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

Marijuana used for medical purposes has the same long term effect on the user as marijuana used for recreation. Marijuana use can cause impairment of short-term memory, attention, motor skills, reaction time, and the organization and integration of complex information.

Marijuana use alters perceptions and creates time distortion and can cause drowsiness and lethargy. Heavy marijuana use can cause apathy, decreased motivation, and impair cognitive performance and can cause mental health problems.

Employees who use marijuana off-duty are still effected by it. Impaired cognition that can cause lapses in judgement can remain for a long period. Memory defects can last as long as six weeks. See: Abbie Crites-Leoni, Medicinal Use of Marijuana: Is the Debate a Smoke Screen for Movement Toward Legalization? 19 J. Legal Med. 273, 280 (1998) (citing Schwartz, et al., Short- Term Memory Impairment in Cannabis-Dependent Adolescents, 143 Am. J. Dis. Child. 1214 (1989)

Employers may be liable for the actions of employee who use marijuana especially those employees in safety sensitive positions. The more chronic the use of “medical” marijuana the higher the risk.

VIOLATIONS OF FEDERAL LAW

Will employers have to accommodate marijuana use that violates federal law? Marijuana, remains illegal under federal law because of its “high potential for abuse,” its lack of any “currently accepted medical use in treatment in the United States,” and its “lack of accepted safety for use … under medical supervision.”Gonzales v. Raich, 545 U.S. 1 (2005); United States v. Oakland Cannabis Buyers’ Cooperative, 532 U.S. 483 (2001)

IF THIS BILL PASSES “MEDICAL” MARIJUANA WILL RESULT IN MORE MARIJUANA USE AMONG EMPLOYEES

As consumers we all pay for lost productivity and job-related accidents in the final costs of the produced goods and higher insurance premiums due to workplace accidents. Drug using employees are not as safe. They are 3.6 times more likely to be involved in a work-related accident than their non-using employee, and 5 times more likely to file workers’ compensation claims. As many as 50% of all workers’ compensation claims may involve substance abuse.[FN1]

The U.S. Postal Service did a study that showed that substance abusers have 55% more accidents, experience 85% more on-the-job injuries, and have a 78% higher rate of absenteeism when compared to non-substance abusing employees.[FN2] A report by the National Safety Council claimed that 80% of those injured in serious drug-related work accidents are not the drug using employees, but innocent employees and others.[FN3]

Drug using employees commit workplace crimes. There is a very significant statistical correlation between drug use and criminal conduct.[FN4]

Substance abuse also causes:
Domestic and financial difficulties for employees;
Poor judgment in employment decision making;
Potential embarrassment to the employer as a result of off-duty conduct, which may be publicized, including criminal charges, diversion of supervisory and managerial time;
Damage to company property; and
Time devoted to discipline and grievance matters.[FN5]

While the studies vary somewhat, it is clear that there is substantial substance abuse in the workplace and it has a powerful negative impact on our economy and productivity. The increased use of “medical” marijuana will magnify all these problems.

References

[FN1] Current, The Truth About Drug Testing: Answers to the Questions Everyone Is Asking, p. 3 (1st Ed., Fort Lauderdale, FL, 1998).

[FN2] “Pre-employment Drug Testing: Association with EAP, Disciplinary, and Medical Claims Information” U.S. Postal Service, Personnel Research and Development Branch, Office of Selection and Evaluation, July 1992.

[FN3] Wisotsky, The Ideology of Drug Testing [Ideology of Drug Testing], 11 Nova L Rev 763, 768 (1987).

[FN4] See Stewart, Proof Positive of Drug Link to Crime, Wall St J, May 28, 1987, at 26, col 3.

[FN5]Alcohol & Drugs in the Workplace: Costs, Control and Controversies, A BNA Special Report [Costs, Control and Controversies], 7 (Bureau of National Affairs, Washington, D.C. 1986)

Source: David Evans sent to DFAF May 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

Montana and other states that have legalized medical marijuana are seeing a backlash, with public anger rising and politicians passing laws to slow the proliferation of pot shops and bring order to what has become a wide-open, Wild West sort of industry.

They are looking to avoid what happened in California, which allowed the pot industry to grow so out of control that at one point Los Angeles had more medical marijuana shops than Starbucks – about 1,000 by one count.

“Yeah, it’s out of control – and it needs control, if not extinction,” Montana Sen. Jim Shockley said Friday. “There’s no control over distribution. There’s no control over who’s growing it. There’s no control in dosage.”

Fourteen states have legalized medical marijuana, beginning with California in 1996, and the District of Columbia followed suit this month. The laws allow chronically ill people to buy marijuana with permission from a doctor.

But many of these states passed their laws without working out the details. And they weren’t ready for the boom in pot shops that occurred this past year after the Obama administration announced it wouldn’t prosecute medical marijuana users.

In some places, law enforcement officials and civic leaders are complaining that there are too many marijuana dispensaries, that buyers and sellers are falling victim to robberies and break-ins, that driving-under-the-influence arrests are on the rise, and that the pot is being sold indiscriminately and winding up on the black market.
Some state and local governments are now rushing to put regulations in place.

Colorado lawmakers passed sweeping rules this month for pot growers and the estimated 1,100 shops selling marijuana, creating a new state bureaucracy led by auditors and criminal investigators who would monitor the industry to make sure, for example, that the drug is being sold only to patients who have a doctor’s recommendation.

Regulators expect only about half of the state’s dispensaries to continue operating under the stricter rules.
The Billings City Council approved a six-month moratorium on new medical marijuana businesses in May after the violence against pot businesses the previous two nights. On Thursday, the city of about 90,000 people ordered 25 of Billings’ 81 pot businesses to shut down after discovering they were not properly registered with the state.

Los Angeles officials recently took steps to shut down hundreds of dispensaries and ensure that the remaining ones meet stringent new guidelines. Owners must undergo a background check, their stores must be 1,000 feet from schools, parks and other gathering sites, and their pot must be tested at an independent laboratory.

Montana’s medical board is considering curbing mass screenings and teleconferences that make it easy for people to get a marijuana card. Montana in recent days has seen “cannabis caravans,” mobile operations that pass through town, charging people $100 to $150 for a doctor’s recommendation to smoke pot.
The push for tighter regulation has infuriated medical marijuana users.
“They are creating ordinances and moratoriums that are blatantly against the law,” said Jason Christ, founder of the Montana Caregivers Network, the group that organizes the cannabis caravans. “They do not serve to protect the welfare of our citizens, and they do no good.”

In Colorado earlier this month, veterans in wheelchairs, college students and dispensary owners packed legislative hearings to speak out against the regulations. The hearings lasted eight hours and reached a fever pitch when several people had to be removed for shouting at lawmakers.

Medical marijuana has been around for more than five years in Montana, but the boom came this past year. The number of registered users in Montana, a state with a population of just under 1 million, has gone from 2,923 last June to about 15,000 today. The number of registered suppliers has increased from 919 to about 5,000.

DUI arrests involving marijuana have skyrocketed, as have traffic fatalities where marijuana was found in the system of one of the drivers, Montana narcotics chief Mark Long told a legislative committee last month.
Also, Montana confidentiality laws prevent law enforcement from knowing where most medical marijuana businesses are, and civic leaders complain they don’t know whether the shops are up to city and fire codes or close to churches, schools or parks.

During Colorado’s legislative debate, state Sen. Chris Romer quoted the Grateful Dead as he contemplated the spectacle of lawmakers actually passing regulations for the legal sale of marijuana: “What a long, strange trip it’s been.”

Source: The Associated Press Friday, May 21, 2010

Montana and other states that have legalized medical marijuana are seeing a backlash, with public anger rising and politicians passing laws to slow the proliferation of pot shops and bring order to what has become a wide-open, Wild West sort of industry.
They are looking to avoid what happened in California, which allowed the pot industry to grow so out of control that at one point Los Angeles had more medical marijuana shops than Starbucks – about 1,000 by one count.
“Yeah, it’s out of control – and it needs control, if not extinction,” Montana Sen. Jim Shockley said Friday. “There’s no control over distribution. There’s no control over who’s growing it. There’s no control in dosage.”
Fourteen states have legalized medical marijuana, beginning with California in 1996, and the District of Columbia followed suit this month. The laws allow chronically ill people to buy marijuana with permission from a doctor.
But many of these states passed their laws without working out the details. And they weren’t ready for the boom in pot shops that occurred this past year after the Obama administration announced it wouldn’t prosecute medical marijuana users.
In some places, law enforcement officials and civic leaders are complaining that there are too many marijuana dispensaries, that buyers and sellers are falling victim to robberies and break-ins, that driving-under-the-influence arrests are on the rise, and that the pot is being sold indiscriminately and winding up on the black market.
Some state and local governments are now rushing to put regulations in place.
Colorado lawmakers passed sweeping rules this month for pot growers and the estimated 1,100 shops selling marijuana, creating a new state bureaucracy led by auditors and criminal investigators who would monitor the industry to make sure, for example, that the drug is being sold only to patients who have a doctor’s recommendation.
Regulators expect only about half of the state’s dispensaries to continue operating under the stricter rules.
The Billings City Council approved a six-month moratorium on new medical marijuana businesses in May after the violence against pot businesses the previous two nights. On Thursday, the city of about 90,000 people ordered 25 of Billings’ 81 pot businesses to shut down after discovering they were not properly registered with the state.

Los Angeles officials recently took steps to shut down hundreds of dispensaries and ensure that the remaining ones meet stringent new guidelines. Owners must undergo a background check, their stores must be 1,000 feet from schools, parks and other gathering sites, and their pot must be tested at an independent laboratory.
Montana’s medical board is considering curbing mass screenings and teleconferences that make it easy for people to get a marijuana card. Montana in recent days has seen “cannabis caravans,” mobile operations that pass through town, charging people $100 to $150 for a doctor’s recommendation to smoke pot.
The push for tighter regulation has infuriated medical marijuana users.
“They are creating ordinances and moratoriums that are blatantly against the law,” said Jason Christ, founder of the Montana Caregivers Network, the group that organizes the cannabis caravans. “They do not serve to protect the welfare of our citizens, and they do no good.”
In Colorado earlier this month, veterans in wheelchairs, college students and dispensary owners packed legislative hearings to speak out against the regulations. The hearings lasted eight hours and reached a fever pitch when several people had to be removed for shouting at lawmakers.
Medical marijuana has been around for more than five years in Montana, but the boom came this past year. The number of registered users in Montana, a state with a population of just under 1 million, has gone from 2,923 last June to about 15,000 today. The number of registered suppliers has increased from 919 to about 5,000.
DUI arrests involving marijuana have skyrocketed, as have traffic fatalities where marijuana was found in the system of one of the drivers, Montana narcotics chief Mark Long told a legislative committee last month.
Also, Montana confidentiality laws prevent law enforcement from knowing where most medical marijuana businesses are, and civic leaders complain they don’t know whether the shops are up to city and fire codes or close to churches, schools or parks.
During Colorado’s legislative debate, state Sen. Chris Romer quoted the Grateful Dead as he contemplated the spectacle of lawmakers actually passing regulations for the legal sale of marijuana: “What a long, strange trip it’s been.”

