After alcohol, marijuana is the drug most abused by teens. In fact,
marijuana is the most widely used illicit substance in the United
States and recent data show an uptrend in teen marijuana use
during 2009. Unfortunately, it is still viewed today by many as being the
same drug it was 45 years ago, despite significant changes.

Prevalence of Use by
Teens in the past 30 ays (2008)
monitoringthefuture.org
Marijuana:
8th grade – 5.8%,
10th grade- 13.8%,
12th grade – 19.4%

It is a Stronger Drug Today. Delta9-tetrahydrocannabinol, A.K.A. “THC” is
the active ingredient in marijuana that creates the intoxication. From the
1960’s – 1970’s marijuana was around 1/2 % – 3% THC. For 35 years following the 70‘s, the potency of
marijuana slowly increased to 4% by 1995.

2. Average Age of First Use is Younger Today.
Replicated studies since 1997 have provided a convergence of data suggesting that “early onset of first
intoxication,” as an independent variable, significantly increases the probability of developing addiction. 4
Today the average age of first intoxication is 12 years old. This compares to the 1960’s when marijuana
was primarily used by college students.
One study by (1997) Grant & Dawson, shows the probability of a person developing addiction based
on age of first intoxication in the chart below. In addition to age as a variable if the drug-user has a
genetic family history of addiction then the risk factor is increased by 15 percent. See chart below.

3. Marijuana Then vs. Today – A Picture is Worth a Thousand Words:

Marijuana Then:

Paraphernalia Then:

Marijuana Today:

20 – 25% THC)

Paraphernalia Today

Vaporizer, Grinder, Blunt Wrap

Clearly this is not the same marijuana used 40 years ago or certainly prior to 1995. For many, this grade of
marijuana has only been accessible from “cannabis clubs.” At the same time, because the cost of the marijuana
in the clubs was so expensive, many card holders still purchased marijuana from dealers on the street.
However, with the economic contraction high grade marijuana prices have fallen in many of the cannabis clubs
and access is now easier. Moreover, seeds to grow highly potent marijuana are easily purchased via the internet.
Clients in our program state that “the weed is so sticky I need to use a weed grinder to break it up if I want to
roll a blunt.”

4. Withdrawal From the Drug Can Occur Today:

t the 2009 medical doctor’s CSAM conference in San Francisco, a focus was on how to manage marijuana
withdrawal with Gabapentin. Withdrawal symptoms include loss of appetite, problems sleeping and anxiety.
Clearly people did not experience withdrawal 40 years ago and medicines weren’t being explored to manage
withdrawal symptoms. Finally, with regard to teens, any drug being abused inhibits normal neural, emotional
and social development, which can create a pathological relationship to intoxication resulting in negative
consequences with school, family, money, friendships, romantic attachments, health, mental health, sports,
employment, etc.

Final Thoughts: Evaluations, Education
&Treatment

Marijuana is not the innocuous drug that some believe it to be.
Too often parents and professionals base their understanding of
the drug from their own personal use 20 years ago. One of the
biggest challenges facing professionals
who specialize in the treatment of teen
and young adult addictive disorders is
that the intervention is not only with the
individual, but it is also with the family,
other health care professionals, schools,
and legal system, who might “minimize”
or discount the severity of marijuana
abuse. Statements such as “It is only
marijuana,” “at least it isn’t oxycontin,
meth, etc” are examples of the type of
denial described as “minimizing.” These messages from
various systems support denial for the individual who is having
consequences in different areas of their life because of the drug.
For this reason, intervention must occur with the individual,
family and community in order to be effective. It is also
important that if families are seeking help for their child who is
abusing drugs, they should seek professionals who are specially
trained in adolescent and young adult addiction. If you are a
parent or a professional working with teens and it is discovered
that they have used, regardless of the frequency, an evaluation
by a specialist is warranted. The individual needs to become
educated, explore their relationship to intoxication and examine
how it has already impacted different areas of their life in
addition to learning new affect regulation and relational skills to
move beyond this in their life. In addition, the family needs
education on teen addiction, an understanding on how the brain,
emotional, and social development are thwarted by drug use.
An examination of parental denial & enabling is needed as well
as help with developing and implementing a good home
contract, drug testing and education regarding how to be both a
supportive resource for their child meanwhile maintaining a
zero tolerance of drug use.

Sources:
1. Janet E. Joy, Stanley J. Watson, Jr., and John A Benson, Jr., “Marijuana and Medicine:
Assessing the Science Base,” Division of Neuroscience and Behavioral Research, Institute of
Medicine (Washington, DC: National Academy Press, 1999).
2. http://www.monitoringthefuture.org/data/09data.html#2009data-drugs
3. http://www.justice.gov/ndic/pubs37/37035/national.html
4. (1997) Grant & Dawson, Journal of Substance Abuse, Vol. 9
5. http://www.oas.samhsa.gov/newUsers.html
6. (1997) Grant & Dawson, Journal of Substance Abuse

New research suggests that people who smoke and drink heavily are more at risk for oral cancer, the Researchers from King’s College in London, England, found an increase in oral cancer among men and women in their 20s and 30s who smoke and binge drink.

The researchers said that when tobacco smoke combines with alcohol, it produces dangerous levels of cancer-causing chemicals that attack the lining of the mouth.

“Our data show that smoking, drinking and poor diet are major risk factors, and that the younger people start smoking and drinking, the higher the risk,” said Newell Johnson, a professor of oral pathology at King’s College

Source: Daily Telegraph,  London  reported Nov. 9.2004

Record numbers of teenagers are requiring drug treatment as a result of smoking skunk, the highly potent cannabis strain that is 25 times stronger than resin sold a decade ago.

More than 22,000 people were treated in 2007  for cannabis addiction – and almost half of those affected were under 18. With doctors and drugs experts are warning that skunk can be as damaging as cocaine and heroin, leading to mental health problems and psychosis for thousands  – an IoS editorial states that there is growing proof that skunk causes mental illness and psychosis.

The decision comes as statistics from the NHS National Treatment Agency show that the number of young people in treatment almost doubled from about 5,000 in 2005 to 9,600 in 2006, and that 13,000 adults also needed treatment.

The skunk smoked by the majority of young Britons bears no relation to traditional cannabis resin – with a 25-fold increase in the amount of the main psychoactive ingredient, tetrahydrocannabidinol (THC), typically found in the early 1990s. New research being published in this week’s Lancet (2008)  will show how cannabis is more dangerous than LSD and ecstasy. Experts analysed 20 substances for addictiveness, social harm and physical damage. The results will increase the pressure on the Government to have a full debate on drugs, and a new independent UK drug policy commission being launched next month will call for a rethink on the issue.

The findings last night reignited the debate about cannabis use, with a growing number of specialists saying that the drug bears no relation to the substance most law-makers would recognise. Professor Colin Blakemore, chief of the Medical Research Council, who backed the original Independent  campaign for cannabis to be decriminalised, has also changed his mind.

He said: “The link between cannabis and psychosis is quite clear now; it wasn’t 10 years ago.”

Many medical specialists agree that the debate has changed. Robin Murray, professor of psychiatry at London’s Institute of Psychiatry, estimates that at least 25,000 of the 250,000 schizophrenics in the UK could have avoided the illness if they had not used cannabis. “The number of people taking cannabis may not be rising, but what people are taking is much more powerful, so there is a question of whether a few years on we may see more people getting ill as a consequence of that.”

“Society has seriously underestimated how dangerous cannabis really is,” said Professor Neil McKeganey, from Glasgow University’s Centre for Drug Misuse Research. “We could well see over the next 10 years increasing numbers of young people in serious difficulties.”

Politicians have also hardened their stance. David Cameron, the Conservative leader, has changed his mind over the classification of cannabis, after backing successful calls to downgrade the drug from B to C in 2002. He abandoned that position last year, before the IoS revealed that he had smoked cannabis as a teenager, and now wants the drug’s original classification to be restored.

Source  IoS  Dec. 2008

PATIENTS suffering the effects of cannabis abuse are being treated by Tasmanian public hospitals every day, says a leading health authority.

People with short-term drug-induced psychosis and longer-term mental illness, compounded by pot smoking, are seeking medical help at an increasing rate.   Mental Health Services clinical statewide director Peter Norrie said the Royal Hobart Hospital was seeing many cannabis cases.

First-time pot smokers were turning up at the Royal with full-blown psychosis — delusional, confused and anxious.   Other more regular pot smokers with long-term mental illness were fronting for treatment for episodes likely to have been triggered or related to using cannabis. 

“These days it’s close to every day,” said Dr Norrie, who is a senior clinical consultant psychiatrist at the Royal.   He said he was talking about “drug-induced psychosis or long-term mental illness associated with pot smoking”.   Dr Norrie said it was “very common” for first-time users to present with “floridly psychotic” behaviour.

He said psychiatrists were increasingly concerned with the link between substance abuse and mental illness.   Cannabis use had been linked with depression, anxiety and schizophrenia. International studies show modern strains of marijuana are from three to 10 times stronger than those used by previous generations.

“Clinically psychiatrists have suspected a link for many years and the latest research seems to confirm this,” Dr Norrie said.

“The chicken-and-egg debate has raged for years whether pot causes psychosis or people with a tendency to psychotic illness are predisposed to smoke pot.”

Dr Norrie said the first signs of schizophrenia were often a lack of engagement with society. But those symptoms could also be what is commonly known as “typically teenage” or a sign of the onset of depression.

Disengaged teenagers could then turn to cannabis.

If psychosis did occur it was hard to tell whether smoking pot was a cause or a symptom. Dr Norrie said some pot smokers appeared to be able to continue the habit without serious mental illness but others were prone to individual cases of psychosis or longer-term mental disease.

“There’s a certain group of people who smoke pot who are unlikely to develop mental illness but there’s certainly a significant number of the population who suffer from mental illness and pot smoking adds to the risk,” Dr Norrie said.

Drug-induced psychosis usually consists of paranoia, confusion and anxiety.

Sufferers present with memory problems and delusions. They can believe they have special powers, hear and see things that are not there and are unable to distinguish what is real.

Source: Sunday Tasmanian 30th January 2005

Last Updated: 2005-04-01 9:09:08 -0400 (Reuters Health)

NEW YORK (Reuters Health) – Even in clinical situations where cannabis is administered orally at low doses, psychotic reactions can occur, Swiss researchers report the current issue of BMC Psychiatry.

Recreational cannabis use has been associated with psychotic reactions, but this is the first such report in closely monitored subjects participating in a clinical trial, note Dr. Bernard Favrat and colleagues at Institut Universitaire de Medicine Legale in Lausanne.

Favrat’s group was conducting a study to examine the effects of ingestion of THC (delta-9-tetrahydrocannabinol) on psychomotor function and driving performance in eight occasional cannabis users.

The first case of psychosis was in a 22-year-old man given 20 milligrams of dronabinol, a synthetic THC. Ninety minutes after dronabinol administration he experienced severe anxiety and symptoms of psychosis, and was unable to perform the two psychometric tests.

Levels of THC and its active metabolite 11-OH-THC in the blood at the time of the strong adverse effects were 1.8 and 5.2 nanograms per milliliter, respectively.

The second case was also a 22-year-old man who developed severe anxiety one hour after taking 16.5 milligrams of a THC compound, when his THC blood level was 6.2 nanograms per milligram and 11-OH-THC was 3.9 nanograms per milligram. For several hours he was unable to perform psychometric tests

The authors note that smoking a 3.5-percent marijuana cigarette leads to blood concentrations of THC in the range of 50 to 100 nanograms per milliliter. They believe that oral administration produces higher levels of 11-OH-THC, with slower elimination.

Alternatively, they suggest that “consuming oral cannabis may produce more potent, yet unknown psychotomimetic metabolites of THC.”

“Doctors and users should be aware of the increasing availability of oral cannabis in ‘special’ drinks or food as well as in medications under development,” which can result in “significant psychotic reactions,” Favrat’s group cautions.

SOURCE: BMC Psychiatry, April 1,2005.

Physicians who encounter myocardial infarction in teenagers should consider the possibility that the teens may have ingested K2, a form of synthetic cannabinoid, researchers said.

“Although chest pain is a common presenting complaint of teenagers seen in emergency departments, chest pain from cardiac causes remains exceedingly rare,” Colin Kane, MD, a pediatric cardiologist at the UT Southwestern Medical Center in Dallas, and colleagues wrote in the December issue ofPediatrics. “Use of illicit drugs causing chest pain and myocardial ischemia, however, must remain part of the differential diagnosis.”

The researchers reported on three cases of myocardial infarction in teenagers following ingestion of K2. Designer drugs containing synthetic cannabinoids have become more popular among teens, but little is known about their health implications.

K2 is a collection of herbs and spices that have been treated with a synthetic cannabinoid. The effects are said to be stronger than naturally occurring cannabis.

“These types of drugs give a marijuana-like effect but do not show up on drug screens,” Kane explained to MedPage Today. Therefore, careful questioning may be needed to elicit information about K2 exposure, the authors suggested.
All three cases involved 16-year-old males with no previous health problems. Each complained of chest pains of at least three days’ duration and presented between August and November of 2010.

Initial electrocardiograms revealed ST-segment elevation and high troponin levels. There was no personal or family history of early cardiac problems. Urine drugs screens noted the presence of THC in two patients. No other drugs, including cocaine and amphetamines, were found.

“When the first patient came we initially thought it was a virus that was affecting his heart,” said Kane. “The day after he was hospitalized, the chest pain, ECG, and laboratory test all changed dramatically. We went back to the patient and were more persistent about anything else he might have done. It just isn’t normal for a 16-year-old to have a heart attack.”
Shortly thereafter, two new cases presented with similar findings. After establishing that these males also had smoked K2, Kane and colleagues became concerned because their patients were not having just chest pains, but actual heart attacks.

“I have since then seen a number of kids in my practice who have smoked K2 and complained of chest pains,” said Kane. “I haven’t seen any other frank heart attacks.”

This led them to wonder if there was something different about the K2 that was in circulation at that time. Another option is that teenagers were showing up in the emergency room, but the heart attacks were not found because it is so atypical in the age group.

“It is disconcerting and frightening that K2 is relatively easy to obtain and could have such serious health consequences,” said Kane. “Emergency and primary care doctors need to ask patients specifically about the use of K2 and synthetic marijuana. If the clinical findings fit, physicians should take the extra step and look for heart damage, even in previously healthy teenagers.”

Source:   www.pediatrics.aappublications.org at University of Florida on November 14, 2011

ABSTRACT: The aim of the present study was to determine the risk of lung cancer associated with cannabis smoking.

A case–control study of lung cancer in adults less than55 yrs of age was conducted in eight district health boards in New Zealand. Cases were identified from the New Zealand Cancer Registry and hospital databases. Controls were randomly selected from the electoral roll, with frequency matching to cases in 5-yr age groups and district health boards. Interviewer-administered questionnaires were used to assess possible risk factors, including cannabis use. The relative
risk of lung cancer associated with cannabis smoking was estimated by logistic regression.

In total, 79 cases of lung cancer and 324 controls were included in the study. The risk of lung cancer increased 8% (95% confidence interval (CI) 2–15) for each joint-yr of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 5–9) for each pack-yr of cigarette smoking, after adjustment for confounding variables including cannabis smoking. The highest tertile of cannabis use was associated with an increased risk of lung cancer (relative risk 5.7 (95% CI 1.5–21.6)), after adjustment for confounding variables including cigarette smoking.

In conclusion, the results of the present study indicate that long-term cannabis use increases the risk of lung cancer in young adults.

Source Eur Respir J 2008; 31: 280–286 2008

 Q: How can I tell if my child has been using marijuana?

A: There are some signs you might be able to see. If someone is high on marijuana, he or she might:

 Seem dizzy and have trouble walking;

• Seem silly and giggly for no reason;
• Save very red, bloodshot eyes; and
• Have a hard time remembering things that just happened.

 When the early effects fade, the user can become very sleepy.

 Parents should be aware of changes in their child’s behavior, although this may be difficult with teens. Parents should look for withdrawal, depression, fatigue, carelessness with grooming, hostility and deteriorating relationships with family members and friends.

 In addition, changes in academic performance, increased absenteeism or truancy, lost interest in sports or other favourite activities, and changes in eating or sleeping habits could be related to drug use. However, these signs may also indicate problems other than using drugs.

In addition, parents should be aware of:

 Signs of drugs and drug paraphernalia, including pipes and rolling papers;

• Odour on clothes and in the bedroom;
• Use of incense and other deodorizers;
• Use of eye drops; and
• Clothing, posters, jewellery, etc., promoting drug use.

 Source: The National Institute on Drug Abuse  2010

The headline below from the Daily Mail on the 18th October 2011, suggests that 50% of the population of America favour legalizing marijuana.   However  Jose Paulo Carneiro, a statistics expert from Brazil,  writes a critique of this survey and shows that the results issued by Gallup Poll are not what they seem to be suggesting.
The saying ‘Lies, Damn Lies and Statistics’ comes to mind.    NDPA
*  *  *  *  *  *
Record high: Gallup poll shows FIFTY per cent of Americans favour legalising marijuana    -    18th October 2011
• Up from 46 per cent last year
• Liberals and those 18 to 29 most in favour
• Americans 65 and older most oppose
Read more: http://www.dailymail.co.uk/news/article-2050348/Legalisation-marijuana-50-Americans-favour.html#ixzz1boJx8Vwj
*  *  *  *  *  *
 
“First of all, what is the methodology of this survey? What is the universe? Of course, it cannot be all the Americans.   Suppose it is the American population between 15 and 64 years (approximately 205.7 million).

If the sample were a simple random sample (that is, all the individuals have the same probability of being selected), the fact that the sample size is a tiny proportion of the population would not matter, because in the formula for the sample standard deviation (let us call it s) of a proportion to be estimated, the size N of the universe only appears in a factor, which, for a sample size of 1,005, equals 0.999995, which is practically 1. 
 
Then, the maximum value for s, which occurs precisely for the 50% proportion and is independent of N, reduces to 1.6%. This means (supposing, as usual, the normality of the sampling distribution) that there is a probability of 95% that a real proportion of 50% will appear in the sample between 46.8% and 53.2% (this is the meaning of the phrase “the survey error is 3.2%”), which is a very acceptable value.
 
The problem is not in the sample size. The problem is that a telephone survey is not a simple sample survey, because not all individuals have the same chance of being selected. If you don’t have a telephone number, your probability of being selected is zero. If you have three telephone numbers and your neighbor has only one, your probability of being selected is three times his. Moreover, even inside a specific household, the probabilities are different. In certain households (mine, for instance), the probability that the husband answers the phone is very small compared with the probability that the wife does it. And, what is worse: the sample is biased, because there may be – and usually there is – a specific profile of people who answer, opposed to that of people who don’t answer the call.

In summary, it is very surprising that an Institute so renowned as Gallup, in a country so developed in matters of survey and research, makes a telephone survey and draws a conclusion about the opinion of “half of the Americans”.

Jose Paulo Carneiro, Expert in Statistics and Surveys, Rio de Janeiro, Brazil. Oct.2011

A single cannabis joint has the same effect on the lungs as smoking up to five cigarettes in one go, indicates research published ahead of print in the journal Thorax.

The researchers base their findings on 339 adults up to the age of 70, selected from an ongoing study of respiratory health, and categorised into four different groups.

These comprised those who smoked only cannabis, equivalent to at least one joint a day for five years; those who smoked tobacco only, equivalent to a pack of cigarettes a day for at least a year; those who smoked both; and those who did not smoke either cannabis or tobacco.

All the participants had high definition x-ray scans (computed tomography) taken of their lungs and they took special breathing tests designed to assess how well their lungs worked.

They were also questioned about their smoking habits.
Seventy five people smoked only cannabis, and 91 smoked both. Eighty one people did not smoke either, and 92 smoked only tobacco.

Combined smokers tended to use less tobacco, the findings showed.
Cannabis smokers complained of wheeze, cough, chest tightness and phlegm. But emphysema, the progressive and crippling lung disease, was only seen in those who smoked tobacco, either alone or in combination.
But cannabis still damaged the lungs and stopped them from working properly.

It diminished the numbers of small fine airways, which are important for transporting oxygen and waste products to and from the blood vessels effectively.
And it damaged the large airways of the lung, blocking airflow, and forcing the lungs to work harder.
The extent of this damage was directly related to the number of joints smoked, with higher consumption linked to greater incapacity.

The effect on the lungs of each joint was equivalent to smoking between 2.5 and five cigarettes in one go.
The authors explain that the impact of cannabis is strongly associated with the way in which it is smoked. It is usually smoked without a filter, and at a higher temperature. Smokers tend to inhale more deeply and to hold their breath for longer.

Source:  Retrieved August 8, 2009, from http://www.sciencedaily.com

Abstract

Since 1996, 16 states and the District of Columbia in the United States have enacted legislation to decriminalize marijuana for medical use. Although marijuana is the most commonly detected non alcohol drug in drivers, its role in crash causation remains unsettled. To assess the association between marijuana use and crash risk, the authors performed a meta-analysis of 9 epidemiologic studies published in English in the past 2 decades identified through a systematic search of bibliographic databases. Estimated odds ratios relating marijuana use to crash risk reported in these studies ranged from 0.85 to 7.16. Pooled analysis based on the random-effects model yielded a summary odds ratio of 2.66 (95% confidence interval: 2.07, 3.41). Analysis of individual studies indicated that the heightened risk of crash involvement associated with marijuana use persisted after adjustment for confounding variables and that the risk of crash involvement increased in a dose-response fashion with the concentration of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol detected in the urine and the frequency of self-reported marijuana use. The results of this meta-analysis suggest that marijuana use by drivers is associated with a significantly increased risk of being involved in motor vehicle crashes.

Source:  Epidemiology Rev (2011) doi: 10.1093/epirev/mxr017

1. Killian A. Welch, MD, MRCPsych  et al 

Correspondence:: kwelch1@staffmail.ed.ac.uk

Background
No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia.

Aims
To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia.

Method
Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance.

Results
Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F = 7.66, P = 0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis.

Conclusions
These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

 
Source:  bjp.rcpsych.org   Sept.2011

The price of cannabis has declined more than 40% (4.9% p.a.) in real terms during the 1990s, far greater than for most other agricultural products. Cannabis price may be declining because of increasing use of more efficient hydroponic cultivation techniques and also because decreasing law enforcement lowered the ‘full cost’ of cannabis. The number of national arrests and prosecutions per 100,000 population fell by almost one third between 1996 and 2001. Penalties also became less severe. If cannabis price had been constant, consumption of beer would have been 2.4% higher, wine 4.9% higher, spirits 9.8% higher and cannabis 10.4% lower.

Comment: As the health, social and economic costs of alcohol are greater than for cannabis, decreasing cannabis prices may have reduced harm from legal drugs.

Source: Clements KW. The Australian Journal of Agricultural and Resource Economics. 2004. 48:2; 271-300

Killias M., Isenring G.L., Gilliéron G. et al.
European Journal of Criminology: 2011, 8(3), p. 171–186.

Studies of a ‘natural experiment’ in Switzerland in the 2000s suggested that the effective re-criminalisation of cannabis production and distribution did diminish availability and use of the drug. The results contradict other findings suggesting that national policies have little effect on cannabis use.

Summary
A ‘natural experiment’ in Switzerland in the 2000s revealed the impacts of changes in the enforcement of cannabis production and distribution laws. By 2001, in response to public sentiment Switzerland had already relaxed its enforcement of laws against the use and distribution of cannabis. At this time the government prepared reforms to enshrine this in law by officially tolerating the sale, possession and use of small amounts of cannabis (usually below 5g), and the production and sale of larger quantities as long as producers and retailers agreed to act under strict control by police and the Department of Agriculture. Though this change had yet to be implemented, in anticipation over the following years visible and quasi-official structures of production, distribution and sale emerged. Concerned over some of the consequences, in 2003 and again in 2004 the Swiss parliament rejected the proposed changes. Over the following months, police and prosecutors resumed former more repressive policies, especially in respect of production and distribution. As a result, shops and production centres were closed during 2005 and 2006. It was this reversal which offered the opportunity to evaluate the impact of tolerance of legal production and distribution versus lack of tolerance.

Main findings
Early in 2004 shortly before most of their shops were closed, a survey of cannabis retailers suggested that competition between shops was quite stiff, particularly in respect of price. Nearly all felt they had to provide excellent products and service to keep their customers. Though many said they had never sold high strength and/or smokeable cannabis, this conflicted with the number of prosecutions for selling cannabis whose main active ingredient (THC) was above the legal limit.

In summer 2004 when many cannabis shops were still operating, two young men aged around 18 conducted ‘test purchase’ operations at 50 shops. Of these, 29 sold cannabis without reservation and 26 did so regardless of the young men’s age. Usually, the fake clients asked for 5g or the quantity available for about 50 Swiss francs. The quantities actually sold generally varied between 3.8g and 6.5g and THC levels between 8% and 28%, averaging 16%. Overall, the study confirmed that minors easily obtained high-strength cannabis. Most samples contained THC close to the average of 16% and prices varied little around 11 Swiss francs per gram. In short, quality and prices were fairly well standardised.
In 2009 when all known cannabis shops had closed, a second ‘test purchase’ operation was conducted, but this time to test the availability of supplies on the now fully illicit market. Two young men walked through inner-city areas where police said cannabis was most available, looking for potential dealers. Over 15 afternoons they made 29 relevant contacts; during 27 they were able to obtain cannabis. All the sales took place in streets and parks. Usually the fake clients were able to spot a dealer in under 20 minutes. The quantity purchased varied far more than in 2004, ranging from 0.38 to nearly 13 grams. Equally inconsistent were prices, varying greatly between 8 and 200 francs per gram. A typical price was 28 francs. The THC content varied between 4% and 18% and averaged 12%, lower than in 2004. At every transaction, the fake clients asked whether the dealer might be able or willing to supply other substances. Only one said they could.

Compared to 2004, typical prices paid per gram had increased from 11 to 28 francs and the variability in price and quantity was much greater and THC content lower. From the relatively standardised market of 2004, by 2009 the price structure was, from the clients’ point of view, relatively obscure and bore little relation to the origin or strength of the product.

The authors’ conclusions
The results of our studies suggest that legal policies can strongly affect production, supply, distribution and sale of cannabis. The switch from a liberal to a more repressive policy meant that large-scale agricultural was partly replaced by small-scale production on private premises, and sales moved back from shops to the streets. Formerly an export country, illegal import of cannabis in to Switzerland resumed, though probably not enough to compensate for lost local production. For users without links to home-based production networks, availability of cannabis may have decreased substantially, probably prompting decreased consumption. However, the market and its price structure became far more variable and obscure. Prices soared, possibly reflecting reduced supply and more marginal and criminal suppliers. Street sales favoured cheating because quantities cannot be accurately weighed and suppliers had little interest in repeat sales to unknown customers, feeling little need to gain their trust. On the other hand, and contrary to a widely held view, markets for cannabis and other substances seem to have remained separated.

Surveys in Switzerland and abroad suggest that policies making cannabis more easily available were followed by increasing rates of use, whereas Switzerland’s opposite policy after 2004 was associated with a drop in both the prevalence and frequency of cannabis use. Establishing to what extent policy changes caused changes in use is for the moment impossible, but data is consistent with the assumption that policies affect the availability and (indirectly) use of cannabis.

This draft entry is currently subject to consultation and correction by study authors.
Last revised 06 October 2011
Source : European Journal of Criminology: 2011, 8(3), p. 171–186.

ONE in four people carries genes that increases vulnerability to psychotic illnesses if he or she smokes cannabis as a teenager, scientists have found.

A common genetic profile that makes cannabis five times more likely to trigger schizophrenia and similar disorders has been identified, increasing pressure on the Government to reverse the drug’s reclassification from Class B to Class C.

The increased risk applies to people who inherit variants of a gene named COMT who also smoked cannabis as teenagers. About a quarter of the population have this genetic make-up, and up to 15 per cent of the group are likely to develop psychotic conditions if exposed to the drug early in life.

Neither the drug nor the gene raises the risk of psychosis by itself.

The study, led by Avshalom Caspi and Terrie Moffitt, of the Institute of Psychiatry at King’s College London, offers the best explanation yet for the way that cannabis has a devastating psychiatric impact on some users but leaves most unharmed. Scientists had suspected that genetic factors were responsible for this divide, but a gene had not been pinpointed.

The findings, to be published in Biological Psychiatry, also reinforce a growing consensus that nature and nurture are not mutually exclusive forces but combine to affect behaviour and health. The King’s team has previously identified genes that raise the risk of depression or aggression, but only in conjunction with environmental influences.

Mental health campaigners said that the results vindicated their concerns about the decision last year to downgrade cannabis to a Class C drug, which means that possession is no longer an arrestable offence.

Marjorie Wallace, chief executive of the mental health charity Sane, said that it was becoming clear that cannabis placed millions of users at risk of lasting mental illness. About fifteen million Britons have tried cannabis, and between two million and five million are regular users, according to the Home Office British Crime Survey. The research suggests that a quarter could be at risk.

The evidence will be considered by a review of the drug’s classification announced last month by the Home Secretary. It may be possible to develop a test for genetic susceptibility to cannabis. “If we were able genetically to identify the vulnerable individuals in advance, we would be able to save thousands of minds, if not lives,” Ms Wallace said.

Dr Caspi, however, rejected the idea of screening based on the COMT gene. “Such a test would be wrong more often than it is right. Cannabis has many other adverse effects, especially on developing teenagers, on respiratory health and possibly on cognitive function. Effects may be pronounced among a genetically vulnerable group but that doesn’t mean we should encourage others not genetically vulnerable to use cannabis.”

The King’s team tracked 803 men and women born in Dunedin, New Zealand, in 1972 and 1973, who were enrolled at birth in a research project. Each was interviewed at 13, 15 and 18 about cannabis use, tested to determine which type of COMT genes they had inherited, and followed up at 26 for signs of mental illness.

COMT was chosen as it is known to play a part in the production of dopamine, a brain-signalling chemical that is abnormal in schizophrenia. It comes in two variants, known as valine or methionine, and every person has two copies, one from each parent.

Among people with two methionine variants, the rate of psychotic illness was 3 per cent, the background rate for the general population, regardless of whether they had used cannabis as teenagers.

Among those with two valine variants the rate was 3 per cent for non-users but 15 per cent for those who had smoked cannabis in their teens.

Dr Caspi said research had shown that the valine gene variant and cannabis affect the brain’s dopamine system in similar fashion, suggesting that they deliver a “double dose” that can be damaging. The work needs to be replicated by others to confirm the findings, Dr Caspi said. It also is possible that the gene involved is not COMT but a neighbour.

THE DRUG OF CHOICE FOR MILLIONS

• Cannabis was reclassified from a Class B to a Class C drug in January 2004. Possession remains illegal, but is not an arrestable offence. The Home Secretary has asked for a review by November
• The Home Office estimates that fifteen million people have tried cannabis, two million to five million are regular users and reclassification has saved 199,000 hours’ police work
• Liberalisation campaigners argue that millions smoke the drug with fewer ill-effects than others suffer from alcohol or tobacco
• A recent study at Maastricht University found that cannabis doubles the risk of schizophrenia, hallucinations and paranoia among a genetically susceptible group

Source: www.timesonline.co.uk 14 April 2005

Cannabis causes chaos in the brain as nerve activity becomes uncoordinated and inaccurate, a study has found. The results may help explain links between cannabis and schizophrenia, scientists believe.
Researchers at the University of Bristol measured the brain responses of rats given a drug that mimics the psychoactive ingredient in cannabis. They found that the drug completely disrupted co-ordinated brain waves across the hippocampus and prefrontal cortex.
The first brain region plays a key role in the formation of memories. The second is essential to planning, decision making and social behaviour. Both are heavily implicated in schizophrenia. Rats exposed to the cannabis-like drug became unable to make accurate decisions when navigating through a maze.
The research is reported today in the Journal of Neuroscience.
Study leader Dr Matt Jones said: “Marijuana abuse is common among sufferers of schizophrenia and recent studies have shown that the psychoactive ingredient of marijuana can induce some symptoms of schizophrenia in healthy volunteers.
“These findings are therefore important for our understanding of psychiatric diseases, which may arise as a consequence of ‘disorchestrated brains’ and could be treated by retuning brain activity.” Co-author Michal Kucewicz, also from the University of Bristol, said: “These results are an important step forward in our understanding of how rhythmic activity in the brain underlies thought processes in health and disease.”
The research was part of a Medical Research Council-funded collaboration between the university and drug company Eli Lilly & Co.

Source: The Independent. 26th October 2011

(St. Petersburg, FL) The National Survey on Drug Use and Health conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA) and released this week shows a significant rise in marijuana use. In 2007, 4.4 million Americans 12 and older used marijuana; as of 2010 that number has risen to 17.4 million. The National Office of Drug Control Policy’s Director, Gil Kerlikowske, said the increases are prominent in states in which “medical” marijuana is legal. The survey also shows that 21.5 percent of young adults aged 18 to 25 used illicit drugs in 2010, an increase from 19.6 percent in 2008.

“Other than the lone voice of Director Kerlikowske and large marijuana dispensary raids by the DEA, the Obama Administration has basically turned a blind eye to the medi-pot issue, a matter that fuels the rise in marijuana use and continues to be the biggest scam ever to be perpetrated on the American public. While a crude toxic weed is peddled to sick and dying people as a medicine, our government has done far too little to protect the public. It is absolutely no surprise to me that marijuana use has sharply increased,” said Calvina Fay, executive director of Drug Free America Foundation, Inc. and Save Our Society From Drugs.

“Surveys have shown for years that when the perception of the harms of drugs decreases, use rises. The ruse that marijuana is a medicine has created a false sense that this addictive, dangerous drug is not harmful, but in fact helpful. Clearly, this belief has contributed to the increase of marijuana use among young people. In order to protect the public, it is time for our government to take its head out of the sand and aggressively push back against marijuana legalization for any purposes! Perhaps it’s time to withhold federal funds from states that fail to uphold our nation’s drug laws,” Fay concluded.

Source: Press Release Drug Free America Foundation 9th Sept.2011

Mar 24, 2011

Marijuana use during adolescence and young adulthood increases the risk of psychotic symptoms, while continued cannabis use may increase the risk for psychotic disorder in later life, concludes a new study published in the British Medical Journal.

Cannabis is the most commonly used illicit drug in the world, particularly among adolescents, and is consistently linked with an increased risk for mental illness. However, it is hasn’t been clear whether the link between cannabis and psychosis is causal, or whether it is because people with psychosis use cannabis to “self- medicate” their symptoms.

So a team of researchers, led by Professor Jim van Os from Maastricht University in the Netherlands, investigated the association between cannabis use and the incidence and persistence of psychotic symptoms over 10 years.

The study occurred in Germany and involved a random sample of 1,923 teens and young adults from the ages of 14 to 24.

Incident cannabis use almost doubled the risk of later incident psychotic symptoms, even after accounting for factors such as age, sex, socioeconomic status, use of other drugs, and other psychiatric diagnoses. Furthermore, in those with cannabis use at the start of the study, continued use of cannabis over the study period increased the risk of persistent psychotic symptoms. There was no evidence for self medication effects as psychotic symptoms did not predict later cannabis use.

These results “help to clarify the temporal association between cannabis use and psychotic experiences,” the authors said in their study summary. “In addition, cannabis use was confirmed as an environmental risk factor impacting on the risk of persistence of psychotic experiences.”

