As a pilot project for a larger study of the health consequences of smoking marijuana, we compared the medical experience of persons who self-reported frequent marijuana smoking but who never smoked tobacco with that of a demographically matched group who reported never smoking tobacco or marijuana. To our knowledge, this study is the first to review the medical records of a large number of non-tobacco smoking marijuana users.

Study Population

Study subjects were selected from members of the Kaiser Permanente Medical Care Program who had at least one multiphasic health checkup (MHC) at the Oakland or San Francisco, California, medical centers between July 1979 and December 1985. The multiphasic health checkup was completed by about 30,300 persons per year during the study period; the examination was discontinued at San Francisco in 1980. The MHC population has been described previously and has provided the data for numerous studies of smoking and drinking habits. 1,2

The Kaiser Permanente membership is demographically and socially heterogeneous, reflecting the diversity of the San Francisco Bay Area population, but impoverished and undereducated persons are underrepresented. 3 Persons who take the MHC tend to be more health conscious and better educated than Kaiser Permanente members in general. 4,5

The MHC examinees were given several questionnaires documenting demographic and social characteristics, medical history, health habits, the use of tobacco and marijuana (questionnaire administered from July 1979 to 1986), and the use of alcohol (questionnaire administered from 1978 to 1985). About 86% of the examinees completed the tobacco or marijuana use questionnaire, and 80% completed the alcohol use questionnaire.

Definitions of Study Groups

About 14,600 respondents to the tobacco-marijuana survey during the study period smoking marijuana more than six times in their lifetimes and that they currently smoked marijuana. Among these persons, a group of 746 marijuana smokers reported smoking marijuana almost every day and never smoking tobacco.

We defined the first MHC at which the tobacco-marijuana survey was completed as the index MHC for the marijuana smoking group. We selected a comparison group of nonsmokers from respondents who reported never smoking marijuana or tobacco. For each marijuana smoking subject, we attempted to match a nonsmoker by sex, age (birth year), race (Asian, African American, white), and index MHC date (within a month). We initially matched controls with 709 marijuana smokers. To control for varying lengths of Kaiser Permanente membership, we selected for study those pairs in which both members were enrolled in Kaiser for either at least one or at least two years after the index MHC. This process left 486 pairs for whom medical charts were reviewed (65% of the 746 original marijuana smokers). An additional 70 persons were excluded from this report because of the unavailability of an alcohol questionnaire after December 1985. The final sample thus consisted of 452 marijuana smokers and 450 nonsmokers.

Data Sources

The index MHC questionnaire provided information on sex, age, race, education, and marital status; self-reported health status (a checklist of 34 medical conditions); the existence of serious illnesses; hospital admissions in the past year; and the presence of problems with drugs. Data on marijuana and tobacco use, duration of marijuana use, and number of days ill with a cold, flu, or sore throat were obtained from the supplemental tobacco-marijuana survey. We used a drinking status measure derived in previous studies from items regarding quantity and frequency of drinking on the alcohol survey. 6 Six drinking categories were defined for this study: abstainer, ex-drinker, occasional (<1 drink per month), less than one drink per day but more than one per month, one to two drinks per day, and three or more drinks per day. The small number of ex-drinkers was combined with abstainers in the main analyses.

Kaiser Permanente outpatient medical records were reviewed by two trained medical records technicians who were unaware of subjects' marijuana smoking status. The medical records of each pair of subjects were reviewed for the same follow-up period, which was either one or two years after the index MHC date, depending on the length of membership in the Kaiser program. Following a written protocol, records reviewers identified all office visits to a physician or nurse practitioner. Prenatal visits were excluded, as were telephone contacts, letters, and visits for procedures only, such as ultrasonograms. As many as three illnesses were coded as reasons for the visit, using the International Classification of Diseases, 9th Revision, codes. 7 Each visit was assigned to one of three categories for this report: respiratory conditions (codes 460 to 519), injuries and poisonings (codes 800 to 999), or other diseases and conditions (all other codes). If more than one, the reason listed first was used. Inpatient data were obtained from Kaiser Permanente computer-based hospital admission files. All hospital admissions were included. Because of the small number of hospital admissions during the follow-up period, we combined all diagnoses in the analysis.

