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Marijuana Use, Diet, Body Mass Index, and Cardiovascular Risk Factors (from the CARDIA Study)

      Marijuana use has been associated with increased appetite, high caloric diet, acute increase in blood pressure, and decreases in high-density lipoprotein cholesterol and triglycerides. Marijuana is the most commonly used illicit drug in the United States, but its long-term effects on body mass index (BMI) and cardiovascular risk factors are unknown. Using 15 years of longitudinal data from 3,617 black and white young adults participating in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether marijuana use was associated with caloric intake, BMI, and cardiovascular risk factors. Of the 3,617 participants, 1,365 (38%) reported ever using marijuana. Marijuana use was associated with male gender, tobacco smoking, and other illicit drug use. More extensive marijuana use was associated with a higher caloric intake (2,746 kcal/day in never users to 3,365 kcal/day in those who used marijuana for ≥1,800 days over 15 years) and alcohol intake (3.6 to 10.8 drinks/week), systolic blood pressure (112.7 to 116.5 mm Hg), and triglyceride levels (84 to 100 mg/dl or 0.95 to 1.13 mmol/L, all p values for trend <0.001), but not with higher BMI and lipid and glucose levels. In multivariate analysis, the associations between marijuana use and systolic blood pressure and triglycerides disappeared, having been mainly confounded by greater alcohol use in marijuana users. In conclusion, although marijuana use was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors, such as high caloric diet, tobacco smoking, and other illicit drug use, which all have long-term detrimental effects on health.
      Marijuana is currently used by 14.6 million Americans, making it the most commonly used illicit drug in the United States.
      • Compton W.M.
      • Grant B.F.
      • Colliver J.D.
      • Glantz M.D.
      • Stinson F.S.
      Prevalence of marijuana use disorders in the United States 1991–1992 and 2001–2002.

      Results from the 2002 National Survey on Drug Use and Health (NSDUH). Available at: http://oas.samhsa.gov/NHSDA/2k3NSDUH/2k3results.htm#ch2. Accessed on December 5, 2005.

      Despite the high prevalence of marijuana use, few studies have assessed its health effects. Marijuana use appears to stimulate appetite, increase food and caloric intake, and induce acute increases in body weight under research ward conditions.
      • Mendelson J.H.
      Marijuana use. Biologic and behavioral aspects.
      • Foltin R.W.
      • Fischman M.W.
      • Byrne M.F.
      Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory.
      Cross-sectional epidemiologic studies to date on marijuana use and body mass index (BMI) have yielded conflicting results.
      • Smit E.
      • Crespo C.J.
      Dietary intake and nutritional status of US adult marijuana users results from the Third National Health and Nutrition Examination Survey.
      • Mittleman M.A.
      • Lewis R.A.
      • Maclure M.
      • Sherwood J.B.
      • Muller J.E.
      Triggering myocardial infarction by marijuana.
      Marijuana smoke, which is close in content to tobacco smoke,
      • Tashkin D.P.
      • Baldwin G.C.
      • Sarafian T.
      • Dubinett S.
      • Roth M.D.
      Respiratory and immunologic consequences of marijuana smoking.
      has been associated with acute increases in blood pressure
      • Sidney S.
      Cardiovascular consequences of marijuana use.
      • Johnson S.
      • Domino E.F.
      Some cardiovascular effects of marijuana smoking in normal volunteers.
      and decreases in high-density lipoprotein (HDL) cholesterol and triglycerides.
      • Kalofoutis A.
      • Dionyssiou-Asteriou A.
      • Maravelias C.
      • Koutselinis A.
      Changes of HDL-lipid composition as related to delta 9-THC action.
      A possible effect of marijuana on HDL cholesterol might occur, as is the case for tobacco. One study found a decreased time to onset of chest pain on a treadmill test in patients with angina pectoris,
      • Aronow W.S.
      • Cassidy J.
      Effect of marijuana and placebo-marijuana smoking on angina pectoris.
      and another indicated that marijuana might acutely trigger myocardial infarction.
      • Mittleman M.A.
      • Lewis R.A.
      • Maclure M.
      • Sherwood J.B.
      • Muller J.E.
      Triggering myocardial infarction by marijuana.
      Although several mechanisms exist by which marijuana use might contribute to the development of long-term cardiovascular conditions, data are limited to the short-term effects of marijuana.
      • Sidney S.
      Cardiovascular consequences of marijuana use.
      Using 15 years of longitudinal data, we assessed whether marijuana use was associated with caloric intake, BMI, and cardiovascular risk factors.

