerns that marijuana legalization will result in increased adolescent usage, addiction and its associated risks for them.

 A downloadable web source for parents can be found at this link, Marijuana Talk Kit, from Partnership for Drug-free Kids.

The American College of Pediatricians is a national medical association of licensed physicians and healthcare professionals who specialize in the care of infants, children, and adolescents. The mission of the College is to enable all children to reach their optimal physical and emotional health and well-being.

A PDF copy of this statement is available here: Marijuana Use Detrimental to Youth

 

Source: http://www.acpeds.org/marijuana-use-detrimental-to-youth  Sept.2015

References

1. Wang GS, Roosevelt G, Le Lait MC, Martinez EM., Bucher-Bartelson B, Bronstein AC, and Heard K, “Association of Unintentional Pediatric Exposures with Decriminalization of Marijuana in the United Sates,” Annals of Emergency Medicine, February 3, 2014. http://www.annemergmed.com/article/S0196-0644(14)00079-1/abstract. Accessed September 6, 2014.

 

2. Cerda M, Wall M, Keyes KM, Galea S, Hasin D.  “Medical marijuana laws in 50 states: investigating the relationship between state legalization of medical marijuana and marijuana use, abuse and dependence” Drug Alcohol Depend. 2012 Jan 1;120(1-3):22-7.

3.Youth Risk Behavior Surveillance – United States, 2011. Morbidity and Mortality Weekly Report (MMWR)/Jun 8, 2012/ Vol. 61/No.4.http://www.cdc.gov/mmwr/pdf/ss/ss6104.pdf. Accessed September 6, 2014.

 

4. Palamar JJ, Omapad DC, and Petkova E, “Correlates of Intentions to Use Cannabis Among U.S. High School Seniors in the Case of Cannabis Legalization,”International Journal of Drug Policy. 2014 May;25(3):424-35.

 

5. Salomonsen-Sautel S, Sakai J, Thurston C, et. al. “Medical Marijuana Use Among Adolescents in Substance Abuse Treatment.” J Am Acad Child Adolescent Psychiatry. July 2012; 51(7):694-702.

 

6. Anderson DM, Hansen B, Rees DI. “Medical Marijuana Laws and Teen Marijuana Use” A working paper IZA DP No. 6592 May 2012 (Accessed September 6, 2014 from: http://ftp.iza.org/dp6592.pdf)

 

7. Harper S, Strumpf E, and Kaufman J. “Do Medical Marijuana Laws Increase Marijuana Use? Replication Study and Extension.”  Annals of Epidemiology. 2012;22:207–212. http://www.medicine.mcgill.ca/epidemiology/harper/web/papers_files/Harper-Ann%20Epidemiol-2012.pdf. Accessed September 6, 2014.

 

8. Lynne-Landsman SD, Livingston MD, and Wagenaar AC.  Effects of State Medical Marijuana Laws on Adolescent Marijuana Use. American Journal of Public Health: August 2013, Vol. 103, No. 8, pp. 1500-1506.

 

9. Choo EK, Benz M, Zaller N, Warren O, Rising KL, McConnell KJ. TheImpact of State Medical Marijuana Legislation on Adolescent Marijuana Use. Journal of Adolescent Health, 2014.

 

10. Wall M., et.al. “Commentary on Harper S, Strumpf EC, Kaufman JS. Do Medical Marijuana Laws Increase Marijuana Use? Replication Study and Extension” Annals of Epidemiology. July 2012;22(7): 536-537.

11. Wilkinson ST, and D’Souza DC. “Problems with the Medicalization of Marijuana” JAMA Vol. 311 No. 23 p. 2377 (June 18, 2014).

 

12. The American Medical Association, American Society of Addiction Medicine, National Institute on Drug Abuse of the NIH, American Academy of Pediatrics, American Academy of Child and Adolescent Psychiatry, American Academy of Ophthalmology, American Glaucoma Society, National Multiple Sclerosis Society, National Comprehensive Cancer Network, American Cancer Society, and the Narcotics Enforcement Officers Association.

13. Drug Facts. National Institute on Drug Abuse. www.drugabuse.gov/drugs-abuse/marijuana. Published December 2012.

 

14. What is the Scope of Marijuana Use in the United States? National Institute on Drug Abuse. http://www.drugabuse.gov/publications/research-reports/marijuana/what-scope-marijuana-use-in-united-states. Published July 2012.

 

15.National Survey on Drug Use and Health. Substance Abuse and Mental Health Administration.http://www.samhsa.gov/data/NSDUH/2012SummNatFindDetTables/NationalFindings/NSDUHresults2012.htm#ch2.13Published 2014.

 

16. National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality. http://www.samhsa.gov/data/2K13/CBHSQ128/sr128-typical-day-adolescents-2013.htm. Published 2013.

 

17. Hallfors DD, Waller MW, Ford CA, Halpern CT, Brodeish PH, and Iritani B. Adolescent depression and suicide risk: Association with sex and drug behavior. American Journal of Preventive MedicineVolume 27, Issue 3, October 2004, Pages 224–231, Tables 3 and 4.

18. Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use.Lancet. 2009 Oct 17;374(9698):1383-91.

 

19. Want to know more? Some FAQs about marijuana. National Institute on Drug Abuse. http://www.drugabuse.gov/publications/marijuana-facts-parents-need-to-know/want-to-know-more-some-faqs-about-marijuana. Updated March 2014. Accessed July 10, 2012.

 

20. Available treatments for marijuana use disorders. National Institute on Drug Abuse. http://www.drugabuse.gov/publications/research-reports/marijuana/available-treatments-marijuana-use-disorders. Updated March 2014.

 

21. Nistler C, Hodgson H, Nobrega FT, Hodgson CJ, Wheatley R, Solberg G. Marijuana and adolescents. Minn Med. 2006 Sept:49-51.

22. How Does Marijuana Affect Your Brain and Body? National Institute on Drug Abuse. http://www.drugabuse.gov/publications/research-reports/marijuana/how-does-marijuana-use-affect-your-brain-body. Accessed September 23, 2014. Brain. 2012 Jul;135(7):2245-55. Accessed June 4, 2012. http://www.ncbi.nlm.nih.gov/pubmed?term=effect of long-term cannabis use and zalesky.

 

23. Ashton CH. Pharmacology and effects of cannabis: A brief review. Brit Jrnl Psych. 2001;178: 101-106.

 

24.   Iowa Department of Public Safety. Division of Narcotics Enforcement.http://www.dps.state.ia.us/DNE/marijuana.shtml. Accessed September 23, 2014.

 

25. Gilman JM, Kuster JK, Lee S, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci. 2014;34(16): 5529-5538.

 

26. Smith MJ, Cobia DJ, Wang L, et al. Cannabis-related working memory deficits and associated subcortical morphological differences in healthy individuals and schizophrenia subjects. Schizophr Bull. 2014 Mar;40(2):287-99.

 

27. Meier MH, Caspi A, Harrington H, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. ProcNatlAcadScie 2012 Oct 2;109(40):E2657-64.Available at http://www.ncbi.nlm.nih.gov/pubmed?term=persistent%20cannabis%20users%20and%20meier. Accessed on August 27, 2012.

 

28. Zalesky A, Solowji N, Yucel M, et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain. 2012 Jul;135(7):2245-55. Accessed June 4, 2012. http://www.ncbi.nlm.nih.gov/pubmed?term=effect of long-term cannabis use and zalesky.

 

29. How does marijuana use affect school, work, and social life? National Institute of Drug Abuse. http://www.drugabuse.gov/publications/research-reports/marijuana/how-does-marijuana-use-affect-school-work-social-life. Published July 2012.

30. Polen, MR, Sidney, S, Tekawa, IS, Sadler, M, Friedman, GD. Health care use by frequent marijuana smokers who do not smoke tobacco. West J Med. 1993;158(6):596–601.

 

31. Silins E, Horwood LJ, Patton GC, Ferguson DM, Olsson CM, Hutchinson DM, et.al. Young adult sequelae of adolescent cannabis use: an integrative analysis The Lancet Psychiatry, Volume 1, Issue 4, Pages 286 – 293, September 2014 http://www.thelancet.com/journals/lancet/article/PIIS2215036614703074/table?tableid=tbl2&tableidtype=table_id&sectionType=red.

32. Topics in brief: Marijuana. National Institute on Drug Abuse.http://www.drugabuse.gov/publications/topics-in-brief/marijuana. Published December 2011. Accessed September 22, 2014.

 

33. Patton, G.C., Coffey, C., Carlin, J.B., Degenhardt, L., Lynskey, M. & Hall, W. “Cannabis Use and Mental Health in Young People: Cohort Study,” British Medical Journal 325, no. 7374 (November 23, 2002):1195-8.

 

34. Caspi, A, Moffitt, TE, Cannon, M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-Omethyltransferase gene: Longitudinal evidence of a gene X environment interaction. Biol Psych. 2005;57(10):1117–1127. Cited inhttp://www.drugabuse.gov/publications/research-reports/marijuana/there-link-between-marijuana-use-mental-illness.

 

35.Sewell RA, Poling J, and Sofuoglu M. The effect of cannabis compared with alcohol on driving. Am J Addict. 2009; 18(3): 185-193.http://222.ncbi.nlm.nih.gov/pmc/articles/PMC2722956/

 

36. Brady J, Li G. Trends in alcohol and other drugs detected in fatally injured drivers in the United States, 1999-2010. Am J Epidemio. (2014); 10.1093/aje/kwt327.

 

37. Mittleman MA, Lewis RA, Maclure M. Triggering myocardial infarction by marijuana. Circ. 2001;103(23): 2805-9.

 

38. Daling JR, Doody DR, Sun X. Association of marijuana use and the incidence of testicular germ cell tumors. Can. 2009; 115: 1215–1223.

39. Simon S. Study links marijuana use to testicular cancer. American Cancer Society. http://www.cancer.org/cancer/news/study-links-marijuana-use-to-testicular-cancer. Published September 12, 2012. Accessed March 28, 2013.

40. Meeks JJ, Sheinfeld J, Eggener SE. Environmental toxicology of testicular cancer. UrolOnc: SemOrigInv. 2012 Mar/Apr; 30(2): 212-215.

 

41. Lacson JCA, Carroll JD, Tuazon E, Castelao EJ, Bernstein L, Cortessis VK. Population-Based Case-Control Study of Recreational Drug Use and Testis Cancer Risk Confirms an Association Between Marijuana Use and Nonseminoma Risk. Cancer. 2012 September:5374-5383.http://onlinelibrary.wiley.com/doi/10.1002/cncr.27554/pdf. Accessed September 30, 2014.

 

42. The Encyclopedia of Psychoactive Drugs: Marijuana – Its Effects on Mind and Body; Hermes, Galperin, Chelsea House Publishers; 1992.Fried PA, Smith AM. A literature review of the consequences of prenatal marijuana exposure. An emerging theme of a deficiency in aspects of executive function.NeurotoxicolTeratol. 2001;23(1):1-11.

 

43. Fried PA, Smith AM. A literature review of the consequences of prenatal marijuana exposure. An emerging theme of a deficiency in aspects of executive function. NeurotoxicolTeratol. 2001;23(1):1-11.

 

44. Smithsonian.com, Modern Marijuana is Often Laced with Heavy Metals and Fungus. Published March 2015. http://www.smithsonianmag.com/science-nature/modern-marijuana-more-potent-often-laced-heavy-metals-and-fungus-180954696/?no-ist. Accessed March 26, 2015.

 

45. National Survey of American Attitudes on Substance Abuse XIV: Teens and Parents. Columbia Center for Alcohol & Substance Abuse. http://www.casacolumbia.org/addiction-research/reports/national-survey-american-attitudes-substance-abuse-teens-2012. Published 2012.

46. The Importance of Family Dinners VII. Columbia Center for Alcohol & Substance Abuse. http://www.casacolumbia.org/upload/2011/2011922familydinnersVII.pdf. Published September 2011. Accessed January 29, 2013.

47. AACAP Marijuana Legalization Policy Statement. American Academy of Child & Adolescent Psychiatry. https://www.aacap.org/AACAP/Policy_Statements/2014/aacap_marijuana_legalization_policy.aspx. Published April 15, 2014.

48.   The Legalization of Marijuana in Colorado: The Impact. http://www.rmhidta.org/html/2015%20PREVIEW%20Legalization%20of%20MJ%20in%20Colorado%20the%20Impact.pdf. Accessed 9/22/15.

There is, naturally, a hope amongst parents whose child is desperately ill with seizures that a new treatment will help.  Many parents in the USA have been convinced that medical marijuana may be the answer – and some have even moved home in order to be able to legally purchase this substance.  Sadly however, it has been shown that whilst this substance may be able to help some patients it can also have disastrous effects on others.  There is much research going on with a purified and uniform preparation of cannabidiol (CBD) called Epidiolex to see if this can indeed become a genuine treatment for epileptic seizures.  Until then, parents should be advised not to use the products available in ‘medical marijuana dispensaries’ – which are not regulated for purity or uniformity and could be dangerous for their children. (see letter below).

This situation has come about because of the shameful way so called medical marijuana has been used as a wedge to introduce the recreational use of the substance – dating from the statement made in the seventies  by Keith Stroup in a post debate encounter at Emory University in the USA when he said “we’ll be using the issue as a red herring to give marijuana a good name’.

This is the current position of the American Epilepsy Society, as written in a letter from Dr. Brooks-Kayal to a Pennsylvania legislator:

March 22, 2015

Dear Representative,

As Pennsylvania considers enacting new cannabis legislation (HB 193), I write to offer the perspective of the American Epilepsy Society (AES), the leading U.S. organization of clinical and research professionals specializing in the treatment and care of people with epilepsy.

Epilepsy is the most common and potentially devastating neurological disease that affects people across the lifespan. In America, one in 26 people will be diagnosed with epilepsy at some time in the course of their life – more will experience an isolated seizure. Epilepsy is associated with significant morbidity and mortality and is associated with many co-morbidities including depression, cognitive dysfunction, and autism. Today between 2.2 and 3 million Americans, including almost 400,000 children, live with epilepsy, with one third living with treatment-resistant seizures that do not respond to current medications.

The American Epilepsy Society position on medical marijuana as a treatment option for people with epilepsy is informed by the current research and supported by the position statements from the American Academy of Neurology, the American Academy of Pediatrics and the American Medical Association. Additionally, a 2014 survey of practitioners published in the journal Epilepsy Currents found that the majority of epilepsy practitioners agreed with and supported the AES position.

Specifically, AES has called for more research, for the rescheduling of marijuana by the DEA to ease access for clinical studies, and has supported the compassionate use program of GW Pharmaceuticals, where a is being administered under the guidance and close monitoring of an appropriate medical professional. AES has also been highly supportive of the double-blind clinical trial now underway by GW Pharmaceuticals and of the forthcoming clinical trial by INSYS Therapeutics.

These clinical trials utilize a vastly different substance than the artisanal cannabis products that are being considered for use in Pennsylvania, and that have been used in Colorado. As you likely know, medical marijuana and its derivatives are legal in Colorado, but you may not realize that the content of these products is not regulated for purity or uniformity. A study by a team from Children’s Hospital Colorado that was presented during the AES Annual Meeting in December 2014 and has recently been accepted for publication in the journal Epilepsy & Behavior, found that artisanal “high CBD” oils resulted in no significant reduction in seizures in the majority of patients and in those for whom the parents reported improvements, these improvements were not associated with improvement in electroencephalograms (EEGs), the gold standard monitoring test for people with epilepsy.

Additionally, in 20% of cases reviewed seizures worsened with use of cannabis and in some patients there were significant adverse events. These are not the stories that you have likely heard in your public hearings, but they are the reality of practitioners at Children’s Hospital Colorado who have cared for the largest number of cases of children with epilepsy treated with cannabis in the U.S.

The families and children coming to Colorado are receiving unregulated, highly variable artisanal preparations of cannabis oil prescribed, in most cases, by physicians with no training in pediatrics, neurology or epilepsy. As a result, the epilepsy specialists in Colorado have been at the bedside of children having severe dystonic reactions and other movement disorders, developmental regression, intractable vomiting and worsening seizures that can be so severe they have to put the child into a coma to get the seizures to stop. Because these products are unregulated, it is impossible to know if these dangerous adverse reactions are due to the CBD or because of contaminants found in these artisanal preparations. The Colorado team has also seen families who have gone into significant debt, paying hundreds of dollars a month for oils that do not appear to work for the vast majority. For all these reasons not a single pediatric neurologist in Colorado recommends the use of artisanal cannabis preparations. Possibly of most concern is that some families are now opting out of proven treatments, such as surgery or the ketogenic diet, or newer antiseizure medications because they have put all their hope in CBD oils.

AES is sympathetic to the desperation parents of children with severe, treatment-resistant epilepsy feel, and understand the need for compassionate or promising new therapies in in appropriate and controlled circumstances. We are however opposed to the use of artisanal preparations of unregulated compounds of cannabis that contain unverified content and are produced by people with no experience in pharmaceutical production. That is what is currently happening in Colorado and may soon be happening in multiple states across the county as they legalize the use of medical marijuana products.

The products currently provided in Colorado do not meet the FDA definition of expanded or compassionate use. The FDA requires compassionate use therapies to meet the same criteria as an investigational new drug which require standard purity, content and content uniformity testing of the product. None of these criteria are met in the products being given to people with epilepsy in Colorado and we are seeing the distressing results noted above. And yet, these and other similar products are being considered for use in Pennsylvania.

It is also worth noting that in late February 2015, the FDA issued several warning letters to firms that claim that their products contain CBD. The FDA has tested those products and, in some of them, did not detect any CBD as claimed on the label. Because there is no standard for these products, the market is increasingly flooded with a wide variation of products and states which approve access to these preparations will bear the burden of monitoring for quality and controlling for the continuity of supply.

In sum, there simply is no clinical, controlled research to support the adoption of new CBD legislation for epilepsy such as your state is considering. The anecdotal results of a few families in Colorado, shared in the media, should not be the basis for law making. The rush by states to pass CBD legislation has created an unusual situation where people with epilepsy and their families are demanding access to a highly variable homegrown substance that may or may not be beneficial and the medical and scientific community lacks the necessary efficacy and safety data to make good treatment decisions regarding cannabis for people with epilepsy, especially in children.

The new legislation in most states places epilepsy practitioners in an untenable situation where they are expected, or in some states directed by law, to respond to requests for these highly variable artisanal products with no protocols, no research and no clinical guidelines regarding dosing or side-effects, and no assurance that the cannabis products that are to be recommended are pure, safe or uniform, making it nearly impossible to know if we are truly “Doing No Harm.”

We need to accelerate the clinical research and wait to act until we have results to support decisions. If there are components of cannabis with specific therapeutic values we need to know this and we need to develop pharmacy grade compounds that utilize these components to help the nearly one million people living with drug resistant epilepsy. And if the harmful aspects of cannabis outweigh the therapeutic benefits, we need to find out now, before more medically fragile children have been exposed to cannabis products that are not effective and may risk damage to vital organs, brain development, or worse.

We urge you and your fellow committee members to delay adoption of new cannabis legislation and to continue to support and encourage new research. If we can be of additional help please contact our Executive Director, Eileen Murray, at emurray@aesnet.org.

Thank you for your consideration of our position.

Sincerely,

Amy Brooks-Kayal, MD,  President, American Epilepsy Society.  Chief and Ponzio Family Chair, Children’s Hospital Colorado,  Professor of Pediatrics and Neurology, University of Colorado School of Medicine

Legalization keeps rolling ahead. But because of years of government roadblocks on research, we don’t know nearly enough about the dangers of marijuana—or the benefits

Yasmin Hurd raises rats on the Upper East Side of Manhattan that will blow your mind.

Though they look normal, their lives are anything but, and not just because of the pricey real estate they call home on the 10th floor of a research building near Mount Sinai Hospital. For skeptics of the movement to legalize marijuana, the rodents are canaries in the drug-policy coal mine. For defenders of legalization, they are curiosities. But no one doubts that something is happening in the creatures’ trippy little brains.

In one experiment, Hurd’s rats spent their adolescence getting high, on regular doses of tetrahydrocannabinol (THC), the psychoactive compound in marijuana. In the past, scientists have found that rats exposed to THC in their youth will show changes in their brain in adulthood. But Hurd asked a different question: Could parental marijuana exposure pass on changes to the next generation, even to offspring who had never been exposed to the drug?

So she mated her rats, but only after she had waited a month to make sure the drug was no longer in their system. She raised the offspring, along with another group of rats that shared the same life experiences except for the THC. She then trained the children to play a game alone in a box. The prize: heroin.

Press one lever to get a shot of saline into the jugular vein. Press the other to get a rush of opiates. Initially, the rats with THC-exposed parents performed about the same as the rats with sober parents. But when Hurd’s team changed the rules, requiring the rats to work harder for the drug, differences emerged. The rats with drug-using parents pushed the lever more than twice as much. They wanted the heroin more.

When she analyzed the brains of the rats, she also found differences in the neural circuitry of the ones with drug-using parents. Even the grandkids have begun to show behavioral differences in how they seek out rewards. “This data tells us we are passing on more things that happen during our lifetimes to our kids and grandkids,” Hurd explains, though it remains unclear how those changes manifest in humans. “I wasn’t expecting these results, and it’s fascinating.”

Welcome to the encouraging, troubling and strangely divided frontier of marijuana science. The most common illicit drug on the planet and one of the fastest-growing industries in America, pot remains–surprisingly–something of a medical mystery, thanks in part to decades of obstruction and misinformation by the federal government. Potentially ground breaking studies on the drug’s healing powers are being done to find treatments for conditions like epilepsy, posttraumatic stress disorder (PTSD), Alzheimer’s disease, Parkinson’s disease, sickle-cell disease and multiple sclerosis. But there are also new discoveries about the drug’s impact on recreational users.

The effects are generally less severe than those of tobacco and alcohol, which together cause more than 560,000 American deaths annually. Unlike booze, marijuana isn’t a neurotoxin, and unlike cigarettes, it has an uncertain connection to lung cancer. Unlike heroin, pot brings almost no risk of sudden death without a secondary factor like a car

crash. But science has also found clear indications that in addition to short-term effects on cognition, pot can change developing brains, possibly affecting mental abilities and dispositions, especially for certain populations. The same drug that seems relatively harmless in moderation for adults appears to be risky for people under age 21, whose brains are still developing. “It has a whole host of effects on learning and cognition that other drugs don’t have,” says Jodi Gilman, a Harvard Medical School researcher who has been studying the brains of human marijuana users. “It looks like the earlier you start, the bigger the effects.”

Beyond Reefer Madness

That relatively measured tone is a far cry from the shrill warnings of Harry J. Anslinger, the first commissioner of the Federal Bureau of Narcotics, who in the 1930s set the standard for America’s fraught debate over marijuana with wild exaggerations. “How many murders, suicides, robberies, criminal assaults, holdups, burglaries and deeds of maniacal insanity it causes each year, especially among the young, can only be conjectured,” he wrote as part of a campaign to terrify the country. As recently as the 1970s, President Richard Nixon talked about the drug as a weapon of the nation’s enemies. “That’s why the communists and the left-wingers are pushing the stuff,” he was recorded saying in private. “They’re trying to destroy us.”

The official line today is better grounded in data and research. And the new focus is squarely on brain development. “I am most concerned about possibly harming the potential of our young people,” says Dr. Nora Volkow, the head of the National Institute for Drug Abuse (NIDA), which funds Hurd’s and Gilman’s work. “That could be disastrous for our country.”

But decades of prohibition and official misinformation continue to shape public views. “The government did not spend as much effort in finding out the facts about marijuana,” says Hurd. “That strategy of scaring people rather than provide knowledge has made people sceptical now when they hear anything negative.”

As states now rush to legalize pot and unwind a massive criminalization effort, the federal government is trying to play catch-up on the science, with mixed success. The only federal marijuana farm, at the University of Mississippi, has recently expanded production with a $69 million grant in March, and Volkow has expressed a new openness to studies of marijuana’s healing potential. In the coming months, Uncle Sam will begin a 10-year, $300 million study with thousands of adolescents to track the harm that marijuana, alcohol and other drugs do to the developing brain. High-tech imaging will allow researchers for the first time to map the effects of marijuana on the brain as humans age.

But scientists and others point out that a shift to fund the real science of pot still has a long way to go. The legacy of the war on drugs haunts the medical establishment, and federal rules still put onerous restrictions on the labs around the country that seek to work with marijuana, which remains classified among the most dangerous and least valuable drugs. “We can do studies on cocaine and morphine without a problem, because they are Schedule II,” explains Fair Vassoler, a researcher at Tufts University who has replicated Hurd’s rat experiment with synthetic pot. “But marijuana is Schedule I.”

That means that under the law, marijuana has “no medical benefit,” even though 23 states have legalized pot as medicine and NIDA acknowledges that “recent animal studies have shown that marijuana can kill certain cancer cells and reduce the size of others.” And marijuana researchers face barriers even higher than those faced by

scientists studying other Schedule I drugs, like heroin and LSD. Pot studies must pass intensive review by the U.S. Public Health Service, a process that has delayed and thwarted much research for more than 15 years. The result is sometimes a catch-22 for scientists seeking to understand the drug. “The government’s research restrictions are so severe that it’s difficult to find and show the medical benefit,” says neurobiologist R. Douglas Fields, the chief of the nervous-system-development section at the National Institutes of Health (NIH).

That all may change soon. On Capitol Hill, a left-right coalition of Senators Kirsten Gillibrand of New York, Rand Paul of Kentucky and Cory Booker of New Jersey introduced a bill in March to federally legalize medical marijuana in states that have already approved it. “For far too long,” said Paul, a Republican candidate for President, “the government has enforced unnecessary laws that have restricted the ability of the medical community to determine the medicinal value of marijuana.”

The Cannabinoid System

Harm researchers and neuroscientists aren’t completely deadlocked. They agree on at least one thing. Marijuana’s positive and negative effects both spring from the same source: the body’s endocannabinoid system. First discovered in the late 1990s, it’s a complex neural system that researchers are only beginning to fully comprehend.

A little Brain Science 101: Human grey matter contains around 86 billion neurons, a type of cell that essentially talks to other cells in the brain through electrochemical processes. Neurons talk to each other through chemical messengers known as neurotransmitters–including dopamine, serotonin, glutamate and compounds called endocannabinoids–which in turn send instructions to your body about what to do.

Researchers now know the body produces endocannabinoids, which activate cannabinoid receptors in the brain. Interestingly, one plant on earth produces a similar compound that hits those same receptors: marijuana. Just as poppy-derived morphine mimics endorphins, marijuana-derived cannabinoids like THC and cannabidiol (CBD) mimic endocannabinoids, which impact feelings of hunger and pleasure. Cannabinoid receptors are especially widespread in the brain, where they play a key role in regulating the actions of other neurotransmitters.

“The more we investigate the hidden recesses of the brain, the more it seems like practically every neuron either releases endocannabinoids or can sense them using cannabinoid receptors,” explains Gregory Gerdeman, a neuroscientist and endocannabinoid researcher at Florida’s Eckerd College. Neurotransmitters carry out brain communication through synapses. “But too much synaptic excitation is poisonous–it damages cells,” says Gerdeman. “Endocannabinoids are a mechanism for putting on the brakes when that toxic level of excitation is approached.”

Cannabinoids like CBD may be thought of as neuro-protectants–that is, brain protectors. In fact, the NIH actually owns a patent (No. 6630507) on cannabinoids as neuro-protectants, based on the work of researcher Aiden Hampson and his mentor, Nobel Prize–winning neuroscientist Julius Axelrod. They found that CBD showed particular promise in limiting neurological damage in patients with Alzheimer’s disease and Parkinson’s disease and in those who have suffered a stroke or head trauma.

Endocannabinoids also play a role in the regulation of pain, mood, appetite, memory and even the life and death of individual cells. Curiously, cannabinoid receptors aren’t

densely packed in the medulla (within the brain stem), which controls breathing and the cardiovascular system. That’s why a heroin overdose can be fatal–the drug shuts down the respiratory control center – but a marijuana overdose generally can’t. PTSD researchers are keen to crack the cannabinoid code because the compounds appear to play a role in extinguishing unpleasant memories. “Part of what happens with PTSD is that the brain’s stress buffers have been blown out by trauma,” says Gerdeman. “Endocannabinoids within the amygdala”–the brain region important for emotional learning and memory–“act as a key mechanism for what we call memory extinction.”

But what accounts for the potentially healing effects of pot in some can cause harm in others. That’s because endocannabinoids appear to play a critical role in the development of the adolescent brain. If the brain were a house, the childhood years would be spent pouring the foundation and framing up the walls. Adolescence is when the wiring and plumbing get finished. Neural networks are refined and strengthened through pruning. The strong synapses, axons and dendrites are preserved, the weak culled.

Researchers now believe the cannabinoid system plays a critical role in this neural fine-tuning. This is where the worries about teenage pot use come to the fore. At the precise moment when the brain relies on a finely calibrated dose of endocannabinoids, the adolescent weed smoker floods the system. “If you actively and repeatedly overload the endogenous cannabinoid system,” says Volkow, “you are going to disrupt that very well-orchestrated system.”

That disruption may lie at the heart of still inconclusive science about marijuana’s impact on human behavior, especially among younger users. Early studies suggest that there may be long-lasting impacts on mental acuity, higher brain function and impulse control for younger users. There is also a well-documented connection between pot smoking and schizophrenia, a condition that affects about 1% of the U.S. population. Scientists have been aware of the link since the 1970s. Among those with a family history of mental illness, marijuana can hasten the emergence of schizophrenia.

Researchers are trying to identify the mechanisms in play. “Many genes are undoubtedly involved in risk for schizophrenia,” says Dr.Michael Compton, a professor at Hofstra North Shore–LIJ School of Medicine and the head of psychiatry at New York City’s Lenox Hill Hospital. “But there are also a host of social or environmental influences at work.” For a subset of the population, the earlier the initiation of marijuana use, the earlier the onset of psychosis.

Here’s why that matters: The later schizophrenia emerges, the greater the likelihood of recovery. Schizophrenia onset in a 15-year-old is often permanently life-altering. In a 24-year-old, it can be less damaging, because the person has had the chance to accomplish more psychological and social-developmental milestones. But that doesn’t mean all teenage pot users are smoking themselves into mental illness. Darold Treffert, the Wisconsin psychiatrist who first documented the marijuana-schizophrenia link in the 1970s, puts it this way: “Perhaps some persons can safely use marijuana, but schizophrenics cannot.” A test or a clear genetic marker to identify kids who are vulnerable to schizophrenia is likely years away.

The Healing Possibilities

While American research on the potential harms from marijuana is booming, the U.S. continues to lag in funding investigations into the possible benefits. In the late 1990s, the U.S. and British governments commissioned separate studies of medical marijuana.

The U.K. study was spurred by multiple-sclerosis patients’ using pot to calm spasticity. The U.S. study, done by the Institute of Medicine, was in response to California’s 1996 legalization of medical marijuana.

Both studies reached a similar conclusion: medical pot wasn’t a hippie’s delusion. The research showed that the stuff held real therapeutic potential for specific conditions, including epilepsy, chronic pain and glaucoma. The British responded by treating marijuana as a plant with biotech prospects. U.K. officials licensed GW Pharmaceuticals, a start-up lab in Salisbury, England, to grow weed and develop cannabinoid drugs, some of which U.S. scientists like Hurd use in their research.

The Americans, meanwhile, doubled down on the war on drugs. Barry McCaffrey, Bill Clinton’s drug czar, was outraged at the Institute of Medicine’s results. “I think what the IOM report said is that smoked marijuana is harmful, particularly for those with chronic conditions,” he said–pretty much the opposite of the report’s conclusions. Nonetheless, he and then Attorney General Janet Reno vowed to prosecute medical-marijuana patients and doctors who prescribed the drug. Shortly thereafter, the U.S. Department of Health and Human Services adopted even tougher strictures against the study of marijuana as a medicine.

The federal anti-pot policies resulted in a strange kind of scientific trade deficit. The U.S. leads the world in studies of marijuana’s harm, but we’re net importers of data dealing with its healing potential. THC discoverer Raphael Mechoulam runs the world’s leading cannabinoid lab at the Hebrew University of Jerusalem. Spanish biologist Manuel Guzmán is doing cutting-edge work on the potential of cannabinoids to retard the growth of glioblastoma, one of the deadliest forms of brain cancer. Canada’s health agency may soon approve the world’s first clinical trial to test medical marijuana on military and police veterans with PTSD.

There are signs of change at home, though. This year, the Colorado department of public health awarded $9 million in grants for medical-marijuana research, funded with tax revenue from state-licensed pot stores. They will be among the first U.S. clinical trials to look into the effectiveness of marijuana for childhood epilepsy, irritable-bowel disease, cancer pain, PTSD and Parkinson’s disease. Dr.Kelly Knupp, a paediatric-epilepsy specialist at Children’s Hospital in Denver, will track children using high-CBD marijuana strains to calm seizures. “Some of these children can have 100 to 200 seizures a day,” Knupp says. “We’re hoping we can measure seizure frequency to see if there’s any improvement” among kids trying the cannabinoid medicine.

This Is a Rat on Drugs

Back at Hurd’s Upper East Side lab, the rats have begun to show the way. In a separate experiment, she gave heroin-addicted rats doses of CBD and found that it decreased their willingness to work hard for more heroin, suggesting that parts of marijuana could help human drug addicts stay clean. She is now testing that hypothesis by giving CBD tablets, made in England, to recovering human addicts in New York City.

She is also continuing to study the behavior of rats whose only exposure to marijuana’s active ingredients came through the DNA passed on to them from their parents or grandparents. That research suggests that THC may have epigenetic effects, which have been found in other drugs like cocaine and heroin, changing the way genes express themselves in the brains of offspring. This doesn’t necessarily mean that parents who smoked weed in high school have damaged their kids, because those changes may be

overrun by other behaviors. The science is too new to know for sure. “It’s not a given that this is going to happen,” Hurd explains of her rats. “They tell us the potential.”

That word–potential–still qualifies much of what is known about pot, but it won’t be that way for long. The science of pot is likely to expand in the coming years, and it could boom if federal restrictions are lifted. What the government once dismissed as a communist plot that prompted murderous rages has turned out to be a window into the very workings of the human mind. In the years to come, researchers may yet find genetic markers that predispose people to pot-induced psychotic reactions, map out the specific ways in which THC changes the brain and find new medicines for some of the most intractable illnesses. Until then, the great marijuana experiment will continue in a country where 1 in 10 adults–and 35% of high school seniors–admit to conducting their own, mostly recreational, research.

Barcott is a journalist who has contributed to the New York Times, National Geographic and other publications. Scherer is TIME’s Washington bureau chief. Portions of this article were adapted from Barcott’s new book Weed the People: The Future of Legal Marijuana in America, published by TIME Books.  the Future of Legal Marijuana in America,” is now available wherever books are sold, including Amazon.com, Barnes & Noble and Indiebound.

Source:  May 25, 2015 issue of TIME.

CLEARING THE HAZE

….The ugly truth is that Colorado was suckered. It was promised regulation and has been met by an industry that fights tooth and nail any restrictions that limit its profitability.”  Ben Cort, Director of Professional Relations for the Center for Additction Recovery and rehabilitation at the University Of Colorado Hospital

Source:   http://gazette.com/clearingthehaze

 

REGULATION STILL INEFFECTIVE

But how it would work was described only in general terms and sound bites before voters headed to the polls to make a decision Gov. John Hickenlooper later would call “reckless” and “a bad idea” and new Colorado Attorney General Cynthia Coffman declared “not worth it” to dozens of state attorneys general last month.

Source:http://www.washingtonexaminer.com/regulation-still-ineffective/article/2562323?custom_click=rss

 

NO APPROVED MEDICINE IN MARIJUANA

Dr. Stuart Gitlow, a physician serving as president of the American Society of Addiction Medicine, does not mince words: “There is no such thing at this point as medical marijuana,” he said. It’s a point he has made routinely for the past decade, as advocates for marijuana legalization have claimed the drug treats an array of serious illnesses, or the symptoms of illnesses, including cancer, depression, epilepsy, glaucoma and HIV, the virus that causes AIDS.

