Drug Watch International

MARIJUANA RESEARCH REVIEW

Poor results shown using THC to treat AIDS wasting syndrome

Both dronabinol (Marinol) and megesterol (Megace) are approved for use in AIDS wasting to stimulate appetite. This study by Timpone et al, AIDS Research and Human Retroviruses, Vol.13, No.4, 1997, put 52 advanced AIDS patients into one of four treatment groups. The first received 2.5 mg of dronabinol twice a day and experienced a 4.4-lb. weight loss. The second group received 750 mg of megesterol per day, and a 14 lb. weight gain was recorded. The third received 750 mg of megesterol plus the dronabinol and showed less weight gain than megesterol alone. Those in the fourth group, who received only 250 mg of megesterol plus the dronabinol, reflected a slight weight loss of approximately .07 lb.. Only 39 patients completed the 12-week study period. Serious adverse effects related to dronabinol included confusion, anxiety, emotional instability, euphoria and hallucinations.  It was concluded that dronabinol alone was ineffective in treating AIDS wasting and, if anything reduced the beneficial effects of megesterol.

Comment: This study, using controls, supports earlier ones which have shown relatively poor results with oral THC for AIDS wasting. It illustrates that THC does not effect the desired weight gain even though it stimulates appetite. The drug megesterol, marketed as Megace, was shown to be far superior for that purpose. 

Tashkin study in perspective:  Marijuana smoking has serious negative impact on life expectancy

Tashkin et al. measured the lung function of 131 heavy marijuana users, 112 smokers who used both tobacco and marijuana, 65 tobacco smokers, and 86 non­smokers in Los Angeles (Tashkin et al. Am Journ Respiratory and Critical Care Medicine 155:141-148, 1997). Participants were tested up to six times over seven years, but only 75% (255) of the subjects were followed up. The use of marijuana did not cause a decline in lung function by itself nor did it worsen the decline of lung function observed in tobacco smokers. The test for lung function used in this study, FEV₁ measures the amount of air expelled from the lung after one second and is used to test lung function in patients with emphysema and obstructive lung disease. The author comments, and has shown previously, that marijuana causes pre-cancerous changes in lung cells, and bronchitis in people who smoke the drug alone, similar to those changes noted in tobacco smokers (Tashkin, D. et al Am Rev Resp Dis 135:209-216, 1987). While marijuana is not, according to those data, a risk for chronic lung disease, there is a higher incidence of acute bronchitis, chronic bronchitis, infection, and probably malignancy. The lung function test does not exclude those effects of marijuana and, as the authors state, "...the data do not imply that regular marijuana smoking is free of harmful pulmonary effects."

Comment: The results of this study need to be put in context since it was done in Los Angeles and all groups had a decrease in this lung function with age. This change, which may be due to environmental factors such as smog, makes it difficult to detect adverse changes with this small number of patients since lung function declines in everybody in the study. The follow-up period is short for chronic emphysema, and only 65% of participants were followed. Also, the group not followed (35% of total initial participants) may not be representative. For example, during this period eight marijuana/tobacco smokers, two marijuana smokers, and three tobacco smokers died compared to one non­smoker. The non-smoker died of breast cancer whereas AIDS (two deaths), violence (three deaths), suicide (one death), and drug overdose (one death), were all seen in marijuana users. For a 25-49 year old age group this is a high death rate, i.e., 4% for marijuana users, 4% for tobacco users and 1.1% for non-smokers. The only conclusive outcome of this study is that marijuana smoking, like tobacco, has serious negative impact on life expectancy. ##

Pancreas function impaired by alcohol and Marinol/marijuana

Because alcohol consumption has been observed to impair liver function and it is well documented that THC impairs the immune system, Whitfield et all did a retrospective chart review of HIV positive patients (Alcoholism: Clinical and Experimental Research 21:122-127,1997) to ascertain the impact of alcohol and Marinol/marijuana use on the pancreas of those patients being treated with anti-retroviral therapies which are known to cause pancreatic damage. In patients using the drug DDI with Marinol/marijuana (no distinction was made by the authors), the CD4 cell (a lymphocyte cell which is deficient in AIDS patients) count decreased and the pancreatic enzyme levels increased (a sign of damage) when compared to patients using the same drug who DID NOT use

Marinol/marijuana. Alcohol affected pancreatic function in the groups receiving the drugs AZT and DDC as well. Patients who ceased alcohol use improved pancreas function over the ensuing year in all therapy groups. Continued Marinol/marijuana in four of six patients did not further suppress the already very low count of CD4 immune cells but the author thought the damage to these patients' immune system was "too great to analyze their clinical status accurately.