      Methods

      Study design

      The Coronary Artery Risk Development in Young Adults (CARDIA) study is a multicenter, longitudinal study of the development of coronary artery disease risk factors in young adults. The cohort enrolled 5,115 black and white adults who were 18 to 30 years of age in 1985 to 1986 and recruited from 4 metropolitan areas (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California). With informed consent of participants and approval of the institutional review board at each site, participants underwent 6 examinations to date (examinations in 1985 to 86 and at years 2, 5, 7, 10, and 15). Details of the study design have been published elsewhere.
      • Friedman G.D.
      • Cutter G.R.
      • Donahue R.P.
      • Hughes G.H.
      • Hulley S.B.
      • Jacobs Jr, D.R.
      • Liu K.
      • Savage P.J.
      CARDIA study design, recruitment, and some characteristics of the examined subjects.

      Study sample

      Of the 4,993 surviving participants, 3,672 (74%) completed the year 15 examination. We excluded from all analyses participants with missing data on marijuana use at baseline and year 15 (n = 42) and on all cardiovascular risk factors (n = 13), with a final sample of 3,617 participants.

      Marijuana use

      A detailed, self-administered questionnaire of current and ever use of illicit drugs based on questionnaire items from the National Household Survey on Drug Abuse
      • Braun B.L.
      • Murray D.M.
      • Sidney S.
      Lifetime cocaine use and cardiovascular characteristics among young adults the CARDIA study.
      was administered at each examination. Ever users of marijuana were asked about the number of days of use in the previous 30 days at each visit and about lifetime use of marijuana (1 to 9, 10 to 99, 100 to 499, or ≥500 times). To better assess marijuana use over the long study period and to account for heavy marijuana users who may have consumed it >500 times in their life, we constructed an index of interval marijuana use over 15 years and used it as the main predictor for all analyses. We used number of days with marijuana exposure in the previous 30 days before the different examinations as an estimate of frequency of use, and multiplied that number by the number of months between each examination to obtain an estimate of overall interval exposure to marijuana. We assumed that changes in amount of marijuana use occurred halfway between completed examinations. A similar estimation has been used in a longitudinal study of the effects of marijuana on lung function.
      • Taylor D.R.
      • Fergusson D.M.
      • Milne B.J.
      • Horwood L.J.
      • Moffitt T.E.
      • Sears M.R.
      • Poulton R.
      A longitudinal study of the effects of tobacco and cannabis exposure on lung function in young adults.
      We used the measurement of the previous 30 days because it has been shown to be more reliable than lifetime use.
      • Harrison E.R.
      • Haaga J.
      • Richards T.
      Self-reported drug use data what do they reveal?.
      For categories of marijuana exposure, we used <180, 180 to 1,799, and ≥1,800 days, which correspond to average exposures of <1, 1 to 9, and ≥10 days/month over the 15-year study period, similar to the categories used in the Third National Health and Nutrition Examination Survey (NHANES III).
      • Smit E.
      • Crespo C.J.
      Dietary intake and nutritional status of US adult marijuana users results from the Third National Health and Nutrition Examination Survey.
      We also tested other indicators of marijuana use, including current use in the previous 30 days and lifetime use at the year-15 examination.

      BMI and cardiovascular risk factors

      To calculate BMI, weight was measured with subjects in light clothing to the nearest 0.2 kg with a calibrated balance beam scale and height without shoes to the nearest 0.5 cm using a vertical ruler.
      • Pereira M.A.
      • Jacobs Jr, D.R.
      • Van Horn L.
      • Slattery M.L.
      • Kartashov A.I.
      • Ludwig D.S.
      Dairy consumption, obesity, and the insulin resistance syndrome in young adults the CARDIA Study.
      Waist circumference was measured in duplicate at the minimum abdominal girth. The same methods, training, and certification procedures were used at each examination. Hawksley’s random zero was used to measure blood pressure.
      • Pereira M.A.
      • Jacobs Jr, D.R.
      • Van Horn L.
      • Slattery M.L.
      • Kartashov A.I.
      • Ludwig D.S.
      Dairy consumption, obesity, and the insulin resistance syndrome in young adults the CARDIA Study.
      After a 5-minute rest, the right arm blood pressure of a seated participant was assessed at 3 1-minute intervals. The 2 final blood pressure values were averaged to decrease variability. Fasting plasma levels of total cholesterol, HDL cholesterol, triglycerides, and glucose were measured at baseline and year 15 according to CARDIA protocol.
      • Pletcher M.J.
      • Varosy P.
      • Kiefe C.I.
      • Lewis C.E.
      • Sidney S.
      • Hulley S.B.
      Alcohol consumption, binge drinking, and early coronary calcification findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
      For patients who did not fast for ≥8 hours before clinical examinations, data on triglycerides and glucose were considered missing.

