Costa Rican study observes short term memory loss in long term cannabis users

To test the hypothesis that long term cannabis use is associated with deficits in short term memory, working memory, and attention span, two groups of long term users (one with an average age of 45 and the other an average age of 28) were compared to non-users matched for age and socioeconomic status (Fletcher et al Arch Gen Psychiatry 53:1051-1057, 1996). Polydrug users, or users who did not abstain for the required 72 hours, were excluded from the study. At follow-up the users had been smoking approximately five joints a day, two to seven days a week. It was observed that older users (average duration of cannabis use 34 years) had both impaired short term memory and impaired ability to give attention to a task compared to non-users. In the younger cohort (average duration of use eight years) no differences between users and non-users were noted.

Comment: This study confirms observed problems with memory and attention associated with long term cannabis use. The failure to find these changes in younger, less chronic users may reflect the need for a cumulative neurotoxic dose threshold to be exceeded. Again, these patients were abstinent for three days. Performance after recent doses would likely have been worse. The authors noted that the risks of long-term use are "likely to be magnified in a more technological society," and that "Certain occupations may carry particular risk because of safety issues and effects on productivity and learning." They stressed that the findings of the study "suggest a need to focus on the prevention of cannabis use... to reduce the risk of consumption of drugs...".

Study of marijuana-using college students shows impairment

Pope and Yurgelun-Todd (JAMA 275:521-527, 1996) studied the neuropsychological test performance of 65 college undergraduates, 19 to 24 hours after a supervised period of abstinence in a treatment center. All had positive urine for cannabinoids and claimed to have used marijuana an average of 29 days out of the last 30 . They found that attention and decision making function, as well as learning and general intellectual function, were reduced compared to 64 controls who had smoked marijuana a median of 1 day in the previous 30 and had negative urine cannabinoids. Even when baseline intellectual ability and the use of alcohol were considered, the impairment to heavy users was still significant. The authors thought this could be due to the effects of marijuana on the brain systems important for concentration and attention. An accompanying editorial by Block (JAMA 275:560-561, 1996) discusses the alternative explanation for the abnormalities, i.e., a withdrawal syndrome effect.

Comment: Reductions in intellectual functioning during marijuana use have long been observed and, of course, would impair learning ability in college students. The control group in this study were light users. It would have been of interest to study non-users since one would expect the differences to be even more striking. The editorialist, Robert I. Block, Ph.D., University of Iowa College of Medicine, points out that alcohol also affects cognitive ability. However, the Pope/ Yurgelun-Todd study controlled for this and observed that "the differences observed in this study were indeed due to residual effects of marijuana use" and not the effects of alcohol or other substances.

New Zealand marijuana users view drug's impact on their lives

A survey designed to diagnose the impact of cannabis use on financial position, health, outlook on life, friendships, home life, and work opportunities (Huw, T., Drug and Alcohol Dependence 42:201-207, 1996), was mailed to 1000 New Zealand subjects, aged 18-35. There was a 53% response rate to the questionnaire which was based on previous surveys designed for alcoholism. Of the 528 respondents, 62% claimed never to have used marijuana and did not complete the survey. Thirty-eight percent (199) admitted some lifetime marijuana use. Heavy users (108) were people who reported using more than 50 times in their life. Of these, about half had been daily users (3 - 4 joints per day) at some time. Of heavy users, 24% experienced panic attacks following use and 15% experienced psychosis. Twenty-three subjects thought that cannabis had harmed their physical health, citing frequent nausea and/or vomiting, headaches, and persistent coughing as some of the associated problems. While 70 subjects reported continued use despite problems related to use, the study concluded that only 58 of them were actually dependent on cannabis.

Comment: The lack of a control group of non- users weakens the findings of this study. However, this may be counterbalanced by the tendency of respondents in self-administered questionnaires to under-report adverse consequences. As the authors point out, "In any study, particularly those regarding illegal activities such as drug use, willingness to participate does not guarantee honesty...There may also be a tendency for drug users to understate the problems and exaggerate the benefits of drugs in order to justify continued use." Nonetheless, the 22% of respondents reporting anxiety/panic attacks, and a 15% prevalence of psychosis, are alarming and need to be studied further.

Cannabis withdrawal syndrome observed by founders of Haight Ashbury Free Clinics

Reporting in the Journal of Substance Misuse, 2:49-53, 1997, D. E. Smith and R. B. Seymour, founders and directors of the Haight Ashbury Free Clinics, review the neuropharmacology of cannabis and cannabis dependence. They observed that there is "ample evidence that cannabis is a dangerous substance" and that increased potency in recent years has increased both the danger and the factors that lead to physical dependence. They further observed that chronic marijuana users have the profile of addictive disease, i.e., compulsion, loss of control, and continued use even in the presence of adverse consequences. Supporting their years of observation, the authors quoted a statement by NIDA Senior Investigator Billy Martin who said "The fact that people do seek treatment for marijuana dependence is evidence of marijuana withdrawal in humans." They also noted that addicted individuals often respond well to recovery programs like Marijuana Anonymous (similar to Alcoholics Anonymous). The authors stated that "... it is not uncommon to hear chronic marijuana smokers in long term recovery comment that it was several years into abstinence before they were truly aware of the adverse effects marijuana had on their thinking and behavior."

Comment: It is of interest to note that in the past these two authors often downplayed the dangers of marijuana use, saw no evidence of the existence of marijuana addiction, and favored legalization. Their personal experience, coupled with significant inroads in scientific research on marijuana over the past 20 years, has changed that perspective. r Non-psychoactive cannabinoid derivative can protect injured brain A non-psychotropic cannabinoid derivative, dexanabinol, has been shown in animals and humans to provide protection to the brain after injury. Early clinical trials in the United Kingdom and Israel have shown lack of adverse side effects and reduced injury to the brain even after a single dose given six hours after the initial event (cited by Fishman, R. H., The Lancet 348:1436, 1996). The exact mechanism by which the synthetic cannabinoid works involves blocking toxic effects of chemicals liberated after the trauma and also by limiting the effects of free radicals which damage brain cells. The results of research on dexanabinol were presented by Dr. Mechoulam, a professor of pharmacology at Hadassah Medical School in Jerusalem, at the November 15, 1996 meeting of the Society of Neurotrauma . Comment: A neuroprotective agent would find many uses in clinical medicine. It is of interest that the useful action of this cannabinoid can be divorced from any psychoactive properties. The future of cannabinoids as medical treatment will come from synthetic drugs tailored for therapeutic benefit but lacking the adverse effects of crude marijuana.

Material used in this publication has been reviewed and commented on by William M. Bennett,MD, Professor of Medicine, Division of Nephrology, Clinical Pharmacology and Hypertension at Oregon Health Sciences University, Portland, Oregon