Marijuana is the most commonly used illegal drug in the United States. Over 65 million Americans (31% of the US population aged 12 and older) are estimated to have used marijuana: 1 its mean retail sales value in the United States is approximately $10 billion.2 Despite its long-standing popularity and increasing use among youth in recent years,1,3 we still know little about long-term health risk associated with marijuana use. Harvard policy analyst Mark Kleiman recently concluded that "aside from the almost self-evident proposition that smoking anything is probably bad for the lungs, the quarter century since large numbers of Americans began to use marijuana has produced remarkably little laboratory or epidemiological evidence of serious health damage done by the drug."4(p.253) Similar appraisals of the health effects of cannabis were offered in the two most comprehensive reviews from the 1980s.5,6

More currently, Hall and co-authors concluded that while there are no well-established health or psychological effects of chronic cannabis use, the following were considered to be probable major adverse effects: respiratory diseases associated with smoking as the method of administration, including chronic bronchitis and pre malignant histopathological changes in the lung; development of a cannabis dependence syndrome; and subtle forms of cognitive impairment.7(p. 16)

The only other large-scale study of marijuana use and mortality was performed in a cohort of 45,540 male Swedish conscripts, aged 18 through 20 years at baseline and followed for 15 years.8 In this study, the relative risk (RR) for mortality associated with marijuana use (more than 50 times) was 1.2 (95% confidence interval[C]=0.8, 1.9) after adjustment for social background.

We report here the findings of a study of the relationship of marijuana use to mortality in a cohort of over 65.000 members of a large prepaid health plan. Data on marijuana use in this cohort were collected before the "war on drugs" escalated in the latter half of the 1980s, which may have resulted in under reporting of illegal drug use.9 Mortality is one of several health outcomes being studied; other endpoints include cancer incidence and outpatient utilization for respiratory illnesses and injuries. We have hypothesized that marijuana use would be associated with increased risk of respiratory disease and injury.

The main overall findings were an increased risk of total mortality associated with marijuana use in men but not in women. The increased risk of total mortality in men was explained by the strong relationship between marijuana use and AIDS mortality. Marijuana use was unassociated with non-AIDS mortality in men.

The question of the effect of marijuana use on AIDS mortality is an important one. Marijuana use has been advocated as a therapeutic adjunct to ameliorate the nausea and loss of appetite commonly associated with the wasting syndrome in AIDS.17 We have provided substantial evidence that the increased risk of AIDS mortality in the total study cohort probably resulted from uncontrolled confounding by homosexual behavior. Other studies have reported a substantially higher prevalence of marijuana use in homosexual and bisexual men, supporting the hypothesis that marijuana use is a marker for homosexuality or bisexuality.18-20

There are several other potential explanations for the increased risk of AIDS in marijuana users. Marijuana smoking might theoretically place AIDS patients at increased risk of infection because of its irritative effects on the respiratory system or because of infectious contaminants (e.g., fungi) in marijuana. Other potential explanations include marijuana use as a result of having HIV and AIDS, rather than preceding the disease; and possible immunosuppressive properties of marijuana.

The use of alcohol and nonmedical psychoactive drugs, including marijuana, is associated with risky sexual behavior such as unprotected intercouse,20 but methodological limitations have made it impossible to determine causality.21 Marijuana use may serve to a certain extent as a marker of intravenous drug use. However, the relative risk of AIDS mortality associated with marijuana use did not diminish when the analysis was limited to men who were nonsmokers of tobacco and occasional alcohol drinkers, a subgroup unlikely to contain many parental drug users. Additional evidence against marijuana as a marker for parental drug use was the finding of only one case of infective endocarditis in Kaiser Permanente hospitalization record of the AIDS decedents.

The lack of increased mortality during the first 5 years of follow-up suggests that therapeutic use of marijuana at baseline for AIDS-related symptoms has little, if any, explanatory effect on the association between marijuana use and AIDS. Furthermore, the majority of AIDS patients initiated marijuana use long before the onset of clinical disease; nearly two thirds (65%) of AIDS patients reported initiation before 1976, when HIV infection in the San Francisco Bay area was either nonexistent or negligible.22

While marijuana and its psychoactive cannabanoids possess known immunosuppressive qualities, there is no consensus as to whether typical doses result in clinical immunosuppression in humans.23 Marijuana use has been associated with a higher prevalence of seropositivity for HIV in some cross-sectional studies of homosexual and bisexual men,20.24 but it has not been shown to be an independent predictor of seroconversion,25 not does it increase the risk of AIDS in seropositive men.24

The nearly significant increase in mortality risk from injury or poisoning for female current marijuana users was consistent with our hypothesis that marijuana use is a risk factor for death due to injury. Marijuana is known to decrease psychomotor performance; some studies have implicated its use in motor vehicle crashes.7(pp43-50) Marijuana use is also strongly associated with alcohol use, another major risk for accidental death. There were too few deaths to meaningfully study the other main hypothesis, that marijuana use would be associated with increased respiratory disease mortality. Another study performed on a subgroup of this cohort showed that daily or near-daily marijuana users who were not tobacco cigarette smokers had a 19% higher risk of outpatient visits for respiratory disorders than non users of both substances.26

The major limitations of this study include its reliance on self-report for ascertainment of marijuana use status; the inability to study changes in marijuana use status during follow-up; a lack of lengthy follow-up into the geriatric age range (maximum follow-up, 12.5 years; maximum age reached, 63 years); a lack of information regarding other illegal drug use; and potential underascertainment of mortality (noted earlier). Estimates of marijuana use were similar to those obtained during this period by the National Household Survey on Drug Abuse, the most authoritative source of illegal drug use information for US adults.27 The lack of longitudinal data regarding use status is common to many cohort studies. It seems unlikely that "ever" marijuana use status would have changed substantially over time, because relatively few adults in this cohort are likely to have initiated marijuana use during follow-up in a period (1980s) when there was a marked secular decline in self-reported marijuana use in the United States.1 It is possible that relationships between marijuana use and mortality might be found with longer-term follow-up or later in life. It is likely that if information on subjects' use of other illegal drugs had been available, adjustment for other drug use would have lowered the relative risk estimates for marijuana use.