Source: The Associated Press Friday, May 21, 2010

Cannabinoids may suppress tumor invasion in highly invasive cancers, according to a study published online December 25 in the Journal of the National Cancer Institute.
Cannabinoids, the active components in marijuana, are used to reduce the side effects of cancer treatment, such as pain, weight loss, and vomiting, but there is increasing evidence that they may also inhibit tumor cell growth. However, the cellular mechanisms behind this are unknown.
Robert Ramer, Ph.D., and Burkhard Hinz, Ph.D., of the University of Rostock in Germany investigated whether and by what mechanism cannabinoids inhibit tumor cell invasion.
Cannabinoids did suppress tumor cell invasion and stimulated the expression of TIMP-1, an inhibitor of a group of enzymes that are involved in tumor cell invasion.
“To our knowledge, this is the first report of TIMP-1-dependent anti-invasive effects of cannabinoids. This signaling pathway may play an important role in the antimetastatic action of cannabinoids, whose potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials,” the authors write.

Source: Journal of the National Cancer Institute (2007, December 27). Cannabinoids May Inhibit Cancer Cell Invasion. ScienceDaily. Retrieved July 18, 2008, from http://www.sciencedaily.com¬ /releases/2007/12/071226004546.htm

Marijuana and its main psychoactive component, THC, exert a plethora of behavioral and autonomic effects on humans and animals.
Some of these effects are the cause of the widespread illicit use of marijuana, while others might be involved in the potential therapeutic use of this drug for the treatment of several neuronal disorders. The great majority of these effects of THC are mediated by cannabinoid receptor type 1 (CB1), which is abundantly expressed in the central nervous system. The exact anatomical and neuronal substrates of each action, however, were previously unknown. Using an advanced genetic approach, Krisztina Monory and colleagues at the Johannes Gutenberg University Mainz discovered that specific neuronal subpopulations mediate the distinct effects of THC. Their work is published online this week in the open-access journal PLoS Biology.
In their study, the researchers generated mutant mice lacking CB1 expression in defined neuronal subpopulations but not in others. These mice were treated with THC, and typical effects of the drug on motor behavior, pain, and thermal sensation were scored. Their discovery of the neural substrates underlying specific effects of THC could lead to a refined interpretation of the pharmacological actions of cannabinoids. Moreover, these data might provide the rationale for the development of drugs capable of selectively activating CB1 in specific neuronal subpopulations, thereby better exploiting cannabinoids’ potential therapeutic properties. http://www.plos.org/

Source: News-Medical.net Oct. 2007

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

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

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

Source: The New England Journal of Medicine, Volume 336(16) , 17 April 1997, pp 1184-1187

———————————————-

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

A Cognitive and Psychiatric Study

Originally, those asserting that crude marijuana should be approved for medical use claimed that it should be available for the terminally ill or those suffering from intractable pain. The scope of projected uses rapidly expanded to include “debilitating” conditions, which might be anything that the user perceived was a handicap or impairment. 

Marijuana contains numerous unique compounds known as cannabinoids.  Several of these have been synthesized and developed into useful drugs for specific medical use but these drugs are devoid of the more than 2000 impurities found in smoked cannabis, and the potency and dose of these manufactured drugs can be carefully adjusted to the patient.

In a recent study by Drs. Ghaffar and Feinstein, in the journal Neurology, 2008:71:164-169,(Multiple sclerosis and cannabis: a cognitive and psychiatric study),  found that patients with multiple sclerosis (MS) who were regular smoking of street cannabis had more extensive cognitive abnormalities compared to patients with MS who don’t use cannabis.  The study did not note this disparity in the controlled pharmaceutical use of cannabis-based medicinal extracts (CBMEs).  The authors, in response to an inquiry in the January 6, 2009 issue of Neurology, stated that “Based on the existing literature, it seems unlikely that the cognitive problems identified in our cannabis smokers are a function of a withdrawal syndrome, but we cannot be certain this given the limitations in our data.”   This statement acknowledges that there is a “withdrawal syndrome” for cannabis and that “cognitive problems” are associated with withdrawal from cannabis. 
Source:  Journal Neurology, 2008:71:164-169

Researchers at Brigham and Women’s Hospital found that patients taking cannabinoid medicines for pain may be getting “high,” but these effects were unrelated to relief from their pain symptoms. Results of their study, one of the first to examine the addictive potential of this class of pain medicine, were presented today at the American Academy of Pain Medicine’s 25th Annual Meeting.
In the study, Ajay Wasan, MD MSc and colleagues found that when used for non-cancer pain management, the cannabinoid class of medicines (such as dronabinol), got patients “high,” but the majority of subjects experienced significant pain relief independent of these psychoactive effects. Results indicate that these medicines have the likelihood of an addiction similar to smoking marijuana, leading researchers to conclude the abuse potential of this class should be studied further.
Using the Addiction Research Center Inventory (ARCI), the gold-standard for determining the abuse liability of substances, Dr. Wasan and colleagues at McLean Hospital looked at two different patient populations to compare the effects of medicinal, synthetic cannabinoid and marijuana. The first population was suffering from pain, and took each of the following at separate visits where they were observed for eight hours: placebo, 10mg, or 20 mg of dronabinol. The second population was not suffering from pain, but they were monitored every 30 minutes after smoking a high and low strength marijuana cigarette. Participants in both populations were given the ARCI every hour. After two hours, patients in the first population (synthetic cannabinoid medicine) were found to have the same psychoactive effects that patients from the second population (smoked marijuana) did after 30 minutes.
“Based on our study we believe the addictive qualities of this class of medicines need more investigation. In our study, patients taking the medicine, like the patients smoking the marijuana, were, essentially, stoned. However, they didn’t report less pain, indicating the pain relief properties were independent of the psychoactive effects,” said Dr. Wasan, lead author of the study, and director of clinical pain research at Brigham and Women’s Hospital. “We discovered that both the synthetic cannabinoid medicines we studied and marijuana have similar psychoactive properties and suggestive of an addiction potential.”
Source:  http://www.painmed.org/

Dale Deutsch, Ph.D., Professor of Biochemistry and Cell Biology at Stony Brook University and colleagues discovered a new molecular mechanism for the processing of endocannabinoids, brain compounds similar to THC, the active ingredient in marijuana, and essential in physiological processes such as pain, appetite, and memory.
Reported online this week in the Proceedings of the National Academy of Sciences (PNAS) , the finding could pave the way for new medicines for pain, addiction, appetite control and other disorders.
Dr. Deutsch and colleagues in the Departments of Biochemistry and Cell Biology (Martin Kaczocha) and Neurobiology and Behavior (Sherrye Glaser, Ph.D.) are the first to successfully identify two known fatty acid binding proteins (FABPs) that carry the endocannabinoid anandamide (AEA), a neurotransmitter, from the cell membrane to interior of the cell where it is destroyed. This identification enabled the research team to inhibit FABPs in various laboratory experiments and thereby reduce AEA breakdown inside cells. In their study, “Identification of intracellular carriers for the endocannabinoid anandamide,” the researchers report that they decreased the breakdown of AEA in some instances by approximately 50 percent.
“Inhibiting FABPs could potentially raise the levels of AEA in the brain’s synapses,” says Dr. Deutsch. “Naturally occurring AEA levels have been shown to curb pain without the negative side effects, such as motor coordination problems, from molecules like THC. Therefore, it makes sense to target AEA for therapeutic purposes.”
He emphasizes that their groundbreaking discovery of the role of FABPs in transporting this class of neurotransmitters may prove to be a crucial step in developing novel drug targets for endocannabinoids by way of inhibiting FABPs. In support of the research, The State University of New York (SUNY) Stony Brook Office of Technology Licensing and Industry Relations (OTLIR) has filed U.S. Patent applications comprising the discovery.
The OTLIR manages all intellectual property matters for the SUNY Research Foundation. In actively marketing this unlicensed technology created by Dr. Deutsch, the Stony Brook OTLIR welcomes commercial entities interested in partnering with the University. The licensing agent for the project is Adam DeRosa of the OTLIR.

The breakdown of AEA requires two factors. First, there needs to be a mechanism for transporting AEA to the location where it is inactivated because AEA is a fatty compound and thus unable to move inside the watery cellular environment. Second, the cell must express an enzyme called FAAH, which controls the breakdown and inactivation of AEA. In the laboratory, the researchers coaxed a nonneuronal cell type (COS-7) to express FAAH. These FAAH-expressing COS-7 cells were able to break down AED efficiently, indicating that the intracellular AEA transport mechanism was already present and operation in these cells. The researchers identified these carriers as two separate FABPs.
Dr. Deutsch believes that because a transporter for the AEA class of neurotrasmitters had never been discovered until the Stony Brook findings, continued research may explain many unanswered questions about AEA. Future research may uncover more knowledge about AEA transport, as well as the entire role these neurotransmitters play in pain, inflammation, appetite control, addiction, and perhaps other physiological processes related to many human disorders.
The research was funded by the National Institute on Drug Abuse, part of the National Institutes of Health.
Source: http://www.stonybrook.edu/   25th March 2009

Marijuana’s active ingredient may form the basis for new antiviral drugs that fight cancer-causing herpes viruses.

Professor Peter Medveczky, MD, of the University of South Florida’s medical microbiology and immunology department, and H. Lee Moffitt Cancer Center &Research Institute in Tampa, and colleagues worked on the study.

Their report appears in the Sept. 15 issue of the journal BMC Medicine.

Key IngredientThe researchers focused on marijuana’s active ingredient, delta-9-tetrahydrocannibol (THC).

In tissue culture tests, THC blocked the reactivation of various types of herpes viruses. Infection with herpes virus is recurrent and lifelong. The virus lies dormant in nerve tissue in infected people after symptoms have gone away. Later the virus can reactivate itself leading to an increasing number of viruses and causing another symptomatic infection.

In the study, researchers tested THC against various herpes viruses including Kaposi’s sarcoma-associated herpes virus (KSHV) and Epstein-Barr virus.

Kaposi’s sarcoma, prevalent among people with AIDS and a common form of cancer in Africa, stems from KSHV.

Cancers of cells from the immune system such as Burkitt’s lymphoma and Hodgkin’s disease are associated with Epstein-Barr virus, a member of the herpes virus family.

In the presence of THC, cells infected with the viruses couldn’t reactivate.

THC may interfere with a gene called ORF50, which is found in these herpes viruses, say the researchers. This gene helps turn on the virus’s machinery that is involved with reactivating the virus; it also helps start viral replication.

Not a Fix for HerpesThe researchers also tested THC on herpes simplex-1, which causes cold sores. It didn’t work.

THC appears to specifically work against herpes viruses that cause these tumors — gamma herpes viruses.

New Drugs Ahead?The findings may lead to the development of new drugs that thwart cancer-causing herpes viruses from reactivating, say the researchers.

Any new antiviral drugs based on THC would not have marijuana’s psychoactive effects.

The next step is testing THC’s benefits on lab animals.

No Pot PrescriptionAccording to a news release, Medveczky says that since THC can suppress the immune system, smoking marijuana might do more harm than good to patients infected with these viruses who often have weakened immune systems.

“Our findings do not recommend that people take pot to prevent or treat cancers associated with gamma herpes viruses,” says Medveczky in the news release.

Marijuana-like drug eludes scientists; As Ricky Williams fights social anxiety disorder with marijuana, scientists are working to take advantage of the plant’s anti-anxiety properties while avoiding the drug’s side effects.