Source:http://www.washingtonexaminer.com/no-approved-medicine-in-marijuana/article/2562336

 

LEGALIZATION DIDN’T UNCLOG PRISONS

Of all the misunderstandings about marijuana’s impact on the country, perhaps none is greater than the belief that America’s courts, prisons and jails are clogged with people whose only offense was marijuana use. This is the perception, but statistics show few inmates are behind bars strictly for marijuana-related offenses, and legalization of the drug will do little to affect America’s growing incarceration numbers.

Source:http://www.washingtonexaminer.com/legalization-didnt-unclog-prisons/article/2562326

 

DRUG USE A PROBLEM FOR EMPLOYERS

“This is a very troublesome issue for our industry, but I do not see us bending or lowering our hiring standards,” Johnson said. “Our workplaces are too dangerous and too dynamic to tolerate drug use. And marijuana? In many ways, this is worse than alcohol. I’m still in shock at how we (Colorado) voted. Everyone was asleep at the wheel.”

Source:http://www.washingtonexaminer.com/drug-use-a-problem-for-employers/article/2562334

 

MEDICAL MARIJUANA INDUSTRY STILL GROWING

And amid all the hoopla around legalized recreational pot, its older cousin, the medical marijuana (MMJ) industry — with 505 stores throughout Colorado — quietly continued to grow, adding patients by the thousands who seemingly had no problem finding physicians willing to diagnose what critics say are often phantom medical conditions. Statewide, the number of people on the Medical Marijuana Registry grew 4 percent in 2014 — the first year of legal recreational sales — from 111,030 to 115,467 by year’s end.

Source:http://www.washingtonexaminer.com/medical-marijuana-industry-still-growing-in-colorado/article/2562335

The fall of the Roman Empire is the subject of much debate, and includes attention to the possible role of their aqueducts, lined with lead. More likely, the decline was the result of lead poisoning caused by the consumption of grape juice boiled in lead cooking pots. The aristocracy of Rome consumed as much as two liters of wine a day — almost three bottles — adding alcoholism to the risk of lead poisoning. 

Lead poisoning has an impact on intelligence, even at concentrations as low as 10 micrograms per deciliter. In the New England Journal of Medicine on April 17, 2003, Richard L. Canfield writes that children between the ages of 3 and 5 suffer a decline of 7.4 IQ points from environmental lead exposure. That figure represents a substantial loss of intellectual capacity. There is no effective treatment for children so exposed. One can be grateful for a dedicated public health campaign to mitigate this powerful yet avoidable toxin in the lives of children.

That said, no one is advocating that pregnant woman splash lead-based paint in their nursery. Unlike another substance that also holds high risk during the prenatal period. Incredibly, it is a substance that for pregnant women is more than permitted, it is encouraged by some advocates. That substance is marijuana. In the life of the developing adolescent, heavy marijuana exposure is associated with brain abnormalities, emotional disruption, memory decline, and yes, loss of IQ; a decline of an estimated 8 points into adulthood, according to research by M. Meier in the Proceedings of the National Academy of Sciences in October, 2012. But what of prenatal exposure, from maternal marijuana use?

The website Cannabis Culture provides an answer in a 1998 article. The opening graphic is of a dreamy, topless woman who is in the late-term of her pregnancy. She is curled around a hookah. Under advice from a “Dr. Kate,” she is told that smoking marijuana while pregnant is not only safe, but that “cannabis can be a special friend to pregnant women in times of need.” It is said to mellow out those periods of morning sickness and to reduce anxiety.

The potential impact of such misinformation is widespread. According to the 2012 National Survey of Drug Use and Health, the rate of illicit drug use in 2012 was 18.3 percent among pregnant women aged 15 to 17. The drug being used is overwhelmingly marijuana.

An article by L. Goldschmidt in Neurotoxical Teratology in April/May 2000 concluded “Prenatal marijuana use was significantly related to increased hyperactivity, impulsivity and inattention syndrome (as well as) increased delinquency.” The marijuana used by pregnant women in this study would almost certainly be seen today as low-potency.

Recent research is even more specific concerning the damage. For instance, Xinyu Wang published on Dec. 15, 2004 in Biological Psychiatry results from examination of foetal brains. It noted, “Marijuana is the illicit drug most used by pregnant women, and behavioral and cognitive impairments have been documented in cannabis-exposed offspring.”

Their results showed “specific alterations of gene expression in distinct neuronal populations of the fetal brain as a consequence of maternal cannabis use.” The reduction was correlated with the amount of maternal marijuana intake during pregnancy, and particularly affected male fetuses. The THC “readily crosses the placenta and can thus affect the fetus,” while “longitudinal human studies have shown motor, social, and cognitive disturbances in offspring who were exposed to cannabis prenatally.” Finally, “school children exposed in utero to marijuana were also weak in planning, integration and judgment skills.”

The authors also note “Depending on the community, 3 percent to 41 percent of neonates born in North America are exposed in utero to marijuana.” Marijuana, the president has assured us in an interview with  David Remnick  (The New Yorker, Jan. 27, 2014), is “no more dangerous than alcohol.” To which he could now add, “and for the newly born, only marginally more dangerous than lead.” With this president, you take your assurances where you may.

In Colorado today, marijuana is treated as a legal recreational indulgence and is hawked as a medicine. Moreover, adolescent use of this substance, in the form of the new, highly potent industrial dope now being produced, is soaring. Included in that population of adolescent users are young females, some of whom are, or shortly will be, pregnant.

Murray is a former White House chief scientist and currently a senior fellow at the Center for Substance Abuse Policy at Hudson Institute in Washington, D.C.

Source:http://www.utsandiego.com/news/2014/sep/25/pregnancy-marijuana/    Sept   2014

D.A.R.E. America joins every major public health association, including the American Medical Association, the American Psychiatric Association, the American Society of Addiction Medicine, and other groups in opposing the legalization of marijuana. Simply put, legalization would drastically increase marijuana use and use disorder rates, as well as hamper public safety and health at a cost of billions to society in lost productivity, impaired driving, health care, and other costs. 

Of particular concern to D.A.R.E. is the relaxed attitude regarding the use of marijuana, which will lead to increased accessibility and reduced perception of harm. This will undoubtedly contribute to greater youth use and abuse of the drug.

Legalized marijuana means ushering in the next “Big Tobacco.” Already, private holding groups and financiers have raised millions of start-up dollars to promote businesses that will sell marijuana and marijuana-related merchandise.  The former head of Strategy for Microsoft has even said he wants to “mint more millionaires than Microsoft” with marijuana and that he wants to create the “Starbucks of marijuana.” A massive industry has exploded in the legal marijuana states of Washington and Colorado.

Colorado’s experience is already going poorly. Colorado is the first jurisdiction to fully legalize marijuana and sell marijuana in state-licensed stores. And already in its first year, the experience is a disaster. Calls to poison centers have skyrocketed, incidents involving kids coming to school with marijuana candy and vaporizers have soared, and explosions involving butane hash oil extraction have increased. Employers are reporting more workplace incidents involving marijuana use, and deaths have been attributed to ingesting marijuana “edibles.” Open Colorado newspapers and magazines on your web browser (or look at the real thing) on any given day and you will find pages of marijuana advertisements, coupons, and cartoons. Remember Joe Camel and candy cigarettes? The marijuana industry offers a myriad of marijuana-related products such as candies, sodas, ice cream, and cartoon-themed paraphernalia and vaporizers, which are undoubtedly attractive to children and teens.i  As Al Bronstein, medical director of the Rocky Mountain Poison and Drug Center recently told the Denver Post, “We’re seeing hallucinations, they become sick to their stomachs, they throw up, they become dizzy and very anxious.” Bronstein reported that in 2013 there were 126 calls concerning adverse reactions to marijuana. From January to April 2014 alone the center receive 65 calls.ii Dr. Lavonas, also from the Rocky Mountain Poison and Drug Center, said in 2014 that emergency rooms have seen a spike in psychotic reactions from people not accustomed to high potency marijuana sold legally, severe vomiting that some users experience, and children and adults having problems with edibles. iii 

No advocate for marijuana legalization will openly promote making marijuana available to minors. However, it would be unwise to believe that relaxed attitudes about the drug, reduced perceptions of harm and increased availability will not result in increased youth use and abuse of marijuana. Children are the marijuana marketer’s future customers. Just as alcohol and tobacco companies have been charged with promoting their goods to children, so has the Colorado marijuana industry. In March 2014, the Colorado legislature was forced to enact legislation to prohibit edible marijuana products from being package to appeal to children. “Keeping marijuana out of the hands of kids should be a priority for all of us,” said Governor Hickenlooper, before signing the bill.iv But that was not enough.  

As discussed above, Dr. George Sam Wan of the Rocky Mountain Poison and Drug Center and his colleagues compared the proportion of marijuana ingestions by young children who were brought to an emergency room before and after October 2009, when Colorado drug enforcement laws regarding medical marijuana use were relaxed. The researchers found no record of children brought into the ER in a large Colorado children’s hospital for marijuana-related poisonings between January 2005 and September 30, 2009 — a span of 57 months. It is a different story following legalization.v Dr. Bronstein reported twenty-six people have reported poisonings from marijuana edibles this year, when the center started tracking such exposures. Six were children who swallowed innocent-looking edibles, most of which were in plain sight. Five of those kids were sent to emergency rooms, and two to hospitals for intensive care.vi

The scientific verdict is in: marijuana can be addictive and dangerous. Despite denials by legalization advocates, marijuana’s addictiveness is not debatable: 1 in 6 kids who ever try marijuana, according to the National Institutes of Health, will become addicted to the drug. Today’s marijuana is not your “Woodstock weed” – it can be 5-10 times stronger than marijuana of the past.vii More than 400,000 incidents of emergency room admissions related to marijuana occur every year, and heavy marijuana use in adolescence is connected to an 8-point reduction of IQ later in life, irrespective of alcohol use.

Marijuana legalization would cost society in real dollars, and further inequality in America. Alcohol and tobacco today give us $1 for every $10 that we as society have to pay in lost social costs, from accidents to health damage.viii The Lottery and other forms of gambling have not solved our budget problems, either. We also know these industries target the poor and disenchantedix – and we can expect the marijuana industry to do the same in order to increase profits. 

IF THEY SAY…

YOU SAY…

Marijuana is not addictive.

Science has proven – and all major scientific and medical organizations agree – that marijuana is both addictive and harmful to the human brain, especially when used as an adolescent. One in every six 16 year-olds (and one in every eleven adults) who try marijuana will become addicted to it.x

Marijuana MIGHT be psychologically addictive, but its addiction doesn’t produce physical symptoms.

Just as with alcohol and tobacco, most chronic marijuana users who attempt to stop “cold turkey” will experience an array of withdrawal symptoms such as irritability, restlessness, anxiety, depression, insomnia, and/or cravings.xi

Lots of smart, successful people have smoked marijuana. It doesn’t make you dumb.

Just because some smart people have done some dumb things, it doesn’t mean that everyone gets away with it. In fact, research shows that adolescents who smoke marijuana once a week over a two-year period are almost six times more likely than nonsmokers to drop out of school and over three times less likely to enter college.xii In a study of over 1,000 people in 2012, scientists found that using marijuana regularly before the age of 18 resulted in an average IQ of six to eight fewer points at age 38 versus to those who did not use the drug before 18.xiii These results still held for those who used regularly as teens, but stopped after 18. Researchers controlled for alcohol and other drug use as well in this study. So yes, some people may get away with using it, but not everyone.

No one goes to treatment for marijuana addiction.

More young people are in treatment for marijuana abuse or dependence than for the use of alcohol and all other drugs.xiv

Marijuana can’t hurt you.

Emergency room mentions for marijuana use now exceed those for heroin and are continuing to rise.xv

 

IF THEY SAY…

YOU SAY…

I smoked marijuana and I am fine, why should I worry about today’s kids using it?

Today’s marijuana is not your Woodstock Weed. The psychoactive ingredient in marijuana—THC—has increased almost six-fold in average potency during the past thirty years.xvi

Marijuana doesn’t cause lung cancer.

The evidence on lung cancer and marijuana is mixed – just like it was 100 years ago for smoking – but marijuana contains 50% more carcinogens than tobacco smokexvii and marijuana smokers report serious symptoms of chronic bronchitis and other respiratory illnesses.xviii

Marijuana is not a “gateway” drug.

We know that most people who use pot WON’T go onto other drugs; but 99% of people who are addicted to other drugs STARTED with alcohol and marijuana. So, indeed, marijuana use makes addiction to other drugs more likely.xix

Marijuana does not cause mental illness.

Actually, beginning in the 1980s, scientists have uncovered a direct link between marijuana use and mental illness. According to a study published in the British Medical Journal, daily use among adolescent girls is associated with a fivefold increase in the risk of depression and anxiety.xx  Youth who begin smoking marijuana at an earlier age are more likely to have an impaired ability to experience normal emotional responses.xxi

 

The link between marijuana use and mental health extends beyond anxiety and depression. Marijuana users have a six times higher risk of schizophreniaxxii, are significantly more likely to development other psychotic illnesses.

Marijuana makes you a better driver, especially when compared to alcohol.

Just because you may go 35 MPH in a 65 MPH zone versus 85 MPH if you are drunk, it does not mean you are driving safely! In fact, marijuana intoxication doubles your risk of a car crash according to the most exhaustive research reviews ever conducted on the subject.xxiii

 

IF THEY SAY…

YOU SAY…

Marijuana does not affect the workplace.

Marijuana use impairs the ability to function effectively and safely on the job and increases work-related absences, tardiness, accidents, compensation claims, and job turnover.xxiv

Marijuana simply makes you happier over the long term.

Regular marijuana use is associated with lower satisfaction with intimate romantic relationships, work, family, friends, leisure pursuits, and life in general.xxv

Marijuana users are clogging our prisons.

A survey by the Bureau of Justice Statistics showed that 0.7% of all state inmates were behind bars for marijuana possession only (with many of them pleading down from more serious crimes). In total, one tenth of one percent (0.1 percent) of all state prisoners was marijuana-possession offenders with no prior sentences. Other independent research has shown that the risk of arrest for each “joint,” or marijuana cigarette, smoked is about 1 arrest for every 12,000 joints.xxvi

Marijuana is medicine.

 

 

Marijuana may contain medical components, like opium does. But we don’t smoke opium to get the effects of Morphine. Similarly we don’t need to smoke marijuana to get its potential medical benefit.xxvii

The sick and dying need medical marijuana programs to stay alive.

 

Research shows that very few of those seeking a recommendation for medical marijuana have cancer, HIV/AIDS, glaucoma, or multiple sclerosis;xxviii and im most states that permits the use of medical marijuana, less than 2-3% of users report having cancer, HIV/AIDS, glaucoma, MS, or other life-threatening diseases.xxix

Marijuana should be rescheduled to facilitate its medical and legitimate use.

 

Rescheduling is a source of major confusion. Marijuana meets the technical definition of Schedule I because it is not an individual product with a defined dose. You can’t dose anything that is smoked or used in a crude form. However, components of marijuana can be scheduled for medical use, and that research is fully legitimate. That is very different than saying a joint is medicine and should be rescheduled.xxx

 

IF THEY SAY…

YOU SAY…

Smoking or vaporizing is the only way to get the medical benefits of marijuana.

 

No modern medicine is smoked. And we already have a pill on the market available to people with the active ingredient of marijuana (THC) in it – Marinol. That is available at pharmacies today. Other drugs are also in development, including Sativex (for MS and cancer pain) and Epidiolex (for epilepsy). Both of these drugs are available today through research programs.xxxi

Medical marijuana has not increased marijuana use in the general population.

Studies are mixed on this, but it appears that if a state has medical “dispensaries” (stores) and home cultivation, then the potency of marijuana and the use and problems among youth are higher than in states without such programs. This confirms research in 2012 from five epidemiological researchers at Columbia University. Using results from several large national surveys, they concluded, “residents of states with medical marijuana laws had higher odds of marijuana use and marijuana abuse/dependence than residents of states without such laws.xxxii

Legalization is inevitable – the vast majority of the country wants it, and states keep legalizing in succession.

The increase in support for legalization reflects the tens of millions of dollars poured into the legalization movement over the past 30 years. Legalization is not inevitable and there is evidence to show that support has stalled since 2013.

Alcohol is legal, why shouldn’t marijuana also be legal?

Our currently legal drugs – alcohol and tobacco – provide a good example, since both youth and adults use them far more frequently than illegal drugs. According to recent surveys, alcohol use is used by 52% of Americans and tobacco is used by 27% of Americans, but marijuana is used by only 8% of Americans.xxxiii

 

IF THEY SAY…

YOU SAY…

Colorado has been a good experiment in legalization.

 

 

 

Colorado has already seen problems with this policy. For example, according to the Associated Press: “Two Denver Deaths Linked to Recreational Marijuana Use”. One includes the under-aged college student who jumped to his death after ingesting marijuana cookie.

 

The number of parents calling the poison-control hotline to report their kids had consumed marijuana has risen significantly in Colorado.

Marijuana edibles and marijuana vaporizers have been found in middle and high schools.xxxiv

We can get tax revenue if we legalize marijuana.

With increased use, public health costs will also rise, likely outweighing any tax revenues from legal marijuana. For every dollar gained in alcohol and tobacco taxes, ten dollars are lost in legal, health, social, and regulatory costs.xxxv And so far in Colorado, tax revenue has fallen short of expectations.

I just want to get high. The government shouldn’t be able to tell me that I can’t.

 

Legalization is not about just “getting high.” By legalizing marijuana, the United States would be ushering in a new, for-profit industry – not different from Big Tobacco. Already, private holding groups and financiers have raised millions of start-up dollars to promote businesses that will sell marijuana and marijuana-related merchandise. Cannabis food and candy is being marketed to children and are already responsible for a growing number of marijuana-related ER visits.xxxvi

 

Edibles with names such as “Ring Pots” and “Pot Tarts” are inspired by common children candy and dessert products such as “Ring Pops” and “Pop Tarts.” Moreover, a large vaporization industry is now emerging and targeting youth, allowing young people and minors to use marijuana more easily in public places without being detected.xxxvii

 

IF THEY SAY…

YOU SAY…

Legalization would remove the black market and stop enriching gangs.

Criminal enterprises do not receive the majority of their funding from marijuana. Furthermore, with legal marijuana taxed and only available to adults, a black market will continue to thrive. The black market and illegal drug dealers will continue to function – and even flourishxxxviii – under legalization, as people seek cheaper, untaxed marijuana.

 

 

Pot plants grow at a medical marijuana dispensary in San Jose Photograph by David Paul Morris/Bloomberg

Months after her biotechnology company sold for $40 million, Jessica Tonani is on Seattle’s Highway 99, where Kurt Cobain in his final days shot heroin in cheap motels. She’s scoring a gram of Blueberry Kush.

Tonani doesn’t plan to smoke the pot. Her typical procedure is to isolate some of its DNA and bank it, sequence its genetic profile, and test it for bacteria. After her stop at Choice Wellness, a medical marijuana store in one of the states where pot is newly legal, she buys the same strain in three more places (often collecting a “new-patient gift” of pot-infused gummi bears or goldfish). The goal for her new company, Verda Bio, is to build a database bringing order to billions of potential DNA combinations and, eventually, create stable strains that people can grow like a Red Delicious apple. Right now, Tonani says, people using pot for health conditions—legal in 23 U.S. states—are doing the equivalent of rummaging through their medicine cabinet blindfolded. One day they might get Tylenol; another, mouthwash. Even when they buy the same strain from the same place, it might not have the same effect because of differences in how each plant is grown. The variety Harlequin, for example, is sometimes recommended for children with epilepsy because it’s high in cannabidiol, or CBD, a non-psychedelic pot compound that appears to limit seizures.

Tonani analyzed more than 20 samples of Harlequin along with Analytical 360, a Seattle testing lab, and found that 22 percent were high in the psychedelic tetrahydrocannabinol, or THC, and had almost no CBD. Any kids taking it were likely just getting stoned.

Tonani is also looking at contaminants to determine where they’re introduced and how to control for them. The first two samples turned up a long list of nastiness, including the fecal bacteria Enterobacter asburiae and the vaginal bacteria Gardnerella vaginalis. What this means, politely, is that many people handling pot don’t wash their hands.

The irony of legalization in the U.S. is that recreational users often now have more certainty of their weed’s safety than people with legitimate conditions whose suffering was part of the original justification. Washington State, for example, requires its few dozen recreational stores to test pot for contaminants and to display THC and CBD content. There’s no such rule for the far more numerous medical pot stores—as many as 300 in the Seattle area alone—which are still in a legal gray area after the state legislature failed to pass a bill regulating them this year.

“It’s exactly the opposite of the way it should be,” says Randy Oliver, chief science officer at Analytical 360. Oliver says his lab gives failing grades to about 15 percent of the recreational samples it tests for mold, potentially dangerous to sick people with compromised immune systems. Medical pot stores rarely seek tests of mold and other contaminants, he says.

Some of the latest states permitting medical marijuana, including Florida and Utah, have done so by allowing only a type that’s verified as low in THC and high in CBD. Colorado, the other state to permit recreational use, doesn’t require contaminant testing for medical marijuana centers, though most test on their own, says Natriece Bryant, a spokeswoman for the state’s Marijuana Enforcement Division. Colorado also has rules on hand-washing and sanitation for those locations.

In the dispensaries Tonani visits, there’s little consistency. The waiting room in one place is like a doctor’s office, with plush leather chairs and stacks of manila folders. At another, lit with a harsh bulb over a marijuana plant growing in a converted shower, the guy at the counter says he’s never found that certain strains work any better for ailments. Just find one that gets you really high and numbs the pain, he says. Tonani, 38, who co-founded GnuBIO, a DNA sequencing company sold (PDF) in April to Bio-Rad Laboratories (BIO), has a personal as well as financial interest in pot’s future. She turned to the drug a decade ago for a gastrointestinal condition that led to the removal of part of her stomach, multiple surgeries, and twice-weekly intravenous infusions. Her doctor has since asked her to counsel other patients who think pot might help, and she’s frustrated not to have better answers.

While Colorado is spending $9 million on research into marijuana’s potential medical benefits, there’s little federal funding because of pot’s classification as a Schedule I dangerous drug. Many of the cannabis breakthroughs—like Sativex, a mouth spray for multiple sclerosis sufferers developed by the U.K.’s GW Pharmaceuticals (GWPH)—have occurred overseas. Verda Bio, which may raise money from investors later this year, hopes to eventually generate revenue from licensing or sales of stable plant varieties and cannabis-based treatments, Tonani says.

“I honestly believe it saved my life,” she says of pot. “But it’s just not a medical system right now. Some people get lucky, and some people don’t.” Source: http://www.businessweek.com/ 8th August 2014

CORRESPONDENCE FROM TEN DOCTORS

To the Editor: In their article, Volkow et al. (June 5 issue)1 state that marijuana may have adverse health effects, particularly on the vulnerable brains of young people. Potential mechanisms underlying the effect of marijuana on the cerebrovascular system are indeed complex, although a temporal relationship between the use of marijuana (natural or synthetic) and stroke in young people has recently been described.2,3 Simultaneously, the presence of multifocal intracranial arterial vasoconstriction was observed, which was reversible in some cases after cessation of cannabis exposure.3 Thus, stroke, which is still underdiagnosed, may potentially play a role in neuronal damage related to marijuana use, even in young people without cardiovascular risk factors. Furthermore, tetrahydrocannabinol (THC), a major component of cannabis, has been shown experimentally to impair the function of the mitochondrial respiratory chain and to increase the production of reactive oxygen species in the brain.4 Both of these processes are key events during stroke,5 suggesting that THC may also increase a patient’s vulnerability to stroke. In the ongoing shift toward marijuana legalization, physicians should probably inform marijuana users, whether they are using it for recreational purposes or therapeutic indications, about the risk of stroke with potential severe disability.

Valérie Wolff, M.D. Olivier Rouyer, M.D., Ph.D. Bernard Geny, M.D., Ph.D. Fédération de Médecine Translationnelle de Strasbourg, Strasburg, France bernard.geny@chru-strasbourg.fr

To the Editor:

Volkow et al. focus primarily on the neurocognitive and societal effects of marijuana use. We wish to note the known and potentially unknown infectious risks of marijuana, which were not discussed.

Recreational use of marijuana has been associated with a multistate outbreak of salmonellosis, illustrating the potential for widespread exposure through either inadvertent contamination during growing and storage or purposeful adulteration.1 More worrisome are the risks of marijuana use for medical purposes, particularly by the population of immunocompromised patients. Prior reports have documented the frequent contamination of marijuana with fungal organisms and the potential for severe complications, including death.2-4 These risks are not well studied and thus are poorly defined.

To date, 23 states allow the medical use of marijuana; however, dispensaries are currently not subject to regulation or quality control. We believe that the infectious risks need to be better defined, which would allow for appropriate regulatory oversight. The current approach places patients (unknowingly) at undue risk for acquisition of severe, and often lethal, infections.

George R. Thompson, III, M.D. Joseph M. Tuscano, M.D. University of California, Davis, Medical Center, Sacramento, CA grthompson@ucdavis.edu

To the Editor:

One safety aspect that is not discussed by Volkow et al. is the potential for interactions between marijuana and medications. Cannabis sativa Linnaeus products contain more than 700 distinct chemical entities. The relative abundance of these chemical entities in marijuana products and in human plasma can vary considerably depending on numerous factors, including the geographic location of cultivation, the method of preparation or administration, and the cultivar administered.

In vitro studies have shown that constituents of cannabis are potent and broad-spectrum inhibitors of key drug-metabolizing enzymes and transporters, including CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and P-glycoprotein.1-4 Other data from in vitro studies suggest the potential for enzyme induction, especially of CYP1A2.

Case reports support the risk of pharmacokinetic interactions; however, clinical studies have been equivocal. Notably, these studies have not replicated the long-term high potency and high dose achieved by some marijuana users (e.g., hashish users). Health care providers need to maintain a high level of suspicion for drug interactions in their patients who use marijuana products.

Carol Collins, M.D. University of Washington, Seattle, WA carolc3@u.washington.edu

The authors reply: We thank Wolff et al., Thompson and Tuscano, and Collins for their correspondence regarding potential adverse consequences of marijuana use that were not explicitly highlighted in our recent review. Given the shifting landscape of marijuana use, it is critically important that we be on the lookout for the emergence of predictable or unexpected health effects. This is particularly important when it comes to the potential of marijuana to negatively affect persons with various medical conditions, to interact with specific medications, or to influence the course of heretofore unstudied conditions. It will also be important to support the targeted research needed to understand the effects, both positive and negative, that may result from patients experimenting with marijuana in an attempt to relieve their specific symptoms. These studies should also focus on the possibility that such patients may forego evidence-based treatments while chasing after the purported therapeutic benefits of marijuana. Finally, we encourage particular attention to research targeting the effects of marijuana and other substances on adolescents, whose actively developing brains make them a particularly vulnerable population.1,2

Nora D. Volkow, M.D. Wilson M. Compton, M.D. Susan R.B. Weiss, Ph.D. National Institutes of Health, Bethesda, MD nvolkow@nida.nih.gov

Since publication of their article, the authors report no further potential conflict of interest.

Source:  Adverse Health Effects of Marijuana Use N Engl J Med 2014; 371:878-879 August 28, 2014 DOI: 10.1056/NEJMc1407928

Facts and Talking Points

Components of marijuana have medical value, but that does not mean we should smoke or vaporize non standardized products to get that value.

Recently, due to CNN and other media outlets, there has been a flood of interest in CBD a component contained in marijuana.  CBD does not get you high, and as such, it has been generally bred out of modern, smoked marijuana. But it can be grown under special conditions.

There is some limited anecdotal and other evidence showing CBD effectiveness for epilepsy, especially in children.

We should find a way to get CBD to patients who need it, but we owe those who suffer a product with safety assurances. Many products on the current “medical” marijuana market have no such assurances, are never tested in FDA-registered labs, and have no guarantees of quality and content or information on dosing or side effects.

For those who might benefit from CBD, a company in Britain has developed a standardized CBD product which will soon be in clinical trials in the U.S. and which may also be available from physicians through special FDA-approved channels.

What is CBD?

 CBD and THC are the two primary cannabinoids produced by the cannabis (marijuana) plant. CBD does not have THC like psychoactivity. CBD was essentially bred out of high potency modern recreational cannabis, but there has been recent interest in its therapeutic potential. As a result, a number of breeders claim to have “high CBD” strains and numerous purveyors are selling products that they claim are high in CBD. However, many of these products also contain significant levels of THC.

How does CBD work?

CBD works through a number of complex mechanisms. Preclinical studies indicate that

CBD has analgesic (pain relieving), anti-convulsant, anti-psychotic and neuroprotective effects. Unlike THC, it does not bind to the CB1 or CB2 cannabinoids receptors, which is why it does not produce THC-like psychoactivity.

Many groups are trying to sell or give away CBD in different states without going through any FDA or NIH process. However these products have no such safety assurances.

SAM is working on a long-term solution to expand and accelerate the current research so that every patient who might benefit from CBD can obtain it.

Are these CBD products safe? 

“High CBD” plant material usually also contains varying levels of THC, sometimes significant amounts. Most simple extraction processes cannot reliably extract CBD solely or primarily. Indeed, extremely complex and expensive equipment is required to remove the THC from a “high CBD” extract.  The situation is made more hazardous by the fact that existing research demonstrates that, in many cases, large doses of CBD are needed to achieve a specific therapeutic effect. Accordingly, a child taking a therapeutic dose of CBD (100-1000 milligrams per day) would potentially also be exposed to a large amount of THC. For example, using a 10:1 preparation, a child who ingested 300 mg of CBD per day would also be ingesting 30mg of THC. That is the equivalent of three of the highest dose (10mg) Marinol capsules, which would make most adult patients intoxicated.  A 2:1 or 1:1 plant ratio product would contain even higher levels of THC.

What is the legal status of CBD?

Because CBD is a component of the cannabis/marijuana plant, it is a Schedule

I substance under the federal Controlled Substances Act (CSA). The FDA has recently confirmed that CBD is, indeed, a Schedule I substance. Lisa Kubaska, PharmD, who works for the FDA’s Center for Drug Evaluation and Research stated in an email to an inquiry from a journalist:“CBD meets the definition of Schedule 1 under the Controlled Substance Act.”  For example, some companies advertise the following as “high CBD” strains:

Harlequin at 11.6%/6.9% CBD: THC;

Canna Tonic at 8.11%/6.9% CBD: THC;

Sour Tsunami at 7.24%/4.32% CBD: THC (see http://www.synergymmj.com/products.html).

It is also unclear whether their advertised ratios are accurate, i.e., whether the testing results are valid. Recent internet comments by parents complain that batches of “artisanal” CBD products do not have a consistent or anticipated effect and/or they are horrified that their children become “high”. This is a problem because medicines should be standardized and consistent among batches.  Finally, in many cases, the “high CBD” products may be contaminated by pesticides, synthetic fertilizers, and dangerous microbes.  Pesticides are neurotoxic, which could be quite dangerous to children with epilepsy. A number of physicians are reporting instances of bacterial infections, allegedly resulting from the use of these products.

Don’t you need some THC to synergize with CBD?

There is absolutely no reliable scientific evidence that THC is necessary to synergize the effects of CBD. Instead, there is evidence from preclinical research that THC may be pro-convulsant in sensitive brains; other research indicates that chronic use of THC can impair IQ in adolescents. Physicians are beginning to report instances of THC toxicity in children taking “high CBD” preparations, e.g., high anxiety, increased seizures, insomnia, etc. Until more is known, the most conservative course of action would be to remove THC entirely from a CBD product.

Why is there so much interest in CBD now?

 A number  of years ago, Project CBD in California, inspired by research being conducted by GW Pharmaceuticals in the U.K. (see below), began to educate interested patients and others about the therapeutic potential of CBD, which was virtually absent in high-THC marijuana in the U.S. Indeed, before GW embarked on its cannabinoid research and development program, many individuals in the U.S. believed that CBD was an inert compound. There were also anecdotal reports of some adults with epilepsy who discovered that inhaled marijuana seemed to prevent or reduce their seizures. As more and more scientific research demonstrated that CBD had a variety of therapeutic effects, interest in the use of CBD in epilepsy grew.

The CNN program hosted by Dr. Sanjay Gupta in August 2013 portrayed the case of a little girl with horrible, life-threatening intractable epilepsy. According to Dr. Gupta, her condition was greatly improved by a CBD-rich preparation produced by a company in Colorado. Understandably, this program resulted in enormous interest in CBD from families of children with epilepsy. As desperate parents sought “high CBD” products wherever they could purchase them, a number of dispensaries and other opportunistic vendors began to sell these products. However, the labelled potency and composition are often inaccurate and uneven, depending on the marijuana strain from which they come, the methods of manufacture used to prepare them, and the quality of the testing facility/procedures. At many places in the cultivation and manufacturing process, lack of standardization can result in higher levels of THC and lower levels of CBD –as well as the varying levels of dangerous microbes or pesticides -in the final preparation, e.g. growing from seed rather than clones; differences in the cultivation, harvesting, and drying conditions; uneven decarboxylation; and use of toxic extraction chemicals, such as butane or non-pharmaceutical ethanol.

Should the law be changed to allow high CBD, low THC products? 

 A state considering such a change in law should look to the example of other states where “high-CBD” products are legal for medical use, such as California.

In California, various preparations are available, and children can readily be given these products with 1) parental consent and 2) a physician’s recommendation.

Nevertheless, for the reasons stated above, the “legality” of these products has not made properly tested and standardized CBD products available to parents.

Products vary in consistency; testing laboratories do not provide reproducible and reliable results; testing each batch is expensive; most testing CBD laboratories do not test for pesticides or microbes; parents do not know how to prepare extracts from plant materials; the products themselves can be expensive; no dosing information is available; and more. Legislation is a blunt instrument, and any change in state law will, necessarily, be quite broad (e.g. “high CBD, low THC”) to permit various opportunistic growers and vendors to enter the state and prey upon vulnerable parents. Unless an elaborate testing system is established and enforced by the state, this will not ensure the safe, tested, and standardized products that parents seek for their children. Even certain more popular products are of uncertain composition, quality and efficacy. Companies selling these products have not made public the composition/ratio of an adequate number of batches, nor have they provided full battery anonymized case studies showing how many patients benefit and to what extent, how many patients get little or no benefit, what side effects they experience, and what they charge for the product. At most, 11 “selected” case studies have been presented, all of which show

However, these are anecdotal cases reported by parents, and it is unlikely that current CBD preparations work for all seizure conditions.

Source:  www.learnaboutsam.org  2013

Filed under: Medicine and Marijuana :

Here is an excellent op-ed by Howard Samuels, president of The Hills Treatment Center in Los Angeles. He uses Kevin’s point that legalization is a step too far and addresses the real purpose behind the marijuana legalization movement   – recreational use.

 

Legalizing pot isn’t about medicine, it’s about getting high

 

Howard C. Samuels, author of “Alive Again: Recovering from Alcoholism and Drug Addiction,” is the founder and president of The Hills Treatment Center in Los Angeles.

 

(CNN) — At first glance, my 11-year-old son seems like your everyday, all-American kid. He loves baseball and basketball, plays Xbox with his friends when they come over, and posts innocuous pictures of the family dog on his Instagram feed. Given these mundane facts about the boy, you can imagine my surprise when, while watching the news (again, seemingly from out of nowhere) he asked me, “If pot is so bad, why are they trying to legalize it?”

 

And, just like that, the long and involved talk my wife and I had given our children about drugs was tossed out the window.  We had explained the harmful effects of marijuana. Like cigarettes, smoking marijuana introduces tar, carbon monoxide and cancer-causing agents into your body.

 

Neither my wife nor I anticipated that our son would be stopped on the street by unscrupulous potheads petitioning outside of the local grocery store and being fed a line of rhetoric that went against what we were trying to teach him.

 

It turns out that potheads weren’t exactly the problem; they were the symptom. Let me tell you why.  If you have a fever and you go to the doctor and he tells you that you have pneumonia, do you ask him to treat the fever, or do you ask him to treat the pneumonia? Most of us would ask him to treat the pneumonia because the pneumonia is the problem; the fever is the symptom.

 

It’s the same way with the argument about the legalization of marijuana. I’m not interested in focusing on the symptom; I want to eradicate the problem. And the problem is that we’re even considering legalizing marijuana at all.