Source: British Medical Journal March 2011

Chronic cannabis abuse raises nerve growth factor serum concentrations in drug-naive schizophrenic patients
Maria C. Jockers-Schertibi, Uta Matthies. Heidi Danker-Hopfe, Undine E. Lang Richard
Ivlahlberg and Rainer heliweg
Department of Psychiatry and Psychotherapy, Char ftc-University Medicine Berlin Campus Benjamin F,thjkiin. Berth,. German
Long-term cannabis abuse may increase the risk of schizophrenia. Nerve growth factor (NGF) is a pleiotropic neurotrophic prOtein that is implicated in development, protection and regeneration of NFG sensitive neurones. We tested the hypothesis that damage to neuronal cells in schizophrenia is precipitated by the consumption of cannabis and other neurotoxic substances, resulting in raised NGF serum concentrations and a younger age for disease onset. The NGF serum levels of 109 consecutive drug-naive schizophrenic patients were measured and compared with those of healthy controls. The results were correlated with the long-term intake of cannabis and other illegal drugs. Mean (± SD) NGF serum levels of
61 control persons (33.1 ± 31.0 pg and 76 schizophrenics who did not consume illegal drugs (26.3 ± 19.5 pg/mi) did not differ significantly, Schizophrenic patients with regular cannabis intake (> 0.5 g on average
per day for at least 2 years) had significantly raised NGF serum levels of 412.9 ± 288.4 pg/mI Cu 21) compared to controls and schizophrenic patients not consuming cannabis (p c 0001). In schizophrenic patients who abused not only cannabis, but also additional substances, NGF concentrations were as high as 2336.2 ± 1711.4 pg C = 12). On average, heavy cannabis consumers suffered their first episode of schizophrenia 3.5 years (n = 21) earlier than schizophrenic patients who abstained from cannabis. These results indicate that cannabis is a possible risk factor for the development of schizophrenia. This might be reflected in the raised NGF-serum concentrations when both schizophrenia and long-term cannabis abuse prevail.
Discussion
These results demonstrate that serum NOF concentrations in untreated schizophrenic patients differed greatly depending on their long-term intake of drugs of abuse. Whereas he drug-naive schizophrenic patients who had not consumed illegal substances n the past showed no significant difference in senim NGF concentrations, those abusing cannabis for longer than 2 years showed significantly elevated N compared to healthy controls. This has been shown unequivocally not only by a descriptional data analysis, but also by a confirmatory study design (Table 2). Schizophrenic patients with long-term abuse of multiple substances showed an even greater increase in their serum NGF concentrations up to 90-fold above non-abusing schizophrenic patients (Fig. I).
NGF-plasma le ‘els in 26 male schizophrenic patients who had been kept free of neuroleptics for 14 days were reported to be significantly lower than those observed in controls (Bersani er a!., 1999 By contrast, in our much larger sample of patients, we found no significant differences with respect to senim NGF concentrations between schizophrenic patients and controls. However, our patients were comp!etely drug-naive whereas the patients of the formerly cited study previously had been treated with antipsvchotics for various time spans. It is known that haloperidol can remain in the cerebral tissue for as long as year after application (Konihuber et at, 1999) thereby possibly modulating and influencing NGF values by its antidopaminergic properties. For this reason, a drug-free period of l days might be too short to rule out the pharmacologEca effects of footer antipsychotic medication on the NOF concentration. Haloperidol reduces the basal tTGF plasma levels in eight formerly neuroleptic’ free schizophrenic patients (ALoe et at. 1997). One explanation could he cosecretion of ‘1GF with prolactin. with both being contro by activation of the dopamirie D: receptor subtype Missale er a!.. L 996) that, in turn, can be blocked by the antidopaminer dnig haloperidol. Moreover brain-derived neurotrophic factor (BDNF). another NGF-re]ated neurotrophin. was 1-cc shown to be decreased in he serum of chronic schizophrenic patients who were already treated with neuroleptics Tovooka ci at. 2002). However. we demonstrated highly signLticant elevations ot he NOF serum levels in schizophrenic patients who had consumed significant amounts of cannabis in the past i more than 0.5 per day over at least 2 years). There’s strong circumstantial evidence for neuronal damage by toxic drugs, but only a few { neurochenhical) studies to supporr this. Schizophrenia. a disease of alleged neurodevelopmental origin. o begins in M. C. JOCKERS-SCHERCJBL ETAL.: SCHIZOPHRENIA! CANNABIS AND NERVE GROWTH FACTOR 443 1 I
adolescence at age 6—24 years and is thought to coincide with increased vulnerability to cannabinoids. sometimes avert triggered by them (Andreasson era!.. 1987: Linszen eta!.. 994). In analogy to the situation in neurodegenerative disease (for reviews, see Heliweg et a!, 1998; Siegel and Chauhan, 2000). the high levels of NOF observed in our study might reflect the assumed adverse effects induced by cannabis consumption in schizophrenia development.
At present, the causes and mechanisms of the observed rise in NGF serum concentrations in schizophrenia following long-term cannabis abuse remain speculative. Similarly, from the present data, it is not possible to establish whether the rise in NGE levels is due to disease development (enhanced by cannabis) as a stale marker or whether NOF was even already high before disease onset. Theoretically, patients at risk for an unfavourable outcome of schizophrenia due to repeated cannabis consumption could be assumed to be a different patient population altogether and show premorbid rises in NOF concentrations as a risk-trait variable. 1 a small sample (n = I of subjects without schizophrenia, but regular cannabis consumption of at least 0.5 g per day for longer than 2 years. we found no such elevation of NOF measurements in the serum. The same was true when serum NGF concentrations were measured in otherwise healthy controls acutely intoxicated with cannabis ( 5; Anders and He unpublished data), These findings indicate that the rise in NOF concentrations is not an effect of chronic cannabis consumption per Se but rather reflects the combined damaging effects of cerebral vulnerability in schizophrenia and the chronic toxicity of long-term cannabis abuse. The earlier onset of schizophrenia in the cannabis consum ing patients (Table I) further substantiates this hypothesis.
Greatly raised NGF serum concentrations have been demon strated hi chronic diseases such as alcohol dependence (Aloe a at.. 1996) or Behcet’s disease (lockers-Scherlibi C a 1996). They are not specific for a certain diagnosis. but rather are a marker for chronicity of disease, and possibly for poor prognosis as seen in Behcet’s disease. Our finding of even greater serum NOF concen [ in schizophrenic patients with a long-terni consumption of additional substances with neuroroxic effects is consistent with the hypothesis of an NOF correlation with the cumulative dose and toxicity of drugs. The rise was up to 90-fold of the mean NGF serum concentrations of schizophrenic patients without drug consumption, which corresponds to the highest endogenous ?TGF concentrations reported for man to date. Accordingly, cumulative doses of ecstacy have been demonstrated to be neurotoxic and exert delayed and/or chronLc cerebral alterations (Ricaurte and \lcCann. 992). showing altered glucose metabolism in Positrone emission tomography studies in the hippocampus and amygdala of seven chronic ecstacy users (Obrocki er a!,. 1999). Previous magnetic resonance imaging studies with chronic drug abusers of various drugs including cocaine, amphetamines and psvchedelics. also showed minor structural brain changes (Aasley et at.. 1993). However, the investigators did note that the study probands had also been consuming alcohol, Therefore, the structural central nervous system changes did not clearly reflect those effects exclusively attributable to illegal drugs, but possibly also those due at least in part to alcohol. To avoid such confounding factors in our study, we excluded those patients who consumed alcohol on a re basis, This explains the lack of a control group vith polvsubstance abuse but no schizophrenia because we were unable to find probands that were otherwise reasonably healthy and
consumed no alcohol. Certainly, this remains a field for future mse arch.
The origin of the NOF measured in serum is speculative: On the one hand, serum NGF could well stem from a central source and reflect the contral neurotrophin state, especially in pathological conditions such as preclinical Alzheimer’s disease (Schaub er a!.. 2002). On the other hand, it could retlect a peripheral immun ological reaction in terms of a cytokine released from peripheral immune cells (for reviews, see Levi-Montalcini el c 1996; Hel er a!.. 1998). Schizophrenia has been connected to autoimmune disease (Ganguli er aI.. 1994; Jones and Cannon. 1998) and to inflammatory disease (Lin eLa!.. 199B). both possibly resulting in central or peripheral immune responses. An argument could be made about the principal evidence for a role of the neurotrophins NOF or BDNF in conjunction with schizophrenia. In the meantime, there are a number of experiments indicating a connection between BDNF and schizophrenia (Toyooka et at 2002) and some indicating NOF as not only having a role as a peripheral cytokine. but also as a factor relevant to schizophrenia (for a review, see Aloe et ci., 2000).
In summary, we suggest that the raised NOF serum concentrations found in schizophrenics with long-term cannabis abuse, and more so in schizophrenics with long-term abuse of additional drugs, reflect the amount of cerebra! damage by the combined effects of a primary cerebral vulnerability resulting from schizophrenia and the supposed additional drug-neurotoxicity. Apart from the biochemical evidence of an additive effect of schizophrenia and cannabis consumption on NGF serum concen ations in our confirmatory study design, we also demonstrated an earlier ons of disease in schizophrenic patients consuming cannabis chronically, thereby underlining a precipitating effect of the drug on disease onset. Those two findings am suggestive of a correlation but further studies are required to confirm this hypo thesis. Thus, cannabis use may be a risk factor in schizophrenia development, but a predisposition to schizophrenia and cannabis use combined (but neither one independently) appears to be linked to increased NOR production.
Acknowledgement
We would like to thank Dr Hans Scherubl manuscript and giving valuable advice.
Address for correspondence
darth C Jockers-Scherubi Department of Psychiatry and Psychotherapy C h an re-University
‘ledicine Berlin Eschenn 3 :4050 Berlin Germany
Email: mar i .joc ke rs @ med i zi ii. fu—be ri in. de
References
for looking over the
Aasley .1 Storsaeter 0, tqilsen C, Smevik 0, Rinck P (1993) Minor structural brain changes in young drug abusers. Acta Neurol Scand 87:210-214

Source:
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V2003 British Aisociatlon For Psychopharmacology (ISSN Oz I
SAGE PublicaUons. London. Thousand Oaks. CA and Naw Delhi
0269—08111200312117:4: 439—445; O38O3

Men who use marijuana may increase their risk for developing testicular cancer. A
recent study of several hundred Washington State men with testicular cancer showed an association between current marijuana use and the more aggressive of the two types of the disease. Moreover, the association was strongest among men with a long history of regular marijuana use.

To firmly link marijuana use and the cancer, however, scientists will need to replicate the findings among large groups of men across many geographical regions and identify the underlying biological mechanisms, says NIDA-funded researcher Dr. S. K. Dey of the Cincinnati Children’s Hospital Medical Center, who collaborated on the study with Drs. Janet Daling and Stephen M. Schwartz and colleagues at the Fred Hutchinson Cancer Research Center and the University of Washington.

During the past 50 years, the number of new cases of testicular cancer reported annually in the United States has nearly doubled. So has the percentage of the general population who report having smoked marijuana at least once. Dr. Dey suspected that the two trends might be related, although exposure to various environmental factors may also be involved. Along with the simultaneous rise in rates, there are biological reasons to hypothesize a connection between the drug and the cancer. Research has shown that marijuana smoking reduces sperm production and male fertility, and other work has linked diminished fertility to increased risk of testicular cancer. Cannabinoid receptors— the cell-membrane proteins that bind to a component of marijuana as well as to the naturally occurring compounds known as endocannabinoids—occur on the cell
membranes of sperm, the testes (see photograph), the uterus, and embryos, as well as on brain neurons. Marijuana smoking causes widespread effects in the endocrine and reproductive systems and might alter the growth of somatic and germ cells in the testes, resulting in testicular cancer.

The research team interviewed 369 men who were diagnosed with testicular cancer between 1999 and 2006 and 979 men who never had the disease. They recruited all of the study participants from three counties in Washington State and controlled statistically for smoking, drinking, and other testicular cancer risk factors. Approximately 70 percent of each group reported smoking marijuana at least once. The researchers found that the odds of having testicular cancer were 70 percent higher among men who reported current marijuana use compared with nonusers. In addition, the researchers observed 80 percent higher odds of testicular cancer among men who started to use marijuana before age 18 compared with nonusers. They also found that the odds for testicular cancer among men who used marijuana at least weekly were twice that of nonusers.

Of the two categories of testicular cancer, nonseminomas and seminomas, the former was strongly associated with a history of marijuana smoking, but the latter had little or no association, Dr. Dey says. Nonseminomas occur in younger men, grow more rapidly, and have lower survival rates. While a man diagnosed with seminomas is 98 percent as likely as someone without the disease to still be alive 10 years later, the figure for someone diagnosed with a nonseminoma ranges from 46 percent to 92 percent, depending on the tumor subtype.
The association between marijuana smoking and nonseminomas, but not seminomas, is difficult to explain, says Dr. Dey. The rates for both types of cancer have been rising, and subnormal fertility and certain environmental exposures during puberty—such as chemicals that affect estrogen and androgen production—are risk factors for both.
“My colleagues and I hope our study sparks similar epidemiological investigations of the relationship between testicular cancer and marijuana abuse around the world,” says Dr. Dey. “These results may also spur animal research, which is essential for interpreting our findings.” Animal research, he says, will be required to determine whether marijuana’s psychoactive ingredient, delta-9 tetrahydrocannabinol (THC), or its other components increase the risk of testicular cancer. Studies with animals may also search for molecular pathways connecting marijuana and testicular cancer. Such studies would probably focus
on marijuana’s activation of the neurotransmitter system that underlies its psychoactive, endocrine, and reproductive effects.
“If these interesting findings are replicated in a large, nationally representative group of participants, then future research should delve into the molecular mechanism underlying the association,” says Dr. Vishnudutt Purohit of NIDA’s Division of Basic Neuroscience and Behavioral Research. He notes that the study by Drs. Dey, Daling, and Schwartz is part of NIDA-supported research to determine how drugs of abuse affect the cardiovascular, pulmonary, reproductive, and immune systems of the body.
(For more information on these cancers, see http://seer.cancer.gov/publications/survival/surv_testis.pdf.)

SOURCE
Daling, J.R., et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer 115(6):1215–1223, 2009.
December 2010 NIDA Notes/ Volume 23, Number 3

Abstract

BACKGROUND:

The development of the fetal endocannabinoid receptor system may be vulnerable to maternal cannabis use during pregnancy and may produce long-term consequences in children. In this study, we aimed to determine the relationship between gestational cannabis use and childhood attention problems and aggressive behavior.

METHODS:

Using a large general population birth cohort, we examined the associations between parental prenatal cannabis and tobacco use and childhood behavior problems at 18 months measured using the Child Behavior Checklist in N=4077 children. Substance use was measured in early pregnancy.

RESULTS:

Linear regression analyses demonstrated that gestational exposure to cannabis is associated with behavioral problems in early childhood but only in girls and only in the area of increased aggressive behavior (B=2.02; 95% CI: 0.30-3.73; p=0.02) and attention problems (B=1.04; 95% CI: 0.46-1.62; p<0.001). Furthermore, this study showed that long-term (but not short term) tobacco exposure was associated with behavioral problems in girls (B=1.16; 95% CI: 0.20-2.12; p=0.02). There was no association between cannabis use of the father and child behavior problems.

CONCLUSIONS:

Our results suggest that intrauterine exposure to cannabis is associated with an increased risk for aggressive behavior and attention problems as early as 18 months of age in girls, but not boys. Further research is needed to explore the association between prenatal cannabis exposure and child behavior at later ages. Our data support educating future mothers about the risk to their babies should they smoke cannabis during pregnancy.

Source: http://www.ncbi.nlm.nih.gov/pubmed/21470799 4th April 2011

It requires 70 gallons of diesel fuel to produce one indoor Cannabis plant, or 140 gallons with smaller, less-efficient gasoline generators. In California, the top-producing state, indoor cultivation is responsible for about 3% of all electricity use or 8% of household use, somewhat higher than estimates previously made
for British Columbia.17 This corresponds to the electricity use of 1 million average
California homes, greenhouse-gas emissions equal to those from 1 million average cars, and energy expenditures of $3 billion per year. Due to higher electricity prices and cleaner fuels used to make electricity, California incurs 70% of national energy costs but contributes only 20% of national CO2 emissions from indoor Cannabis cultivation.

From the perspective of individual consumers, a single Cannabis cigarette represents 2 pounds of CO2 emissions, an amount equal to running a 100-watt light bulb for 17 hours assuming average U.S. electricity emissions (or 30 hours on California’s cleaner grid).

The emissions associated with one kilogram of processed Cannabis are equivalent to those of driving across country 5 times in a 44-mpg car. One single production module doubles the electricity use of an average U.S. home and triples that of an average California home. The added electricity use is equivalent to running about 30 refrigerators.

Producing one kilogram of processed Cannabis results in 3,000 kilograms of CO2 emissions. The energy embodied in the production of inputs such as fertilizer, water, equipment, and building materials is not estimated here and should be considered in future assessments.

Source: http://evan-mills.com/energy-associates/Indoor.html April 2011

The research demonstrates for the first time that cannabinoid receptors called CB2, which can be activated by cannabis use, are present in human sensory nerves in the peripheral nervous system, but are not present in a normal human brain.
Drugs which activate the CB2 receptors are able to block pain by stopping pain signals being transmitted in human sensory nerves, according to the study, led by researchers from Imperial College London.
Previous studies have mainly focused on the other receptor activated by cannabis use, known as CB1, which was believed to be the primary receptor involved in pain relief. However, as CB1 receptors are found in the brain, taking drugs which activate these receptors can lead to side-effects, such as drowsiness, dependence and psychosis, and also recreational abuse.
The new research indicates that drugs targeting CB2 receptors offer a new way of treating pain in clinical conditions where there are currently few effective or safe treatments, such as chronic pain caused by osteoarthritis and pain from nerve damage. It could also provide an alternative treatment for acute pain, such as that experienced following surgical operations.

The new study showed that CB2 receptors work to block pain with a mechanism similar to the one which opiate receptors use when activated by the powerful painkilling drug morphine. They hope that drugs which target CB2 might provide an alternative to morphine, which can have serious side effects such as dependency, nausea and vomiting.

Praveen Anand, Professor of Clinical Neurology and Principal Investigator of the study from the Division of Neurosciences and Mental Health at Imperial College London, said: ”Although cannabis is probably best known as an illegal recreational drug, people have used it for medicinal purposes for centuries. Queen Victoria used it in tea to help with her period pains, and people with a variety of conditions say that it helps alleviate their symptoms.

“Our new study is very promising because it suggests that we could alleviate pain by targeting the cannabinoid receptor CB2 without causing the kinds of side-effects we associate with people using cannabis itself.”
The researchers reached their conclusions after studying human sensory nerve cells in culture with CB2 receptor compounds provided by GlaxoSmithKline, and also injured nerves from patients with chronic pain.
The researchers are now planning to conduct clinical trials of drugs which target CB2 in patients with chronic pain at Imperial College Healthcare NHS Trust, which has integrated with Imperial College London to form the UK’s first Academic Health Science Centre.

Source: Anand et al. Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain, 2008; 138 (3): 667 DOI: 10.1016/j.pain.2008.06.007

Cannabis contains a chemical called THC, which binds to, and activates, proteins in the brain known as ‘CB1 cannabinoid receptors’. Activating these receptors can relieve pain and prevent epileptic seizures; but it also causes the mood-altering effect experienced by people who use cannabis as a recreational drug.

Now, Professor Maurice Elphick and Dr Michaela Egertová from Queen Mary’s School of Biological and Chemical Sciences may have found a way of separating out the effects of cannabis – a discovery which could lead to the development of new medicines to treat conditions such as epilepsy, obesity and chronic pain. The research is described in the December issue of the journal Molecular Pharmacology.

Working in collaboration with scientists based in the USA*, they have identified a protein that binds to the CB1 receptors in the brain. But unlike THC, this ‘Cannabinoid Receptor Interacting Protein’ or CRIP1a, suppresses the activity of CB1 receptors.

Professor Elphick explains: “Because CRIP1a inhibits the activity of the brain’s cannabinoid receptors, it may be possible to develop drugs that block this interaction, and in turn enhance CB1 activity. This may give patients the pain relief associated with CB1 activity, without the ‘high’ that cannabis users experience.”

Leslie Iversen FRS, Professor of Pharmacology at the University of Oxford and author of The Science of Marijuana, commented on the new findings: “This interesting discovery provides a completely new insight into the regulation of the cannabinoid system in the brain – and could offer a new approach to the discovery of cannabis-based medicines in the future.”

“CB1 Cannabinoid Receptor Activity Is Modulated by the Cannabinoid Receptor Interacting Protein CRIP1a” is published online in the December issue of Molecular Pharmacology.
The Elphick laboratory in the School of Biological & Chemical Sciences at Queen Mary is supported by grants from UK research councils (BBSRC, MRC) and the Wellcome Trust.

Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Queen Mary, University of London. April 2011

Ronald I. Herning, PhD, Warren E. Better, MS, Kimberly Tate, BS and Jean L. Cadet, MD

From the Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, National Institutes of Health,Baltimore,MD.

Address correspondence and reprint requests to Dr. Ronald I. Herning, Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, PO Box 5180, Baltimore, MD21224; e-mail: rherning@intra.nida.nih.gov

Objective: To determine possible effects of prolonged marijuanause on the cerebrovascular system during a month of monitoredabstinence and to assess how the intensity of current use mighthave influenced cerebrovascular perfusion in these marijuanausers.

Method: The authors recorded blood flow velocity in the anteriorand middle cerebral arteries using transcranial Doppler sonographyin three groups of marijuana users who differed in the intensityof recent use (light: n = 11; moderate: n = 23; and heavy: n= 20) and in control subjects (n = 18) to assess the natureand duration of any potential abnormalities. Blood flow velocitywas recorded within 3 days of admission and 28 to 30 days ofmonitored abstinence on an inpatient research unit in orderto evaluate subacute effects of the drug and any abstinence-generatedchanges.

Results: Pulsatility index, a measure of cerebrovascular resistance,and systolic velocity were significantly increased in the marijuanausers vs control subjects. These increases persisted in theheavy marijuana users after a month of monitored abstinence.

Conclusions: Chronic marijuana use is associated with increasedcerebrovascular resistance through changes mediated, in part,in blood vessels or in the brain parenchyma. These findingsmight provide a partial explanation for the cognitive deficitsobserved in a similar group of marijuana users.

Source:  NEUROLOGY 2005;64:488-493

Background

Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence(before age 15) with those who started later.

 Aims

To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls.

Method

We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA).

 Results

The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning.

Conclusions

Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive

functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Source:  The British Journal of Psychiatry (2011) 198, 442–447. doi: 10.1192/bjp.bp.110.077479

“Many studies have linked marijuana use with early onset of psychosis. The question is, does smoking marijuana cause earlier psychosis? A new review of 83 studies involving more than 22,000 participants seeks an answer.

The meta-analysis found that people who smoked marijuana developed psychotic disorders an average 2.7 years earlier than people who did not use cannabis
Context  A number of studies have found that the use of cannabis and other psychoactive substances is associated with an earlier onset of psychotic illness.
Objective  To establish the extent to which use of cannabis, alcohol, and other psychoactive substances affects the age at onset of psychosis by meta-analysis.
Data Sources  Peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non–substance-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science.
Study Selection  Studies in English comparing the age at onset of psychosis in cohorts of patients who use substances with age at onset of psychosis in non–substance-using patients. The searches yielded 443 articles, from which 83 studies met the inclusion criteria.
Data Extraction  Information on study design, study population, and effect size were extracted independently by 2 of us.
Data Synthesis  Meta-analysis found that the age at onset of psychosis for cannabis users was 2.70 years younger (standardized mean difference = –0.414) than for nonusers; for those with broadly defined substance use, the age at onset of psychosis was 2.00 years younger (standardized mean difference = –0.315) than for nonusers. Alcohol use was not associated with a significantly earlier age at onset of psychosis. Differences in the proportion of cannabis users in the substance-using group made a significant contribution to the heterogeneity in the effect sizes between studies, confirming an association between cannabis use and earlier mean age at onset of psychotic illness.
Conclusions  The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.
Matthew Large, BSc(Med), MBBS, FRANZCP; Swapnil Sharma, MBBS, FRANZCP; Michael T. Compton, MD, MPH; Tim Slade, PhD; Olav Nielssen, MBBS, MCrim, FRANZCP
Source: Arch Gen Psychiatry. Published online February 7, 2011. doi:10.1001/archgenpsychiatry.2011.5

Abstract

Delta (9)-tetrahydrocannabinol (THC), the most important psychoactive substance in cannabis, is frequently detected in blood from apprehended drivers suspected for drugged driving. Both experimental and epidemiological studies have demonstrated the negative effects of THC upon cognitive functions and psychomotor skills. These effects could last longer than a measurable concentration of THC in blood. Culpability studies have recently demonstrated an increased risk of becoming responsible in fatal or injurious traffic accidents, even with low blood concentrations of THC. It has also been demonstrated that there is a correlation between the degree of impairment, the drug dose and the THC blood concentration. It is very important to focus on the negative effect of cannabis on fitness to drive in order to prevent injuries and loss of human life and to avoid large economic consequences to the society.

 Source:  Tidsskr Nor Laegeforen. 2007 Mar 1;127(5):583-4.

Abstract

Delta (9)-tetrahydrocannabinol (THC), the most important psychoactive substance in cannabis, is frequently detected in blood from apprehended drivers suspected for drugged driving. Both experimental and epidemiological studies have demonstrated the negative effects of THC upon cognitive functions and psychomotor skills. These effects could last longer than a measurable concentration of THC in blood. Culpability studies have recently demonstrated an increased risk of becoming responsible in fatal or injurious traffic accidents, even with low blood concentrations of THC. It has also been demonstrated that there is a correlation between the degree of impairment, the drug dose and the THC blood concentration. It is very important to focus on the negative effect of cannabis on fitness to drive in order to prevent injuries and loss of human life and to avoid large economic consequences to the society.

Source:  Tidsskr Nor Laegeforen. 2007 Mar 1;127(5):583-4.

There has been much debate about whether cannabis might cause or exacerbate psychotic illnesses or whether characteristics of persons who tend to develop these conditions make them more likely to use the drug.

Authors of a new meta-analysis that found that earlier use of cannabis may trigger earlier onset of psychotic disorders say that their study supports a causative role.

Source: JAMA, March 2, 2011 – Vol. 305, No. 9

• Those who started smoking the drug at college were 90 per cent more likely to have psychotic symptoms in their mid-20s
• Some users suffered psychotic symptoms including hallucinations, delusions and disordered thoughts
Young people who use cannabis are doubling their risk of developing psychotic symptoms, experts warn. And mental health problems persist among those who continue using it compared with those who stop, according to research by an international team of scientists.
Their study adds to mounting evidence that smoking cannabis can trigger psychotic illnesses such as schizophrenia in vulnerable youngsters. It appears to demolish counter-arguments that cannabis does not cause symptoms of mental illness, or that some turn to the drug as a form of self-medication to deal with them.
The research also shows a link with psychosis at a very early stage of use among young people who previously never experienced such symptoms. They include paranoid ideas, hallucinations, hearing voices or bizarre behaviour.
The study, by a team from Germany, the Netherlands and the Institute of Psychiatry in London, focused on more than 1,900 volunteers aged 14 to 24 living in Germany. It followed up with the group after three years and eight years.
Those who had not previously used cannabis but began to during the study had double the risk of developing psychotic symptoms, it found. If they carried on using it, they were at an increased risk of psychotic experiences compared with those who did not. There was also no evidence that suffering psychotic symptoms was likely to result in people turning to cannabis for relief.
Reporting on their findings in the British Medical Journal, the team concluded: ‘Cannabis use precedes the onset of psychotic symptoms in individuals with no history of them.’
Cannabis may also increase the risk of lasting harm to mental health by making such symptoms persist with continued use. Last month, Australian researchers found that cannabis use accelerates the onset of full-blown mental illness almost three years earlier in people at risk.
Sir Robin Murray, professor of psychiatric research at the Institute of Psychiatry, said of the latest study: ‘It is one of ten prospective studies all pointing in this same direction. In short, it adds a further brick to the wall of evidence showing that use of traditional cannabis is a contributory cause of psychoses like schizophrenia.
‘It adds new information by showing that it is those who show psychotic symptoms within a few years of initiating cannabis use who are especially likely to develop persistent psychotic symptoms if they persist in their use of cannabis.’
Previous research has shown that a quarter of the population has a genetic predisposition which makes them ten times more likely to develop psychosis and other schizophrenia-like symptoms after smoking cannabis. Experts warn that anyone with pre-existing mental health problems or family history is at increased risk of mental illness if they use cannabis.
In a BMJ commentary, Professor Wayne Hall, from the University of Queensland, and Professor Louisa Degenhardt, from the Burnet Institute in Melbourne, say the link is biologically plausible and more information should be given to young people about the risks. ‘The case is strengthened by evidence that regular cannabis use in adolescence predicts poorer educational outcomes, increased risk of using other illicit drugs, increased risk of depression and poorer social relationships in early adulthood’, they added.

Source: http://www.dailymail.co.uk/health/article 2nd March 2011

Although growing literature suggests that long-term marijuana use is associated with a wide range of adverse health consequences, many people believe it is relatively harmless and should be legalized, the researchers noted. “However, this study shows long-term, heavy cannabis use causes significant brain injury, memory loss, difficulties learning new information, and psychotic symptoms, such as delusions of persecution [paranoia], delusions of mind-reading, and bizarre social behaviors in even non-vulnerable users,” said lead researcher Murat Yucel, from the ORYGEN Research Centre and the Neuropsychiatry Centre at the University of Melbourne.
This new evidence plays an important role in further understanding the effects of marijuana and its impact on brain functioning, Yucel said. “The study is the first to show that long-term cannabis use can adversely affect all users, not just those in the high-risk categories such as the young, or those susceptible to mental illness, as previously thought,” he said.
The report was published in the June issue of the Archives of General Psychiatry.
In the study, Yucel’s team did high-resolution MRIs on 15 men who smoked more than five joints a day for more than 10 years. They compared those with scans of 16 men who did not In addition, all the men took verbal memory tests and were examined for symptoms of psychiatric disorders. “The more marijuana used, the more these individuals were likely to show reduced brain volumes in the hippocampus and amygdala, as well as being more likely to develop symptoms of psychotic disorders and to have significant memory impairment,” Yucel said.
In fact, the hippocampus of marijuana users was 12 percent smaller, and the amygdala was 7.1 percent smaller than among nonusers. In addition, men who used marijuana also had symptoms of psychiatric disorders, Yucel’s group found. The hippocampus is associated with the regulation of emotion and memory, while the amygdala controls fear and aggression.
“There is ongoing controversy concerning the long-term effects of cannabis on the brain,” Yucel said. “These findings challenge the widespread perception of cannabis as having limited or no harmful effects on brain and behavior. Although modest use may not lead to significant neurotoxic effects, these results suggest that heavy daily use might indeed be toxic

SOURCE: Murat Yucel, Ph.D., ORYGEN Research Centre, Melbourne Neuropsychiatry Centre, University of Melbourne, Australia; Adam Bisaga, M.D., assistant professor, psychiatry, Columbia University, and addiction psychiatrist, New York State Psychiatric Institute, New York City; June 2008, Archives of General Psychiatry

Summary

Background

Whether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes.

Methods

We searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from 4804 references were included. Data extraction and quality assessment were done independently and in duplicate.

Findings

There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1•41, 95% CI 1•20—1•65). Findings were consistent with a dose-response effect, with greater risk in people who used cannabis most frequently (2•09, 1•54—2•84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately. Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding effect was present for both psychotic and affective outcomes.

Interpretation

The evidence is consistent with the view that cannabis increases risk of psychotic outcomes independently of confounding and transient intoxication effects, although evidence for affective outcomes is less strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.

Source: The Lancet, Volume 370, Issue 9584, Pages 319 – 328, 28 July 2007

Abstract:

Context A number of studies have found that the use of cannabis and other psychoactive substances is associated with an earlier onset of psychotic illness.
Objective To establish the extent to which use of cannabis, alcohol, and other psychoactive substances affects the age at onset of psychosis by meta-analysis.
Data Sources Peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non–substance-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science.
Study Selection Studies in English comparing the age at onset of psychosis in cohorts of patients who use substances with age at onset of psychosis in non–substance-using patients. The searches yielded 443 articles, from which 83 studies met the inclusion criteria.
Data Extraction Information on study design, study population, and effect size were extracted independently by 2 of us.
Data Synthesis Meta-analysis found that the age at onset of psychosis for cannabis users was 2.70 years younger (standardized mean difference = –0.414) than for nonusers; for those with broadly defined substance use, the age at onset of psychosis was 2.00 years younger (standardized mean difference = –0.315) than for nonusers. Alcohol use was not associated with a significantly earlier age at onset of psychosis. Differences in the proportion of cannabis users in the substance-using group made a significant contribution to the heterogeneity in the effect sizes between studies, confirming an association between cannabis use and earlier mean age at onset of psychotic illness.
Conclusions The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.
(Full text available here) – http://archpsyc.ama assn.org/cgi/content/full/archgenpsychiatry.2011.5

Source: . Archives of General Psychiatry, 7th February 2011

Background

The associations between age of onset of cannabis use and educational achievement were examined using data from three Australasian cohort studies involving over 6000 participants. The research aims were to compare findings across studies and obtain pooled estimates of association using meta-analytic methods.

Methods

Data on age of onset of cannabis use (<15, 15–17, never before age 18) and three educational outcomes (high school completion, university enrolment, degree attainment) were common to all studies. Each study also assessed a broad range of confounding factors.

Results

There were significant (p < .001) associations between age of onset of cannabis use and all outcomes such that rates of attainment were highest for those who had not used cannabis by age 18 and lowest for those who first used cannabis before age 15. These findings were evident for each study and for the pooled data, and persisted after control for confounding. There was no consistent trend for cannabis use to have greater effect on the academic achievement of males but there was a significant gender by age of onset interaction for university enrolment. This interaction suggested that cannabis use by males had a greater detrimental effect on university participation than for females. Pooled estimates suggested that early use of cannabis may contribute up to 17% of the rate of failure to obtain the educational milestones of high school completion, university enrolment and degree attainment.

Conclusions

Findings suggest the presence of a robust association between age of onset of cannabis use and subsequent educational achievement.

Source: www.sciencedirect.com April 2010

1. 12/17 states (including DC) with “medical” marijuana” have 20% + traffic fatalities involving drugs
70.6% of states with MMJ laws have driver fatalities testing positive for drugs of 20% or greater

2. 13/17 states with “medical” marijuana” has 19% + traffic fatalities involving drugs (Arizona)
76% of states with MMJ have driver fatalities testing positive for drugs of 19% or higher

3. 3/17 states with “medical” marijuana” laws that have low rates of driver fatalities also have low rates of testing for drugs (Oregon, Rhode Island, Maine: not tested 79%, 41%, 100% ).

4. 1/17 states with “medical” marijuana”, New Mexico, tests all, but has anomalous 1% positive tests (an outlier, along with Mississippi, North Carolina).
Drug testing of drivers in fatal accidents should be 100%!

STATES WITHOUT “MEDICAL MARIJUANA” LAWS HAVE LOWER PREVALENCE OF DRIVER FATALITIES INVOLVING DRUGS: 27%

1. 24/33 states with no “medical” marijuana” laws have fewer than 20% of driver fatalities involving drugs
73% of states with no “medical marijuana” laws have fewer than 20% driver fatalities testing positive for drug.

2. 9/33 states with no “medical” marijuana” approval have 20% or more driver fatalities involving drugs.
27% of states with no “medical marijuana” laws have 20% or more of driver fatalities involving drugs

3. Ct, state with highest number of fatalities also has highest rate of testing, 99%
Prevalence of driver fatalities involving drugs is three times higher, on average, in states with approved “medical marijuana” laws.

Source: Bertha Madras PhD Harvard Medical School Dec. 2010

Amsterdam bans smoking of marijuana in some public places

AMSTERDAM – A majority of the city council in Amsterdam voted in favour of introducing a city-wide ban on smoking marijuana in public in areas where young people smoking joints have been causing public nuisance.
The decision comes after a successful trial ban in the De Baarsjes district of Amsterdam.
The experimental ban led to less public nuisance, city district De Baarsjes concluded after the year-long trial.
Source: Expatica.com Jan 2007

BY MARK HENDERSON, SCIENCE CORRESPONDENT

ONE in four people carries genes that increases vulnerability to psychotic illnesses if he or she smokes cannabis as a teenager, scientists have found.
A common genetic profile that makes cannabis five times more likely to trigger schizophrenia and similar disorders has been identified, increasing pressure on the Government to reverse the drug’s reclassification from Class B to Class C.

The increased risk applies to people who inherit variants of a gene named COMT who also smoked cannabis as teenagers. About a quarter of the population have this genetic make-up, and up to 15 per cent of the group are likely to develop psychotic conditions if exposed to the drug early in life.
Neither the drug nor the gene raises the risk of psychosis by itself.
The study, led by Avshalom Caspi and Terrie Moffitt, of the Institute of Psychiatry at King’s College London, offers the best explanation yet for the way that cannabis has a devastating psychiatric impact on some users but leaves most unharmed. Scientists had suspected that genetic factors were responsible for this divide, but a gene had not been pinpointed.
The findings, to be published in Biological Psychiatry, also reinforce a growing consensus that nature and nurture are not mutually exclusive forces but combine to affect behaviour and health. The King’s team has previously identified genes that raise the risk of depression or aggression, but only in conjunction with environmental influences.
Mental health campaigners said that the results vindicated their concerns about the decision last year to downgrade cannabis to a Class C drug, which means that possession is no longer an arrestable offence.
Marjorie Wallace, chief executive of the mental health charity Sane, said that it was becoming clear that cannabis placed millions of users at risk of lasting mental illness. About fifteen million Britons have tried cannabis, and between two million and five million are regular users, according to the Home Office British Crime Survey. The research suggests that a quarter could be at risk.
The evidence will be considered by a review of the drug’s classification announced last month by the Home Secretary. It may be possible to develop a test for genetic susceptibility to cannabis. “If we were able genetically to identify the vulnerable individuals in advance, we would be able to save thousands of minds, if not lives,” Ms Wallace said.
Dr Caspi, however, rejected the idea of screening based on the COMT gene. “Such a test would be wrong more often than it is right. Cannabis has many other adverse effects, especially on developing teenagers, on respiratory health and possibly on cognitive function. Effects may be pronounced among a genetically vulnerable group but that doesn’t mean we should encourage others not genetically vulnerable to use cannabis.”
The King’s team tracked 803 men and women born in Dunedin, New Zealand, in 1972 and 1973, who were enrolled at birth in a research project. Each was interviewed at 13, 15 and 18 about cannabis use, tested to determine which type of COMT genes they had inherited, and followed up at 26 for signs of mental illness.
COMT was chosen as it is known to play a part in the production of dopamine, a brain-signalling chemical that is abnormal in schizophrenia. It comes in two variants, known as valine or methionine, and every person has two copies, one from each parent.
Among people with two methionine variants, the rate of psychotic illness was 3 per cent, the background rate for the general population, regardless of whether they had used cannabis as teenagers.
Among those with two valine variants the rate was 3 per cent for non-users but 15 per cent for those who had smoked cannabis in their teens.
Dr Caspi said research had shown that the valine gene variant and cannabis affect the brain’s dopamine system in similar fashion, suggesting that they deliver a “double dose” that can be damaging. The work needs to be replicated by others to confirm the findings, Dr Caspi said. It also is possible that the gene involved is not COMT but a neighbour.
THE DRUG OF CHOICE FOR MILLIONS
• Cannabis was reclassified from a Class B to a Class C drug in January 2004. Possession remains illegal, but is not an arrestable offence. The Home Secretary has asked for a review by November
• The Home Office estimates that fifteen million people have tried cannabis, two million to five million are regular users and reclassification has saved 199,000 hours’ police work
• Liberalisation campaigners argue that millions smoke the drug with fewer ill-effects than others suffer from alcohol or tobacco
• A recent study at Maastricht University found that cannabis doubles the risk of schizophrenia, hallucinations and paranoia among a genetically susceptible group

Source: www.timesonline.co.uk 14 April 2005

The State Government figures show that out of 4619 drivers pulled over, one in 73 tested positive to either cannabis or methamphetamines. This compared to an average of one in 250 drivers testing positive for alcohol. The results surprised police.