MEDICINE

Ricky Williams’ claim that marijuana helps stave off social anxiety may have scientific merit, but developing a drug that could produce similar results will take years, medical experts said Thursday.

In lab animals, higher levels of cannabinoids — the compounds found in marijuana, and which occur naturally in the brain — sometimes decrease anxiety.

Scientists are trying to develop a drug that would replicate this effect in humans. But even under the rosiest circumstances, it will take nearly a decade to bring the drug to market.

In the meantime, scientists recommend against smoking marijuana to relax.

”One of the reasons humans use marijuana is because it reduces anxiety,” said Cecilia Hillard, a professor of pharmacology at the Medical College of Wisconsin, ”On the other hand, the reason most often cited for stopping using marijuana is that it causes anxiety.”

Daniele Piomelli, the scientist who is developing the cannabinoid-based drug, is more blunt.

”Cannabis is not a very good medicine,” he said.

PROMISING TESTS

A compound Piomelli developed at the University of California at Irvine slows the breakdown of the canabinoids that occur naturally in the brain.

Tests in mice and rats suggest this may reduce anxiety without causing the memory loss, appetite increase and decrease in cognitive function associated with smoking marijuana. Human trials of the compound are slated to begin within two years, Piomelli said.

But drugs that work in mice often fail in people, and several experts said they were not aware of any studies that used marijuana to treat anxiety in humans.

Scientists following federal recommendations have studied marijuana to treat multiple sclerosis, advanced HIV and cancer-related pain. The government has approved a marijuana-like drug to treat chemotherapy-induced nausea.

It’s more difficult for psychiatrists to study marijuana.

”It’s kind of hard to do that research, because of the illegal nature of the drug,” said Dianne Chambless, a University of Pennsylvania psychologist who studies social-anxiety disorder. Chambless said therapy for social-anxiety disorder often helps patients relax by understanding that the whole world is not judging their every move – which might not be the case for a star running back like Williams. ”For most people with social anxiety everybody really isn’t watching you or judging you, but for people in his position, people really are,” she said. ”It’s a very tough position to be in.”

Studies Find High Medical Marijuana Use

Two new Canadian studies conclude that more patients are using marijuana for multiple sclerosis and epilepsy than researchers had thought, Health Day News reported June 8.

One study of 136 epilepsy patients from the University of Alberta Epilepsy Clinic found that nearly half had used marijuana in their lifetime; one in five had used it in the past year; 15 percent had used it in the past month; 13 percent used marijuana more than 48 days a year; and 8 percent used it more than half the days of the year.

“Studies suggest one-third of the general population uses alternative healthcare on a yearly basis,’ said study author Dr. Donald Gross. “Not surprisingly, patients tend to look to alternative therapies in situations where conventional medicine has been unsuccessful, in particular for chronic medical situations. The finding of increased marijuana use in epilepsy patients with longer duration of disease and frequent seizures is consistent with the findings regarding other forms of non-conventional therapies.”

The second study of 205 multiple-sclerosis patients in Halifax, Nova Scotia, found that 20 percent of patients who were medical-marijuana users used the drug more than once a week. Eight patients said they used marijuana more than once a day.

“We have learned several things from these patients,’ said study author Mark Ware of McGill University in Montreal. “Firstly, that pain and spasms are not the only reasons for use, and the effects of marijuana on mood, sleep, and stress are important areas of therapeutic need and should be addressed in clinical trials. Secondly, there is a wide variance in doses used, ranging from single puffs to more than a gram at a time. Clinical trials will also need to include early dose-finding phases and allow for subject variability in dose adjustments.’

He added, “Thirdly, marijuana appears to be well-tolerated, though some subjects experienced intolerable side effects and deterioration of symptoms.’

The studies appear in the June 8 issue of the journal Neurology.
Source:

(One study of 136 patients and the second of 205 can hardly be extrapolated to “one-third of the population”.)

A new study suggests that a form of marijuana that occurs naturally in our lungs may hold the key to fighting all kinds of coughs. An international research team reports the marijuana-related chemical in our lungs controls how our airways expand and contract. They say the findings could lead to new treatments for a variety of respiratory problems, without the addictive qualities of marijuana or codeine, a traditional cough treatment. Scientific studies from the l970 s had shown that delta-9-tetrahydrocannabinol the active ingredient in marijuana improved chronic asthma symptoms for some patients but worsened symptoms in others. Why this happened remained a puzzle. Researchers found that rats and guinea pigs have a chemical called anandamide, which is similar to marijuana’s active ingredient, that causes the dual effect. Anandamide locks onto the surface of lung muscle cells and controls how the lungs respond to various chemical agents that trigger dry coughing. Piomelli found anandamide’s influence depends on how much the lungs already are contracted. For example, if the lungs were already tense, anandamide relaxed them. Yet if the airways were relaxed, the chemical triggered lung constriction.

While seeming paradoxical, Piomelli says anandamide’s true function may be as a regulatory mechanism. “What we want with our muscles is not for them to be completely relaxed or completely contracted. We want them to be always at a certain level of contraction, ready to go further up or further down,” Piomelli says. Anandamide may control that balance. To test that theory, the researchers severed the vagus nerve, which keeps lung muscles contracted to a certain tone, relaxing the lung. When anandamide was given to these animals, the lungs contracted again, while it had no effect on animals with an intact vagus nerve. “It looks like it’s some sort of compensatory factor,” says Piomelli. Piomelli says the findings could lead to new treatments for chronic cough, asthma, hay fever, certain cancers and chronic obstructive pulmonary disease. in animals with a cough produced by capsaicin, the active ingredient in red pepper, giving anandamide orally stopped the cough. It seems that (the researchers] are able to block bronchospasm or the irritation that occurs from capsaicin with anandamide.” Piomelli says anandamide shows promise as an alternative to current cough treatments. “Codeine, the mother of all cough suppressants, acts on the cough centre in the brain,” says Piomelli. “Because it’s a central effect, codeine, which is basically a derivative of morphine ,.. produces sedation, respiratory depression you can even die of codeine intoxication.” However, since anandamide acts on nerves in the trachea and lungs and is quickly eliminated from the body, an inhaler could potentially control the cough without any side effects. Piomelli says don’t smoke marijuana for asthma, because it could trigger lung constriction and make the problem worse.

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 gain 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 Aizheimer’s disease

The drug has already been approved in the US for the treatment of anorexia in patients with HIV/Aids and nausea associated with chemotherapy. In the UK, a THC cannabinoid is also being tested in a trial to see if cannabis-based drugs can ease post-operative pain. In the latest US trial, 48 patients with an average age of 77 who had experienced problems with agitation and had been diagnosed with anorexia were studied. All lived in a dementia unit or a care home. Researchers assessed their cognitive skills and looked at how they coped with daily life. They were then given daily doses of five milligrams of Dronabinol per day, which was gradually increased to 10 mg a day. They were also given anti-psychotic drugs, which reduce delusions and have a calming effect, and at least four other medications to control behaviour. After a month, it was found all the patients had gained weight. Two thirds experienced a significant improvement in agitation.
No adverse events such as falls, seizures or depressions were reported.

Dr Joshua Shua-Haim, medical director at the Meridian Institute for Aging, who led the study, said.. “Our research suggests dronabinol may reduce agitation and improve appetite in patients with Alzheimer’s disease, when traditional therapies are not successful.


Source:Presented at Annual Conference of the International
Psychogeriatric Association in Chicago,2003

The three year CAMS (cannabis in multiple sclerosis) trial, involving more than 600 patients in the United Kingdom, has yielded no definitive verdict on whether the drug can ease the symptoms of multiple sclerosis. The study, funded by the Medical Research Council, was published in last week’s issue of the Lancet ( 2003;362: 1517-26)
Fifteen weeks’ treatment with oral capsules containing either whole cannabis extract or tetrahydrocannabinol (THC), the drug’s principal active ingredient, did not produce a significant improvement in spasticity as measured by the widely used Ashworth scale. But in face to face interviews, patients assigned to the treatment arm of the double blinded trial were more likely than those receiving placebo to report a subjective improvement in symptoms. The participants reported significant improvements in pain, sleep quality, spasms, and spasticity, though not in irritability, depression, tiredness, tremor, or energy. The researchers found that patients taking the cannabis derivative showed an improvement in the time taken to walk 10 metres.

The proportion of patients reporting improvements in spasticity was 61% in the arm receiving cannabis extract (n=121, 95% confidence interval 55% to 68%),
60% in the arm receiving THC (n=108, 53% to 67%),
and 46% (n=91, 39% to 53%) in the placebo arm.

The lead researchers, John Zajicek, consultant neurologist at Plymouth Hospitals NHS Trust, and Professor Alan Thompson, consultant neurologist at the National Hospital for Neurology and Neurosurgery, London, cautioned that about three quarters of the patients given cannabis had guessed they were taking active medication, and half of those receiving placebo had guessed that they were not receiving cannabis.

Dr Zajicek said: “The primary aim of the trial was to measure, as objectively as possible, the actual physical changes in limb spasticity in MS patients, and we found no evidence of this. “Although we based the study around spasticity, we also wanted to capture any treatment effects among the other important symptoms described by people with MS. When patients were asked to describe how they felt that their symptoms,including spasticity, had been affected, the picture was very different. They felt some of the impact of their painful and distressing symptoms had been eased. “We did see a high placebo effect in this trial and it may be indicative of how much patients gain by taking part in clinical trials, irrespective of the treatment they are given. Patients experienced very few side effects from the treatments, and, given that how a patient feels is an important part of improving health, cannabis based treatments may be of benefit to some patients.”

Mike Barnes, professor of neurological rehabilitation at the University of Newcastle, said: “The results of this study are mixed, but the positive aspects undoubtedly outweigh the negatives. It is my hope that in the near future, people with MS will have access to cannabis derived medicines on the NHS.”


Source:Issue of the Lancet 15th Nov 2003.

A major clinical trial in Britain finds that marijuana-based pills may have more of a psychological than physiological effect on patients with multiple sclerosis (MS).
According to the three-year study, which involved 630 MS patients, marijuana had no effect on muscle stiffness or spasticity, but most patients reported that it reduced their symptoms and improved their mobility.

“The primary aim of the trial was to measure, as objectively as possible, the actual physical changes in limb spasticity in MS patients, and we found no evidence of this,” said Dr John Zajicek of the University of Plymouth, who led the study.

However, Zajicek said that additional research is needed because the study’s subjective results “provide some evidence that cannabinoids could be clinically useful in treatment of symptoms of MS.” He added, “The results of this study present an interesting and complex picture of the value of cannabis-derived medicines for treating MS.”
The study’s findings are published in the Nov. 8, 2003 issue of The Lancet.


Source:The Times of London reported Nov7 2003

A new study shows, for the first time, that the release of the body’s own marijuana-like compounds is crucial to stress-induced analgesia – the body’s way of initially shielding pain after a serious injury.

The work, led by scientists at the University of Georgia and the University of California, Irvine, may yield a target for new drug therapies that will completely bypass the current arguments over the use of medical marijuana. In theory, the new research makes it possible to design a pill that will have the same pain relieving effects as smoked marijuana, but through an indirect mechanism that could also reduce unwanted psychoactive side effects and not have the same political baggage.