 

Let’s take a look at the medical marijuana issue in Los Angeles (where I live) and we can see where legalization takes us. It has been my experience that anyone can get a medical marijuana card in L.A.; all you need is $25-$100 and the ability to lie about needing it. You just make an appointment with some company, walk in and state your problem(s) and why you need a card (with no proof of medical conditions whatsoever) and you will be prescribed a card that is good for one year. It’s a toothless system that isn’t well-regulated.

 

Why are some of the people who petition for legalizing marijuana so passionate about it? Because when you smoke pot, you get loaded. You fry your brain. That’s why the patients I see in my treatment center call it “getting baked.” Pot is all about getting really high.

 

Now, I have nothing against people who smoke pot. In fact, I believe it is a crime to put someone in prison for smoking pot. Honestly, do we really need some idiot frat boy to get picked up during Mardi Gras for smoking pot and find himself locked in a cage with a monster for six months? Kevin Sabet, a former senior adviser to the White House Office of National Drug Control Policy poses a terrific point when he says that criminal processing for possession of marijuana needs improvement, but legalization is a step too far.

 

Marijuana supporters like to argue that marijuana is similar to alcohol. While alcohol is legal, it also accounts for tens of thousands of deaths every year in car accidents or other drinking-related misfortunes. But we can’t turn the clock back on that one because it’s too embedded in our society.

 

Supporters of marijuana say that marijuana should be legalized because old people and women and children who have ailments like glaucoma or cancer or intractable seizures need it.   It is painful to watch people suffer. I am not against helping people. In a perfect world, a woman suffering from cancer should be able to get a prescription from her doctor, go to a pharmacy, acquire her medical marijuana, go home and recuperate from her last round of chemotherapy. But we don’t live in a perfect world, and you don’t need a Ph.D. to see that the spirit of that argument is being exploited by people who aren’t using the marijuana for medical reasons at all; they are using it to get high.

 

Introducing legalized marijuana into our culture would be like using gasoline to put out a fire, because it stunts growth.

 

Do you know why we don’t see potheads out in public? It’s because they’re sitting at home smoking weed and staring at their television sets or playing video games all day. Do you have any idea how many marijuana addicts I encounter at my rehab on a daily basis? They talk about wanting to be productive. But what pot does is it kills their motivation — it destroys people’s ability to go out and work and to have a career. It makes them want to do nothing but lie around all day. Is that what you want for your children? Is that what you want for your loved ones?

 

And how do you market marijuana? We have only just now moved into an era where cigarette smoking is commonly known to be harmful, but now advertisers have a new product to sell. Who do you think they’re going to market their product to? Not you or me, because we’re not stupid enough to believe the lie; we know too much. They’re going to follow in the footsteps of the cigarette companies in the 1980s and market this stuff to young people.

 

The very idea of that sickens me. I know what marijuana does to the human mind because I started smoking weed when I was 15 years old. It literally robbed me of my motivation to participate in my own life. I was absolutely OK with sitting around all day eating cookies and watching television and getting high with my friends. But, to go out and earn a living and do something with my life? That was all stuff that I was going to do later after I came down off of the marijuana. But, then I’d smoke some more and think, “Why bother?” . . . and, eventually, I started shooting heroin. If my family had not intervened and sought professional help, I would probably still be wandering aimlessly through the streets today; searching for that elusive “perfect high.”

 

Even if you only stay with marijuana in your repertoire of illicit drugs to abuse, it will never yield positive results. Ever.

 

And, I posit this to marijuana abusers everywhere: Are you really that weak? Are you really that uncomfortable in your own skin that you can’t handle living your life or having real experiences without being high? Is it really impossible for you to live life without a drug? Because, if it is, it breaks my heart and I feel sorry for you. Because that’s no way to live.

 

And my kid, he’s going to know the truth about you. He’s going to know that every time you approach him arguing for the legalization of marijuana, what you’re really doing is asking him to vote to make it OK for you to spend the rest of your life half-baked on your sofa, too stoned to go out and play with your own kids or do the things you’ve

always dreamed of doing. To my kid, I’m going to say that this means one less competitor on his road to a successful and fulfilling life.

 

And, to the potheads who are so passionate about being allowed to smoke their lives away, I have only one thing to say: Dream On.

Source: http://www.cnn.com/2013/08/09/opinion/samuels-pot-addiction/  

Filed under: Medicine and Marijuana :

THE FOLLOWING PAPER SHOWS EXTRACTS FROM A REPORT PUBLISHED IN AUGUST 2013 – SHOWING THE IMPACT OF MARIJUANA LEGALISATION AND SO-CALLED MEDICAL MARIJUANA FROM 2009.  THIS REPORT IS SHOCKING AND SHOULD BE CAREFULLY READ IN FULL BY ANY POLITICIANS CONSIDERING CHANGING DRUG POLICY LAWS.

NDPA SUGGESTS YOU GO ONLINE TO ACCESS THE FULL REPORT.

THE LEGALIZATION OF MARIJUANA IN COLORADO: THE IMPACT Vol. 1/August 2013 Executive Summary

2006 – 2008: There were between 1,000 and 4,800 medical marijuana cardholders and no known dispensaries operating in Colorado.

2009 – 2012: There were over 108,000 medical marijuana cardholders and 532 licensed dispensaries operating in Colorado by November 2012.

 

Colorado Youth Marijuana Use: In 2011, the national average for youth 12 to 17 years old considered “current” marijuana users was 7.64 percent which was the highest average since 1981. The Colorado average percent was 10.72.

 

Colorado Adult Marijuana Use: In 2011, the national average for young adults ages 18 to 25 considered current marijuana users was at 18.7 percent. The Colorado average was 27.26 percent.

 

Colorado Emergency Room – Marijuana Admissions: From 2005 through 2008 there was an average of 741 visits per year to the emergency room in Colorado for marijuana-related incidents involving youth. That number increased to 800 visits per year between 2009 and 2011.

 

Colorado Marijuana-Related Exposure Cases: From 2005 through 2008, the yearly average number of marijuana-related exposures for children ages 0 to 5 years was 4. For 2009 through 2012, that number increased 200 percent to an average of 12 per year.

 

Diversion of Colorado Marijuana (General): From 2005 to 2008, compared to 2009 to 2012, interdiction seizures involving Colorado marijuana quadrupled from an average per year of 52 to 242. During the same period, the average number of pounds of Colorado marijuana seized per year increased 77 percent from an average of 2,220 to 3,937 pounds. A total of 7,008 pounds was seized in 2012

 

Beginning in the spring of 2009, Colorado experienced an explosion to over 20,000 new medical marijuana patient applications and the emergence of over 250 medical marijuana dispensaries (allowed to operate as “caregivers”). One dispensary owner claimed to be a primary caregiver to 1,200 patients. Government took little or no action against these commercial operations.

By the end of 2009, new patient applications jumped from around 6,000 for the first seven years to an additional 38,000 in just one year. Actual cardholders went from 4,800 in 2008 to 41,000 in 2009. By mid-2010, there were over 900 marijuana dispensaries identified by law enforcement.

In 2010, law enforcement sought legislation to ban dispensaries and reinstate the one-to-five ratio of caregiver to patient as the model. However, in 2010 the Colorado Legislature passed HB-1284 which legalized medical marijuana centers (dispensaries), marijuana cultivation operations, and manufacturers for marijuana edible products. By 2012, there were 532 licensed dispensaries in Colorado and over 108,000 registered patients, 94 percent of who qualified for a card because of severe pain.

 

Traffic fatalities in Colorado decreased 16 percent1, from 2006 to 2011, which is consistent with national trends. During the same six years in Colorado, traffic fatalities involving drivers testing positive for just marijuana increased 114 percent.2

• In 2006 in Colorado, traffic fatalities involving drivers testing positive for marijuana represented 5 percent of the total traffic fatalities. By 2011, that percent more than doubled to 13 percent.2

• In 2006, drivers testing positive for marijuana were involved in 28 percent of fatal vehicle crashes involving drugs. By 2011 that number had increased to 56 percent.2

 

DUID (Driving Under the Influence of Drugs)

Victim Voice President Ed Wood shares his perspective on drugged driving:

“Drivers on drugs are involved in a remarkably high proportion of fatalities. When we look at only collisions where drivers’ blood tests were reported, we see that 36 percent of the fatalities involved drivers testing positive for drugs, and 20 percent tested positive for marijuana. These percentages held steady from 2006 through 2009 (averaging 29 percent and 12 percent respectively), but the marijuana numbers took a big jump to 17 percent in 2010 and again to 20 percent in 2011 after dispensaries were established.”

 

 

The French National Institute for Transportation and Safety Research, in a study published in 2005 by the British Medical Journal, concludes that even small amounts of marijuana could double the chances of a driver suffering a crash and larger doses could more than triple the risk.

• According to the Columbia University School of Public Health, the risk of an automobile crash is almost 2.7 times higher among marijuana users than non-users. The more marijuana smoked in terms of frequency and potency, the greater likelihood of a crash.4

 

• Glenn Davis, Highway Safety Manager, Colorado Department of Transportation (CDOT), Office of Transportation Safety, said that of drug-related deaths, half involved marijuana. He stated, “You have a substance [marijuana] that causes impairment that is more readily available than it was two years ago.” Davis said that was because of the increasing use of medical marijuana in Colorado.5

 

• The National Highway Traffic Safety Administration (2009) found more people are driving on weekend nights under the influence of marijuana (8.3 percent) compared to alcohol (2.2 percent).6

 

• Close to one out of four teens admit to driving under the influence of alcohol or drugs and, of those, 75 percent do not believe smoking marijuana adversely affects their driving.7

 

• The National Highway Traffic Safety Administration (2004) found that marijuana significantly impairs one’s ability to safely operate a motor vehicle. They cite: decreased car handling performance, inability to maintain headway, impaired time and distance estimation, increased reaction time, lack of motor coordination and impaired sustained vigilance.8

• An article published in the Volume 34, 2012 edition of Epidemiologic Reviews examined nine studies conducted over the past two decades on marijuana and car crash risks. Their conclusion: “Drivers who tested positive for marijuana, or self-reported using marijuana, are more than twice as likely as other drivers to be involved in motor vehicle crashes.”

 

A study published by the National Institute of Health Public Access in 2009 showed that the effects of marijuana vary more between the individual than the effects of alcohol. The study also states that laboratory tests and driving studies show, “Cannabis may acutely impair several driving-related skills in a dose-related fashion but the effects between individuals varies more than they do with alcohol because of tolerance, the difference in smoking techniques and different absorption of THC.” The study warns that patients who smoke marijuana should be counseled to have a designated driver if possible or to wait at least three hours after smoking.10

• A 2009 study published by the Institute for the Study of Labor in Germany claimed that states with legalized medical marijuana actually had a drop in traffic deaths. This study was not peer reviewed. The states selected were Vermont with only 400 cardholders, Rhode Island with only 3,000 cardholders and Montana which had only 6,000 cardholders.11

• A study by Dalhousie University (Halifax, Nova Scotia, Canada) Associate Professors Ashbridge and Hayden published in the British Medical Journal on February 9, 2012 showed: “Driving under the influence of cannabis was associated with a significantly increased risk of motor vehicle collisions compared with unimpaired driving.

 

Students’ Current Marijuana Use

In 2011, nearly one out of four of the Boulder County School District high school students (9th – 12th grade) surveyed indicated that they were current marijuana users.  This is more than three times the national rate.

o In academic school years 2008 – 2010, an average of 20.75 percent of Adams County high school students surveyed indicated they were current marijuana users (at least once in the last 30 days). That number increased 39 percent during academic years 2010 – 2012 to 28.85 percent.

 

In the academic school years 2008 – 2010, an average of 5.65 percent of Adams County middle school students surveyed indicated they were current marijuana users (at least once in the last 30 days). That number increased 50 percent during academic years 2010 – 2012 to 8.5 percent.11

 

 

Colorado Springs Drug Testing High School Referrals o Drug-related referrals for high school students testing positive for marijuana have increased each year from 2007 – 2012. During 2007 – 2009 an average of 5.6 students tested positive for marijuana.

During 2010 – 2012 the average number of students who tested positive for marijuana increased to 17.3 students per year.

 

In 2007, tests positive for marijuana made up 33 percent of the total drug screenings, by 2012 that number increased to 57 percent.

 

Detected THC levels in the students increased by 76 percent after 2009. § 2007 – 2009 the average THC level quantified = 225 nanograms.

2010 – 2012 the average THC level quantified = 396 nanograms.

 

Current Marijuana Use Rates for 12th-Graders

In 2011, the average of 12th graders using marijuana in the last 30 days:  Nationally – 28.0 percent12 (22.6 percent2 according to the National Institute for Drug Abuse [NIDA])

Colorado – 31.2 percent10

Denver Public Schools – 32 percent6

Boulder County High Schools – 36 percent3

 

High School Senior Daily Use of Marijuana o Nationally in 2011, of the 12th grade respondents, 6.6 percent reported smoking marijuana daily, which is the highest level since 1981 when the rate was 7 percent. In 2011, 7.8 percent of Colorado’s high school seniors reported using marijuana 40 or more times per month.  Another 2.9 percent reported using marijuana between 20 and 39 times a month.

 

Colorado Department of Education- Drug Related Suspensions and Expulsions

There was a 32 percent increase in drug-related expulsions and suspensions from the 2008 – 2009 academic year to 2009 – 2010 academic year.7

For the academic years ending in 07, 08, and 09, drug related expulsions/suspensions remained stable with an average of 3,782.7

For the academic years ending in 10, 11, and 12, drug-related expulsions/suspensions increased to an average of 5,217.7 This is a 37 percent increase.

 

“Drug violations shot up dramatically in Colorado schools during the 2009-2010 school year, reversing a decade of steady decline…”9

Rebecca Jones, reporter, EdNews Colorado

 

 

• The average reported past month marijuana use for young adults (ages 18-25) in 2011: o The national average = 18.78 percent

o The Colorado average = 27.26 percent

 

• The average reported past month marijuana use for adults (ages 26+) in Colorado has increased from 5.32 percent in 2008 to 8.19 percent in 2011. That is a 54 percent increase.

 

 

Drug Abuse Warning Network (Ages 12 – 17) Data: o Colorado ER visits per year related to marijuana only:

2005 – 2008 = 741 average visits per year

2009 – 2011 = 800 average visits per year

 

In 2011, Colorado ER data showed that marijuana-related incidents accounted for 26 percent of the total ER visits, compared to 21 percent nationally.

 

 

• Young children (ages 0 to 5) marijuana-related exposures in Colorado

 

During the years 2006 – 2008, the average number of marijuana-related exposures for ages 0 to 5 was 4 per year.1

For the years 2009 – 2012, the average number of marijuana-related exposures for ages 0 to 5 was 12 per year.1 § This is a 200 percent increase.

 

 

El Paso Intelligence Center, National Seizure System

NOTE: This only includes those cases in which Colorado marijuana was actually seized and reported. It is unknown how many

Colorado marijuana loads were not detected or, if seized, were not reported.

 

El Paso Intelligence Center (EPIC) has established the National Seizure System (NSS) for voluntary reporting interdiction seizures throughout the country.

 

 

Many state highway patrols have done a good job reporting their highway seizures. RMHIDTA was able to identify the number of interdiction seizures involving marijuana from Colorado destined for other states in the country.

 

• In 2012, there were 274 Colorado marijuana interdiction seizures destined for other states compared to 54 in 2005. This is a 407 percent increase.

 

• Of the 274 seizures in 2012, there were 37 different states destined to receive marijuana from Colorado. The most common destinations were Kansas (37), Missouri (30), Illinois (22) Texas (18), Wisconsin (18), Florida (16) and Nebraska (13). There were some seizures in which the destination state was unknown.

• From 2005 – 2008, compared to 2009 – 2012, the average number of interdiction seizures per year involving Colorado marijuana more than quadrupled from 52.2 to 242.

• From 2005 – 2008, compared to 2009 – 2012, the total average number of pounds of Colorado marijuana seized from interdictions increased 77 percent from an average of 2,220 pounds to 3,937.

 

• In 2012, there were 7,008 pounds of Colorado marijuana seized by interdictions that were destined for other states in the country.

 

• The top three Colorado counties identified as the source for the marijuana in 2012 were Denver (141), Boulder (27) and El Paso (24).

 

Dispensary “Patient” Sells Fifty Percent of His Dispensary Marijuana to Juveniles: On May 31, 2012, North Metro Task Force executed a residential search warrant in Thornton, COLORADO where a 19-year-old male was selling marijuana. The suspect admitted to selling marijuana for two years but recently expanded his business after getting his medical marijuana card. He stated that he gets the marijuana he sells from a dispensary in the Denver Metro area. The suspect admitted he purchases approximately 5 to 6 ounces of marijuana per week. He sells 60 percent while using or sharing the other 40 percent. He estimated that his profit is approximately 30 percent. He admitted to three to four drug sales per day, seven days per week. He also stated that 50 percent of these sales are directly to juveniles. He said dispensary marijuana is easy to get and is of high quality.

Impaired Driver Cites Ease of Getting Dispensary Marijuana: In April 2012, the Thornton Police Department (COLORADO) contacted a driver who admitted to smoking marijuana while driving. She failed voluntary roadside tests and was arrested. During a search of her vehicle officers found 3 ounces of marijuana with dispensary stickers. In an interview she admitted she does not have a medical marijuana card. She stands in front of dispensaries and asks people to buy her marijuana. She admitted that she had done this multiple times and had never gone away empty handed. When asked why she goes to dispensaries, she stated that the marijuana is better but the main reason was availability. She said she never had to wait more than two hours to get a couple ounces of marijuana. Conversely, when she was buying from other sources she sometimes would have to wait and never get what she wanted. She noted the ease and certainty of buying marijuana has made using dispensaries well worth it.

 

In a press release dated August 13, 2012, Colorado Attorney General John Suthers stated, “It is becoming clear that as predicted in the 2010 legislative hearings, Colorado is becoming a significant exporter of marijuana to the rest of the country.”

A 2011 report from the Drug Enforcement Administration – Denver Field Division states, “Colorado’s medical marijuana system allows for a widespread exportation and illicit marijuana distribution…. Colorado is on track to become a primary source of supply for high-grade marijuana throughout the country.”2

Nebraska State Patrol Sergeant Dana Korell: “Marijuana out of Colorado is having a local impact. It is flooding, just flooding the marketplace. It’s everywhere.”3

Cheyenne County (Nebraska) Sheriff John Jensen claims legalizing marijuana in Colorado changed local drug trafficking in a way not seen in his seventeen years in law enforcement. “Now you have dispensaries, you have grow houses in our neighboring states that are growing a much better product.” “Now we’re getting the high-grade marijuana” coming across the border.3

The Intelligence Center’s analysis of the illegal drug market in the Midwest High Intensity Drug Trafficking Area, which includes Nebraska, found “demand for high-potency marijuana has increased during the last three years, fueling both increased indoor hydroponic grows and importation from California and Colorado.”4

 

United States Postal Inspection Service (USPIS) “Prohibited Mailing of Narcotics”

(PMN) drug database:

This database does not capture parcels with smaller amounts of marijuana which are handled administratively.

 

• From 2010 – 2013, the number of intercepted parcel packages of marijuana from Colorado, has increased each year:

2010: 15 parcels

2011: 36 parcels

2012: 158 parcels § Over ten times the number seized in 2010

2013: 209 parcels – only as of May 2013 (five months)

 

• From 2010 – 2012 the total pounds of marijuana seized from packages mailed from Colorado has increased each year:

In 2010: total of 57 pounds were seized

In 2011: total of 68 pounds were seized

In 2012: total of 262 pounds were seized § Nearly five times the amount seized in 2010

These figures only reflect packages seized. They do not count packages of Colorado marijuana that were mailed and reached the intended destination.

 

In 2013: 205 pounds have been seized – as of May 2013 (five months)

 

• Between 2010 and 2012, the number of states destined to receive marijuana mailed from Colorado has increased each year:

In 2010 – 10 states

In 2011 – 24 states

In 2012 – 29 states

In 2013 – 23 states in only the first three months

It is called dabbing, and it is something the marijuana legalization movement would rather you didn’t know about. As crack is to powdered cocaine, so a dab is to a joint of marijuana: the same drug, in a much more concentrated form. But butane hash oil, or BHO, the end product of dabbing, is seen by many in the movement as a potential public relations disaster.  It’s easy to find instructions on the Internet for making butane hash oil. (Not to be confused with the hash oil of the 1970s produced, most commonly, using sieves, ice, naphtha, or acetone to separate the THC-rich trichomes from the rest of the plant material.) Butane hash oil, produced by “blasting” butane through top-quality marijuana, then “purging” away the butane, looks a bit like beeswax and allegedly boosts THC content to a mind-blowing 70 to 90 per cent. The most potent of today’s varietals rarely reach or exceed 20 per cent. The result is known as wax, shatter, honey oil, and about a dozen other monikers. It is smoked using a glass tube and a red-hot piece of metal, not unlike the hippie “hot knives” method of smoking. As Andrew Sullivan wrote at his blog, The Dish: “Going on the basis of such super high purity alone, even the funkiest colored trichome crystal encased high-grade leaf starts to look like steam punk technology in a fossil fuel world.”  Or, in the pithy phrasing favored by High Times: “A quantum leap forward in stoner evolution.” In a High Times magazine article last year, author Bobby Black wrote about the central problem, namely that “the techniques used to make and consume BHO bear an eerie resemblance to those used for harder drugs like meth and crack.” This creates “a fear that seeing teenagers wielding blowtorches or blowing themselves up on the evening news might incite a new anti-pot paranoia that could set the legalization movement back decades.” It happened when wine and ale became whiskey and gin, according to one school of thought. It happened again when hand dried, hand rolled tobacco became the machine rolled cigarette. And it happened when powdered cocaine became crack. Increasingly concentrated forms of plant drugs became more potent, more addictive, more expensive—and more socially disruptive. Has it happened in a high-tech way with good old friendly organic backyard marijuana? And is BHO any more dangerous to users than regular weed? The butane technique is controversial, and the effects of ingesting marijuana that has previously been supersaturated with that particular solvent are intensely debated in the weed world. Marijuana collectives in California have been selling “butane honey oil” to qualified medical marijuana customers for some time now. There are tasting parties called “Wax Wednesdays.” But the state has made it illegal to produce BHO. David Downs, writing last month in Oakland’s East Bay Express, reported on a state appellate courting hearing in San Francisco, “in which an attorney for defendant Ryan Schultz worked to overturn the San Francisco resident’s three-year probation sentence for operating a BHO ‘drug lab.’ Meanwhile, several blocks away at permitted pot dispensaries, the fruits of such drug labs are on sale for upwards of $50 per gram.”  The defendant’s case was not helped when, in January, “two blasters blew themselves up in a San Diego motel, resulting in hospitalization, followed by drug lab charges.” And just to confuse the matter a bit more, BHO production is legal in Colorado, and other medical marijuana states are considering it. The health verdict on all this isn’t in yet. The primary danger of BHO may be its manufacture, and in all the Richard Pryor-type explosions that lie ahead. Even High Times seems to be a bit wary of it. The magazine “strongly discourages anyone who has not been professionally trained from making BHO on their own.” Ventilation, it seems, is the key.  It’s unlikely, but not impossible, that the amount of residual butane inhaled could constitute a health threat. Cheap butane contains various impurities, and there has been at least one reported case of chemical epiglottitis, a condition in which inflammation caused by a chemical blocks off the windpipe. But as one marijuana backer told High Times, “you can actually get epiglottitis from hot coffee if you swallow it incorrectly.” In February, The Federal Emergency Management Agency (FEMA) was moved to issue a formal bulletin on the matter: “Butane is highly explosive, colorless, odorless and heaver than air and therefore can travel along the floor until it encounters an ignition source…. Reported fires and explosions have blown out windows, walls, and caused numerous burn injuries.”  Bob Melamede, an associate professor of biology at the University of Colorado and the CEO of Cannabis Science Inc., told High Times: “If you have contaminants (i.e., pesticides, herbicides, fungi) on your plant, that’s going to come off into the extract. Then, when you evaporate the solvent, you’ll actually be concentrating those things—and THAT’S the real danger.”

Source:  ADDICTION INBOX

THE SCIENCE OF SUBSTANCE ABUSE JUNE 2, 2013 Photo Credit: http://www.hightimes.com/

Dr Gregory K Pike
Director, Adelaide Centre for Bioethics and Culture
May, 2013

Introduction
As long as humans have suffered from ailments, medicine has sought treatments. To attempt to alleviate suffering is a mark of the better face of humanity, or at least recognition that we all, at one time or another, are subject to illnesses that need relief. Hence, maladies are markers of our shared condition and an opportunity for our better qualities to find expression.
The search for healing has taken many turns down the centuries, and along the way there have been good and bad treatments, effective ones, futile ones, burdensome ones, ‘miraculous’ ones, deceptive ones and downright dangerous ones. Just as humans can act wisely or foolishly, so treatments have been wisely or foolishly developed and employed. And noble motives are no guarantee that genuinely good treatments will be used.
As the scientific enterprise has grown and understanding of human biology advanced, so has our understanding of the biological basis of medicine. While our knowledge is far from complete, modern medicine now has an impressive array of treatments, and in many cases cures. There will always be mistakes, more inquiry, refinement, and new discoveries, but the general trend is moving forwards with hope for improvements and new ways of alleviating human suffering.
Modern medicine is not only built upon understanding human biology, but also upon an understanding of human nature itself. This is where a proper appreciation of human nature aligns with an ethical framework directed towards the good of the person receiving treatment. Hence, medicine has always developed codes of ethics that serve as a foundation or point of constant referral against which the discipline measures any new development. A sound ethical framework also recognizes the place of the patient within a community and also the unique nature of the relationship between patient and physician.
It is within this broad context that the question of medical marijuana needs to be considered.
At the outset an important distinction needs to be made, and that is between use and abuse. Health practitioners are aware of the abuse of legally available pharmaceuticals; for example, benzodiazepines like Xanax, opiates like Morphine and Oxycodone, antipsychotics like Seroquel, and amphetamines like Ritalin and Adderall. These are substances used for treatment of defined medical conditions that at the same time can be abused. Health practitioners are also aware of the abuse of illicit drugs like heroin, cocaine, cannabis and amphetamine. These substances have been deemed to have either no or limited medical application along with a high risk of abuse as ‘recreational’ drugs. Moreover, the link between such abuse and the phenomenon of addiction makes these substances especially problematic.

The term ‘medical marijuana’ has been used variably, but will be taken here to mean smoking the herbal product. This is to be distinguished from other means of delivery of the crude product, which could include tinctures, taking in an oral form, or vaporizing. The active ingredient(s) can also be isolated and taken orally or by nasal spray.

How does marijuana work?
The active ingredients in cannabis exert their effects by acting upon specific receptor sites in the brain and elsewhere. Much like the better understood endogenous opiate receptor system upon which drugs like morphine, codeine and heroin act, there is an endogenous cannabinoid receptor system upon which cannabis acts, or more correctly, upon which the active ingredients act, which are primarily tetrahydrocannabinol (THC) and cannabidiol (CBD). And just as there are naturally occurring substances within the brain that act upon opiate receptors, that is, the endorphins and enkephalins, there are naturally occurring substances which act upon cannabinoid receptors. The two identified so far are anandamide and 2-arachidonoylglycerol (2-AG).
The cannabinoid receptor system is widespread throughout the brain and serves a range of functions that are gradually becoming better understood. So far the system has been shown to be involved in motor control, cognition, emotional responses, motivated behaviour, learning and memory, appetite, pain and neuroprotection.
When cannabis is smoked and the active ingredients enter the bloodstream they are able to act upon these systems. Given that the systems are so widespread and complex, THC and CBD act upon many different processes that are involved in the functions listed above. Hence, it is not surprising that when someone smokes cannabis it affects their coordination, emotional responses, appetite, memory and ability to learn, ability to think clearly and rationally, and so on. Since the purpose of smoking cannabis ‘recreationally’ is to get high, the doses involved typically interfere with these systems in an adverse way and therefore the result of sustained exposure gives rise to the harms associated with cannabis. The endocannabinoid system is effectively swamped by THC, CBD and the other ingredients in marijuana at well beyond the natural physiological stimulation that occurs with anandamide and/or 2-AG.
The harms caused by cannabis are still being explored, but there is reasonable and growing evidence to indicate that the risks are significant, particularly with respect to mental health, where the results may be psychosis, depression, anxiety, memory deficits, impaired learning and motivation. These harms are of particular relevance for the developing brain and so all that can be done to protect young people from the harm of smoking cannabis should be a priority. Other harms include risks associated with immediate effects, for example due to impact upon motor control and decision-making, changes in perception and anxiety and possibly blacking out. Long term harms may also include risk of certain cancers and other respiratory diseases.
It is also important to note that the intrinsic harm of addiction makes all the difference. Substances with addictive potential are categorically unique and add a problematic dimension that must be taken into proper account when considering any possible therapeutic effect.
Human beings place a high value on freedom. To be free to act as an autonomous agent, to make real choices about how to live one’s life, is universally valued and desired. The essence of addiction is the loss of freedom, the substantial impairment of voluntary control over one’s behaviour … Addiction causes serious harm to individuals as well as to their friends, relatives and the community. It is the type of problem that varies not only in degree but also with considerable individual distinctiveness. It can be an intensely personal inner struggle that remains private, or a painfully public and alienating experience.1
It is estimated that approximately 10% of those who smoke cannabis will develop an addiction. The phenomenon of withdrawal should also be considered as one of the harmful effects of cannabis dependence. It includes, headaches, irritation, nausea, depression, insomnia, anxiety, poor appetite and restlessness. 2

Is Marijuana Medicine?
If marijuana has medicinal value, the first question to be asked is, “In what form might it have medicinal value?” Currently, many people claim that smoking marijuana treats a medical condition. Research directed towards this question will be considered shortly, along with a series of related questions about abuse, harm, and other social and legal issues that are largely prudential in nature – but are nonetheless important and with far-reaching implications.
The modern scientific approach to medicines typically follows a path of inquiry directed towards obtaining the most beneficial form of a medicine to treat a specified condition. For example, while opium has been recognised for its medicinal value for many centuries, the active ingredients codeine and morphine have now been extracted and subjected to extensive research and analysis over many years. We now have both in various formulations with known dosage and purity, a body of information on side-effects, known indications and contraindications, knowledge of therapeutic targets, patient populations for whom treatment is appropriate, and knowledge of abuse potential. No medical authority would ever prescribe or even recommend smoking opium, not only because of the availability of formulations of active ingredients which are superior, but also because of the harm of smoking as a delivery system.
Might not THC, CBD and other ingredients in marijuana likewise be useful medicines?
This is an important question in its own right regardless of the ‘recreational’ abuse of marijuana, and this area of research has gained considerable traction as discoveries about the endocannabinoid system in the brain have been made.
Currently there are 4 formulations of active ingredients, dronabinol (Marinol), nabilone, nabiximols (Sativex) and rimonabant. The first two are THC lookalikes, whereas Nabiximols is a marijuana extract containing both THC and CBD. Rimonabant is a cannabinoid receptor blocker which was initially marketed as an anti-obesity drug in Europe in 2006 before being withdrawn soon after when side effects including serious depression and suicidal ideation were found to be frequent.
Dronabinol was approved by the US Food and Drug Administration (FDA) in 1985 for treating chemotherapy-induced nausea and vomiting and AIDS-related wasting, and although proven effective, both dronabinol and nabilone have not become the mainstays of treatment mainly because of their side effects, which include sedation, anxiety, dizziness, euphoria/dysphoria and hypotension, as well as the presence of superior alternatives.
Dronabinol and nabilone have also been shown to produce symptomatic relief of neuropathic pain and the spasticity associated with multiple sclerosis. However, whilst patients report alleviation of spasticity, measures of objective changes are mixed. In a recent study by Kraft and co-workers, an orally administered extract of cannabis containing mainly THC was found to have no beneficial impact on acute pain and may possibly have enhanced pain sensation.3 This study highlights not only the complex nature of pain itself, but also the importance of identifying specific therapeutic contexts in which THC may or may not be useful.
It should be noted that while these studies are conducted much like other studies on medical agents, a particular problem arises because the psychoactive side effects of dronabinol and nabilone make it difficult to maintain appropriate blinding, which is a basic requirement of a randomized controlled trial. In other words, when the research subjects become aware that they are receiving the active ingredient and not the placebo, their perception of therapeutic value is potentially confounded and a study’s claim of therapeutic advantage over placebo may be compromised.
Nabiximols is an interesting example of a novel form of delivery by nasal spray that has the advantage of rapid absorption. By including both THC and CBD together, it may be that CBD limits some of the adverse side effects common with THC alone. It has been licensed for the treatment of cancer pain and neuropathic pain.
The role of CBD in potentially mitigating some of the adverse effects of THC may prove to be a valuable finding. It also highlights why use of the raw herbal product could be even more problematic than already thought, because as new strains have been developed, the amount of THC has risen at the same time as the amount of CBD has declined. In some strains, CBD is virtually absent. When production of cannabis is permitted by the public for medical use, there is no control over the levels of active ingredients and in particular the ratio of THC to CBD.
One final variation on delivery systems involves vaporization of the herbal product. This means of delivery is about as close as possible to smoked marijuana. Some clinical trials are currently underway.
It is important to note that with each of these formulations little is known about the medium to long term adverse effects. However, given that there is evidence for long-term harm arising from studies of those who smoke cannabis regularly, significant caution should be exercised about these formulations of active ingredients.
Research on smoked marijuana has occurred in parallel with research on the active ingredients. Smoked cannabis has been found to improve appetite and weight gain in HIV patients without adverse effect on viral load.4,5 However, again the validity of the results may be affected by poor blinding, and the effectiveness would of course need to be balanced against adverse effects.
Following the establishment of the Center for Medicinal Cannabis Research (CMCR) at the University of California in 1999, the number of research projects on smoked cannabis has increased. Several clinical studies have been published on neuropathic pain and experimentally induced pain. In general the results show a modest analgesic effect of smoked cannabis over placebo.6,7,8
It is important to note that most of the subjects in these studies were cannabis experienced, so the results may not be able to be extrapolated to cannabis naïve patients. Moreover, because the subjects were cannabis-experienced, it is likely that blinding was compromised and hence the findings should be interpreted with this in mind.
In 1999, the US Institute of Medicine (IOM) undertook an analysis of all the available evidence on the clinical utility of cannabis in its various forms. In its recommendations it made clear that,
The goal of clinical trials of smoked cannabis would not be to develop cannabis as a licensed drug, but rather to serve as a first step towards the possible development of non-smoked rapid-onset cannabinoid delivery systems.9
Similarly, the FDA has stated,
No sound scientific studies supported the medical use of marijuana for treatment in the United States and no animal or human data supported the safety or efficacy of marijuana for general medical use. There are alternative FDA-approved medications in existence for treatment of many of the proposed uses of smoked marijuana.10

Why did the FDA come to this conclusion?
Their position is grounded in an approach to the development of medicines that must take into consideration a range of factors. To be accepted as a medicine, the following criteria must be met,

    The drug’s chemistry must be known and reproducible
    There must be adequate safety studies
    There must be adequate and well-controlled studies proving efficacy
    The drug must be accepted by qualified experts
    The scientific evidence must be widely available 11

Smoked marijuana does not meet these criteria and hence the FDA has not approved its use as a medicine.
Of additional concern is the fact that the herbal product is produced with little or no quality assurance and may therefore be contaminated by microbes, other pathogens, heavy metals and pesticides. This would not be tolerated for other medicines over which the FDA has regulatory control.
It is not surprising that other peak organisations like the American Medical Association, the American College of Physicians, the American Nurses Association, the American Cancer Society, the American Glaucoma Foundation, the National Multiple Sclerosis Society, the American Academy of Pediatrics and the American Society of Addiction Medicine all support the FDA approval process and have expressed either opposition to or concern over the use of smoked marijuana as a therapeutic product.12
It is important that peak bodies like the FDA in the US and the Therapeutic Goods Administration (TGA) in Australia are able to maintain their position as the gatekeepers of the regulatory process by which new medicines become available to the public. They are undermined when, by alternate regulatory means, medicines are made available. This is the case in the US where States have enacted legislation that makes smoked marijuana available for medical purposes without FDA approval.
A dangerous precedent is set by approval processes that are effectively achieved by popular vote of citizens who are not expert judges of medical efficacy, side-effects, abuse potential, or ethics of the doctor-patient relationship. Popular vote is also risky because the public is then at the mercy of pressure from groups who are using medical marijuana as a beachhead for generalised legal access to marijuana.
Medical Marijuana in the US and elsewhere
Smoked marijuana for medical purposes is now legal in 18 US States. The first was California in 1996 when the citizen referendum Proposition 215 was passed by a majority of 56% to 44%. Most of the medical marijuana in the US is grown and utilized in California and Colorado.
In California it is estimated that there are between 250,000 and 300,000 people who have physician approval for their use of marijuana.13 This number is so large that it clearly serves those who are not only within the category of the seriously ill and dying, which were the grounds upon which many campaigns were argued. In Colorado, which has twice as many medical marijuana users per capita as California, 2% of the population is registered.14 This yields approximately 100,000 people.
Whilst there is limited data, some aspects of the demographic profile of medical marijuana registrants appears to be similar in the different States. The average age of registrants in Colorado is 40 years of age and 69% are male.15 Even so, there are 40 under the age of 18. In a UK study, users were predominantly young, male and recreationally familiar with cannabis.16 A Californian study revealed users to be approximately 75% male, 60% white, and mostly from a background of recreational use.17 In a separate study, 89% had started using before the age of 19, and 90% were daily smokers.18 In another recent Californian study, it was found that applicants to the medical marijuana program self-reported their use of marijuana for pain relief (82.6%), improved sleep (70.6%), relaxation (55.6%), muscle spasms (41.3%), headache (40.8%), relief of anxiety (38.1%), improved appetite (38.0%), relief of nausea and vomiting (27.7%), and relief of depression (26.1%).19
These observations are consistent with the specified conditions for which marijuana can be used in California, along with those covered by the catchall phrase, ‘or any other illness for which marijuana provides relief’. The conditions vary in each of the States, but by and large, the breadth of conditions for which marijuana can be used is relatively expansive.
In Nevada, the majority of marijuana is used for generalised conditions; for example, 53% for severe pain, 29% for muscle spasms, and 11% for severe nausea.20 There is no straightforward way to assess each of these conditions objectively. The remaining 7% are for glaucoma, HIV+/AIDS, cancer and cachexia (wasting).
The demographic data and usage data reveal that most registrants have come from a background of recreational use and are smoking marijuana for conditions which cannot be easily objectively verified. This is not to necessarily argue that registrants do not have medical conditions which they believe may be treated by marijuana, but simply to note that this mode of drug delivery and means of treatment are not subject to the usual controls put in place for ensuring the good of the patient. There is also no straightforward way to assess whether someone might simply be seeking marijuana for ‘recreational’ use under the guise of medical treatment, and thereby exposing themselves to a litany of avoidable harms.
In most of the States, marijuana can be grown by registrants or by a caregiver, and often the amounts involved allow for considerable excess beyond use for medical reasons. For example, in Oregon, registrants can possess 6 mature plants and 24 ounces of usable cannabis. Morgan has calculated that 24 ounces of cannabis can be rolled into 1896 joints.21
Despite the fact that most States permit users to grow their own marijuana, but do not permit dispensaries, they are nevertheless proliferating. In the city of Denver in Colorado, there are “more dispensaries than public schools, liquor stores, or even Starbucks coffee shops”.22 The incentive for owners is considerable. Average monthly cost for consumers has been estimated to be between $562 and $2250. Moreover, as there is no FDA approval, no insurer will contribute.23
In Colorado, dispensaries advertise a variety of products and offer free samples.24 In Nevada tourists are greeted with large billboards advertising medical marijuana.25 This is an industry that is growing and operates in a fashion unlike other providers of medical products.
A particular problem arises in contexts where cannabis can be legally provided by a cooperative, which must source their product from the black market, as in California. The result of this is stimulation of the illegal production of cannabis. In their submission to the NSW inquiry into medical marijuana, Hall & Farrell comment:
The effect of these forms of liberalization has been to create a quasi-legal system of cannabis production and distribution in many parts of California and some of this cannabis is sold to recreational users.26
There seems little doubt that marijuana is being diverted from medical programs for ‘recreational’ purposes. The Las Vegas Metropolitan Police Department recorded an enormous 1200 percent increase in grow site seizures between 2006 and 2010.27
In Colorado, 48.8 percent of adolescents admitted to substance abuse treatment obtained their marijuana from someone registered to use medically.28 The authors conclude:
Diversion of medical marijuana is common among adolescents in substance treatment. These data support a relationship between medical marijuana exposure and marijuana availability, social norms, frequency of use, substance-related problems and general problems among teens in substance treatment.
In a recent study by Cerda and co-workers, it was found that states with medical marijuana laws had higher rates of use, abuse and dependence.29 The authors are careful not to assume a causal link, and acknowledge that there are several possible mechanisms by which medical marijuana laws could lead to increased abuse. Harper and coworkers suggest that there is unlikely to be a causal link.30
In a retrospective case study series of marijuana exposure in children under 5 years of age presenting to emergency hospital departments in Colorado, it was found that children had been exposed over a 6 month period. Importantly, 4 of the 5 children came from home environments where medical marijuana cards were present.31
One of the complications of States enacting laws such as these is that cannabis remains a schedule 1 drug and hence possession and use is a federal offence. The laws therefore represent a strange and messy juxtaposition between State and Federal legislation. This is not only a difficult and inconsistent regulatory environment but also one in which there is potential for laws to come into disrepute. This is especially the case since the Obama administration issued a statement in 2009 indicating it would give low priority to the prosecution of individuals in those states with medical marijuana laws.32 Thus a deterrent for dispensaries to provide a federally prohibited substance was removed.