      Dietary assessment

      CARDIA administered the participant dietary questionnaire at baseline and year-7 examinations. To improve the accuracy of estimating diet intake, we averaged the intake reported during these 2 diet interviews.
      • Pereira M.A.
      • Jacobs Jr, D.R.
      • Van Horn L.
      • Slattery M.L.
      • Kartashov A.I.
      • Ludwig D.S.
      Dairy consumption, obesity, and the insulin resistance syndrome in young adults the CARDIA Study.
      The CARDIA Diet History queries usual dietary practices and obtains quantitative food frequency over the previous 28 days.
      • McDonald A.
      • Van Horn L.
      • Slattery M.
      • Hilner J.
      • Bragg C.
      • Caan B.
      • Jacobs Jr, D.
      • Liu K.
      • Hubert H.
      • Gernhofer N.
      • et al.
      The CARDIA dietary history development, implementation, and evaluation.
      The reliability and validity of this Diet History was assessed in 128 young adults.
      • Liu K.
      • Slattery M.
      • Jacobs Jr, D.
      • Cutter G.
      • McDonald A.
      • Van Horn L.
      • Hilner J.E.
      • Caan B.
      • Bragg C.
      • Dyer A.
      • et al.
      A study of the reliability and comparative validity of the cardia dietary history.
      Correlations between daily nutrient intakes and calorie-adjusted nutrient values from the 2 histories were generally in the range of 0.50 to 0.80 for whites, but often lower for blacks, with most in the range of 0.30 to 0.70. Correlations between mean daily nutrient intakes from this Diet History and means from 7 randomly scheduled 24-hour recalls were generally >0.50.

      Covariates

      At year 15, we estimated total ethanol consumption per week in milliliters of ethanol and the usual number of drinks per week.
      • Pletcher M.J.
      • Varosy P.
      • Kiefe C.I.
      • Lewis C.E.
      • Sidney S.
      • Hulley S.B.
      Alcohol consumption, binge drinking, and early coronary calcification findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
      We also collected self-reported race, gender, age, number of years of education completed, annual income, smoking status, and illicit drug use. We measured physical activity at year 15 with the Physical Activity History Questionnaire, which has been shown to be a valid, reliable indicator of physical activity.
      • Jacobs DR H.L.
      • Haskell W.L.
      • Pirie P.
      • Sidey S.
      Validity and reliability of short physical activity history CARDIA and the Minnesota Heart Health Program.
      Physical fitness was determined based on the duration of treadmill testing at baseline.
      • Carnethon M.R.
      • Gidding S.S.
      • Nehgme R.
      • Sidney S.
      • Jacobs Jr, D.R.
      • Liu K.
      Cardiorespiratory fitness in young adulthood and the development of cardiovascular disease risk factors.

      Statistical analysis

      To avoid obscuring a nonlinear (“J-” or “U-shaped”) relation, we categorized participants by their average marijuana use over the 15-year study period (never, <180, 180 to 1,799, or ≥1,800 days), as previoualy described. We used chi-square tests for trend for categorical variables and tests for trend for continuous variables across marijuana-use categories. We compared means of dietary factors and adjusted for age, race, gender, study center, and caloric intake
      • Pereira M.A.
      • Jacobs Jr, D.R.
      • Van Horn L.
      • Slattery M.L.
      • Kartashov A.I.
      • Ludwig D.S.
      Dairy consumption, obesity, and the insulin resistance syndrome in young adults the CARDIA Study.
      using linear regression. Because diet was only measured at baseline and year 7, we performed a sensitivity analysis using only baseline data for the association between marijuana use and diet intake. We used multiple linear regressions to assess relations between marijuana use over 15 years, BMI, and cardiovascular risk factors in 2000 to 2001. We first examined the unadjusted associations and then adjusted for potential confounders based on biologic plausibility and for baseline level of the dependent variable. We also tested whether relations between marijuana use and diet, BMI, or cardiovascular risk factors might differ by race and gender with a prespecified p value <0.05 for interaction, but no significant interactions were found. All analyses were performed with SAS 8 (SAS institute, Cary, North Carolina) and verified by the CARDIA Data Coordinating Center.