“There is no prescription or over the counter drug that allows us to manipulate the level of the brain’s marijuana-like compounds,” said Andrea Hohmann, a neuroscientist in the department of psychology at the University of Georgia and co-author of the paper. “This is the first time anyone has shown that one of the body’s naturally occurring cannabinoids, a compound known as 2-AG, has anything to do with pain regulation under natural conditions.”

The study was published today in the journal Nature.

Hohmann’s co-author, Daniele Piomelli at the University of California-Irvine, is the discoverer of a compound that blocks the breakdown of this marijuana-like compound called 2-AG, and it is that blocking compound, patented by UC-Irvine, that could become the new drug of choice for those suffering from pain or stress conditions. Importantly, it would not require people to smoke marijuana to obtain relief or wrestle with the legal issues surrounding the drug.

Others from UGA involved in the study include faculty members Philip Holmes and Jonathon Crystal and students Richard Suplita, Nathan Bolton and Mark Neely.

Authors from UC-Irvine include Darren Fegley and Regina Mangieri, in addition to Piomelli. Other co-authors are Jocelyn Krey and Michael Walker from Brown University; Andrea Duranti, Giorgio Tarzia and Andrea Tontini from the University of Urbino Carlo Bo in Italy; and Marco Mor from the University of Parma, also in Italy. All were crucial in designing and synthesizing the enzyme inhibitor.

Scientists have long known that injured athletes or even gunshot victims have a period of time in which the body’s pain reaction is delayed. This effect is called “stress-induced analgesia.” By the mid-1990s, researchers had targeted the sites of action of the brain’s naturally occurring marijuana-like compounds as having a crucial role in blocking pain, but no one understood the conditions in which these compounds were released to block pain.

Researchers along the way found out there are two kinds of stress-induced analgesia mechanisms, opioid and nonopioid (or “opioid independent”).

Hohmann and colleagues discovered that the opioid-independent form was produced by release of the brain’s own marijuana-like compounds.

“We showed that cannabinoid receptors were involved in this remarkable phenomenon,” said Hohmann, “because blocking the receptors where marijuana acts virtually erased this opioid-independent form of stress analgesia.”

If this is true, was there a compound that could also prolong the action of these compounds, making them work better? The answer lay in Piomelli’s pioneering work on inhibitors that break down the brain’s own marijuana-like compounds.

“If we design chemicals that tweak the levels of these transmitter substances in the brain,” said Piomelli, “we might be able to boost their normal effects.”

When rats used in Hohmann’s study were given the compound developed by Piomelli and his collaborators at the University of Urbino Carlo Bo and the University of Parma, it increased stress-induced analgesia dramatically, proving the connection between pain suppression and the release of these marijuana-like compounds.

The enzyme that inhibits the formation of the naturally occurring marijuana-like compound 2-AG is called monoacylglycerol lipase, and it is this enzyme that could be a target for therapeutic drug intervention to help those in pain.

A new drug increasing the body’s own marijuana-like compounds could work similar to something like Prozac, which blocks the body’s reuptake of the compound serotonin, causing it to be active longer, Hohmann said.

Apparently, several parts of the brain are involved in the effect, most notably a structure in the midbrain known as the periaqueductal gray. In this region, stress causes the release of the naturally occurring marijuana-like compounds in the brain.

A drug derived from the new research would likely be more effective and specific than smoked marijuana, said Hohmann.

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

Cannabinoids have been suggested to have therapeutic value as analgesics and in various conditions, including migraine headaches, nausea and vomiting, wasting syndrome and appetite stimulation in HIV-infected patients, muscle spasticity due to multiple sclerosis or spinal cord injury, movement disorders such as Parkinson’s disease, epilepsy, and glaucoma. When new therapeutic indications are suggested, two major factors should be taken into account: what are the adverse effects of the treatment and how does its effectiveness compare with that of existing alternatives?
In this week’s issue two high quality systematic reviews shed light on the therapeutic potential of cannabinoids in the management of pain and the nausea and vomiting induced by chemotherapy. Campbell et al sought and examined all randomised controlled trials that. compared the efficacy and safety of cannabinoids with those of conventional analgesics.   The nine trials included 222 patients, of whom 128 had cancer (five studies), two chronic non malignant pain (two studies, one patient per trial), and the rest postoperative pain. Cannabinoids were no more effective than codeine in controlling acute and chronic pain and they had undesirable effects in depressing the central nervous system. These studies are mostly from 1970s. Since then we have learnt to use non-steroidal anti-inflammatory analgesics alone and in combination with opioids in both cancer related and postoperative pain. There is thus no need for cannabinoids for these indications.
In chronic non cancer pain, however, we do need more effective analgesics than those currently available. Cannabinoids have anti-inflammatory effects, but it is difficult to believe that they would beat the anti-inflammatory drugs available today. Neuropathic pains, particularly those with spastic components are one area where cannabinoids may have potential. Future research may provide us with better cannabinoid compounds with potential new therapeutic applications. However, the current information is that the adverse effects of cannabinoids outweigh their effectiveness. About a year ago in the BMJ Strang et al asked for a more informed debate about the therapeutic use of cannabinoids, and this week’s two systematic reviews contribute to this debate. On current evidence cannabinoids can be recommended only for use in controlled clinical trials in carefully selected conditions for which there is no effective treatment. The launch of the first large multicentre trial on cannabis in the control of pain and tremors in multiple sclerosis is the first step on this way.

This study  examined the anti-emetic (anti-nausea) properties of the cannabinoid, Cannabidiol (CBD) which, as opposed to THC, has no psychoactive properties. The authors state that the results of this study are the first to demonstrate that the non-psychoactive component of marijuana [cannabis], cannabidiol [CBD], and its synthetic analog, cannabidiol dimethylheptyl [CBD-DMH], interfere with nausea and with condition nausea in rats.

In findings that contradict earlier research, a team of scientists reports that marijuana does not improve the often painful symptoms of multiple sclerosis (MS). Their small study found that a synthetic form of tetrahydrocannabinol (THC), the active ingredient in marijuana, and a plant extract were no better at relieving severe spasticity or muscle contraction compared with an inactive placebo.  Patients’ muscle tone improved while taking marijuana but their self-reported ratings on a scale measuring their overall disability declined.
And while marijuana was found to be safe, some patients experienced mild side effects such as headache and dizziness, particularly after taking the plant extract, according to the report in the May 14th issue of Neurology.
MS is a neurodegenerative disorder in which the slow destruction of myelin – the thin, protective coating that insulates nerve fibres in the brain and spine – can lead to numbness, muscle weakness and stiffness, impaired vision and coordination problems.
A previous study in mice indicated that marijuana might help to relieve these painful spasms.  However, the amount of the drug used in mice would not be tolerated in humans, the researchers explain.  While their study included just 16 patients, it is the largest randomized, controlled clinical trial to investigate the use of marijuana to treat MS.
“Compared to placebo, neither THC nor plant-extract treatment reduced spasticity,” Dr. Joep Killestein from the VU Medical Centre in Amsterdam, the Netherlands, told Reuters Health.  “Even though the sample size is too small to be conclusive, our study was the largest and longest completed study addressing cannabinoid therapy in MS so far.”
The authors suggest that the dose used in the study may have been too low to show any beneficial effects, or giving the drug in capsule form may have slowed its absorption.
“THC is absorbed reasonably well from the gut, but the process is slow,” Killestein and colleagues explain.
In the study, patients took an inactive pill (placebo), a marijuana plant extract or synthetic THC for 4 weeks. The researchers measured muscle tone and overall disability, and patients responded to questions assessing their quality of life.

Cannabinoid  has no impact on spasticity associated with MS

In a report published in the scientific journal Movement Disorders, Vol. 17, No. 1.2002, Fox and associates.A Randomised, Double-Blind, Placebo-Controlled crossover study designed to see whether Nabilone would be effective in the treatment of muscle spasm (dystonia) associated with multiple sclerosis found no significant reduction in dystonia following treatment with nabilone”
Though the researchers seemed to have expected more favorable results, these results are consistent with a controlled, double-blind study done in 1995 on balance and coordination of MS patients, using smoked Marijuana Although the participants claimed to have relief from symptoms, high tech monitoring equipment showed that smoking marijuana actually made it worse.

Study shows MS patients further impaired by smoking Low-THC marijuana

‘Greenburg et al, in their paper in Clinical Pharmacology and Therapeutics Vol. 55:324-328,1994, performed a double-blind randomized, placebo-controlled study of inhaled marijuana smoke on balance and coordination responses in ten adult patients with spastic multiple sclerosis, and normal volunteers who were matched for age, sex, and weight. A sophisticated computer-controlled video system was used to identiFY responses. The study showed that marijuana smoking enhanced the abnormalities already present in MS patients and that smoking just one marijuana cigarette containing 1.5% delta-9 THC increased the objective errors in these responses. The authors concluded that marijuana smoking impairs coordination and balance in patients with spastic MS.

Nation’s Youth Turning Away from Marijuana, as Perceptions of Risk Rise; Most Adults with Substance Abuse Problems Are Employed

Secretary Tommy G. Thompson announced today that there is a five percent decline in the number of American youth between the ages of 12 and 17 who have ever used marijuana. Current use of marijuana plummeted nearly 30 percent among 12 and 13 year olds. The findings were included in the 2003 National Survey on Drug Use and Health released today at the annual Recovery Month press conference.

The findings, released by HHS’ Substance Abuse and Mental Health Services Administration (SAMHSA), show that while overall, the change in the category “current use of any illicit drug” was not statistically significant, the use of some drugs decreased sharply. For youth, 12-17, past year use of Ecstasy and LSD dropped precipitously, by 41 percent for Ecstasy and 54 percent for LSD. Overall, 19.5 million Americans ages 12 and older, 8 percent of this population, currently use illicit drugs. The data indicate that of the 16.7 million adult users (18 and older) of illicit drugs in 2003, about 74 percent were employed either full time or part time.

SAMHSA Administrator Charles Curie said: “Employers who think alcohol and drug abuse will never be a problem in their workplace need to consider that more than three quarters of adults who have serious drug and or alcohol problems are employed. Encouraging employees to find help when they need it can result in fewer accidents and fewer workers absent on Monday morning. It may even save an employee’s life, family, or job. Creating a drug-free workplace program or enhancing an existing program can lead to a healthier, more productive work force and be an important part of solving one of our nation’s most persistent problems.”
The survey found that of the 19.4 million adults (age 18 and over) characterized with abuse of or dependence on alcohol or drugs (19.4 million) in 2003, 14.9 million (77 percent) were employed either full or part time. This amounts to over ten percent of full-time workers as well as over ten percent of part-time workers.

Marijuana continues to be the most commonly used illicit drug, with 14.6 million current users (6.2 percent of the population). The study shows that there were an estimated 2.6 million new marijuana users in 2002. About two thirds of these new users were under age 18, and about half were female.

An important positive change detected by the survey was an increase in the perception of risk in using marijuana once a month or more frequently. Both youth and young adults reported a significant increase in their awareness of the risks of smoking marijuana. Particularly striking was the 20 percent decline between 2002 and 2003 in the number of youth that were “heavy users” of marijuana (those smoking either daily or 20 or more days per month). Perceived availability of the drug also declined significantly among youth.