What is the impact on the medical profession?
It has long been recognised that the relationship between patient and physician is a unique one. It is unlike the relationship between consumer and service provider in many other professions, largely because of the vulnerability of the patient, but also because the physician is entrusted with direct engagement with diagnosis and treatment that deals closely with the person’s body and its integrity. It has an intimacy that calls forth particular ethical reflection and guidance.
Codes of ethics have been developed to govern the relationship, the oldest being the Hippocratic Oath. Even older is the basic requirement primum non nocere, ‘do no harm’. More recently, the Declaration of Geneva states, “The health of my patient will be my first consideration.” All of these are designed to protect the patient and ensure that care is directed towards their well-being, recovery, and ultimately, flourishing. Hence, physicians have a duty of care and a fiduciary responsibility to their patients. They should also be aware of potential conflicts of interest.
In the modern context, the standard of care typically requires the physician to perform an examination, and if necessary implement appropriate diagnostic tests, take a patient’s history to check for possible contraindications, check for the failure of other treatments, communicate with the person’s other health professionals, and assess response to treatment and monitor adverse effects.
Medical marijuana programs generally fail in some or all of these normal requirements, compromising the doctor-patient relationship and potentially putting the patient at risk. Doctors are placed in a difficult position when asked to provide a substance that is federally controlled, is of unknown purity, potentially contaminated, and about which there is limited evidence on indications, contraindications, adverse effects and dosage.
It is not surprising that many physicians are unwilling to recommend marijuana to their patients. In Colorado, for example, 10% of recommendations were made by one physician and 49% by just 15.33 Some doctors may also be concerned about their legal liability if harm were to come to a patient. In one case, a physician recommended
marijuana to a 20 year old pregnant woman without examining her or documenting her pregnancy. The child was born and tested positive for marijuana.34
In some contexts there are clearly conflicts of interest. Some physicians are employees of dispensaries and therefore have personal interest in recommending cannabis.35
In a recent letter to the American Journal of Psychiatry, a medical practitioner described a case where a young man with a history of psychiatric problems was recommended medical marijuana. His problems were exacerbated, eventually resulting in hospitalization for psychosis. He eventually withdrew from marijuana and recovered.36 This case highlights not only the risk of psychosis with marijuana, but also the failure of a duty of care by a recommending physician.

Who is driving medical marijuana initiatives?
The impetus behind legislative changes for medical marijuana comes from several different sources.
Those who have been using marijuana in the belief that it is treating their medical condition are often strong advocates for legal change. As we have seen, there is therapeutic potential in cannabis, so there is some rationale behind pressure from those who find relief for their symptoms. However, not only is anecdotal evidence alone an unreliable path to new medicines, but the complications with ‘recreational’ use make it very difficult to sift out a real benefit from a sense of ‘feeling better’.
There are also individual health practitioners who may believe that some of their patients could benefit from medical marijuana, and hence they may advocate for legislative change.
However, by far the most active players are those who would like to see marijuana legally available for ‘recreational’ purposes. Some of these groups as well as individuals have been pressing for change for decades and with medical marijuana, they see the opportunity for a beachhead. The rationale is based upon the idea that the image of marijuana will be considerably softened by its use as a medicine. They would also likely be aware that medical marijuana constitutes such a regulatory mess that as more people use medical marijuana, policing of ‘recreational’ use becomes more difficult. To some in authority it may appear simpler to accede to pressure for full legalization.
Groups like the National Organisation for the Reform of Marijuana Laws (NORML) have been agitating for medical marijuana for a long time, as has the Drug Policy Alliance. However, particular individuals have also put in considerable funds. These include billionaire financier George Soros and insurance magnate Peter Lewis. It is estimated that Lewis alone has spent between $40 and $60 million on medical marijuana initiatives since the early 80s.37

Soros-watcher Rachel Ehrenfeld has described the Soros strategy as set forth to pro-legalisation group Drug Policy Foundation in the early nineties:
… in 1993 Soros gave DPF a “set of suggestions to follow if they wanted his assistance: Come up with an approach that emphasizes `treatment and humanitarian endeavors,’ he said … target a few winnable issues, like medical marijuana and the repeal of mandatory minimums.” Apparently, they took his advice.38

Conclusion
Medical marijuana is an example of a complex blurring of the lines between use and abuse, between potential medical utility and ‘recreational’ use. Concern about the use of smoked marijuana being made publically available has been vindicated by the spread of medical marijuana legislation throughout the US and the proliferation of dispensaries providing marijuana for dubious purposes including ‘recreational’ use.
The situation has made it difficult for policing and compromised the medical profession. It undermines the FDA process of approval of medicines and complicates State-Federal relations. By doing so it has the potential to bring the regulatory process as well as the law itself into disrepute.
The active ingredients in cannabis are showing promise for therapeutic use and may prove to be useful for the treatment of various ailments. Ironically, permission to smoke marijuana for medical purposes may delay the development of cannabinoid medicines by ‘muddying the waters’ and drawing valuable resources away from genuine research.
Colorado psychiatrist Christian Thurstone puts it well:
In the absence of credible data, this debate is being dominated by bad science and misinformation from people interested in using medical marijuana as a step to legalization for recreational use. Bypassing the FDA’s well-established approval process has created a mess that especially affects children and adolescents. Young people, who are clearly being targeted with medical marijuana advertising and diversion, are most vulnerable to developing marijuana addiction and suffering from its lasting effects.”39
When reflected upon years from now, how will medical marijuana be viewed?
With the advent of treatments designed to work with the body’s own cannabinoid system, the medical use of marijuana should fade as a topic of heated debate to a footnote in the history of medicine.40

1 Pike, GK, The Debate on Drug Law Reform, paper delivered at the Catholic Bioethics Colloquium, Melbourne, January 2013.
2 NSW Government Health Department fact sheet on Cannabis, May 2011.
3 Kraft B et al., Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology 109(1):101-10, 2008
4 Abrams DI et al., Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Annals of Internal Medicine 139(4): 258-266, 2003
5 Haney M et al., Dronabinol and Marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. Psychopharmacology(Berl) 181(1): 170-178, 2005
6 Abrams DI et al., Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 68(7): 515-521, 2007
7 Ellis RJ et al., Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 34(3):672-680, 2009
8 Wilsey B et al., A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. Journal of Neurology 253(10): 1337-1341, 2006
9 Joy JE et al., Marijuana and Medicine: Assessing the Science Base. Division of Neuroscience and Behavioral Health. Institute of Medicine. Washington DC, National Academy Press, 1999,
10 See DOJ, DEA, “Lyle E. Craker; Denial of Application,” 74 Fed. Reg. 2101, 2104 (Jan. 14, 2009).
11 Barthwell AG, Early findings in Controlled Studies of Herbal Cannabis: A Review. The Journal of Global Drug Policy and Practice, June 24, 2010
12 Barthwell, Op. Cit. See also http://nrfocus.org/latest_topics/is-marijuana-medicine/
13 Bostwick JM, Blurred Boundaries: The Therapeutics and Politics of Medical marijuana. Mayo Clinic Proceedings 87(2): 172-186, 2012
14 Nussbaum AM & Thurstone C, Mile High Macaroons: The Medicalization of Marijuana in Colorado. The Journal of Global Drug Policy and Practice 5: 5-15, 2011
15 Medical Marijuana registry program update [Internet]. Denver CO: Colorado Department of Public Health and environment, c2011 Mar 31
See www.cdphe.state.co.us/hs/medicalmarijuana/statistics.html
16 Ware MS et al., The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract. 59(3): 291-295, 2005
17 Reinarman C et al., Who are medical marijuana patients? Population characteristics from nine California assessment clinics. J Psychoactive Drugs 43(2): 128-135, 2011
18 O’Connell TJ & Bou-Matar CB, Long term marijuana users seeking medical cannabis in California (2001-2007): demographics, social characteristics, patterns of cannabis and other drug use of 4117 applicants. Harm Reduction Journal 4:16, 2007
19 Nunberg H et al., An Analysis of Applicants Presenting to a Medical Marijuana Specialty Practice in California. Journal of Drug Policy Analysis 4(1): Article 1, 2011
20 Raybuck T, Medical Marijuana, Nevada’s Big Gamble. The Journal of Global Drug Policy and Practice 5(2), 2011
21 Morgan S, The Impact of Oregon’s Marijuana Program, The Journal of Global Drug Policy and Practice
22 Nussbaum & Thurstone, Op. Cit., 2011
23 Barthwell, AG, Marijuana Dispensaries and the Federal Government: Recommendations to the Obama Administration 2009: Part 1, The Journal of Global Drug Policy and Practice
24 Nussbaum & Thurstone, Op. Cit., 2011
25 Raybuck, Op. Cit., 2011
26 Hall W & Farrell M, Submission No 46 to the New South Wales Inquiry into use of cannabis for medical purposes, 13 Feb 2013
27 Raybuck, Op. Cit., 2011
28 Thurstone C, Lieberman SA & Schmiege SJ, Medical marijuana diversion and associated problems in adolescent substance treatment. Drug Alcohol Dependence 118(2-3):489-492, 2011
29 Cerda M et al., Medical marijuana laws in 50 states: investigating the relationship between state legalization of medical marijuana and marijuana use, abuse and dependence, Drug Alcohol Depend. 120(1-3): 22-27, 2012
30 Harper S et al., Do medical marijuana laws increase marijuana use? Replication study and extension, Ann Epidemiol 22: 207-212, 2012
31 Wang GS et al., A case series of marijuana exposures in pediatric patients less than 5 years of age, Child Abuse & Neglect: The International Journal 35(7): 563-565, 2011
32 Johnston D & Lewise NA, Obama administration to stop raids on medical marijuana dispensers. The New York Times Mar 19 2009
See http://www.nytimes.com/2009/03/19/us/19holder.html?_r=0
33 Nussbaum & Thurstone, Op. Cit., 2011
34 Nussbaum AM et al., “But my Doctor Recommended Pot”: Medical Marijuana and the Patient-Physician Relationship, J Gen Intern Med 26(11): 1364-7, 2011
35 Nussbaum AM et al., Op. Cit., 2011
36 Pierre JM, Psychosis associated with medical marijuana: risk vs. benefits of medicinal cannabis use. Am J Psychiatry 167(5): 598-9, 2010
37 O’Connor C, High Roller: How Billionaire Peter Lewis Is Bankrolling Marijuana Legalization, Forbes Magazine, April 2012 See http://www.forbes.com/sites/clareoconnor/2012/04/20/high-roller-how-billionaire-peter-lewis-is-bankrolling-marijuana-legalization/
38 Rachel Ehrenfeld, May 1996, The Movement to Legalize Drugs in the United States: Who’s Behind It? Downloaded from the Capital Research website (www.capitalresearch.com).
39 http://nrfocus.org/latest_topics/is-marijuana-medicine/
40 Mack A & Joy J, Marijuana as Medicine? The science beyond the controversy. 2001

Filed under: Medicine and Marijuana :

I. INTRODUCTION

Recently, the federal government has expanded its enforcement actions against commercialized “medical marijuana” operations. In the wake of those enforcement efforts, the governors of Washington, Rhode Island, and Colorado have petitioned the Drug Enforcement Administration (DEA) to reschedule marijuana.

Specifically, the petition asks the DEA to reclassify marijuana from Schedule I to Schedule II under the Federal Controlled Substances Act (CSA).

The governors contend that such rescheduling will eliminate the conflict between state and federal law and enable states to establish a “regulated and safe system to supply legitimate patients who may need medical cannabis.”

The current petition takes a unique approach. It seeks to move marijuana and also all tetrahydrocannabinols, including delta-9-THC— the primary psychoactive component of marijuana—to Schedule II “for medicinal purposes only.”

In other words, the petition requests that “marijuana and related items [be] removed from Schedule I and rescheduled as ‘medical cannabis in Schedule II.’”

Marijuana advocacy organizations, such as the Marijuana Policy Project (MPP) and Americans for Safe Access (ASA) are urging other governors around the country to join onto the petition. The petition has garnered considerable publicity, but, as MPP acknowledges, “rescheduling is not a cure-all.”

This is an understatement. Indeed, for the reasons described below, it is not even a significant step in the direction that the governors, MPP, and ASA hope to move .This Article begins with a brief background of the Controlled Substances Act and then discusses the process of rescheduling, the meaning of Schedule II drugs (which is the classification called for by the governors), the legal definition of a drug with “medical use,” and Schedule II implications on both research and state and federa lregulations. The conclusion states that despite the vociferous calls for a federal marijuana reclassification, such a move would still not allow marijuana to be legally prescribed and distributed as a drug with medical use and that it is unnecessary for the legitimate claim of the need for more research into the drug. Instead, calling for rescheduling is a misguided effort that will only serve to increase the stridency of the political rhetoric in this debate. The proposal ignores the fact that the current provisions of the CSA and the Food, Drug, and Cosmetic Act(FDCA) together already restrict the availability of controlled substances products to such medical purposes. Moreover, the petition offers no alternate means or criteria for identifying such legitimate medical use.

II BACKGROUND

A. The Controlled Substances Act

Congress enacted the Controlled Substances Act in 1970 as part of the Comprehensive Drug Abuse Prevention and Control Act of 1970,replacing the previous patchwork of federal legislation governing psychoactive and potentially addictive substances.

Congress acted for a dual purpose: (1) to control and regulate the licit and illicit trade in, and use of, such substances; and (2) to implement the U.S. obligations under the Single Convention on Narcotic Drugs 1961, and subsequently, the Convention on Psychotropic Drugs 1971. As a signatory to these treaties, the U.S. is required by federal legislation to establish a range of requirements and prohibitions seeking to ensure that all psychoactive substances are used solely for legitimate medical and scientific purposes.

Therefore, the CSA already requires that controlled substances be used only for such purposes. As discussed more fully below, the CSA and FDCA contain coordinated provisions designed to ensure that properly manufactured, tested, and standardized medications are made available by qualified and licensed practitioners to patients.

The CSA governs all aspects of the handling of covered substances (“controlled substances”), including import/export, manufacturing, distribution, dispensing, individual possession, and research. The CSA divides such substances into five categories or “schedules,” depending on a substance’s usefulness as a modern medication on the one hand, and its potential for abuse/addiction on the other.

The CSA also requires that each person or entity who handles a controlled substance (until it reaches the ultimate consumer) be licensed or registered with the DEA, and each registrant must adhere to specific measures designed to ensure that controlled substances are manufactured, distributed, and dispensed only(1) for legitimate medical or scientific purposes, and (2) to patients legitimately in need of the substance.

B. How Are Drugs Rescheduled?

A substance may be rescheduled in several ways. First, an “interested party” may initiate an administrative action by filing a petition with the DEA, as did the governors of Washington and Rhode Island. Second, the DEA itself can initiate such an action.

Third, a product containing a controlled substance will be scheduled as part of the

Food and Drug Administration (FDA) approval process. Finally, Congress may reschedule or schedule a substance by legislation, although this has very rarely occurred in the past.

The scheduling process examines eight factors:

* (1)The drug’s actual or relative potential for abuse;

* (2) Scientific evidence of its pharmacological effect, if known;

* (3) The state of current scientific knowledge regarding the drug or other substance;

* (4) Its history and current pattern of abuse;

* (5) The scope, duration, and significance of abuse;

* (6) What, if any, risk there is to public health;

* (7) Its psychic or physiological dependence liability; and

* (8) Whether the substance is an immediate precursor of a substance already controlled under [the CSA].

Both the FDA and DEA analyze these factors, although the FDA’s recommendations on any scientific and medical issues are binding on the DEA. When enacting the CSA in 1970, Congress placed marijuana in Schedule I, along with other psychoactive substances of botanical origin ,such as psilocybin, ibogaine, mescaline, and peyote.

Substances in Schedule I have:

* “a high potential for abuse[;]”

* (2) no “currently accepted medical use” in the U.S.; and

* (3) lack “accepted safety for use .. . under medical supervision.”

Schedule I substances may only be used in research studies that are supervised by the FDA and licensed by the DEA. By contrast, Schedule II substances have:

* “a high potential for abuse” (as with Schedule I);

* (2) “a currently accepted medical use” in the U.S. or “a currently accepted medical use with severe restrictions[;]” and

* (3) abuse “may lead to severe psychological or physical dependence.”

Schedule II substances may be prescribed by physicians and dispensed by pharmacists

only when incorporated into specific FDA-approved products. Interpreting this statutory language as meaning “Schedule II substances may be prescribed,” however, is dangerously incomplete and may result in significant confusion. Such confusion underlies the governors’ current petition.

C. Schedule II Substances Are Not Directly Prescribed

Part of the confusion over the actual significance of Schedule II status stems from a misunderstanding of the interrelated, but distinct, functions of the CSA and the FDCA. The CSA and FDCA work together to ensure that medications meet exacting standards of quality, safety, and efficacy and that, when these medications contain controlled substances, they are handled in a manner that will ensure access to legitimate patients while minimizing abuse and diversion.

The CSA classifies substances into categories or schedules, generally by the International Non-proprietary Name (INN) or generic name of the active chemical ingredient (Active Pharmaceutical Ingredient or API). Each substance has a separate drug code. Generally, all such medical products, when approved for marketing by the FDA and scheduled by the DEA, are placed in the same schedule as the substance they contain.

By contrast, under the FDCA, the FDA approves specific medical products

produced by a particular “innovator” (for branded products) or generic manufacturers.

For example, oxycodone, an opioid, is classified as a Schedule II substance.

Specific products, such as OxyContin® (an extended release form), are also in Schedule II. Physicians prescribe a specific branded or generic product, in a particular dose and dosage form. In some cases, a more complex or “differential” scheduling occurs. That is, the pure or even “street” version of an API may be scheduled separately from a substance comprised of an FDA-approved formulation containing that active ingredient.

For example, gamma hydroxybutyricacid or sodium oxybate (“GHB”), the “date rape” drug, is a Schedule I substance. However, a separate substance or drug code has been created for all GHB-containing formulations that have passed through the FDA approval process. This separate substance is in Schedule III, as is any product containing it, such as Xyrem® . Similarly, tetrahydrocannabinols are in Schedule I, but a separate substance comprising an FDA-approved formulation of synthetic THC (called dronabinol) is in Schedule III. Specific products containing that substance are Marinol® and its generics.

The DEA has recently proposed to create a separate category or drug code (and hence, substance) for “marihuana extract,” although at present this substance remains in Schedule I. In short, the fact that a substance is in Schedule II (or even III-V)does not mean that the substance itself (as contrasted with specific branded or generic products containing it) can be directly prescribed and dispensed. This is particularly true for botanical raw plant material, for several reasons. First, botanical raw material can vary significantly in its composition. For example, depending on the strain, the opium poppy can produce differing amounts of morphine, codeine, thebaine, or oripavine.

A prescription designating “opium” or even “concentrate of poppy straw”

would not indicate the precise formulation of active ingredients (and, therefore, the dose) that the physician intends the patient to use in treatment.

Second, raw plant material can be contaminated by fungi and other dangerous microbes, depending on the cultivation, harvesting and storage practices employed (including storage by a wholesaler or retailer). These and other contaminants can be more reliably identified and removed during various processes of manufacturing, extraction, and formulation. Third, there is currently no method of administering raw plant material, which ensures that the patient receives a reproducible dose of active ingredients each time, in a manner that does not create any toxic by products. Indeed, no raw plant material has ever been approved by the FDA for sale by prescription, although a number of psychoactive plant and other botanical raw materials are listed in Schedule II of the CSA.

The governors’ petition contends that, “with modern DNA analysis” using polymerase chain reaction (PCR) and gel electrophoresis testing among other validated analytical

techniques, a “compounding pharmacist could easily and inexpensively quantify the levels of cannabinoids.”

Indeed, it avers that “accurate analytical kits are available” to enable “extremely accurate characterization[s] of a plant’s genetic make-up.”

However, the petition provides no evidence (nor even any citations) that such technology exists and that the results of such testing would provide proof of quality and batch-to-batch consistency that would meet the standards of modern medicine and be satisfactory to the FDA.

A recent documentary on the Discovery Channel examined the practices of Harborside Health Center in Oakland, California—by its own admission, the largest marijuana dispensary on the planet—revealed that the buds(which are distributed directly to member-patients) are merely examined visually using a microscope. The documentary noted that Steep Hill Laboratory tests some plant material, but there was no evidence that Steep Hill’s instrumentation and techniques are “validated,” that its operators are properly trained and educated, that its reference standards are accurate, or that its results are replicable by other laboratories. The FDA has established extremely high standards in the area of Chemistry, Manufacturing, and Controls (CMC) to ensure that a medication is consistent in composition, stable over a reasonable period of time, and not contaminated with excessive impurities.

Recently, a company seeking to develop a generic to Marinol® was forced to abandon one of its product development programs because of CMC issues. In light of the challenges faced even by pure synthetic cannabinoids products, it is unlikely that an individual testing raw botanical material would be able to demonstrate this exacting level of consistency. Furthermore, herbal plant materials would likely be administered through smoking or vaporization. The FDA has also established extremely rigorous CMC criteria for inhaled products. Metered dose inhalers must meet demanding standards in order to ensure that they maintain “consistent dosing and particle size distribution. ..throughout the expiration dating period.”

Notably, virtually all inhaled products have been approved only for pulmonary conditions, such as asthma. Vaporized products for non-pulmonary conditions have faced considerable concern from FDA.

It is therefore not surprising that crude botanical opiate or other materials are not prescribed and dispensed .Marketed medications containing pure opiate APIs (morphine, codeine, etc.) were available at the time the CSA was enacted. Therefore, the crude raw botanical materials from whence they were derived—opium (latex), poppy straw, and concentrate of poppy straw— were placed in Schedule II along with those APIs.9

However, their Schedule II status does not allow physicians to prescribe dried opium or poppy straw, or even the pure APIs derived from them, but rather only specific products containing those APIs.

The same would apply to marijuana, even if the plant material were reclassified to Schedule II, along with poppy straw. Imagine for a moment that the “medical marijuana” advocates were instead “medical opium” advocates and that various states passed laws decriminalizing (or affirmatively authorizing and regulating) the cultivation and distribution of opium plant material, i.e., opium latex or poppy straw. Even though opium latex and poppy straw are each in Schedule II, there would still be a conflict between such state laws and both the CSA and the FDCA. As a well-known drug reform advocacy website states, “if poppies are grown as sources for opiates, there is no question that it violates the CSA.” Furthermore, physicians would not be authorized to prescribe, nor pharmacists to dispense, dried opium latex or poppy straw. In order to be prescribed, a specific product containing opiate APIs would have to pass muster in the FDA approval process. Therefore, the mere act of placing herbal marijuana in Schedule II would not make it available to patients nor address the conflict between state and federal law.

D. Pharmacist Compounding

The petition appears to rely heavily on the premise that, if marijuana were moved to Schedule II, pharmacists could blend and dispense raw marijuana plant material upon the prescription of a physician. However, under the FDCA, a pharmacist’s compounding authority is quite limited. The FDA generally permits “traditional” compounding, which involves the preparation of a medication that is tailored to the specific needs of a particular patient, based on an unsolicited physician’s prescription.

It does not include wide scale manufacturing of products by pharmacists; this runs afoul of the FDCA: The drugs that pharmacists compound are not FDA-approved and lack an FDA finding of safety and efficacy. However, FDA has long recognized the important public health function served by traditional pharmacy compounding. FDA regards traditional compounding as the extemporaneous combining, mixing, or altering of ingredients by a pharmacist in response to a physician’s prescription to create a medication tailored to the specialized needs of an individual patient.

Traditional compounding typically is used to prepare medications that are not available commercially, such as a drug for a patient who is allergic to an ingredient in a mass-produced product, or diluted dosages for children. Through the exercise of enforcement discretion, FDA historically has not taken enforcement actions against pharmacies engaged in traditional pharmacy compounding .Rather, FDA has directed its enforcement resources against establishments whose activities raise the kinds of concerns normally associated with a drug manufacturer and whose compounding practices result in significant violations of the new drug, adulteration, or misbranding provisions of the FDCA.

Therefore, it is unlikely that rescheduling would enable pharmacists to prepare marijuana-based products for a significant number of patients. Moreover, pharmacists are only authorized to dispense a controlled substance to a patient based on a legitimate prescription from a physician. Under the CSA, a prescription must contain the drug name, strength, dosage form, quantity prescribed, and directions for use.

Again, there is no evidence that a pharmacist could “easily” prepare a blend of cannabis plant material that would meet these requirements and the standards of FDA-approved modern medications. Presumably, the governors’ petition is referring to the testing technologies currently employed by the panoply of marijuana “testing laboratories” that provide services to some dispensaries. However, in a recent article authored by the Director of the California branch of the National Organization for the Reform of Marijuana Laws (NORML), approximately one third of laboratories examined demonstrated “unacceptable deviations of more than 25% from the mean.”

The remaining laboratories were consistent only to within approximately 20%.

This might meet the standards for testing the potency of seized cannabis (which serve law enforcement and policy development purposes), but it would certainly not meet the standards of pharmaceutical testing for prescription medications administered to patients. Furthermore, other evidence from around the country suggests that laboratory results are even less reliable.

E. Accepted Medical Use

The primary difference between Schedule I and II substances lies in the phrase “currently accepted medical use in treatment in the United States.” This phrase is not defined in the CSA. However, the DEA has developed a five-part test for determining which substances are classified as Schedule II that has been upheld by federal courts:

* The drug’s chemistry must be known and reproducible;(2) There must be adequate safety studies;

* (3) There must be adequate and well-controlled studies proving efficacy;

* (4) The drug must be accepted by qualified experts; and

* (5) The scientific evidence must be widely available.

Mere anecdotal evidence (reports of specific cases), state laws, or even the policy positions of medical organizations, are not sufficient to satisfy these criteria, but rather only data from robust, controlled studies are sufficient to satisfy them.

Not surprisingly, FDA approval of a 1 product is sufficient (although not necessary) to establish that such product has an accepted medical use in the U.S. The governors’ petition asserts that there is a “consensus of medical opinion concerning medical acceptability of cannabis amongst the largest groups of physicians in the United States.”

In support of this statement, the petition states that the American Medical Association (AMA)allegedly reversed its position that marijuana should remain a Schedule I substance.

However, contrary to the governors’ petition, the AMA does not believe that there has been sufficient research to justify making herbal marijuana available as a prescription medication: “Despite more than 30 years of clinical research, only a small number of randomized ,controlled trials have been conducted on smoked cannabis.”

Furthermore, while the AMA’s Report does state that the Schedule I status should be “reviewed,” it limits the purpose of such review to the “goal of facilitating the conduct of clinical research and development of cannabinoid-based medicines, and alternate delivery methods.” The AMA does not recommend that marijuana should be rescheduled in order that it can be directly prescribed and dispensed in its raw form to patients. In fact, the AMA recommendation cautions that, “this should not be viewed as an endorsement of state-based medical cannabis programs, the legalization of marijuana,

or that scientific evidence on the therapeutic use of cannabis meets the current standards for a prescription drug product .”

In the body of its report, the AMA further clarified its position by stating: The AMA supports the concept of drug approval by scientific and regulatory review to establish safety and efficacy, combined with appropriate standards for identity, strength, quality, purity, packaging, and labelling, rather than by ballot initiative or state legislative action.

The future of cannabinoid-based medicine lies in the rapidly evolving field of botanical drug substance development, as well as the design of molecules that target various aspects of the endocannabinoid system. To the extent that rescheduling marijuana out of Schedule I will benefit this effort, such a move can be supported. The term “botanical drug substance” is derived from an FDA guidance document Guidance for Industry: Botanical Drug Products It refers, not to herbal plant material, but to extracts or similar preparations of the active botanical components.

As the AMA Report states:

The crude botanical substance can become a “botanical drug substance” through processes of extraction, blending, addition of excipients, formulation, and packaging in a defined manner. Particular attention is devoted to product composition because botanicals are complex mixtures of chemical/structural components. Similar to conventional products, a botanical drug substance must undergo animal toxicity studies, and demonstrate its safety and efficacy in randomized, double-blind, placebo-controlled trials. Additional pharmacologic and toxicologic studies are required if a non-oral route (e.g., inhalation) of administration is contemplated. If the substance is intended to treat chronic conditions, 6 to 12 months in long-term safety extension studies is considered sufficient.

Therefore, rather than accepting that marijuana meets the accepted standards for modern medicine, the AMA is essentially stating that research into crude marijuana plant material is a dead end.

ANALYSIS

A. Application of the FDCA and CSA to Intrastate Manufacturing/Cultivation and Distribution Under the Federal Constitution, Congress has specific enumerated powers and can only pass legislation pursuant to one of those powers. Under the Commerce Clause, Congress has the power to regulate commerce amongst the states.

The U.S. Supreme Court has expansively defined the scope of activity that involves or affects interstate commerce. With regard to the CSA, the Court has ruled that, under the Commerce Clause, the CSA is valid as applied to “the intrastate ,non-commercial cultivation and possession of cannabis for personal medical purposes” on the advice of a physician. Similarly, the FDA broadly interprets the reach of the FDCA, which applies to products in, or that are introduced or delivered for introduction into, or received in, interstate commerce. A product is a “drug,” subject to the quality, safety, and efficacy requirements of the FDCA if it is “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” or is “intended to affect the structure or any function of the body. A “new drug” cannot be introduced or delivered for introduction into interstate commerce unless approved by the FDA.

In light of the interconnectedness of many aspects of the national economy, it is highly likely that any marijuana medical product would be deemed to affect interstate commerce, particularly if the transaction has a commercial aspect.

The use of the internet or other publication method to advertise a product creates an additional connection to the channels of interstate commerce. Therefore, intrastate manufacture and distribution of marijuana products would not avoid the requirements and restrictions of the CSA and FDCA. Accordingly, a physician would not be able to prescribe, or a pharmacist to dispense, a marijuana medical product unless that product had secured FDA marketing approval

B. Rescheduling Is Not Necessary To Make Marijuana Products Available For Research

A committee of the California Medical Association recently called for the rescheduling of marijuana “so it can be tested and regulated.” However, it is not necessary for marijuana to be rescheduled in order for legitimate research to proceed. Schedule I status does not prevent a product from being tested and researched for potential medical use.

The FDA (and its Controlled Substances Staff) will allow an investigational product containing a controlled substance (including Schedule I substances) to be tested in a clinical (human) trial if there is adequate evidence of safety from non-human studies.

The CSA imposes stringent security, record keeping, and other requirements, but these apply equally to Schedule I and Schedule II substances. Under the CSA, the only differences between Schedule I and II are rather technical.

Before granting a Schedule I research registration, the DEA will separately inquire whether the FDA believes that the researcher is qualified and competent and the trial design will elicit scientifically valid data. A Schedule I research registration must be renewed each year, whereas research registrations for other controlled substances are valid for three years.

Schedule I research registrations are protocol, as well as substance, specific.