      Results

      Participant characteristics

      Baseline characteristics are presented in Table 1. Most marijuana users (89%) reported using marijuana for <1,800 days over the specified 15 years (average 10 days/month). Only 37 participants (1%) used marijuana for ≥3,600 days (20 days/month), 14 of whom used it for ≥4,500 days (25 days/month). Higher marijuana use was associated with male gender, tobacco smoking, use of other illicit drugs, less education, and lower income. Higher marijuana use was associated with higher physical activity and physical fitness, but these differences were not significant after adjusting for gender, race, and study center (p >0.10 for the 2 comparisons). Correlations across interval marijuana use over the 15 years, current use in the previous 30 days, and lifetime use at the year-15 examination were high (all r values >0.60, p <0.001).
      Table 1Participant characteristics in 2000 to 2001 according to average marijuana use from 1985 to 2000 in the CARDIA study
      CharacteristicsMarijuana Use Over 15-Year Study Period
      These categories of marijuana exposure correspond to average exposures of <1, 1 to 9, and ≥10 days/month over the 15-year study period, similar to the categories used in the NHANES III.5
      p Value
      Chi-square tests for trend for categorical variables and F tests for trend for continuous variables across marijuana-use categories.
      Never User<180 Days180–1,799 Days≥1,800 Days
      (n = 2,252)(n = 610)(n = 601)(n = 154)
      Sociodemographics
       Age (yrs)40.3 ± 3.739.9 ± 3.640.1 ± 3.640.1 ± 3.60.63
       Race/gender<0.001
        White women717 (70%)180 (18%)106 (10%)22 (2%)
        Black women681 (68%)163 (16%)135 (13%)27 (3%)
        White men513 (57%)158 (18%)166 (18%)66 (7%)
        Black men351 (50%)110 (16%)195 (28%)40 (6%)
       Yrs of education15.2 ± 2.514.8 ± 2.613.9 ± 2.413.8 ± 2.4<0.001
       Annual income (dollars/yr)<0.001
        <25,000287 (50%)112 (20%)143 (25%)30 (5%)
        25,000–49,999543 (60%)152 (17%)161 (18%)52 (6%)
        50,000–99,999855 (65%)204 (16%)198 (15%)51 (4%)
        ≥100,000551 (69%)133 (17%)93 (12%)21 (3%)
      Substance use<0.001
       Never smoker
      Smoking status was categorized as current (≥5 cigarettes/week for ≥3 months), former (smoking regularly before the interview but currently not smoking), and never.
      1,606 (74%)291 (13%)230 (11%)47 (2%)
       Former smoker
      Smoking status was categorized as current (≥5 cigarettes/week for ≥3 months), former (smoking regularly before the interview but currently not smoking), and never.
      358 (54%)145 (22%)120 (18%)36 (5%)
       Current smoker
      Smoking status was categorized as current (≥5 cigarettes/week for ≥3 months), former (smoking regularly before the interview but currently not smoking), and never.
      296 (37%)173 (22%)250 (32%)72 (9%)
       No. of cigarettes/day in smokers12.4 ± 9.511.8 ± 8.312.3 ± 8.914.1 ± 11.60.14
       Alcohol consumption (ml/d)6.2 ± 13.512.5 ± 19.921.9 ± 43.032.8 ± 44.5<0.001
       Cocaine use
      Illicit drug use was defined as ≥1 day of drug use (cocaine, crack, opiate, and amphetamine) in the previous month, consistent with previous CARDIA reports.13
      6 (14%)6 (14%)18 (42%)13 (30%)<0.001
       Crack use
      Illicit drug use was defined as ≥1 day of drug use (cocaine, crack, opiate, and amphetamine) in the previous month, consistent with previous CARDIA reports.13
      6 (10%)11 (19%)31 (53%)10 (17%)<0.001
       Opiate use
      Illicit drug use was defined as ≥1 day of drug use (cocaine, crack, opiate, and amphetamine) in the previous month, consistent with previous CARDIA reports.13
      1 (6%)2 (12%)11 (65%)3 (18%)<0.001
       Amphetamine use
      Illicit drug use was defined as ≥1 day of drug use (cocaine, crack, opiate, and amphetamine) in the previous month, consistent with previous CARDIA reports.13
      2 (17%)6 (50%)4 (33%)0 (0%)0.04
      Physical activity
       Mean exercise units
      Assessed using a standard instrument. Energy expenditure for all moderate and vigorous activities was calculated in exercise units.20
      326.4 ± 271.8355.9 ± 292.6405.9 ± 308.7395.3 ± 289.5<0.001
       Mean physical fitness (min)
      Physical fitness was based on duration (minutes) of treadmill testing.21
      9.6 ± 3.19.9 ± 3.09.9 ± 3.110.4 ± 3.00.002
      Data are presented as mean ± SD or number of patients (percentage).
      low asterisk These categories of marijuana exposure correspond to average exposures of <1, 1 to 9, and ≥10 days/month over the 15-year study period, similar to the categories used in the NHANES III.
      • Smit E.
      • Crespo C.J.
      Dietary intake and nutritional status of US adult marijuana users results from the Third National Health and Nutrition Examination Survey.
      Chi-square tests for trend for categorical variables and F tests for trend for continuous variables across marijuana-use categories.
      Smoking status was categorized as current (≥5 cigarettes/week for ≥3 months), former (smoking regularly before the interview but currently not smoking), and never.
      § Illicit drug use was defined as ≥1 day of drug use (cocaine, crack, opiate, and amphetamine) in the previous month, consistent with previous CARDIA reports.
      • Braun B.L.
      • Murray D.M.
      • Sidney S.
      Lifetime cocaine use and cardiovascular characteristics among young adults the CARDIA study.
      Assessed using a standard instrument. Energy expenditure for all moderate and vigorous activities was calculated in exercise units.
      • Jacobs DR H.L.
      • Haskell W.L.
      • Pirie P.
      • Sidey S.
      Validity and reliability of short physical activity history CARDIA and the Minnesota Heart Health Program.
      # Physical fitness was based on duration (minutes) of treadmill testing.
      • Carnethon M.R.
      • Gidding S.S.
      • Nehgme R.
      • Sidney S.
      • Jacobs Jr, D.R.
      • Liu K.
      Cardiorespiratory fitness in young adulthood and the development of cardiovascular disease risk factors.