The results of this year’s survey demonstrate that anti-drug messages inside and outside of school, participation in religious and other activities, parental disapproval of substance use and positive attitudes about school are linked to lower rates of youth marijuana use. For example, those exposed to anti-drug messages outside of school had rates of current marijuana use that were 25 percent lower than those not reporting such exposure (7.5 percent vs. 10.0 percent). Youth who believe that their parents would “strongly disapprove” of marijuana had use rates fully 80 percent lower than those who reported that their parents would not “strongly disapprove” (5.4 percent vs. 28.7 percent).

The numbers of binge and heavy drinkers did not change between 2002 and 2003. About 54 million Americans ages 12 and older participated in binge drinking at least once in the 30 days prior to being surveyed. These people had five or more drinks on one or more occasion in the past month. There were 16.1 million heavy drinkers, who had five or more drinks on five or more occasions in the past month. The highest prevalence of binge and heavy drinking in 2003 was among young adults ages 18-25, with both binge and heavy drinking at their peak at age 21.

There were 10.9 million drinkers under legal age (ages 12-20) in the month prior to the survey interview in 2003. This is 29 percent of this age group. Of these, nearly 7.2 million (19.2 percent) were binge drinkers and 2.3 million (6.1 percent) were heavy drinkers.

Drunk driving declined from the 2002 survey, but drugged driving remained similar to that reported in the 2002 survey. An estimated 13.6 percent of persons aged 12 or older drove under the influence of alcohol at least once in the 12 months prior to their interviews (32.3 million people) in 2003, a decrease from 14.2 percent (33.5 million) in 2002. An estimated 10.9 million persons reported driving under the influence of an illicit drug during the past year. This is 4.6 percent of the population ages 12 and older.

Against the backdrop of generally good news, the non-medical lifetime use of prescription pain relievers showed a five percent increase for the population 12 and older, with young adults (18-25) experiencing a 15 percent increase in lifetime, as well as current use. Over all, current use of prescription pain relievers non-medically remained stable from 2002-2003. There was a statistically significant increase in lifetime non-medical use of Vicodin, Lortab, or Lorcet from 13.1 million to 15.7 million. Percocet, Percodan, or Tylox misuse in a lifetime increased from 13.1 million to 15.7 million people. Hydrocodone lifetime non-medical use increased from 4.5 million people to 5.7 million; OxyContin lifetime misuse increased from 1.9 million people to 2.8 million; non-medical methadone use increased from 0.9 million to 1.2 million; and non-medical use of Tramadol increased from 52,000 to 186,000 from 2002 to 2003.

Estimates for persons who currently used psychotherapeutic drugs taken non-medically are similar in 2003 to estimates for 2002. There were 6.3 million persons currently using prescription medications non-medically in 2003, about 2.7 percent of the population ages 12 or older. Of these, an estimated 4.7 million used prescription pain relievers; 1.8 million used tranquilizers; 1.2 million used stimulants, including methamphetamine; and 0.3 million used sedatives.

There were an estimated 2.3 million persons who currently used cocaine in 2003, 604,000 of whom used crack. One million persons used hallucinogens, including LSD, PCP, Ecstasy and other substances, and 119,000 people were estimated to currently use heroin. These projections are all similar to estimates for these drugs in 2002. But, past month inhalant use among youth ages 16 or 17 increased from 0.6 percent in 2002 to 1.0 percent in 2003. Methamphetamine use did not change significantly between 2002 and 2003, with 600,000 past month users each year.

The survey reported 21.6 million Americans in 2003 classified with dependence on drugs, alcohol, or both (9.1 percent of the population ages 12 and older). Over 20 million persons needed but did not receive treatment for an alcohol or drug problem in 2002 and 2003, but the number receiving specialized substance abuse treatment declined from 2.3 million in 2002 to 1.9 million in 2003. Of the 20 million people in need of treatment in 2003 who did not receive it, about 1 million recognized that need. Only 273,000 tried to obtain treatment and were unable to access it. The other 764,000 made no effort to get treatment.

The report found a major correlation between serious mental illness and substance dependence and abuse. In 2003, an estimated 4.2 million adults suffered from serious mental illness and substance dependence or abuse in the past year. Adults who used illicit drugs were more than twice as likely to have serious mental illness, compared to adults who did not use an illicit drug. In 2003, 18.1 percent of adult past-year users of illicit drugs had serious mental illness that year, while the rate was 7.8 percent among adults who had not used an illicit drug. Among adults with substance dependence or abuse, 21.6 percent had serious mental illness, compared to 8.0 percent among those who did not have dependence or abuse.

Among adults with serious mental illness in 2003, 21.3 percent (4.2 million people) were dependent on or abused alcohol or illicit drugs. The rate among adults without serious mental illness was only 7.9 percent.

Tobacco use rates in the past month remained essentially the same from 2002 to 2003, with 70.8 million people reporting current use of a tobacco product. Of these, 60.4 million smoked cigarettes in the past month, 12.8 million smoked cigars, 7.7 million used smokeless tobacco and 1.6 million smoked tobacco in pipes. There were significant declines in past year and lifetime cigarette use among youths ages 12 to 17 between 2002 and 2003, and a decline in the rate of cigarette smoking among young females.

The 2003 survey is based on interviews with 67,784 respondents ages 12 and older who were interviewed in their homes. This includes persons residing in dormitories or homeless shelters. Not included in the survey are persons on active military duty, in prisons, or other institutionalized populations or people who are homeless but not in shelters. Lifetime use is defined as ever used a substance in one’s lifetime. Past year use is having used the substance at least once in the past 12 months. Current use is use in the past 30 days.

Marijuana indicators continued upward trends that began in the early 1990s. In 2002, however, marijuana ED mentions stabilized, after rising from almost 600 to 1,200 from 1999 to 2001. When found as the sole drug in a hospital ED situation, patients typically present with symptoms of a panic or anxiety attack.

As in past years, marijuana precipitated more admissions into addiction treatment programs than any other illicit drug in the Twin Cities in 2003. Overall, one out of five (22.8 percent) people entering addiction treatment programs reported marijuana as the primary substance problem, compared with only 8 percent in 1991. Most (77.3 percent) were males, and 68.3 percent were white. For many, it was the first treatment experience (44.2 percent), which can reflect a relatively short abuse history. The average age of first marijuana use was 13.7 years.

Marijuana was overwhelmingly the primary drug among adolescents and young adults in treatment. Among treatment admissions under age 18, a whopping 73.2 percent reported marijuana as the primary substance problem, and among youth age 18 – 25, 34.8 percent. In contrast, among patients age 26 to 34, 14.6 percent reported marijuana as the primary substance problem, and among patients 35 and older, only 4.5 percent.

In 2003 in Minneapolis, 48.3 percent of adult male arrestees tested positive for marijuana. Nationwide, it ranged from a high of 54.9 percent in Oklahoma City, to a low of 30.9 percent in Honolulu and 31.9 percent in Salt Lake City.  The median across all cities was 44.1 percent.

Marijuana, readily available according to multiple sources, sold for $5 per joint, and could be purchased by any metropolitan area middle school student. Standard, commercial grade marijuana sold for $50 per quarter ounce, $150–$175 per ounce, and $600–$900 per pound. Higher potency “BC Bud” from British Columbia was increasingly available and sold for $100 per quarter ounce and up to $600 per ounce.

Marijuana joints that are dipped in formaldehyde, which is often mixed with phencyclidine (PCP), are known as “wets,” “wet sticks,” “water,” or “wet daddies.” Marijuana joints containing crack cocaine are known as “primos.”

A short article on two Canadian surveys (self-reporting by users) showing that many epilepsy and multiple sclerosis patients self-medicate with marijuana. The author states that social and legal obstacles have hampered clinical advances in the study of cannabis sativa for medical treatment of a variety of neurological symptoms.

“Cannabis use may be occurring in these settings but there is little scientific evidence of its effectiveness for neurological symptoms. No controlled data lend support to its use for epilepsy. Small studies in multiple sclerosis have shown variable results against spasticity and no effect for tremor. A large [660 subjects] randomized trial comparing oral THC, oral cannabis extract, and placebo showed no effect on spasticity (measured by the Ashworth scale), despite participants reporting fewer spasms and less pain.

“Some of the many variables facing clinical investigators include different drug formulations (cannabis extracts, synthetic cannabinoids), uncertain dose, and multiple methods of delivery (some patients insist cannabis is effective only when smoked). Difficulties in trial design include a strong placebo effect and maintenance of double-blind status. A recurrent theme in multiple sclerosis trials is no effect on an objective primary outcome despite subjective improvement. Valid, reliable, and responsible objective measures are needed.

The Canadian survey data, Wingerchuk states, “suggest that people with recreational drug experiences are more likely to use cannabis for neurological symptom relief, and are at greater risk of becoming active or dependent users than the general population.”

Although Wingerchuk indicates that “hazards of regular cannabis use, such as persistent mood disorders and cognitive dysfunction, should be considered,” no mention is made of the many social, economic and criminal hazards associated with marijuana use.

The question of whether a clinically significant marijuana (cannabis) withdrawal syndrome exists remains controversial. In spite of the mounting clinical and preclinical evidence suggesting that such a syndrome exists (Beardsley et al., 1986; Budney et al., 2001; Holson et al., 1989; Huestis et al., 2001), the DSM-IV does not include marijuana withdrawal as a diagnostic category. The clinical syndrome has been characterized by restlessness, anorexia, irritability and insomnia that begin less than 24 hours after discontinuation of marijuana, peak in intensity on days 2 to 4, and last for seven to 10 days (Budney et al., 1999; Haney et al., 1999; Mendelson et al., 1984).

The question of whether this syndrome is clinically significant is important, not only because marijuana is the most commonly used illicit drug in the United States (Johnston et al., 2001), but also because marijuana has been shown to produce dependence at rates comparable to other drugs of abuse (Kandel et al., 1997; Kessler et al., 1994) and because relapse rates among individuals seeking treatment for marijuana dependence are similar to those with other drugs of abuse (Budney et al., 1998; Stephens et al., 1993). Furthermore, many violent crimes are committed by individuals undergoing withdrawal from drugs of abuse, including marijuana (Kouri et al., 1997; Peters and Kearns, 1992). If a clinically significant marijuana withdrawal syndrome does exist, the omission of this syndrome from the DSM-IV might contribute to the perception that behavioral or pharmacological treatment regimens for marijuana dependence are not necessary.

We conducted two studies in our laboratory to determine whether abstinence from marijuana after long-term use results in withdrawal symptoms, to identify those symptoms and to quantify their severity (Kouri and Pope, 2000; Kouri et al., 1999). The first study focused specifically on whether abrupt discontinuation of marijuana following chronic use results in changes in aggressive behavior (Kouri et al., 1999).

To measure aggressive behavior, we used the Point Subtraction Aggression Paradigm (PSAP). This computer test has been used to detect changes in aggressive responses following acute administration of a number of drugs, and its external validity has been demonstrated in a number of studies of male and female parolees with histories of violent behavior (Cherek and Lane, 1999; Cherek et al., 1996).