The results come just two days after research by the National Drug and Alcohol Research Centre showed 57 per cent of clubbers admitted driving under the influence of alcohol and 52 per cent under the influence of cannabis. The VicRoads-commissioned study reported that just under half of those surveyed admitted driving soon after taking other drugs.

43% said they had taken ecstasy and 42 % speed.

Source: Minister for Police & Emergency Services. Victoria. Australia. April 15 2005

[Correspondence]
Tashkin, Donald P.; Roth, Michael D.; Dubinett, Steven M.
UCLA School of Medicine; Los Angeles, CA 90095-1690

———————————————-

To the Editor: You point to largely experiential evidence of the medicinal
benefits of marijuana and the apparent absence of serious short-term toxicity.
However, a note of caution is warranted. Although it is true that smoking
marijuana carries no immediate risk of death, there may be serious adverse
effects in the very patients for whom medicinal marijuana is most commonly
considered (i.e., those whose immune defenses are already compromised by AIDS or
cancer plus chemotherapy). For example, in patients with AIDS, marijuana use has
been associated with the development of both fungal and bacterial pneumonias.
[1,2] Moreover, among HIV-positive persons, marijuana use has been shown to be a
risk factor for rapid progression from HIV infection to AIDS and the acquisition
of opportunistic infections or Kaposi’s sarcoma, or both. [3]

Cellular studies and studies in animals lend support to these potential health
consequences of marijuana. For example, delta-9-tetrahydrocannabinol has been
shown to have immunosuppressive effects on macrophages, natural killer cells,
and T cells, as well as on the response of mice to opportunistic infection. [4]
In our own studies, [5] (and unpublished data) we recovered alveolar macrophages
from the lungs of habitual marijuana smokers and found a significant reduction
in their ability to kill fungi, bacteria, and tumor cells, as well as a
deficiency in their ability to produce protective inflammatory cytokines, such
as tumor necrosis factor (alpha).

Donald P. Tashkin, M.D.

Michael D. Roth, M.D.

Steven M. Dubinett, M.D.

UCLA School of Medicine; Los Angeles, CA 90095-1690

REFERENCES

1. Denning DW, Follansbee SE, Scolaro M, Norris S, Edelstein H, Stevens DA.
Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N Engl J Med
1991;324:654-62. Bibliographic Links

2. Caiaffa WT, Vlahov D, Graham NM, et al. Drug smoking, Pneumocystis carinii
pneumonia, and immunosuppression increase risk of bacterial pneumonia in human
immunodeficiency virus-seropositive injection drug users. Am J Respir Crit Care
Med 1994;150:1493-8. Bibliographic Links

3. Tindall B, Cooper DA, Donovan B, et al. The Sydney AIDS Project: development
of acquired immunodeficiency syndrome in a group of HIV seropositive homosexual
men. Aust N Z J Med 1988;18:8-15. Bibliographic Links

4. Newton CA, Klein TW, Friedman H. Secondary immunity to Legionella pneumophilia
and Th1 activity are suppressed by delta-9-tetrahydrocannabinol. Inject Infect
Immun 1994;62:4015-20.

5. Sherman MP, Campbell LA, Gong H Jr, Roth MD, Tashkin DP. Antimicrobial and
respiratory burst characteristics of pulmonary alveolar macrophages recovered
from smokers of marijuana alone, smokers of tobacco alone, smokers of marijuana
and tobacco, and nonsmokers. Am Rev Respir Dis 1991;144:1351-6. Bibliographic
Links Accession Number: 00006024-199704170-00025

Results of a new survey into cannabis use showed that 1 in 3, 15 year olds has now smoked cannabis. 18% of pupils aged 11 to 18 had taken drugs in the previous 12 months. 13% had tried cannabis in the previous year, by the age of 15, that had risen to 31%. 28% of pupils sold they had been offered cannabis. Harder drugs like cocaine ecstasy and amphetamines had been touted to 1 in 5 schoolchildren. A Dept of Health spokesman said that the no. of pupils taking drugs had decreased slightly from 20% in 2001 to 1870 in 2002. This is all in a survey of 10000 pupils by the National Centre for Social Research and The National Centre for Educational Research.

Source: Survey of 10,000 pupils by National centre for Social Research & National centre for Educational Research. Reported in daily Mail 29 March 2003

Adolescents’ use of marijuana may increase the risk of heroin addiction later in life, a new study suggests. Researchers say the work adds to “overwhelming” evidence that people under 21 should not use marijuana because of the risk of damaging the developing brain.
The idea that smoking cannabis increases the user’s chance of going on to take harder drugs such as heroin is highly contentious. Some dub cannabis a “gateway” drug, arguing that peer pressure and exposure to drug dealers will tempt users to escalate their drug use. Others insist that smoking cannabis is unrelated to further drug use.
Now research in rats suggests that using marijuana reduces future sensitivity to opioids, which makes people more vulnerable to heroin addiction later in life. It does so by altering the brain chemistry of marijuana users, say the researchers.
“Adolescents in particular should never take cannabis – it’s far too risky because the brain areas essential for behaviour and cognitive functioning are still developing and are very sensitive to drug exposure,” says Jasmin Hurd, who led the study at the Karolinska Institute in Sweden.
But Hurd acknowledges that most people who use cannabis begin in their teens. A recent survey reported that as many as 20% of 16-year-olds in the US and Europe had illegally used cannabis in the previous month.

“Teenage” rats

In order to explore how the adolescent use of cannabis affects later drug use, Hurd and colleagues set up an experiment in rats aimed to mirror human use as closely as possible.
In the first part of the trial, six “teenage” rats were given a small dose of THC – the active chemical in cannabis – every three days between the ages of 28 and 49 days, which is the equivalent of human ages 12 to 18. The amount of THC given was roughly equivalent to a human smoking one joint every three days, Hurd explains. A control group of six rats did not receive THC.
One week after the first part was completed, catheters were inserted in all 12 of the adult rats and they were able to self-administer heroin by pushing a lever.
“At first, all the rats behaved the same and began to self-administer heroin frequently,” says Hurd. “But after a while, they stabilised their daily intake at a certain level. We saw that the ones that had been on THC as teenagers stabilised their intake at a much higher level than the others – they appeared to be less sensitive to the effects of heroin. And this continued throughout their lives.”
Hurd says reduced sensitivity to the heroin means the rats take larger doses, which has been shown to increase the risk of addiction.

Drug memory

The researchers then examined specific brain cells in the rats, including the opioid and cannabinoid receptors. They found that the rats that had been given THC during adolescence had a significantly altered opioid system in the area associated with reward and positive emotions. This is also the area linked to addiction.
“These are very specific changes and they are long-lasting, so the brain may ‘remember’ past cannabis experimentation and be vulnerable to harder drugs later in life,” Hurd says.
Neurologist Jim van Os, a cannabis expert at the University of Maastricht in the Netherlands told New Scientist the research was a welcome addition to our understanding of how cannabis affects the adolescent brain.
“The issue of cross-sensitisation of cannabis/opioid receptors has been a controversial one, but these findings show the drug’s damaging effects on the reward structures of the brain,” van Oshe says. “There is now overwhelming evidence that nobody in the brain’s developmental stage – under the age of 21 – should use cannabis.”

Source: On line edition of Neuropsychopharmacology. Reported in NewScientist.com July 2006

Yes, despite what potheads claim. Doctors in Greece compared the mental abilities of 20 people who had smoked dope four times a week for 15 years with 20 who had used it for less than seven years, and 24 never-smokers. They were given 15 words to learn, and asked to repeat them later. The average score for the long-term smokers was 7; for the shorter-term smokers, 9; for the never-users, 12. It is the latest in many studies showing repeated ‘soft’ drug abuse damages the brain. This isn’t surprising because marijuana’s active ingredient, tetrahydro cannabinol (THC), is highly fat-soluble. As our brain is the organ with the highest concentration of fat, THC makes a beeline for it and stays there for

Source: The Guardian Saturday September 30, 2006

27 October 2006

Researchers have found altered neural synchronization in people who smoke cannabis, providing evidence to support the link between the use of this drug and schizophrenia.

Altered neural synchronization has previously been demonstrated in patients with schizophrenia. This led Patrick Skosnik (Indiana University, Bloomington, USA) and team to suggest that such alterations may represent a neurophysiological link between schizophrenia symptoms and the neurobehavioral effects of cannabis.

The researchers assessed neural synchronization using electroencephalograms (EEG) to measure auditory steady-state potentials, eg, auditory click trains at specific frequencies – 20, 30, and 40 Hz – in 17 cannabis users and 16 drug naïve individuals.

The cannabis users showed decreased EEG power and signal-to-noise ratio at the stimulation frequency of 20 Hz compared with non-drug users.

Skosnik and colleagues note that there was no significant difference between the two groups with regard to noise power, indicating that the altered neural synchronization in cannabis users was due to decreased signal strength of oscillating circuits and not the increased noise stemming from neural background activity.

The cannabis users also demonstrated increased schizotypal personality characteristics, as assessed on the Schizotypal Personality Questionnaire, compared with controls. However, there was no significant difference between the two groups in scores on the Wechsler Adult Intelligence Scale. This demonstrates that any alterations in neural synchrony were not associated with generalized cognitive or sensory deficits, the researchers note.

Further analysis revealed that scores on the Schizotypal Personality Questionnaire positively correlated with total years of cannabis use. In addition, schizotypy scores negatively correlated with 20 Hz power, indicating that cannabis-using individuals scoring higher in schizotypy had larger deficits in neural synchronization.

“These data provide evidence for neural synchronization and early-stage sensory processing deficits in cannabis use,” the team writes in the American Journal of Psychiatry.

“Given that there is tight coupling of the endocannabinoid and dopamine systems, it appears possible that genetic anomalies leading to altered dopamine activity may interact with early cannabis exposure to produce overt psychosis.”

Source: Am J Psychiatry 2006; 163: 1798–1805
©2006 Current Medicine Group Ltd

New research shows that a synthetic analogue of the active component [THC] of marijuana may reduce the inflammation and prevent the mental decline associated with Alzheimer’s disease.

“This research is not only a major step in our understanding [of] how the brain reacts to Alzheimer’s disease, but may also help open a route to novel anti-Alzheimer’s drugs,” says Raphael Mechoulam, professor emeritus of medicinal chemistry at Hebrew University in Jerusalem and discoverer of marijuana’s active component.

To show the preventive effects of cannabinoids on Alzheimer’s disease, researchers at the Cajal Institute and Complutense University in Madrid, led by Maria de Ceballos, conducted studies using human brain tissue, as well as experiments with rats.

Source:The Journal of Neuroscience February 23, 2005

The active ingredient in marijuana may stall decline from Alzheimer’s disease, research suggests. Scientists showed a synthetic version of the compound may reduce inflammation associated with Alzheimer’s and thus help to prevent mental decline. They hope the cannabinoid may be used to developed new drug therapies. The research, by Madrid’s Complutense University and the Cajal Institute, is published in the Journal of Neuroscience.

Source:http://www.biopsychology.com/index. Feb 2005

A cannabis-based drug could help people with Alzheimer’s disease by giving them the “munchies”, researchers say.

Patients with the condition often experience weight loss because they stop recognising when they are hungry. The study does not suggest they should be given cannabis to smoke – instead, they tested a synthetic version of a cannabis extract. It was found the cannabinoid led to weight and reduced agitation, another symptom of the disease. The researchers from the Meridian Institute for Aging in New Jersey looked at a drug called dronabinol which is an artificial version of delta-9 THC, the active ingredient in cannabis.

Dronabinol may reduce agitation and improve appetite in patients with Alzheimer’s disease

Dr Joshua Shua-Haim, Meridian Institute for Aging

Source: BBC report 21 Aug.2003

June 28, 2004
Vol. 13, Issue 26

Nine behaviours and attitudes differentiate students who used marijuana before age 15 from those who had not, according to an analysis of data from the 2002 Maryland Adolescent Survey (MAS). Overall, one-fifth of Maryland 12th grade students reported using marijuana before age 15. A scale of 9 warning signs of early marijuana use among 12thgraders was developed from an analysis of the MAS data (see below). The scale also detected early use among 8th and 10th graders. The more warning signs a student had, the more likely he or she was to have used marijuana early . For example, approximately three-fourths of 12th graders with 6 or more warning signs were early marijuana users, compared to 3% of 12th graders with no warning signs. Students with more warning signs also reported using a greater number of other illegal drugs*and experiencing a greater number of serious problems **resulting from drug and alcohol use report, “Warning Signs for Early Marijuana Users Among Maryland’s Public School Students,” discusses the implications of these findings for intervening with youth and implementing prevention programs. Complimentary copies of the report can be ordered by contacting CESAR at cesar@cesar.umd.eduor 301-405-9770.

Behaviors•
Cigarette use before age 15
•Alcohol use before age 15
•20 or more unexcused absences
•Drug arrest
•Alcohol arrest
Attitudes/Opinions
•Smoking marijuana is safe
•Smoking cigarettes is safe
•My parents think it’s okay to smoke marijuana
•My parents think it’s okay to smoke

SOURCE: Maryland Drug Early Warning System (DEWS), CESAR, “Warning Signs for Early Marijuana Users Among Maryland’s Public School Students,” DEWS Investigates, June 2004. For more information, contact Dr. Eric Wish at ewish@cesar.umd.edu.

J. Michael Walsh, Ph.D.
October 12, 2010
The consumption of illegal psychoactive drugs (e.g. amphetamines, cocaine, marijuana, opiates, etc.) is a problem of growing concern in many countries around the world, as these substances are increasingly detected in impaired and injured drivers. Drugged driving is a serious public health concern because it puts not only the user at risk, but all others who share the road. Despite the mounting evidence that drugged driving is common, the American public seems unaware of this fact. Perhaps this is because drugged drivers are less frequently detected, prosecuted, or referred to treatment, compared to drunk drivers.
Other than alcohol, Marijuana is the most prevalent drug detected in impaired and injured drivers. Marijuana affects areas of the brain that control the body’s movements, balance, coordination, memory, and judgment abilities, and its effects last for hours after the drug is used. Evidence from both on-the-road and simulated driving studies indicate marijuana can negatively influence a driver’s attentiveness, perception of time and speed, and the ability to draw on information obtained through past experiences.
Driving is a complex task that requires continuous information processing and coordinated responses to ever-changing traffic, while operating a multi-ton vehicle. Clearly, illegal drugs like marijuana that alter a driver’s normal brain functioning can create an extremely dangerous situation.

Source: www.ofSubstance.gov/blogs Tuesday, October 12, 2010

The excerpts below are from two Rand studies, Would Legalizing Marijuana in California Help?
Beau Kilmer, Jonathan P. Caulkins, Brittany M. Bond, Peter H. Reuter 2010

And What We Do and Don’t Know About the Likely Effects of Decriminalization and Legalization by Robert J. MacCoun and Peter Reuter. 1999

Since it is often difficult to read the whole of a large study I have pulled out parts which I think may be useful to those of us fighting the legalisation of drugs – with particular reference to Prop. 19 in California

Taken together, the available evidence suggests that the nonprice impact on consumption might be on the order of a 35-percent increase in past-month use. Given the ambiguity and noisiness of the data, estimates in the range of 5 to 50 percent seem plausible.

Throughout California in 2008, there were 181 admissions to hospitals in which marijuana abuse or dependence was listed as the primary reason for the hospitalization. Even though the average charge per episode exceeded $22,000, the total cost of these episodes is just over $2 million, so relatively small vis-à-vis the other costs and savings.

Perhaps more important from a cost perspective are the additional 25,000 admissions for which marijuana is listed as a supplemental diagnosis (second, third, or fourth diagnosis). Of these cases, nearly 4,000 were for schizophrenia (with an average charge of $20,300 per episode) and another 2,300 were for psychoses (with an average cost of $12,700). As the scientific
literature is still unclear as to whether marijuana use causes these conditions or just complicates treating them, we do not consider the cost here of these nonprimary diagnoses. More research is needed before an accurate assessment can be conducted, but the implications of these research findings could be important in terms of the burden imposed. For more details
on this, see Pacula (2010a).

Dependence and Abuse
How would the number of marijuana users meeting clinical criteria for abuse or dependence change with a change in the policy? Over this decade, the number of users meeting these criteria in the previous year as a fraction of people reporting use of marijuana in the past year in nationally representative samples has been fairly stable (~16 percent). One way to project what
could happen to dependent users post-legalization is to assume that this relationship between the number dependent and past-year users remains the same.

We start by making an assumption about legalization’s effect on consumption. For this example, we consider a 58-percent increase in annual consumption and refer interested readers to Pacula (2010a) for more information about this starting value. With 525,000 users estimated to meet Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV)
criteria for marijuana abuse or dependence in California in 2009 (Pacula, 2010a), a 58-percent increase would suggest a rise of 305,000, bringing the total number of users meeting clinical criteria for abuse or dependence to 830,000. Of course, there is tremendous uncertainty surrounding this number because of uncertainty about the baseline assumptions that generated
the predicted change in annual prevalence. If we adopt alternative plausible assumptions, we generate a range of 144,000 to 380,000, implying that the total number of users meeting clinical criteria for abuse or dependence would be in the range of 669,000 to 905,000.

There are currently no estimates in the literature of the social cost of a user meeting clinical criteria for abuse or dependence; thus, it is not possible to quantify this increase’s budgetary impact on California taxpayers. But, to the extent that dependence and abuse impose costs in the form of reduced productivity, higher health-care costs, or lost time with the family, a rise
in dependence represents a real loss to the citizens of California.

Drugged Driving
While driving under the influence of marijuana or any other intoxicating substance can be risky, a question remains about whether marijuana use impairs individuals sufficiently to cause crashes and fatalities. While there is significant experimental literature suggesting a diminished effect on response rates and performance under very strictly controlled conditions, evidence
from epidemiological studies has been less conclusive (Ramaekers et al., 2004; Blows et al., 2005). The notable exception in the literature are cases in which alcohol is used in conjunction with marijuana, in which case the evidence is clear that the combined effect of these two drugs impairs driving significantly more than alcohol alone (Bramness, Khiabani, and two drugs impairs driving significantly more than alcohol alone (Bramness, Khiabani, andMørland, 2010; Jones et al., 2003; Dussault et al., 2002).

Given the current uncertainty of the science in determining the role of marijuana use alone in accidents, it is impossible to determine how much an increase in marijuana use would translate into more accidents or, worse
yet, fatal crashes. However, a simple calculation suggests that, if someone believes that marijuana is causally responsible for many crashes that involve marijuana using drivers, legalization’s effect on crashes could be a first-order concern for them. Based on Fatality Analysis Reporting System (FARS) data, Crancer and Crancer (2010) report that blood tests established that one or both drivers had used marijuana near the time of the accident in 5.5 percent of passenger-vehicle fatal crashes (2008 in California). Causality is complicated in multicar crashes, but, even just considering single-vehicle fatal crashes, Crancer and Crancer found that 126 fatalities in crashes with marijuana involved drivers, 75 percent of whom had alcohol levels below 0.08.
There is no empirical evidence concerning an elasticity of fatal accident rates with respect to marijuana price, prevalence, or quantity consumed, and, as we have underscored repeatedly, there is enormous uncertainty concerning how legalization might affect those outcomes.

However, 50- or 100-percent increases in use cannot be ruled out; nor can the possibility that marijuana-involved traffic crashes would increase proportionally with use. So it would be hard to dismiss out of hand worries that marijuana legalization could increase traffic fatalities by at least 60 per year (126 × 50% = 63)—especially since this represents increases in fatalities
associated only with single-vehicle crashes and ignores the role marijuana might play in multivehicle fatalities. See Pacula (2010a) for a more detailed analysis. There is no satisfactory way to compare the importance of some number of traffic deaths to dollar-denominated outcomes, such as tax
revenues, but, when economists are forced to come up with such a number, they often use figures on the order of $4 million to $9 million per death (Viscusi and Aldy, 2003). Whereas we are reasonably confident that additional costs of marijuana treatment and of ED mentions and hospitalizations related directly to use per se are not first-order concerns, we cannot rule out that possibility with respect to legalization’s effects on drugged driving.

Use of Other Substances
Legalization will reduce marijuana prices and increase marijuana use. Either effect could affect the use of other substances. We take them up in reverse order. Increased marijuana use could lead to greater use of other substances in various ways. For example, it is possible that becoming dependent on marijuana affects neural pathways in a way that increases vulnerability to abusing other substances. However, almost all the literature and
controversy concerns a possible causal effect of use short of dependence.

The use of marijuana typically precedes the use of such substances as cocaine and heroin, and people who use marijuana earlier and more heavily are more likely to go on to more and heavier use of these substances (Kandel, 2002). These facts have given rise to the so-called gateway
hypothesis—the hypothesis being that the pattern is not merely coincidence but instead reflects causal linkages, so that anything that increases or reduces use of marijuana might thereby cause an increase or reduction in use of these other substances.

Few topics in the drug-policy literature have stirred greater passions than the gateway hypothesis. While everyone agrees about the descriptive facts (e.g., cocaine use is usually preceded by marijuana use), there are sharp differences about whether the patterns reflect a causal relationship and, if so, what the causal mechanism is. Skeptics are fond of pointing out that
cocaine use is also usually preceded by drinking milk (i.e., most cocaine users tried milk before they first experimented with cocaine, but no one believes that drinking milk puts one at risk for greater cocaine use).
The gateway effect, if it exists, has at least two potential and quite different sources (MacCoun, 1998). One interpretation is that it is an effect of the drug use itself (e.g., trying marijuana increases the taste for other drugs or leads users to believe that other substances are more pleasurable or less risky than previously supposed). A second interpretation stresses peer groups
and social interactions. Acquiring and using marijuana regularly may lead to differentially associating with peers who have attitudes and behaviors that are prodrug generally, not only with respect to marijuana. One version of this is the possibility that those peers will include people who sell other drugs, reducing the difficulty of locating potential supplies. If the latter
is the explanation, then legalization might reduce the likelihood of moving on to harder drugs compared to the current situation.

Many studies have examined the gateway effect, and Room et al. (2010, p. 35) provide a concise appraisal of the international, multidisciplinary evidence:
Cannabis use is more strongly associated with other illicit drug use than alcohol or tobacco use, and the earliest and most frequent cannabis users are the most likely to use other illicit drugs. Animal studies provide some biological plausibility for a causal relationship between cannabis and other types of illicit drug use. Well-controlled longitudinal studies suggest that selective recruitment to cannabis use does not wholly explain the association between cannabis use and the use of other illicit drugs. This is supported by discordant twin studies [that] suggest that shared genes and environment do not wholly explain the association. Nonetheless, it has been difficult to exclude the hypothesis that the pattern of use reflects the common characteristics of those who use cannabis and other drugs. We say nothing more about gateway effects because there simply is no consensus about it.

Farrelly et al. (2001) use a proxy for marijuana use, and their results suggest that, when marijuana use goes up, so does tobacco use.

Cocaine. A number of studies suggest that marijuana and cocaine are economic complements, but many of these studies use the problematic decriminalization variable as a proxy for marijuana price (Thies and Register, 1993; Grossman and Chaloupka, 1998; Saffer and Chaloupka,
1999). Williams and colleagues (2006) use actual marijuana prices in their analysis of cocaine use among college students in the United States. For college students in the 1990s, they estimate the cross-price participation elasticity for cocaine to be between -0.44 and -0.49.
This means that a 10-percent decrease in the price of marijuana would increase the prevalence of cocaine use by 4.4 to 4.9 percent.

Excerpts below from the Rand Testimony to the Subcommittee on Criminal Justice, Drug Policy and Human Resources of the House Committee on Government Reform – July 13th l999 (Peter Reuter and Robert J. MacCoun

Several lines of evidence on the deterrent effects of marijuana laws and on decriminalization experiences in the United States. the Netherlands and Australia –suggest that eliminating (or significantly reducing) criminal penalties for first-time possession of small quantities of marijuana has either no effect or a very small effect on the prevalence of marijuana use.
….. Decriminalisation was not associated with any detectable changes in adolescent attitudes toward marijuana. [now, in 2010 we can already see that
So-called medical marijuana and Prop.19 in CA have changed adolescent attitudes

….The initial decriminalization (in the Netherlands) phase had no detectable impact on levels of cannabis use, consistent with evidence from the US and Australia. Survey data showed literally no increase in youth or adult use from 1976 to about l984, and Dutch rates were well below those in the US. …..But between l980 and l988 (the commercialization regime mid l980s to l995) the number of coffee shops selling cannabis in Amsterdam increased tenfold,…. .….and began to promote the drug more openly.

As commercial access and promotion increased, the Netherlands saw rapid growth in the number of cannabis users, an increase not mirrored in other nations. Whereas 15% of l8-20 year olds reported having used marijuana in l984, the figure more than doubled to 33% in 1992. Since l992 the Dutch figure has continued to rise but that growth is paralleled in the US and most other rich Western nations…..

…..Legalization would eliminate the harms caused by prohibition, but it would not eliminate the harms caused by drug use……..we believe that legalization would significantly increase the number of drug users and the quantity of drugs consumed. ……

……If legalization produced a significantly large increase in total use, total drug harm would go up, even if each incident of use became somewhat safer. Because Total Drug Harm = Average Harm Per Use x Total Use, total harm can rise even if average harm goes down………….Thus legalization is a very risky strategy for reducing drug-related harm.

Recent research has clarified a number of important questions concerning adverse effects of cannabis on health. A causal role of acute cannabis intoxication in motor vehicle and other accidents has now been shown by the presence of measurable levels of Delta(9)-tetrahydrocannabinol (THC) in the blood of injured drivers in the absence of alcohol or other drugs, by surveys of driving under the influence of cannabis, and by significantly higher accident culpability risk of drivers using cannabis. Chronic inflammatory and precancerous changes in the airways have been demonstrated in cannabis smokers, and the most recent case-control study shows an increased risk of airways cancer that is proportional to the amount of cannabis use. Several different studies indicate that the epidemiological link between cannabis use and schizophrenia probably represents a causal role of cannabis in precipitating the onset or relapse of schizophrenia. A weaker but significant link between cannabis and depression has been found in various cohort studies, but the nature of the link is not yet clear. A large body of evidence now demonstrates that cannabis dependence, both behavioral and physical, does occur in about 7-10% of regular users, and that early onset of use, and especially of weekly or daily use, is a strong predictor of future dependence. Cognitive impairments of various types are readily demonstrable during acute cannabis intoxication, but there is no suitable evidence yet available to permit a decision as to whether long-lasting or permanent functional losses can result from chronic heavy use in adults. However, a small but growing body of evidence indicates subtle but apparently permanent effects on memory, information processing, and executive functions, in the offspring of women who used cannabis during pregnancy. In total, the evidence indicates that regular heavy use of cannabis carries significant risks for the individual user and for the health care system.

Source: Prog Neuropsychopharmacol Biol Psychiatry. 2004 Aug;28(5):849-63.

Neurobiology of cannabis–recent data enlightening driving disturbances

Abstract

During the last decades a new landscape of cannabis has been designed on account of: the increase in its use the greater youth of its users; the increase in the content of its main active constituent tetrahydrocannabinol (THC) and a lot of new epidemiological and neurobiological data. THC displays an exceptional lipophilicity, allowing its cerebral storage, leading to long lasting effects, by far more lasting than its presence in blood, and beyond the period throughout the intoxicated people feel a disablement. This is linked to its slow release from brain areas in which large proportion of spare receptors exists (reserve receptors). THC disturbs cognition and various skills required in driving. It may be responsible for psychiatric troubles: anxiety, depression, suicide attempt, psychotic attack, triggering of schizophrenia. It potentiates the alcohol effects and incites to alcohol drinking. It displays close relationships with dependence to heroin. This new landscape of cannabis urges to make a radical alteration in the public communication about this drug of abuse as it has yet collected so many troubles, accidents or tragedies.

Source: Ann Pharm Fr. 2006 May;64(3):148-59.

Dose related risk of motor vehicle crashes after cannabis use.

Abstract

The role of Delta(9)-tetrahydrocannabinol (THC) in driver impairment and motor vehicle crashes has traditionally been established in experimental and epidemiological studies.
Experimental studies have repeatedly shown that THC impairs cognition, psychomotor function and actual driving performance in a dose related manner. The degree of performance impairment observed in experimental studies after doses up to 300 microg/kg THC were equivalent to the impairing effect of an alcohol dose producing a blood alcohol concentration (BAC) >/=0.05 g/dl, the legal limit for driving under the influence in most European countries. Higher doses of THC, i.e. >300 microg/kg THC have not been systematically studied but can be predicted to produce even larger impairment.
Detrimental effects of THC were more prominent in certain driving tasks than others. Highly automated behaviors, such as road tracking control, were more affected by THC as compared to more complex driving tasks requiring conscious control.
Epidemiological findings on the role of THC in vehicle crashes have sometimes contrasted findings from experimental research. Case-control studies generally confirmed experimental data, but culpability surveys showed little evidence that crashed drivers who only used cannabis are more likely to cause accidents than drug free drivers.
However, most culpability surveys have established cannabis use among crashed drivers by determining the presence of an inactive metabolite of THC in blood or urine that can be detected for days after smoking and can only be taken as evidence for past use of cannabis. Surveys that established recent use of cannabis by directly measuring THC in blood showed that THC positives, particularly at higher doses, are about three to seven times more likely to be responsible for their crash as compared to drivers that had not used drugs or alcohol.
Together these epidemiological data suggests that recent use of cannabis may increase crash risk, whereas past use of cannabis does not. Experimental and epidemiological research provided similar findings concerning the combined use of THC and alcohol in traffic. Combined use of THC and alcohol produced severe impairment of cognitive, psychomotor, and actual driving performance in experimental studies and sharply increased the crash risk in epidemiological analyses.

Source¨ Drug Alcohol Depend. 2004 Feb 7;73(2):109-19

Schizophr Bull. 2010 Mar 11. [Epub ahead of print]
The Impact of Substance Use on Brain Structure in People at High Risk of Developing Schizophrenia.
Welch KA, McIntosh AM, Job DE, Whalley HC, Moorhead TW, Hall J, Owens DG, Lawrie SM, Johnstone EC.
1Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK.
Abstract
Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.

Vlahov, D. et al. Increased Use of Cigarettes, Alcohol, and Marijuana among Manhattan, New York, Residents after the September 11th Terrorist Attacks. American Journal of Epidemiology. 155(11):988-996, June 1, 2002.
Found that New Yorkers who increased their use of marijuana, tobacco or alcohol in after September 11 had increased chances of developing Post Traumatic Symptoms. Marijuana increased both PTS symptoms and depression more than the other substances.

In a large drug use survey of men born between 1944-1954, found that marijuana users who use the drug to cope with problems are more depressed than those who do not use to cope with problems.
Musty, R. Kaback, L. Relationships between motivation and depression in chronic marijuana users. Life Sciences. Volume 56, Issues 23-24, 5 May 1995, Pages 2151-2158.
Compared heavy and moderate marijuana users on several motivation and depression scales. Found that heavy users’ lack of motivation is correlated with their level of depression.
Bovasso, G. Cannabis Abuse as a Risk Factor for Depressive Symptoms.
Am J Psychiatry 158:2033-2037, December 2001.
People with a diagnosis of cannabis abuse at baseline were four times more likely than those with no cannabis abuse diagnosis to have depressive symptoms at the follow-up assessment, after adjusting for age, gender, antisocial symptoms, and other baseline covariates. In particular, these participants were more likely to have experienced suicidal ideation and anhedonia during the follow-up period.

Source: GREEN B. RITTER C. Marijuana use and depression. Journal of health and social behavior. 2000, vol. 41, no1, pp. 40-49 (1 p.3/4)

Smoking cannabis is more harmful than cigarettes and more likely to
trigger cancer, according to a report.

Just three cannabis ‘joints’ a day can cause the same amount of damage to the lungs as an entire packet of 20 cigarettes.

The British Lung Foundation says that when cannabis and tobacco are
smoked together, the harmful effects are significantly worse.

Its research suggests young cannabis smokers may also be at greater risk of throat and gullet cancers.

The foundation found that tar from cannabis joints contains 50 per cent more cancer-causing toxins than cigarettes made from tobacco alone.

Eight million Britons are thought to smoke cannabis, which some experts believe is a ‘gateway’ to harder drugs such as heroin and cocaine.

Earlier this year, researchers found that 79 per cent of children
thought cannabis was safe while only 2 per cent recognised there are
health risks from smoking the drug.

Dame Helena Shovelton, chief executive of the British Lung Foundation, said the harmful effects of cannabis had been swept under the carpet.

‘People are under the illusion it is safe to smoke cannabis. Our report
shows it is very dangerous to lung health, at least as dangerous as tobacco.

‘It seems society is in the same position as when research first showed the harm caused by tobacco. It took 15 years for the Government to take notice but we don’t want to repeat the mistakes of the past.’

Dame Helena said cannabis available today is 15 times stronger than the drug smoked in the 1960s. ‘This means studies carried out at that time will probably have underestimated the effects of cannabis smoking,’ she explained.

‘Puff and inhalation volume with cannabis is up to four times higher
than with tobacco – in other words you inhale deeper and hold your
breath with the smoke for longer before exhaling.

‘This results in more poisonous carbon monoxide and tar entering into
the lungs,’ Dame Helena said.

The foundation’s report – A Smoking Gun? – analyses research from around the world.

It found cannabis smokers have a higher level of chronic and acute
respiratory-conditions such as coughingwheezing and bronchitis. ‘When cannabis is smoked together with tobacco then the effects are additive’, it says.

Some studies suggest cannabis smoking may trigger chronic obstructive pulmonary disease which kills 32,000 people in Britain every year, the foundation’s report adds.

‘Research linking cannabis smoking to the development of respiratory
cancer exists although there have also been conflicting findings.

‘Not only does the tar in a cannabis cigarette contain many of the same carcinogens as tobacco smoke, but the concentrations of these are up to 50 per cent higher in the smoke of a cannabis cigarette,’ it says.

Benzyprene, found in the tar of cannabis joints, can change the make-up of one of the genes which suppresses tumours and could therefore make cancer more likely for people who smoke joints.

There are also more than 75 case studies of young cannabis smokers with cancers of the throat and gullet – diseases usually rare in people under 60.

Source: Daily Mail
Monday 11 Nov 2002

A new compound similar to the active component of marijuana (cannabis) might provide effective pain relief without the mental and physical side effects of cannabis, according to a study in the July issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

The synthetic cannabinoid (cannabis-related) compound, called MDA19, seems to avoid side effects by acting mainly on one specific subtype of the cannabinoid receptor. “MDA19 has the potential for alleviating neuropathic pain without producing adverse effects in the central nervous system,” according to the study by Dr Mohamed Naguib of The University of Texas M.D. Anderson Cancer Center.

MDA19 Works on a Single Cannabinoid Receptor
The researchers performed a series of experiments to analyze the pharmacology and effects of the synthetic cannabinoid MDA19. There are two subtypes of the cannabinoid chemical receptor: CB1, found mainly in the brain; and CB2, found mainly in the peripheral immune system.

Dr. Naguib’s group has been doing research to see if the cannabinoid receptors—particularly CB2—can be a useful target for new drugs to treat neuropathic pain. Neuropathic pain is a difficult-to-treat type of pain caused by nerve damage, common in patients with trauma, diabetes, and other conditions.

MDA19 was designed to have a much stronger effect on the CB2 receptor than on the CB1 receptor. In humans, MDA19 showed four times greater activity on the CB2 receptor than on the CB1 receptor. In rats, the difference was even greater. The experiments also showed that MDA19 had “protean” effects, so-called after the shape-shifting Greek sea god Proteus—under different conditions, it could either block or activate the cannabinoid receptors.

In rats, treatment with MDA19 effectively reduced specific types of neuropathic pain, with greater effects at higher doses. At the same time, it did not seem to cause any of the behavioral effects associated with marijuana.

Potential to Develop Effective Pain Drugs that Avoid Side Effects
The “functional selectivity” of MDA19—the fact that it acts mainly on the CB2 receptor and has a range of effects under differing conditions—could have important implications for drug development. “[W]ith functionally selective drugs, it would be possible to separate the desired from the undesired effects of a single molecule through a single receptor,” Dr. Naguib and colleagues write.
This means that MDA19 could be a promising step toward developing medications that have the pain-reducing effect of cannabinoids while avoiding the mental and physical side effects of marijuana itself. However, more research will be needed before MDA19 or other agents that act on the CB2 receptor are ready for testing in humans.

“These elegant studies by Professor Naguib demonstrate remarkable analgesic properties for this synthetic cannabinoid,” comments Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia &Analgesia. “The studies suggest a novel mechanism for this protean agonist. Although preliminary, these studies suggest that synthetic cannabinoids may be significant step forward for patients suffering from neuropathic pain.”

SOURCE : www.news-medical.net 2nd July 2010

California data on drivers involved in passenger vehicle fatal crashes using Marijuana were analyzed to determine the impact on traffic safety and to provide information on the possible impact of an initiative, the Tax and Regulate Cannabis Initiative or “TC2010” which is on the California ballot in November 2010 to reform and partially legalize Marijuana.