As noted earlier, relatively few adverse clinical health effects from the chronic use of marijuana have been documented in humans.7(p16) The criminalization of marijuana use may itself be a health hazard, since it may expose the consumer to violence and criminal activity.28 While reducing the prevalence of drug abuse is a laudable goal, we must recognize that marijuana use is widespread despite the long-term, multibillion dollar War on Drugs. Therefore, medical guidelines regarding its prudent use should be established skin to the commonsense guidelines that apply to alcohol use. Unfortunately, clinical research on potential therapeutic uses for marijuana has been difficult to accomplish in the United States, despite reasonable evidence for the efficacy of tetrahydrocannabinol (THC) and marijuana as anti emetic and anti glaucoma agents and the suggestive evidence for their efficacy in the treatment of other medical conditions, including AIDS.7(pp185-262)

In summary, this study showed little, if any effect of marijuana use on non-AIDS mortality in men and on total mortality in women. The increased risk of AIDS mortality in male marijuana users probably did not reflect a causal relationship, but most likely represented uncontrolled confounding by male homosexual behavior. The risk of mortality associated with marijuana use was lower than that associated with tobacco cigarette smoking.

1. "Preliminary Estimates from the 1994 National Household Survey." Advance Report No. 10, Rockville, Md.: Substance Abuse and Mental Health Services Administration; 1995.

2. "What America's Users Spend on Illegal Drugs," Washington, DC: Office of National Drug Control Policy; 1991.

3. Johnston LD, O'Malley PM, Bachman JD. "National Survey Results on Drug Use from the Monitoring the Future Study," 1975-1994,

Vol. 1 Rockville, Md: National Institute on Drug Abuse; 1995. DHHS Publication NIH 95-4026

4. Kleiman, MAR. Against Excess: Drug Policy for Results .New York, NY: Basic Books; 1992:253

5 "Report of an ARF/WHO Scientific Meeting on the Adverse Health and Behavioral Consequences of Cannabis Use. " Toronto, Ont., Canada: Addiction Research Foundaton; 1981.

6. National Academy of Science, Institute of Medicine, "Marijuana and Health," Washington, DC: National Academy Press; 1982

7. Hall W, Solowizjn, Lemon J. "The Health and Psychological Consequences of Cannabis Use. Caberra, Australia: Australian Government Publishing Service: 1994. National Drug Strategy, Vol. 25.

8. Andreasson S, Allebeck P. Cannabis and mortality among young men: a longitudinal study of Swedish conscripts. Scand J Soc Med. 1990; 18:9-15.

9. Sidney S. Evidence of discrepant data regarding trends in marijuana use and supply. 1985-1988. J Psychoactive Drugs. 1990;22:319-324.

17. Grinspoon L, Bakalar JB, "Marijuana, the Forbidden Medicine" New Haven, Conn: Yale University Press; 1993

18. Stall R, Wiley J. A comparison of alcohol and drug use patterns of homosexual and heterosexual men: the San Francisco Men's Health Study. "Drug Alcohol Depend." 1988; 22:63-73.

19. Skinner WF, Otis MD. "Drug Use among Lesbian and Gay People: Design, Insights, and Policy Issues from the Trilogy Project. In: Proceedings of the Research Symposium on Alcohol and Other Drug Problem Prevention among Lesbians and Gay Men. Sacramento, Calif.: California Dept of Alcohol and Drug Programs; October 1992: 34-60.

20. Ostrow DG. Substance use and HIV-transmitting behaviors among gay and bisexual men. In: Battjes RJ. Sloboda Z, Grace WC, eds. "The Context of HIV Risk among Drug Users and Their Sexual Partners. Rockville, Md. National Institute on Drug Abuse; 1994. NIDA Research Monograph 143.

21. Leigh BC, Stall R. Substance use and risky sexual behavior for exposure to HIV; issues in methodology, interpretation and prevention. Am Psychl. 1993; 48: 1035-1048.

22. Jaffe HW, Darrow WW, Echenberg DF, et al. The acquired immunodeficiency syndrome in a cohort of homosexual men. Ann Intern Med. 1985; 103:210-214.

23. Hollister LE. Marijuana and immuity. J Psychoactive Drugs. 1992; 24 (2): 159-164.

24. Kaslow RA, Blackwelder WC, Ostrow DG, et al. No evidence for a role of alcohol or other psychoactive drugs in accelerating immunodeficiency in HIV-1 positive individuals: a report from the multicenter AIDS cohort study. JAMA. 1989; 261: 3424-3429.

25. Ostrow DG, Difranceisco WJ, Chmiel JS, Wagstaff DA, Wesch J. A case-control study of human immunodeficiency virus type 1 seroconversion and risk-related behaviors in the Chicago MACC/CCS cohort, 1984-1992. Am J Epidemiol. 1985; 142: 875-883.

26. Polen MR, Sidney S, Tekawa IS, Sadler M, Friedman G. Health care use by frequent marijuana users who do not smoke tobacco. West J Med. 1993; 158:596-601.

27. "National Household Survey on Drug Abuse: Main Findings "1985. Rockville, Md: National Institute on Drug Abuse; 1985. DHHS publication ADM 88-1586.