      Dietary intake and marijuana use

      After adjustment for age, gender, race, and study center, marijuana use was associated with higher total caloric intake (Figure 1) and higher alcohol intake (p for trend <0.001 for the 2 comparisons; Table 2). The higher calories in marijuana users were mostly explained by larger intakes of all macronutrients. The relative contribution of alcohol to total calories increased across marijuana-use categories (p for trend <0.001), whereas the contribution of carbohydrates and protein slightly decreased (p values for trend <0.001 and 0.04, respectively). Marijuana use was particularly associated with beer and liquor intakes (p for trend <0.001 for the 2 comparisons). However, alcohol consumption was at a moderate level even in the high marijuana group (mean 1.5 drinks/day). Further adjustment for the greater physical activity in marijuana users yielded similar results. These associations did not differ qualitatively in stratified analysis by race and gender. An alternative cross-sectional analysis examining baseline marijuana use and baseline dietary patterns yielded similar results.
      Figure thumbnail gr1
      Figure 1Daily calories according to average marijuana use from 1985 to 2000 in the CARDIA study. Mean daily intake from total calories and each diet component (kilocalories per day) is shown (column height). Daily calories are adjusted for age, race, gender, and study center. Marijuana use was associated with higher total caloric intake (p for trend <0.001). The relative contribution of alcohol (black bars) to total calories increased across marijuana categories (p for trend <0.001), the contribution of carbohydrates (white bars) and protein (cross-hatched bars) slightly decreased (p for trend <0.001 and 0.04, respectively), and that of saturated fat (light gray bars) and unsaturated fat (dark gray bars) did not significantly differ.
      Table 2Adjusted mean values of dietary factors according to average marijuana use from 1985 to 2000 in the CARDIA study
      Means for dietary factors are adjusted for age, race, gender, study center, and caloric intake. Means for drinks per week are adjusted for age, race and gender, and study center.
      Characteristics
      To improve the accuracy of estimating diet intake, we averaged the intake reported during the 2 CARDIA diet interviews, similar to a previous CARDIA report.16
      Marijuana Use Over 15-Year Study Periodp Value
      Tests for trend across marijuana-use categories.
      Never User<180 Days180–1,799 Days≥1800 Days
      (n = 2,252)(n = 610)(n = 601)(n = 154)
      Dietary factors
      Participants with missing values for dietary factors (n = 66) were excluded from those analyses.
       Daily caloric intake (kcal/d)2,7462,8843,4283,365<0.001
       Saturated fat (% daily calories)13.213.313.113.30.89
       Unsaturated fat (% daily calories)23.323.523.323.10.37
       Carbohydrates (% daily calories)48.546.846.545.6<0.001
       Protein (% daily calories)14.614.414.614.20.04
      Alcohol
       Alcohol (% daily calories)1.83.33.94.9<0.001
       Drinks of alcohol/wk3.66.19.010.8<0.001
        Wine0.81.31.41.10.07
        Beer2.13.55.77.6<0.001
        Liquor0.71.31.92.1<0.001
      low asterisk Means for dietary factors are adjusted for age, race, gender, study center, and caloric intake. Means for drinks per week are adjusted for age, race and gender, and study center.
      To improve the accuracy of estimating diet intake, we averaged the intake reported during the 2 CARDIA diet interviews, similar to a previous CARDIA report.
      • Pereira M.A.
      • Jacobs Jr, D.R.
      • Van Horn L.
      • Slattery M.L.
      • Kartashov A.I.
      • Ludwig D.S.
      Dairy consumption, obesity, and the insulin resistance syndrome in young adults the CARDIA Study.
      Tests for trend across marijuana-use categories.
      § Participants with missing values for dietary factors (n = 66) were excluded from those analyses.