A total of 1240 persons were killed in the last five years in fatal motor vehicle crashes involving Marijuana. 230 were killed in 2008. Use has increase steadily in the last ten years and is now at 5.5% in fatal passenger vehicle crashes. The use in single vehicle fatal crashes where most drivers are tested shows an involvement rate of 8.3%.

The largest increases occurred in the 5 years following the establishment of the Medical Marijuana Program in January 2004. For the five years following legalization there were 1240 fatalities in fatal crashes, compared to the 631 fatalities for the five years prior, for an increase of almost 100%.

In 2008 there were 8 counties where more than 16% of the drivers in fatal crashes tested positive for Marijuana. Five of the 8 counties had rates over 20% Based on this experience, a use rate of 16% to 20% is very likely. A rate increase to only 16%, would result in 670
fatalities, and at 20% we would have about 840 fatalities annually. The 20% level would be more than triple the present level of 230 fatalities in 2008. At these levels, Marijuana would rival alcohol at 17.9%, as the top cause of traffic fatalities.

If “TC2010” passes, tax income on Marijuana is estimated at $1.4 billion annually compared to an estimated $4 billion or more economic loss from Marijuana related fatal crashes.
Over 80% of the Marijuana drivers are male, with a median age of 25. In addition, about half (48%) of the drivers using Marijuana also were legally intoxicated. About 75% of the drivers that used Marijuana did not use any other drug. About 1.2 fatalities were reported for each Marijuana involved driver.

Authors: Alfred Crancer and Alan Crancer

Source: -Received June 2010 from Drug Free America Foundation

“This report summarises the key findings from a report exploring public attitudes towards illegal drugs and drug misuse in Scotland, based on data from the 2009 Scottish Social Attitudes survey. It focuses in particular on attitudes towards opiate misuse, and on views of potential policy responses to this. However, it also places such attitudes in the context of wider views and experiences of illegal drugs.”

Main Findings
■ Support for legalising cannabis – which increased in Scotland (as in the rest of the UK) in the late 1990s – has fallen considerably in more recent years, from 37% in 2001 to 24% in 2009. Attitudes towards prosecution for possession of cannabis for personal use also hardened between 2001 and 2009.

■ Most people said taking cocaine occasionally is wrong – 76% rated it as 4 or 5 on a scale where 5 meant ‘very seriously wrong’.

■ 45% of people agreed that ‘Most people who end up addicted to heroin have only themselves to blame’, while just 27% disagreed.

■ Around half (53%) disagreed that ‘most heroin users come from difficult backgrounds’ (29% agreed).

■ Among those in paid employment, around half (47%) said they would be ‘very’ or ‘fairly comfortable’ working alongside someone they knew had used heroin in the past, while around 1 in 5 would be uncomfortable.

■ Just a quarter (26%) said they would be comfortable with someone who was receiving help to stop using heroin moving near to them, while half (49%) would be uncomfortable.

■ There was no public consensus on what should be the top government priority for tackling heroin use in Scotland – 32% chose ‘tougher penalties for those who take heroin’, 32% ‘more help for people who want to stop using heroin’ and 28% ‘more education about drugs’.

■ Just 16% agreed that people who possess heroin for personal use should not be prosecuted (compared with 34% for cannabis).

■ Public support for providing clean needles to injecting drug users fell from 62% in 2001 to 50% in 2009.

■ Opinion on educating young people about safer drug use was split – 44% agreed that young people should be given information about how to use drugs more safely, but 40% disagreed.

■ Four out of five (80%) agreed that ‘the only real way of helping drug addicts is to get them to stop using drugs altogether’. However, 29% agreed that ‘most heroin users can never stop using drugs completely’, while 27% said they neither agreed nor disagreed or did not know.

■ 63% disagreed that ‘Someone who has been a heroin addict can never make a good parent, even if their drug problems are in the past’.

■ Around two thirds (64%) said that young children of heroin users should be placed into temporary foster care until the parents stop taking heroin. A further 1 in 5 believed the child should stay at home while the family receives help from social workers and just 8% said the child should be permanently adopted by another family.

The full report is also accessible online.

Source: http://uwsnealb.wordpress.com/2010/05/28/scottish-social-attitudes-survey-2009-public-attitudes-to-drugs-and-drug-use-in-scotland/ May 25 2010

Troubled sleep is a commonly cited consequence of adolescent drug use, but it has rarely been studied as a cause. Nor have there been any studies of the extent to which sleep behavior can spread in social networks from person to person to person. Here we map the social networks of 8,349 adolescents in order to study how sleep behavior spreads, how drug use behavior spreads, and how a friend’s sleep behavior influences one’s own drug use. We find clusters of poor sleep behavior and drug use that extend up to four degrees of separation (to one’s friends’ friends’ friends’ friends) in the social network. Prospective regression models show that being central in the network negatively influences future sleep outcomes, but not vice versa. Moreover, if a friend sleeps ≤7 hours, it increases the likelihood a person sleeps ≤7 hours by 11%. If a friend uses marijuana, it increases the likelihood of marijuana use by 110%. Finally, the likelihood that an individual uses drugs increases by 19% when a friend sleeps ≤7 hours, and a mediation analysis shows that 20% of this effect results from the spread of sleep behavior from one person to another. This is the first study to suggest that the spread of one behavior in social networks influences the spread of another. The results indicate that interventions should focus on healthy sleep to prevent drug use and targeting specific individuals may improve outcomes across the entire social network.

Source: Mednick SC, Christakis NA, Fowler JH (2010) The Spread of Sleep Loss Influences Drug Use in Adolescent Social Networks. PLoS ONE 5(3): e9775. doi:10.1371/journal.pone.0009775

Abstract
California data on drivers involved in passenger vehicle fatal crashes using Marijuana were analyzed to determine the impact on traffic safety and to provide information on the possible impact of an initiative, the Tax and Regulate Cannabis Initiative or “TC2010” which is on the California ballot in November 2010 to reform and partially legalize Marijuana.

A total of 1240 persons were killed in the last five years in fatal motor vehicle crashes involving Marijuana. 230 were killed in 2008. Use has increase steadily in the last ten years and is now at 5.5% in fatal passenger vehicle crashes. The use in single vehicle fatal crashes where most drivers are tested shows an involvement rate of 8.3%.

The largest increases occurred in the 5 years following the legalization of Medical Marijuana in January 2004. For the five years following legalization there were 1240 fatalities in fatal crashes, compared to the 631 fatalities for the five years prior, for an increase of almost 100%. In 2008 there were 8 counties where more than 16% of the drivers in fatal crashes
tested positive for Marijuana. Five of the 8 counties had rates over 20%

Based on this experience, a use rate of 16% to 20% is very likely. A rate increase to only 16%, would result in 670 fatalities, and at 20% we would have about 840 fatalities annually. The 20% level would be more than triple the present level of 230 fatalities in 2008. At these levels, Marijuana would rival alcohol at 17.9%, as the top cause of traffic fatalities.

If “TC2010” passes, tax income on Marijuana is estimated at $1.4 billion annually compared to an estimated $4 billion or more economic loss from Marijuana related fatal crashes.
Over 80% of the Marijuana drivers are male, with a median age of 25. In addition, about half (48%) of the drivers using Marijuana also were legally intoxicated. About 75% of the drivers that used Marijuana did not use any other drug. About 1.2 fatalities were reported for each Marijuana involved driver.

Source: Sent by Ronald E. Brooks Northern California High Intensity Drug Trafficking Area June 2010

Recent research has clarified a number of important questions concerning adverse effects of cannabis on health.

A causal role of acute cannabis intoxication in motor vehicle and other accidents has now been shown by the presence of measurable levels of Δ9-tetrahydrocannabinol (THC) in the blood of injured drivers in the absence of alcohol or other drugs, by surveys of driving under the influence of cannabis, and by significantly higher accident culpability risk of drivers using cannabis.

Chronic inflammatory and precancerous changes in the airways have been demonstrated in cannabis smokers, and the most recent case-control study shows an increased risk of airways cancer that is proportional to the amount of cannabis use.

Several different studies indicate that the epidemiological link between cannabis use and schizophrenia probably represents a causal role of cannabis in precipitating the onset or relapse of schizophrenia.

A weaker but significant link between cannabis and depression has been found in various cohort studies, but the nature of the link is not yet clear. A large body of evidence now demonstrates that cannabis dependence, both behavioral and physical, does occur in about 7–10% of regular users, and that early onset of use, and especially of weekly or daily use, is a strong predictor of future dependence.

Cognitive impairments of various types are readily demonstrable during acute cannabis intoxication, but there is no suitable evidence yet available to permit a decision as to whether long-lasting or permanent functional losses can result from chronic heavy use in adults. However, a small but growing body of evidence indicates subtle but apparently permanent effects on memory, information processing, and executive functions, in the offspring of women who used cannabis during pregnancy. In total, the evidence indicates that regular heavy use of cannabis carries significant risks for the individual user and for the health care system.

Source: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 28, Issue 5, August 2004, Pages 849-863

An 18-year-old male presents complaining of crampy abdominal pain, nausea, and intractable vomiting for the past year. The symptoms are episodic, lasting several weeks and remitting for weeks to months.

The patient states that his abdominal pain is 10 out of 10 in severity, and that he has been vomiting up to 20 times each day. He has been evaluated at multiple hospitals, and he has had numerous upper endoscopies, colonoscopies, swallowing studies, and CT and MRI imaging studies, all of which were unrevealing.

He underwent a cholecystectomy, but had no improvement in his symptoms after the surgery. His pain and nausea are unresponsive to antacids and antiemetics.

The patient’s only relief is with hot water bathing: he spends hours each day in the shower with the temperature set as hot as he can bear. The patient’s history is otherwise unremarkable, except that he admits to daily marijuana use beginning at the age of 14.

This patient’s story is typical of cannabinoid hyperemesis, a clinical syndrome characterized by intractable vomiting and abdominal pain associated with the unusual learned behavior of compulsive hot water bathing, occurring in the setting of long-term heavy marijuana use.
Treatment consists of medication for immediate symptomatic relief and marijuana cessation for long-term relief. Symptoms usually remit within weeks of becoming abstinent.

If this disorder is so easily diagnosed and treated, why were the patient’s past doctors confused to the point of performing what might have been an unnecessary surgery? Cannabinoid hyperemesis is a new diagnosis, first described in 2004, and currently sixteen papers on the subject have been published.

Therefore, it is likely that the patient’s prior doctors had never considered this disorder. Second, the pathogenesis of cannabinoid hyperemesis is poorly understood.
How can marijuana, which is used in cancer clinics as an anti-emetic, cause intractable vomiting? And why would symptoms abate in response to high temperature?

The connection between marijuana, vomiting, and heat is non-intuitive, and a medical team unfamiliar with this syndrome would be hard-pressed to reach the diagnosis.
The largest study of cannabinoid hyperemesis to date was the landmark report by Allen et al in 2004 in an area of Southern Australia where marijuana use is largely decriminalized.

The report tracked 10 patients who presented with cyclic vomiting after 3 to 27 years of cannabis abuse and no other history of drug abuse. All but one displayed compulsive hot water bathing; the remaining patient had only experienced his symptoms for 6 months, and the authors theorize that he had not yet learned to associate hot water with symptom palliation.

The 9 compulsive bathers reported that this bizarre behavior occupied hours of their days and said that their symptoms were ameliorated within minutes of bathing and returned when the water cooled. All 10 patients were counseled to cease cannabis use, and 7 did so. Within weeks of cessation, the symptoms resolved for these 7 patients; the remaining 3 patients did not cease cannabis use and continued to have cyclic vomiting and abdominal pain.

After several years of abstinence, 3 patients resumed cannabis use and were hospitalized again with cyclic vomiting and abdominal pain. Once again, 2 of these patients successfully stopped using cannabis, and their symptoms resolved. The remaining patient continued to use cannabis and continued to experience symptoms at the time of publication.
Following the first case report, further cases have been described on three continents.

All patients presented with the classic triad of symptoms described by Allen et al: cyclic vomiting and abdominal pain, an extensive history of cannabis abuse, and palliation with hot water bathing. The fact that this unique triad is preserved in diverse patient populations suggests that there is a pathogenic mechanism that underlies this syndrome.

Several authors have speculated about the pathophysiology of cannabinoid hyperemesis, and though the specifics remain unclear, there is consensus over some of the basic principals: It appears that the high lipophilicity of delta-9-tetrahydrocannabinol (Δ9-THC, the active compound in marijuana) causes cumulative increases in concentration with chronic use, which may lead to toxicity in susceptible patients.

The abdominal pain and vomiting are explained by the effect of cannabinoids on CB-1 receptors in the intestinal nerve plexus, causing relaxation of the lower esophageal sphincter and inhibition of gastrointestinal motility. This finding is supported by gastric emptying studies performed on one of the patients presented by Allen et al, which revealed severely delayed emptying. While cannabis appears to have anti-emetic effects that are centrally mediated, it is possible that these effects predominate at low doses whereas the gastrointestinal effects predominate at the high concentrations that occur with long-term use.

The proposed explanation for compulsive hot water bathing is based on the fact that cannabis disrupts autonomic and thermoregulatory functions of the hippocampal-hypothalamic-pituitary system. There is a high concentration of CB1 receptors within the limbic system, and the hypothalamus in particular is known to be responsible for integrating central and peripheral thermosensory input. Furthermore, Δ9-

THC induces hypothermia in mice in a dose-dependent manner. While this evidence links cannabis to the hypothalamus and to thermoregulation, it does not provide a causal relationship. Two mechanisms proposed by Chang et al are that (1) cannabinoid-induced hypothermia causes the desire for hot water bathing, or (2) hot water bathing is the direct result of CB1 activation in the hypothalamus.

The true mechanism underlying hot water bathing remains enigmatic, and further studies are needed to elucidate the relationship between this bizarre learned behavior and the other features of cannabinoid hyperemesis.

A timely diagnosis of cannabinoid hyperemesis is essential not only to effect proper treatment but also to prevent iatrogenic morbidity and mortality from unnecessary diagnostic procedures and surgical interventions. There are, however, several obstacles to effective diagnosis:

First, the legal status of marijuana makes eliciting an accurate drug history challenging. Second, the bizarre hot water bathing is likely often attributed to psychological conditions such as obsessive-compulsive behavior. Third, the knowledge of the anti-emetic effects of cannabis likely disguises cases of cannabinoid hyperemesis, leading to the erroneous belief that cannabis is treating cyclic vomiting rather than causing it.

Finally, the fact that this syndrome is so recently described and relatively unknown outside an esoteric subset of the GI literature means that most clinicians are unaware of its existence. The following diagnostic criteria adapted from Sontineni et al can be used to facilitate a diagnosis of cannabinoid hyperemesis syndrome:

ESSENTIAL FEATURES
History of chronic cannabis use
Nausea and cyclic vomiting over months
Relief with cessation of cannabis use
SUPPORTING FEATURES
Compulsive hot water bathing with transient relief of symptoms
Colicky abdominal pain
Exclusion of other etiologies (especially gall-bladder and pancreas)
In the case of the 18-year-old patient presented above, asking the open-ended question, “What makes you feel better?” followed by more focused questions regarding the temperature of the water and the history of marijuana use were sufficient to suggest the diagnosis of cannabinoid hyperemesis.
We propose that these questions be used as a screening tool for all patients presenting with cyclic vomiting. Based on our experience and a review of the literature, we believe that these questions may be both sensitive and specific for detecting this unusual syndrome.
The patient presented in this case was counseled on his likely diagnosis.

Though he was initially skeptical, giving him printouts of case reports on cannabinoid hyperemesis syndrome and discussing the etiology of the disease were sufficient to convince him of the diagnosis. He was treated symptomatically in the hospital. Two weeks after discharge, he remains abstinent from marijuana and reports that his symptoms are improving.
Sarah A. Buckley and Nicholas M. Mark both are 4th year medical students at NYU School of Medicine
Faculty reviewed by Robert Hoffman, MD, Director NYU Poison Control Center, Associate Professor Departments of Medicine and Emergency Medicine, NYU Langone Medical Center

Source http://www.clinicalcorrelations.org/?p=2877 July 15th 2010

Q: How can I tell if my child has been using marijuana?
A: There are some signs you might be able to see. If someone is high on marijuana, he or she might:

• Seem dizzy and have trouble walking;
• Seem silly and giggly for no reason;
• Save very red, bloodshot eyes; and
• Have a hard time remembering things that just happened.

When the early effects fade, the user can become very sleepy.

Parents should be aware of changes in their child’s behavior, although this may be difficult with teens. Parents should look for withdrawal, depression, fatigue, carelessness with grooming, hostility and deteriorating relationships with family members and friends.

In addition, changes in academic performance, increased absenteeism or truancy, lost interest in sports or other favorite activities, and changes in eating or sleeping habits could be related to drug use. However, these signs may also indicate problems other than using drugs.

In addition, parents should be aware of:

• Signs of drugs and drug paraphernalia, including pipes and rolling papers;
• Odor on clothes and in the bedroom;
• Use of incense and other deodorizers;
• Use of eye drops; and
• Clothing, posters, jewelry, etc., promoting drug use.

Source: The National Institute on Drug Abuse 2010

Troubled sleep is a commonly cited consequence of adolescent drug use, but it has rarely been studied as a cause. Nor have there been any studies of the extent to which sleep behavior can spread in social networks from person to person to person. Here we map the social networks of 8,349 adolescents in order to study how sleep behavior spreads, how drug use behavior spreads, and how a friend’s sleep behavior influences one’s own drug use. We find clusters of poor sleep behavior and drug use that extend up to four degrees of separation (to one’s friends’ friends’ friends’ friends) in the social network. Prospective regression models show that being central in the network negatively influences future sleep outcomes, but not vice versa. Moreover, if a friend sleeps ≤7 hours, it increases the likelihood a person sleeps ≤7 hours by 11%. If a friend uses marijuana, it increases the likelihood of marijuana use by 110%. Finally, the likelihood that an individual uses drugs increases by 19% when a friend sleeps ≤7 hours, and a mediation analysis shows that 20% of this effect results from the spread of sleep behavior from one person to another. This is the first study to suggest that the spread of one behavior in social networks influences the spread of another. The results indicate that interventions should focus on healthy sleep to prevent drug use and targeting specific individuals may improve outcomes across the entire social network.
Source: Mednick SC, Christakis NA, Fowler JH (2010) The Spread of Sleep Loss Influences Drug Use in Adolescent Social Networks. PLoS ONE 5(3): e9775. doi:10.1371/journal.pone.0009775

A TENFOLD increase in hospital treatment for cannabis poisoning or dependence among people in their 30s and 40s suggests the habit has run out of control for a hard core of long-term users.
Australian research shows that while cannabis consumption overall decreased during the past decade, the rate of hospital treatment rose. Treatment rates are highest among people in their 20s, but the steepest increase has been among older people, with those in their 30s only slightly less likely to seek help than younger people by 2007, the study shows.
Seven years earlier, people in their 30s were being treated at only half the rate of their younger counterparts, according to the findings of the National Drug and Alcohol Research Centre at the University of NSW. Their faster rise in cannabis-related health problems coincided with greater frequency of daily use.
“These people started their use early and have [in some cases] then gone on to develop problems,” the study leader, Amanda Roxburgh, said. “They might not necessarily think that they have a problem with their use until it kicks into crisis mode.” People in their 20s were about 50 per cent more likely to have used cannabis during a one-year period compared with those in their 30s. But of those who did so, nearly 20 per cent of the older age group had developed a daily habit, against about 15 per cent of the younger adults.
Ms Roxburgh, whose results are published in the journal Addiction, said the rise in problematic use might reflect increased cannabis potency, though there was no formal evidence the drug had become stronger. Its falling price suggested it was being produced more efficiently – perhaps through indoor hydroponic cultivation – and this might have made it more accessible.
Jan Copeland, who heads the National Cannabis Prevention and Information Centre, said older people were more likely to consider cannabis safe. “These people come from age groups where cannabis is a benign herb and natural,” she said. “But when you are doing something every day you don’t realise the difficulties when you try to stop”.
Cannabis use among people aged 14 to 19 more than halved between 1996 and 2005, but the study also found pockets of harmful use in that group. Nearly two-thirds of young daily cannabis users reported difficulties controlling their use.
Members of this group were also more likely to report smoking 10 or more cones or joints a day, and if they were treated in hospital for their cannabis use were more likely to be treated for psychosis than older users.
Professor Copeland said young people now understood cannabis could be dangerous, and fewer were experimenting, but dedicated treatment programs were still needed for young people with a serious habit.
Will Temple, chief executive officer of the Watershed drug and alcohol recovery and education centre in Wollongong, said his centre had gone from treating almost no cannabis users to in the past six months treating 30 per cent of clients for cannabis use.
Source: The Sydney Morning Herald 29th March 2010

Monitoring the Future survey shows that while marijuana continues to be the most commonly used illicit drug among teens in the USA, current use of marijuana has dropped by 25 also dropped by seven percent among all three grades combined. Teen use of amphetamines, particularly methamphetamine, dropped significantly in five years and year-over-year, between 2005 and 2006, with less than one percent of teens having used it in the past 30 days.

The survey also noted reductions in the following drug categories between 2001 and 2006, including:

** Marijuana use is down in all categories for all grades combined. Lifetime, past year, and past 30 day use decreased 18 percent, 20 percent, and 25 percent (from 35% to 29%; 26% to 22%; and 17% to 13%, respectively).

** Use of cigarettes is down since 2001 in all four use categories (lifetime, past month, daily, and more than one-half pack per day) in all three grades.

** Youth use of alcohol was also down across the board – in all five use categories (lifetime, past year, past month, daily, and more than five drinks in a row in the last two weeks) and in all three grades over five years.

** Lifetime use of steroids for teens declined among all three grades, with past year and past month use also down among 8th and 10th graders.

Source: Source: nyac@TheAntiDrug.com Dec 2006

Half of all crime suspects arrested by police admit to recently smoking cannabis, astonishing UK Government research reveals. For younger offenders, the figures are even more stark. Some 57% say they have smoked the drug – which Labour controversially downgraded – in the past month. It proves for the first time a firm link between cannabis and serious offending. It is used by more suspects than any other drug – including heroin and crack cocaine. “We have long said that drugs fuel all sorts of crime. This is because they both undermine a person’s sense of responsibility but also because takers and addicts need money to feed their habit,” said Shadow Home Secretary David Davis.

Source: Daily Mail, January 5, 2007.

The Journal of Pediatrics has published a new study which brings to light another troubling consequence of smoking marijuana, particularly during pregnancy.
“Barros and her team looked at 561 infants born to adolescent mothers. Twenty-six of them had been exposed to marijuana, as revealed by tests on the mother’s hair and the infant’s stool. Just one of the mothers had reported smoking pot while pregnant.
Trained examiners, who did not know a child’s marijuana exposure status, tested the neurobehavioral responses of all infants. On average, marijuana-exposed infants scored differently on measures of arousal, regulation and excitability compared to the non-exposed infants…
..Infants exposed to marijuana in the womb show subtle behavioral changes in their first days of life, researchers from Brazil report.
These newborns were more irritable than non-exposed infants, less responsive, and more difficult to calm, Dr. Marina Carvalho de Moraes Barros and colleagues from the Federal University of Sao Paulo and colleagues report. They also cried more, startled more easily, and were more jittery. Such changes, Barros and her team say, have the potential to interfere with mother-child bonding.
Here’s the key point: “It is necessary to counter the misconception that marijuana is a ‘benign drug’ and to educate women regarding the risks and possible consequences related to its use during pregnancy,” Barros and colleagues conclude.”

Source: Journal of Pediatrics Vol.149 Issue 6 Dec. 2006

Research Summary
New research finds that smoking three or four marijuana cigarettes a week for six years could harm lung function and destroy antioxidants that protect cells against heart disease and cancer, Reuters reported Dec. 5.
“Smoking cannabis on a regular basis actually depletes your lung of protective antioxidant substances and this may have chronic long-term implications for young individuals,” said Dr Sarah Nuttall of the University of Birmingham in England.
The study involved a group of 20 people ages 19 to 30 who were either nonsmokers, cigarette smokers, and/or marijuana users. Researchers took blood samples, conducted lung function measurements, and tested for antioxidant markers.
“We found that smokers, compared to nonsmokers, had impaired lung function,” Nuttall said.
Nuttall said that when compared to nonsmokers, marijuana smokers had substantially lower levels of a protective antioxidant and nitric oxide, which is linked to lung function.
“These findings are important in young individuals in which the use of cannabis is increasing and may have serious long-term implications for what is currently regarded as a relatively harmless recreational habit,” she said.
The study’s findings were presented at a meeting of the held recently in London, England.

Source: British Thoracic Society Dec.2003

Research Summary
A study by the British Lung Foundation determined that smoking marijuana is more harmful to the lungs than smoking cigarettes, the BBC reported Nov. 11.
According to the study, smoking three marijuana cigarettes a day can cause the same damage as 20 cigarettes. And those who smoke both marijuana and cigarettes are further increasing their risk of lung damage.
Dr. Mark Britton, chairman of the foundation, said that tar from cannabis cigarettes contains 50 percent more carcinogens than tobacco. Since marijuana smokers tend to inhale up to four times more deeply than tobacco users, more poisonous carbon monoxide and tar enter the lungs, he added.
“These statistics will come as a surprise to many people, especially those who choose to smoke cannabis rather than tobacco in the belief it is safer for them,” said Britton. “It is vital that people are fully aware of the dangers so they can make an educated decision and know the damage they may be causing.”
As a result of the study’s findings, the group is urging the British government to implement a public-health education campaign on the health risks of marijuana smoking.

Source: Link from Join Together February 2007

Maoris have the world’s highest lung-cancer rate, and heavy marijuana use could be a culprit, the New Zealand Herald reported Oct. 10.
About one in five New Zealanders are regular users of marijuana. Researcher Richard Beasley of the Medical Research Institute in Wellington, New Zealand, is working on a study that compares cancer rates between marijuana smokers, tobacco smokers, and nonusers. He recently released a research review concluding that marijuana smoking is more cancerous than tobacco smoking.
Beasley performed the research review for a Wellington coroner who has called for a tougher approach than harm reduction to marijuana use in New Zealand.

Source: New Zealand Herald Oct.l7 2005

Research Summary

Background

Despite the high prevalence of cannabis use in schizophrenia, few studies have examined the potential relationship between cannabis exposure and brain structural abnormalities in schizophrenia.
Aims To investigate prefrontal grey and white matter regions in patients experiencing a first episode of schizophrenia with an additional diagnosis of cannabis use or dependence (n=20) compared with similar patients with no cannabis use (n=31) and healthy volunteers (n=56).
Method Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous magnetic resonance images and automatically segmented into grey and white matter.
Results Patients who used cannabis had less anterior cingulate grey matter compared with both patients who did not use cannabis and healthy volunteers.
Conclusions A defect in the anterior cingulate is associated with a history of cannabis use among patients experiencing a first episode of schizophrenia and could have a role in poor decision-making and in choosing more risky outcomes.
Philip R. Szeszko, PhD, Delbert G. Robinson, MD and Serge Sevy, MD et al
Correspondence: Dr Philip R. Szeszko, Zucker Hillside Hospital, Psychiatry Research, 75–59 263rd Street, Glen Oaks, NY11004, USA. Tel: +1 718 470 8489; fax: +1 718 343 1659; email: szeszko@lij.edu

Source: The British Journal of Psychiatry (2007) 190: 230-236. doi: 10.1192/bjp.bp.106.024521
© 2007 The Royal College of Psychiatrists

James M. Howard,
Independent Biologist

It is my hypothesis that schizophrenia results from reduced fetal brain growth and development due to low maternal DHEA. This is exposed later in life by hormones that interfere with DHEA availability, that is, cortisol and testosterone, along with the natural decline of DHEA that begins around age twenty. Therefore, schizophrenia often occurs following a stressful event (cortisol) in the late teens or early twenties (testosterone and loss of DHEA) or later in life as DHEA reaches very low levels. Schizophrenia is characterized by low DHEA. Individuals with normal DHEA along with reduced fetal DHEA may not develop schizophrenia.
I suggest that the psychoactive chemicals of cannabis exert their effects by binding to androgen receptors. It has been found that THC and CBN inhibit binding of dihydrotestosterone to the androgen receptor (Endocrinology 1980; 107: 848-50). This binding to receptors in the advanced forebrain would reduce executive function and increase lower brain function by redistributing DHEA. That is, blocking access to upper brain receptors would increase lower brain function and increase lower brain functions such as appetite, etc.
DHEA binds to the androgen receptor. Cannabis use would reduce DHEA binding to the androgen receptor. It is this blocking of DHEA at its upper level receptors and subsequent redistribution of availability for lower brain activity that I think produces the effects of cannabis.
It is known that DHEA directly affects the anterior cingulate cortex (Psychopharmacology (Berl) 2006; 188: 541-51). Interference of DHEA binding in the anterior cingulate cortex of individuals with reduced growth and development in this area may reduce both function and maintenance of this area with the result being the symptoms of schizophrenia.

<span style=”font-size: 10pt; font-family: Verdana;”> Abstract: The use of Cannabis sativa preparations, such as hashish and marijuana, is wide-spread among young people, including pregnant women. Despite this concern, the consequences of cannabis exposure on the brain during periods of active brain development, such as the prenatal phase and adolescence, is not well known. Several epidemiological studies support the cannabis gateway hypothesis, where early cannabis use is suggested to increase the risk of initiating use of other illicit drugs, e.g., amphetamine or heroin. However, the nature of such direct links are unclear. Therefore, the aim of this thesis was to test experimentally the cannabis gateway hypothesis, i.e., to determine whether cannabis exposure during periods of active brain development alters reward-related behavior and neurobiology for psychostimulant and opioid drugs by the use of animal models.
In the first study, we examined the effects of early adolescent exposure (postnatal day; PND; 28-32, one injection per day) with the synthetic cannabinoid CB1 receptor agonist WIN55,212-2 and the main psychoactive substance in C. sativa, Δ9-tetrahydrocannabinol (THC) on amphetamine-induced motor behavior and dopamine release in the nucleus accumbens during adolescence. No alterations were evident in the cannabinoid exposed rats, results which did not support the cannabis gateway hypothesis in relation to subsequent psychostimulant abuse.
Next, we investigated the effects of adolescent exposure on subsequent opioid reward-related behavior and the neurobiology of opioid and cannabinoid systems during adulthood. We studied THC exposure across the full adolescent period (PND 28-49), and administered the drug once every third day in order to better mimic the pattern of intermittent use seen in teenagers. The results revealed discrete opioid-related alterations within brain regions highly implicated in reward and hedonic processing (e.g., increased proenkephalin gene expression in the nucleus accumbens and increased mu opioid receptors in the ventral tegmental area). This was coupled to increased heroin intake in a self-administration paradigm and increased morphine conditioned place preference, indicating altered sensitivity to the reinforcing properties of opioids.
Furthermore, in evaluating the adolescent ontogeny of the opioid and cannabinoid systems within limbic-related brain areas, we found that active endocannabinoid- and opioid- related neurodevelopment takes place to a very high extent during this period. Most pronounced were the alterations in endocannabinoid levels in cognitive brain areas, even though alterations were also apparent in reward-related regions.
Finally, we investigated the effects of prenatal cannabis exposure (gestational day 5- PND 2) on subsequent opioid reward-related behavior and neurobiology of the opioid and cannabinoid systems in adulthood. Similar to adolescent cannabis exposure, prenatal exposure induced discrete opioid-related alterations within brain regions highly implicated in reward and hedonic processing. Moreover, elevated heroin-seeking observed during extinction and after food deprivation was evident in the THC exposed rats, suggesting an increased motivation for drug use under conditions of stress.
Taken together, this thesis presents neurobiological support for the cannabis gateway hypothesis in terms of adult opiate, but not amphetamine, abuse, with underlying long-term disturbances of discrete opioid-related systems within limbic brain regions.

<em>Source: Ellgren, Maria Karolinksa Institute Sweden ISBN: 978-91-7357-064-0  Feb.2007
</em>
<span style=”font-size: 10pt; font-family: Verdana;”>

Compared to drugs such as heroin and cocaine, many people consider marijuana a relatively benign substance. But two studies in this issue demonstrate disturbing similarities between marijuana’s effects on the brain and those produced by highly addictive drugs such as cocaine and heroin. One study, described on page 2050, indicates that marijuana withdrawal activates the same stress system in the brain triggered by withdrawal of opiates and alcohol, while the other, reported on page 2048, indicates that marijuana activates the same reward pathway as heroin.

Source : Science 27 June 1997: Vol. 276. no. 5321, pp. 1967 – 1968

Cannabis smoking may cause 5 per cent of lung cancer cases in people up to middle age, according to a New Zealand study which challenges international thinking on the drug.  Around 15 per cent of New Zealand adults under 46 use cannabis, drug-use surveys have found.
 
Researcher Dr Sarah Aldington, of the Medical Research Institute in Wellington, presented the new case-control study to the Thoracic Society conference in Auckland yesterday.
 
Cannabis users may have thought they were safe from lung cancer after a Californian study of more than 1600 people last year found no link between the disease and smoking the drug.  Dr Aldington said the evidence on cannabis and the risk of lung cancer was limited and conflicting. Her study found the risk rose more than five-fold among the third of users smoking the most cannabis.
 
“In conclusion there is a relationship between cannabis smoking and lung cancer in this study,” she said. “Approximately 5 per cent of lung cancer cases in those aged 55 and under may be attributable to cannabis…”   This equates to about 15 new cases a year – in 2002, 306 people aged 18-55 were diagnosed with lung cancer in New Zealand.  The study questioned about 60 people with lung cancer from eight health districts between Waikato and Canterbury and more than 200 “controls” – people randomly selected from electoral rolls in the same areas.
 
They were asked about risk factors, including cannabis and tobacco use.   The researchers calculated that the risk of developing lung cancer increased by about 8 per cent a year for people whose cumulative exposure equated to smoking one joint a day. This was about the same as the increase for someone with a one-pack-a-day tobacco habit.   The younger someone started smoking cannabis, the higher their risk of lung cancer.
 
“Long-term cannabis use increases the risk of lung cancer in young adults, particularly in those who start smoking cannabis at a young age,” the researchers conclude.
 
Dr Aldington said cannabis was the most commonly used recreational drug in the world, used by 161 million people, and its use was increasing in many countries. She said cannabis contained 50 per cent more cancer-causing chemicals than tobacco.  The study has found what the University of California researchers had expected to find but didn’t.   A researcher from that study, Dr Donald Tashkin, said in the Washington Post his group had thought cannabis smokers’ deeper inhalation and tendency to hold smoke in their lungs for longer than tobacco users would contribute to an increased cancer risk.
 
He said earlier work had shown cannabis contained cancer-causing chemicals as potentially harmful as those in tobacco. But cannabis also contained the chemical THC, which might kill ageing cells and keep them from becoming cancerous.
 
Middlemore Hospital clinical director of medicine Associate Professor Jeff Garrett, a leader of the Thoracic Society, said the Aldington study was “a good pilot study. It’s early work, it’s interesting, but there needs to be more work done.”

Source:  New Zealand Herald
Tuesday March 27, 2007

________________________________________
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By Maggie Fox

WASHINGTON (Reuters) – The marijuana being sold across the United States is stronger than ever, which could explain a growing number of medical emergencies that involve the drug, government drug experts on Wednesday.

Analysis of seized samples of marijuana and hashish showed that more of the cannabis on the market is of the strongest grade, the White House and National Institute for Drug Abuse said.

They cited data from the University of Mississippi’s Marijuana Potency Project showing the average levels of THC, the active ingredient in marijuana, in the products rose from 7 percent in 2003 to 8.5 percent in 2006.

The level had risen steadily from 3.5 percent in 1988.

National Institute on Drug Abuse Director Dr. Nora Volkow fears the problem is not being taken seriously because many adults remember the marijuana of their youth as harmless.

“It’s really not the same type of marijuana,” Volkow said in a telephone interview. “This could explain why there has been an increase in the number of medical emergencies involving marijuana.”

According to the Substance Abuse and Mental Health Administration, marijuana was involved in 242,200 visits to hospital emergency rooms in 2005. This means that the patient mentioned using marijuana and does not mean the drug directly caused the accident or condition being treated, SAMHSA says.

The number is up from 215,000 visits in 2004.

The pharmacy department at Mississippi has compiled data on 59,369 samples of cannabis, 1,225 hashish samples, and 443 hash oil samples confiscated since 1975. “The highest concentration of (THC) found in a cannabis (marijuana) sample is 33.12 percent from Oregon State Police,” the report reads.
Hashish and hash oil concentrations are far higher, as they consist of processed plant product.

“Researchers and treatment experts have argued for some time that today’s more powerful marijuana has more harmful effects on users. This report underscores that we are no longer talking about the drug of the 1960s and 1970s — this is Pot 2.0,” John Walters, director of National Drug Control Policy, said in a statement.

Volkow said demand has driven growers to cultivate the stronger stuff. “It is the market,” she said. “Like in the market you favor the best tomatoes. When people buy marijuana, they don’t want a weak cigarette.”

Volkow’s institute has been studying the effects of cannabis, whose active ingredients are very similar to important brain chemicals called endogenous cannabinoids. “It clearly is addictive,” she said.

If children and adolescents use marijuana, it could affect their still-developing brains, she said.

The report said more than 60 percent of teens receiving treatment for drug abuse or dependence report marijuana as their primary drug of abuse.

“Although the overall number of young people using marijuana has declined in recent years, there is still reason for great concern, particularly since roughly 60 percent of first-time marijuana users are under 18 years old,” Volkow said.