Comment: This study is flawed by its retrospective (a look back at charts after the data is gathered) nature and its small numbers of patients in each of the antiviral therapy groups. Over the one year period of follow-up, 25% of the 86 patients had died or were lost to follow-up. Of the remainder, stopping alcohol use in the face of continued anti-AIDS therapy was beneficial. While marijuana/Marinol status was not reassessed, already suppressed CD4 counts did not worsen but also did not improve over the year. The Marinol/marijuana use in patients who died or were lost is not mentioned in the paper. ##

Study reflects double mortality in AIDS patients who used marijuana

The authors, Sidney et al, followed up 65,171 Kaiser Program enrollees, aged 15-49, who had previously completed questionnaires about smoking habits between 1979 and 1985, including marijuana use. Mortality was followed through 1991. The results compared non-use of marijuana or experimentation, that is a life-time use of six or fewer times, with current marijuana use. These results showed no increased risk of mortality in men or women. However, marijuana use in the interval of the questionnaire in the late 1970s and early 1980s was associated with an increased risk of AIDS mortality in men. The authors believe that this association does not imply cause and effect, but is related to the probable male homosexual behavior of this population. The risk of AIDS mortality in users versus non-users was approximately doubled. (Am J Public Health 87:585-590.)

Comment:  This study has many flaws, and despite the interpretation of the data by the authors, the fact is that mortality from AIDS was significantly increased in marijuana users versus non-users. Although a cause and effect relationship is not clearly established, one cannot be excluded. The data supports that smoking anything would not be good for patients with compromised immune systems. The study's major weakness is that there is no follow-up of the patients after the initial self-reporting questionnaire between 1979 and 1985. Thus, it is impossible to tell who continued to use marijuana. Even though the original exposure was only self-reported, the large numbers in this study make it of interest. The literature review by the authors is somewhat disturbing in that they reference numerous non-scientific writings by marijuana legalization activists. Thus, if one pays attention to the findings here and not the rhetoric of the discussion, which seems inappropriate for a scientific article, the fact remains that AIDS mortality in men was doubled in patients who, between 1979 and 1985, used marijuana. Since these individuals were relatively young at the time of exposure, deaths from usual cardiovascular and other causes in this relatively short time follow-up would not be expected. Thus, an adverse effect of marijuana on mortality cannot be excluded by these data. ##

Use of marijuana poses hazards for the elderly

Sussman, S., in Clinical Geriatrics 5:109-119,1997, reviews the use of marijuana in elderly patients in light of the recently passed California and Arizona initiatives which allow self-medication with crude marijuana. He notes two types of users - those who begin use as a means of coping with limitations imposed by advancing age, and those who first used the drug in the 1960's and 1970's and never stopped. Sussman notes a number of reasons why marijuana use is not wise for the elderly. 1) The "high" produces a sense of loss of control and sensations of unreality, 2) Many elderly persons have medical conditions that marijuana can make worse, for instance, it speeds up the heart rate making it risky for anyone with underlying heart disease, 3) It causes slower reaction time, impairment of coordination and diminished attention span all of which predisposes to an increased incidence of accidents. He cites his previous research in which it was found that 30 percent of fatally injured drivers have THC in their blood. 4) Marijuana has frequent interactions with prescription drugs which will cause adverse effects, particularly in those who need multiple medications, and 5) Marijuana is addictive and has withdrawal symptoms. Relapse rates for habitual marijuana users who try to stop are similar to tobacco cigarettes, alcohol and heroin.

Comment: Physicians with elderly patients must be vigilant for marijuana use and discover this by specific history taking. Marijuana smoking is of particular concern for elderly individuals who often suffer from multiple medical conditions, and every effort should be made to inform them of the hazards associated with use. ##

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

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