By contrast, a Schedule II registration is valid for research into all Schedule II substances and protocols. Physicians, if they possess registrations to prescribe and administer products containing controlled substances, may conduct research (if permitted by the FDA and the relevant ethics committee) on any Schedule II substance as a “coincident” or adjunct activity to that registration; they need not obtain a separate research registration from DEA.

These additional Schedule I restrictions can delay a research program but are not insurmountable. Furthermore, it may be possible to make minor amendments to the CSA to “equalize” Schedule I and Schedule II research requirements without necessitating a rescheduling of marijuana. Even in the absence of such a statutory amendment, Schedule I research certainly does go forward. In a recent pharmaceutical company-sponsored human clinical study investigating a product derived from marijuana extracts,

the DEA registered approximately thirty research sites in the U.S. and also registered an importer to bring the product into the U.S. from the U.K., where it was manufactured.

C. Obtaining Raw Plant Material for Research

Schedule II status would not make it easier for medical researchers to obtain marijuana plant material for purposes of research. The U.S.’s obligations under the Single Convention on Narcotic Drugs require that a national agency have exclusive control over the domestic cultivation of marijuana, as well as its importation and exportation.

The National Institute on Drug Abuse (NIDA) primarily implements the responsibilities outlined in the treaty. The NIDA contracts with the University of Mississippi’s National Center for Natural Products Research (NCNPR) to cultivate marijuana for research purposes.

Researchers who obtain grant funding from an institute of the National Institutes of Health (NIH), such as NIDA, can obtain marijuana for their studies, while researchers who are externally funded must undergo the equivalent of a grant review process (a review of their study design by an expert committee of the Public Health Service) in order to obtain such marijuana at cost from NIDA. NCNPR has the ability to produce

standardized marijuana of varying THC potencies. Its cultivation area of five acres has been adequate to supply all marijuana-related studies to date.

Even if marijuana were placed in Schedule II, these treaty obligations would remain in force. This does not, however, mean that it would never be possible to conduct large scale cultivation of marijuana for purposes of commercial medication development, although such cultivation would have to be closely supervised by the NIDA or the DEA, in a manner similar to NCNPR’s “farm.” Furthermore, it is also possible that cultivation would take place in another country (under the auspices of that country’s national agency), and extracts of the active ingredients would be imported into this country for research, just as concentrate of poppy straw is now imported into the U.S. for the development of modern opioid products. Under 100-year old international policies,

most countries, including the U.S., do not cultivate psychoactive plant material for purposes of commercial medication development, but rather import such narcotic raw material(NRM) from a short list of authorized manufacturing/cultivating countries.

Importantly, such extracts are exempt from the Single/Convention’s national agency mandate. As indicated above, this is precisely how marijuana extract-derived medications are currently made available for research in the U.S.

D. State Regulation of Marijuana

Would Schedule II status permit states to regulate the cultivation, sale, and distribution of marijuana for either medical or recreational use? As noted above, the CSA was enacted in part to implement the U.S.’s international obligation to restrict the use of psychoactive substances to legitimate medical and scientific purposes.

Schedule II substances are subject to very strict controls, given that almost all the security and other controls that govern Schedule I substances apply equally to Schedule II substances. Additionally, unlike Schedule I substances, Schedule II substances can be developed into commercialized products, and are therefore subject to production and procurement quotas determined by the DEA. Accordingly, a state could not attempt to establish a regulatory system that undermined or otherwise conflicted with these CSA restrictions. Again, poppy straw is a Schedule II substance, as is morphine, but a state could not create a regulatory structure that was more lenient than that established by the CSA.

E. Marijuana as a Federally-Illegal Substance

Placing marijuana in Schedule II would not eliminate its status as an illegal substance under the CSA. While the severity of many of the CSA’s criminal penalties are keyed to the schedule of the substance in question, this is not entirely true for marijuana.

There are statutes under the CSA that prescribe specific penalties for manufacturing, distributing or dispensing (or possessing with intent to do the same) of certain quantities of marijuana. Furthermore, even considering those statutes that are keyed to a substance’s schedule, the same criminal penalties apply equally to Schedule I and II substances.

Thus, none of these statutes would be directly affected by a change in marijuana’s schedule. Finally, the CSA provides that it is illegal to possess any controlled substance without a valid prescription from a physician. Again, under the FDCA, a medical product cannot be manufactured and sold (a precursor for it to be prescribed) unless the product has been approved by the FDA.

Hence, transferring crude herbal marijuana to Schedule II would have no impact on these statutes

CONCLUSION

By contrast to the careful and detailed structure of the CSA, the governors’ petition offers no criteria or guidelines that would clearly identify the scope of legitimate “medical use.” At present in California, and in several other states, it is widely recognized that the concept of “medical use” of marijuana is highly questionable. For payment of a small cash sum, almost anyone can obtain a physician’s “recommendation” to purchase, possess, and use marijuana for alleged medical purposes. Indeed, numerous studies have shown that the most customers of these dispensaries do not suffer from chronic, debilitating conditions such as HIV, AIDS, or cancer.

Parties on both sides of the argument agree that this system has essentially legalized marijuana for recreational use—at least amongst those individuals able and willing to buy a recommendation. The petition would potentially expand that system on a national scale, permitting any physician in any state to prescribe any form of marijuana for any medical condition. This has nothing to do with its Schedule, because placing marijuana in Schedule II would do nothing to change the fact that it could still not be prescribed— the FDA would first have to approve a specific product. Rather, vociferous calls for rescheduling like these simply muddle and confuse an already highly charged debate.


Source: Dr. Kevin Sabet Wayne Law Review April 1, 2012 Volume 58 No. 1

Filed under: Medicine and Marijuana :

Medical marijuana laws in 50 states: Investigating the relationship between state legalization of medical marijuana and marijuana use, abuse and dependence

Abstract
Background

Marijuana is the most frequently used illicit substance in the United States. Little is known of the role that macro-level factors, including community norms and laws related to substance use, play in determining marijuana use, abuse and dependence. We tested the relationship between state-level legalization of medical marijuana and marijuana use, abuse, and dependence.

Methods

We used the second wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a national survey of adults aged 18+ (n = 34,653). Selected analyses were replicated using the National Survey on Drug Use and Health (NSDUH), a yearly survey of ~68,000 individuals aged 12+. We measured past-year cannabis use and DSM-IV abuse/dependence.

Results

In NESARC, residents of states with medical marijuana laws had higher odds of marijuana use (OR: 1.92; 95% CI: 1.49–2.47) and marijuana abuse/dependence (OR: 1.81; 95% CI: 1.22–2.67) than residents of states without such laws. Marijuana abuse/dependence was not more prevalent among marijuana users in these states (OR: 1.03; 95% CI: 0.67–1.60), suggesting that the higher risk for marijuana abuse/dependence in these states was accounted for by higher rates of use. In NSDUH, states that legalized medical marijuana also had higher rates of marijuana use.

Conclusions

States that legalized medical marijuana had higher rates of marijuana use. Future research needs to examine whether the association is causal, or is due to an underlying common cause, such as community norms supportive of the legalization of medical marijuana and of marijuana use.

Source: Drug and Alcohol Dependence Volume 120, Issues 1–3, 1 January 2012

Filed under: Medicine and Marijuana,USA :
1. INCREASED USE AMONG ADULTS AND YOUTH
The number of teenage and adult users will double or triple if marijuana is legalized. This will mean an additional 17 to 34 million adult and young users in the United States. [FN1]
Marijuana businesses will promote their products and package them in attractive ways to increase their market share (see attached pictures of marijuana “candy”).
ASK YOURSELF: Do you think increased marijuana use among teenagers and adults is good for our country and its future?
2. NEGATIVE IMPACT ON YOUTH
Marijuana can cause disinterest in activities, lower grades and isolation from the family. It can permanently impair brain development. Problem solving, concentration, motivation and memory are negatively affected. Teens who use marijuana are more likely to engage in delinquent and dangerous behavior and experience increased risk of schizophrenia and depression including being three times more likely to have suicidal thoughts. [FN2]
Marijuana-using teens are more likely to have multiple sexual partners and engage in unsafe sex. [FN3]
Our drug treatment facilities are full of young people dealing with marijuana related problems. One study of children in treatment showed that, 48% were admitted for abuse or addiction to marijuana, while only 19.3 % for alcohol and 2.9 % for cocaine, 2.4 % for methamphetamine and 2.3 % for heroin. [FN4]
Marijuana use accounts for tens of thousands of marijuana related complaints at emergency rooms throughout the United States each year. Over 99,000 are young people. [FN5]
Despite arguments by the drug culture to the contrary, marijuana is addictive. [FN6] The levels of THC (marijuana’s psychoactive ingredient) have never been higher. Higher potency marijuana is a major factor why marijuana is the number one drug causing young people to enter treatment and why there has been a substantial increase in the number of Americans in treatment for marijuana dependence. [FN7]
ASK YOURSELF: Would you want your son or daughter to become involved in using marijuana?
3. IMPAIRED AND DANGEROUS DRIVING
Marijuana significantly impairs the ability to safely operate a motor vehicle. Driving problems include: decreased handling performance, inability to maintain headway, impaired time and distance estimation, increased reaction times, sleepiness, impaired sustained vigilance and lack of motor coordination. [FN8]
Marijuana is the most prevalent drug found in fatally injured drivers testing positive for drugs. [FN9]
More than 12 % of high school seniors admitted to driving under the influence of marijuana in the two weeks prior being surveyed. [FN10]
13 % of high school seniors said they drove after using marijuana while only 10 % drove after having five or more drinks. Vehicle accidents are the leading cause of death among those aged 15 to 20. [FN11]
A study of high school students showed that about 28,000 seniors each year admitted that they were in at least one accident after using marijuana. [FN12]
ASK YOURSELF: Do you want more impaired drivers on our interstates and roadways?
4. INCREASED-RISK EMPLOYEES
Employees who tested positive for marijuana had 55% more industrial accidents and 85% more injuries compared to those that tested negative on a pre-employment exam and they had absenteeism rates 75% higher than those that tested negative. [FN13]
Marijuana use can cause impairment of short-term memory, attention, motor skills, reaction time, and the organization and integration of complex information. Marijuana use can cause decreased motivation and can cause mental health problems. Employees who use marijuana off-duty are still effected by it at work for the next few days. Impaired cognition can remain for a long period. Memory defects can last as long as six weeks. [FN14]
Employers may be liable for the actions of employees who use marijuana especially those employees in safety sensitive positions.
ASK YOURSELF: If you were an employer, would you want to hire an employee who uses marijuana?
5. MARIJUANA USE AND TRAUMA
A study of all patients admitted to a shock-trauma unit showed 34.7% had used marijuana very recently. [FN15]
In a study of seriously injured drivers admitted to a shock-trauma center, 26.9 % of the drivers tested positive for marijuana. [FN16]
ASK YOURSELF: Is using marijuana a safe thing to do?
If you answered ‘no’ to any one of the above questions, then you should also say ‘no’ to legalizing marijuana for recreational use.
FOR MORE INFORMATION VISIT: www.dfaf.org
References
[FN1] Based on experience in the US and Europe when marijuana laws have been relaxed, the number of users will double or triple. See, Speaking Out Against Drug Legalization, U.S. Department of Justice, Drug Enforcement Administration (DEA), Washington, DC U.S.A. 2010, www.DEA.gov, pages 46 and 57; Currently, there are 16.7 million regular marijuana users in the US (12 years old or older.) SAMHSA, 2009 Annual Survey on Drug Use and Health, September 2010; The benchmark surveys of drug use show that that perception of harm with respect to marijuana has dropped off since the drive to legalize marijuana began. The benchmark surveys are the Monitoring the Future Survey, which has tracked drug use among American high school students annually since 1975 and the National Household Survey on Drug Abuse, which has tracked drug use among Americans ages 12 and older since 1972. Monitoring the Future, National Institutes of Health, National Institute on Drug Abuse, available on the Internet at www.monitoringthefuture.org; Overview of Findings from the 2002 National Survey on Drug Use and Health (Office of Applied Studies, NHSDA Series H-21, DHHS Publication No. SMA 03- 3774). Rockville, MD; Conducted for SAMHSA (the Substance Abuse and Mental Health Services Administration, Department of Health and Human Services) by North Carolina’s Research Triangle Institute.
[FN2] DEA Position on Marijuana, U.S. Department of Justice, Drug Enforcement Administration (DEA), Washington, DC U.S.A. July 2010, www.DEA.gov, pages 23-26 and 33-34; Speaking Out Against Drug Legalization, DEA, pages 51-53
[FN3] Bovassco, G., American Journal of Psychiatry, 2001
[FN4] “Non-medical Marijuana: Rite of Passage or Russian Roulette?” July 1999 obtained at website www.casacolumbia.org; Kaplan, H.B., Martin, S.S., Johnson, R.J., and Robbins, C.A., Escalation of marijuana use: Application of a general theory of deviant behavior. Journal of Health and Social Behavior.1986:27:44-61; Clayton, R.R., and Leukefeld, C.G., The prevention of drug use among youth; implications of “legalization” Journal of Primary Prevention. 1992:12:289-302
[FN5] Drug Abuse Warning Network, 2004: National Estimates of Drug-Related Emergency Department Visits U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration http://DAWNinfo.samhsa.gov/
9[FN6] The Occurrence of Cannabis Use Disorders and Other Cannabis Related Problems Among First Year College Students, Addictive Behaviors 33(3):397-411, March 2008; Compton, Dewey & Martin, Cannabis dependence and tolerance production, Advances in Alcohol and Substance Abuse 1990:9:129-147; Miller & Gold, The diagnosis of marijuana cannabis dependence, Journal of Substance Abuse Treatment 1989:6:183-192; Clayton & Leukefeld, The prevention of drug use among youth: implications’ of legalization, Journal of Prevention 1992:12:289-302; Kaplan, Martin, Johnson & Robbins, Escalation of marijuana use: Application of a general theory of deviant behavior, Journal of Health and Social Behavior 1986:27:44-61; “Regular or Heavy Use of Cannabis Was Associated with Increased Risk of Using Other Illicit Drugs” Addiction, 2006; 101:556-569; “As Marijuana Use Rises, More People Are Seeking Treatment for Addiction” -Wall Street Journal, 2 May 2006; “Twenty-Five Year Longitudinal Study Affirms Link Between Marijuana Use and Other Illicit Drug Use” – Congress of the United States,14 March 2006; “New Study Reveals Marijuana is Addictive and Users Who Quit Experience Withdrawal”- All Headline News, 6 February 2007; “Escalation of Drug Use in Early Onset Cannabis Users Vs. Co-twin Controls” – Journal of the American Medical Association, 2003; 289:4
[FN7]  New Report Finds Highest-Ever Levels of THC in US Marijuana, June 12, 2008, http://www.whitehousedrugpolicy.gov/news/press08/061208.html
[FN8] National Highway Traffic Safety Administration, Use of Controlled Substances and Highway Safety; A Report to Congress (U.S. Dept. of Transportation, Washington, D.C., 1988); “White House Drug Czar Launches Campaign to Stop Drugged Driving.” Office of National Drug Control Policy Press Release. 19 November 2002
[FN9] “One-third of Fatally Injured Drivers with Known Test Results Tested Positive for at Least one Drug in 2009.CESARFAX. Vol. 19, Issue 49. December 20, 2010. www.cesar.umd.edu.
[FN10] Ibid.
[FN11] Drug-Impaired Driving by Youth Remains Serious Problem. NIDA News Release, October 29, 2007. http://www.drugabuse.gov/newsroom/07/NR10-29.html.
[FN12] O’Malley, Patrick and Johnston, Lloyd. “Unsafe Driving by High School Seniors: National Trends from 1976 to 2001 in Tickets and Accidents After Use of Alcohol, Marijuana and Other Illegal Drugs.” Journal of Studies on Alcohol. May 2003; The DEA Position On Marijuana, DEA.gov
[FN13] Abbie Crites-Leoni, Medicinal Use of Marijuana: Is the Debate a Smoke Screen for Movement Toward Legalization? 19 J. Legal Med. 273, 280 (1998) (citing Schwartz, et al., Short- Term Memory Impairment in Cannabis-Dependent Adolescents, 143 Am. J. Dis. Child. 1214 (1989))
[FN14] ONDCP, “Marijuana: Know the Facts”, October 2010
[FN15] Soderstrum, C., Trifillis, A., Shankar, B., Clark, W., and Cowley, R. Marijuana and Alcohol Use among 1023 Patients. Archives of Surgery, 123 (June 1988): 733–37; Skolnick, Illicit Drugs take still another toll; death or injury from vehicle-associated trauma, JAMA 1990:263:3122-3125; Soderstrom, Drug involvement among drivers admitted to a regional trauma center, Presented at the Transportation Research Board 70th Annual Meeting (Washington, D.C., Jan. 15, 1991).
[FN16] DuPont, Robert. “National Survey Confirms that Drugged Driving is Significantly More Widespread than Drunk Driving.” Commentary, Institute for Behavior and Health, July 17, 2009. page 1. http://www..ibhinc.org.
Some of this information was borrowed with permission from: Healthy and Free Colorado, affiliated with the Colorado Drug Investigators Association, POB 372394, Denver, CO 80237
WHO’S REALLY IN PRISON FOR MARIJUANA?
Drug legalization advocates claim that prisons are overflowing with people convicted for only simple possession of marijuana. This claim is aggressively pushed by groups seeking to relax or abolish marijuana laws. A more accurate view is that the vast majority of inmates in prison for marijuana have been found guilty of more than simple possession. They were convicted for drug trafficking, or for marijuana possession along with other offences. Many of those in prison for marijuana entered a guilty plea to a marijuana charge to avoid a more serious charge. In the US, just 1.6 percent of the state inmate population were held for offences involving only marijuana, and less than one percent of all state prisoners (0.7 percent) were incarcerated with marijuana possession as the only charge. An even smaller fraction of state prisoners were first time offenders (0.3 percent). The numbers on the US federal prisons are similar. In 2001, the overwhelming majority of offenders sentenced for marijuana crimes were convicted for trafficking and only 63 served time for simple possession. [FN1]
Plea Bargains Distort the Picture
The standard practice in drug cases is for the offender to be given the opportunity to plead guilty in exchange for lighter punishment thus sparing the taxpayers the expense and risk of a trial. If the offender is only charged with one crime, the prosecutor will typically offer a shorter sentence to a lesser charge. If the offender has multiple charges, the common practice is to dismiss one charge in exchange for a guilty plea to another lesser charge, especially if the government feels the offender can provide valuable assistance to law enforcement by providing information on drug trafficking.
Drug legalization advocates claim that nearly one-third of all federal drug defendants are charged with marijuana offences. [FN2] However, only a tiny percentage of that number are actually convicted for marijuana possession. [FN3]
There are a number of circumstances under which a simple-possession marijuana offender might receive a sentence to prison. For example, this may happen if:
1. the marijuana offence was committed while the offender was on probation or parole;
2. an offender charged with a more serious crime pleads guilty to the lesser offence of marijuana possession but as part of a plea bargain is required to serve a prison sentence;
3. the offender has a criminal history, particularly one involving drugs or violent crime;
4. the violation took place in a designated drug-free zone (such as on school property); or
5. the marijuana sentence runs concurrent with the sentence for one or more other offences;
How Much Marijuana Did the Average Offender Possess to Get a Prison Sentence?
According to US Bureau of Justice Statistics estimates based on a survey of federal prisoners, the median amount of marijuana involved in the conviction of marijuana-only possession offenders was 115 pounds. [FN4] This is far more than is needed for personal use.
References
[FN1]  Who’s Really in Prison for Marijuana?, Office of National Drug Control Policy,
www.whitehousedrugpolicy.gov; Substance Abuse and Treatment, State and Federal Prisoners, 1997,” BJS Special Report, January 1999, NCJ 172871; Unpublished BJS estimates based on the 1997 Survey of Inmates in State and Federal Correctional Facilities, National Archive of Criminal Justice Data; Prison and Jail Inmates at Midyear 2002, Bureau of Justice Statistics Bulletin, April 2003, NCJ 198877; Prisoners in 2002, Bureau of Justice Statistics, July 2003, NCJ 200248; Who’s Really in Prison for Marijuana?, Office of National Drug Control Policy, www.whitehousedrugpolicy.gov
[FN2] Pot Violators Comprise Largest Percentage of Federal Drug Offenders, Department of Justice Study Shows, NORML News, August 30, 2001; Who’s Really in Prison for Marijuana?, Office of National Drug Control Policy, www.whitehousedrugpolicy.gov
[FN3] US Sentencing Commission’s 2001 Sourcebook of Federal Sentencing Statistics; Who’s Really in Prison for Marijuana?, Office of National Drug Control Policy, www.whitehousedrugpolicy.gov
[FN4] Who’s Really in Prison for Marijuana?, Office of National Drug Control Policy, www.whitehousedrugpolicy.gov
WE CANNOT LEGALIZE MARIJUANA BECAUSE ITS USE HAS DESTRUCTIVE HEALTH AND SOCIAL CONSEQUENCES.
Most of the arguments in favor of drug legalization focus on marijuana. However, marijuana is far more powerful today than it was years ago and it serves as an entry point for the use of other illegal drugs. This is known as the “gateway effect.” Despite arguments from the drug culture to the contrary, marijuana is addictive. This addiction has been well described in the scientific literature and it consists of both a physical dependence (tolerance and subsequent withdrawal) and a psychological habituation. [FN1]
According to a US report released in June of 2008, the levels of THC – the psychoactive ingredient in marijuana – have reached the highest ever amounts since scientific analysis of the drug began in the late 1970s. The average amount of THC has now reached average levels of 9.6 percent (the highest level in one of the samples was 37.2 percent). This compares to the average of just under 4 percent reported in 1983. Additionally, higher potency marijuana may be contributing to a substantial increase in the number of American teenagers in treatment for marijuana dependence. According to the U.S. 2006 National Survey on Drug Use and Health (NSDUH), among Americans age 12 and older there are 14.8 million current (past-month; 6.0 percent) users of marijuana and 4.2 million Americans (1.7 percent) classified with dependency or abuse of marijuana. Additionally, the latest information from the U.S. Treatment Episode Data Set (TEDS, 2006), reports that 16.1% of drug treatment admissions were for marijuana as the primary drug of abuse. This compares to 6% in 1992. A similar trend is taking place in the Netherlands, where new data indicate that the number of people seeking assistance for cannabis there has risen, from 1,951 in 1994 to 6,544 in 2006 – a 235 percent increase.  [FN2] In 2006, the average THC concentration in Dutch marihuana was 16% which is even higher than that in the US. [FN3]
Marijuana is an addictive drug. It poses significant health consequences to its users, including those who may be using it for “medical” purposes. In the U.S., marijuana is the number one drug that young people are in treatment for. [FN4]
The use of marijuana in early adolescence is particularly dangerous. Adults who used marijuana early were five times more likely to become dependent on any drug and eight times more likely to use cocaine and fifteen times more likely to use heroin later in life.” [FN5]
The damage to health caused by marijuana
Drug legalization advocates claim that marijuana is less dangerous than drugs like cocaine, heroin, and methamphetamine. Some European countries have lowered the classification of marijuana based on the false perception that it is less harmful. However, studies over the last few years give us a lot of new information about marijuana. They show that marijuana is not harmless but that it is toxic and addictive. Recent studies show the following destructive effects of marijuana use: [FN6]
birth defects
      the worsening of pain
      respiratory system damage
      links to cancer
      AIDS – marijuana opens the door to Kaposi’s sarcoma
      brain damage
      strokes
      immune system damage
      mental illness
      violence
      infertility
hepatitis
References
[FN1] http://www.unodc.org/unodc/en/frontpage/why-should-we-care-about-cannabis.html; The Occurrence of Cannabis Use Disorders and Other Cannabis Related Problems Among First Year College Students, Addictive Behaviors 33(3):397-411, March 2008;Compton, Dewey & Martin, Cannabis dependence and tolerance production, Advances in Alcohol and Substance Abuse 1990:9:129-147; Miller & Gold, The diagnosis of marijuana cannabis dependence, Journal of Substance Abuse Treatment 1989:6:183-192; Clayton & Leukefeld, The prevention of drug use among youth: implications’ of legalization, Journal of Prevention 1992:12:289-302; Kaplan, Martin, Johnson & Robbins, Escalation of marijuana use: Application of a general theory of deviant behavior, Journal of Health and Social Behavior 1986:27:44-61; Bailey, Flewelling & Rachal, Predicting continued use of marijuana among adolescents: the relative influence of drug-specific and social context factors, Journal of Health and Social Behavior 1992:33:51-66; “Regular or Heavy Use of Cannabis Was Associated with Increased Risk of Using Other Illicit Drugs” Addiction, 2006; 101:556-569; “As Marijuana Use Rises, More People Are Seeking Treatment for Addiction” -Wall Street Journal, 2 May 2006; “Twenty-Five Year Longitudinal Study Affirms Link Between Marijuana Use and Other Illicit Drug Use” – Congress of the United States,14 March 2006; “New Study Reveals Marijuana is Addictive and Users Who Quit Experience Withdrawal”- All Headline News, 6 February 2007; “Cannabis Withdrawal Among Non-Treatment-Seeking Adult Cannabis Users” -The American Journal on Addiction, 2006; 15:8-14; “Escalation of Drug Use in Early Onset Cannabis Users Vs. Co-twin Controls” – Journal of the American Medical Association, 2003; 289:4
[FN2]  New Report Finds Highest-Ever Levels of THC in US Marijuana, June 12, 2008, http://www.whitehousedrugpolicy.gov/news/press08/061208.html
[FN3] The Netherlands Drug Situation 2007 – National Drug Monitor, European Monitoring Centre for Drugs and Drug Addiction 2008, pgs. 107 and 108
[FN4] Non-medical Marijuana: Rite of Passage or Russian Roulette?” July 1999 obtained at website www.casacolumbia.org; The Occurrence of Cannabis Use Disorders and Other Cannabis Related Problems Among First Year College Students, Addictive Behaviors 33(3):397-411, March 2008.
[FN5] What Americans Need to Know about Marijuana.” Office of National Drug Control Policy. October 2003. Page 9.; The DEA Position On Marijuana, DEA.gov
[FN6]  Birth Defects – Risk of Selected Birth Defects with Prenatal Illicit Drug Use, Hawaii, 1986-2002, Journal of Toxicology and Environmental Health, Part A, 70: 7-18, 2007
Pain – “Too Much Cannabis Worsens Pain” – BBC News, 24 October 2007; “Study Finds that Marijuana Won’t Stop Multiple Sclerosis Pain”- Neurology, 2002; 58:1404-1407
Respiratory System Damage – “Marijuana Associated with Same Respiratory Symptoms as Tobacco,” YALE News Release. 13 January 2005. www.yale.edu/opa/newsr/05-01-13-01.all.htm (14 January 2005); Marijuana Smoke Contains Higher Levels of Certain Toxins Than Tobacco Smoke, Science Daily, December 18, 2007; Marijuana Smokers Face Rapid Lung Destruction – As Much as 20 Years Ahead of Tobacco Smokers, Science Daily, January 27, 2008; “Respiratory and Immunologic Consequences of Marijuana Smoking”- Journal of Clinical Pharmacology, 2002; 42:71S-81S
Cancer – “Association Between Marijuana Use and Transitional Cell Carcinoma”- Adult Urology, 2006; 100-104
AIDS/HIV – “Marijuana Component Opens The Door For Virus That Causes Kaposi’s Sarcoma” -Science Daily, 2 August 2007
Brain Damage – “Neurotoxicology; Neurocognitive Effects of Chronic Marijuana Use Characterized.” Health & Medicine Week. 16 May 2005; “Marijuana May Affect Blood Flow in Brain” – Reuters, 7 February 2005;
Strokes – “More Evidence Ties Marijuana to Stroke Risk” – Reuters Health, 22 February 2005
Immune System Damage – “Immunological Changes Associated with Prolonged Marijuana Smoking” -American College of Allergy, Asthma and Immunology, 17 November 2004
Mental Illness, Schizophrenia, Depression – Kearney, Simon. “Cannabis is Worst Drug for Psychosis.” The Australian. 21 November 2005; Curtis, John. “Study Suggests Marijuana Induces Temporary Schizophrenia-Like Effects.” Yale Medicine. Fall/Winter 2004; “Cannabis-Related Schizophrenia Set to Rise, Say Researchers” – Science Daily, 26 March 2007; “Report: Using Pot May Heighten Risk of Becoming Psychotic” – Associated Press, 26 July 2007; “Marijuana Linked to Schizophrenia, Depression” – British Medical Journal, 21 November 2007; “Anterior Cingulate Grey-Matter Deficits and Cannabis Use in First-Episode Schizophrenia” The British Journal of Psychiatry, 2007; 190: 230-236; Marijuana Increases the Risk of Both Psychosis In Non-Psychotic People As Well As Poor Prognosis For Those With Risk of Vulnerability to Pyschoses” American Journal of Epidemiology, 2002; 156:319-327; Psychophysiological Evidence of Altered Neural Synchronization in Cannabis Use: Relationship to Schizotypy” Am J Psychiatry, 2006; 163:1798-1805
Violence – “Cannabis ‘Linked to Aggression'” – Scotsman.com News, Press Association 2006; “Marijuana Had a Greater Effect on Increasing the Degree of Violent Behavior in Non-Delinquent Individuals Than in Delinquent Individuals” – J Addict. Dis. 2003; 22:63-78
Infertility – “Marijuana Firmly Linked to Infertility” – Scientific American, 22 December 2000
Hepatitis –  Clinical Gastroenterology and  Hepatology 2008, Vol. 6, No.1, pages 69-75, captioned “Influence of Cannabis use on Severity of Hepatitis C Disease”
The continued push in the USA  for marijuana to be legalised ‘for medicinal purposes’ has resulted in many States allowing the substance to be sold in so-called ‘marijuana dispensaries’.  However closer investigation has shown the majority of people purchasing the substance are not those with serious and even terminal illnesses, but existing drug users wanting to justify their purchase and use.  They are able to get co-operative doctors to sign a form saying that they need to use marijuana to help with ‘back pain or headaches’ or similar trivial illnesses.  The item below shows that as far back as l989 it was shown that for genuinely ill patients a pharmaceutically prepared  drug called Marinol (or Nabilone) could be legally prescribed by a doctor if it was shown to be helpful – without the many drawbacks to smoking crude marijuana. There is now a pharmaceutically prepared medicine made from extracts of marijuana called Sativex and there is therefore no need for anyone to smoke marijuana for medicine. 
 
Rescheduling of Marijuana Denied (1989)
During the late 1980s, as a proposed solution to the enormous drug problem in the United States, a small, but vocal minority began supporting the wholesale legalization of drugs, particularly marijuana. However, in December 1989, DEA Administrator Jack Lawn overruled the decision of one administrative law judge who had agreed with marijuana advocates that marijuana should be moved from Schedule I to Schedule II of the Controlled Substances Act. This proposed rescheduling of marijuana would have allowed physicians to prescribe the smoking of marijuana as a legal treatment for some forms of illness.
Administrator Lawn maintained that there was no medicinal benefit to smoking marijuana. While some believed that smoking marijuana alleviated vomiting and nausea experienced by cancer patients undergoing radiation, scientific studies indicated otherwise. These also showed that smoking marijuana did not benefit patients suffering from glaucoma or multiple sclerosis. In addition, it was found that smoking marijuana might further weaken the immune systems of patients undergoing radiation and might speed up, rather than slow down, the loss of eyesight in glaucoma patients. It was found that pure Delta-9-Tetrahydrocannabinol (THC), one of 400 chemicals commonly found in marijuana, had some effect on controlling nausea and vomiting. However, pure THC was already available for use by the medical community in a capsule form called Marinol. For these reasons, and the fact that no valid scientific studies offered proof of any medicinal value of marijuana, Administrator Lawn maintained that marijuana should remain a Schedule I controlled substance.

Even smart people make mistakes, sometimes surprisingly large ones.  A current example is drug legalization, which way too many smart people consider a good idea.  They offer three bad arguments.

First, they contend, “the drug war has failed”, despite years of effort we have been unable to reduce the drug problem.  Actually, as imperfect as surveys may be, they present overwhelming evidence that the drug problem is growing smaller and has fallen in response to known, effective measures.  Americans use illegal drugs at substantially lower rates than when systematic measurement began in 1979, down almost 40 percent.  Marijuana use is down by almost half since its peak in the late 1970s, and cocaine use is down by 80 percent since its peak in the mid-1980s.  Serious challenges with crack, meth, and prescription drug abuse have not changed the broad overall trend: Drug use has declined for the last 40 years, as has drug crime.

The decades of decline coincide with tougher laws, popular disapproval of drug use, and powerful demand reduction measures such as drug treatment in the criminal justice system and drug testing.  The drop also tracks successful attacks on supply, as in the reduction of cocaine production in Colombia and the successful attack on meth production in the United States.  Compared with most areas of public policy, drug control measures are quite effective when properly designed and sustained.

Drug enforcement keeps the price of illegal drugs at hundreds of times the simple cost of producing them.  To destroy the criminal market, legalization would have to include a massive price cut, dramatically stimulating use and addiction.  Legalization advocates typically ignore the science.  Risk varies a bit, but all of us and a variety of other living things, monkeys, rats, and mice, can become addicted if exposed to addictive substances in sufficient concentrations, frequently enough, and over a sufficient amount of time.  It is beyond question that more people using drugs, more frequently, will result in more addiction.

About a third of illegal drug users are thought to be addicted (or close enough to it to need treatment), and the actual number is probably higher.  There are now at least 21 million drug users, and at least 7 million need treatment.  How much could that rise?  Well, there are now almost 60 million cigarette smokers and over 130 million who use alcohol each month.  It is irrational to believe that legalization would not increase addiction by millions.  

We can learn from experience.  Legalization has been tried in various forms, and every nation that has tried it has reversed course sooner or later.  America’s first cocaine epidemic occurred in the late 19th century, when there were no laws restricting the sale or use of the drug.  That epidemic led to some of the first drug laws, and the epidemic subsided.  Over a decade ago the Netherlands was the model for legalization.  However, the Dutch have reversed course, as have Sweden and Britain (twice).  The newest example for legalization advocates is Portugal, but as time passes the evidence there grows of rising crime, blood-borne disease, and drug usage.

The lessons of history are the lessons of the street. Sections of our cities have tolerated or accepted the sale and use of drugs.  We can see for ourselves that life is not the same or better in these places, it is much worse.  If they can, people move away and stay away.  Every instance of legalization confirms that once you increase the number of drug users and the addicted, it is difficult to undo your mistake.

The most recent form of legalization, pretending smoked marijuana is medicine, is following precisely the pattern of past failure.  The majority of the states and localities that have tried it are moving to correct their mistake, from California to Michigan.  Unfortunately, Washington, D.C., is about to start down this paths.  It will end badly.

The second false argument for legalization is that drug laws have filled our prisons with low-level, non-violent offenders.  The prison population has increased substantially over the past 30 years, but the population on probation is much larger and has grown almost as fast.  The portion of the prison population associated with drug offences has been declining, not growing. The number of diversion programs for substance abusers who commit crimes has grown to such an extent that the criminal justice system is now the single largest reason Americans enter drug treatment.

Despite constant misrepresentation of who is in prison and why, the criminal justice system has steadily and effectively focused on violent and repeat offenders. The unfortunate fact is that there are too many people in prison because there are too many criminals. With the rare exceptions that can be expected from human institutions, the criminal justice system is not convicting the innocent.

Most recently, crime and violence in Central America and Mexico have become the third bad reason to legalize drugs.  Even some foreign leaders have joined in claiming that violent groups in Latin America would be substantially weakened or eliminated if drugs were legal.

Many factors have driven this misguided argument.  First, while President Álvaro Uribe in Colombia and President Felipe Calderón in Mexico demonstrated brave and consequential leadership against crime and terror, such leadership is rare.  For both the less competent and the corrupt, the classic response in politics is to blame someone else for your failure.

The real challenge is to establish the rule of law in places that have weak, corrupt, or utterly inadequate institutions of justice.  Yes, the cartels and violent gangs gain money from the drug trade, but they engage in the full range of criminal activities, murder for hire, human trafficking, bank robbery, protection rackets, car theft, and kidnapping, among others.  They seek to control areas and rule with organized criminal force.  This is not a new phenomenon, and legalizing drugs will not stop it.  In fact, U.S. drug laws are a powerful means of working with foreign partners to attack violent groups and bring their leaders to justice.