According to the National Survey on Drug Use and Health 4.1 million Americans, or 1.7 percent of the population, report they use marijuana.

Source: Reuters Health. 26th April 2007

Abstract:
The use of Cannabis sativa preparations, such as hashish and marijuana, is wide-spread among young people, including pregnant women. Despite this concern, the consequences of cannabis exposure on the brain during periods of active brain development, such as the prenatal phase and adolescence, is not well known. Several epidemiological studies support the cannabis gateway hypothesis, where early cannabis use is suggested to increase the risk of initiating use of other illicit drugs, e.g., amphetamine or heroin. However, the nature of such direct links are unclear. Therefore, the aim of this thesis was to test experimentally the cannabis gateway hypothesis, i.e., to determine whether cannabis exposure during periods of active brain development alters reward-related behavior and neurobiology for psychostimulant and opioid drugs by the use of animal models.
In the first study, we examined the effects of early adolescent exposure (postnatal day; PND; 28-32, one injection per day) with the synthetic cannabinoid CB1 receptor agonist WIN55,212-2 and the main psychoactive substance in C. sativa, Δ9-tetrahydrocannabinol (THC) on amphetamine-induced motor behavior and dopamine release in the nucleus accumbens during adolescence. No alterations were evident in the cannabinoid exposed rats, results which did not support the cannabis gateway hypothesis in relation to subsequent psychostimulant abuse.
Next, we investigated the effects of adolescent exposure on subsequent opioid reward-related behavior and the neurobiology of opioid and cannabinoid systems during adulthood. We studied THC exposure across the full adolescent period (PND 28-49), and administered the drug once every third day in order to better mimic the pattern of intermittent use seen in teenagers. The results revealed discrete opioid-related alterations within brain regions highly implicated in reward and hedonic processing (e.g., increased proenkephalin gene expression in the nucleus accumbens and increased mu opioid receptors in the ventral tegmental area). This was coupled to increased heroin intake in a self-administration paradigm and increased morphine conditioned place preference, indicating altered sensitivity to the reinforcing properties of opioids.
Furthermore, in evaluating the adolescent ontogeny of the opioid and cannabinoid systems within limbic-related brain areas, we found that active endocannabinoid- and opioid- related neurodevelopment takes place to a very high extent during this period. Most pronounced were the alterations in endocannabinoid levels in cognitive brain areas, even though alterations were also apparent in reward-related regions.
Finally, we investigated the effects of prenatal cannabis exposure (gestational day 5- PND 2) on subsequent opioid reward-related behavior and neurobiology of the opioid and cannabinoid systems in adulthood. Similar to adolescent cannabis exposure, prenatal exposure induced discrete opioid-related alterations within brain regions highly implicated in reward and hedonic processing. Moreover, elevated heroin-seeking observed during extinction and after food deprivation was evident in the THC exposed rats, suggesting an increased motivation for drug use under conditions of stress.
Taken together, this thesis presents neurobiological support for the cannabis gateway hypothesis in terms of adult opiate, but not amphetamine, abuse, with underlying long-term disturbances of discrete opioid-related systems within limbic brain regions.
ISBN: 978-91-7357-064-0

Source: Karolinska Institute online 9th Feb.2007

Abstract: Spano MS, Ellgren M, Wang X, Hurd YL.

Karolinska Institute, Department of Clinical Neuroscience, Psychiatry Section, S-17176 Stockholm, Sweden.

BACKGROUND: Prenatal cannabis exposure is a growing concern with little known about the long-term consequences on behavior and neural systems relevant for reward and emotional processing.
METHODS: We used an animal model to study the effects of prenatal exposure to Delta(9)-tetrahydrocannabinol (THC) on heroin self-administration behavior and opioid neural systems in adult males (postnatal day 62). Rats were exposed to THC (.15 mg/kg) or vehicle from gestational day 5 to postnatal day 2. RESULTS: Both pretreatment groups showed similar heroin intake, but THC-exposed rats exhibited shorter latency to the first active lever press, responded more for low heroin doses, and had higher heroin-seeking during mild stress and drug extinction. THC exposure reduced preproenkephalin (PENK) mRNA expression in the nucleus accumbens during early development, but was elevated in adulthood; no adult striatal changes on preprodynorphin mRNA or PENK in caudate-putamen. PENK mRNA was also increased in the central and medial amygdala in adult THC-exposed animals. THC animals had reduced heroin-induced locomotor activity and nucleus accumbens mu opioid receptor coupling.
CONCLUSIONS: This study demonstrates enduring effects of prenatal THC exposure into adulthood that is evident on heroin-seeking behavior during extinction and allostatic changes in mesocorticolimbic PENK systems relevant to drug motivation/reward and stress response.

Source: : Biol Psychiatry. 2007 Feb 15;61(4):554-63. Epub 2006 Jul 28.

Scientists have shown how cannabis may trigger psychotic illnesses such as schizophrenia.
A King’s College London team gave healthy volunteers the active ingredient tetrahydrocannabinol (THC).
They then recorded reduced activity in an area of the brain which keeps inappropriate thoughts at bay. THC levels are thought to have doubled in street cannabis in recent years – at the expense of other ingredients which may have a beneficial effect.

A separate study has shown that one of these ingredients – cannabidiol (CBD) – has the potential to dampen down psychotic symptoms, and could form the basis of new treatments. The research will be discussed at a conference on the impact of cannabis use to be held at the Institute of Psychiatry at King’s College this week.
Dependency
Although figures are not kept, it is estimated that as many as 500,000 people in the UK may be dependent on cannabis. Increasing numbers of people are seeking help for cannabis problems at specialist clinics. In 2005, only heroin users accounted for a greater proportion of patients. Experts are concerned that street cannabis is becoming increasingly potent. It is thought that average THC content has risen from 6% to 12% in recent years.
The Institute of Psychiatry study gave THC, CBD or placebo capsules to adult male volunteers who had not abused cannabis. They then carried out brain scans, and a battery of tests, and found that those who took THC showed reduced activity in an area of the brain called the inferior frontal cortex, which keeps inappropriate thoughts and behaviour, such as swearing and paranoia in check.
The effects were short-lived, but some people appeared more vulnerable than others.
In a second study, a team from Yale University administered THC intravenously. Even at relatively low doses, they found 50% of healthy volunteers began to show symptoms of psychosis. Volunteers who already had a history of psychotic symptoms appeared to be particularly vulnerable.
Side effects
A third study, by the University of Cologne, compared the effect of CBD and a commonly used anti-psychotic medicine, Amisulpride, on 42 patients with a history of schizophrenia.
After four weeks both groups showed a reduction in psychotic symptoms, but the CBD group were less prone to side effects, such as muscle stiffness and weight gain.

The researchers warned that THC and CBD compete with each other biochemically, so a rise in THC levels would blunt any positive impact of CBD. Professor Robin Murray, a consultant psychiatrist at the Institute of Psychiatry, said the research provided the strongest evidence that cannabis had a significant impact on the brain.
He said proving a long-term effect was extremely difficult, as it was not ethical or feasible to stimulate long-term psychosis in volunteers.
However, he said: “If something has an active effect in inducing the symptoms of psychosis after one dose, then it would not be at all surprising if repeated use induced the chronic condition.”
Professor Murray also warned that the high potency cannabis now widely available was likely to pose a much bigger risk to health than the significantly weaker formulations of previous years. “It is similar to comparing the effect of drinking a glass of wine at the weekend with drinking a bottle of vodka every day.”
Marjorie Wallace, of the mental health charity Sane, called the research a “significant contribution” to the understanding of the dangers of cannabis.
“Sane has been saying for years that there is a link between psychosis and the drug, particularly in its more potent forms.
“We strongly urge the government to heed the growing evidence and take urgent action to warn young people that some of them are risking lifelong mental illness – that they are playing Russian roulette with their minds.”

Source: BBC NEWS: 2007/04/30

A drug which reduces the desire for marijuana and blocks its effect on the brain has been successfully tested in rats. Scientists say the findings may translate into better therapies for cannabis addiction in humans.
Rodents given a compound derived from a plant in the buttercup family lose their hankering for a synthetic version of tetrahydrocannabinol (THC) – the active compound in marijuana. The treatment also blocked a reward response in the animals’ brains when they did receive synthetic THC.
In the first part of the experiment, Steven Goldberg at the National Institute on Drug Abuse in Maryland, US, and his colleagues placed rats in a cage with a lever the animals could push. Each time the rats leaned on the lever, they received a dose of the synthetic THC through a small tube running into their body.
Over a period of three weeks the rats learned to enjoy the effects of synthetic THC and frequently self-administered the drug. By comparison, rats that received saline solution did not press the lever often.
Goldberg’s team then injected the rats with a compound derived from the seeds of the Delphinium brownii plant, which is in the buttercup family. The compound, known as methyllycaconitine (MLA), had a dramatic effect on the animals’ behaviour.

Blocking dopamine
On the day that they received MLA they pushed the lever for synthetic THC 70% less than before. The drug did not seem to otherwise change the rats’ movement and coordination, and had no other apparent side effects.
The scientists also took a close look at the effects of MLA on the rats’ brains. They used a technique called microdialysis to take tiny fluid samples from a reward-signalling area of the brain known as the nucleus accumbens, which sits near the base of the head.
When rats receive synthetic THC, levels of the reward chemical dopamine normally shoot up in the nucleus accumbens – but MLA blocked the release of dopamine in this brain region.
“The increases in dopamine are virtually non-existent because of MLA,” says Goldberg. He adds that MLA did not lower dopamine levels below normal amounts. This is important, says Goldberg, because it suggests that a similar therapy for humans would not interfere with normal reward signalling in the brain.
He notes that the drug Rimonobant, which makes monkeys less likely to self-administer THC, has been linked to depression in humans.
The exact mechanism by which MLA works remains a mystery. Scientists know that MLA binds to specific cell receptors in the brain called alpha-7 nicotinic receptors. They speculate that cannabis indirectly triggers these receptors, but cannot do so when the receptors are blocked by MLA.

Human potential
There is a genuine need for medications to help cannabis addicts overcome their drug problem, according to Goldberg: “About 10% of the people who experiment with it go on to heavy use and have trouble voluntarily giving it up. I think there is a proportion of the population who need ways to make them stop.”
Drug-makers have recently made medications such as Chantix available to help people quit tobacco smoking. But researchers say that these drugs affect different nicotinic receptors than those triggered by THC.
And while some people have pushed Rimonobant as a possible remedy for addiction, Goldberg says that more options – such as one based on MLA – must be explored: “Each patient is different and what works in one might not work in another.”

Source: Journal of Neuroscience (DOI: 10.1523/JNEUROSCI.0027-07.2007)

May 23, 2007
Research Summary

A compound known as methyllycaconitine (MLA) appears to block craving for and the effects of a synthetic version of THC, the main active ingredient in marijuana, New Scientist reported May 22.
Animal tests revealed that MLA, derived from Delphinium brownii, a plant in the buttercup family, cut craving for THC and blocked the brain’s reward response for the drug. Rats that received injections of MTA pushed a lever for doses of THC 70 percent fewer times than on days where they did not receive MLA.
Studies of the rats’ brains also showed that THC did not increase dopamine levels when MLA was present. “The increases in dopamine are virtually nonexistent because of MLA,” said lead researcher Steven Goldberg of the National Institute on Drug Abuse, who said the findings could have implications for addiction treatment for humans.

Source: The study was published in the Journal of Neuroscience.

Smoking marijuana in early pregnancy can cause infertility. A study at Vanderbilt University found that marijuana influences a signal that helps embryos pass safely from the ovary to the lining of the uterus.
Investigators found that when mice were given tetrahydrocannabinol, the major active component of marijuana, the embryos failed. They speculated that the chemical caused a fatty acid deficiency triggering a breakdown in the signaling system and making the embryo miss the crucial window for implantation in the uterus.
“We have shown before if you tinker with the normal timing of implantation in the uterus, it can create adverse ripple effects throughout the course of pregnancy leading to compromised pregnancy outcome,” said Dr. Sudhansu Dey of Vanderbilt University. Now the scientists are learning what happens on the molecular level that influences implantion.
“The take-home message would be, if you have fertility problems and you are smoking either marijuana or tobacco cigarettes, stop,” said Herbert Schuel, professor emeritus of anatomy and cell biology in the School of Medicine at the University of New York at Buffalo. “The same kinds of effects are produced by nicotine and tobacco smokers.”

Source NewsMax.com Sept.2006

Abstract

The goal of the present study was to examine the rate of cannabis use among participants in the Cognitive Assessment and Risk Evaluation (CARE) Program, a longitudinal program for individuals who are “at risk” for developing a psychotic disorder. Cannabis abuse was assessed in 48 individuals identified as at risk for psychosis based on subsyndromal psychotic symptoms and/or family history. At 1 year follow-up, 6 of the 48 (12.5%) at risk subjects had made the transition to psychosis. Of the 32 subjects who had no use or minimal cannabis use, one subject (3.1%) converted to psychosis. Of the 16 subjects who met criteria for cannabis abuse/dependence, five (31.3%) converted to psychosis. The results show a significant association between cannabis abuse and conversion to psychosis in this sample. Nicotine use was also found to be significantly associated with later conversion. The significant associations between cannabis and nicotine abuse and conversion to psychosis in individuals at risk for schizophrenia suggest that early identification and intervention programs should screen for and provide education about the deleterious effects of these substances.
Winston De La Haye, M.D., M.P.H. Lecturer and Consultant Psychiatrist Dept. of Community Health & Psychiatry, University of the West Indies, Mona, JAMAICA

Source: Source: Psychiatry Research 2007; 151: 151-154

Summary

While there is a wealth of research into the health impact of tobacco smoking, there is relatively little on the effects of cannabis smoking.
Research investigating whether the inhalation of cannabis smoke causes damage to the lungs and airways focuses on whether this effect is independent of the effects of tobacco smoke or not.
In general, the studies indicate that there is an increased negative health impact on those who smoke cannabis compared to those who do not smoke at all. When cannabis is smoked together with tobacco then the effects are additive.
However, what is not clear is whether it is the addition of the cannabis or the tobacco which is more harmful or whether this is the result of the combined effects of equally harmful substances.
Some key findings emerge from the research:
• The cannabis smoked today is much more potent that that smoked in the 1960s. The average cannabis cigarette smoked in the 1960s contained
about 10mg of tetrahydrocanabinol (THC), the ingredient which accounts for the psychoactive properties of cannabis, compared to 150mg of THC today. This means that longitudinal studies carried out in the 1960s and 1970s may not be
indicative of the effects of cannabis cigarettes
smoked today.
• Studies comparing the clinical effects of habitual cannabis smokers versus nonsmokers demonstrate a significantly higher prevalence of chronic and acute respiratory symptoms such as chronic cough and sputum production, wheeze and acute bronchitis episodes.
• 3-4 Cannabis cigarettes a day are associated with the same evidence of acute and chronic bronchitis and the same degree of damage to the
bronchial mucosa as 20 or more tobacco cigarettes a day.
• Cannabis tends to be smoked in a way which increases the puff volume by two-thirds and depth of inhalation by one-third. There is an
average fourfold longer breath-holding time with cannabis than with tobacco. This means that there is a greater respiratory burden of carbon
monoxide and smoke particulates such as tar than when smoking a similar quantity of tobacco.
• Cannabis smoking is likely to weaken the immune system. Infections of the lung are due to a combination of smoking-related damage to the
cells lining the bronchial passage (the fine hair-like projection on these cells filter out inhaled microorganisms)and impairment of the principal immune cells in the small air sacs caused by cannabis.
• The evidence concerning a possible link between cannabis smoking and Chronic Obstructive Pulmonary Disease (COPD) has not
yet been conclusively established. A number of studies indicate a causal relationship between the two whereas others contradict these findings.
• Research linking cannabis smoking to the development of respiratory cancer exists although there have also been conflicting findings. Not
only does the tar in a cannabis cigarette contain many of the same known carcinogens as tobacco smoke but the concentrations of these are up to 50% higher in the smoke of a cannabis cigarette. It also deposits four times as much tar on the respiratory tract as an unfiltered cigarette of the same weight. Smokers of cannabis and tobacco have shown a greater increase in cellular abnormalities indicating a cumulative effect of smoking both.
• The THC in cannabis has been shown to have a short term bronchodilator effect. This has lead to suggestions that THC may have therapeutic benefits in asthma. However, the noxious gases, chronic airway irritation or malignancy after long term use associated with smoking would seem likely to negate these benefits.

Recommendations
From a clinical perspective the main effects of smoking cannabis on the lungs are increased risk of pulmonary infections and respiratory cancers. Benzpyrene, a known constituent of the tar of cannabis cigarettes has been shown to promote alterations in one of the most common tumour suppressor genes, p53, hence facilitating the development of respiratory cancer. Gene p53 is
thought to play a role in 75% of all lung cancers. The British Lung Foundation recommends a public health education campaign aimed at young people to ensure that they are fully aware of the increased risk of pulmonary infections and respiratory cancers associated with cannabis smoking. The increased potency of the cannabis smoked today compared to the cannabis smoked twentythirty years ago suggests that earlier studies may underestimate the effects of cannabis smoking. In addition the lack of conclusive evidence concerning
the link between cannabis smoking and Chronic Obstructive Pulmonary Disease (COPD) underlines the need for further research.
The British Lung Foundation recommends that further research is undertaken to take into account the increased potency of today’s cannabis and to establish what link (if any) there is between COPD and cannabissmoking.

Source: British Lung Foundation Report ‘A Smoking Gun’ 2007

Smoking marijuana as a teenager could raise the risk of developing schizophrenia and psychotic symptoms as a young adult, according to a new study that compared the prevalence of mental illness among marijuana users and non-users.
Bloomberg News reported March 2 that researcher John McGrath of the University of Queensland, Australia, and colleagues studied 3,801 young-adult sibling pairs and concluded that those who used marijuana the longest (six or more years) were twice as likely to develop schizophrenia or delusional disorders. They also were four times more likely than non-users to score highly on a test gauging psychotic-like experiences.
Higher scores on the test also were seen among those who used marijuana for less than three years.

Source: www.jointogether.org March 2010

 Marijuana use at a young age significantly increased the risk of psychosis in young adulthood, Australian investigators reported.

Young adults who reported a longer duration since first exposure to marijuana had a two- to fourfold greater prevalence of three different psychosis-related outcomes, John McGrath, MD, PhD, of the Queensland Center for Mental Health Research in Wacol, and colleagues concluded in an article published online in Archives of General Psychiatry.

Apart from the implications for policy makers and health planners, we hope our findings will encourage further clinical and animal model-based research to unravel the mechanisms linking cannabis use and psychosis, the researchers concluded.

Several prospective-cohort studies have demonstrated an association between early marijuana use and an increased risk of psychosis. On the basis of such studies, reviews of the issue have generally concluded that early use of marijuana, or cannabis, is a modifiable risk factor for psychosis-related outcomes, the authors wrote.

However, some concern has persisted about potential methodologic biases and unmeasured confounders in the cohort studies. In an effort to address the concern, McGrath and colleagues examined the association between cannabis use and psychosis in 3,800 participants in a long-term evaluation of pregnancy and outcomes. In contrast to prior cohort studies, the authors incorporated a subset analysis involving 228 sibling pairs.

“If a significant association between cannabis use and psychosis-related outcomes was not detected in sibling pairs, it would seriously weaken the argument that cannabis use was a risk-modifying factor for psychosis-related outcomes,” they wrote.

Participants were born between 1981 and 1984 at a single hospital in Brisbane. Mothers and their offspring were followed up at five, 14, and 21 years after birth. At the 21-year follow-up, McGrath and colleagues retrospectively assessed cannabis use among the offspring, whose age averaged 20 and ranged from 18 to 23.

Cannabis use was assessed by means of the young adults’ responses to two questions: In the last month, how often did you use cannabis, marijuana, pot, etc.? At what age did you first use cannabis?
Possible responses to the first question were never, every day, every few days, once or so, and not in the past month.

Investigators separated the cohort into four groups on the basis of self-reported cannabis use. One group included never-users, and the remaining three groups were categorized by duration since first use of cannabis: three years or less, four to five years, six years or more.

Investigators compared participants’ history of cannabis use with three psychosis-related outcomes: non-affective psychosis, hallucinations (assessed by the Computerized International Diagnostic Interview), and the Peters et al Delusions Inventory (PDI) score (Schizophr Bull 2004; 30: 1005-1022).

The authors found that 65 participants met criteria for a diagnosis of non-affective psychosis, and 233 reported at least one hallucination-related incident. The PDI has a score range of 0-21, and participants were grouped into PDI quartiles representing scores of =2, 3 or 4, 5 to 7, and =8.

The authors analyzed the results by means of two statistical models, one adjusted for participant sex and age at testing and the other adjusted for sex, age at testing, presence of hallucinations at the 14-year follow-up, and parental history of mental illness.

Using never-users as the reference, the odds ratio for non-affective psychosis increased from 1.5 to 2.1 or 2.2 in the two models as duration of first cannabis use increased. The odds for hallucinations increased from 1.4 to 2.5 and 1.5 to 2.8.

Comparing the lowest and highest quartiles of PDI scores, the authors found that the odds of a higher score increased from 1.6 to 4.0 or 4.3 as duration since first cannabis use increased.  Associations for all three psychosis-related outcomes were statistically significant in both models (P=0.001 to P<0.001).

The sibling analysis was limited to the PDI scores. For each pair, the authors calculated difference scores for duration since first cannabis use and PDI total score. The association between time since first cannabis use and PDI score remained statistically significant in the sibling subset analysis.

Limitations of the study included: retrospective self-reporting of time since first cannabis use, lack of data on cumulative exposure to cannabis, no clinical validation of non-affective psychosis diagnosis and lack of use of the instrument at the 14-year follow up, and loss of participants at the 21-year mark with significant differences in the group lost to follow up compared with those retained.

Source:. “Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults” Arch Gen Psychiatry 2010; DOI: 10.1001/archgenpsychiatry.2010.6.

Teens who smoke marijuana are at a greater risk of developing schizophrenia and psychotic symptoms in the future, a new study has found.
After observing more than 3800 youngsters, researchers learnt that people who used the drug for six or more years were twice as likely to suffer from delusional disorders than those who never used it. Researchers from Queensland Brain Institute, at the University of Queensland, quizzed 3801 young adults who were born in Brisbane between 1981 and 1984.
Among the 1272 participants who had never used marijuana, 26 (2 per cent) were diagnosed with psychosis, while the 322 people who had used marijuana for six or more years, 12 (3.7 per cent) were diagnosed with the illness. The average age of the participants was about 20. According to the authors, the study was the first to look at sibling pairs to discount genetic or environmental influence.
“This is the most convincing evidence yet that the earlier you use cannabis, the more likely you are to have symptoms of a psychotic illness,” the Sydney Morning Herald quoted Dr McGrath, a professor at the institute, as saying in a statement.
McGrath added: “The message for teenagers is: if they choose to use cannabis they have to understand there’s a risk involved.” The study noted: “Apart from the implications for policy makers and health planners, we hope our findings will encourage further clinical and animal-model research to unravel the mechanisms linking cannabis use and psychosis.”
The research has been published online by the Archives of General Psychiatry.

Source: Health Wise Feb 28 2009

A new American study suggests that parental monitoring can help bring down the cases of marijuana use by adolescents.
Psychologists Andrew Lac and William Crano of the Claremont Graduate University examined various studies to find the connection between parental monitoring (when parents know where their children are, what company are they in and what they are doing) and adolescent marijuana use.
Lac and Crano selected 17 studies containing data on over 35,000 participants. They assessed parental monitoring on the basis of admissions made by adolescent themselves and not their parents’ reports of keeping an eye on their children. The researchers found a strong link between parental monitoring and the decreased use of marijuana by adolescents.
The authors write: “Our review suggests that parents are far from irrelevant, even when it comes to an illegal and often secretive behavior on the part of their children.” They also believe that their analysis might come in handy for marijuana-prevention programs that are aimed at parents.
The findings of the review have been published in the latest issue of Perspectives on Psychological Science, a journal of the Association for Psychological Science. (ANI)

Source: Health Wise November 17th, 2009

Teens and young adults who are heavy marijuana users are more likely than non-users to have disrupted brain development, according to a new study that appeared last month in the Journal of Psychiatric Research.

Pediatric researchers found abnormalities in areas of the brain that interconnect regions involved in memory, attention, decision-making, language and executive functioning skills. The findings are of particular concern because adolescence is a crucial period for brain development and maturation.

The researchers caution the study is preliminary and does not demonstrate that marijuana use causes the brain abnormalities. However, “Studies of normal brain development reveal critical areas of the brain that develop during late adolescence, and our study shows that heavy cannabis use is associated with damage in those brain regions,” said study leader Manzar Ashtari, Ph.D., director of the Diffusion Image Analysis and Brain Morphometry Laboratory in the Radiology Department of The Children’s Hospital of Philadelphia.

Working with child psychiatrist Sanjiv Kumra, M.D., Ashtari and colleagues performed imaging studies on 14 young men from a residential drug treatment center in New York, as well as 14 age-matched healthy controls. All the study subjects were males, with an average age of 19. The researchers performed the imaging studies at Long Island Jewish Medical Center.

The 14 subjects from the drug treatment center all had a history of heavy cannabis use during adolescence. Most had smoked marijuana from age 13 till age 18 or 19, and reported smoking nearly six marijuana joints daily in the final year before they stopped using the drug.

The study team performed a type of magnetic resonance imaging scan called diffusion tensor imaging (DTI) that measures water movement through brain tissues. The abnormal patterns of water diffusion that were found among the young adults with histories of marijuana use suggest damage or an arrest in development of the myelin sheath that surrounds brain cells, Ashtari said. Myelin provides a coating around brain cells similar to insulation covering an electrical wire. If myelin does not function properly, signaling within the brain may be slower.

Myelin gives its color to the white matter of the brain, and covers the nerve fibers that connect different brain regions. The study’s results suggest early-onset substance use may alter the development of white matter circuits, especially those connections among the frontal, parietal and temporal regions of the brain. Abnormal white matter development could slow information transfer in the brain and affect cognitive functions

Source: the Journal of Psychiatric Research. Reported in CADCA Coalitions online Feb 24 2010

Theresa H M Moore, Stanley Zammit, Anne Lingford-Hughes, Thomas R E Barnes, Peter B Jones, Margaret Burke, Glyn Lewis
Summary
Background – Whether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes.
Methods – We searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from 4804 references were included. Data extraction and quality assessment were done independently and in duplicate.
Findings – There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1•41, 95% CI 1•20–1•65). Findings were consistent with a dose-response eff ect, with greater risk in people who used cannabis most frequently (2•09, 1•54–2•84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately.
Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding eff ect was present for both psychotic and aff ective outcomes.
Interpretation The evidence is consistent with the view that cannabis increases risk of psychotic outcomes independently of confounding and transient intoxication eff ects, although evidence for aff ective outcomes is less strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now suffi cient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.

Source: The Lancet Vol.370 pp 319-328 July 2007

New research shows that specific variations in the cannabis receptor gene (CB1) may be associated with the development of one or more symptoms of marijuana dependence in adolescents. This is one of the first studies looking specifically at the link between marijuana dependence and CB1 variations.

Background: Marijuana is the most commonly abused illegal substance among adolescents and young adults, and those who begin using at this stage are about twice as likely as adults to become dependent. Genetic variations in the CB1 receptor—the brain target for the psychoactive ingredient in marijuana—is a logical candidate gene to study as a potential contributor to vulnerability to marijuana dependence. Therefore, researchers examined the associations between specific variants in the CB1 gene and the rates of marijuana dependence.

Study Design: The scientists collected DNA from 541 youths aged 17 or older who had used marijuana at least five times recently. After interviews to identify one or more DSM-IV symptoms of dependence, 327 were established as cases; the remaining 214 had no symptoms and served as controls. All subjects were genotyped for four specific DNA sequence variations of the CB1 gene.

What They Found: One CB1 variant (found in 21 percent of the general population) was associated with a lower rate of having one or more marijuana dependence symptoms, while two others (present in 12 percent of the general population) were linked to increased likelihood of developing dependence symptoms.

Comments from the Authors: Identifying gene variants that may afford some protection against marijuana dependence may have important implications for intervention. However, it is likely that multiple genes and their interactions with environmental events influence marijuana and other drug addictions. Therefore, some level of genetic protection may not necessarily protect an adolescent from becoming dependent on drugs or suffering other related health consequences.

What’s Next: Future studies should examine these genetic variants for other drug-related traits, as well as additional DNA sequence variations for possible drug abuse associations.

Publication: The study, led by Dr. Christian J. Hopfer of the University of Colorado, was published in volume 141B, pages 895-901 (2006) of the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics).

Source:NIDA Newscan 27th Aug. 2007

Beshay M, Kaiser H, Niedhart D, Reymond MA, Schmid RA.
Division of General Thoracic Surgery, University Hospital Berne, Switzerland.

Background: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. Study design: Retrospective case series. Methods: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). Results: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p=0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. Conclusions: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the future.

Source: Pubmed. Eur J Cardiothorac Surg. 2007 Oct 9;

Cannabis use has been found to co-exist with a range of mental health symptoms and disorders (a concurrence referred to hereafter as co-morbidity). Large-scale epidemiological surveys have found higher rates of psychotic, affective, anxiety, and behavioural disorders among individuals with substance use disorders than in the general population (Degenhardt, Hall & Lynskey, 2001; Farrell et al., 2001; Merikangas et al., 1998). The majority of individuals seen at publically-funded mental health services have psychosis (including schizophrenia), bipolar disorder, or severe personality disorder, especially borderline personality disorder. Though there has been a dearth of studies on the latter, there have been several attempts to develop treatments for cannabis use for the former conditions (Edwards et al., 2006; Barrowclough et al., 2001; Baker et al, 2006; Kavanagh et al., 2002). Recent Australian studies have found cannabis use in individuals with psychosis to be significantly greater than have comparable international studies (Wade et al., 2006; Wade et al., 2007; Hinton, Edwards & Elkins, 2008) in a similar population of patients with recent-onset psychosis.
Source: www.npic.au 2009 Management of Cannabis and Related Disorders

Animal studies show that daily marijuana use could permanently alter serotonin and norepinephrine levels in the brain, raising the risk of depression and anxiety, according to researcher Gabriella Gobbi of McGill University.
The Canadian Press reported Dec. 17 that Gobbi studied the brain chemistry of 18 adolescent lab rats exposed daily to marijuana and found that they had decreased levels of mood-controlling serotonin and higher levels of the stress hormone norepinephrine.
Gobbi said that the effects were magnified because the adolescent brain is still developing. “These permanent changes in the brain are also linked to certain mental illnesses, like schizophrenia,” she said. “And we showed that even if we stopped the cannabis use at the end of adolescence, the changes were still detectable in adulthood.”
A future study will concentrate on adolescent marijuana use among humans.
Source: Neurobiology of Disease. 5th Dec.2009

Comments on above article:

Posted by JBrennan on 08 Jan 10 07:25 PM EST
I smoked marijuana daily at 17 years old and have felt different ever since stopping that, I ended up having more difficulty relaxing, sleeping, and finding energy than I did before daily marijuana use. Today I take amino acids that increase the amount of serotonin and norepinephrine, and it makes me feel normal again. It’s true that my one case doesn’t necessarily prove or disprove anything about marijuana, but I find it funny that there are people who immediately dismiss evidence of marijuana’s harmful affects while immediately claiming that marijuana is harmless, as if the brain is so easy to figure out that they already know everything there is to know about marijuana’s affects on the brain.
Posted by Paula D. Gordon on 09 Jan 10 04:30 AM EST
For additional information and perspectives on the harmfulness of marijuana, see http://gordondrugabuseprevention.com and http://spiritualharmofmarijuana.com It is interesting to note that there are references to work on both website that speak about the long term effects of marijuana use.

Posted by jgogek on 08 Jan 10 03:24 PM EST
The conclusions of this research would not surprise me at all. I find it disturbing when I read the comments in JoinTogether from advocates of recreational and medical marijuana immediately trying to denigrate any new finding on neurologic and other impacts of marijuana. Caring people should be concerned about the possible health impacts of commonly used substances — if not for themselves then at least for other people. Personal beliefs about marijuana use should be trumped by public health concerns. The science on marijuana impact continues to unfold and it should guide public policy. Personal wishes about individual marijuana use should not affect public policy.

Using a highly sensitive new test, scientists in Europe are reporting “convincing evidence” that marijuana smoke damages the genetic material DNA in ways that could increase the risk of cancer.

Researchers note that toxic substances in tobacco smoke can damage DNA and increase the risk of lung and other cancers. However, there has been uncertainty over whether marijuana smoke has the same effect. Scientists are especially concerned about the toxicity of acetaldehyde, present in both tobacco and marijuana. However, it has been difficult to measure DNA damage from acetaldehyde with conventional tests.
The research was carried out by Rajinder Singh, Jatinderpal Sandhu, Balvinder Kaur, Tina Juren, William P. Steward, Dan Segerback and Peter B. Farmer from the Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine and Karolinska Institute, Sweden.
Raj Singh said: “Parts of the plant Cannabis sativa, also known as marijuana, ganja, and various street names, are commonly smoked as a recreational drug, although its use for such purposes is illegal in many countries.
The scientists describe development and use of a modified mass spectrometry method that showed clear indications that marijuana smoke damages DNA.
“There have been many studies on the toxicity of tobacco smoke. It is known that tobacco smoke contains 4000 chemicals of which 60 are classed as carcinogens. Cannabis in contrast has not been so well studied. It is less combustible than tobacco and is often mixed with tobacco in use. Cannabis smoke contains 400 compounds including 60 cannabinoids. However, because of its lower combustibility it contains 50% more carcinogenic polycyclic aromatic hydrocarbons including naphthalene, benzanthracene, and benzopyrene, than tobacco smoke.”
The authors added: “It is well known that toxic substances in tobacco smoke can damage DNA and increase the risk of lung and other cancers. Scientists were unsure though whether cannabis smoke would have the same effect. Our research has focused on the toxicity of acetaldehyde, which is present in both tobacco and cannabis.”
The researchers add that the ability of cannabis smoke to damage DNA has significant human health implications especially as users tend to inhale more deeply than cigarette smokers, which increases respiratory burden. “The smoking of 3-4 cannabis cigarettes a day is associated with the same degree of damage to bronchial mucus membranes as 20 or more tobacco cigarettes a day,” the team adds.
“In conclusion, these results provide evidence for the DNA damaging potential of cannabis [marijuana] smoke, implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development,” the article states. “The data obtained from this study suggesting the DNA damaging potential of cannabis smoke highlight the need for stringent regulation of the consumption of cannabis cigarettes, thus limiting the development of adverse health effects such as cancer.”

Source Chemical Research in Toxicology, 2009; 22 (6): 1181 DOI: 10.1021/tx900106y

Here’s another reason to “keep off the grass.” Researchers in Canada report that marijuana smoke contains significantly higher levels of several toxic compounds — including ammonia and hydrogen cyanide — than tobacco smoke and may therefore pose similar health risks.

David Moir and colleagues note that researchers have conducted extensive studies on the chemical composition of tobacco smoke, which contains a host of toxic substances, including about 50 that can cause cancer. However, there has been relatively little research on the chemical composition of marijuana smoke.
In this new study, researchers compared marijuana smoke to tobacco smoke, using smoking machines to simulate the smoking habits of users. The scientists found that ammonia levels were 20 times higher in the marijuana smoke than in the tobacco smoke, while hydrogen cyanide, nitric oxide and certain aromatic amines occurred at levels 3-5 times higher in the marijuana smoke, they say. The finding is “important information for public health and communication of the risk related to exposure to such materials,” say the researchers.
The study, “A Comparison of Mainstream and Sidestream Marijuana and Tobacco Cigarette Smoke Produced under Two Machine Smoking Conditions,” is scheduled for the Dec. 17 issue of ACS’ Chemical Research in Toxicology.

Source: ScienceDaily. Retrieved December 29, 2009, from http://www.sciencedaily.com /releases/2007/12/071217110328.htm

In a finding that challenges the increasingly popular belief that smoking marijuana is less harmful to health than smoking tobacco, researchers in Canada are reporting that smoking marijuana, like smoking tobacco, has toxic effects on cells.

Rebecca Maertens and colleagues note that people often view marijuana as a “natural” product and less harmful than tobacco. As public attitudes toward marijuana change and legal restrictions ease in some countries, use of marijuana is increasing.
Scientists know that marijuana smoke has adverse effects on the lungs. However, there is little knowledge about marijuana’s potential to cause lung cancer due to the difficulty in identifying and studying people who have smoked only marijuana.
The new study begins to address that question by comparing marijuana smoke vs. tobacco smoke in terms of toxicity to cells and to DNA. Scientists exposed cultured animal cells and bacteria to condensed smoke samples from both marijuana and tobacco. There were distinct differences in the degree and type of toxicity elicited by marijuana and cigarette smoke.
Marijuana smoke caused significantly more damage to cells and DNA than tobacco smoke, the researchers note. However, tobacco smoke caused chromosome damage while marijuana did not.

Source: The Genotoxicity of Mainstream and Sidestream Marijuana and Tobacco Smoke Condensates. Chemical Research in Toxicology, Online July 17, 2009 DOI: 10.1021/tx9000286

People with multiple sclerosis (MS) who smoke marijuana are more likely to have emotional and memory problems, according to new research.