Analysis

Differences in the distribution of baseline characteristics were evaluated with X.sup.2 tests. Poisson regression was used to estimate the relative risk for the marijuana smoking group versus the nonsmoking group of outpatient visits or hospital admissions. The matched-pairs design was dropped in the analysis, and the variables used for matching were instead controlled statistically to avoid dropping both members of a pair when only one member was missing data on a covariate. Covariates in each regression model included alcohol consumption, age, sex, race, educational level, and marital status. Terms for marijuana exposure interacting with drinking status were introduced to examine possible interaction effects. The SAS statistical analysis package was used for all analyses. 8

Results

Characteristics of the marijuana smokers and the nonsmokers at the time of the index MHC are compared in Table 1. Marijuana smokers had a lower educational level and were less likely to be married than nonsmoking subjects. Alcohol drinking levels differed dramatically between the two groups, with marijuana smokers being more likely to drink alcohol and (among current drinkers) to drink more heavily. Marijuana smokers reported more days ill with a cold, flu, or sore throat in the past year and were more likely than the nonsmoking group to report having a serious problem with drugs. TABULAR DATA 1 OMITTED

A total of 6,088 visits were recorded, including 3,206 among the marijuana smoking group and 2,882 among the nonsmoking group. At least one outpatient visit for respiratory problems was made by 36% of the marijuana smokers versus 33% of the nonsmokers, 39% versus 28% made at least one visit for injury, and 94% versus 93% made at least one visit for other reasons. After adjustment for covariates, the marijuana smoking group showed small but statistically significant increased risks of outpatient visits for all three categories of conditions (Table 2). TABULAR DATA 2 OMITTED

Interaction between marijuana smoking and alcohol consumption was significant in relation to visits for injury and for other reasons but not in relation to visits for respiratory problems. The percentage distributions of visits for injury (none versus is greater or less than 1) by drinking level suggest that the generally higher injury risk for the marijuana smoking group compared with the nonsmoking group was reduced in the heaviest drinking level (Table 3). For other diseases, the difference in risk was higher in the nondrinking and heaviest drinking levels (Table 3). TABULAR DATA 3 OMITTED

The duration of marijuana smoking was associated in different ways with the three categories of visits (Table 4). The risk of respiratory visits was significantly elevated for persons who had smoked marijuana for less than ten years, but not for those who had smoked for ten years or more. Among marijuana smokers, there was a negative association between duration of smoking and risk of visits for respiratory problems (P =.0002). For injury visits, however, a longer duration of marijuana smoking was associated with a greater risk. Compared with the nonsmoker group, persons who had smoked marijuana for 15 years or more had twice the risk of visits for injury. A test for linear trend was significant ( P=.0001). For other types of visits, only those who had smoked marijuana for five to nine years had a significantly increased risk compared with the nonsmoker group, and the other duration categories did not follow a consistent pattern. TABULAR DATA 4 OMITTED

There were 86 hospital admissions in the two study groups. The relative risk for the marijuana smoking group compared with the nonsmoker group was elevated but not statistically significant (relative risk RR = 1.51; 95% confidence interval CI = 0.93, 2.46; P = .10). A duration of marijuana use of less than five years was of borderline significance (RR = 2.02; 95% CI = 0.98, 4.15; P =06). There was no significant interaction between marijuana smoking and alcohol use.

Discussion

Although epidemiologic studies concerning the health consequences of smoking marijuana are relatively few, a long-term use of marijuana has been implicated as a possible hazard to mental, pulmonary, immune, and reproductive functioning, 9 and marijuana intoxication has been implicated as a risk factor for accidents and injuries. 10 Because marijuana is usually ingested by smoking, possible respiratory effects have naturally been the most frequently investigated.

Compared with tobacco smokers, marijuana smokers typically smoke fewer cigarettes per day but consume more of the cigarette, inhale longer and more deeply, and retain the smoke longer in the lungs. 11 This probably explains why the respiratory deposition of tar and adsorption of carbon monoxide in experimental subjects were four and five times higher, respectively, after smoking marijuana than after smoking tobacco. 12 Because of the high prevalence of cigarette smoking among marijuana smokers, however, it has been difficult to assess the independent association between marijuana smoking and respiratory disease, including lung cancer. 13 Marijuana use has been linked to respiratory problems. 14-17 In one study, heavy smokers of marijuana, whether or not they also smoked tobacco, reported more chronic bronchitis symptoms and more acute bronchitis episodes than nonsmokers of either marijuana or tobacco. 15 Heavy marijuana smoking, with or without concomitant tobacco smoking, appears to affect large (but not small) airway function adversely and to produce histologic lesions in the airways. 15,16,18 A positive association between smoking "nontobacco cigarettes" (presumed to be marijuana) and respiratory symptoms in smokers and nonsmokers of tobacco was reported in a population survey in Tucson, Arizona. Lung function was decreased among male--but not female--smokers of nontobacco cigarettes more than among tobacco smokers. 19

Marijuana has repeatedly been found to be the second most common drug, after alcohol, present in the blood of nonfatally and fatally injured persons, 20,21 although the role marijuana may play in injury-producing events remains uncertain. 22 Laboratory studies have shown decreased driving-related skills after smoking marijuana. 10 In one experimental study, driving performance declined substantially after ingesting marijuana and alcohol together, but did not decline after taking either substance alone.