Legalization advocates usually claim that alcohol prohibition caused organized crime in the United States and its repeal ended the threat.  This is widely believed and utterly false.  Criminal organizations existed before and after prohibition.  Violent criminal organizations exist until they are destroyed by institutions of justice, by each other, or by authoritarian measures fueled by popular fear.  No honest criminal justice official or family in this hemisphere will be safer tomorrow if drugs are legalized, and the serious among them know it.

Are the calls for legalization merely superficial, silly background noise in the context of more fundamental problems?  Does this talk make any difference? Well, suppose someone you know said, “Crack and heroin and meth are great, and I am going to give them to my brothers and sisters, my children and my grandchildren.”  If you find that statement absurd, irresponsible, or obscene, then at some level you appreciate that drugs cannot be accepted in civilized society.  Those who talk of legalization do not speak about giving drugs to their families, of course; they seem to expect drugs to victimize someone else’s family.

Irresponsible talk of legalization weakens public resolve against use and addiction.  It attacks the moral clarity that supports responsible behavior and the strength of key institutions.  Talk of legalization today has a real cost to our families and families in other places.  The best remedy would be some thoughtful reflection on the drug problem and what we say about it.

Source: http://www.weeklystandard.com/author/john-p.-walters 7th May 2012

 Several jurisdictions in the U.S. have taken steps toward decriminalizing marijuana possession for personal use or when prescribed by a physician for medicinal purposes. Other jurisdictions have pending ballot initiatives or legislative bills proposing such changes in the law.
The Board of Directors of the National Association of Drug Court Professionals (NADCP) has determined that it is essential for drug court practitioners to be fully and objectively informed about the effects of marijuana on their participants and the public at-large. This document briefly reviews the scientific evidence concerning the effects of marijuana.

Incarceration for Marijuana Possession

It is exceedingly rare to be incarcerated in the U.S. for the use or possession of marijuana. According to the National Center on Addiction & Substance Abuse at Columbia University (CASA, 2010), less than 1 percent (0.9%) of jail and prison inmates in the U.S. were incarcerated for marijuana possession as their sole offense.
Excluding jail detainees who may be held pending booking or release on bond, the rates are even lower. Prison inmates sentenced for marijuana possession account for 0.7 percent of state prisoners and 0.8 percent of federal prisoners (see Table). And, considering that many of those prisoners pled down from more serious charges, the true incarceration rate for marijuana possession can only be described as negligible.
State Prisoners Federal Prisoners
Marijuana offense only 1.6% N.R.
Marijuana possession only 0.7% 0.8%
First-time marijuana possession 0.3% N.R.

Source: Office of National Drug Control Policy, Who’s Really in Prison for Marijuana? [NCJ #204299] (citing BJS, 1999, Substance abuse and treatment, state and federal prisoners, 1997 [NCJ #172871]; U.S. Sentencing Commission, 2001 Sourcebook of Federal Sentencing Statistics). N.R. = not reported. 2

Addiction Potential

By the early 1990’s, the scientific community had concluded from rigorous laboratory and epidemiological studies that marijuana is physiologically and psychologically addictive. Every drug of abuse has what is called a dependence liability, which refers to the statistical probability that a person who uses that drug for nonmedical purposes will develop a compulsive addiction. Based upon several nationwide epidemiological studies, marijuana’s dependence liability has been reliably determined to be 8 to 10 percent (Anthony et al., 1994; Brook et al., 2008; Budney & Moore, 2002; Kandel et al., 1997; Munsey, 2010; Wagner & Anthony, 2002). This means that one out of every 10 to 12 people who use marijuana will become addicted to the drug.
Importantly, the dependence liability of any drug increases with more frequent usage. Individuals who have used marijuana at least five times have a 20 to 30 percent likelihood of becoming addicted to the drug, and those who use it regularly have a 40 percent likelihood of becoming addicted (Budney & Moore, 2002).
The hallmark feature of physical addiction is the experience of uncomfortable or painful withdrawal symptoms whenever levels of the substance decline in the bloodstream. This is, in part, what drives addicts to continue abusing drugs or alcohol despite suffering severe negative medical, legal and interpersonal consequences. Carefully controlled, rigorous laboratory studies have proven beyond further dispute that marijuana addiction is associated with a clinically significant withdrawal syndrome. When marijuana-addicted individuals stop using the drug, they experience symptoms of irritability, anger, cravings, decreased appetite, insomnia, interpersonal hypersensitivity, yawning and/or fatigue (Budney et al., 2001; Preuss et al., 2010). In fact, the features and severity of the marijuana withdrawal syndrome are virtually indistinguishable from those of nicotine (cigarette) withdrawal.
A second hallmark feature of addiction is psychosocial dysfunction resulting from repeated use of the substance. The most commonly diagnosed symptoms of psychosocial dysfunction among marijuana addicts include persistent procrastination, bad or guilty feelings, low productivity, low self-confidence, interpersonal or family conflicts, memory problems and financial difficulties (Budney & Moore, 2002; NIDA, 2005). This constellation of symptoms has been collectively referred to as an “amotivational syndrome” (e.g., Hubbard et al., 1999) because marijuana abusers tend to be characteristically languid and often achieve considerably below their true intellectual potentials.
Based on this substantial body of empirical research, the American Psychiatric Association (APA) has long recognized cannabis dependence as a valid and reliable psychiatric disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM is the official psychiatric diagnostic classification system in the U.S. A diagnosis of cannabis dependence has been continuously included in the 3rd and 4th editions of the DSM since 1980 (APA, 1980, 1987, 1994, 2000). In the soon-to-be published 5th edition of the DSM, a cannabis withdrawal syndrome will now also be officially recognized as part of the diagnostic criteria for cannabis dependence.

Medical Harm

In many respects, smoked marijuana has the potential to be as, or more, harmful than cigarettes. Although marijuana does not contain nicotine, it does contain 50 to 70 percent more carcinogenic compounds, including tar, than cigarettes (NIDA, 2005; Hubbard et al., 1999). Marijuana also produces high levels of a particular enzyme which converts certain hydrocarbons into their carcinogenic or malignant forms (NIDA, 2005).
Although gram for gram, marijuana smoke is clearly more carcinogenic than cigarette smoke, it is difficult to predict whether actual incidence rates of induced cancers are likely to be as high as they are for cigarettes. On one hand, cannabis smokers tend to use the drug on fewer occasions than cigarette smokers. On the other hand, they typically inhale larger amounts of the drug per occasion, hold the smoke in their lungs for longer intervals of time, and are unlikely to employ filters. This makes it difficult to compare the predicted magnitudes of the harms. The best estimate from the National Institutes of Health (NIH) is that a person who smokes five marijuana cigarettes per week is likely to be inhaling as many cancer-causing chemicals as one who smokes a full pack of cigarettes every day.1
See U.S. Dept. of Justice, Drug Enforcement Administration, Exposing the myth of medical marijuana: The facts. Available at http://www.justice.gov/dea/ongoing/marijuanap.html.
Like nicotine, cannabis increases heart rate, alters blood pressure, can induce tachycardia (rapid or irregular heartbeat), increases myocardial (heart) stress, decreases oxygen levels in the circulatory system, and exacerbates angina (Hubbard et al., 1999). As a result, a person’s risk of a heart attack is increased four-fold during the first hour after smoking marijuana (NIDA, 2005).
There is no question that regular marijuana use is associated with a wide spectrum of chronic respiratory ailments. A nationally representative study of 6,728 adults found heavy marijuana use to be substantially associated with chronic bronchitis, coughing on most days, wheezing, abnormal chest sounds and increased phlegm (Moore et al., 2005).
Marijuana has undisputed negative effects on cognitive functioning, including memory, learning and motor coordination. These negative effects persist long after the period of acute intoxication, averaging approximately 30 days of residual cognitive impairment (Bolla et al., 2002; NIDA, 2005; Pope et al., 2001). This means that individuals are apt to wrongly believe they are capable of performing critical tasks, such as driving a car, operating heavy machinery, caring for children or solving work-related intellectual problems, when in fact they may be performing in the mildly to moderately impaired range of functioning.
Like any drug, marijuana’s negative effects tend to be most pronounced in elderly persons, individuals with chronic medical illnesses, and those with compromised immune systems. This is of particular concern given that marijuana is being specifically touted for “medicinal” use by elderly patients, cancer patients, and those with immunodeficiency syndromes such as HIV/AIDS (e.g., Munsey, 2010). Rather than benefiting such individuals, marijuana has the serious potential to further suppress or compromise their immune systems and exacerbate the disease process (NIDA, 2005).

Medicinal Effects

Marijuana is a “Schedule I” drug according to the Drug Enforcement Administration (DEA), meaning it has a high abuse potential and no recognized medical indication. However, the Food and Drug Administration (FDA) has approved a particular ingredient within marijuana (THC) in a non-smoked form for certain medical indications, such as for treatment of nausea, vomiting and poor appetite. Recent studies have also supported its use in treating chronic neuropathic pain (e.g., Munsey, 2010).
To date, research indicates that oral THC (when administered at adequate doses) is as effective as smoked marijuana in achieving these therapeutic effects (e.g., Munsey, 2010). Anecdotal testimonials are the only evidence favoring smoked marijuana over oral THC for therapeutic purposes. Further research is called for to determine whether other compounds within marijuana might have medicinal properties as well, but at this juncture any such indications are purely experimental and speculative.
Regardless, smoked marijuana could no more be considered a “medication” than cigarettes or alcohol. Although cigarettes and alcohol have undeniable effects that many people may find palliative (such as alleviating short-term stress), they are very “dirty” drugs. This means they contain dozens, if not hundreds, of other physiologically active compounds which are irrelevant to their palliative effects and may actually work at cross-purposes against those effects. For example, many people believe alcohol and nicotine lower their stress level, but in fact these drugs are proven to increase anxiety, lower stress tolerance and exacerbate insomnia over the longer term. These drugs are also associated with a host of serious medical conditions, including cancer, heart disease, liver disease and respiratory illnesses. For these reasons, physicians would rarely, if ever, “prescribe” these drugs to treat a medical condition.
More research is needed to isolate the potential therapeutic effects of specific compounds within marijuana, and to determine how to administer those compounds in a manner that is medically safe and does not threaten to cause heart, lung and other diseases. Administering the “dirty” form of the drug would never be a legitimate medical end-goal.

Impact on Crime

Two recent meta-analyses (advanced statistical procedures) have concluded that marijuana use during adolescence or young adulthood significantly predicts later involvement in criminal activity and criminal arrests (Bennett et al., 2008; Pedersen & Skardhamar, 2010). The risk of criminal involvement was determined to be between 1.5 and 3.0 times greater for cannabis users than for non-users. 5 The results suggest that, all else being equal, cannabis users are at a statistically increased risk for associating with antisocial individuals, engaging in illegal conduct, and eventually getting a criminal record.

Conclusion

Marijuana is an intoxicating and addictive drug that poses serious medical risks akin to those of nicotine and alcohol. Although some physicians may consider it to have palliative indications, no national or regional medical or scientific organization recognizes marijuana as a medicine in its raw or smoked form.
If marijuana becomes decriminalized or legalized in a given jurisdiction, this does not necessarily require drug court practitioners to abide its usage by their participants. The courts have long recognized restrictions on the use of a legal intoxicating substance (i.e., alcohol) to be a reasonable condition of bond or probation where the offender has a history of illicit drug involvement. If there is a rational basis for believing cannabis use could threaten public safety or prevent the offender from returning to court for adjudication, appellate courts are likely to uphold such restrictions in the drug court context.
Individuals who have a valid medical prescription for marijuana present a more challenging issue, but one that is probably also not insurmountable. Under such circumstances, the judge might subpoena the prescribing physician to testify or respond to written inquiries about the medical justification for the prescription. In addition, the court may be authorized by the rules of evidence or rules of criminal procedure to engage an independent medical expert to review the case and offer a medical recommendation or opinion. Having a Board-certified addiction psychiatrist on hand to advise the drug court judge may provide probative evidence about whether a particular marijuana prescription is medically necessary or indicated.
It remains an open question what degree of deference appellate courts are likely to give to the conclusions of a treating physician. In the absence of clear precedent, the best course of action is to develop a factual record and make a particularized decision in each case about the medical necessity for the prescription and the rationale for restricting marijuana usage during the term of criminal justice supervision.
If judges make these decisions based on a reasonable interpretation of medical evidence presented by qualified experts, it seems unlikely that drug courts — which were specifically designed to treat seriously addicted individuals — could not restrict access to an intoxicating and addictive drug as a condition of criminal justice supervision.

About NADCP

It takes innovation, teamwork and strong judicial leadership to achieve success when addressing drug-using offenders in a community. That’s why since 1994 the National Association of Drug Court Professionals (NADCP) has worked tirelessly at the national, state and local level to create and enhance Drug Courts, which use a combination of accountability and treatment to compel and support drug-using offenders to change their lives.
Now an international movement, Drug Courts are the shining example of what works in the justice system. Today, there are over 2,400 Drug Courts operating in the U.S., and another thirteen countries have implemented the model. Drug Courts are widely applied to adult criminal cases, juvenile delinquency and truancy cases, and family court cases involving parents at risk of losing custody of their children due to substance abuse.
Drug Court improves communities by successfully getting offenders clean and sober and stopping drug-related crime, reuniting broken families, intervening with juveniles before they embark on a debilitating life of addiction and crime, and reducing impaired driving.
In the 20 years since the first Drug Court was founded in Miami/Dade County, Florida, more research has been published on the effects of Drug Courts than on virtually all other criminal justice programs combined. The scientific community has put Drug Courts under a microscope and concluded that Drug Courts significantly reduce drug abuse and crime and do so at far less expense than any other justice strategy.
Such success has empowered NADCP to champion new generations of the Drug Court model. These include Veterans Treatment Courts, Reentry Courts, and Mental Health Courts, among others. Veterans Treatment Courts, for example, link critical services and provide the structure needed for veterans who are involved in the justice system due to substance abuse or mental illness to resume life after combat. Reentry Courts assist individuals leaving our nation’s jails and prisons to succeed on probation or parole and avoid a recurrence of drug abuse and
Today, the award-winning NADCP is the premier national membership, training, and advocacy organization for the Drug Court model, representing over 27,000 multi-disciplinary justice professionals and community leaders. NADCP hosts the largest annual training conference on drugs and crime in the nation and provides 130 training and technical assistance events each year through its professional service branches, the National Drug Court Institute, the National Center for DWI Courts and the National Veterans Treatment Court Clearinghouse.

NADCP publishes numerous scholastic and practical publications critical to the growth and fidelity of the Drug Court model and works tirelessly in the media, on Capitol Hill, and in state legislatures to improve the response of the American justice system to substance-abusing and mentally ill offenders through policy, legislation, and appropriations.
For more information please visit us on the web at www.AllRise.org.

Source: National Association of Drug Court Professionals. Sept. 2010

In 1996 a ballot initiative in California was approved (Prop. 215, and its successor SB420), which allowed for a smoked (!) leaf of unknown chemical composition, unregulated doses of psychoactive ingredients and hundreds of other potentially hazardous chemicals, to treat serious medical conditions, including “AIDS, anorexia, arthritis, cachexia, cancer, chronic pain, glaucoma, migraine, persistent muscle spasms, seizures, epilepsy, severe nausea, any other chronic or persistent medical symptom that substantially limits the ability of the person to conduct major life activities”. Prop 215 passage had nation-wide ramifications and set off a cascade of ballot initiatives in other states, including Montana.

A. MARIJUANA AS MEDICINE

1. The most obvious objection to Prop 215 is the use of smoking as a delivery system for drugs, after a 40 year national campaign to end smoking.
2. The second objection is the poor quality or no evidence for marijuana’s safety and efficacy in treating a myriad of diseases listed in the ballot initiatives

A few years after Prop 215 passed in California, Governor G. Davis funnelled millions of dollars into medical marijuana research, to seek validation, after the fact, for these “ballot-approved” medical claims. After a decade of funding, this California Center for Medicinal Cannabis Research has issued 24 publications.
Only 3/24 reports focus specifically on clinical studies to examine the effectiveness of marijuana in treating diseases listed in the ballot initiative. Only one medical condition is explored, neuropathic pain in AIDS patients. Intriguingly, recruited subjects were required to be experienced marijuana smokers and all subjects were maintained on other painkillers, but the manuscripts do not report any details on other painkillers. In the majority of observational studies published on the “therapeutic” effects of smoked marijuana, there is no reporting of side effects (e.g. intoxication, cognitive impairment, etc), information that the FDA considers essential for FDA approval. These include whether marijuana produced a feeling of “high” (“euphoria”), being impaired, feeling sedated and showing cognitive impairment in objective tests of learning, speed recall, attention.

As for the other medical indications for marijuana, five major clinical trials were discontinued because the investigators could not recruit enough patients, despite extensive advertising, to study marijuana effectiveness for relief of cancer pain, muscle spasticity, multiple sclerosis, severe nausea and vomiting, neuropathic pain. The intent to investigate was present, but candidate patients refused to enroll. It raises significant questions as to why 16 of the remaining research projects did not address the core reason for the state funding, whether marijuana is effective in all the medical conditions and indications specified in 215 and SB420.
3. The third objection, of national significance, is that ballot initiatives circumvent stringent Federal FDA standards, a direct threat and challenge toour elaborate, technical- and evidence-based, national drug approval system. FDA standards have protected Americans from fraudulent, dangerous or ineffective drugs for decades, with an approval system, although imperfect, that is among the most rigorous in the world. Consider the wise FDA response to ballot initiatives for the sham cancer treatment laetrile, their denial of thalidomide approval and a myriad of other drugs deemed unsafe and unacceptable by rigorous standards. Circumvention of FDA approval by a ballot initiative is a dangerous precedent, a slippery slope that can create chaos in the evidence-based approval process for medicines.

B. FDA REQUIREMENTS

The FDA requires that a drug:
a. is a pure compound
b. its chemistry, manufacturing, and composition of matter are tightly
controlled so that each batch is identical
c. its production methods are validated
d. its shelf life is known and can be dated to protect patients from a degraded chemical
e. its microbiology is known (batches of chemicals contaminated with bacteria are rejected)
f. its pharmacology and toxicology in animals is known
g. its rate of entry, bioavailability, toxicology are known
h. its dose response, efficacy, safety are known
i. its side effect profile is documented.
j. after approval, requires case reports and safety updates to be submitted to the FDA for ongoing evaluation.

Ballot initiatives for alleged treatments erode this carefully constructed process and lead to compromised quality of our nation’s medications.
The FDA ruling on marijuana as medicine is given below. It has not changed. Marijuana is listed in schedule I of the Controlled Substances Act (CSA), the most restrictive schedule.

• The Drug Enforcement Administration (DEA), which administers the CSA, continues to support that placement and FDA concurred because marijuana met the three criteria for placement in Schedule I under 21 U.S.C. 812(b)(1)
• Marijuana has a high potential for abuse has no currently accepted medical use in treatment in the United States
• Lacks accepted safety for use under medical supervision.
• There is sound evidence that smoked marijuana is harmful.
• A past evaluation by HHS agencies, FDA, SAMHSA and NIDA, concluded that no sound scientific studies      supported medical use of marijuana for treatment in the United States
• No animal or human data supported the safety or efficacy of marijuana for general medical use.
• There are alternative FDA-approved medications in existence for treatment of many of the proposed uses of smoked marijuana
• A growing number of states have passed voter referenda (or legislative actions) making smoked marijuana available for a variety of medical conditions upon a doctor’s recommendation.
• These measures are inconsistent with efforts to ensure that medications undergo the rigorous scientific scrutiny of the FDA approval process and are proven safe and effective under the standards of the FD&C Act.
• Accordingly, FDA, as the federal agency responsible for reviewing the safety and efficacy of drugs, DEA as the federal agency charged with enforcing the CSA, and the Office of National Drug Control Policy, as the federal coordinator of drug control policy, do not support the use of smoked marijuana for medical purposes.

C. THE PRACTICE OF MEDICINE IS IMPACTED BY MARIJUANA AS MEDICINE BALLOT INITIATIVES.

Medicine increasingly is evidence-based but marijuana has no academic presence in medical training or scholarship.

Contrary to good medical practice, there is no requirement:

a. to issue a prescription (only a recommendation)
b. extract medical history
c. give a detailed medical exam
d. discuss long term treatment, effects or follow-up
e. provide informed consent
f. consult with other physicians
g. keep proper records that support recommending marijuana instead of safe approved alternatives
h. have a good faith relationship with a patient rather than a “marijuana mill”
i. be able to identify substance abusers or the addicted.
j. Forewarn patients on maintaining control of their product

Contrary to regulations governing pharmacies, dispensaries have:
k. no product liability
l. no product regulation
m. no chain of custody
n. no accountability
o. no pharmacists trained in drug-drug interactions of appropriate dose
measures and requirements

Summary.
Over the past 150 years the US moved rapidly away from plants as medicines to purified products, for obvious reasons: the composition of a plant is unknown, the composition of its thousands of constituents are uncontrolled and the long term effects of each of these chemicals, alone or together on body, brain, behavior are unknown. At the time these ballots passed and presently, marijuana’s scientific record was not sufficient to fulfill FDA’s rigorous standards of safety, efficacy, consistent dosing and side effect profile. The evidence for smoked marijuana as a safe and effective treatment for over 12 diseases (e.g. glaucoma, Alzheimer’s disease), including the myriad forms of chronic pain that respond to different class of drugs does not begin to meet professional and FDA standards.
D. RESTRICTIVE MARIJUANA LAWS ARE DRIVEN PRIMARILY BY PERSONAL AND PUBLIC CONSIDERATIONS.

Maintaining restrictions on marijuana are more compelling than ever, as marijuana potency and availability soar, in parallel with escalating scientific evidence of marijuana’s adverse consequences.

Acute effects of marijuana on brain function.
Unlike opioids, marijuana is not likely to cause death by overdose but it resides in Schedule I because of its high abuse liability, and no medical indications – essentially because it adversely disturbs brain function and biology. A Saturday night marijuana binge is intoxicating in the short term, but it can also produce residual cognitive deficits (on learning and memory) for several days. (Marijuana 
research protocols generally wait at least 5-30 days for marijuana to clear, before measuring long term residual cognitive effects). These deficits are readily quantified, are exaggerated in schizophrenics, and refute advocacy for marijuana treatment of Alzheimer’s disease. Who is compromised by marijuana? The student in class who can’t focus, the construction worker at risk for injury, the unemployed who is less likely to find work, the poor, the high school drop-out, the criminal. It is unacceptable for soldiers, airline pilots, nuclear power plant operators, federal workers to test positive for marijuana.
Should it be acceptable for teachers, day care providers, construction workers, students, machine operators, miners, parents, or drivers? A 2009 National Highway Traffic Safety Administration (NHTSA) report showed that more people are driving on weekend nights under the influence of marijuana (8.3%) than alcohol (2.2%). Emergency department mentions of marijuana in the US have increased from 281,619 to 374,435 during 2004-2008, in parallel with linear increases in marijuana potency and marijuana addiction.

Enduring effects: marijuana addiction.
Marijuana is addictive in about 9-10% of users and progression to addiction reportedly is more rapid than progression to nicotine addiction. Abstinence in the heavily addicted unmasks physical and psychological neuroadaptation, manifest by an unnerving withdrawal syndrome. Nation-wide, more 
people harbor a medical (DSM-IV) diagnosis of marijuana abuse/addiction than any other illicit drug and more youth are DSM-IV positive for marijuana than for alcohol, as a percentage of users. Extrapolating from national statistics, an average cost for addiction treatment is $4,000 for ambulatory care and at least four times that amount for residential care. This can add billions of dollars for marijuana treatment needs nationally.
Marijuana and youth.
There is no reasonable evidence that marijuana sold for “medical purposes” will prevent diversion to young adolescents. Our abysmal failure at preventing youth cigarette smoking or alcohol consumption should be our intuitive guide. Youthful users of marijuana are at particular risk. The addiction rates of marijuana are 6-fold higher in young adolescents who initiate marijuana use at age 14 or younger. Early onset of marijuana use is also associated with addiction to other drugs in adulthood, including alcohol and heroin. Some have speculated that genetics, cigarettes smoking, social environment, poverty, child abuse, psychiatric conditions confer this higher risk in the young. But how to explain that adolescent rats exposed to the most active constituent of marijuana, delta-9-tetrahydrocannabinol or THC, only during adolescence, seek heroin at higher rates after they mature into adults compared with matched controls, and display a fundamental change in brain opioid systems long after their last dose? Social, environmental, poverty, child abuse, psychiatric conditions do not apply to inbred rats – the drug alone alters the trajectory of brain and behavioral development.

Marijuana use and neuropsychiatric disorders.
In nine population studies of more than 75,000 people from seven different countries, early marijuana use was found to be associated with an average two-fold higher risk for later-onset psychosis and schizophrenia. The influential medical journal Lancet, which declared in 1995 that “The smoking of cannabis, even long term, is not harmful to health.” changed this conclusion in 2007, by stating that “Research published since 1995, including the systematic review in 
this issue, leads us now to conclude that cannabis use could increase the risk of psychotic illness… governments would do well to invest in sustained and effective education campaigns on the risks to health of taking cannabis.” A current debate is being waged on whether to revise comparative risk assessment in the Global Burden of Disease (GBD) to include the attribution of psychosis to marijuana use. Degenhardt et al argue that the risk assessment should be included because the evidence is as good as that for many other risk
factors in the GBD. Some scientists have estimated that marijuana contributes about 8% to new cases of schizophrenia. If this estimate is accurate, unfettered marijuana access in California conceivably would add 25,000+ cases of schizophrenia, with an estimated cost of caring for this cohort for 30 years in excess of $6 billion (based on a low estimate of $8,000/per patient/year).

Long term heavy marijuana use.
Heavy daily marijuana use across protracted periods can exert harmful effects on brain tissue and mental health. Brain imaging of long-term heavy marijuana users has shown exposure-related structural abnormalities in brain regions critical for learning, memory and emotional responses, with changes associated 
with impaired verbal memory and other symptoms. Abnormal brain size and brain circuitry of adolescent marijuana users have also been recently documented. Compromised academic performance, school drop-out, and a host of other adverse consequences are elevated in high school or college students who use marijuana. Accurate price tags for these lost educational and employment opportunities don’t exist, but at the very least, they should weigh heavily on the citizens’ conscience. Peripheral health is also affected, as marijuana use is associated with increased risks for bronchitis, compromised pulmonary function, precancerous lung changes, cardiovascular events, problematic pregnancies, teratogenic and hormonal effects. Despite this evidence, 2009 was a banner year for marijuana use in our nation. Compared with 2008, 1.5 million more marijuana users were added to the ranks in 2009. The steady decline in marijuana use among youth over the past 6 years was reversed in 2009.
Marijuana use among 12-17 year olds increased by over 7%, with a 14% increase among boys, and a 13% increase among college students. Expanding acceptance of medical marijuana and proliferating availability conceivably are driving reduced perception of harm and a pivotal rise in use.

Authors’ Biography: Bertha K. Madras is a Professor of Psychobiology in the Department of Psychiatry at Harvard Medical School and former Deputy Director for Demand Reduction in the White House Office of National Drug Control Policy.

Source: Sent to Drugwatch International Feb.2 2011

Filed under: Medicine and Marijuana :

Marijuana used for medical purposes has the same long term effect on the user as marijuana used for recreation. Marijuana use can cause impairment of short-term memory, attention, motor skills, reaction time, and the organization and integration of complex information. Marijuana use alters perceptions and creates time distortion and can cause drowsiness and lethargy. Heavy marijuana use can cause apathy, decreased motivation, and impair cognitive performance and can cause mental health problems. Employees who use marijuana off-duty are still effected by it. Impaired cognition that can cause lapses in judgement can remain for a long period. Memory defects can last as long as six weeks. See: Abbie Crites-Leoni, Medicinal Use of Marijuana: Is the Debate a Smoke Screen for Movement Toward Legalization? 19 J. Legal Med. 273, 280 (1998) (citing Schwartz, et al., Short- Term Memory Impairment in Cannabis-Dependent Adolescents, 143 Am. J. Dis. Child. 1214 (1989)

Employers may be liable for the actions of employee who use marijuana especially those employees in safety sensitive positions. The more chronic the use of “medical” marijuana the higher the risk.

VIOLATIONS OF FEDERAL LAW

Will employers have to accommodate marijuana use that violates federal law? Marijuana, remains illegal under federal law because of its “high potential for abuse,” its lack of any “currently accepted medical use in treatment in the United States,” and its “lack of accepted safety for use … under medical supervision.”Gonzales v. Raich, 545 U.S. 1 (2005); United States v. Oakland Cannabis Buyers’ Cooperative, 532 U.S. 483 (2001)

IF THIS BILL PASSES “MEDICAL” MARIJUANA WILL RESULT IN MORE MARIJUANA USE AMONG EMPLOYEES

As consumers we all pay for lost productivity and job-related accidents in the final costs of the produced goods and higher insurance premiums due to workplace accidents. Drug using employees are not as safe. They are 3.6 times more likely to be involved in a work-related accident than their non-using employee, and 5 times more likely to file workers’ compensation claims. As many as 50% of all workers’ compensation claims may involve substance abuse.[ EN1]

The U.S. Postal Service did a study that showed that substance abusers have 55% more accidents, experience 85% more on-the-job injuries, and have a 78% higher rate of absenteeism when compared to non-substance abusing employees.[ EN2] A report by the National Safety Council claimed that 80% of those injured in serious drug-related work accidents are not the drug using employees, but innocent employees and others.[ EN3]

Drug using employees commit workplace crimes. There is a very significant statistical correlation between drug use and criminal conduct.[ EN4]

Substance abuse also causes:

Domestic and financial difficulties for employees;

Poor judgment in employment decision making;

Potential embarrassment to the employer as a result of off-duty conduct, which may be publicized, including criminal charges, diversion of supervisory and managerial time;

Damage to company property; and

Time devoted to discipline and grievance matters.[EN5]

While the studies vary somewhat, it is clear that there is substantial substance abuse in the workplace and it has a powerful negative impact on our economy and productivity. The increased use of “medical” marijuana will magnify all these problems.

References

[EN1] Current, The Truth About Drug Testing: Answers to the Questions Everyone Is Asking, p. 3 (1st Ed., Fort Lauderdale, FL, 1998).

[EN2] “Pre-employment Drug Testing: Association with EAP, Disciplinary, and Medical Claims Information” U.S. Postal Service, Personnel Research and Development Branch, Office of Selection and Evaluation, July 1992.

[EN3] Wisotsky, The Ideology of Drug Testing [Ideology of Drug Testing], 11 Nova L Rev 763, 768 (1987).

[EN4] See Stewart, Proof Positive of Drug Link to Crime, Wall St J, May 28, 1987, at 26, col 3.

[EN5]Alcohol & Drugs in the Workplace: Costs, Control and Controversies, A BNA Special Report [Costs, Control and Controversies], 7 (Bureau of National Affairs, Washington, D.C. 1986)

Source: Attorney David Evans in email to Drug Free America Foundation June 2010

Filed under: Medicine and Marijuana :

Two NIDA-funded studies identify health risks that  underscore the importance of curbing marijuana abuse.

BY PATRICK ZICKLER, NIDA Notes Contributing Writer                             

A large new epidemiological study suggests that marijuana smoke can cause the same types of respiratory damage as tobacco smoke. Significant associations between marijuana smoking and a variety of respiratory diseases also have been confirmed by an extensive review of clinical literature.

MONITORING THE EFFECTS OF TOBACCO AND MARIJUANA

Dr. Brent Moore and colleagues at Yale University, the National Cancer Institute, and the University of Vermont evaluated data from a nationally representative sample of 6,728 adults. Their analysis indicated that a history of more than 100 lifetime episodes of smoking marijuana, with at least one episode in the past month, increased an individual’s risk of chronic bronchitis, coughing on most days, wheezing, chest sounds without a cold, and increased phlegm.

“The most significant difference between tobacco smoke and marijuana smoke is their principal active ingredients—nicotine in tobacco and delta-9-tetrahydrocannabinol (THC) in marijuana. Beyond that, marijuana contains at least as much tar and half again as many carcinogens as smoke from conventional tobacco,” says Dr. Moore. “Quitting marijuana smoking may benefit respiratory health as much as quitting cigarettes, in addition to the clear and considerable health, psychological, and social benefits of no longer abusing an illicit drug.”

The information Dr. Moore and his colleagues analyzed was gathered through the third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994. Participants included 4,789 nonsmokers of either tobacco or marijuana; 1,525 smokers of tobacco but not marijuana; 320 smokers of both marijuana and tobacco; and 94 who smoked marijuana only. On average, marijuana abusers had smoked the drug on 10 of the preceding 30 days, with 16 percent reporting daily or almost daily smoking. Tobacco smokers consumed roughly the same number of cigarettes—averaging 19.2 per day—whether or not they also smoked marijuana. Survey participants answered questions about their experiences of a range of respiratory symptoms and were examined for signs of respiratory abnormalities.

 

 

The researchers concluded that tobacco smokers who also smoked marijuana had a higher prevalence of most respiratory symptoms than tobacco-only smokers. Compared with tobacco-only smokers, however, those who also smoked marijuana were less likely to have had pneumonia during the previous year or to show spirometric evidence of obstructive pulmonary disorder. Commenting on this finding, Dr. Moore says that it is important to note that the marijuana smokers in the sample were significantly younger (average age 31.2 years) than the tobacco smokers (average age 41.5 years). “The marijuana-related respiratory effects correspond to a relatively young population, and NHANES III did not ask participants older than age 59 about drug use,” he adds. “It is likely that respiratory effects will be higher in older marijuana smokers, and, because of the high prevalence of tobacco use among marijuana smokers, there appears to be an increased risk for illness due to cumulative effects of smoking both drugs.”

MARIJUANA’S LONG-TERM PULMONARY EFFECTS

Further evidence of marijuana’s respiratory toxicity emerged from a study conducted by Dr. Donald Tashkin at the University of California, Los Angeles. Dr. Tashkin conducted an extensive review of clinical and epidemiological research to determine the extent to which chronic marijuana smoking might lead to long-term pulmonary effects and diseases similar to those caused by tobacco. Unlike the NHANES III data examined by Dr. Moore, the studies evaluated by Dr. Tashkin made it possible to assess a possible association between marijuana smoking and respiratory cancers.

The results of animal and cell culture studies are mixed with respect to the carcinogenic effects of THC, some studies showing that THC promotes lung cancer growth and others showing an anti-tumoral effect on a variety of malignancies. Although the results of epidemiological studies are also mixed, a large, recently completed case-control study has failed to find a direct link between marijuana use (including heavy use) and lung, throat, or other head and neck cancers. “Nevertheless, there is evidence that suggests precarcinogenic effects in respiratory tissue,” Dr. Tashkin says. “Biopsies of bronchial tissue provide evidence that regular marijuana smoking injures airway epithelial cells, leading to dysregulation of bronchial epithelial cell growth and eventually to possible malignant changes.” Moreover, he adds, because marijuana smokers typically hold their breath four times as long as tobacco smokers after inhaling, marijuana smoking deposits significantly more tar and known carcinogens within the tar, such as polycyclic aromatic hydrocarbons, in the airways. In addition to precancerous changes, Dr. Tashkin found that marijuana smoking is associated with a range of damaging pulmonary effects, including inhibition of the tumor-killing and bactericidal activity of alveolar macrophages, the primary immune cells within the lung.

Taken together, Dr. Tashkin’s survey of clinical and epidemiological studies and Dr. Moore’s assessment of self-reported and clinically observed effects provide an extensive catalog of respiratory and pulmonary damage associated with marijuana smoking. Smokers are subject to:

·         Coughing and phlegm production on most days;

·         Wheezing and other chest sounds;

·         Acute and chronic bronchitis;

·         Injury to airway tissue, including edema (swelling), increased vascularity, and increased mucus secretion;    

·         Impaired function of immune system components (alveolar macrophages) in the lungs.

Moore, B.A., et al. Respiratory effects of marijuana and tobacco use in a U.S. sample. Journal of General Internal Medicine 20(1):33-37, 2005. [Full Text]

Tashkin, D.P. Smoked marijuana as a cause of lung injury. Monaldi Archives for Chest Disease 63(2):93-100, 2005. [Abstract]

Hashibe, M., et al. Marijuana use and aerodigestive tract cancers: a population-based case control study. Cancer Epidemiology, Biomarkers & Prevention (In Press).