“This is the first study to show that smoking marijuana can have a harmful effect on the cognitive skills of people with MS,” said study author Anthony Feinstein, MPhil, PhD, of the University of Toronto. “This is important information because a significant minority of people with MS smoke marijuana as a treatment for the disease, even though there are no scientific studies demonstrating that it is an effective treatment for emotional difficulties.”
Feinstein noted that MS itself can cause cognitive problems. “In addition, cognitive problems can greatly affect the quality of life for both patients and their caregivers,” he said.
For the study, researchers interviewed 140 Canadian people with MS. Of those, 10 people had smoked marijuana within the last month and were defined as current marijuana users. The marijuana users were then each matched by age, sex, the length of time they had MS, and other factors to four people with MS who did not smoke marijuana.
The researchers then evaluated the participants for emotional problems such as depression, anxiety and other psychiatric disorders. They also tested the participants’ thinking skills, speed at processing information, and memory.
The study found marijuana smokers performed 50 percent slower on tests of information processing speed compared to MS patients who did not smoke marijuana. There was also a significant association between smoking marijuana and emotional problems such as depression and anxiety.
People with MS have higher rates of depression and suicide compared to the general population. “Since marijuana can induce psychosis and anxiety in healthy people, we felt it was especially important to look at its effects on people with MS,” Feinstein said.

Source: the online edition of Neurology, February 13, 2008

Progression to daily marijuana use in adolescence may hasten the onset of symptoms leading up to psychosis, an Emory University study finds. The study was published in the November issue of the American Journal of Psychiatry.

The researchers analyzed data from 109 hospitalized patients who were experiencing their first psychotic episode. The results showed that patients who had a history of using marijuana, or cannabis, and increased to daily pot smoking experienced both psychotic and pre-psychotic symptoms at earlier ages.
“We were surprised that it wasn’t just whether or not they used cannabis in adolescence that predicted the age of onset, rather it was how quickly they progressed to becoming a daily cannabis user that was the stronger predictor,” said Michael Compton, lead author and assistant professor of psychiatry in the Emory School of Medicine.
The study also found a gender difference: The female subjects who progressed to daily pot smoking had a greater increased risk for the onset of psychosis than the males.
Marijuana is the most abused illicit substance among people with schizophrenia, the most extreme form of psychosis, and previous research has shown that smoking pot is likely a risk factor for the disease.
The Emory study also focused on what is known as the prodromal period, when a person has symptoms such as unusual sensory experiences, which are often precursors to frank hallucinations and delusions. Prodromal symptoms can occur months, or years, before a diagnosis of psychosis. About 30 to 40 percent of prodomal teenagers will eventually develop schizophrenia or another psychotic disorder.
“The prodromal period is especially important because it’s considered to be a critical time for preventive intervention,” says Elaine Walker, a co-investigator of the study and professor of psychology and neuroscience at Emory.
The study also involved researchers from Emory’s Rollins School of Public Health and Georgia State University. It was funded by the National Institute of Mental Health.

Source: American Journal of Psychiatry, 2009; 166 (11): 1251 DOI: 10.1176/appi.ajp.2009.09030311

Testicular germ cell tumors (TGCTs) are the most common type of cancer in American men between the ages of 15 and 34. For the last 50 years, the incidence of TGCTs has increased yearly in the United States and many other Western countries. A corresponding increase in marijuana abuse during this time period has been suggested as a potential causative factor. Chronic marijuana use is known to affect the body’s hormone and reproductive systems, disruption of which can potentially lead to cancer development. To test this hypothesis, researchers funded by NIDA interviewed 371 men aged 18 to 44 in Seattle and Puget Sound, Washington who had been treated for an invasive TGCT between 1999 and 2006, and 979 men from the same area who had not had testicular cancer. The researchers asked all participants about their lifetime marijuana and hashish use, as well as cigarette, alcohol, and other recreational drug use. They also collected data on other suspected risk factors for TGCT, including cryptorchidism (an undescended testicle) and a family history of TGCT. The researchers found that current marijuana use was associated with a 70 percent increased risk of nonseminoma TGCTs, but was not associated with risk of seminoma. (Seminoma and nonseminoma are the two subtypes of TGCT.) For nonseminoma tumors, the risk increased more for frequent (at least weekly) marijuana use and for use beginning in adolescence. This increased risk was independent of any other measured risk factor. The authors conclude that additional studies are needed to confirm these results, and to understand the biological processes that may link marijuana use to an increase in risk for nonseminoma TGCTs.

Daling JR, Doody DR, Sun X, Trabert BL, Weiss NS, Chen C, Biggs ML, Starr JR, Dey SK, Schwartz SM. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer. 2009 Mar 15;115(6):1215-23.

Source: NIDA Addiction Research News December 11, 2009

http://www.drugabuse.gov/newsroom/09/NS-12.html

A new study funded by NIDA has used brain-imaging technology to show that during a decision game, chronic marijuana users show less activity in an error-processing part of their brains than peers who do not use marijuana. These results provide preliminary evidence in the debate on whether substance abusers willfully ignore their problem or whether cognitive deficits prevent them from fully understanding their addiction and its potential consequences. Functional magnetic resonance imaging (fMRI) of 16 heavy marijuana users and 16 non-drug-using peers provided real-time pictures of brain activity during the decision game. The marijuana abusers in the study did not make more mistakes during the game than participants who did not use the drug, but they were significantly less likely to recognize that they had made the mistakes. Non-marijuana-using participants were aware of 91 percent of their mistakes during the game, and marijuana abusers were aware of only 77 percent of their mistakes. fMRI revealed that when they made errors that they did not consciously recognize, the marijuana abusers showed less activity than the other participants in an area of the brain called the anterior cingulate cortex (ACC). The authors caution that marijuana withdrawal may have played some role in the lack of error awareness, as higher scores in several categories on a marijuana craving questionnaire were associated with poorer error awareness. However, if drug abusers cannot monitor their behavior accurately, this deficit in awareness may contribute to their continued use of a drug despite the consequences or to their continued associations with situations that make them liable to relapse.

Hester R, Nestor L, Garavan H. Impaired Error Awareness and Anterior Cingulate Cortex Hypoactivity in Chronic Cannabis Users. Neuropsychopharmacology. 2009 Jun 24. [Epub ahead of print]

Source: NIDA Addiction Research News December 11, 2009

http://www.drugabuse.gov/newsroom/09/NS-12.html

Clinical studies, like those by Barbara Mason at Scripps Institute, have documented a marijuana withdrawal syndrome among a minority of users. Are we prepared to say that marijuana is addictive? Why didn’t we identify this syndrome years ago?

Nora Volkow: Absolutely, there is no doubt that some users can become addicted to marijuana. In fact, well over half of the close to 7 million Americans classified with dependence or abuse of an illicit drug are dependent on or abuse marijuana. It is important to clarify that while withdrawal is one of the criteria used to diagnose an addiction (which also includes compulsive use in spite of known adverse consequences), it is possible for an individual to suffer withdrawal symptoms without he or she being addicted to an abused substance.

Now, to answer your specific question, the reason for the relatively late realization that people who abuse marijuana can develop a cannabis withdrawal syndrome (CWS) if they try to quit is probably the result of at least two factors. First is the fact (which you hint at already) that a clinically relevant cannabis withdrawal syndrome may only be expected in a subgroup of cannabis-dependent patients. This may be partially explained by marijuana’s uptake into and slow release from fat cells, which can occur over days or weeks after last use. Thus, cessation of marijuana use may not be so abrupt, and could thereby diminish signs of withdrawal. The second factor relates to the small to negligible associations between recalled and prospectively assessed withdrawal symptoms, which may have precluded many previous, recall-based studies from detecting or properly characterizing CWS. It is also worth pointing out that other addictions (e.g., cocaine) were also not initially thought of as capable of triggering withdrawal symptoms.”
Source: http://addiction-dirkh.blogspot.com/2009/12/q-with-nora-volkow.html?

The daily consumption of cannabis predisposes to the appearance of psychosis and schizophrenia, and those episodes of psychosis which are fruit of this substance present certain specific characteristics, both before their appearance and in the clinical presentation of the psychosis.

This is one of the conclusions of the doctoral thesis “Neurodevelopment and environmental stress in initial psychosis: transversal analysis of the ESPIGAS study”, carried out by researcher Miguel Ruiz Veguilla, of the Institute of Neurosciences of the University of Granada (Spain) and supervised by professors Manuel Gurpegui Fernández de Legaria and Jorge Cervilla Ballesteros. Ruiz Veguilla is also the person in charge fo the Unit of Development Neuropsychiatry of Jaén (Spain).
This work has studied the risk factors associated with schizophrenia, identifying and characterizing in depth those psychosis associated with a continual consumption of cannabis. They carried out a study with 92 subjects, 50 of which had developed a psychosis without presenting signs of an “abnormal neurodevelopment”, this is, they had been doing well academically, they had a group of friends (no social isolation) and they presented a good motor coordination. In addition, these subjects did not show a family history of episodes of psychosis in first or second degree.

Identifying a new type of psychosis
The research work carried out by Miguel Ruiz Veguilla has identified a connection between cannabis consumption and psychosis in subjects with a good premorbid performance, and without signs of minor neurological alterations, which in his opinion might point out “a psychopathological way associated with psychosis in subjects with less predisposition”.
Thus, 66% of the patients with psychosis who participated in the study and had a normal neurodevelopment admitted to have consumed cannabis daily or almost every day, whereas 43% of the participants with markers of an abnormal neurodevelopment (those already indicated: bad previous social and academic behaviour, a family history and a “clumsier” attitude when they carry out tasks of motor coordination and complex motor acts) were drug users too.
In the light of the results of his doctoral thesis, the researcher of the University of Granada says that, after having identified a type of psychosis where the environmental factor plays a more relevant role, we should now answer the question of which is the prognosis, in the long term, of those subjects with a good previous behaviour, whose psychosis is associated with a high consumption of cannabis.
The results of this research work have been published in the journals Schizophrenia Research and European Psychiatry.

Source: December 29, 2009, from http://www.sciencedaily.com/releases/2009/03/090325132328.htm

Canadian teenagers are among the largest consumers of cannabis worldwide. The damaging effects of this illicit drug on young brains are worse than originally thought, according to new research by Dr. Gabriella Gobbi, a psychiatric researcher from the Research Institute of the McGill University Health Centre. The new study, published in Neurobiology of Disease, suggests that daily consumption of cannabis in teens can cause depression and anxiety, and have an irreversible long-term effect on the brain.

“We wanted to know what happens in the brains of teenagers when they use cannabis and whether they are more susceptible to its neurological effects than adults,” explained Dr. Gobbi, who is also a professor at McGill University. Her study points to an apparent action of cannabis on two important compounds in the brain — serotonin and norepinephrine — which are involved in the regulation of neurological functions such as mood control and anxiety.
“Teenagers who are exposed to cannabis have decreased serotonin transmission, which leads to mood disorders, as well as increased norepinephrine transmission, which leads to greater long-term susceptibility to stress,” Dr. Gobbi stated.
Previous epidemiological studies have shown how cannabis consumption can affect behaviour in some teenagers. “Our study is one of the first to focus on the neurobiological mechanisms at the root of this influence of cannabis on depression and anxiety in adolescents,” confirmed Dr. Gobbi. It is also the first study to demonstrate that cannabis consumption causes more serious damage during adolescence than adulthood.
Dr. Gabriella Gobbi is a researcher at the neuroscience axis of the Research Institute of the McGill University Health Centre and also a psychiatrist and associate professor at the Department of Psychiatry, McGill University.

Source:
McGill University Health Centre (2009, December 20). Cannabis damages young brains more than originally thought, study finds. ScienceDaily. Retrieved December 29, 2009, from http://www.sciencedaily.com¬ /releases/2009/12/091217115834.htm

Scientists have been studying cannabinoids, substances that are chemically related to the ingredients found in marijuana, for more than two decades, hoping to learn more about how the drug produces its effects–both therapeutic and harmful. Marijuana has been reported effective in the treatment of multiple sclerosis, glaucoma, nausea caused by chemotherapy and wasting caused by AIDS. However, like all drugs, it also causes numerous unwanted side effects, including hypothermia, sedation, memory impairment, motor impairment and anxiety. Research on cannabinoids could someday yield new, more effective drugs or drug combinations.

At Temple University’s School of Pharmacy and Center for Substance Abuse Research (CSAR), one of only a few centers in the nation focused on the basic science of substance abuse, several researchers are investigating how cannabinoids produce pharmacological effects in rats.
One such study, “L-NAME, a nitric oxide synthase inhibitor, and WIN 55212-2, a cannabinoid agonist, interact to evoke synergistic hypothermia,” published in the February issue of the Journal of Pharmacology and Experimental Therapeutics, reveals how cannabinoids produce one of the drug’s most robust actions, hypothermia, or decreased body temperature.
According to lead author Scott Rawls, Ph.D., assistant professor of pharmacodynamics at Temple’s School of Pharmacy, “To operate at maximum efficiency, the body needs to maintain a stable, normal temperature. When the body’s temperature is altered, as in hypothermia, normal body functions, such as blood pressure and circulation, are impaired.”
Marijuana operates via two receptors in the body. One receptor, called CB1, is located in the brain and produces the drug’s psychoactive effects, including euphoria and dizziness. The other receptor, CB2, is found throughout the body and impacts the immune system. Substances in marijuana bind to one of these receptors and set off a chemical process that leads to an effect, such as hypothermia. Scientists have focused on this chemical process at the molecular level to pinpoint the exact molecules involved.
Knowing that the molecule nitric oxide (NO) plays an important role in the regulation of body temperature, the Temple researchers set out to determine what role it might play in cannabinoid-induced hypothermia. By combining a cannabinoid with a substance that blocked NO synthesis, they found that cannabinoid-induced hypothermia increased more than two-fold.
“This demonstrates the possibility that NO plays a part in regulating the impact of cannabinoids on body temperature and other cannabinoid-mediated actions,” said Rawls. “These findings could be helpful in determining the mechanisms that underlie some of the pharmacological actions of marijuana,” he added.
Rawls’ research team is currently investigating the impact of cannabinoids on other physiological systems, such as analgesia and movement, and the brain neurotransmitters that mediate those systems.

Source: . ScienceDaily. Retrieved July 18, 2008, from http://www.sciencedaily.com¬ /releases/2004/03/040309071927.htm

This research study is very encouraging – showing another area of illness where cannabinoids ( extracts of cannabis) may be able to be used medicinally Reputable scientists and researchers, and companies like G W Pharmaceuticals, are excited by the possible use of extracts of cannabis as treatments for some illnesses.
Please note however, this is not a recommendation for smoking raw cannabis – any substance taken into the body via smoking is harmful and can lead to severe health problems.Use of cannabinoids (marijuana) could assist in the treatment of post-traumatic stress disorder patients. This is exposed in a new study carried out at the Learning and Memory Lab in the University of Haifa’s Department of Psychology.

The study, carried out by research student Eti Ganon-Elazar under the supervision of Dr. Irit Akirav, was published in the Journal of Neuroscience.

In most cases, the result of experiencing a traumatic event — a car accident or terror attack — is the appearance of medical and psychological symptoms that affect various functions, but which pass. However, some 10%-30% of people who experience a traumatic event develop post-traumatic stress disorder, a condition in which the patient continues to suffer stress symptoms for months and even years after the traumatic event. Symptoms include reawakened trauma, avoidance of anything that could recall the trauma, and psychological and physiological disturbances. One of the problems in the course of treating trauma patients is that a person is frequently exposed to additional stress, which hinders the patient’s overcoming the trauma.

The present study, carried out by Dr. Akirav and research student Eti Ganon-Elazar, aimed to examine the efficiency of cannabinoids as a medical treatment for coping with post-traumatic stress. The researchers used a synthetic form of marijuana, which has similar properties to the natural plant, and they chose to use a rat model, which presents similar physiological responses to stress to that of humans.

The first stage of the research examined how long it took for the rats to overcome a traumatic experience, without any intervention. A cell colored white on one side and black on the other was prepared. The rats were placed in the white area, and as soon as they moved over to the black area, which they prefer, they received a light electric shock. Each day they were brought to the cell and placed back in the white area. Immediately following exposure to the traumatic experience, the rats would not move to the black area voluntarily, but a few days later after not receiving further electric shocks in the black area, they learned that it is safe again and moved there without hesitation.

Next, the researchers introduced an element of stress. A second group of rats were placed on a small, elevated platform after receiving the electric shock, which added stress to the traumatic experience. These rats abstained from returning to the black area in the cell for much longer, which shows that the exposure to additional stress does indeed hinder the process of overcoming trauma.

The third stage of the research examined yet another group of rats. These were exposed to the traumatic and additional stress events, but just before being elevated on the platform received an injection of synthetic marijuana in the amygdala area of the brain — a specific area known to be connected to emotive memory. These rats agreed to enter the black area after the same amount of time as the first group — showing that the synthetic marijuana cancelled out the symptoms of stress. Refining the results of this study, the researchers then administered marijuana injections at different points in time on additional groups of rats, and found that regardless of when exactly the injection was administered, it prevented the surfacing of stress symptoms.

Dr. Akirav and Ganon-Elazar also examined hormonal changes in the course of the experiment and found that synthetic marijuana prevents increased release of the stress hormone that the body produces in response to stress. According to Dr. Akirav, the results of this study show that cannabinoids can play an important role in stress-related disorders. “The results of our research should encourage psychiatric investigation into the use of cannabinoids in post-traumatic stress patients,” she concludes.

Source: University of Haifa (2009, November 4). Use Of Cannabinoids Could Help Post-traumatic Stress Disorder Patients. ScienceDaily. Retrieved November 12, 2009, from http://www.sciencedaily.com¬ /releases/2009/11/091104091726.htm

Yes, despite what potheads claim. Doctors in Greece compared the mental abilities of 20 people who had smoked dope four times a week for 15 years with 20 who had used it for less than seven years, and 24 never-smokers. They were given 15 words to learn, and asked to repeat them later. The average score for the long-term smokers was 7; for the shorter-term smokers, 9; for the never-users, 12. It is the latest in many studies showing repeated ‘soft’ drug abuse damages the brain. This isn’t surprising because marijuana’s active ingredient, tetrahydro cannabinol (THC), is highly fat-soluble. As our brain is the organ with the highest concentration of fat, THC makes a beeline for it and stays there for

Source: The Guardian Saturday September 30, 2006

Patients with chronic hepatitis C (HCV) infection should not use marijuana (cannabis) daily, according to a study published in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute. Researchers found that HCV patients who used cannabis daily were at significantly higher risk of moderate to severe liver fibrosis, or tissue scarring. Additionally, patients with moderate to heavy alcohol use combined with regular cannabis use experienced an even greater risk of liver fibrosis. The recommendation to avoid cannabis is especially important in patients who are coinfected with HCV/HIV since the progression of fibrosis is already greater in these patients.

“Hepatitis C is a major public health concern and the number of patients developing complications of chronic disease is on the rise,” according to Norah Terrault, MD, MPH, from the University of California, San Francisco and lead investigator of the study. “It is essential that we identify risk factors that can be modified to prevent and/or lessen the progression of HCV to fibrosis, cirrhosis and even liver cancer. These complications of chronic HCV infection will significantly contribute to the overall burden of liver disease in the U.S. and will continue to increase in the next decade.”

This is the first study that evaluates the relationship between alcohol and cannabis use in patients with HCV and those coinfected with HCV/HIV. It is of great importance to disease management that physicians understand the factors influencing HCV disease severity, especially those that are potentially modifiable. The use and abuse of both alcohol and marijuana together is not an uncommon behavior. Also, individuals who are moderate and heavy users of alcohol may use cannabis as a substitute to reduce their alcohol intake, especially after receiving a diagnosis like HCV, which affects their liver. Researchers found a significant association between daily versus non-daily cannabis use and moderate to severe fibrosis when reviewing this factor alone. Other factors contributing to increased fibrosis included age at enrollment, lifetime duration of alcohol use, lifetime duration of moderate to heavy alcohol use and necroinflammatory score (stage of fibrosis). In reviewing combined factors, there was a strong (nearly 7-fold higher risk) and independent relationship between daily cannabis use and moderate to severe fibrosis. Gender, race, body mass index, HCV viral load and genotype, HIV coinfection, source of HCV infection, and biopsy length were not significantly associated with moderate to severe fibrosis.

Of the 328 patients screened for the study, 204 patients were included in the analysis. The baseline characteristics of those included in the study were similar to those excluded with the exception of daily cannabis use (13.7 percent of those studied used cannabis daily versus 6.45 percent of those not included). Patients who used cannabis daily had a significantly lower body mass index than non-daily users (25.2 versus 26.4), were more likely to be using medically prescribed cannabis (57.1 percent versus 8.79 percent), and more likely to have HIV coinfection (39.3 percent versus 18.2 percent).

The prevalence of cannabis use amongst adults in the U.S. is estimated to be almost 4 percent. Regular use has increased in certain population subgroups, including those aged 18 to 29.

Hepatitis is an inflammation of the liver. Hepatitis C is the most common form of hepatitis and infects nearly 4 million people in the U.S., with an estimated 150,000 new cases diagnosed each year. While it can be spread through blood transfusions and contaminated needles, for a substantial number of patients, the cause is unknown. This form of viral hepatitis may lead to cirrhosis, or scarring, of the liver. Coinfection of hepatitis C in patients who are HIV positive is common; about one quarter of patients infected with HIV are infected with hepatitis C. The majority of these patients, 50 to 90 percent, were infected through injection drug use. Hepatitis C ranks with alcohol abuse as the most common cause of chronic liver disease and leads to about 1,000 liver transplants yearly in the U.S.

Source: http://www.medicalnewstoday.com/articles/95434.php 29.01.08

Singapore — 23 January 2008

A study in a Wiley-Blackwell journal – Respirology – finds that the development of bullous lung disease occurs in marijuana smokers approximately 20 years earlier than tobacco smokers.

A condition often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke, bullous lung disease (also known as bullae) is a condition where air trapped in the lungs causes obstruction to breathing and eventual destruction of the lungs.

At present, about 10% of young adults and 1% of the adult population smoke marijuana regularly.
Researchers find that the mean age of marijuana-smoking patients with lung problems was 41, as opposed to the average age of 65 years for tobacco-smoking patients.

The study “Bullous Lung Disease due to Marijuana” also finds that the bullous lung disease can easily go undetected as patients suffering from the disease may show normal chest X-rays and lung functions.
High-resolution CT scans revealed severe asymmetrical, variably sized bullae in the patients studied. However, chest X-rays and lung functions were normal in half of them.

Lead author Dr. Matthew Naughton says, “What is outstanding about this study is the relatively young ages of the lung disease patients, as well as the lack of abnormality on chest X-rays and lung functions in nearly half of the patients we tested.” He added, “Marijuana is inhaled as extremely hot fumes to the peak inspiration and held for as long as possible before slow exhalation. This predisposes to greater damage to the lungs and makes marijuana smokers are more prone to bullous disease as compared to cigarette smokers.”

Patients who smoke marijuana inhale more and hold their breath four times longer than cigarette smokers. It is the breathing manoeuvres of marijuana smokers that serve to increase the concentration and pulmonary deposition of inhaled particulate matter – resulting in greater and more rapid lung destruction.

Source:http://www.aushealthcare.com.au/news/news_details.asp?nid=10642 23rd January 2008

Study could potentially help clinicians treat marijuana addiction

Research by a group of scientists studying the effects of heavy marijuana use suggests that withdrawal from the use of marijuana is similar to what is experienced by people when they quit smoking cigarettes. Abstinence from each of these drugs appears to cause several common symptoms, such as irritability, anger and trouble sleeping – based on self reporting in a recent study of 12 heavy users of both marijuana and cigarettes.

“These results indicate that some marijuana users experience withdrawal effects when they try to quit, and that these effects should be considered by clinicians treating people with problems related to heavy marijuana use,” says lead investigator in the study, Ryan Vandrey, Ph.D., of the Department of Psychiatry at the Johns Hopkins University School of Medicine.

Marijuana is the most widely used illicit drug in the United States. Admissions in substance abuse treatment facilities in which marijuana was the primary problem substance have more than doubled since the early 1990s and now rank similar to cocaine and heroin with respect to total number of yearly treatment episodes in the United States, says Vandrey.

He points out that a lack of data, until recently, has led to cannabis withdrawal symptoms not being characterized or included in medical reference literature such as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, (DSM-IV) or the International Classification of Diseases, 10th edition (ICD-10). Since the drafting of the DSM-IV in 1994, an increasing number of studies have surfaced suggesting that cannabis has significant withdrawal symptoms. What makes Vandrey’s recent study unique is that it is the first study that compares marijuana withdrawal symptoms to withdrawal symptoms that are clinically recognized by the medical community – specifically the tobacco withdrawal syndrome.

“Since tobacco withdrawal symptoms are well documented and included in the DSM-IV and the IDC-10, we can infer from the results of this comparison that marijuana withdrawal is also clinically significant and should be included in these reference materials and considered as a target for improving treatment outcomes,” says Vandrey.

Vandrey added that this is the first “controlled” comparison of the two withdrawal syndromes in that data was obtained using rigorous scientific methods – abstinence from drugs was confirmed objectively, procedures were identical during each abstinence period, and abstinence periods occurred in a random order. That tobacco and marijuana withdrawal symptoms were reported by the same participants, thus eliminating the likelihood that results reflect physiological differences between subjects, is also a strength of the study.

Interestingly, the study also revealed that half of the participants found it easier to abstain from both substances than it was to stop marijuana or tobacco individually, whereas the remaining half had the opposite response. “Given the general consensus among clinicians that it is harder to quit more than one substance at the same time, these results suggest the need for more research on treatment planning for people who concurrently use more than one drug on a regular basis,” says Vandrey.

Vandrey’s study, which appears in the January issue of the journal Drug and Alcohol Dependence, followed six men and six women at the University of Vermont in Burlington and Wake Forest University School of Medicine in Winston-Salem, N.C., for a total of six weeks. All were over 18 (median age 28.2 years), used marijuana at least 25 days a month and smoked at least 10 cigarettes a day. None of the subjects intended to quit using either substance, did not use any other illicit drugs in the prior month, were not on any psychotropic medication, did not have a psychiatric disorder, and if female, were not pregnant.

For the first week, participants maintained their normal use of cigarettes and marijuana. For the remaining five weeks, they were randomly chosen to refrain from using either cigarettes, marijuana or both substances for five-day periods separated by nine-day periods of normal use. In order to confirm abstinence, patients were given daily quantitative urine toxicology tests of tobacco and marijuana metabolites. Withdrawal symptoms were self reported on a daily basis Monday through Friday using a withdrawal symptom checklist that listed scores for aggression, anger, appetite change, depressed mood, irritability, anxiety/nervousness, restlessness, sleep difficulty, strange dreams and other, less common withdrawal symptoms. Patients also provided an overall score for discomfort they experienced during each abstinence period.

Results showed that overall withdrawal severity associated with marijuana alone and tobacco alone was of similar frequency and intensity. Sleep disturbance seemed to be more pronounced during marijuana abstinence, while some of the general mood effects (anxiety, anger) seemed to be greater during tobacco abstinence. In addition, six of the participants reported that quitting both marijuana and tobacco at the same time was more difficult than quitting either drug alone, whereas the remaining six found that it was easier to quit marijuana or cigarettes individually than it was to abstain from the two substances simultaneously.

Vandrey recognizes that the small sample size is a limitation in this study, but the results are consistent with other studies indicating that marijuana withdrawal effects are clinically important.

Source: http://www.eurekalert.org/pub_releases/2008-01/jhmi-mwa012408.php :
Eric Vohr evohr1@jhmi.edu Johns Hopkins Medical Institutions

HONG KONG (Reuters) – Smoking a joint is equivalent to 20 cigarettes in terms of lung cancer risk, scientists in New Zealand have found, as they warned of an “epidemic” of lung cancers linked to cannabis.
Studies in the past have demonstrated that cannabis can cause cancer, but few have established a strong link between cannabis use and the actual incidence of lung cancer.
In an article published in the European Respiratory Journal, the scientists said cannabis could be expected to harm the airways more than tobacco as its smoke contained twice the level of carcinogens, such as polyaromatic hydrocarbons, compared with tobacco cigarettes.
The method of smoking also increases the risk, since joints are typically smoked without a proper filter and almost to the very tip, which increases the amount of smoke inhaled. The cannabis smoker inhales more deeply and for longer, facilitating the deposition of carcinogens in the airways.
“Cannabis smokers end up with five times more carbon monoxide in their bloodstream (than tobacco smokers),” team leader Richard Beasley, at the Medical Research Institute of New Zealand, said in a telephone interview.
“There are higher concentrations of carcinogens in cannabis smoke … what is intriguing to us is there is so little work done on cannabis when there is so much done on tobacco.”
The researchers interviewed 79 lung cancer patients and sought to identify the main risk factors for the disease, such as smoking, family history and occupation. The patients were questioned about alcohol and cannabis consumption.
In this high-exposure group, lung cancer risk rose by 5.7 times for patients who smoked more than a joint a day for 10 years, or two joints a day for 5 years, after adjusting for other variables, including cigarette smoking.
“While our study covers a relatively small group, it shows clearly that long-term cannabis smoking increases lung cancer risk,” wrote Beaseley.

“Cannabis use could already be responsible for one in 20 lung cancers diagnosed in New Zealand,” he added.
“In the near future we may see an ‘epidemic’ of lung cancers connected with this new carcinogen. And the future risk probably applies to many other countries, where increasing use of cannabis among young adults and adolescents is becoming a major public health problem.”
(Reporting by Tan Ee Lyn; Editing by Alex Richardson)

Source: http://www.reuters.com/article/healthNews/ Jan. 29 2008

The study’s demonstration of a
strong association between cannabis
use and periodontitis experience by
age 32 years indicates that long-term
smoking of cannabis is detrimental to
the periodontal tissues and that public
health measures to reduce the prevalence
of cannabis smoking may have
periodontal benefits for the population.

To our knowledge, no previous
studies have examined this relationship,
so there are no data with which
to compare the findings. Determining
whether the association exists in other
populations should be a priority for
periodontal epidemiological research.

The nature of the biological mechanism
for the observed association is
currently unclear. The periodontal
effects of tobacco smoke are thought
to occur via the systemic effects of
nicotine and other toxic constituents
on immune function and the inflammatory
response within the periodontal
tissues. Cannabis contains more
than 400 compounds, including more
than 60 cannabinoids; the noncannabinoid
constituents are similar to
tobacco (except for nicotine), and
those have been reported to carry systemic
health risks and have histopathological
effects that are similar to
those of tobacco smoke.

Although definitively establishing the
periodontal effects of exposure to cannabis
smoke we should await confirmation
in other populations and settings,
health promoters and dental and medical
practitioners should take steps to
raise awareness of the strong probability
that regular cannabis users may be
doing damage to the tissues that support
their teeth.

Source: Jama Feb.6 2008 Vol.299 No.5

A study has found that heavy cannabis smoking is a major cause of gum disease.

The investigation, which tracked a group of 1000 people born in Dunedin in 1972-73, found heavy cannabis use was responsible for more than one-third of the new cases of gum disease by age 32.

The study involved researchers from the University of Otago, King’s College in London, Duke University and the University of North Carolina in the United States. Professor Murray Thomson from University of Otago School of Dentistry said toxins in cannabis smoke were detrimental to periodontal health. “The problem is not the smoke itself – it’s what’s in the smoke,” he said. “In the mouth, there is a fine balance between tissue destruction and tissue healing and the various toxins in cannabis smoke disrupt that.”

Professor Thomson said gum disease was one of the most common diseases of adulthood, and caused problems such as the loss of support for the teeth. There was also emerging evidence it could be a risk factor for heart disease, stroke and pre-term birth.

Heavy cannabis users are those who smoke cannabis 41 times or more per year between the ages of 18 and 32.

The study is the first to have investigated whether smoking anything other than tobacco is detrimental for the gums. The evidence has been published in the prestigious Journal of the American Medical Association.

Source: New Zealand Herald.6 Feb 2008

Cannabis use in British teenagers has increased tenfold in the last 20 years
Children who smoke cannabis are twice as likely to get into trouble – both in the classroom and outside the school gates. Boys turn to vandalism, theft and fights, while girls misbehave at school, a four-year study of thousands of pupils aged between 11 and 15 found.
Young males are also up to twice as likely to have committed “delinquent” acts such as vandalism or carrying a knife. And teenage cannabis users have double the chance of developing emotional and psychiatric problems in later life. The finding was released as Gordon Brown comes under pressure to reverse Labour’s downgrading of cannabis.
Calling on the Government to do more to combat drug use in teenagers, researcher Laura Grant said: “Cannabis has been regarded as potentially being a gateway drug to harder drug use, leading to mental health issues, leading to memory loss or impairment and having an impact on learning and social behaviour.
“I have spoken to kids that smoke cannabis every single night, they get up and go to grammar school and get good grades. “This really is a hidden issue that needs to be tackled.”
She added: “These young people are still attending school and are at odds with the general perception of what the typical young person is like who engages in these acts.
“It is no great leap to imagine that this school-attending high risk group may be a further risk of later life problems as a result of their early drug use: mentally, socially and emotionally.” Miss Grant, a sociologist at Queen’s University Belfast, studied data tracking the health and habits of almost 4,000 Northern Irish schoolchildren.
By the age of 15, more than 40 per cent had tried cannabis – a five-fold increase on four years earlier, the British Psychological Society’s annual conference in Dublin heard. She added it was unclear why cannabis had different effects on boys and girls.
A fifth of those studied were judged to be at risk of developing mental health problems in later life, with cannabis users running up to double the risk of other children.
Cannabis use in British teenagers has increased tenfold in the last 20 years. By the age of 16, almost four in ten will have tired cannabis and almost one in ten is a regular user. In 2005, 10,000 youngsters aged between 11 and 17 were treated for cannabis use.
Previous studies have shown a clear link between cannabis use in the teenage years and mental illness in later life. It is thought that used during the developmental years, the drug may do permanent damage to the developing brain.
Source: Daily Mail 5th April 2008

People who smoke different strains of cannabis appear to have different psychological symptoms, depending on the cannabinoid combination contained within a particular strain, UK study findings suggest.

Two of the various cannabinoids contained in cannabis – delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) – have almost opposing action, as THC is psychomimetic and CBD is anxiolytic and possesses antipsychotic properties.

To examine the ink between proneness to psychosis and the presence of delusions and the ratio of CBD to THC, Celia Morgan and H Valerie Curran, from University College London, studied 140 individuals from an ongoing longitudinal drug study.

Hair samples were analyzed using gas chromatography/mass spectrometry for the presence of cannabinoids, allowing the identification of 20 individuals with only THC in their hair, 27 with THC+CBD, and 85 with no cannabinoids. The eight individuals who screened positive for CBD only in their hair were excluded due to the small number.

In order to assess psychosis proneness, the team administered the short form of the Oxford Liverpool Inventory of Life Experiences (OLIFE) questionnaire, while Peter’s Delusion Inventory (PDI) was used to examine delusional thinking.

There were no significant differences between the THC and THC+CBD groups in terms of THC levels, and no differences between the three groups in terms of age or drug use other than cannabis. There were no significant differences in the subjective estimates of cannabis use between the THC and THC+CBD groups, aside from the number of days taken to smoke 3.5 g, at 10.2 days versus 5.0 days.

Individuals in the THC group had significantly higher scores on the OLIFE factor of unusual experiences, a marker for positive schizophrenia-like symptoms, than both the THC+CBD and controls groups, while THC+CBD individuals had significantly lower introvertive anhedonia scores than both controls and THC individuals.

Furthermore, THC individuals had significantly higher scores than controls on the PDI, at averages of 8.15 versus 5.48, with THC+CBD patients showing only a trend for greater scores, at an average of 7.22.

The team writes in the British Journal of Psychiatry: “This study is the first to demonstrate that hair analytic techniques can be used to define subsets of cannabis users. The implications of these findings are that people who smoke different strains of cannabis manifest different psychological symptoms.”

They add: “Moreover, this suggests that smoking strains of cannabis containing CBD in addition to THC may be protective against the psychotic-like symptoms induced by THC alone.”

Source : Apr 18, 2008 MedWire News Current Medicine Group

Long-term harmful effects of marijuana (MJ) include risk for heart attacks and strokes in addition to impaired learning and memory. The active chemical in MJ called delta-9-tetrahyrdocannabinol (THC) is believed to exert these effects by binding to cannabinoid (CB) receptors located on several cell types in various organs. Scientists have found CB receptors in many organs including the brain, heart, liver, kidney, and spleen.

In this study, researchers investigated if persistent heavy MJ use might be associated with changes in different blood proteins in order to check if the abnormalities in the identified proteins might be related to other side-effects of marijuana.

The study was conducted with 18 long term heavy MJ users and 24 non-drug using volunteers. People with major medical and psychiatric illnesses, hypertension, head injury, HIV positive, alcohol dependency and other drug usage, were excluded from the study. Blood proteins were measured in both control volunteers and MJ users using a new method (protein chip) that has the potential to identify several new target proteins. That approach showed that apolipoprotein C-III (apoC-III) showed significant increases in MJ abusers. ApoC-III belongs to a large family of proteins that interact with lipids and helps lipids to move into and out of cells. ApoC-III is involved in transport of triglycerides and delays the breakdown of triglycerides. Increases in apoC-III levels in the blood occur in parallel with increases in triglyceride levels.

Even though we still don’t understand how heavy MJ use might cause increases in apoC-III levels, this protein might be one of the reasons why some MJ users have increased risks of heart attack and strokes.

Source: Neuroscience Article Date: 13 May 2008

Murat Yu¨ cel, PhD, MAPS; Nadia Solowij, PhD; Colleen Respondek, BSc; Sarah Whittle, PhD; Alex Fornito, PhD;
Christos Pantelis, MD, MRCPsych, FRANZCP; Dan I. Lubman, MB ChB, PhD, FRANZCPContext:

Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human
brain.