In a Swedish study following a cohort of 45,540 male military conscripts for 15 years, heavier cannabis users had a nearly three times greater risk of death than nonusers, but the association did not remain statistically significant after control for the use of alcohol, other drugs, and social background variables. 24 In another study of the same Swedish cohort, heavier cannabis users had an elevated risk of schizophrenia compared with nonusers, even after adjusting for psychosocial covariates. 25

As the first evidence based on medical records of nontobacco smoking, daily marijuana users, our results make a unique contribution to the growing research on the harmful health effects of marijuana. Our finding of an increased risk of respiratory-related outpatient visits expands the evidence suggesting that frequent marijuana smoking may increase the risk of respiratory illness independent of tobacco smoking. Marijuana smokers in our study also reported a higher prevalence of upper respiratory tract infections compared with nonsmokers. On the other hand, the duration of marijuana smoking appeared to be inversely related to the risk of outpatient visits for respiratory problems. This result was contrary to our expectation and remains an issue for future research. In our data, long-term marijuana smokers may be the "survivors" of a selection process in which persons who experienced respiratory symptoms were more likely to quit smoking marijuana early in the process.

We also found increased risks of injury-related and other (nonrespiratory, noninjury) outpatient visits among marijuana smokers, suggesting that marijuana use may have many adverse health effects. The complex interaction between marijuana and alcohol use in relation to the risk of medical care use in both of these areas underscores the important role of alcohol in combination with marijuana. 26,27 The duration of marijuana use appeared to be positively related to the risk of making injury-related visits. As with respiratory-related visits, this result was unexpected. It is not clear why a longer use of marijuana would be associated with a greater injury risk and a lower respiratory risk, but these results deserve additional study. The duration of marijuana use was not related to the risk of other types of outpatient visits.

Marijuana smokers in our study also tended to have an elevated risk of being admitted to a hospital. Although the association was not statistically significant, it was consistent with our results regarding medical office visits and thus supports the hypothesis that marijuana smoking is associated with adverse health effects.

Several caveats should be noted. We had no data regarding the use of other drugs such as cocaine; if associated with marijuana use, they may account for the observed differences. Only 6% of the marijuana smokers, however, reported having serious problems with drugs at their index MHC.

Another potential problem is our reliance on self-reporting. The use of illegal or socially undesirable substances such as tobacco, alcohol, marijuana, and other drugs may well be underreported. 28 We are unable to assess this possible bias. Our study subjects, however, completed their questionnaires in a health care setting in which confidentiality was assured.

Finally, our study was intended to serve as a pilot "hypothesis-generating" study of marijuana smoking and health. Restricting subjects to nonsmokers of tobacco allowed us to efficiently assess an association between marijuana use and respiratory illnesses independent of tobacco use but at the cost of studying an unrepresentative sample of marijuana smokers, many of whom smoke tobacco. 29

In summary, daily marijuana smoking appears to be associated with respiratory conditions even among persons who never smoked tobacco. This association is consistent with a possible independent deleterious effect of marijuana smoking on respiratory health. Frequent marijuana use also appears to be intimately linked to alcohol consumption as a risk factor for injury-related and other medical care. These data are limited, but a larger study in progress (S.S., principal investigator) should elucidate the joint roles of tobacco and marijuana in relation to respiratory health and of alcohol and marijuana in relation to traumatic injuries and other illnesses. This study will include never users, former users, and current users of marijuana, tobacco, and alcohol and will examine medical experience and mortality over a longer period.

Physicians and other primary care professionals may wish to consider counseling patients who frequently smoke marijuana about the potentially widespread harm its use may entail. In our study, physicians recorded marijuana use in the medical records of only 3% of the marijuana smokers, all of whom smoked daily or almost daily. As evidence of the health consequences of smoking marijuana accumulates, physicians should take note of this possibly

important health behavior.

Acknowledgment

This work was assisted by Susan Reinheimer, Patricia O'Rourke, Harald Kipp, Merrill Jackson, and Diana Holt.

CI = confidence interval

MHC = multiphasic health checkup

RR = relative risk

(*) See also the editorial by D. P. Tashkin, MD, "Is Frequent Marijuana Smoking Harmful to Health?" on pages 635-637 of this issue.

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