      BMI, cardiovascular risk factors, and marijuana use

      In unadjusted analysis (Table 3), marijuana use was not significantly associated with BMI, but it did seem to be associated with larger waist girth (p for trend 0.04). We also noted a positive linear relation between marijuana use and systolic blood pressure (p for trend <0.001), but not for diastolic blood pressure. Marijuana use was also associated with higher triglyceride levels (p for trend <0.001), but not with total cholesterol, HDL cholesterol, and glucose levels.
      Table 3Body mass index (BMI) and cardiovascular risk factors in 2000 to 2001 according to average marijuana use from 1985 to 2000 in the CARDIA study
      CharacteristicsMarijuana Use Over 15-Year Study Periodp Value
      Tests for trend across marijuana-use categories.
      Never User<180 Days180–1,799 Days≥1,800 Days
      (n = 2,252)(n = 610)(n = 601)(n = 154)
      Anthropometric measurements
       BMI (kg/m2)28.9 ± 0.128.5 ± 0.328.7 ± 0.328.0 ± 0.50.14
       Waist girth (cm)89.0 ± 0.389.1 ± 0.691.4 ± 0.691.0 ± 1.20.04
      Blood pressure (mm Hg)
       Systolic112.7 ± 0.3112.8 ± 0.6114.7 ± 0.6116.5 ± 1.2<0.001
       Diastolic74.5 ± 0.273.9 ± 0.574.8 ± 0.575.4 ± 0.90.24
      Lipids
       Total cholesterol
        mg/dl184.2 ± 0.8184.6 ± 1.5184.9 ± 1.5189.6 ± 3.10.07
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      4.77 ± 0.024.78 ± 0.044.79 ± 0.044.91 ± 0.08
       HDL cholesterol
        mg/dl51.0 ± 0.451.0 ± 0.850.6 ± 0.851.0 ± 1.20.96
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      1.32 ± 0.011.32 ± 0.021.31 ± 0.021.32 ± 0.03
       Triglycerides
        mg/dl84.1 ± 0.992.0 ± 0.992.9 ± 0.9100.0 ± 0.9<0.001
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      Triglycerides levels were log-transformed for statistical analyses because the distribution was skewed.
      0.95 ± 0.011.04 ± 0.011.05 ± 0.011.13 ± 0.01
      Glucose
        mg/dl86.7 ± 0.486.3 ± 0.986.8 ± 0.987.4 ± 1.60.57
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      4.81 ± 0.024.79 ± 0.054.82 ± 0.054.85 ± 0.09
      Values are means ± SE. Participants with missing values for waist girth (n = 13), lipid values (n = 42), and glucose (n = 50) were excluded from those analyses.
      low asterisk Tests for trend across marijuana-use categories.
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      Triglycerides levels were log-transformed for statistical analyses because the distribution was skewed.
      In multivariate analysis, associations between marijuana use and waist girth, systolic blood pressure, and triglycerides disappeared (Table 4). These associations were mainly confounded by greater alcohol use in marijuana users and demographic characteristics. For example, marijuana users were more likely to be men and to drink more alcohol, characteristics associated with high blood pressure. Because BMI may be on the causal pathway between marijuana use and cardiovascular risk factors, we repeated our multivariate models without BMI and obtained