Objective: To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor–rich regions of the brain, the hippocampus and the amygdala.

Design: Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging.
Setting: Participants were recruited from the general community and underwent imaging at a hospital research facility.
Participants: Fifteen carefully selected long-term (_10 years) and heavy (_5 joints daily) cannabis-using men (mean age, 39.8 years; mean duration of regular use, 19.7
years) with no history of polydrug abuse or neurologic/mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years).
Main Outcome Measures: Volumetric measures of the hippocampus and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured.
Results: Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P=.001), with a relatively (and significantly [P=.02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippocampal volume was inversely associated with
cumulative exposure to cannabis during the previous 10 years (P=.01) and subthreshold positive psychotic symptoms (P_.001). Positive symptom scores were also associated with cumulative exposure to cannabis (P=.048).
Although cannabis users performed significantly worse than controls on verbal learning (P_.001), this did not correlate with regional brain volumes in either group.
Conclusions: These results provide new evidence of exposure-related structural abnormalities in the hippocampus and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.
Arch Gen Psychiatry. 2008;65(6):694-701
THERE IS CONFLICTING evidence regarding the long-term effects of regular cannabis use. Although growing literature suggests that long-term cannabis use is associated
with a wide range of adverse health consequences,1-4 many people in the community,
as well as cannabis users themselves, believe that cannabis is relatively harmless and should be legally available.

With nearly 15 million Americans using cannabis in a given month, 3.4 million using cannabis daily for 12 months or more, and 2.1 million commencing use every year,5 there is a clear need to conduct robust investigations that elucidate the long-term sequelae of long-term cannabis
use.
The strongest evidence against the notion that cannabis is harmless comes from the animal literature6-9 in which longterm cannabinoid administration has been shown to induce neurotoxic changes in the hippocampus, including decreases in neuronal volume, neuronal and synaptic density, and dendritic length of CA3 pyramidal neurons. Although such work suggests
that exposure to cannabinoids may be neurotoxic in animals, much less is known about the neurobiologic consequences of long-term cannabis exposure in humans.
Only a handful of brain imaging studies have been conducted in human cannabis users, with inconsistent findings reported.
Early cannabis research using pneumoencephalography10 reported cerebral atrophy in a small sample (N=10) of cannabis users, but further studies using computed tomography11-13 did not detect any abnormalities, despite the potential confounds of polydrug use, comorbid neurologic/
psychiatric diagnoses, and a lack of appropriate comparison groups.
Author Affiliations: ORYGEN
Research Centre (Drs Yu¨ cel,Whittle, and Lubman) and Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health (Drs Yu¨ cel, Whittle, Fornito, and Pantelis), Melbourne, Australia; School of Psychology and Illawarra
Institute for Mental Health, University of Wollongong, Wollongong, Australia (Dr Solowij and
Ms Respondek); and Schizophrenia Research Institute, Sydney, Australia (Dr Solowij).
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©2008 American Medical Association. All rights reserved.
Downloaded from www.archgenpsychiatry.com , on June 3, 2008 recent structural magnetic resonance imaging (MRI) studies have also reported contradictory findings, ranging from
no global or regional changes in brain tissue volume or composition14-16 to gray and white matter density changes, either globally17 or in focal regions, most notably in the
hippocampal and parahippocampal areas.18,19 However, these previous studies used imaging techniques with relatively coarse spatial and anatomical resolution and typically focused on samples with multiple substance use or comorbid psychiatric disorders and on only moderate levels of cannabis use (ie, _2 joints per day). Indeed, despite strong evidence of neurotoxicity in the animal literature, 6-9 to our knowledge, no neuroimaging study has examined the neurobiologic sequelae of long-term heavy cannabis use while controlling for the important confounds of polydrug abuse and co-occurring psychiatric disorders.
In this study, we used high-resolution 3-T MRI to assess volumetric changes in 2 cannabinoid-rich regions of the brain (the hippocampus and the amygdala) known to be susceptible to the neurotoxic effects of cannabis exposure in a sample of long-term heavy users carefully
screened for polysubstance abuse and mental disorders.
Given the growing literature regarding an association between cannabis use and the development of psychosis20 and cognitive impairment,16,21 we also assessed for subthreshold
psychotic symptoms and verbal learning ability in this otherwise psychologically healthy sample.
METHODS
PARTICIPANTS
Male cannabis users with long histories of regular and heavycannabis use (n=15) and nonusing healthy male volunteers (n=16) matched on age, estimated premorbid intelligence (National
Adult Reading Test),22 years of education, and state and trait anxiety (Spielberger State-Trait Anxiety Inventory)23 were recruited from the general community via a variety of advertisements
(Table). Cannabis users had lower Global Assessment of Functioning scale scores and greater depressive symptoms (as measured using the Hamilton Depression Rating Scale)24 than the comparison group; however, there were no current or lifetime histories of diagnosable medical, neurologic, or psychiatric conditions as assessed using the Structured Clinical Interview
for DSM-IV Axis I Disorders, Patient Edition.25 All the control subjects also underwent a Structured Clinical Interview for DSM-IV Axis I Disorders, Non-Patient Edition.25 Subthreshold
psychotic symptoms were probed using the Scale for the Assessment of Positive Symptoms26 and the Scale for the Assessment of Negative Symptoms.27 Regarding alcohol use, the
groups did not differ in levels of current consumption, lifetime use, or history of abuse or dependence; and no participant drank more than 24 standard alcoholic drinks per week.
Significantly more cannabis users were also tobacco smokers (_2=22.9, P_.001) (Table). For all users, cannabis was the primary drug of abuse, with only limited experimental use of other
illicit drugs (generally _10 lifetime episodes).
PROCEDURE
Participants were assessed on 2 occasions, usually 1 week apart. In the first test session, participants completed demographic, clinical, and substance use history assessments. In the second test session, they completed the Rey Auditory Verbal Learning
Test (RAVLT) and underwent structural MRI.
Participants were asked to abstain from using substances for at least 12 hours before each test session, and cannabis users reported abstaining from cannabis for a mean of 21.3 hours before
the first test session (median, 14 hours; range, 10-72 hours) and a mean of 19.8 hours before the second test session (median, 17 hours; range, 12-48 hours). Urine samples were obtained
from users on 4 occasions and from controls on 2 occasions to corroborate self-reported abstinence. Specifically, for cannabis users, samples were obtained on the evening before
each test session and on the day of testing. For controls, samples
were collected only on the day of testing. Examination of these
samples demonstrated that all but 1 cannabis user had cannabinoid
metabolites (11-nor-_9-tetrahydrocannabinol-9-
carboxylic acid creatinine normalized) detected in urine samples
from the first test session, and levels were generally high
(evening: median, 467 ng/mg [range, 0-2320 ng/mg]; day of
testing: median, 447 ng/mg [range, 0-11 293 ng/mg]). From the
second test session, 2 users returned a 0 reading; otherwise,
cannabinoid metabolite levels were again high (evening: median,
456 ng/mg [range, 0-3511 ng/mg]; day of testing: median,
389 ng/mg [range, 0-4470 ng/mg]). The levels of urinary
cannabinoid metabolites generally corroborate the selfreported
patterns of heavy cannabis use in the sample. All but
2 control subjects returned a 0 reading for cannabinoid metabolites
across both test sessions. The 2 controls with positive
urine samples reported only minimal and very occasional
exposure to cannabis. The median level of cannabinoid metabolites
in controls at the first test session was 0 ng/mg (range,
0-184 ng/mg) and at the second test session was 0 ng/mg (range,
0-180 ng/mg).
STRUCTURAL MRI
The MRI data were obtained using a 3-T scanner (Intera; Phillips
Medical Systems NA, Bothell, Washington) at the Symbion
Clinical Research Imaging Centre, Prince of Wales Medical
Research Institute, Sydney. A 3-dimensional volumetric
spoiled gradient–recalled echo sequence generated 180 contiguous
coronal slices. The imaging parameters were as follows:
echo time, 2.9 milliseconds; repetition time, 6.4 milliseconds;
flip angle, 8°; matrix size, 256_256; and 1-mm3 voxels.
Hippocampal, amygdala, whole brain, and intracranial volumes
were measured using established reliable protocols28-31
and were delineated by a trained rater (S.W.) masked to group
information. Specifically, the hippocampal boundaries were as
follows: posterior, the slice with the greatest length of continuous
fornix; medial, the open end of the hippocampal fissure
posteriorly, the uncal fissure in the hippocampal body, and the
medial aspect of the ambient gyrus anteriorly; lateral, the temporal
horn of the lateral ventricle; inferior, the white matter inferior
to the hippocampus; superior, the superior border of the
hippocampus; and anterior, the alveus was used to differentiate
the hippocampal head from the amygdala. The anterior border
was the most difficult to identify consistently and was aided
by moving between slices before and after the index slice. The
amygdala boundaries were as follows: posterior, the appearance
of amygdala gray matter above the temporal horn; superolateral,
the thin strip of white matter that separates the amygdala
from the claustrum and the tail of the caudate; medial, the
angular bundle, which separates the amygdala from the entorhinal
cortex; superomedial, the semilunar gyrus; inferior, the
hippocampus; inferolateral, the temporal lobe white matter and
the extension of the temporal horn; and anterior, the slice anterior
to the appearance of the optic chiasm. Whole brain volumes
were estimated using the Brain Extraction Tool method32
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to separate brain from nonbrain tissue. After brain/nonbrain
segmentation, each voxel was classified into gray matter, white
matter, or cerebrospinal fluid using FAST Model statistical software.
33 Only gray and white matter were used in the estimate
of whole brain volumes. The intracranial cavity was delineated
from a sagittal reformat of the original 3-dimensional data
set. The major anatomical boundary was the dura mater below
the inner table, which was generally visible as a white line.
Where the dura mater was not visible, the cerebral contour was
outlined. Other landmarks included the undersurfaces of the
frontal lobes, the dorsum sellae, the clivus, and the posterior
arch of the craniovertebral junction.
Interrater and intrarater reliabilities were assessed by means
of the intraclass correlation coefficient (ICC) (absolute agreement)
using 15 brain images from a separate MRI database established
specifically for this purpose and that has previously
been delineated by another expert rater. For the hippocampus,
interrater ICC reliabilities were 0.92 (right) and 0.91 (left)
and intrarater ICC reliabilities were 0.98 (right) and 0.95 (left).
For the amygdala, interrater ICC reliabilities were 0.85 (right)
and 0.88 (left) and intrarater ICC reliabilities were 0.93 (right)
and 0.97 (left). Once reliability was established, the rater (S.W.)
delineated the regions of interest for the images acquired from
the present study.
STATISTICAL ANALYSES
Whole brain volume, age, educational level, and estimated IQ
were not significantly different between the 2 groups and were,
therefore, not used as covariates (Table). Regional gray matter
volumes for the hippocampus and amygdala were corrected for
the effect of the intracranial cavity using a previously described
formula34 and were analyzed using analyses of variance,
with hemisphere (left or right) and region (hippocampus
and amygdala) as within-subject factors and group as the
between-subject factor. Main effects and interactions were evalu-
Table. Demographic, Clinical, Drug Use, and MRI Volumetric Measures
Measure
Long-term Cannabis Users
(n=15)
Nonusing Control Subjects
(n=16) P Valuea
Age, mean (SD), y 39.8 (8.9) 36.4 (9.8) .31
IQ, mean (SD) 109.2 (6.3) 113.9 (8.1) .09
RAVLT score, mean (SD)
Sum of 5 learning trials 43.8 (8.8) 57.4 (10.1) _.001
20-min delay 8.9 (4.1) 12.3 (3.7) .009b
Educational level, mean (SD), y 13.4 (3.2) 14.8 (3.7) .28
GAF scale score, mean (SD) 72.0 (11.2) 80.8 (9.4) .02
HAM-D score, mean (SD) 5.87 (3.2) 2.56 (1.9) _.001b
STAI, mean (SD)
State anxiety 34.3 (9.8) 32.9 (9.4) .67
Trait anxiety 39.3 (9.7) 39.0 (8.2) .92
SAPS score, mean (SD) 8.1 (7.9) 0.6 (1.2) _.001b
SANS score, mean (SD) 11.7 (8.5) 1.4 (1.4) _.001b
Cannabis use
Duration of regular use, mean (SD) [range], yc 19.7 (7.3) [10-32] NA NA
Age started regular use, mean (SD) [range], yc 20.1 (6.9) [12-34] NA NA
Current use, mean (SD), d/mod 28 (4.6) NA NA
Current use, mean (SD), cones/mod,e 636 (565) NA NA
Cumulative exposure, past 10 y, mean (SD)f 77 816 (66 542) NA NA
Cumulative exposure, lifetime, mean (SD)f 186 184 (210 022) 12.7 (12.2) _.001
Estimated episodes of use, median (range) 62 000 (4600-288 000) 11 (0-30) _.001
Alcohol use, mean (SD), standard drinks/wk 9.6 (6.1) 6.8 (5.0) .19
Tobacco use, mean (SD), cigarettes/d 16.5 (8.9) 7.5 (9.2) .20
Brain volumes, mean (SD), mm3
Intracranial cavity 1 546 237 (94 018) 1 607 590 (136 386) .14
Whole brain 1 310 780 (90 778) 1 374 123 (105 673) .09
Hippocampus .002g
Left hemisphere 2849 (270) 3240 (423)
Right hemisphere 2949 (244) 3348 (400)
Amygdala .01g
Left hemisphere 1766 (98) 1878 (190)
Right hemisphere 1601 (143) 1744 (158)
Abbreviations: GAF, Global Assessment of Functioning; HAM-D, Hamilton Depression Rating Scale; MRI, magnetic resonance imaging; NA, not applicable;
RAVLT, Rey Auditory Verbal Learning Test; SAPS, Scale for the Assessment of Positive Symptoms; SANS, Scale for the Assessment of Negative Symptoms;
STAI, State-Trait Anxiety Inventory.
aTwo-tailed t test unless otherwise indicated.
bMann-Whitney test.
cRegular use was defined as at least twice a month.
dCannabis users had used at this level for most of their drug-using history.
eA cone is the small funnel into which cannabis is packed to consume through a water pipe in a single inhalation. Without the loss of sidestream smoke, the
quantity of tetrahydrocannabinol delivered by this method is estimated as equating 3 cones to 1 cigarette-sized joint. Thus, the cannabis users in this study
smoked the equivalent of 212 joints per month, or approximately 7 joints per day.
fExpressed as cones for users and as episodes for controls. Estimates of lifetime exposure beyond 10 years in these very long-term users became skewed and
unreliable; hence, the 10-year estimate was used in correlational analyses.
gRegion_group analysis of variance.
(REPRINTED) ARCH GEN PSYCHIATRY/VOL 65 (NO. 6), JUNE 2008 WWW.ARCHGENPSYCHIATRY.COM
696
©2008 American Medical Association. All rights reserved.
Downloaded from www.archgenpsychiatry.com , on June 3, 2008
ated using Greenhouse-Geisser–corrected degrees of freedom,
with _=.05. Effect sizes, expressed as Cohen d, are also reported
for pairwise contrasts. Only effects involving group (cannabis
users vs nonusers) and associations with cannabis use
parameters are reported because this was the primary focus of
the present study. Group comparisons of performance on the
RAVLT and measures of subthreshold psychotic symptoms
(using the Scale for the Assessment of Positive Symptoms and
the Scale for the Assessment of Negative Symptoms) were conducted
using independent-samples t tests or Mann-Whitney tests
for nonnormally distributed data. Pearson product moment correlational
analyses were conducted to examine the behavioral
(ie, symptom and cognitive) relevance of any identified group
differences in regional brain volumes and the association
between these brain changes and parameters of cannabis use.
These analyses were necessarily exploratory given the limited
sample size.
RESULTS
GROUP CONTRASTS
In the analysis of regional gray matter volumes, there
was a significant main effect of group (F1,29=12.98,
P=.001) and a region_group interaction (F1,29=6.25,
P=.02). This result and the post hoc pairwise analyses
demonstrated reduced hippocampal volumes in cannabis
users (F1,29=11.14, P=.002 corrected; a reduction of
12.1% in the left and 11.9% in the right hippocampus
relative to controls), with a very large effect size (Cohen
d: left hippocampus, 1.17; and right hippocampus,
1.27) (Figure 1). Cannabis users also had smaller
amygdala volumes (F1,29=7.31, P=.01 corrected; a
reduction of 6.0% in the left amygdala and 8.2% in the
right amygdala relative to controls), with large effect
sizes (Cohen d: left amygdala, 0.80; and right amygdala,
0.99). The region _ group interaction reflects that the
overall reduction in hippocampal volume was relatively
(and significantly) greater than the reduction in amygdala
volume (12.0% in the hippocampus vs 7.1% in the
amygdala). In the analysis of subthreshold psychotic
symptoms, cannabis users reported significantly higher
positive symptoms (Scale for the Assessment of Positive
Symptoms; z=−3.57, P_.001) and negative symptoms
(Scale for the Assessment of Negative Symptoms;
z=−3.66, P_.001) than nonusing controls. Regarding
verbal learning, cannabis users displayed significantly
poorer performance than controls on the RAVLT measures
(sum of words recalled across the 5 learning trials:
z=−3.97, P_.001; and free recall after a 20-minute
delay: z=−2.61, P=.009).
CORRELATIONAL ANALYSES
There was a significant inverse association between left
hippocampal volume and cumulative cannabis exposure
during the previous 10 years (r=−0.62, P=.01; accounting
for 38% of the variance in left hippocampal volume)
(Figure 2A). When 1 participant with relatively
higher cumulative cannabis exposure and small hippocampal
volume was excluded, 22% of the variance was
still accounted for despite falling short of significance in
the reduced sample (r=−0.47, P=.09). There was also an
association between left hippocampal volume and positive
symptoms (r=−0.77, P_.001) (Figure 2B) and between
positive symptoms and cumulative cannabis exposure
(r=0.52, P=.048) (Figure 2C). The associations
between left hippocampal volume and cumulative cannabis
exposure and between left hippocampal volume and
positive symptoms remained after controlling for the effects
of global functioning (Global Assessment of Functioning
scale) and depressive symptoms (Hamilton Depression
Rating Scale). No other associations were found
between other brain volumetric measures, cannabis use,
and psychotic symptoms, and they did not vary as a function
of alcohol or tobacco use. Measures of RAVLT performance
did not correlate with hippocampal or amygdala
volumes in either controls or cannabis users.
COMMENT
To our knowledge, this is the first human study of longterm
heavy cannabis users to demonstrate marked
exposure-related hippocampal volume reductions.
These findings corroborate previous animal research,6-9
suggesting that long-term heavy cannabis use is associated
with significant and localized hippocampal volume
reductions that relate to increasing cumulative cannabis
exposure. In addition, the present findings are consis-
tent with the view that cannabis use increases the risk
of psychotic symptoms and informs the debate concerning
the potential long-term hazardous effects of cannabis
in this regard. The bilateral reduction in amygdala
volume is a novel but not unexpected finding given the
dense concentration of cannabinoid receptors in this
region.35
Although these findings are consistent with those of
a previous study,18 it is difficult to directly compare these
results with those of other human studies given that past
work used MRI with lower magnetic field strength and
spatial resolution and did not conduct region-of-interest–
based analyses (eg, performed whole-brain voxel-based
analyses18). Tzilos et al14 conducted the only other study,
to our knowledge, that investigated cannabis users with
a relatively long history of use (specifically, an average
duration of use of 22.6 years, or 18.9 years of daily use)
and their study is, therefore, most comparable with the
present study. Although they found no effects of longterm
cannabis use on hippocampal volume, the authors
acquired their images at a lower field strength and with
a coarser spatial resolution (1.5 T with 3-mm-thick slices
vs 3 T with 1-mm-thick slices in the present study), an
important consideration given the size of the brain structures
investigated. Moreover, their region of interest was
less specific to the hippocampus relative to the present
measure because they also included the parahippocampal
gyrus. Furthermore, there was a relatively large age
discrepancy between their users and controls (38.1 vs 29.5
years), and the minimum duration of exposure to cannabis
was considerably lower in their sample (as little as
1 year of cannabis exposure), but, overall, their sample
reported an average of 20 100 lifetime episodes of use.
In contrast, the minimum duration of exposure to cannabis
in the present sample was 10 years, with an average
of 62 000 episodes of use. Thus, despite a similar mean
duration of use, the present sample used more than 3 times
as much cannabis, which may explain the finding of a
dose-response relationship between hippocampal volume
and cumulative cannabis use. Further highresolution
MRI work is necessary to characterize precisely
the dosage of cannabis required for significant brain
changes to occur.
The pattern of use in the present sample is consistent
with heavy cannabis use patterns that have previously
been reported in other Australian studies. For example,
Copeland and colleagues36 reported median daily intake
of 8 cones (the small funnel into which cannabis is packed
to consume through a water pipe in a single inhalation)
in an Australian sample of cannabis users seeking treatment
for cannabis dependence, ranging up to 125 cones
per day in the heaviest user, with 11% reporting cannabis
smoking throughout the day. The heaviest user herein
reported smoking 80 cones per day (approximately 25
joints smoked throughout the day). This pattern of cannabis
use is not dissimilar to the heaviest cannabis users
from other studies of non–treatment-seeking samples of
Australian cannabis users.37,38
Despite the large magnitude of effects observed, it remains
unclear whether these volumetric reductions
reflect neuronal or glial loss, a change in cell size, or a
reduction in synaptic density (eg, dendritic arborization),
all of which have been reported in rodent studies.
6-9 For example, Scallet and colleagues9 found striking
tetrahydrocannabinol-induced residual decreases in
the mean volume of hippocampal neurons and their nuclei
and a 44% reduction in the number of synapses up
to 7 months after the last exposure to tetrahydrocannabinol.
Moreover, Landfield and colleagues7 administered
tetrahydrocannabinol 5 times a week for 8 months
(approximately 30% of the rat lifespan, and comparable
in frequency and duration to the present sample) and
found significant tetrahydrocannabinol-induced decreases
in neuronal density in the hippocampus. Such
findings may help explain the mechanisms underlying
gross hippocampal and amygdala volume loss seen in this
sample of long-term heavy cannabis users.
Left Hippocampal Volume, mm3
In the present study, hippocampal volume in the cannabis-
using group was inversely correlated with cumulative
exposure to the drug in the left, but not right, hemisphere.
Previous functional imaging studies16,39 have found
reduced left hippocampal activation during cognitive performance
in cannabis users, and there is evidence to suggest
that hippocampal abnormalities in psychiatric disorders
such as schizophrenia are more prominent in the
left hemisphere.40 These findings converge to suggest that
the left hippocampus may be particularly vulnerable to
the effects of cannabis exposure and may be more closely
related to the emergence of psychotic symptoms. In this
context, it is interesting that we found a significant inverse
correlation between left hippocampal volume and
positive symptoms. Cannabis use was also positively correlated
with positive symptoms, suggesting that there are
complex associations among exposure to cannabis, hippocampal
volume reductions, and psychotic symptoms.
Given these relationships, it is possible that the exposurerelated
hippocampal reduction may reflect heavy cannabis
use in response to preexisting or developing psychotic
symptoms. However, there is limited empirical
support for long-term self-medication of subthreshold psychotic
symptoms with cannabis and stronger support for
the induction of psychotic symptoms subsequent to cannabis
exposure.20 As such, it seems more likely that prolonged
heavy use of cannabis induced subthreshold psychotic
symptoms and that both of these factors are
associated with hippocampal volume loss. These symptoms
were subthreshold because these cannabis-using participants
were carefully screened for current and past history
of mental disorders. Furthermore, the fact that the
mean age of the present cannabis-using sample was nearly
40 years suggests that these symptoms are unlikely to reflect
a prodrome. One speculation is that the present participants
were less genetically vulnerable to developing
a psychotic disorder subsequent to cannabis use,41,42 allowing
them to smoke heavily for many years. Future longitudinal
work assessing the emergence of hippocampal
reductions and psychotic symptoms with continued exposure
to cannabis, and how these are related to polymorphic
variations in susceptibility genes for psychotic
disorders, will prove useful in better characterizing these
relationships.
Given that cannabis users had significantly greater depressive
symptom scores than controls and that there is
an association between depression and hippocampal volume
reduction,43 it could also be argued that depressive
symptoms may be another mediating factor in the relationship
between cannabis use and hippocampal volume
reduction. However, there are a variety of important
considerations that make this unlikely. First, there
was no significant association between hippocampal volumes
and depressive symptom scores. Second, the relationship
between left hippocampal volume and quantity
of cannabis used was maintained after statistically
controlling for depressive symptoms. Finally, the overwhelming
evidence suggests that hippocampal reductions
in major depressive disorder tend to occur in the
more persistent forms of the disorder (eg, multiple episodes,
repeated relapses, or long illness duration).43,44 This
was not the case in the present sample of cannabis users,
who scored less than 6.0 on the Hamilton Depression
Rating Scale, had never been diagnosed as having
major depression, and did not seek treatment for any depressive
disorder.
Cannabis users showed poorer performance on measures
of verbal learning, consistent with previous findings.
Although some functional imaging studies have
found reduced left hippocampal blood flow and activation
during verbal (and visual) learning tasks in cannabis
users, we found no correlation between RAVLT
performance measures and hippocampal volume in either
controls or cannabis users. It is likely that anatomical volume
is a less sensitive measure than brain activation for
identifying correlations with behavioral performance. This
is a particularly pertinent consideration given that the
performance measures on the RAVLT are likely to reflect
the operation of numerous cognitive processes not
necessarily related to hippocampal function. Future work
using experimental tasks designed to more specifically
probe memory functions mediated by the hippocampus
may be useful in this regard.
The bilateral reduction in amygdala volume is a novel
but not unexpected finding given the dense concentration
of cannabinoid receptors in this region.35 There were
no cognitive, psychotic, or depressive symptom associations
with reduced volume in the amygdala. However,
this region has been significantly implicated in cannabinoid-
associated emotional and reward-related learning
and memory processes.47,48 Given that these aspects of
learning have not been examined in human cannabis users,
they would seem to serve as a potentially informative
avenue forward to help elucidate the functional relevance
of such volumetric reduction in the amygdala.
The relationship between long-term cannabis use and
brain abnormalities is complex. Although a limitation of
this study may be the residual effects of cannabis in light
of the fact that the cannabis users in this study were required
to be cannabis free for only 12 to 24 hours before
MRI, such issues are likely to be more pertinent for studies
examining more dynamic aspects of brain functioning
(eg, activations and cognition).49 The present structural
findings are unlikely to relate to the recent effects
of cannabis use because we are unaware of any evidence
that suggests that the hippocampus and amygdala can
change in volume by 6% to 12% in short periods. However,
although we maintain that the present results reflect
brain changes associated with long-term heavy cannabis
use rather than the consequences of recent exposure,
further longitudinal work is required to assess whether
such changes are reversible across more protracted periods
of abstinence.
Another limitation of this study is the relatively small
sample size, although the sample was exceptionally unique
in that participants were very long-term and heavy cannabis
users (mean of 5-7 joints per day for _10 years)
without polydrug use or co-occurring neurologic or diagnosable
mental disorders. As such, we conducted the
first, to our knowledge, “pure” examination of the effects
of heavy and protracted exposure to cannabis in humans.
The large effect sizes of the main findings suggest
that these results are robust and reproducible. These findings
are further strengthened by the observed dose-
response relationships between hippocampal volume reductions
and cumulative cannabis use.
There is ongoing controversy concerning the longterm
effects of cannabis on the brain. These findings
challenge the widespread perception of cannabis as having
limited or no neuroanatomical sequelae. Although
modest use may not lead to significant neurotoxic effects,
these results suggest that heavy daily use might indeed
be toxic to human brain tissue. Further prospective,
longitudinal research is required to determine the
degree and mechanisms of long-term cannabis-related
harm and the time course of neuronal recovery after abstinence.
Correspondence: MuratYu¨ cel, PhD,MAPS,ORYGENResearch
Centre, 35 Poplar Rd (Locked Bag 10), Melbourne,

Source: Arch.Gen.Psychiatry. Vol.65 June 2008

WASHINGTON (CNN) — The earlier a young person uses marijuanathe greater the risk for mental health problems later in life, the director of National Drug Control Policy said Tuesday, basing his conclusion on a survey of medical research.

“We’re trying to get out the word that the last 10 years of research have helped to alert us to the use of marijuana in particular is a very dangerous risk for the mental health of our young people,” John Walters said at a news conference.
He said the conclusion runs against popular culture that often considers marijuana a low-risk recreational drug.
Walters cited a government study that found a base rate of mental illness at between 8 percent and 9 percent among Americans 18 and older. For those who use marijuana, he said, “That increases to 12-and-a-half percent.”
And, he added, “For those who have used marijuana prior to age 12, the rate of mental illness jumps to 21 percent.”
The rate was half that, or 10.5 percent, for adults who first used marijuana at age 18 or older.
Those were the findings of the National Survey on Drug Use and Health, an annual survey sponsored by the Substance Abuse and Mental Health Services Administration.
Walters did not directly address the possibility of confusing cause and effect — that is, that people with mental problems might be more inclined to use drugs.
One study he cited was published last year in the Archives of General Psychiatry. It involved 600 pairs of same-sex twins, one of whom was dependent on marijuana and one of whom was not. The twin who was dependent was almost three times as likely to think about suicide and attempt suicide than his brother or sister, the study found.
Neil McKeganey, who heads the University of Glasgow’s Center for Drug Misuse Research, was at the press conference in support of Walters.
“It is leading us to look again at this so-called recreational drug,” he said. “Kids who start to use marijuana at a young age are much more likely to suffer serious, long-term mental health problems.”
The parents of a teenager who committed suicide last year were also at the news conference, and they linked their son’s death to his marijuana use.
Tanya Skaggs, of Colorado Springs, Colorado, said, “He had a severe lack of judgment that was because of the marijuana, this destructive behavior was continuing,” in the months leading up to his death.
The parents were unable to break his marijuana use, Skaggs said, despite counseling, searching his room for pot and random drug tests.
“We just never thought that something like this could happen to us. But it does, and it did,” she said. “We wish we could have helped.”
Agenda ‘detrimental to your children’
Walters downplayed whether the medical use of marijuana undercuts the impact of warnings to young people against pot use.
The question was tied to a decision by Canada last month to approve the prescription drug Sativex, an oral spray that contains the active ingredient of marijuana, to treat the symptoms of multiple sclerosis.
He responded, “We believe that there’s a clear distinction” between validated medical benefits and what he said could be “a bunch of ads where people testify that their mother, dying, smoked a joint and was saved, and that means marijuana is medicine.”
“Your children are being educated,” he said of such advertising. “But they’re being told lies. And they’re being told things that are designed to push a particular agenda which is detrimental to your children, and detrimental to the country.”
Group calls for national discussion
Meanwhile, a Washington-based nonprofit group released a report recommending changes in the way authorities handle drug offenses, citing a “disproportionate” focus on “low-level marijuana users.”
“The ‘war on drugs’ in the 1990s was, essentially, a ‘war on marijuana,’” said the report by the Sentencing Project, which was founded in 1986 to promote alternative sentencing programs.
A national analysis covering 1990 to 2002 found that, of a 450,000 rise in drug arrests during that period, 82 percent of the increase was for marijuana, and 79 percent was for marijuana possession alone.
Marijuana arrests now make up 45 percent of the nation’s 1.5 million drug arrests annually, the report said, and an estimated $4 billion is spent each year on marijuana offenders.
“The growth in marijuana arrests over the 1990s has not led to a decrease in use or availability, nor an increase in cost,” the group said. “Meanwhile, billions are being spent nationally.”
The report calls for “a national discussion regarding the zealous prosecution of marijuana use and its consequences for allocation of criminal justice resources and public safety.”
“Law enforcement has focused disproportionately on low-level possession charges as a result of the nation’s lack of a thoughtful strategy,” it said.
Source:www.WordPress.com June 2008

• Compared to 12- and 13-year olds who have frequent family dinners, those who have infrequent family dinners are six times likelier to use marijuana, four times likelier to use tobacco, and three times likelier to use alcohol.
• Compared to teens who attend religious services at least weekly, those who never attend services are more than twice as likely to try cigarettes, and twice as likely to try marijuana and alcohol.
• Compared to teens who have frequent family dinners, those who have infrequent family dinners are one and a half times likelier to report getting grades of C or lower in school. 

Source: www.casacolumbia.org   Sept.2009

Does the use of cannabis predicate the use of other illegal drugs ? The study quoted below shows that the risk of someone using other illegal drugs is 90 times higher for 16 – 17 year olds who used cannabis at least weekly. It is essential that parents who believe their child is involved in cannabis use tackle this situation and do not turn a blind eye. Read the story (at the end of this article) by Ginger Katz….

There are two main difficulties to clarifying that marijuana is a gateway substance, but even so there is some good evidence.

The first difficulty is varying definitions of “gateway”. If one defines it as to how rare is the case of someone using other illicit drugs without ever using mj before that, there can be no dispute that a gateway effect or phenomenon exists. If one defines it as an absolute, as in, anyone who uses marijuana will use other illicit drugs, then it is clearly not true, since most who use marijuana don’t progress to other drugs. I think the meaning you’re using here, John, (correct me if not) is whether there are aspects to marijuana use that directly increase the odds that other drugs will be used, rather than just situational or reverse-correlation explanations for why other illicit drug use is so rarely found without prior marijuana use.

The second difficulty is that causality is complex and multi-faceted: even if direct causality is involved, some of the other trends that cause people to question causality (e.g. that early marijuana use is a sign of troubled development, which itself can account for increased likelihood of later use of other substances) are also true in many cases.

All the above not withstanding, one of the best studies I have seen to document the direct role of marijuana in later illicit drug use is one done in New Zealand, reported in the article “The developmental antecedents of illicit drug use: Evidence from a 25-year longitudinal study”, by David M. Fergusson, Joseph M. Boden, and L. John Horwood. The journal citation is Drug and Alcohol Dependence 96 (2008) 165-177. They looked at many potential risk factors and found predictive associations from childhood based on parental use, on the youth’s exposure to sexual abuse in childhood, on gender (male was at more risk), on novelty-seeking, and on childhood conduct disorders. They then moved into additional analysis where, “the statistical model was extended and refined by the inclusion of a series of time-dynamic covariates and controls for reverse causality.” Sifting through associations that included cannabis use, association with substance-using peers, alcohol use, cigarette smoking, and novelty-seeking, they found that except for some persistence in the novelty seeking factor, “accounting for substance use and peer factors reduced the associations
between the childhood fixed factors and illicit drug use and abuse/dependence to statistical non-significance.”

They then focus on cannabis use: “of the time-dynamic factors included in the final models, cannabis use had the largest and most complex associations. In particular, the study findings suggested an interactive relationship between age and the use of cannabis in the development of other forms of illicit drug involvement. In this relationship the effects of cannabis use were the strongest at younger ages, and declined progressively with age. Furthermore, the size of association depended on the extent of use of cannabis. The net results of these findings is that risks of illicit drug use were over 90 times higher amongst 16-17-year olds who used cannabis at least weekly when compared to non-users of cannabis. By the age of 25, these risks had reduced to nearly eight times higher. In addition, these associations were controlled for reverse causality by including a lagged measure of other illicit drug use in the model. These findings are consistent with the view that exposure to cannabis use increases risks of other forms of illicit drug use and abuse/dependence, even when allowance is taken of childhood factors and possible reverse causal associations.”

The authors note that the finding that “much of the association between childhood factors and other forms of illicit drug use and abuse/dependence was mediated via cannabis use” is important “in the light of claims that the association between cannabis and other forms of illicit drug use can be explained by common childhood factors …” “The present study suggests quite the opposite conclusion in which cannabis use mediated the effects of childhood factors on later illicit drug abuse.
Source: Alan Markwood of www.chestnut.org reporting to DrugWatch International. Oct.2009

There are two main difficulties to clarifying that marijuana is a gateway substance, but even so there is some good evidence.

The first difficulty is varying definitions of “gateway”. If one defines it as to how rare is the case of someone using other illicit drugs without ever using mj before that, there can be no dispute that a gateway effect or phenomenon exists. If one defines it as an absolute, as in, anyone who uses marijuana will use other illicit drugs, then it is clearly not true, since most who use marijuana don’t progress to other drugs. I think the meaning you’re using here, John, (correct me if not) is whether there are aspects to marijuana use that directly increase the odds that other drugs will be used, rather than just situational or reverse-correlation explanations for why other illicit drug use is so rarely found without prior marijuana use.

The second difficulty is that causality is complex and multi-faceted: even if direct causality is involved, some of the other trends that cause people to question causality (e.g. that early marijuana use is a sign of troubled development, which itself can account for increased likelihood of later use of other substances) are also true in many cases.

All the above not withstanding, one of the best studies I have seen to document the direct role of marijuana in later illicit drug use is one done in New Zealand, reported in the article “The developmental antecedents of illicit drug use: Evidence from a 25-year longitudinal study”, by David M. Fergusson, Joseph M. Boden, and L. John Horwood. The journal citation is Drug and Alcohol Dependence 96 (2008) 165-177. They looked at many potential risk factors and found predictive associations from childhood based on parental use, on the youth’s exposure to sexual abuse in childhood, on gender (male was at more risk), on novelty-seeking, and on childhood conduct disorders. They then moved into additional analysis where, “the statistical model was extended and refined by the inclusion of a series of time-dynamic covariates and controls for reverse causality.” Sifting through associations that included cannabis use, association with substance-using peers, alcohol use, cigarette smoking, and novelty-seeking, they found that except for some persistence in the novelty seeking factor, “accounting for substance use and peer factors reduced the associations
between the childhood fixed factors and illicit drug use and abuse/dependence to statistical non-significance.”