Source:NIDA Notes > Vol. 21, No. 1  Oct.2006

 

 

 

 

MINNESOTA COUNTY ATTORNEYS ASSOCIATION

POLICY POSITION

OPPOSING THE MEDICAL USE OF MARIJUANA IN MINNESOTA

Adopted February 16, 2007

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The Minnesota County Attorneys Association (hereafter MCAA) strongly opposes any efforts to use marijuana for medical purposes within the State of Minnesota currently under consideration in the Minnesota Legislature in Senate File No. 345 and House File No. 655 (hereafter S.F. 345). Prosecutors are not alone in our opposition to this proposal. Legalizing marijuana for medicinal uses is also opposed by the Minnesota Sheriff’s Association, the Minnesota Chiefs of Police Association, the National District Attorneys Association, and the U.S. Drug Enforcement Administration. The reasons for the strong opposition to this proposal by these law enforcement organizations are many and are set forth in outline form below.

I. Marijuana is an Addictive Drug That Poses Significant Health Consequences, Even to a Person Using it for “Medical Reasons.”

• Marijuana is an addictive drug that poses significant health consequences to its users, including those who may be using it for medical purposes.
– Marijuana has been proven to be a psychologically addictive drug. Scientists at the National Institute of Drug Abuse have demonstrated that laboratory animals will self administer THC in doses equivalent to those used by humans who smoke marijuana.
– Persons using marijuana, even for medicinal purposes, suffer withdrawal symptoms when use is stopped, such as restlessness, loss of appetite, trouble with sleeping, weight loss and shaky hands.
• The short-term effects of marijuana use include: memory loss, distorted perception, trouble with thinking and problem solving, loss of motor skills, decrease in muscle strength, increased heart rate, and anxiety.
• Long-term use of marijuana may increase the risks of chronic cough, bronchitis, and emphysema, as well as cancer of the head, neck, and lungs.
• Studies have shown smoking marijuana causes a variety of health problems, including cancer, respiratory problems, loss of motor skills, and increased heart rate. It damages the immune system by impairing the ability of T-cells to fight off infections, demonstrating that marijuana can do more harm than good in people with already compromised immune systems.
– Marijuana is a significant health hazard which contains 50-70 percent more carcinogenic hydrocarbons than does tobacco smoke. Using marijuana may promote cancer of the respiratory tract and disrupt the immune system.
– Marijuana contains more than 400 chemicals, including the harmful substances found in tobacco smoke. Smoking one marijuana cigarette deposits almost four times more tar into the lungs than a filtered tobacco cigarette.
– According to the National Institute of Health, studies show that someone who smokes five joints per week may be taking in as many cancer-causing chemicals as someone who smokes a full pack of cigarettes every day.
– Smoked marijuana has also been associated with an increased risk of the same respiratory symptoms as tobacco, including coughing, phlegm production, chronic bronchitis, shortness of breath and wheezing. Because cannabis plants are contaminated with a range of fungal spores, smoking marijuana may also increase the risk of respiratory exposure by infectious organisms (i.e., molds and fungi).
– In a 2003 study, researchers in England found that smoking marijuana for even less than six years causes a marked deterioration in lung function. The study suggests that marijuana use may rob the body of antioxidants that protect cells against damage that can lead to heart disease and cancer.
– Smoking marijuana also weakens the immune system and raises the risk of lung infections. A Columbia University study found that a control group smoking a single marijuana cigarette every other day for a year had a white-blood-cell count that was 39 percent lower than normal, thus damaging the immune system and making the user far more susceptible to infection and sickness.
• Harvard University researchers report that the risk of a heart attack is five times higher than usual in the hour after smoking marijuana.
– Marijuana can cause the heart rate, normally 70 to 80 beats per minute, to increase by 20 to 50 beats per minute or, in some cases, even to double.
• According to two studies, marijuana use narrows arteries in the brain, “similar to patients with high blood pressure and dementia,” and may explain why memory tests are difficult for marijuana users. In addition, “chronic consumers of cannabis lose molecules called CB1 receptors in the brain’s arteries,” leading to blood flow problems in the brain which can cause memory loss, attention deficits, and impaired learning ability.
• The British Medical Journal recently reported: “Cannabis use is associated with an increased risk of developing schizophrenia, consistent with a causal relation. This association is not explained by use of other psychoactive drugs or personality traits relating to social integration.”
– Dr Andrew Campbell, a member of the New South Wales (Australia) Mental Health Review Tribunal, published a study in 2005 which revealed that four out of five individuals with schizophrenia were regular cannabis users when they were teenagers. Between 75-80 percent of the patients involved in the study used cannabis habitually between the ages of 12 and 21.
– A laboratory-controlled study by Yale University scientists, published in 2004, found that THC “transiently induced a range of schizophrenia-like effects in healthy people.
• According to several recent studies, marijuana use has been linked with depression and suicidal thoughts, in addition to schizophrenia. These studies report that weekly marijuana use among teens doubles the risk of developing depression and triples the incidence of suicidal thoughts.
– Marijuana users have more suicidal thoughts and are four times more likely to report symptoms of depression than people who never used the drug.
• Carleton University researchers published a study in 2005 showing that current marijuana users who smoke at least five “joints” per week did significantly worse than non-users when tested on neurocognition tests such as processing speed, memory, and overall IQ.
• Mentions of marijuana use in emergency room visits in this country have risen 176 percent since 1994, surpassing those of heroin. In 2001, marijuana was a contributing factor in more than 110,000 emergency department visits in the United States.
• Users can become dependent on marijuana to the point they must seek treatment to stop abusing it. In 1999, more than 200,000 Americans entered substance abuse treatment primarily for marijuana abuse and dependence.

II. Marijuana Does Not Have Any Proven Medical Value and it is Not Supported for Medicinal Use by Many Prominent National Health Organizations.

Before considering the enactment of this proposed statute, the Legislature is urged to look closely at the medical facts behind this issue. These include:

• Scientific research has not demonstrated that smoked marijuana is helpful as medicine.
• Major medical and health organizations, as well as the clear majority of nationally recognized experts in the fields of medicine, science and scientific research, have concluded that smoking marijuana is not a safe and effective medicine. These organizations include: The American Medical Association, the American Cancer Society, the National Sclerosis Association, the American Glaucoma Association, the American Academy of Ophthalmology, the National Eye Institute, and the National Cancer Institute.
• The American Medical Association (AMA) has rejected pleas to endorse marijuana as a medicine, and instead has urged that marijuana remain a prohibited, Schedule I controlled substance (although it does support further studies, especially those aimed at delivering a “smoke-free inhaled delivery system for marijuana or . . . (THC) to reduce the health hazards associated with the combustion and inhalation of marijuana.”)
• The American Cancer Society “does not advocate inhaling smoke, nor the legalization of marijuana” (although the organization does support carefully controlled clinical studies for alternative delivery methods, specifically a THC skin patch) .
• The American Academy of Pediatrics (AAP) opposes the legalization of marijuana because it believes that “[a]ny change in the legal status of marijuana, even if limited to adults,” [which would include its use for medical purposes] “could affect the prevalence of use among adolescents.” (Similar to the AMA, the AAP supports scientific research on the possible medical use of cannabinoids as opposed to smoked marijuana.)

– The AAP asserted that with regard to marijuana use, “from a public health perspective, even a small increase in use, whether attributable to increased availability or decreased perception of risk, would have significant ramifications.”
• The National Multiple Sclerosis Society (NMSS) states that studies done “have not provided convincing evidence that marijuana benefits people with MS,” and thus marijuana is not a recommended treatment. Furthermore, the NMSS warns that the “long-term use of marijuana may be associated with significant serious side effects.”
• A recent study by the Mayo Clinic, showed THC to be less effective than standard treatments in helping cancer patients regain lost appetites.
• The British Medical Association (BMA) has also voiced extreme concern that down-grading the criminal status of marijuana would “mislead” the public into believing that the drug is safe. [The same holds true in reference to legalizing the use of marijuana for medical purposes.]
– The BMA maintains that marijuana “has been linked to greater risk of heart disease, lung cancer, bronchitis and emphysema.” The 2004 Deputy Chairman of the BMA’s Board of Science said that “[t]he public must be made aware of the harmful effects we know result from smoking this drug.”
• Even the 1999 landmark study of The Institute of Medicine (IOM) which reviewed the supposed medical properties of marijuana (a study often cited by “medical” marijuana advocates) clearly discounts the notion that smoked marijuana is or can become “medicine.” A close review of the IOM study reveals the following:
– While the principal investigators in the IOM study found that the active compounds in marijuana may have medicinal potential for some ailments (the IOM found “… potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation.” ) They pointed out that “[t]he effects of cannabinoids on the symptoms studied are generally modest, and in most cases there are more effective medications [than smoked marijuana].”
– The IOM study concluded that, at best, there in only anecdotal information on the medical benefits of smoked marijuana for some ailments, such as muscle spasticity. For other ailments, such as epilepsy and glaucoma, the study found no evidence of medical value and did not endorse further research.
– The principal investigators of the IOM study explicitly stated that using smoked marijuana in clinical trials “should not be designed to develop it as a licensed drug, but should be a stepping stone to the development of new, safe delivery systems of cannabinoids.”
– The IOM study explained that “smoked marijuana . . . is a crude THC delivery system that also delivers harmful substances.” In addition, “plants contain a variable mixture of biologically active compounds and cannot be expected to provide a precisely defined drug effect.” Therefore, the study concluded that “there is little future in smoked marijuana as a medically approved medication.”

• The Food and Drug Administration and the U.S. Public Health Service have rejected smoking crude marijuana as a medicine. (It is important to note that the Food and Drug Administration (FDA) has never approved medications that are smoked.) This is because not only is it difficult if not impossible to administer safe and regulated dosages of medicine in a smoked form, the harmful chemicals and carcinogens that are by-products of smoking create an entirely new set of health problems.

III. There Already Exists a Legalized Form of “Medical Marijuana” in our Country – It’s Called Marinol (and other approved drugs exist as well to treat these diseases).

• Marinol is an approved pharmaceutical product that is widely available through a doctor’s prescription. It comes in the form of a pill (which can accurately regulate the dose of THC delivered, unlike smoked marijuana), and it is also being studied by researchers for suitability by other delivery methods, such as an inhaler or a patch. The active ingredient of Marinol is synthetic THC, which is the main active chemical found within marijuana. However, unlike marijuana which also contains more than 400 different chemicals (including most of the cancer-causing chemicals found in tobacco smoke), Marinol delivers therapeutic doses of THC in a manner that has been studied and approved by the medical community and the Food and Drug Administration.
• There is, therefore, no medical need to substitute a dangerous and addictive drug like marijuana for an approved prescriptive drug like Marinol that can provide a synthetic form of THC treatment with safe and controlled amounts to assist patients suffering from nausea, vomiting associated with chemo therapy and the loss of appetite associated with AIDS, two of the recognized and approved uses of Marinol.
• Numerous other approved drugs exist to treat the medical problems for which medical use of marijuana would be authorized under S.F. 345. A list of over 20 such medications is set forth in footnote 51 of this document.

IV. Marijuana’s Use As A Medicine Is Contrary to Federal Law as Upheld by Federal Court Decisions (including the U.S. Supreme Court).

• The Federal Controlled Substance Act (CSA) was enacted in 1970 as part of the Comprehensive Drug Abuse Prevention and Control Act. The CSA classifies drugs under five categories (Schedule I–V) based upon their level of danger and acceptance for medical use (among other criteria).
• Schedule I consists of the most restricted drugs under federal law – drugs which have a high potential for abuse, a lack of any accepted medical use, and an absence of any accepted safety criteria for use in medically supervised treatment.
• Marijuana is classified as a Schedule I drug, the manufacture, distribution or possession of which is a federal crime. Manufacture, distribution or possession of marijuana is also a state crime in Minnesota (except possession of small quantities of less than 1.5 oz., which is classified as a petty misdemeanor) .
• States have no authority to change the federal classifications of controlled substances under the CSA (including marijuana) under the Supremacy Clause of the United States Constitution.
• Federal Courts have consistently upheld the classification of marijuana as a Schedule I controlled substance and the fact that marijuana is a dangerous drug with no accepted medical use.
– In 1994, a U.S. Court of Appeals upheld a decision of the Administrator of the Drug Enforcement Administration, who declined to reschedule marijuana from Schedule I to Schedule II of the Controlled Substance Act, finding that marijuana was a drug with “high potential for abuse” which has “no currently accepted medical use in treatment in the United States” and that “there is a lack of accepted safety for use of the drug . . . under medical supervision.”
– The U.S. Court of Appeals found that the DEA Administrator properly relied upon “the testimony of numerous experts that marijuana’s medicinal value has never been proven in sound scientific studies,” noting that physicians supporting use of marijuana for medical purposes (in testimony before an Administrative Hearing Officer) were basing their opinions on “anecdotal evidence, on stories . . . heard from patients, and on . . . impressions about the drug.”
• The most recent and important federal court case on this topic is a 2005 decision of the United States Supreme Court in Gonzales v. Angel, et al., which upheld the authority of federal authorities to enforce federal laws prohibiting the use of marijuana in California for medical purposes as authorized under California law.
– In this decision, the U.S. Supreme Court affirmed that Congress has the authority to regulate controlled substances and “to prohibit entirely the possession or use of substances listed in Schedule I” (including marijuana), except as part of a strictly controlled research project.
• Congress has done just that through passage of the CSA under which marijuana has been designated as a Schedule I drug. In other words, marijuana has been deemed by federal regulation to be an extremely dangerous drug with no general acceptance for medical use.
• If S.F. 345 is passed, it will be in direct conflict with federal law and the U.S. Supreme Court has clearly indicated in Gonzales v. Angel, et al., that federal law takes precedence under the Supremacy Clause of the United States Constitution.
– Consequently, those granted authority to lawfully produce and use marijuana for medical purposes under state law (if S.F. 345 is enacted) will still be committing a federal crime.
• Also, as pointed out by the U.S. Supreme Court in Gonzales v. Angel, et al., legalizing marijuana use for medicinal purposes will clearly lead to increases in the marijuana supply, greater use of marijuana by non-patients and more criminal activity under state law. (See Section VII below for a more specific discussion of this issue.)
• The Minnesota Legislature should not substitute its judgment for that of Congress and the Administrators of the U.S. Drug Enforcement Administration (hereafter DEA) and the Federal Drug Administration (hereafter FDA) as to the fact that marijuana has no general acceptance for medical use and as to defining what is the appropriate way to deliver safe medications to our citizens.
• It is not sound public policy to enact state laws which encourage law abiding citizens to commit federal crimes.

V. Marijuana is a Dangerous Drug that is Associated with Crime and Violence.

• Research shows a link between frequent marijuana use and increased violent behavior.
– Young people who use marijuana weekly are nearly four times more likely than nonusers to engage in violence.
• A large percentage of those arrested for crimes test positive for marijuana. Nationwide, 40 percent of adult males tested positive for marijuana at the time of their arrest.
– Of adult males arrested in the United States for all crimes, 40 percent tested positive for marijuana at the time of their arrest, according to the Director of the U.S. Drug Enforcement Administration.

• In 2003, 3.1 million Americans aged 12 or older used marijuana daily or almost daily in the past year. Of those daily marijuana users, nearly two-thirds “used at least one other illicit drug in the past 12 months.”
– More than half (53.3 percent) of daily marijuana users were also dependent on or abused alcohol or another illicit drug compared to those who were nonusers or used marijuana less than daily.
• There is a strong correlation between drug use and crime. Drug use affects the user’s behavior. In 1997, illicit drug users were:
– approximately 16 times more likely than nonusers to report being arrested for larceny or theft;
– more than 14 times more likely to be arrested for driving under the influence, drunkenness, or liquor law violations; and
– more than 9 times more likely to be arrested on assault charges.

VI. Marijuana is Far More Powerful Today Than it Was 30 Years Ago and it Serves as a Gateway to the Use of Other Illegal Drugs.

• Marijuana is much stronger now than it was decades ago. According to data from the Potency Monitoring Project at the University of Mississippi, the tetrahydrocannabinol (THC) content of commercial-grade marijuana rose from an average of 3.71 percent in 1985 to an average of 5.57 percent in 1998. The average THC content of U.S. produced sinsemilla increased 3.2 percent in 1977 to 12.8 percent in 1997.
– The average THC levels in marijuana in the past two decades has increased form 6 percent to more than 13 percent, with some samples containing THC levels of up to 33 percent (which is far higher than the 1 percent potency levels in marijuana used in the mid-1970’s).
• Marijuana is a gateway drug to the use of other illegal drugs like methamphetamine, heroin and cocaine. Long-term studies of students who use drugs show that very few young people use other illegal drugs without first trying marijuana. The use of marijuana often lowers inhibitions about drug use and exposes users to a culture that encourages the use of other drugs.

• Studies show that of the people who have ever used marijuana, those who started early are more likely to have other problems later on. For example, adults who were early marijuana users were found to be:
– 8 times more likely to have used cocaine.
– 15 times more likely to have used heroin,
– 5 times more likely to develop a need for treatment of abuse or dependence on any drug.
• The Journal of the American Medical Association reported a study of more than 300 sets of same-sex twins. The study found that marijuana-using twins were four times more likely than their siblings to use cocaine and crack cocaine, and five times more likely to use hallucinogens such as LSD.
• The study by Columbia University’s National Center on Addiction and Substance Abuse offers further support for the fact that teens who use marijuana at least once a month are 13 times more likely than other teens to use another drug like cocaine, heroin, or methamphetamine and are almost 26 times more likely than those teens who have never used marijuana to use another illegal drug.
– Other studies show that twelve to seventeen year olds who smoke marijuana are 85 times more likely to use cocaine than those who do not. Sixty percent of adolescents who use marijuana before age 15 will later use cocaine. These correlations are many times higher than the initial relationships found between smoking and lung cancer in the 1964 Surgeon General’s report (nine to ten times higher).
• Health care workers, legal counsel, police and judges indicate that marijuana is a typical precursor to methamphetamine use. For example, Nancy Kneeland, a substance abuse counselor in Idaho, pointed out that “In almost all cases meth users began with alcohol and pot.”

VII. Legalizing Marijuana for Medical Purposes Will Lead to Increased Use of Marijuana By Other Persons, Increased Crime and the Perception that Marijuana is Harmless.
• It is foolish to think that there will be no additional use of marijuana occurring as a result of legalizing its use for medicinal purposes under S.F. 345. First of all there will be no practical way to enforce the law to ensure that marijuana obtained from medical purposes is not used by other persons, including children. Anecdotal information received from prosecutors in other states where similar legislation has been enacted indicates that this is exactly what will occur.
• Under S.F. 345, no person would be subject to arrest or prosecution “for constructive possession, conspiracy, aiding and abetting, being an accessory, or any other criminal offense for being in the presence or vicinity of the medical use.” Consequently, there will be no way to ensure that those who obtain marijuana for a medical purpose will not share it with other persons.
• If this legislation is enacted, it will authorize persons to lawfully grow and sell marijuana. Because marijuana is a widely used illegal substance, incentives will exist for some unscrupulous persons involved in the sale or distribution of “legal marijuana” to steal and distribute the substance for illegal uses.
• Institutions, which are lawfully producing marijuana if this legislation is enacted, would also become easy targets for thieves looking to break in and steal “legally produced” marijuana for illegal distribution purposes.
• It is important to note that the U.S. Supreme Court in its 2005 decision in Gonzales v. Angel, et al., specifically acknowledged that adverse impacts of increasing crime and illegal marijuana use will result from the passage of state laws similar to S.F. 345. In Gonzales, the majority of the U.S. Supreme Court made the following conclusions:
– “The exemption for cultivation by patients and caregivers can only increase the supply of marijuana in the [state] market.”
– “The likelihood that all such production will promptly terminate when patients’ medical needs during their convalescence seems remote, whereas the danger that excesses will satisfy some of the admittedly enormous demand for recreational use seems obvious.”
– “[T]he [fact that the] national and international narcotics trade has thrived in the face of vigorous criminal enforcement efforts suggests that no small number of unscrupulous people will make use of the . . . [state] exemptions to serve their commercial ends whenever it is feasible to do so.”
• Legalizing marijuana for medical purposes will lead many to conclude that the drug is in fact safe.
– In states where the issue of legalizing marijuana for medical purposes has been put on the ballot for voters to decide, well-financed and organized campaigns spearheaded by pro-marijuana legalization groups have contributed to the misperception that marijuana is harmless.
– According to the Office of National Drug Policy, these campaigns are led not by medical professionals or patients-rights groups, but by pro-drug donors and organizations in a cynical attempt to exploit the suffering of sick people.
– This misperception that marijuana is harmless is perhaps most prevalent among teens where it has led to a 140 percent increase in marijuana use among high school seniors from 1994-95.
– The mortal danger of thinking that marijuana is “medicine” was graphically illustrated by a story from California. In the spring of 2004, Irma Perez was “in the thrills of her first experience with the drug ecstasy” when, after taking one ecstasy tablet, she became ill and told friends that she felt like she was “going to die.” Two teenage acquaintances did not seek medical care and instead tried to get Perez to smoke marijuana. When it failed due to her seizures, the friends tried to force feed marijuana leaves to her, “apparently because [they] knew that drug is sometimes used to treat cancer patients.” Irma Perez lost consciousness and died a few days later when she was taken off life support. She was 14 years old.
• Legalizing marijuana for medical purposes will lead to the perception that marijuana is harmless, will result in increased use of it for illegal purposes, and will result in more crime (see Section IV above), endangering our youth and the safety of all citizens in our state.

VIII. Legalizing the Use of Marijuana for Medicinal Purposes Will Increase Dangers Associated With Impaired Driving.

Driving under the influence of marijuana can dramatically impact the safety of citizens within our state as indicated by the following:
• Smoking marijuana impairs the judgment of the smoker and increases the risk of accidents. Many car accidents are caused by drivers using marijuana. In fact, some say just as many as those caused by drivers under the influence of alcohol.
• Marijuana affects many skills required for safe driving: alertness, the ability to concentrate, coordination, and reaction time. These effects can last up to 24 hours after smoking marijuana. Marijuana use can also make it difficult to judge distances and react to signals and signs on the road.
• A roadside study of reckless drivers in Tennessee found that 33 percent of all subjects who were not under the influence of alcohol and who were tested for drugs at the scene of their arrest tested positive for marijuana.
• In a 2003 Canadian study, one in five students admitted to driving within an hour of using marijuana.
• In a 1990 report, the National Transportation Safety Board studied 182 fatal truck accidents and found that just as many of the accidents were caused by drivers using marijuana as were caused by alcohol – 12.5 percent in each case.

Some of the documented consequences of marijuana impaired driving across America include the following:
– The driver of a charter bus, whose 1999 accident resulted in the death of 22 people, had been fired from bus companies in 1989 and 1996 because he tested positive for marijuana four times. A federal investigator confirmed a report that the driver “tested positive for marijuana when he was hospitalized Sunday after the bus veered off a highway and plunged into an embankment.”
– In April 2002, four children and the driver of a van died when the van hit a concrete bridge abutment after veering off the freeway. Investigators reported that the children nicknamed the driver “Smokey” because he regularly smoked marijuana. The driver was found at the crash scene with marijuana in his pocket.
– A former nurse’s aide was convicted in 2003 of murder and sentenced to 50 years in prison for hitting a homeless man with her car and driving home with his mangled body “lodged in the windshield.” The incident happened after a night of drinking and taking drugs, including marijuana. After arriving home, the woman parked her car, with the man still ledged in the windshield, and left him there until he died.
– In April 2005, an eight year old boy was killed when he was run over by an unlicensed 16 year old driver who police believed had been smoking marijuana just before the accident.
– In 2001, George Lynard was convicted of driving with marijuana in his bloodstream, causing a head-on collision that killed a 73 year old man and a 69 year old woman. Lynard appealed this conviction because he allegedly had a “valid prescription” for marijuana. A Nevada judge agreed with Lynard and granted him a new trial. The case has been appealed to the Nevada Supreme Court.
– Duane Baehler, 47, of Tulsa, Oklahoma was “involved in a fiery crash that killed his teenage son” in 2003. Police reported that Baehler had methamphetamine, cocaine and marijuana in his system at the time of the accident.

IX. Summary

For all of the reasons outlined above, legalizing marijuana for medicinal purposes is not in the interests of protecting the public safety of Minnesota’s citizens, nor is it in the best interest of persons who suffer from the types of chronic or debilitating diseases or medical conditions specified in S.F. 345. Marijuana is a dangerous addictive drug that poses significant health risks to those who use it. Legalizing marijuana for “medicinal use” will only increase the access of both youth and adults to marijuana, which will not only increase the likelihood of violent behavior but will often lead to experimentation with other even more dangerous illegal drugs. As noted by the Office of National Drug Control Policy;

“Even if smoking marijuana makes people “feel better”, that is not enough to call it a medicine. If that were the case, tobacco cigarettes could be called medicine because they are often said to make people feel better. For that matter, heroin certainly makes people “feel better” (at least initially), but no one would suggest using heroin to treat a sick person.”

The bottom line is that at the present time, there is no proven medicinal value in using marijuana to treat illnesses or disease and, in fact, a legal form of THC, which can be controlled for its strength and which delivers none of the harmful side effects of smoking marijuana already exists for use through a doctor’s prescription.

Marijuana use, even by those using it for medicinal purposes, is significantly harmful to the body. Smoking pot delivers three to five times the amount of tars and carbon monoxide into the body as does smoking cigarettes and it also damages pulmonary immunity and impairs oxygen diffusion. We agree with the Office of National Drug Control Policy, that it is hard to understand how changes such as these could be good for someone dying of cancer or AIDS.

Perhaps most importantly of all, as a prohibited Schedule I controlled substance under the Federal Controlled Substance Act (CSA), the manufacture, distribution or possession of marijuana is a federal crime. The Minnesota Legislature should not substitute its judgment for that of Congress and the Administrators of the U.S. Drug Enforcement Administration and the Federal Drug Administration as to the fact that marijuana is a dangerous drug with no accepted medical use and as to determining what is the appropriate way to deliver safe medications to our citizens. It is not sound public policy to enact state laws which encourage law abiding citizens to commit federal crimes.

It is for all these reasons that the MCAA strongly opposes the adoption of the law in Minnesota which would legalize the use of marijuana for medicinal purposes. This opposition is shared by associations representing our law enforcement partners within Minnesota.

Filed under: Medicine and Marijuana :

Bertha K. Madras, Ph.D., Deputy Director, Demand Reduction, Office of National Drug Control Policy

This is the second in a series of articles on how specific drugs affect the brain and body.

The brain drain
Myths that downplay the risks associated with drug use permeate youth culture and are embraced to rationalize experimentation with addictive drugs. Scientific evidence can help educators and parents de-bunk these dangerous myths.
Adolescents and young adults are the principal age groups using addictive drugs and are at the greatest risk for experiencing adverse consequences as a result of the early introduction of drugs into their brains. Early drug use can compromise academic achievement, school attendance, homework, participation in extracurricular activities, and school behavior. Drug use at a young age is also associated with addiction, violence, accidents, delinquency, criminal activity, and even death. As with any major public health problem, the inability to predict which young people will suffer detrimental, potentially life-threatening consequences from drug use is itself a reason to engage in widespread prevention efforts.
The brain has approximately one hundred billion nerve cells, with each cell producing 10,000 or more “wires” that connect with other cells. A critical component of brain development is accurate “wiring.” Imaging technologies that compare adolescent brains with those of adults have shown that the “wiring” of the adolescent brain is still immature, compared to the adult brain. Exposure to drugs before brain maturation may affect brain development, interfering with the wiring and circuitry of the brain in much the same way as a computer technician can damage a circuit board by zapping it with electrical jolts during the assembly process.
In the short term, a single dose of a drug can result in poor performance in a school or sports activity, accidents, violence, unplanned risky behavior, and the risk of overdosing. It can trigger repeated drug use, which is associated with serious health consequences, loss of desire to fulfill obligations, truancy, disorderly conduct, and social or family problems. Repeated drug use can also lead to addiction. Studies show that the earlier an adolescent begins using drugs, the more likely he or she will be to develop a substance abuse problem or become addicted to substances. Conversely, if an individual does not start using drugs during the teen years, he or she is less likely to initiate or develop a substance abuse problem later in life.
Statistics make a compelling case for focusing on preventing youth drug use. In 2006, among persons with substance dependence or abuse, the percentage dependent on or abusing illicit drugs was much higher in the 12-17 age group (57.4 percent) than among 18- to 25-year-olds (36.9 percent) or adults age 26 or older (24.1 percent), according to the 2007 National Survey on Drug Use and Health (NSDUH). One hundred eighty-one thousand youth (12-17 year-olds) received treatment for alcohol or illicit drugs (NSDUH 2007). Although prevention is a key to interrupting the progression to addiction, deterring marijuana use and prescription-drug misuse is particularly challenging because of the myths associated with these drugs.
Myth No. 1: Marijuana is a ‘soft’ drug
Marijuana use should not be considered a rite of passage. It is neither a “soft” drug nor a safe drug. The effects of marijuana can last up to 24 hours after administration, continuing to compromise reflexes, cognitive ability, and other brain functions. Driving while under the influence of marijuana is dangerous, as the use of this drug can impair motor function, concentration, and perception, thereby increasing the likelihood of road accidents. According to the 2006 Monitoring the Future study, the percentage of high school students who reported driving under the influence of marijuana (10.6 percent) was nearly as high as the percentage of those driving under the influence of alcohol (12.4 percent).
Accumulating evidence makes a forceful case for abstention from marijuana use. One study found that high school students who abstained from marijuana functioned better than occasional or frequent users during high school and during the transition to adulthood. During high school, abstainers fared better than experimenters and frequent users of marijuana on the basis of school engagement, deviant behavior, family and peer relations, and mental health. They were more likely to do homework and get better grades. When they turned 23, abstainers were twice as likely to graduate from college and much less likely to steal or to sell illicit drugs.
A long-term analysis of marijuana potency funded by the National Institute on Drug Abuse (NIDA) reveals that the strength of marijuana has increased substantially over the past two decades. Today, marijuana is more potent than ever before, and this elevated potency may be leading to an increase in teen marijuana treatment admissions and a rise in the number of marijuana-related emergency room episodes.

These worrisome results add to the growing body of evidence that the effects of youth marijuana use may endure into adulthood. Adolescents who used marijuana are twice as likely to use illicit drugs when they become young adults. In fact, in one study, individuals of twin pairs who used marijuana by age 17 had 2.1 to 5.2 times higher risk of other drug use (cocaine, heroin), alcohol dependence, and drug abuse/dependence than their co-twin who did not use before the age of 17.
Experiments with animals seem to corroborate these findings. Animals, which were not subject to environmental stressors, were exposed to the active ingredient of marijuana during adolescence. They were given a drug-free period and then, as adults, were given access to heroin. After maturation into adulthood, the early-exposed animals consumed higher amounts of heroin and showed greater heroin-seeking behavior than the non-exposed group. The effects of early exposure to marijuana were not restricted to behavior: components of the system in the brain that modulates pain and pleasure were changed in the animals’ adult brains, after exposure during adolescence.
Collectively, these findings suggest that marijuana, introduced during adolescence, may influence the biology of the brain, promote drug-seeking behavior, and affect social function during the transition to adulthood.
How addictive is marijuana, and how realistic is the perception that it is a “soft” drug? The 2007 NSDUH reported that in 2006, among adults aged 18 or older who first tried marijuana at age 14 or younger, 12.9 percent were classified with illicit drug dependence or abuse, a considerably higher number than the percentage (2.2 percent) who had first used marijuana at age 18 or older. Marijuana also ranked first as the most reported illicit drug resulting in abuse/dependence.
Early, frequent use of marijuana may be an independent risk factor for psychosis—even if use precedes the onset of schizophrenia or another form of psychosis. Marijuana may induce acute psychotic symptoms in vulnerable people and a persistent psychosis in some individuals who have not had prior signs of psychosis. Marijuana may also exacerbate psychosis in people with symptoms of schizophrenia, and these effects can persist after the drug is cleared from the body.
As with other addictive drugs, heavy marijuana use has many health and social consequences. Heavy marijuana use into adulthood creates an expanding set of health risks, including exercise-induced heart pain and reduced lung function, as well as objective and self-reports of adverse social consequences. During pregnancy, heavy marijuana use can lead to impaired fetal growth and development.
Myth No. 2: Prescription drugs used for psychoactive effects are safer than “street drugs”
Several classes of controlled prescription drugs—medications prescribed by doctors for legitimate medical purposes—have abuse and addiction potential. These include opioids prescribed for the management of pain, drugs to treat attentional problems and anxiety, and drugs to promote sleep. These drugs are safe and effective when used according to doctors’ prescriptions and advice. Abuse or non-medical use of prescription drugs is the use of drugs not prescribed for the individual, use of drugs solely for the experience or feelings they cause, or use of drugs for which the intended person has made false or inaccurate claims to obtain them.
A disturbing trend emerged last year, when NSDUH reported that first-time non-medical users of prescription drugs now equal first time users of marijuana and that misuse of prescription drugs among 12- and 13-year-olds exceeds marijuana use. The misuse of opioid pain killers is of particular concern because of the large number of users, the high addictive potential, and the potential to induce overdose or death.
Also of concern is that approximately 598,542 visits to emergency departments during 2005 involved the non-medical use of prescription drugs or over-the-counter medication or dietary supplements, with the majority involving multiple drugs (Drug Abuse Warning Network, 2005).
There are many factors contributing to the increased misuse of prescription drugs. There is a perception among young people that prescription drugs are safer than illicit street drugs. Moreover, many teens are not aware of the consequences of prescription drug misuse. Prescription drugs are also more easily attainable from friends and family.
There are indications that long-term misuse of pain medications can lead to addiction, and that intravenous use of this class of drugs places a person at increased risk of HIV and other infectious diseases. Additionally, because many of the prescription drugs that are abused share similarities with illicit drugs in the way they act on the brain, it is probable that some of the harmful consequences will be the same.
It is important for adults to recognize this growing problem and to help young people understand the risks of using prescription drugs non-medically. When used properly, under the supervision of a doctor, prescription drugs can be safe and effective. Used improperly, however, they can have serious consequences.
Preventing initiation and identifying problem use
Using marijuana or misusing prescription drugs in any amount is not safe. Scientists, educators, counselors, community coalitions, prevention experts, and others are working to expose dangerous drug myths and to increase awareness of the adverse physical, mental, emotional, and behavioral changes that can be associated with these substances. Testing students for drug use may help prevent initiation and identify drug users at an early stage, before a dependency sets in, thereby protecting adolescents and their fragile brains from the harmful effects of drug-using behavior.
A complete list of citations for this article is available at www.randomstudentdrugtesting.org

Source: Strategies for Success, Isssue 2 Vol.1 Fall 2007

Filed under: Medicine and Marijuana :

The campaign to legitimize what is called “medical” marijuana is based on two propositions: that science views marijuana as medicine, and that DEA targets sick and dying people using the drug. Neither proposition is true. Smoked marijuana has not withstood the rigors of science – it is not medicine and it is not safe. DEA targets criminals engaged in cultivation and trafficking, not the sick and dying. No state has legalized the trafficking of marijuana, including the twelve states that have decriminalized certain marijuana use.