similar results. Further adjustment for differences in dietary intake did not meaningfully change these associations. We found no consistent evidence of any interaction across gender, race, and marijuana use and any of these outcome measurements. These associations did not differ qualitatively in stratified analyses by race and gender. We also tested other indicators of marijuana use at year 15 (current use in the previous 30 days and lifetime use) and found similar results for these associations.
      Table 4Adjusted levels of body mass index (BMI) and cardiovascular risk factors in 2000 to 2001 according to average marijuana use from 1985 to 2000 in the CARDIA study
      Values are means ± SE and were adjusted for age, gender, race, study center, tobacco use, amount of alcohol per day, other illicit drug use (cocaine, crack, heroin, amphetamine), units of daily physical activity, physical fitness, education, income levels, BMI, and baseline level of the dependent variable.
      CharacteristicsMarijuana Use Over 15-Year Study Periodp Value
      Tests for trend across marijuana-use categories.
      Never User<180 Days180–1,799 Days≥1,800 Days
      (n = 2,252)(n = 610)(n = 601)(n = 154)
      Anthropometric measurements
       BMI (kg/m2)28.8 ± 0.128.6 ± 0.228.8 ± 0.228.9 ± 0.30.65
       Waist girth (cm)89.3 ± 0.189.5 ± 0.289.7 ± 0.390.0 ± 0.50.17
      Blood pressure (mm Hg)
       Systolic113.6 ± 0.3112.9 ± 0.5112.1 ± 0.5112.9 ± 1.10.34
       Diastolic74.8 ± 0.274.2 ± 0.474.0 ± 0.473.9 ± 0.90.28
      Lipids
       Total cholesterol
        mg/dl184.2 ± 0.8184.2 ± 1.2184.6 ± 1.2186.1 ± 2.30.44
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      4.77 ± 0.024.77 ± 0.034.78 ± 0.034.82 ± 0.06
       HDL cholesterol
        mg/dl50.6 ± 0.450.6 ± 0.450.6 ± 0.451.4 ± 0.80.58
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      1.31 ± 0.011.31 ± 0.011.31 ± 0.011.33 ± 0.02
       Triglycerides
        mg/dl86.7 ± 0.988.5 ± 0.987.6 ± 0.992.9 ± 0.90.08
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      Triglyceride levels were log-transformed for statistical analyses because the distribution was skewed.
      0.98 ± 0.011.00 ± 0.010.99 ± 0.011.05 ± 0.01
       Glucose
        mg/dl86.7 ± 0.487.4 ± 0.785.8 ± 0.786.1 ± 1.60.59
        mmol/L
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      4.81 ± 0.024.85 ± 0.044.76 ± 0.044.78 ± 0.09
      low asterisk Values are means ± SE and were adjusted for age, gender, race, study center, tobacco use, amount of alcohol per day, other illicit drug use (cocaine, crack, heroin, amphetamine), units of daily physical activity, physical fitness, education, income levels, BMI, and baseline level of the dependent variable.
      Tests for trend across marijuana-use categories.
      Conversion factors: total cholesterol and HDL cholesterol, 1 mg/dl = 0.0259 mmol/L; triglycerides, 1 mg/dl = 0.0113 mmol/L; glucose, 1 mg/dl = 0.0555 mmol/L.
      § Triglyceride levels were log-transformed for statistical analyses because the distribution was skewed.