They then focus on cannabis use: “of the time-dynamic factors included in the final models, cannabis use had the largest and most complex associations. In particular, the study findings suggested an interactive relationship between age and the use of cannabis in the development of other forms of illicit drug involvement. In this relationship the effects of cannabis use were the strongest at younger ages, and declined progressively with age. Furthermore, the size of association depended on the extent of use of cannabis. The net results of these findings is that risks of illicit drug use were over 90 times higher amongst 16-17-year olds who used cannabis at least weekly when compared to non-users of cannabis. By the age of 25, these risks had reduced to nearly eight times higher. In addition, these associations were controlled for reverse causality by including a lagged measure of other illicit drug use in the model. These findings are consistent with the view that exposure to cannabis use increases risks of other forms of illicit drug use and abuse/dependence, even when allowance is taken of childhood factors and possible reverse causal associations.”

The authors note that the finding that “much of the association between childhood factors and other forms of illicit drug use and abuse/dependence was mediated via cannabis use” is important “in the light of claims that the association between cannabis and other forms of illicit drug use can be explained by common childhood factors …” “The present study suggests quite the opposite conclusion in which cannabis use mediated the effects of childhood factors on later illicit drug abuse.
Source: Alan Markwood of www.chestnut.org reporting to DrugWatch International. Oct.2009

In this new study, researchers compared marijuana smoke to tobacco smoke, using smoking machines to simulate the smoking habits of users. The scientists found that ammonia levels were 20 times higher in the marijuana smoke than in the tobacco smoke, while hydrogen cyanide, nitric oxide and certain aromatic amines occurred at levels 3-5 times higher in the marijuana smoke, they say. The finding is “important information for public health and communication of the risk related to exposure to such materials,” say the researchers.

Source: American Chemical Society (2007, December 18). Marijuana Smoke Contains Higher Levels Of Certain Toxins Than Tobacco Smoke

Driving under the influence of cannabis almost doubles the risk of a fatal road crash, finds a study published online by the British Medical Journal. However its share in fatal crashes is significantly lower than those involving alcohol.The study took place in France and involved 10,748 drivers who were involved in fatal crashes from October 2001 to September 2003. All drivers underwent compulsory tests for drugs and alcohol.

A total of 681 drivers tested positive for cannabis (7%) and 2096 for alcohol (21.4%), including 285 for both (2.9%). Men were more often involved in crashes than women, and were also more often positive for both cannabis and alcohol, as were the youngest drivers, and users of mopeds and motorcycles.

The risk of being responsible for a fatal crash increased as the blood concentration of cannabis increased (known as a dose effect). The odds increased from 1.9 at a concentration of 0-1 ng/ml to 3.1 at or above 5 ng/ml. These effects were adjusted for alcohol and remained significant when also adjusted for other factors.

These results give credence to a causal relationship between cannabis and crashes, say the authors.

Samples show that the prevalence of cannabis (2.9%) within the driving population is similar to that for alcohol (2.7%) at or above 0.5 g/l, they add. However, in France, its share in fatal crashes is significantly lower than that associated with alcohol (2.5% compared with 29% for alcohol).

Source: BMJ-British Medical Journal (2005, December 5). Cannabis Almost Doubles Risk Of Fatal Crashes. ScienceDaily. Retrieved October 5, 2009, from http://www.sciencedaily.com­ /releases/2005/12/051205115540.htm

Conflicting evidence exists regarding the long-term effects of cannabis use, according to background information in the article. “Although growing literature suggests that long-term cannabis use is associated with a wide range of adverse health consequences, many people in the community, as well as cannabis users themselves, believe that cannabis is relatively harmless and should be legally available,” the authors write. “With nearly 15 million Americans using cannabis in a given month, 3.4 million using cannabis daily for 12 months or more and 2.1 million commencing use every year, there is a clear need to conduct robust investigations that elucidate the long-term sequelae of long-term cannabis use.”

Murat Yücel, Ph.D., M.A.P.S., of ORYGEN Research Centre and the Melbourne Neuropsychiatry Centre at the University of Melbourne, Australia, and colleagues from the University of Wollongong performed high-resolution structural magnetic resonance imaging on 15 men (average age 39.8 years) who smoked more than five joints daily for more than 10 years. Their results were then compared with images from 16 individuals (average age 36.4) who were not cannabis users. All participants also took a verbal memory test and were assessed for subthreshold (below the standard of disease diagnosis) symptoms of psychotic disorders, which include schizophrenia and mania.

The hippocampus, thought to regulate emotion and memory, and the amygdala, involved with fear and aggression, tended to be smaller in cannabis users than in controls (volume was reduced by an average of 12 percent in the hippocampus and 7.1 percent in the amygdala). Cannabis use also was associated with sub-threshold symptoms of psychotic disorders. “Although cannabis users performed significantly worse than controls on verbal learning, this did not correlate with regional brain volumes in either group,” the authors write.

“There is ongoing controversy concerning the long-term effects of cannabis on the brain,” the authors write. “These findings challenge the widespread perception of cannabis as having limited or no neuroanatomical sequelae. Although modest use may not lead to significant neurotoxic effects, these results suggest that heavy daily use might indeed be toxic to human brain tissue. Further prospective, longitudinal research is required to determine the degree and mechanisms of long-term cannabis-related harm and the time course of neuronal recovery after abstinence.”

Source: Arch Gen Psychiatry, 2008;65(6):694-701

In a finding that challenges the increasingly popular belief that smoking marijuana is less harmful to health than smoking tobacco, researchers in Canada are reporting that smoking marijuana, like smoking tobacco, has toxic effects on cells.Rebecca Maertens and colleagues note that people often view marijuana as a “natural” product and less harmful than tobacco. As public attitudes toward marijuana change and legal restrictions ease in some countries, use of marijuana is increasing.

Scientists know that marijuana smoke has adverse effects on the lungs. However, there is little knowledge about marijuana’s potential to cause lung cancer due to the difficulty in identifying and studying people who have smoked only marijuana.

The new study begins to address that question by comparing marijuana smoke vs. tobacco smoke in terms of toxicity to cells and to DNA. Scientists exposed cultured animal cells and bacteria to condensed smoke samples from both marijuana and tobacco. There were distinct differences in the degree and type of toxicity elicited by marijuana and cigarette smoke.

Marijuana smoke caused significantly more damage to cells and DNA than tobacco smoke, the researchers note. However, tobacco smoke caused chromosome damage while marijuana did not.

Source: ScienceDaily. September 30, 2009, from http://www.sciencedaily.com­
The Genotoxicity of Mainstream and Sidestream Marijuana and Tobacco Smoke Condensates. Chemical Research in Toxicology, Online July 17, 2009

Using new DNA “fingerprinting” techniques, two University of Minnesota researchers have become the first to unequivocally separate hemp plants from marijuana plants with genetic markers. Hemp, a crop grown for durable fiber and nutritious seed, and marijuana, the most abundant illegal drug of abuse in the United States, both belong to the species Cannabis sativa. They differ in levels of the psychoactive drug tetrahydrocannabinol (THC) but are otherwise difficult to tell apart. The technique holds promise for distinguishing different cultivars (domesticated plant lines) in U.S. criminal cases. It may also prove useful in countries where the cultivation of hemp is permitted but marijuana is illegal, as in Canada and Europe. The work appears in the March issue (volume 51, No. 2) of the Journal of Forensic Science.The new technique is an improvement on previous means of separating the two types of Cannabis, said author George Weiblen, an assistant professor of plant biology in the university’s College of Biological Sciences and College of Food, Agricultural and Natural Resource Sciences. For decades it has been possible to identify THC chemically, but the drug is not present in all plant tissues or throughout a plant’s life cycle. And other researchers have found that genetic markers known as “short tandem repeats,” which are used to identify individuals in paternity and criminal cases, lack the power to distinguish Cannabis cultivars unequivocally.

In tests with three different cultivars of hemp and one of marijuana, the DNA fingerprints of all the cultivars were distinct and nonoverlapping. Weiblen and Shannon L. Datwyler, a postdoctoral associate who is now on the faculty of California State University, Sacramento, found that the AFLP (amplified fragment length polymorphism) technique generated hundreds of genetic markers that together established separate identities for each of the four cultivars.

“We think this technique has the potential to distinguish marijuana varieties as well,” said Weiblen. “It has implications not just for separating hemp from marijuana in countries where hemp cultivation is permitted, but in establishing origins of seized drugs and, therefore, conspiracy in drug distribution networks. It also could be used in criminal defenses against claims of conspiracy.”

The technique chops up DNA and generates numerous fragments of DNA, each defined by particular “marker” DNA sequences that act like bookends. The lengths of the fragments within the bookends were found to vary according to the cultivar. Thus, the pattern of fragment lengths adds up to a composite picture of each cultivar.

“With this technique, we find hundreds of markers scattered across the genome,” said Weiblen. “The larger number of markers, compared to other techniques, gives us the power to separate the cultivars.”

The Cannabis plant has been cultivated for millennia and is important in the global economy as both a licit and an illicit crop, said Weiblen. Hemp is a source of durable fiber that provides an alternative to cotton fabric, among other uses. Cotton requires pesticide application and a hot climate, whereas hemp does not, which makes it suitable for local Minnesota agriculture. Weiblen seeks to screen a wider range of Cannabis cultivars to refine the technique. He is also working to identify regions of the Cannabis genome responsible for drug content in marijuana. If enough can be learned about the genome, it may one day be possible to produce an entirely drug-free hemp plant that looks different from marijuana. Currently, all hemp products are imported into the United States. Developing a new variety that could be cultivated in the United States would reduce American dependence on foreign products while creating a new alternative crop for American farmers.

Source: www.ScienceDaily March 23rd 2006

Nearly one in two teenagers knows someone who has suffered from a mental health problem like paranoia after using cannabis, a survey suggests.Forty-two percent of 11-18 year olds know someone who has experienced memory loss, panic attacks or paranoia from cannabis, drugs information service Frank said.

The survey of 27,000 teenagers found 74% were aware of the risks.

It revealed 18% of teenagers felt under pressure to try the Class B drug.

One in ten thought it made them look cool.

The research, which was carried out on networking website Habbo Hotel, found 64% of young people were aware cannabis could cause panic attacks, 41% knew it could bring on paranoia and 38% thought it could result in memory loss.

Over 50% of teenagers associated cannabis use with losing motivation and doing badly at school or college.

But one in four said they saw cannabis as a “natural” drug, despite the risks.

And 14% of 11-18 year olds admitted using the drug to help them to cope with life.

Chris Hudson, from Frank, said: “The majority of teenagers (55%) don’t want to risk their health by using cannabis, however, some people choose to take the risk; while others wrongly believe cannabis is harmless because it is a plant.

“Cannabis messes with your mind – and reactions can be more powerful with stronger strains such as skunk, which is around twice as potent,” he warned.

Source: BBC Newsbeat 6th Aug.2009

Francesca M. Filbeya, et alCraving is one of the primary behavioral components of drug addiction, and cue-elicited craving is an especially powerful form of this construct. While cue-elicited craving and its underlying neurobiological mechanisms have been extensively studied with respect to alcohol and other drugs of abuse, the same cannot be said for marijuana. Cue-elicited craving for other drugs of abuse is associated with increased activity in a number of brain areas, particularly the reward pathway. This study used functional magnetic resonance imaging (fMRI) to examine cue-elicited craving for marijuana. Thirty-eight regular marijuana users abstained from use for 72 h and were presented with tactile marijuana-related and neutral cues while undergoing a fMRI scan. Several structures in the reward pathway, including the ventral tegmental area, thalamus, anterior cingulate, insula, and amygdala, demonstrated greater blood oxygen level dependent (BOLD) activation in response to the marijuana cue as compared with the neutral cue.

These regions underlie motivated behavior and the attribution of incentive salience. Activation of the orbitofrontal cortex and nucleus accumbens was also positively correlated with problems
related to marijuana use, such that greater BOLD activation was associated with greater number of items on a marijuana problem scale. Thus, cue-elicited craving for marijuana activates the reward neurocircuitry associated with the neuropathology of addiction, and the magnitude of activation of these structures is associated with severity of cannabis-related problems. These findings may inform the development of treatment strategies for cannabis
dependence.

The relationship between craving and drug use behavior is an integral piece of the addiction puzzle. Craving is considered the intense desire for a rewarding object or experience. Cue elicited
craving, induced by exposure to alcohol- or drug-related cues, is a particularly potent form of craving. Previous investigators have reported that subjective craving increases after exposure to cues specific to a variety of drugs of abuse, including cocaine (e.g., tactile cues, videos, i.v. administration, images, guided imagery) heroin (e.g., images) alcohol (e.g., alcohol taste, images, alcohol-related words), and tobacco (e.g., visual and tactile presentations) .

Cue-elicited craving for alcohol and tobacco in particular have important clinical implications and have been the focus of psychosocial and pharmacological intervention efforts.

The advent of functional neuro-imaging has allowed studies of cue-elicited craving to elucidate the neurobiological mechanisms that accompany increased craving. Such neuro-imaging studies
have associated craving with increased activation of reward pathways . The reward circuits involve the dopamine projection from the ventral tegmental area (VTA) to striatal areas (e.g., nucleus accumbens) and the prefrontal cortex (PFC), the repeated activation of which underlies the attribution of incentive salience to otherwise neutral stimuli . Other reward-related areas, including the insula and cingulated gyrus show increased activity with the presentation of drug-related stimuli. Presentation of these stimuli is also associated with increased activity in brain structures that underlie reward and emotion regulation, such as the thalamus and amygdala.

The few published studies of cue-elicited craving for marijuana suggest that it is a reliable and valid phenomenon, analogous to cue-elicited craving for other drugs of abuse. Marijuana-related cues presented in a variety of sensory modalities, elicit increases in self-reported craving. For example, auditory-presented imagery scripts induce craving in marijuana smokers, and the magnitude of this craving varies as a function of the amount of marijuana-related content presented in the script . Craving also increases when abstinent frequent marijuana users are exposed to an auditory script that is paired with a tactile cue, such as a used marijuana pipe or bong .

Importantly, in this paradigm, cue presentation increases craving beyond the effects induced by abstinence. Additionally, marijuana related visual cues elicit greater craving in chronic heavy users than in controls; physiologically, users demonstrate greater skin conductance and larger late positivity of visual event-related brain potentials than controls in response to these stimuli .

The present study was designed to examine the effects of marijuana-related cues on the activation of reward circuitry, and to examine the relationship between these effects and the behavioral symptoms of cannabis dependence. We hypothesized that among regular marijuana users, marijuana-related cues compared with neutral cues, would elicit greater blood oxygen level dependent (BOLD) activity in reward structures (i.e., VTA, striatum, anterior cingulate, and insula). Furthermore, we hypothesized that the magnitude of this response would be associated with the number of problems related to marijuana use.

Results

Compared with the neutral cue, presentation of the marijuana cue elicited significantly greater BOLD activation in a large cluster encompassing several areas, including the VTA, dorsal anterior cingulate cortex, cerebellum, thalamus, pre- and postcentral gyri, inferior frontal gyrus/insula, thalamus, amygdala,

fusiform gyrus, pre- and postcentral gyri, inferior parietal lobe, and superior temporal gyrus (cluster-corrected z_2.3, P_0.05)

BOLD response in several of these differentially activated areas was also significantly positively correlated with total marijuana problem scale (MPS) score (cluster-corrected z _ 2.3, P _ 0.05). These areas included the orbitofrontal cortex (OFC) and nucleus accumbens (NAc) The analyses of correlations with the Structured Clinical Interview for DSM Disorders (SCID) total symptom count, subjective urge ratings, frequency, and duration of use did not meet the significance threshold.

Source: 13016–13021 _ PNAS _ August 4, 2009 _ vol. 106 _ no. 31 www.pnas.org_cgi_doi_10.1073_pnas.0903863106

April 12, 2005
BY MARK HENDERSON, SCIENCE CORRESPONDENT

 ONE in four people carries genes that increases vulnerability to psychotic illnesses if he or she smokes cannabis as a teenager, scientists have found.
A common genetic profile that makes cannabis five times more likely to trigger schizophrenia and similar disorders has been identified, increasing pressure on the Government to reverse the drug’s reclassification from Class B to Class C.

The increased risk applies to people who inherit variants of a gene named COMT who also smoked cannabis as teenagers. About a quarter of the population have this genetic make-up, and up to 15 per cent of the group are likely to develop psychotic conditions if exposed to the drug early in life.
Neither the drug nor the gene raises the risk of psychosis by itself.
The study, led by Avshalom Caspi and Terrie Moffitt, of the Institute of Psychiatry at King’s College London, offers the best explanation yet for the way that cannabis has a devastating psychiatric impact on some users but leaves most unharmed. Scientists had suspected that genetic factors were responsible for this divide, but a gene had not been pinpointed.
The findings, to be published in Biological Psychiatry, also reinforce a growing consensus that nature and nurture are not mutually exclusive forces but combine to affect behaviour and health. The King’s team has previously identified genes that raise the risk of depression or aggression, but only in conjunction with environmental influences.
Mental health campaigners said that the results vindicated their concerns about the decision last year to downgrade cannabis to a Class C drug, which means that possession is no longer an arrestable offence.
Marjorie Wallace, chief executive of the mental health charity Sane, said that it was becoming clear that cannabis placed millions of users at risk of lasting mental illness. About fifteen million Britons have tried cannabis, and between two million and five million are regular users, according to the Home Office British Crime Survey. The research suggests that a quarter could be at risk.
The evidence will be considered by a review of the drug’s classification announced last month by the Home Secretary. It may be possible to develop a test for genetic susceptibility to cannabis. “If we were able genetically to identify the vulnerable individuals in advance, we would be able to save thousands of minds, if not lives,” Ms Wallace said.
Dr Caspi, however, rejected the idea of screening based on the COMT gene. “Such a test would be wrong more often than it is right. Cannabis has many other adverse effects, especially on developing teenagers, on respiratory health and possibly on cognitive function. Effects may be pronounced among a genetically vulnerable group but that doesn’t mean we should encourage others not genetically vulnerable to use cannabis.”
The King’s team tracked 803 men and women born in Dunedin, New Zealand, in 1972 and 1973, who were enrolled at birth in a research project. Each was interviewed at 13, 15 and 18 about cannabis use, tested to determine which type of COMT genes they had inherited, and followed up at 26 for signs of mental illness.
COMT was chosen as it is known to play a part in the production of dopamine, a brain-signalling chemical that is abnormal in schizophrenia. It comes in two variants, known as valine or methionine, and every person has two copies, one from each parent.
Among people with two methionine variants, the rate of psychotic illness was 3 per cent, the background rate for the general population, regardless of whether they had used cannabis as teenagers.
Among those with two valine variants the rate was 3 per cent for non-users but 15 per cent for those who had smoked cannabis in their teens.
Dr Caspi said research had shown that the valine gene variant and cannabis affect the brain’s dopamine system in similar fashion, suggesting that they deliver a “double dose” that can be damaging. The work needs to be replicated by others to confirm the findings, Dr Caspi said. It also is possible that the gene involved is not COMT but a neighbour.
THE DRUG OF CHOICE FOR MILLIONS
•  Cannabis was reclassified from a Class B to a Class C drug in January 2004. Possession remains illegal, but is not an arrestable offence. The Home Secretary has asked for a review by November
•  The Home Office estimates that fifteen million people have tried cannabis, two million to five million are regular users and reclassification has saved 199,000 hours’ police work
•  Liberalisation campaigners argue that millions smoke the drug with fewer ill-effects than others suffer from alcohol or tobacco
•  A recent study at Maastricht University found that cannabis doubles the risk of schizophrenia, hallucinations and paranoia among a genetically susceptible group

Source:  www.timesonline.co.uk  14 April 2005

Dope smokers have a 40 per cent increased risk of developing schizophrenia, and taking it regularly drives the risk up two-fold, Australian research shows.
A new study by psychiatrists has reviewed the latest evidence of links between cannabis use and mental illness, concluding the association is “stronger and clearer than ever”.
A pot smoker is 40 per cent more likely to suffer a psychotic episode than a non-smoker, according to the review of major published international research.
And for people who smoke daily over long periods their risk is 200 per cent higher.
“On the world stage, Australians excel in smoking cannabis, so there are very many people who fit into this category,” said lead researcher Dr Martin Cohen, a psychiatrist at the Hunter New England Mental Health Service.
“In fact we’re number one in the world.
“We know now more than ever that this bodes badly for our mental health.”
The review, published in the latest Australian and New Zealand Journal of Psychiatry, calculates that about 14 per cent of all cases of psychosis would never have occurred had the patient not picked up a joint.
A third of all Australians have smoked at least once in their life, with about 300,000 using daily. And while all had increased their risk to some degree, there was growing evidence that genetics predisposed some people even more.
Scientists have found a gene called COMT that, when faulty, is unable to break down the brain chemical dopamine.
An overload of dopamine triggers psychosis and, as cannabis produces an excess of the chemical, people with this “fault” are vulnerable.
Between 10 and 25 per cent of the population are believed to have the faulty gene, but as yet there is no way to test for it.
The risk is also higher for people who start smoking young and those who use heavily.
A 1998 national drug survey of 14 to 19 year olds showed 20 per cent had smoked in the last week, and 20 per cent of these took their first puff before they turned 12.
“These teenagers are the ones we really need to worry about because their use is changing a developing brain,” Dr Cohen said.
Professor Jan Copeland, director of the National Cannabis Prevention and Information Centre, said the levels of cannabis use had declined significantly since the 1998 survey, especially among school-aged Australians.
“But while we’re deterring many from ever trying, established regular users are still finding it very difficult to give up, putting them at risk of not just psychosis but depression as well,” she said.
Source:  The West.com.au  21st May 2008

Ian Sample, science correspondent
The Guardian
Tuesday June 3 2008

Smoking cannabis for long periods of time may shrink parts of the brain that govern memory, emotion and aggression, according to researchers in Australia. Scientists used magnetic resonance imaging to scan the brains of people who admitted to smoking more than five joints a day for at least 10 years and compared them with brain images taken from non-drug users.

Those who smoked cannabis regularly had on average a 12% smaller hippocampus, the part of the brain which is thought to be involved with emotion and memory, and a 7% smaller amygdala, which plays a role in regulating fear and aggression.

For the study, researchers imaged the brains of 15 cannabis smokers and 16 individuals who did not use the drug. The scientists, led by Murat Yücel at the University of Melbourne and colleagues at the University of Wollongong, said scans on larger numbers of people were needed to confirm the extent of the effect.

“Although modest use may not lead to significant neurotoxic effects, these results suggest that heavy daily use might indeed be toxic to human brain tissue,” the scientists report in the journal Archives of General Psychiatry.

Cannabis users also fared worse in tests of verbal memory and were more likely to have low-level symptoms of psychotic disorders such as schizophrenia and mania.

Last month, a team at New York University scanned the brains of a group of 17- to 30-year-olds who had smoked cannabis two to three times a week for at least a year. In that study, the brains of drug users looked no different from those who had never taken cannabis.

In 2004, Cyril D’Souza, a professor of psychiatry at Yale University, reported that THC, the active ingredient in cannabis, caused fleeting schizophrenia-like symptoms in users, ranging from suspiciousness and delusions to poor memory and attention span.

Source: http://www.guardian.co.uk/science/2008/jun/03/drugs.drugsandalcohol

By Laura Clout
Telegraph News
06/02/2008

Researchers also found that those who took cannabis in adolescence had a greater risk of developing schizophrenia than older users of the drug.

The teenagers, aged 15 and 16, were asked about their drug use before their risk of developing a psychotic disorder was assessed by experts.

More than 5 per cent said they had used cannabis once or more, and one in 100 had used cannabis more than five times. Girls were more likely to take the drug than boys.

The study, carried out by a team at the University of Oulu in Finland, is published on Monday in the British Journal of Psychiatry.

Dr Jouko Miettunen, who led the research said: “These teenagers are likely to be vulnerable to the mental effects, which means they are probably vulnerable to developing psychosis at some point.”

WASHINGTON (CNN) — The earlier a young person uses marijuana the greater the risk for mental health problems later in life, the director of National Drug Control Policy said Tuesday, basing his conclusion on a survey of medical research.
 
“We’re trying to get out the word that the last 10 years of research have helped to alert us to the use of marijuana in particular is a very dangerous risk for the mental health of our young people,” John Walters said at a news conference.
He said the conclusion runs against popular culture that often considers marijuana a low-risk recreational drug.
Walters cited a government study that found a base rate of mental illness at between 8 percent and 9 percent among Americans 18 and older. For those who use marijuana, he said, “That increases to 12-and-a-half percent.”
And, he added, “For those who have used marijuana prior to age 12, the rate of mental illness jumps to 21 percent.”
The rate was half that, or 10.5 percent, for adults who first used marijuana at age 18 or older.
Those were the findings of the National Survey on Drug Use and Health, an annual survey sponsored by the Substance Abuse and Mental Health Services Administration.
Walters did not directly address the possibility of confusing cause and effect — that is, that people with mental problems might be more inclined to use drugs.
One study he cited was published last year in the Archives of General Psychiatry. It involved 600 pairs of same-sex twins, one of whom was dependent on marijuana and one of whom was not. The twin who was dependent was almost three times as likely to think about suicide and attempt suicide than his brother or sister, the study found.
Neil McKeganey, who heads the University of Glasgow’s Center for Drug Misuse Research, was at the press conference in support of Walters.
“It is leading us to look again at this so-called recreational drug,” he said. “Kids who start to use marijuana at a young age are much more likely to suffer serious, long-term mental health problems.”
The parents of a teenager who committed suicide last year were also at the news conference, and they linked their son’s death to his marijuana use.
Tanya Skaggs, of Colorado Springs, Colorado, said, “He had a severe lack of judgment that was because of the marijuana, this destructive behavior was continuing,” in the months leading up to his death.
The parents were unable to break his marijuana use, Skaggs said, despite counseling, searching his room for pot and random drug tests.
“We just never thought that something like this could happen to us. But it does, and it did,” she said. “We wish we could have helped.”
Agenda ‘detrimental to your children’
Walters downplayed whether the medical use of marijuana undercuts the impact of warnings to young people against pot use.
The question was tied to a decision by Canada last month to approve the prescription drug Sativex, an oral spray that contains the active ingredient of marijuana, to treat the symptoms of multiple sclerosis.
He responded, “We believe that there’s a clear distinction” between validated medical benefits and what he said could be “a bunch of ads where people testify that their mother, dying, smoked a joint and was saved, and that means marijuana is medicine.”
“Your children are being educated,” he said of such advertising. “But they’re being told lies. And they’re being told things that are designed to push a particular agenda which is detrimental to your children, and detrimental to the country.”
Group calls for national discussion
Meanwhile, a Washington-based nonprofit group released a report recommending changes in the way authorities handle drug offenses, citing a “disproportionate” focus on “low-level marijuana users.”
“The ‘war on drugs’ in the 1990s was, essentially, a ‘war on marijuana,’” said the report by the Sentencing Project, which was founded in 1986 to promote alternative sentencing programs.
A national analysis covering 1990 to 2002 found that, of a 450,000 rise in drug arrests during that period, 82 percent of the increase was for marijuana, and 79 percent was for marijuana possession alone.
Marijuana arrests now make up 45 percent of the nation’s 1.5 million drug arrests annually, the report said, and an estimated $4 billion is spent each year on marijuana offenders.
“The growth in marijuana arrests over the 1990s has not led to a decrease in use or availability, nor an increase in cost,” the group said. “Meanwhile, billions are being spent nationally.”
The report calls for “a national discussion regarding the zealous prosecution of marijuana use and its consequences for allocation of criminal justice resources and public safety.”
“Law enforcement has focused disproportionately on low-level possession charges as a result of the nation’s lack of a thoughtful strategy,” it said.Source:www.WordPress.com June 2008

It  was fascinating to note in the opening line of one of the recent papers on Alzheimer’s Disease that hippocampal atrophy (or wasting) is completely accepted as a hallmark feature!
 
You will recall the recent Australian Study (abstract below) which demonstrated unequivocally even in quite small samples (of 15 patients in control and THC groups) that cannabis atrophies the hippocampus!
 
Sounds like we need to tell the world!Dr.Stuart Reece, Australia.

 
Alzheimer’s disease (AD) is a genetically heterogeneous disorder characterized by early hippocampal atrophy and cerebral amyloid-β (Aβ) peptide deposition. Using TissueInfo to screen for genes preferentially expressed in the hippocampus and located in AD linkage regions, we identified a gene on 10q24.33 that we call CALHM1. We show that CALHM1 encodes a multipass transmembrane glycoprotein that controls cytosolic Ca2+ concentrations and Aβ levels. CALHM1 homomultimerizes, shares strong sequence similarities with the selectivity filter of the NMDA receptor, and generates a large Ca2+ conductance across the plasma membrane. Importantly, we determined that the CALHM1 P86L polymorphism (rs2986017) is significantly associated with AD in independent case-control studies of 3404 participants (allele-specific OR = 1.44, p = 2 × 10-10). We further found that the P86L polymorphism increases Aβ levels by interfering with CALHM1-mediated Ca2+ permeability. We propose that CALHM1 encodes an essential component of a previously uncharacterized cerebral Ca2+ channel that controls Aβ levels and susceptibility to late-onset AD.
Source: Cell, Vol 133, 1149-1161, 27 June 2008
 
Regional brain abnormalities associated with long-term heavy cannabis use.
CONTEXT: Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human brain. OBJECTIVE: To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor-rich regions of the brain, the hippocampus and the amygdala. DESIGN: Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging. SETTING: Participants were recruited from the general community and underwent imaging at a hospital research facility. PARTICIPANTS: Fifteen carefully selected long-term (>10 years) and heavy (>5 joints daily) cannabis-using men (mean age, 39.8 years; mean duration of regular use, 19.7 years) with no history of polydrug abuse or neurologic/mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years). MAIN OUTCOME MEASURES: Volumetric measures of the hippocampus and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured. RESULTS: Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P = .001), with a relatively (and significantly [P = .02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippocampal volume was inversely associated with cumulative exposure to cannabis during the previous 10 years (P = .01) and subthreshold positive psychotic symptoms (P < .001). Positive symptom scores were also associated with cumulative exposure to cannabis (P = .048). Although cannabis users performed significantly worse than controls on verbal learning (P < .001), this did not correlate with regional brain volumes in either group. CONCLUSIONS: These results provide new evidence of exposure-related structural abnormalities in the hippocampus and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.

Source:  Arch Gen Psychiatry. 2008 Jun;65(6):694-701

Alterations in a molecular brain pathway activated by marijuana may contribute to the cognitive symptoms of schizophrenia, according to a report in the July issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Expression of the cannabinoid 1 receptor (CB1R), the site of action of the main chemical ingredient of marijuana, is significantly reduced in the brains of individuals with schizophrenia. Activation of CB1R impairs signaling by gamma-aminobutyric acid (GABA), an important neurotransmitter essential for core cognitive processes such as working memory. The use of marijuana in individuals with schizophrenia appears to worsen this deficit in GABA synthesis.
Since reduced GABA is known to be present in schizophrenia, these findings suggest possible new drug targets that could help to improve function in people with the mental illness, University of Pittsburgh School of Medicine researchers report.
“Heavy marijuana use, particularly in adolescence, appears to be associated with an increased risk for the later development of schizophrenia, and the course of illness is worse for people with schizophrenia who use marijuana,” said David A. Lewis, M.D., corresponding author of the study and UPMC Endowed Professor in Translational Neuroscience, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine. “We wanted to understand the biological mechanisms that could explain these observations, and with this study, I believe that we can narrow down at least part of the ‘why’ to CB1R, the receptor for both tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, and the brains own cannabinoid chemical messengers.”
Dr. Lewis and his colleagues examined specimens of brain tissue collected after death from 23 people with schizophrenia and 23 normal comparison subjects matched for a number of factors, including age and sex. The researchers evaluated levels of CB1R messenger RNA and protein, and also measured levels of glutamic acid decarboxylase (GAD-67), an enzyme that makes GABA, and cholecystokinin (CCK), a neuropeptide released from GABA neurons that, among other actions, regulates the production of the brain’s own cannabinoids.
“CB1R levels were significantly 15 percent lower in the subjects with schizophrenia,” Dr. Lewis said. “We measured these biochemical messengers using three techniques, and each time got the same answer — less CB1R in people with schizophrenia.” This reduction, he noted, appears to be the brain’s way of compensating for lower levels of GABA, and the use of marijuana defeats this compensation.
“These findings may provide insight into the biological basis of why cannabis use worsens schizophrenia, and, as a result, identify a novel target for new drug development that could improve treatments available for schizophrenia,” said Dr. Lewis.
Other authors include Stephen M. Eggan, Ph.D., and Takanori Hashimoto, M.D., Ph.D., both of the Department of Psychiatry, University of Pittsburgh School of Medicine.
The study was funded by the National Institutes of Health. Additional funding support for Dr. Eggan came from the University of Pittsburgh’s Andrew Mellon Predoctoral and Scottish Rite fellowships.Source: University of Pittsburgh Schools of the Health Sciences (2008, July 8). Schizophrenia Linked To Dysfunction In Molecular Brain Pathway Activated By Marijuana. ScienceDaily. Retrieved July 18, 2008, from http://www.sciencedaily.com¬ /releases/2008/07/080707161411.htm

Scientists at the National Institute on Drug Abuse’s (NIDA) Intramural Research Program in Baltimore, MD, have confirmed for the first time in humans that chemically blocking the body’s cannabinoid receptors can significantly reduce the effects of smoked marijuana. The study appears in the April 14th issue of the Archives of General Psychiatry.Cannabinoid receptors – proteins on the surface of brain cells — are most dense in brain regions involved in thinking and memory, attention and control of movement. Their exact role in humans is not well understood, but animal studies have shown that cannabinoid receptor agonists – compounds that activate the receptor sites – impair learning and memory and increase appetite and food intake. Previous studies in animals have shown that the major effects of tetrahydrocannabinol (THC), the primary psychoactive compound in marijuana, are due to its binding to specific cannabinoid receptors located on the surface of brain cells. These effects appear to be lessened when cannabinoid receptors are blocked by an antagonist.
 
“This research helps point the way toward possible treatment for those addicted to marijuana and perhaps may be useful in finding effective treatments for other disorders related to the cannabinoid system, ” says NIDA director Dr. Alan I. Leshner.
In the study, Dr. Marilyn Huestis and her NIDA colleagues used a cannabinoid receptor antagonist – a compound that binds to the receptor and blocks agonist compounds from activating it. The antagonist, SR141716, was discovered by Sanofi-Synthelabo of Paris, France, and was used in this study with NIDA under a Cooperative Research and Development Agreement (CRADA).
Participants in the study were given either SR141716 or a placebo and two hours later smoked one marijuana cigarette. Those who received SR141716 showed significantly reduced marijuana effects, while those who received the placebo showed typical marijuana intoxication.
The results of the study are an important step in understanding the complex role of the cannabinoid receptor system in the human brain.
“Our findings of a significant blockade of marijuana’s effects after treatment with SR141716, which is highly selective for the CB1-cannabinoid receptor sites, demonstrates for the first time in humans that these receptors play a major role in mediating the effects of marijuana,” Dr. Huestis says.
In their investigation of the role of the cannabinoid system in humans, Dr. Huestis and her colleagues gave increasing doses of SR141716 or placebo to 63 adult men with histories of marijuana use. When individuals received SR141716 before smoking marijuana, there was a dose-dependent reduction in psychological and physical effects of marijuana. At the highest dose of SR141716 (90 mg), volunteers reported a 43% reduction in how “high” they felt, a 38% reduction in how “stoned” they were, and a 43% reduction in “drug effect” as compared to those who received active marijuana and no antagonist. In addition, they had a 59% less increase in heart rate, one of the primary physical effects of marijuana.
The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world’s research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish by calling NIDA Infofax at 1-888-NIH-NIDA (644-6432) or 1-888-TTY-NIDA (889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov.

Source: . ScienceDaily. Retrieved July 23, 2008, from http://www.sciencedaily.com¬ /releases/2001/04/010413080431.htm

Wednesday, September 10, 2008NEW YORK (Reuters Health) – Researchers from Spain have found a strong and independent link between cannabis use and the onset of psychosis at a younger age. The association, they say, cannot be explained by chance, and is not related to gender or the use of other drugs. It is, however, related to the amount of cannabis used.

“The clinical importance of this finding is potentially high,” Dr. Ana Gonzalez-Pinto from Santiago Apostol Hospital in Vitoria, and colleagues write in the Journal of Clinical Psychiatry, given that cannabis use is extremely prevalent among young people.”

The researchers also report that “estimates of the attributable risk suggest that the use of cannabis accounts for about 10 percent of cases of psychosis.”

The findings are based on 131 patients ages 15 to 65 years who needed inpatient care for a first psychotic episode during a 2-year period. The subjects were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders, and clinical and demographic data were also collected.

The results showed a significant gradual reduction in the age at which psychosis began that correlated with an increased dependence on cannabis. Compared with nonusers, age at onset was reduced by 7, 8.5, and 12 years among users, abusers and dependents, respectively, the researchers report.

In further analysis, the effect of cannabis on age at onset “was not explained by the use of other drugs or by gender,” they also note. The finding was similar in the youngest patients, suggesting that this effect was not due to chance.

These results “point to cannabis as a dangerous drug in young people at risk of developing psychosis,” Gonzalez-Pinto and colleagues conclude.

SOURCE: Journal of Clinical Psychiatry, August 2008.