SMOKED MARIJUANA IS NOT MEDICINE
There is no consensus of medical evidence that smoking marijuana helps patients. Congress enacted laws against marijuana in 1970 based in part on its conclusion that marijuana has no scientifically proven medical value. The Food and Drug Administration (FDA) is the federal agency responsible for approving drugs as safe and effective medicine based on valid scientific data. FDA has not approved smoked marijuana for any condition or disease. The FDA noted that “there is currently sound evidence that smoked marijuana is harmful,” and “that no sound scientific studies supported medical use of marijuana for treatment in the United States, and no animal or human data supported the safety or efficacy of marijuana for general medical use.” 2
In 2001, the Supreme Court affirmed Congress’s 1970 judgment about marijuana in United States v. Oakland Cannabis Buyers’ Cooperative et al., 532 U.S. 438 (2001), which held that, given the absence of medical usefulness, medical necessity is not a defense to marijuana prosecution. Furthermore, in Gonzales v. Raich, 125 S.Ct. 2195 (2005), the Supreme Court reaffirmed that the authority of Congress to regulate the use of potentially harmful substances through the federal Controlled Substances Act includes the authority to regulate marijuana of a purely intrastate character, regardless of a state law purporting to authorize “medical” use of marijuana.
The DEA and the federal government are not alone in viewing smoked marijuana as having no documented medical value. Voices in the medical community likewise do not accept smoked marijuana as medicine:
The American Medical Association has rejected pleas to endorse marijuana as medicine, and instead has urged that marijuana remain a prohibited, Schedule I controlled substance, at least until more research is done. 3

• The American Cancer Society “does not advocate inhaling smoke, nor the legalization of marijuana,” although the organization does support carefully controlled clinical studies for alternative delivery methods, specifically a THC skin patch. 4

• The American Academy of Pediatrics (AAP) believes that “[a]ny change in the legal status of marijuana, even if limited to adults, could affect the prevalence of use among adolescents.” While it supports scientific research on the possible medical use of cannabinoids as opposed to smoked marijuana, it opposes the legalization of marijuana. 5

• The National Multiple Sclerosis Society (NMSS) states that studies done to date “have not provided convincing evidence that marijuana benefits people with MS,” and thus marijuana is not a recommended treatment. Furthermore, the NMSS warns that the “long-term use of marijuana may be associated with significant serious side effects.” 6

• The British Medical Association (BMA) voiced extreme concern that down-grading the criminal status of marijuana would “mislead” the public into believing that the drug is safe. The BMA maintains that marijuana “has been linked to greater risk of heart disease, lung cancer, bronchitis and emphysema.” 7 The 2004 Deputy Chairman of the BMA’s Board of Science said that “[t]he public must be made aware of the harmful effects we know result from smoking this drug.”8

• The American Academy of Pediatrics asserted that with regard to marijuana use, “from a public health perspective, even a small increase in use, whether attributable to increased availability or decreased perception of risk, would have significant ramifications.” 9
In 1999, The Institute of Medicine (IOM) released a landmark study reviewing the supposed medical properties of marijuana. The study is frequently cited by “medical” marijuana advocates, but in fact severely undermines their arguments.
After release of the IOM study, the principal investigators cautioned that the active compounds in marijuana may have medicinal potential and therefore should be researched further. However, the study concluded that “there is little future in smoked marijuana as a medically approved medication.” 10

• For some ailments, the IOM found “…potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation.” 11 However, it pointed out that “[t]he effects of cannabinoids on the symptoms studied are generally modest, and in most cases there are more effective medications [than smoked marijuana].”12

• The study concluded that, at best, there is only anecdotal information on the medical benefits of smoked marijuana for some ailments, such as muscle spasticity. For other ailments, such as epilepsy and glaucoma, the study found no evidence of medical value and did not endorse further research. 13

• The IOM study explained that “smoked marijuana . . . is a crude THC delivery system that also delivers harmful substances.” In addition, “plants contain a variable mixture of biologically active compounds and cannot be expected to provide a precisely defined drug effect.” Therefore, the study concluded that “there is little future in smoked marijuana as a medically approved medication.” 14

• The principal investigators explicitly stated that using smoked marijuana in clinical trials “should not be designed to develop it as a licensed drug, but should be a stepping stone to the development of new, safe delivery systems of cannabinoids.” 15
Thus, even scientists and researchers who believe that certain active ingredients in marijuana may have potential medicinal value openly discount the notion that smoked marijuana is or can become “medicine.” DEA has approved and will continue to approve research into whether THC has any medicinal use. As of May 8, 2006, DEA had registered every one of the 163 researchers who requested to use marijuana in studies and who met Department of Health and Human Services standards. 16
One of those researchers, The Center for Medicinal Cannabis Research (CMCR), conducts studies “to ascertain the general medical safety and efficacy of cannabis and cannabis products and examine alternative forms of cannabis administration.”17 The CMCR currently has 11 on-going studies involving marijuana and the efficacy of cannabis and cannabis compounds as they relate to medical conditions such as HIV, cancer pain, MS, and nausea.18
At present, however, the clear weight of the evidence is that smoked marijuana is harmful. No matter what medical condition has been studied, other drugs already approved by the FDA, such as Marinol – a pill form of synthetic THC – have been proven to be safer and more effective than smoked marijuana.
MARIJUANA IS DANGEROUS TO THE USER AND OTHERS
Legalization of marijuana, no matter how it begins, will come at the expense of our children and public safety. It will create dependency and treatment issues, and open the door to use of other drugs, impaired health, delinquent behavior, and drugged drivers. This is not the marijuana of the 1970’s; today’s marijuana is far more powerful. Average THC levels of seized marijuana rose from less than one per cent in the mid-1970’s to a national average of over eight per cent in 2004. 19
And the potency of “B.C. Bud” is roughly twice the national average – ranging from 15 per cent to as high as 25 per cent THC content.20
Dependency and Treatment:
o Adolescents are at highest risk for marijuana addiction, as they are “three times more likely than adults to develop dependency.” 21
This is borne out by the fact that treatment admission rates for adolescents reporting marijuana as the primary substance of abuse increased from 32 to 65 per cent between 1993 and 2003.22 More young people ages 12-17 entered treatment in 2003 for marijuana dependency than for alcohol and all other illegal drugs combined.23

• “Research shows that use of [marijuana] can lead to dependence. Some heavy users of marijuana develop withdrawal symptoms when they have not used the drug for a period of time. Marijuana use, in fact, is often associated with behavior that meets the criteria for substance dependence established by the American Psychiatric Association.” 24

• Of the 19.1 million Americans aged 12 or older who used illicit drugs in the past 30 days in 2004, 14.6 million used marijuana, making it the most commonly used illicit drug in 2004. 25

• Among all ages, marijuana was the most common illicit drug responsible for treatment admissions in 2003, accounting for 15 per cent of all admissions — outdistancing heroin, the next most prevalent cause. 26

• In 2003, 20 per cent (185,239) of the 919,833 adults admitted to treatment for illegal drug abuse cited marijuana as their primary drug of abuse.27
Marijuana as a Precursor to Abuse of Other Drugs:
o Marijuana is a frequent precursor to the use of more dangerous drugs, and signals a significantly enhanced likelihood of drug problems in adult life. The Journal of the American Medical Association reported, based on a study of 300 sets of twins, “that marijuana-using twins were four times more likely than their siblings to use cocaine and crack cocaine, and five times more likely to use hallucinogens such as LSD.” 28
• Long-term studies on patterns of drug usage among young people show that very few of them use other drugs without first starting with marijuana. For example, one study found that among adults (age 26 and older) who had used cocaine, 62 per cent had initiated marijuana use before age 15. By contrast, less than one per cent of adults who never tried marijuana went on to use cocaine. 29

• Columbia University’s National Center on Addiction and Substance Abuse reports that teens who used marijuana at least once in the last month are 13 times likelier than other teens to use another drug like cocaine, heroin, or methamphetamine, and almost 26 times likelier than those teens who have never used marijuana to use another drug. 30

• Marijuana use in early adolescence is particularly ominous. Adults who were early marijuana users were found to be five times more likely to become dependent on any drug, eight times more likely to use cocaine in the future, and fifteen times more likely to use heroin later in life. 31

• In 2003, 3.1 million Americans aged 12 or older used marijuana daily or almost daily in the past year. Of those daily marijuana users, nearly two-thirds “used at least one other illicit drug in the past 12 months.” More than half (53.3 per cent) of daily marijuana users were also dependent on or abused alcohol or another illicit drug compared to those who were nonusers or used marijuana less than daily. 32

• Healthcare workers, legal counsel, police and judges indicate that marijuana is a typical precursor to methamphetamine. For instance, Nancy Kneeland, a substance abuse counselor in Idaho, pointed out that “in almost all cases meth users began with alcohol and pot.” 33
Mental and Physical Health Issues Related to Marijuana:
John Walters, Director of the Office of National Drug Control Policy, Charles G. Curie, Administrator of the Substance Abuse and Mental Health Services Administration, and experts and scientists from leading mental health organizations joined together in May 005 to warn parents about the mental health dangers marijuana poses to teens. According to several recent studies, marijuana use has been linked with depression and suicidal thoughts, in addition to schizophrenia. These studies report that weekly marijuana use among teens doubles the risk of developing depression and triples the incidence of suicidal thoughts. 34

• Dr. Andrew Campbell, a member of the New South Wales (Australia) Mental Health Review Tribunal, published a study in 2005 which revealed that four out of five individuals with schizophrenia were regular cannabis users when they were teenagers. Between 75-80 per cent of the patients involved in the study used cannabis habitually between the ages of 12 and 21. 35 In addition, a laboratory-controlled study by Yale scientists, published in 2004, found that THC “transiently induced a range of schizophrenia-like effects in healthy people.”36

• Smoked marijuana has also been associated with an increased risk of the same respiratory symptoms as tobacco, including coughing, phlegm production, chronic bronchitis, shortness of breath and wheezing. Because cannabis plants are contaminated with a range of fungal spores, smoking marijuana may also increase the risk of respiratory exposure by infectious organisms (i.e., molds and fungi). 37

• Marijuana takes the risks of tobacco and raises them: marijuana smoke contains more than 400 chemicals and increases the risk of serious health consequences, including lung damage. 38

• According to two studies, marijuana use narrows arteries in the brain, “similar to patients with high blood pressure and dementia,” and may explain why memory tests are difficult for marijuana users. In addition, “chronic consumers of cannabis lose molecules called CB1 receptors in the brain’s arteries,” leading to blood flow problems in the brain which can cause memory loss, attention deficits, and impaired learning ability. 39

• Carleton University researchers published a study in 2005 showing that current marijuana users who smoke at least five “joints” per week did significantly worse than non-users when tested on neurocognition tests such as processing speed, memory, and overall IQ. 40

Delinquent Behaviors and Drugged Driving:
o In 2002, the percentage of young people engaging in delinquent behaviors “rose with [the] increasing frequency of marijuana use.” For example, according to a National Survey on Drug Use and Health (NSDUH) report, 42.2 per cent of youths who smoked marijuana 300 or more days per year and 37.1 per cent of those who did so 50-99 days took part in serious fighting at school or work. Only 18.2 per cent of those who did not use marijuana in the past year engaged in serious fighting. 41

• A large shock trauma unit conducting an ongoing study found that 17 per cent (one in six) of crash victims tested positive for marijuana. The rates were slightly higher for crash victims under the age of eighteen, 19 per cent of whom tested positive for marijuana. 42

• In a study of high school classes in 2000 and 2001, about 28,000 seniors each year admitted that they were in at least one accident after using marijuana. 43

• Approximately 15 per cent of teens reported driving under the influence of marijuana. This is almost equal to the percentage of teens who reported driving under the influence of alcohol (16 per cent). 44

• A study of motorists pulled over for reckless driving showed that, among those who were not impaired by alcohol, 45 per cent tested positive for marijuana. 45

• The National Highway Traffic Safety Administration (NHTSA) has found that marijuana significantly impairs one’s ability to safely operate a motor vehicle. According to its report, “[e]pidemiology data from road traffic arrests and fatalities indicate that after alcohol, marijuana is the most frequently detected psychoactive substance among driving populations.” Problems reported include: decreased car handling performance, inability to maintain headway, impaired time and distance estimation, increased reaction times, sleepiness, lack of motor coordination, and impaired sustained vigilance. 46
Some of the consequences of marijuana-impaired driving are startling:
The driver of a charter bus, whose 1999 accident resulted in the death of 22 people, had been fired from bus companies in 1989 and 1996 because he tested positive for marijuana four times. A federal investigator confirmed a report that the driver “tested positive for marijuana when he was hospitalized Sunday after the bus veered off a highway and plunged into an embankment.” 47

• In April 2002, four children and the driver of a van died when the van hit a concrete bridge abutment after veering off the freeway. Investigators reported that the children nicknamed the driver “Smokey” because he regularly smoked marijuana. The driver was found at the crash scene with marijuana in his pocket. 48

• A former nurse’s aide was convicted in 2003 of murder and sentenced to 50 years in prison for hitting a homeless man with her car and driving home with his mangled body “lodged in the windshield.” The incident happened after a night of drinking and taking drugs, including marijuana. After arriving home, the woman parked her car, with the man still lodged in the windshield, and left him there until he died. 49

• In April 2005, an eight year-old boy was killed when he was run over by an unlicensed 16 year-old driver who police believed had been smoking marijuana just before the accident. 50

• In 2001, George Lynard was convicted of driving with marijuana in his bloodstream, causing a head-on collision that killed a 73 year-old man and a 69 year-old woman. Lynard appealed this conviction because he allegedly had a “valid prescription” for marijuana. A Nevada judge agreed with Lynard and granted him a new trial. 51 The case has been appealed to the Nevada Supreme Court.52

• Duane Baehler, 47, of Tulsa, Okalahoma was “involved in a fiery crash that killed his teenage son” in 2003. Police reported that Baehler had methamphetamine, cocaine and marijuana in his system at the time of the accident. 53
Marijuana also creates hazards that are not always predictable. In August 2004, two Philadelphia firefighters died battling a fire that started because of tangled wires and lamps used to grow marijuana in a basement closet. 54

MARIJUANA AND INCARCERATION
Federal marijuana investigations and prosecutions usually involve hundreds of pounds of marijuana. Few defendants are incarcerated in federal prison for simple possession of marijuana.
o In 2001, there were 24,299 offenders sentenced in federal court on drug charges. Of those, only 2.3 per cent (186 people) were sentenced for simple possession. 55
In addition, it is important to recognize that many inmates were initially charged with more serious crimes but negotiated reduced charges to simple possession through plea agreements.56

• According to the latest survey data in a 2005 ONDCP study, marijuana accounted for 13 per cent of all state drug offenders in 1997, and of the inmates convicted of marijuana offenses, only 0.7 per cent were incarcerated for marijuana possession alone. 57
THE FOREIGN EXPERIENCE
The Netherlands
o Due to international pressure on permissive Dutch cannabis policy and domestic complaints over the spread of marijuana “coffee shops,” the government of the Netherlands has reconsidered its legalization measures. After marijuana became normalized, consumption nearly tripled – from 15 per cent to 44 per cent – among 18 to 20 year-old Dutch youth. 58
As a result of stricter local government policies, the number of cannabis “coffeehouses” in the Netherlands was reduced – from 1,179 in 199759 to 737 in 2004, a 37 per cent decrease in 7 years.60

• About 70 per cent of Dutch towns have a zero-tolerance policy toward cannabis cafes.61

• In August 2004, after local governments began clamping down on cannabis “coffeehouses” seven years earlier, the government of the Netherlands formally announced a shift in its cannabis policy through the United National International Narcotics Control Board (INCB). According to “an inter-ministerial policy paper on cannabis, the government acknowledged that ‘cannabis is not harmless’ – neither for the abusers, nor for the community.” Netherlands intends to reduce the number of coffee shops (especially those near border areas and schools), closely monitor drug tourism, and implement an action plan to discourage cannabis use. This public policy change brings the Netherlands “closer towards full compliance with the international drug control treaties with regard to cannabis.” 62

• Dr. Ernest Bunning, formerly with Holland’s Ministry of Health and a principal proponent of that country’s liberal drug philosophy, has acknowledged that, “there are young people who abuse soft drugs . . . particularly those that have a high THC [content]. The place that cannabis takes in their lives becomes so dominant they don’t have space for the other important things in life. They crawl out of bed in the morning, grab a joint, don’t work, smoke another joint. They don’t know what to do with their lives.” 63
Switzerland
Liberalization of marijuana laws in Switzerland has likewise produced damaging results. After liberalization, Switzerland became a magnet for drug users from many other countries. In 1987, Zurich permitted drug use and sales in a part of the city called Platzpitz, dubbed “Needle Park.” By 1992, the number of regular drug users at the park reportedly swelled from a “few hundred at the outset in 1987 to about 20,000.” The area around the park became crime-ridden, forcing closure of the park. The experiment has since been terminated. 64
Canada:
After a large decline in the 1980s, marijuana use among teens increased during the 1990s as young people became “confused about the state of federal pot law” in the wake of an aggressive decriminalization campaign, according to a special adviser to Health Canada’s Director General of drug strategy. Several Canadian drug surveys show that marijuana use among Canadian youth has steadily climbed to surpass its 26-year peak, rising to 29.6 per cent of youth in grades 7-12 in 2003. 65
United Kingdom:
In March 2005, British Home Secretary Charles Clarke took the unprecedented step of calling “for a rethink on Labour’s legal downgrading of cannabis” from a Class B to a Class C substance. Mr. Clarke requested that the Advisory Council on the Misuse of Drugs complete a new report, taking into account recent studies showing a link between cannabis and psychosis and also considering the more potent cannabis referred to as “skunk.” 66

• In 2005, during a general election speech to concerned parents, British Prime Minister Tony Blair noted that medical evidence increasingly suggests that cannabis is not as harmless as people think and warned parents that young people who smoke cannabis could move on to harder drugs. 67
THE LEGALIZATION LOBBY
The proposition that smoked marijuana is “medicine” is, in sum, false – trickery used by those promoting wholesale legalization. When a statute dramatically reducing penalties for “medical” marijuana took effect in Maryland in October 2003, a defense attorney noted that “there are a whole bunch of people who like marijuana who can now try to use this defense.” The attorney observed that lawyers would be “neglecting their clients if they did not try to find out what ‘physical, emotional or psychological'” condition could be enlisted to develop a defense to justify a defendant’s using the drug. “Sometimes people are self-medicating without even realizing it,'” he said. 68

Ed Rosenthal, senior editor of High Times, a pro-drug magazine, once revealed the legalizer strategy behind the “medical” marijuana movement. While addressing an effort to seek public sympathy for glaucoma patients, he said, “I have to tell you that I also use marijuana medically. I have a latent glaucoma which has never been diagnosed. The reason why it’s never been diagnosed is because I’ve been treating it.” He continued, “I have to be honest, there is another reason why I do use marijuana . . . and that is because I like to get high. Marijuana is fun.” 69

• A few billionaires-not broad grassroots support-started and sustain the “medical” marijuana and drug legalization movements in the United States. Without their money and influence, the drug legalization movement would shrivel. According to National Families in Action, four individuals – George Soros, Peter Lewis, George Zimmer and John Sperling – contributed $1,510,000 to the effort to pass a “medical” marijuana law in California in 1996, a sum representing nearly 60 per cent of the total contributions. 70

• In 2000, The New York Times interviewed Ethan Nadelmann, Director of the Lindesmith Center. Responding to criticism that the medical marijuana issue is a stalking horse for drug legalization, Mr. Nadelmann stated: “Will it help lead toward marijuana legalization? . . . I hope so.” 71

• In 2004, Alaska voters faced a ballot initiative that would have made it legal for adults age 21 and older to possess, grow, buy, or give away marijuana. The measure also called for state regulation and taxation of the drug. The campaign was funded almost entirely by the Washington, D.C.-based Marijuana Policy Project, which provided “almost all” the $857,000 taken in by the pro-marijuana campaign. Fortunately, Alaskan voters rejected the initiative. 72

• In October 2005, Denver voters passed Initiative 100 decriminalizing marijuana based on incomplete and misleading campaign advertisements put forth by the Safer Alternative For Enjoyable Recreation (SAFER). A Denver City Councilman complained that the group used the slogan “Make Denver SAFER” on billboards and campaign signs to mislead the voters into thinking that the initiative supported increased police staffing. Indeed, the Denver voters were never informed of the initiative’s true intent to decriminalize marijuana. 73

• The legalization movement is not simply a harmless academic exercise. The mortal danger of thinking that marijuana is “medicine” was graphically illustrated by a story from California. In the spring of 2004, Irma Perez was “in the throes of her first experience with the drug ecstasy” when, after taking one ecstasy tablet, she became ill and told friends that she felt like she was “going to die.” Two teenage acquaintances did not seek medical care and instead tried to get Perez to smoke marijuana. When that failed due to her seizures, the friends tried to force-feed marijuana leaves to her, “apparently because they knew that drug is sometimes used to treat cancer patients.” Irma Perez lost consciousness and died a few days later when she was taken off life support. She was 14 years old. 74
STILL, THERE’S GOOD NEWS
Continued Declines in Marijuana Use among Youth
In 2005, the Monitoring the Future (MTF) survey recorded an overall 19.1 per cent decrease in current use of illegal drugs between 2001 and 2005, edging the nation closer to its five-year goal of a 25 per cent reduction in illicit drug use in 2006. Specific to marijuana, the 2005 MTF survey showed:
Between 2001 and 2005, marijuana use dropped in all three categories: lifetime (13%), past year (15%) and 30-day use (19%). Current marijuana use decreased 28 per cent among 8th graders (from 9.2% to 6.6%), and 23 per cent among 10th graders (from 19.8 per cent to 15.2%). 75
Increased Eradication
As of September 20, 2005, DEA’s Domestic Cannabis Eradication/Suppression Program supported the eradication of 3,054,336 plants in the top seven marijuana producing states (California, Hawaii, Kentucky, Oregon, Tennessee, Washington and West Virginia). This is an increase of 315,628 eradicated plants over the previous year. 76

• For the 2005 eradication season, a total of 5 million marijuana plants have been eradicated across the United States. This is a one million plant increase over last year. The Departments of Agriculture and Interior combined have eradicated an estimated 1.2 million plants during this 2005 eradication season. 77
APPENDIX A
Acronyms used in “The DEA Position on Marijuana”
AAP American Academy of Pediatrics
ACS American Cancer Society
AMA American Medical Association
BBC British Broadcasting Company
B.C. Bud British Columbia Bud
BMA British Medical Association
CB1 Cannabinoid Receptor 1: one of two receptors in the brain’s endocannabinoid (EC) system associated with the intake of food and tobacco dependency.
CMCR Center for Medicinal Cannabis Research
DASIS Drug and Alcohol Services Information System
DEA Drug Enforcement Administration
FDA Food and Drug Administration
HIV Human Immunodeficiency Virus
INCB International Narcotics Control Board
IOM Institute of Medicine
IOP Intraocular Pressure
LSD Diethylamide-Lysergic Acid
MS Multiple Sclerosis
NHTSA National Highway Traffic Safety Administration
NIDA National Institute on Drug Abuse
NMSS National Multiple Sclerosis Society
NORML National Organization for the Reform of Marijuana Laws
NSDUH National Survey of Drug Use and Health
ONDCP Office of National Drug Control Policy
TEDS Treatment Episode Data Set
THC Tetrahydrocannabinol

ENDNOTES
1 As of April 2006, the eleven states that have decriminalized certain marijuana use are Arizona, Alaska, California, Colorado, Hawaii, Maine, Montana, Nevada, Oregon, Rhode Island, Vermont, and Washington. In addition, Maryland has enacted legislation that recognizes a “medical marijuana” defense
2 “Inter-Agency Advisory Regarding Claims That Smoked Marijuana Is a Medicine.” U.S. Food and Drug Administration, April 20, 2006. < http://www.fda.gov/bbs/topics/NEWS/2006/NEW01362.html>.
3 “Policy H-95.952 ‘Medical Marijuana.'” American Medical Association. See also, American Medical Association, Featured Council on Scientific Affairs. “Medical Marijuana (A-01).” June 2001. In 2001, the AMA updated their policy regarding medical marijuana reflecting the results of this study. It should be noted that a few medical organizations have offered limited support to the concept of “medical” marijuana. For example, the American Academy of Family Physicians has said that it opposes the use of marijuana “except under medical supervision and control, for specific medical indications.” Largely at the urging of one activist – a lobbyist and former Board member of NORML – the American Nurses Association has endorsed “medical” marijuana under “appropriate prescriber supervision,” and the American Academy of HIV Medicine, a group of about 1,800 members founded in 2000, has taken the view that marijuana should not only be made available for “medical” use, but should be excluded altogether as a Schedule I drug
4 “Experts: Pot Smoking Is Not Best Choice to Treat Chemo Side-Effects.” American Cancer Society. 22 May 2001.

http://www.cancer.org/docroot/NWS/content/update/NWS_1_1xU_
Experts__Pot_Smoking_Is_Not_Best_Choice_to_Treat_Chemo_Side_Effects.asp
(9 March 2005).
5 Committee on Substance Abuse and Committee on Adolescence. “Legalization of Marijuana: Potential Impact on Youth.” Pediatrics Vol. 113, No. 6 (6 June 2004): 1825-1826. See also, Joffe, Alain, MD, MPH, and Yancy, Samuel, MD. “Legalization of Marijuana: Potential Impact on Youth.” Pediatrics Vol. 113, No. 6 (6 June 2004): e632-e638h.
6 National MS Society. “Information Sourcebook.” National MS Society. December 2004. < www.nationalmssociety.org/pdf/sourcebook/marijuana.pdf> (1 April 2005).
7 “Doctors’ Fears at Cannabis Change.” BBC News. 21 January 2004.
8 Manchester Online. “Doctors Support Drive Against Cannabis.”
Manchester News. 21 January 2004. < http://www.manchesteronline.co.uk/ news/s/78/78826_doctors_support_drive_against_cannabis.html> (25 March 2005).
9 Joffe, Alain, MD, MPH, Yancy, Samuel W., MD, the Committee on Substance Abuse and the Committee on Adolescence, Technical Report: “Legalization of Marijuana: Potential Impact on Youth”, American Academy of Pediatrics, 6 June 2004.
10 Institute of Medicine. “Marijuana and Medicine: Assessing the Science Base.” (1999). Summary. < http://www.nap.edu/html/marimed> (12 April 2005).
11 Id.
12 Institute of Medicine. “Marijuana and Medicine: Assessing the Science Base.” (1999). Executive Summary. < http://www.nap.edu/html/marimed> (11 January 2006).
13 Institute of Medicine. “Marijuana and Medicine: Assessing the Science Base.” (1999). Summary. < http://www.nap.edu/html/marimed> (11 January 2006).
14 Institute of Medicine. “Marijuana and Medicine: Assessing the Science Base.” (1999). Summary. < http://www.nap.edu/html/marimed> (11 January 2006).
15 Benson, John A., Jr. and Watson, Stanley J., Jr. “Strike a Balance in the Marijuana Debate.” The Standard-Times. 13 April 1999.
16 DEA, Office of Diversion Control. 8 May 2006.
17 “CMCR Mission Statement.” Center for Medicinal Cannabis Research. < http://www.cmcr.ucsd.edu/geninfo/mission.htm> (3 February 2005).
18 DEA, Office of Diversion Control. 6 January 2006.
19 Marijuana Potency Monitoring Project. “Quarterly Report #87.” Marijuana Potency Monitoring Project. 8 November 2004.
20 “BC Bud: Growth of the Canadian Marijuana Trade.” Drug Enforcement Administration, Intelligence Division. December 2000.
21 “Teens at High Risk for Pot Addiction.” The Seattle Post-Intelligencer. 6 January 2004.
22 Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Treatment Episode Data Set (TEDS) 1993-2003: National Admissions to Substance Abuse Treatment Services. November 2005, Table 5.1b. < http://wwwdasis.samhsa.gov/teds03/teds_2003_rpt.pdf> (12 January 2006).
23 Id.
24 “Marijuana Myths & Facts: The Truth Behind 10 Popular Misperceptions.” Office of National Drug Control Policy. < http://www.whitehousedrugpolicy.gov/publications/marijuana_myths_facts/index.html> (12 January 2006).
25 Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Overview of Findings from 2004 National Survey on Drug Use and Health. September 2005.
26 Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Treatment Episode Data Set (TEDS) 1993-2003: National Admissions to Substance Abuse Treatment Services. November 2005. Page 74; Table 2.1b. < http://wwwdasis.samhsa.gov/teds03/teds_2003_rpt.pdf> (12 January 2006).
27 Id., Tables 2.1a and 5.1a. There were 284,361 primary marijuana admissions in 2003, with 99,122 of those being juvenile marijuana admissions, meaning that there were 185,239 adult marijuana admissions.
28 “What Americans Need to Know about Marijuana.” Office of National Drug Control Policy. October 2003.
29 Gfroerer, Joseph C., et al. “Initiation of Marijuana Use: Trends, Patterns and Implications.” Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies. July 2002. Page 71.
30 “Non-Medical Marijuana II: Rite of Passage or Russian Roulette?” CASA Reports. April 2004. Chapter V, Page 15.
31 “What Americans Need to Know about Marijuana,” 9.
32 Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Office of Applied Studies. “Daily Marijuana Users.” The NSDUH Report. 26 November 2004.
33 Furber, Matt. “Threat of Meth-‘the Devil’s Drug’-increases.” Idaho Mountain Express and Guide. 28 December 2005.
34 “Drug Abuse; Drug Czar, Others Warn Parents that Teen Marijuana Use can Lead to Depression.” Life Science Weekly. 31 May 2005.
35 Kearney, Simon. “Cannabis is Worst Drug for Psychosis.” The Australian. 21 November 2005.
36 Curtis, John. “Study Suggests Marijuana Induces Temporary Schizophrenia-Like Effects.” Yale Medicine. Fall/Winter 2004.
37 “Marijuana Associated with Same Respiratory Symptoms as Tobacco,” YALE News Release. 13 January 2005. < http://www.yale.edu/opa/newsr/05-01-13-01.all.htm> (14 January 2005). See also, “Marijuana Causes Same Respiratory Symptoms as Tobacco,” January 13, 2005, 14WFIE.com.
38 “What Americans Need to Know about Marijuana,” page 9.
39 “Marijuana Affects Brain Long-Term, Study Finds.” Reuters. 8 February 2005. See also: “Marijuana Affects Blood Vessels.” BBC News. 8 February 2005; “Marijuana Affects Blood Flow to Brain.” The Chicago Sun-Times. 8 February 2005; Querna, Elizabeth. “Pot Head.” US News & World Report. 8 February 2005.
40 “Neurotoxicology; Neurocognitive Effects of Chronic Marijuana Use Characterized.” Health & Medicine Week. 16 May 2005.
41 Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA), Office of Applied Sciences. “Marijuana Use and Delinquent Behaviors Among Youths.” The NSDUH Report. 9 January 2004.
42 “Drugged Driving Poses Serious Safety Risk to Teens; Campaign to Urge Teens to ‘Steer Clear of Pot’ During National Drunk and Drugged Driving (3D) Prevention Month.” PR Newswire. 2 December 2004.
43 O’Malley, Patrick and Johnston, Lloyd. “Unsafe Driving by High School Seniors: National Trends from 1976 to 2001 in Tickets and Accidents After Use of Alcohol, Marijuana and Other Illegal Drugs.” Journal of Studies on Alcohol. May 2003.
44 Id.
45 “White House Drug Czar Launches Campaign to Stop Drugged Driving.” Office of National Drug Control Policy Press Release. 19 November 2002.
46 Couper, Fiona, J., Ph.D., page 11.
47 Orange County Register. “Nation: Drug Test Positive for Driver in Deadly Crash.” Orange County Register. 14 May 1999.
48 Edmondson, Aimee. “Drug Tests Required of Child Care Drivers – Fatal Crash Stirs Change; Many Already Test Positive.” The Commercial Appeal. 2 July 2003.
49 McDonald, Melody and Boyd, Deanna. “Jury Gives Mallard 50 Years for Murder; Victim’s Son Forgives but Says ‘Restitution is Still Required.'” Fort Worth Star Telegram. 28 June 2003.
50 “Boy, 8, Who Was Struck While Riding Bike Dies.” The Dallas Morning News. 25 April 2005.
51 “Lastest News in Brief from Northern Nevada.” The Associated Press State & Local Wire. 30 April 2005.
52 Washoe County District Attorney’s Office. 6 January 2006.
53 The Associated Press. “Police: Driver in Fatal Crash had Drugs in System.” The Associated Press. 1 June 2003.
54 The Associated Press. “Murder Charges Filed in Blaze that Killed Two Firefighters.” The Associated Press. 21 August 2004.
55 Office of National Drug Control Policy. “Who’s Really in Prison for Marijuana?” May 2005. Page 22.
56 “Marijuana Myths & Facts.” Page 22.
57 “Who’s Really in Prison for Marijuana? Page 20.
58 “What Americans Need to Know about Marijuana,” ONDCP, Page 10.
59 Dutch Health, Welfare and Sports Ministry Report. 23 April 2004.
60 INTRAVAL Bureau for Research & Consultancy. “Coffeeshops in the Netherlands 2004.” Dutch Ministry of Justice. June 2005. < http://www.intraval.nl/en/b/b45.html>.
61 Id.
62 International Narcotics Control Board. “INCB Welcomes ‘Crucial and Significant Change in Dutch Cannabis Policy.'” United Nations Information Service. 2 March 2005. The action plan to discourage cannabis use includes elements such as drug prevention campaigns, mass-media anti-drugs campaign, increased treatment efforts to cannabis users, and encouragement of administrative and criminal law enforcement efforts. See also: “International Narcotics Control Board Annual Report Focuses on Need to Integrate Drug Demand, Supply Strategies.” SOC/NAR/924 Press Release. 3 February 2005. < http://www.un.org/News/Press/docs/2005/socnar924.doc.htm> (18 March 2005); “Press Briefing by International Narcotics Control Board.” 3 January 2005. (18 March 2005).
63 Collins, Larry. “Holland’s Half-Baked Drug Experiment.” Foreign Affairs Vol. 73, No. 3. May-June 1999: Pages 87-88.
64 Cohen, Roger. “Amid Growing Crime, Zurich Closes a Park it Reserved for Drug Addicts.” The New York Times. 11 February 1992.
65 Adlaf, Edward M. and Paglia-Boak, Angela, Center for Addiction and Mental Health, Drug Use Among Ontario Students, 1977-2005, CAMH Research Document Series No. 16. The study does not contain data on marijuana use among 12th graders prior to 1999. See also: Canadian Addiction Survey, Highlights (November 2004) and Detailed Report (March 2005), produced by Health Canada and the Canadian Executive Council on Addictions; Youth and Marijuana Quantitative Research’ 2003 Final Report, Health Canada; Tibbetts, Janice and Rogers, Dave. “Marijuana Tops Tobacco Among Teens, Survey Says: Youth Cannabis Use Hits 25-Year Peak,” The Ottawa Citizen, 29 October 2003.
66 Koster, Olinka, Doughty, Steve, and Wright, Stephen. “Cannabis Climbdown.” Daily Mail (London). 19 March 2005. See also. Revill, Jo, and Bright, Martin. “Cannabis: the Questions that Remain Unanswered.” The Observer. 20 March 2005; Steele, John and Helm, Toby. “Clarke Reviews “Too Soft” Law on Cannabis.” The Daily Telegraph (London). 19 March 2005; Brown, Colin. “Clarke Orders Review of Blunkett Move to Downgrade Cannabis.” The Independent (London). 19 March 2005.
67 “Blair’s ‘Concern’ on Cannabis.” The Irish Times. 4 May 2005. See also, Russell, Ben. “Election 2005: Blair Rules Out National Insurance Rise.” The Independent (London). 4 May 2005.
68 Craig, Tim. “Md. Starts to Allow Marijuana Court Plea; Penalty Can be Cut for Medicinal Use.” The Washington Post. 1 October 2003, sec B.
69 From a videotape recording of Mr. Rosenthal’s speech, as shown in “Medical Marijuana: A Smoke Screen.”
70 “A Guide to Drug Related State Ballot Initiatives.” National Families in Action. 23 April 2002. < http://www.nationalfamilies.org/guide/california215.html> (31 March 2005).
71 Wren, Christopher S. “Small But Forceful Coalition Works to Counter U.S. War on Drugs.” The New York Times, 2 January 2000.
72 Brant, Tataboline. “Marijuana Campaign Draws in $857,000.” The Anchorage Daily News. 30 October 2004.
73 Gathright, Alan. “Pot Backers Can’t Stoke Hickenlooper.” Rocky Mountain News. 27 October 2005.
74 Stannard, Matthew B. “Ecstasy Victim Told Friends She Felt Like She Was Going to Die.” The San Francisco Chronicle, 4 May 2004. The Chronicle reported that Ms. Perez was given ibuprofen and “possibly marijuana,” but DEA has confirmed that the drug given to her was indeed marijuana.
75 Monitoring the Future, 2005. Supplemented by information from the Office of National Drug Control Policy press release on the 2005 MTF Survey, December 19, 2005.)
76 DEA Domestic Cannabis Eradication/Suppression Program, 2005 eradication season.
77 Id.
Source: DrugWatch International January 2010

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