Subjects in our study were long-term heavy users of marijuana who reported a history of at least 5,000 separate episodes of marijuana use in their lifetime (the equivalent to smoking once per day for 13.7 years), were smoking at least once daily at the time of recruitment and met DSM-IV criteria for marijuana dependence without meeting criteria for a current Axis I disorder. Subjects were excluded if they reported that they had used another class of drugs more than 100 times in their lifetimes or had consumed more than five alcoholic drinks per day continuously for one month or more in their lifetimes. The controls were composed of two groups: 1) individuals who had not smoked marijuana more than 50 times in their lives and had not smoked more than once per month in the last year and 2) individuals who had formerly smoked marijuana on a daily basis but who had not smoked more than once per week during the last three months. The rationale for using infrequent or former smokers rather than marijuana-naive subjects as controls was to minimize possible confounding variables that might differentiate individuals who had never tried marijuana from those who had. We based this decision on data from our laboratory demonstrating that heavy marijuana users do not differ from occasional users in a wide range of demographic and psychiatric measures (Kouri et al., 1995).

During the study, subjects were required to abstain from smoking marijuana and using any other drugs for 28 consecutive days. To verify abstinence, subjects had to come to the laboratory every day to provide supervised urine samples that we analyzed quantitatively for tetrahydrocannabinol (THC) metabolites. We measured aggressive responses with the PSAP on study days 0 (before abstinence), 1 (after 24 hours of abstinence), 3, 7 and 28.

Subjects were told they would be playing a computer game against an anonymous same-sex subject from the study. In fact, however, this second subject was actually a computer. During the course of each 20-minute computer session, subjects had the option of pressing one of two buttons on the PSAP response panel (labelled “A” or “B”). Pressing button A resulted in the accumulation of points that were exchanged for money at the end of the study. Pressing this button was defined as a non-aggressive response. By pressing button B, subjects could subtract points from the fictitious opponent. Points taken from the opponent, however, were not added to the subject’s counter, and pressing button B was defined as an aggressive response. Aggressive responding was provoked by random subtractions of the subject’s points, which were attributed to the fictitious opponent.

On study day 0 (before marijuana abstinence) and study day 1 (24 hours of marijuana abstinence), the current marijuana users did not differ from past heavy users or light users in the number of aggressive or non-aggressive responses they made. However, current marijuana users were significantly more aggressive on days 3 and 7 of marijuana abstinence compared to their pre-withdrawal levels of aggression and compared to the controls. By day 28, the number of aggressive responses from the current marijuana users was not different from their pre-withdrawal baseline levels or the controls (Figure). These data demonstrate that abstinence from marijuana after chronic use is associated with increases in aggressive responding following provocation. Specifically, during the first week of abstinence, current marijuana users displayed levels of aggression that were significantly higher than before abstinence and higher than the levels displayed by matched controls. Interestingly, the increases in aggressive responding followed a specific time course and then returned to pre-withdrawal levels after 28 days of abstinence. The transient nature of these changes is consistent with other reports of marijuana withdrawal.

The second study was designed to further characterize symptoms of marijuana withdrawal and to quantify their magnitude (Kouri and Pope, 2000). We used the same study entry criteria as in the first study and subjects were required to come to the laboratory every day to provide urine samples and to fill out a daily diary.

The items assessed in the daily diaries were: mood, appetite, sleep, anxiety, irritability, physical tension or agitation, physical symptoms, ability to concentrate, desire to use marijuana, and desire to resume using marijuana at the end of the study. The questions were presented on a 10-point Likert scale with the qualifiers “extremely low” at the zero end of the scale and “extremely high” at the 10-point end of the scale. We obtained pre-withdrawal baseline levels for all of the diary items via a personal interview with each subject before the beginning of the withdrawal period.

Thirty current marijuana users and 30 controls (16 former heavy users and 14 light users) participated in the study. Before the beginning of the abstinence period, the current marijuana users were not different from the former users or the light users on any of the items assessed in the diaries except for the ability to concentrate item. The current users reported a lower ability to concentrate than the controls. Interestingly, the former heavy users were not different from the light users on any of the diary scores during the course of the study. In contrast, the current users reported increases in irritability, anxiety, physical tension and physical symptoms, and decreases in mood and appetite starting on day 1 and peaking between days 7 and 10 of marijuana abstinence.

It is important to note that although, as a group, the current marijuana users experienced an increase in withdrawal symptoms compared to the controls, only 60% of the subjects in the current users group reported a change in symptoms of at least three points in magnitude. The fact that 40% of subjects who had used marijuana regularly for an average of 22 years did not report experiencing severe withdrawal symptoms during abstinence might suggest that physical dependence on marijuana is not as strong as that observed with other drugs of abuse. This may be due, at least in part, to the long half-life of THC. However, many subjects reported that when trying to remain abstinent in the past, the presence of withdrawal symptoms had played an important role in their relapse. Thus, alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana use in chronic users.

Another significant finding is that after 28 days of marijuana abstinence, all of the symptoms returned to pre-withdrawal levels except for irritability and physical tension. It is possible that these two symptoms remained slightly elevated because they represented a premorbid characteristic of the current users and were not a result of marijuana withdrawal. If this is the case, the fact that the former users did not have elevated scores on these two items may reflect a characteristic that potentially differentiates individuals with a history of heavy marijuana use who have successfully stopped from individuals who continue to smoke regularly.

Taken together, the data from these two studies provide further evidence of the existence of a marijuana withdrawal syndrome. An important aspect of both of our studies is that we used two control groups: 1) former heavy marijuana users and 2) individuals who had rarely smoked marijuana during their lives.

It is noteworthy that these control groups were indistinguishable from one another in diary scores or number of aggressive responses on the PSAP, whereas both were significantly distinguishable from the current marijuana users. This observation argues that the elevated diary scores and aggressive responses of the current marijuana users were attributable to marijuana withdrawal, rather than a mere history of marijuana use or some other aspect of subject selection or study design. Future studies should focus not on whether a marijuana withdrawal syndrome exists but rather on determining the clinical significance of this syndrome and the role withdrawal symptoms play in perpetuating marijuana use.

Acknowledgement
These studies were supported by NIDA grants DA10346, DA03994, DA00343. Dr. Kouri is assistant profesor of psychiatry at Harvard Medical School in Boston, Mass.
References
Beardsley PM, Balster RL, Harris LS (1986), Dependence on tetrahydrocannabinol in rhesus monkeys. J Pharmacol Exp Ther

Today, the Florida Department of Law Enforcement (FDLE) released the Florida Medical Examiners Commission’s Report on Drugs Identified in Deceased Persons. The report contains information compiled from autopsies performed by medical examiners across the state in 2003. During that period there were approximately 170,000 deaths. According to the report, 6,767 individuals examined had drugs in the system.

Medical Examiners collected information on the following drugs: Ethyl Alcohol, Amphetamines, Methamphetamines, MDMA (Ecstasy), MDA, MDEA, Alprazolam, Diazepam, Flunitrazepam (Rohypnol), other Benzodiazepines, Cannabinoids, Carisoprodol/Meprobamate, Cocaine, GHB, Inhalants, Ketamine, Fentanyl, Heroin, Hydrocodone, Hydromorphone, Meperidine, Methadone, Morphine, Oxycodone, Propoxyphene, Tramadol, and Phencyclidine (PCP).

The report reveals a decrease in the incidences of Heroin in 2003 when compared with 2002. This decrease includes cases in which the drug levels found during the exams were both lethal and non-lethal. In addition, the report indicates the three most frequently occurring drugs found in decedents were Ethyl Alcohol (3,467), all Benzodiazepines (1,794), and Cocaine (1,614). The drugs that caused the most deaths were Cocaine, all Benzodiazepines, Methadone, Oxycodone, Ethyl Alcohol, Heroin, Alprazolam, and Morphine.

The three drugs that were the most lethal, meaning more than 50 percent of the deaths were caused by the drug when the drug was found, were Heroin (88 percent), Fentanyl (63 percent), and Methadone (60 percent). The report also reveals that excluding newly tracked prescription drugs, prescription drugs of Benzodiazepines, Hydrocodone, Methadone, and Oxycodone continued to be found more often than illicit drugs in both lethal (60 percent) and non-lethal (55 percent) levels during 2003.

“This report shows that with few exceptions, both illicit and prescription drugs persist in being a continuing and increasing danger to the citizens of the State of Florida,” said FDLE Commissioner Guy Tunnell. “While heroin deaths have decreased over the past year, most of the other illicit and prescription drug deaths remain at an alarming level for the year, although decreases are noted during the second half of the year.”

“The results from this report are evidence of the immense danger associated with drug abuse and more specifically prescription drug abuse,” said Jim McDonough, Director of the Florida Office of Drug Control. “Far too many Floridians are dying from prescription drugs. To address this problem Florida will continue to strengthen its efforts in the areas of prevention, treatment, and law enforcement in order to reduce the unacceptable amount of deaths that result from the abuse of prescription drugs.”

The present study investigated whether maternal cigarette smoking and marijuana use during pregnancy were associated with an increased risk of initiation and daily/regular use of such substances among one hundred fifty-two 16- to 21-year-old adolescent offspring. The participants were from a low risk, predominately middle-class sample participating in an ongoing, longitudinal study. Findings indicated that offspring whose mothers reported smoking cigarettes during their pregnancy were more than twice as likely to have initiated cigarette smoking during adolescence than offspring of mothers who reported no smoking while pregnant. Offspring of mothers who reported using marijuana during pregnancy were at increased risk for both subsequent initiation of cigarette smoking (OR=2.58) and marijuana use (OR=2.76), as well as daily cigarette smoking (OR=2.36), as compared to offspring of whose mothers did not report using marijuana while pregnant. There was also evidence indicating that dose-response relationships existed between prenatal exposure to marijuana and offspring’s use of cigarettes and marijuana. These associations were found to be more pronounced for males than females, and remained after consideration of potential confounds. Such results suggest that maternal cigarette smoking and marijuana use during pregnancy are risk factors for later smoking and marijuana use among adolescent offspring, and add to the weight of evidence that can be used in support of programs aimed at drug use prevention and cessation among women during pregnancy.
Porath AJ, Fried PA. Department of Psychology, Carleton University, Ottawa, Ontario, Canada K1S 5B6. aporath@ccs.carleton.ca

Source: PMID: 15734278 [PubMed – indexed for MEDLINE

Club drug hinders long-term recollection, while marijuana limits short-term memory By Steven Reinberg.

Adding to an already hefty body of evidence a new study finds ecstasy users suffer from long-term memory problems while marijuana smokers struggle with short-term memory lapses. The study found those who regularly took the popular club drug ecstasy were 23% more likely to report problems with remembering things than people who are drug-free. And marijuana smokers reported up to 20% more memory problems than non-users.

“There is a lot of evidence that ecstasy users are likely to use other drugs, including cannabis. Users of both substances may therefore be vulnerable to a myriad of memory afflictions, which may represent a time bomb of cognitive problems for later life,” says lead researcher Jacqui Rodgers Rodgers is with the School of Neurology, Neurobiology and Psychiatry at the University of Newcastle in England. The findings appear in the January issue of the Journal of Psychopharmacology.

Collecting data through a Web site, Rodgers and colleagues used a standard questionnaire to assess drug use among the 763 individuals who responded. They also looked closely at a subgroup of 81 ‘typical’ ecstasy users who had taken the drug at least 10 times.

The people were asked about their short-term and long-term memory. They were also asked to rank the probability of scenarios such as finding a television story difficult to follow or forgetting to pass a message on to someone.

The group of ‘typical’ ecstasy users reported their long-term memory to be 14% worse than the 483 people who had never taken ecstasy, and 23% worse than the 242 non-drug users.

“We found that people who regularly take ecstasy report experiencing long-term memory difficulties, and are 23% more likely to report problems with remembering things than nonusers,” she says.

“We also found that people who use cannabis regularly report up to 20% more memory problems than non-users, in terms of short-term memory performance,” Rodgers adds.

Rodgers team also noted the number of mistakes the people made when titling out the questionnaire.

Users of ecstasy – also known as MDMA –made 21% more mistakes on the questionnaire compared with non-ecstasy users and 29% more mistakes than people who did not take drugs at all.

These differences were the same for men and women.

“Our findings may help drug services in the U.K. and elsewhere explain the potential consequences of use, so that people can make an informed decision as to whether to take ecstasy or not,” Rodgers says.

“Users may think that ecstasy is fun and that it feels fairly harmless at the time. However, our results show slight but measurable impairments to memory as a result of use, which is worrying,” she notes. “It’s equally concerning that we don’t realy know what the long-term effects of ecstasy use will be, as it is still a poorly understood drug,” Rodgers adds. “The findings also suggest that ecstasy users who take cannabis are suffering from a double whammy, where both their long-term and short-term memory is being impaired.

“Rodgers team is planning to launch a Web site within the next two months that will include memory tests that may determine whether self-reported memory impairment is actually detectable by objective measurement.

Dr Stephen Koesters, a clinical assistant professor at the College of Medicine and Public Health at Ohio State University, says, “The study has a number of limitations, but does seem to support other studies that have been released in the past.”

“While the specific effects of MDMA are difficult to pinpoint in light of multiple drug use by many patients, self- reporting of the amount and the frequency of drug use, there is certainly a trend in the available literature that suggests memory impairment is a real side effect of MDMA use” he adds.

Whether these effects are cumulative is difficult to determine, Koesters adds.

“Current evidence does suggest that MDMA can be dangerous, both with acute ingestion and to longer-term memory impairment,” Koesters says. “With the current rate that MDMA is being abused, it is not safe to wait 30 or 40 years to see if we have a true epidemic,” he adds.

Source: Journal of Psychopharmacology. Jan 2004 Reported on www.healthday.com

Published: Monday, 20-Feb-2006

A fifth of young adults whose blood vessels ruptured inside their brain abused drugs and more than 40% had malformed blood vessels, according to a study reported Feb. 17 at the American Stroke Association’s International Stroke Conference 2006 in Kissimmee, FL.

The study included 307 patients with intracerebral hemorrhage (ICH) — a stroke caused by a blood vessel bursting inside the brain. Of the 75 patients 49-years-old or younger, 20% had drugs in their system.

“The dominant drug of abuse was cocaine, long recognized as a risk factor for ICH,” said Michael Hoffmann, MD, lead author of the study and director of the stroke program at the University of South Florida-Tampa General Hospital. “Marijuana was another frequently abused drug and is beginning to emerge as a risk factor for stroke. Amphetamines also were commonly abused.”

How these drugs make brain blood vessels prone to rupture is not clear, but is being studied, Dr. Hoffmann said.

The study analyzed the causes and outcomes of ICH patients. 24% of ICH patients in a registry at Tampa General Hospital were ages 18 to 49. Half were women, about two thirds were Caucasian, 15% were black and 12% were Hispanic.

ICH is often linked with high blood pressure in people over age 50, and in this study, 57% of those age 50 and older had it. Only 33% of ICH patients ages 18 to 49 had high blood pressure.

Of the younger patients in the study, 41% had malformed blood vessels, known as arteriovenous malformations, aneurysms or other vascular disorders. Cerebral arteriovenous malformation occurs when blood vessels in the brain develop in an abnormal tangle in which the arteries connect directly to the veins without the normal capillaries between them. A cerebral aneurysm is the bulging of the wall of an artery in the brain. Both these conditions weaken blood vessels and increase the risk of a hemorrhagic (bleeding) stroke.

The good news is that patients under age 50 who experience this vessel rupture inside the brain have better outcomes than older patients.

“Surprisingly, our study showed a low mortality rate compared to population studies,” said Dr. Hoffmann, professor of neurology at USF.

The 30-day mortality was 14.6% for the younger group, significantly lower than for older patients, whose mortality rate was 21%, he said. Previously, national population studies have found a high 30-day mortality rate for stroke patients with ICH. Some epidemiological data have suggested a 45% to 50% mortality rate, Dr. Hoffmann said.

ICH has traditionally been associated with older age groups and higher mortality rates.

Dr. Hoffmann attributes the low mortality rate in younger ICH patients to intensive neurocritical care management at Tampa General. The protocol includes decreasing intracranial pressure and using drains to prevent hydrocephalus, mechanical ventilation, sepsis control, blood pressure control and cooling.

The younger patients came into the emergency room, then were rapidly transferred to a neurocritical care unit within six hours. Typically, patients are hospitalized in the neurocritical care unit for one to eight weeks. Patients were evaluated by MRI, CT and angiography.

“This new way of thinking about how to manage patients with ICH is an important approach, and patients are reaping benefits,” Dr. Hoffmann said.

Most of the younger patients were able to live independently three to six months after their ICH, with only mild to moderate cognitive impairment that tends to improve over time, he said.

Dr. Hoffmann said the degree and nature of disability at six months is now the focus of the extension of this study.

“Intensive neurocritical care is the key to successful outcome,” Dr. Hoffmann said. “Good medical care can salvage a high quality of life after a stroke.”

The study was funded by USF Health and the Tampa General Hospital Stroke Registry. Co-author is Ali Malek, MD, USF assistant professor of neurology.
Source: http://www.hsc.usf.edu ; News-medical.net

In a recent double-blind, placebo-controlled study, using both smoked marijuana and THC infusions, Mathew et al studied the effect of tetrahydrocannabinol (THC) on blood pressure, pulse rate and blood flow to the brain to determine the extent of the phenomenon of dizziness or faiting associated with blood pressure drop when standing up after smoking a joint. A blood pressure drop that results in fainting ‘has considerable clinical relevance. In healthy individuals, it can cause injuries including lacerations and fractures. In individuals with pre-existing cerebrovascular disorders it can lead to stroke and sudden death’. Further it complicates a variety of diseases including multiple sclerosis, diabetes mellitus, Shy Drager syndrome, nephrosis, chronic fatigue syndrome, Parkinsonism, organic dementia and cervical myelopathy’. In ‘elderly ambulatory men’ it was found to be a significant and independent predictor of mortality. 28% of those studied reported severe symptoms, both with smoked marijuana and the THC infusions. The study found that the most marked autonomic change caused by marijuana was increased pulse rate. ‘ The results of the study clearly show loss of cerebral autoregulation and postural syncope (fainting when standing up) after ingestion of marijuana/THC. However the mechanism responsible for these phenomena is unclear.

Note: the 29 subjects were all experienced marijuana smokers. The study was reviewed and approved by the Institution Review Board (IRB) at Duke University Medical Center.
Source: A transcranial Doppler study of the hemodynamics. R J. Mathew et al Pharmacology:
Biochemistry and Behavior 75 (2003) 309-318

Mon Mar 24, 5:33 PM

NEW YORK (Reuters Health) – A new study in rats suggests that prenatal exposure to marijuana may affect offsprings’ behavior and memory, Italian researchers announced Monday.

The findings reaffirm advice for pregnant women and lactating women to avoid marijuana use, according to one of the study’s authors.

“We cannot say that findings in rats can be directly translated to humans,” said Dr. Vincenzo Guomo of the University “La Sapienza’ Roma in Rome via e-mail. “But we know that animal studies can generate predictive information on various aspects of human brain function and could represent an essential step in the development of interventions to manage human diseases.”

“In this regard, our findings suggest that both pregnant and lactating women should avoid the use of marijuana,” Cuomo said.

The findings are pub]ished in the advance online edition of the journal Proceeding of the National Academy of Sciences (news – web sites).

Although marijuana is one of the most widely used illegal drugs, studies of its effects on pregnant women and their offspring have had conflicting results, said Cuomo.

This may be explained by possible impurities in the drug and by the use of tobacco along with marijuana, according to Cuomo. Rigorous studies on the effects of marijuana in pregnancy are reratively rare, Cuomo said.

However, some researchers have for many years been following relatively large numbers of children whose mothers smoked marijuana during pregnancy, according to the Italian researcher. In general, their findings suggest that exposure to marijuana during pregnancy is related to later adverse effects on mental and motor development, Cuomo said.

In the current study, Cuomo’s team injected pregnant rats with a synthetic compound that is similar to a chemical found in marijuana. The daily dose in rats corresponded to the low-to-moderate dose people get when they smoke marijuana.

Among the rats born to exposed mothers, the researchers identified memory and behavioral problems. The offspring of exposed mothers were hyperactive, though this difference in behavior was not long lasting. However, rats whose mothers bad been exposed to the marijuana-like compound did have memory problems, according to the report.

The results of the study, Cuomo said, are in line with clinical data showing that the use of marijuana by women during pregnancy has negative consequences on the mental function and behavior of their children.

SOURCE: Proceedings of the National Academy of Sciences 2003/lO1073/pnas.05378491 30.

JULIE A. CHACKO, JARED G. HEINER, WENDY SIU, MARIE MACY, AND MARTHA K. TERRIS

ABSTRACT

Objectives: Marijuana smoking has been implicated as a causative factor in traditionally tobacco-related tumours of the head and neck and of the lung. When associated with marijuana use, such tumours occur in a much younger patient population than do similar tumours in tobacco smokers. Owing to the large number of young men with a history of marijuana presenting with transitional cell carcinoma to VA facilities, this study was designed to compare the marijuana use among young (aged less than 60 years) transitional cell carcinoma patients with that among age-matched controls.

Methods: Fifty-two men aged less than 60 years presenting consecutively with transitional cell carcinoma and 104 age-matched controls (defined by having no history of transitional cell carcinoma, hematuria, or irritative voiding symptoms, as well as unremarkable results on urinalysis and urine cytology) completed questionnaires about exposure to various potential carcinogens, including radiation, Agent Orange, smoked or processed meats, dyes, tobacco, and marijuana.

Results: Of the 52 transitional cell carcinoma patients, 46(88.5%) reported a history of habitual marijuana usage, and 72 (69.2%) of the age-matched controls gave a history of habitual marijuana use. This difference was statistically significant (P = 0) In those with transitional cell carcinoma, marijuana use significantly correlated with tumour stage, grade, and number of recurrences.

Conclusions: Marijuana smoking might increase the risk of transitional cell carcinoma.
Source: UROLOGY 61:100—104, 2006. © 2006 Elsevier Inc.

A little light relief in amongst all the serious data – there are occasionally sections – which although still serious – can bring a smile to one’s face. One such is this extract from the book ‘Marijuana – Deceptive Weed’ by Professor Gabriel Nahas.

Experiments carried out in Germany by Luff (1972) indicate that driving under the effects of Cannabis intoxication induced by active material is hazardous. Twelve young volunteers Ingested 3.2 gr. of a potent preparation, and were tested under actual driving conditions. They passed through 35 stop signs, ignored three red lights, made 233 parking mistakes, ran through l9 pedestrian crossings, demolished a simulated wall of plastic blocks and ran over a large stuffed lion. The dose of delta-9-THC these volunteers absorbed was certainly elevated (60 – 100 mg) but the results are nevertheless sobering.

Source: ‘Marijuana – Deceptive Weed’ by Professor Gabriel Nahas, O.B.E., Ph.D. Published Raven press NY 1975.

The aim of this conference was to review the pharmacological and molecular basis of the therapeutic properties of marijuana and THC, and to evaluate their clinical applications. Fifty scientists and physicians from the United States, Israel, France, Germany and Sweden gathered for two days to present papers in their areas of expertise.

The prolonged storage of THC in the body, whatever its route of absorption, was again discussed in reference to the persistent properties of this drug, even after its acute effects have dissipated. The marijuana cigarette manufactured and distributed by the National Institute on Drug Abuse for clinical research contains toxic substances in greater amounts than those contained in a tobacco cigarette of the same weight. NIDA has not been able to develop a standard marijuana cigarette with uniform concentrations of THC devoid of tars and other noxious agents. THC, taken orally, has been approved by the FDA for the treatment of vomiting and as an appetite stimulant under the name of “Marinol.’ This drug may be prescribed by physicians; however, it is not as effective as other presently available medications.

The addiction/tolerance mechanisms of THC and marijuana are similar to those induced by opiates, cocaine, nicotine and alcohol. The evidence of persistent, abnormal biochemical alterations (produced by THC in the brain and recorded with PET scans) were presented by scientists from Brockhaven National Laboratory. These were related to the persistent alterations by marijuana of the brain molecular mechanism, which control DNA expression and correlated with changes in memory, attention, awareness, and goal-oriented behavior. THC interacts with ‘receptors’ in brain cells, which are part of a regulatory “anandamide cannabinoid” system that regulates the function of brain cells and their neuro-transmission (signal transduction). Through this mechanism, THC interacts with the receptors to brain neurotransmitters (norepinephrine, dopamine, GABA, acetylcholine), altering the release of these substances. By the same mechanism, THC modifies the effects of many drugs commonly used like psycho-stimulants and psycho-depressant, opiates, alcohol and stimulants: some are enhanced and some are decreased. THC acts as a major ‘deregulator’ of all brain regulation of basic bodily functions. However, unlike ‘anandamide’ and its physiological ligands, THC sticks to the receptor molecule for hours, even days, and disturbs its signalling function in a persistent fashion. This fundamental impairment of the intracellular signalling mechanism can be observed in all cells of vital body organs: brain, heart, lung, kidney, immunity cells, and the reproductive system, carrying the risk of impairing future generations before they are born.

THC receptors identical to those of the brain cells have been identified in cells of the immunity system, of sex organs and of germ cells (gametes). They are present on the head of sperm cells and in the cells of the testes that generate the sperm. These molecular studies confirm those performed in 1976-1978, by researchers at Columbia University who reported that marijuana smokers had decreased sperm count and abnormal forms of sperm. This alteration of sperm was due to the effect of THC on spermiogenesis, the process of sperm formation in the testes. Marijuana is ‘gametotoxic’, toxic to germ cells, and is fetotoxic, impairing foetal development and is in animal species.

Marijuana in the treatment of pain was discussed in a special international panel. The difficulty of separating the subjective perception of pain from its objective measurement was discussed, and it appears to be insuperable to solve; marijuana smoking can actually lower the threshold of pain perception. THC is not an effective all-purpose analgesic when compared to aspirin, Tylenol or opiates. An evaluation of THC and of marijuana smoke in the following conditions was discussed: emesis and vomiting in cancer chemo-therapy (where orally administered THC or marijuana smoking were less effective than alternate medications); glaucoma (where THC and smoked marijuana were not deemed acceptable); use of marijuana and THC have proven unsuitable as sedative or for pain management in anesthesiology; in neurological disorders, epilepsy and multiple sclerosis. In management of the AIDS wasting syndrome, the reported therapeutic results of THC and of marijuana smoke were inconclusive.

The effects of marijuana in psychiatry were evaluated in the following conditions: schizophrenia, alcoholism and acute psychiatric syndromes. Marijuana smoking may trigger some of these ailments or worsen their course.

Dr. Paul C. ]anssen, who has designed some of the most widely used medications in psychiatry, anaesthesia and dermatology, gave a special lecture entitled: How to Search for the Ideal Drugs of the Future.’ He emphasized the importance of obtaining a perfect fit between a drug and a specifically localized receptor in order to obtain the ideal therapeutic effect. Cannabinoids do not seem to possess this property of ideal therapeutic drugs.

International conference held at New York University School of Medicine March 20-21, 1998. (A brief precis from 700 pages!)

Documents the harm to young people from marijuana use. The Denver-area teenagers studied were in delinquency/substance abtise treatment and most were dependent on marijuana, although most reported behavior problems predated, and were not initially caused by, drug use. Most of the dependent youth had let marijuana control their lives, interfering with school, home, and work situations and with driving. Three-quarters of the dependent young people spent much time in getting, using or recovering from the effects of marijuana. Two-thirds had given up important activities to use or acquire marijuana. Most of these dependent children experienced withdrawal symptoms when they tried to quit marijuana. Among other findings of this study:

Marijuana is a strong reinforcer of itself, propelling further use.
Among the dependent youth, even moderate marijuana use commonly led to dependence. For those who had used marijuana at least 6 times, 83% developed dependence.
Progression in marijuana use was significantly more rapid than for alcohol.
An anti-drug prevention organization recently compiled an extensive bibliography of studies showing marijuana’s harm. This is available from DNE/Strategic Intelligence upon request.
Aside from the harm caused by marijuana directly, its role as a “gateway drug” has been well established. Marijuana use is of particular concern because, for some, it is a forerunner of use of other drugs with their attendant problems. Documentation of the association of marijuana with abuse of more serious drugs was reported in the June 1997 Bulletin. One study showed that the earlier a person starts using marijuana, the more likely it is that they will at least experiment with other drugs. This is shown in the graph below and suggests that the longer marijuana use can be prevented, the better the chance for a drug-free life.
Risk of using other drugs varies directly with how young a person is when they start using marijuana

Source:Recent research conducted at the University of Colorado and published in Drug and Alcohol Dependence
How Marijuana Use Relates to Other Drug Use
(Based on Federal Drug Use Figures)

This study examines the extent to which alcohol and drug use is related to violent and nonviolent criminal activity among adolescent males. Based on data collected from 312 youthful offenders at a public juvenile facility, the findings reveal that in comparison to marijuana and heroin, alcohol use is more strongly and consistently associated with both violent and nonviolent offenses. When other factors are introduced into the analysis, the results show that while an adolescent’s criminal history and racial identity are relatively more important in predicting criminal activity overall, the effect of substance use (especially alcohol and marijuana) continues to be present.

Source: Dawkins, M. Adolescence 32(126):395-405, 1997
Availability: Marvin P Dawkins, Department of Sociology Coral Gables FL 33124

The aim of this conference was to review the pharmacological and molecular basis of the therapeutic properties of marijuana and THC, and to evaluate their clinical applications. Fifty scientists and physicians from the United States, Israel, France, Germany and Sweden gathered for two days to present papers in their areas of expertise.
The prolonged storage of THC in the body, whatever its route of absorption, was again discussed in reference to the persistent properties of this drug, even after its acute effects have dissipated. The marijuana cigarette manufactured and distributed by the National Institute on Drug Abuse for clinical research contains toxic substances in greater amounts than those contained in a tobacco cigarette of the same weight. NIDA has not been able to develop a standard marijuana cigarette with uniform concentrations of THC devoid of tars and other noxious agents. THC, taken orally, has been approved by the FDA for the treatment of vomiting and as an appetite stimulant under the name of “Marinol.’ This drug may be prescribed by physicians; however, it is not as effective as other presently available medications
The addiction/tolerance mechanisms of THC and marijuana are similar to those induced by opiates, cocaine, nicotine and alcohol. The evidence of persistent, abnormal biochemical alterations (produced by THC in the brain and recorded with PET scans) were presented by scientists from Brockhaven National Laboratory. These were related to the persistent alterations by marijuana of the brain molecular mechanism, which control DNA expression and correlated with changes in memory, attention, awareness, and goal-oriented behavior. THC interacts with ‘receptors’ in brain cells, which are part of a regulatory “anandamide cannabinoid” system that regulates the function of brain cells and their neuro-transmission (signal transduction). Through this mechanism, THC interacts with the receptors to brain neurotransmitters (norepinephrine, dopamine, GABA, acetylcholine), altering the release of these substances. By the same mechanism, THC modifies the effects of many drugs commonly used like psycho-stimulants and psycho-depressant, opiates, alcohol and stimulants: some are enhanced and some are decreased. THC acts as a major ‘deregulator’ of all brain regulation of basic bodily functions. However, unlike ‘anandamide’ and its physiological ligands, THC sticks to the receptor molecule for hours, even days, and disturbs its signalling function in a persistent fashion. This fundamental impairment of the intracellular signalling mechanism can be observed in all cells of vital body organs: brain, heart, lung, kidney, immunity cells, and the reproductive system, carrying the risk of impairing future generations before they are born.
THC receptors identical to those of the brain cells have been identified in cells of the immunity system, of sex organs and of germ cells (gametes). They are present on the head of sperm cells and in the cells of the testes that generate the sperm. These molecular studies confirm those performed in 1976-1978, by researchers at Columbia University who reported that marijuana smokers had decreased sperm count and abnormal forms of sperm. This alteration of sperm was due to the effect of THC on spermiogenesis, the process of sperm formation in the testes. Marijuana is ‘gametotoxic’, toxic to germ cells, and is fetotoxic, impairing foetal development and is in animal species.
Marijuana in the treatment of pain was discussed in a special international panel,. The difficulty of separating the subjective perception of pain from its objective measurement was discussed, and it appears to be insuperable to solve; marijuana smoking can actually lower the threshold of pain perception. THC is not an effective all-purpose analgesic when compared to aspirin, Tylenol or opiates. An evaluation of THC and of marijuana smoke in the following conditions was discussed: emesis and vomiting in cancer chemo-therapy (where orally administered THC or marijuana smoking were less effective than alternate medications); glaucoma (where THC and smoked marijuana were not deemed acceptable); use of marijuana and THC have proven unsuitable as sedative or for pain management in anesthesiology; in neurological disorders, epilepsy and multiple sclerosis. In management of the AIDS wasting syndrome, the reported therapeutic results of THC and of marijuana smoke were inconclusive.
The effects of marijuana in psychiatry were evaluated in the following conditions: schizophrenia, alcoholism and acute psychiatric syndromes. Marijuana smoking may trigger some of these ailments or worsen their course.
Dr. Paul C. ]anssen, who has designed some of the most widely used medications in psychiatry, anaesthesia and dermatology, gave a special lecture entitled: How to Search for the Ideal Drugs of the Future.’ He emphasized the importance of obtaining a perfect fit between a drug and a specifically localized receptor in order to obtain the ideal therapeutic effect. Cannabinoids do not seem to possess this property of ideal therapeutic drugs.