      Discussion

      In this population-based study of young adults, marijuana use was associated with higher caloric intake but was not independently associated with BMI or cardiovascular risk factors. Although marijuana use was not independently associated with physiologic markers of increased cardiovascular risk, it was strongly associated with other unhealthy behaviors, such as high dietary energy intake, tobacco smoking, and use of other illicit drugs, which have long-term detrimental effects on health.
      Our results showing higher energy and alcohol intake with more extensive marijuana use are consistent with the data from the NHANES III.
      • Smit E.
      • Crespo C.J.
      Dietary intake and nutritional status of US adult marijuana users results from the Third National Health and Nutrition Examination Survey.
      In our data, the higher total energy intake was explained by greater intake of all macronutrients and alcohol in marijuana users. The mechanisms by which marijuana increased appetite have not been well understood, but an important role of cannabinoid receptors and endogenous cannabinoid system has been suggested.
      • Black S.C.
      Cannabinoid receptor antagonists and obesity.
      Oral rimonabant, a new cannabinoid receptor-1 selective receptor antagonist, has been found to decrease appetite and body weight in humans and is in phase III clinical trials for the treatment of obesity.
      • Black S.C.
      Cannabinoid receptor antagonists and obesity.
      Because of the high energy diet in marijuana users, we would expect a higher BMI value in marijuana users, at least in unadjusted analyses, which was not identified in our data or those from the NHANES III.
      • Smit E.
      • Crespo C.J.
      Dietary intake and nutritional status of US adult marijuana users results from the Third National Health and Nutrition Examination Survey.
      However, other factors may play a role in this relation, such as a higher metabolic rate in marijuana users. In a placebo-controlled study of 8 participants, smoking marijuana caused a 28% increase in the metabolic rate, as measured by dioxide consumption.
      • Zwillich C.W.
      • Doekel R.
      • Hammill S.
      • Weil J.V.
      The effects of smoked marijuana on metabolism and respiratory control.
      A higher metabolic rate in marijuana users might explain the lack of association between marijuana use and BMI, despite a high energy diet. In contrast with the NHANES III,
      • Smit E.
      • Crespo C.J.
      Dietary intake and nutritional status of US adult marijuana users results from the Third National Health and Nutrition Examination Survey.
      we found that marijuana users had similar but not lower BMI values. There are several explanations for this difference. First, the association identified in the NHANES III was not very strong; BMI was only clinically different in heavy users (marijuana use ≥11 days/month), with a mean BMI of 24.7 versus 26.0 kg/m2 in lower marijuana users and 26.6 kg/m2 in noncurrent users.
      • Smit E.
      • Crespo C.J.
      Dietary intake and nutritional status of US adult marijuana users results from the Third National Health and Nutrition Examination Survey.
      In the NHANES III, differences in BMI remained after adjusting for age, gender, education, cigarette smoking, and caloric intake (p = 0.003), but the investigators did not adjust for other potential confounders such as physical activity and alcohol use.
      Previous studies have demonstrated the effects of short-term marijuana use on cardiovascular risk factors. In contrast, total exposure to marijuana over 15 years appears not to be associated with important differences in cardiovascular risk factors. The discrepancy between our results and those of studies showing acute increased blood pressure after marijuana use might be explained by the tolerance that develops to the acute effects of marijuana over a few weeks.
      • Sidney S.
      Cardiovascular consequences of marijuana use.
      In contrast to our findings, a previous cross-sectional study found that marijuana use was an independent predictor for systolic blood pressure among 86 black male students.
      • Adams L.L.
      • Washburn R.A.
      • Haile G.T.
      • Kuller L.H.
      Behavioral factors and blood pressure in black college students.
      However, this cross-sectional association was not found in black female students and was not adjusted for alcohol consumption or other participant characteristics aside from BMI. As shown in our study, higher alcohol use in marijuana users is a potentially important confounder of this association because alcohol is an important risk factor for high blood pressure.
      • Klatsky A.L.
      • Friedman G.D.
      • Siegelaub A.B.
      • Gerard M.J.
      Alcohol consumption and blood pressure Kaiser-Permanente Multiphasic Health Examination data.
      In contrast to the effect of tobacco smoking on HDL cholesterol,
      • Quensel M.
      • Agardh C.D.
      • Nilsson-Ehle P.
      Nicotine does not affect plasma lipoprotein concentrations in healthy men.
      our data showed no association between marijuana use and HDL cholesterol. Potential explanations are the relatively low lifetime dose of marijuana compared with tobacco smoking or the content of marijuana that is close to that of tobacco, except for the presence of cannabinoids in marijuana and nicotine in tobacco.
      • Tashkin D.P.
      • Baldwin G.C.
      • Sarafian T.
      • Dubinett S.
      • Roth M.D.
      Respiratory and immunologic consequences of marijuana smoking.
      Whether it is nicotine or other compounds in tobacco that decrease HDL cholesterol is controversial from the results of studies about nicotine replacement therapy.
      • Quensel M.
      • Agardh C.D.
      • Nilsson-Ehle P.
      Nicotine does not affect plasma lipoprotein concentrations in healthy men.
      • Moffatt R.J.
      • Biggerstaff K.D.
      • Stamford B.A.
      Effects of the transdermal nicotine patch on normalization of HDL-C and its subfractions.
      Our results indirectly suggest that the nicotine in tobacco smoke, and not the other chemicals that are identical in marijuana and tobacco smoke, causes the decrease in HDL cholesterol observed in tobacco smokers in other studies.
      • Garrison R.J.
      • Kannel W.B.
      • Feinleib M.
      • Castelli W.P.
      • McNamara P.M.
      • Padgett S.J.
      Cigarette smoking and HDL cholesterol the Framingham offspring study.
      One potential explanation for the lack of association between marijuana use and cardiovascular risk factors is the relatively low lifetime dose compared with tobacco smoking. The total lifetime dose of marijuana in marijuana users, even heavy ones, is generally much lower than the total lifetime dose of tobacco smoke in tobacco users. For example, most tobacco users smoke everyday compared with only 1% of participants in the CARDIA who used marijuana ≥20 days/month. In addition, a typical regular marijuana user smokes the equivalent of ≤1 marijuana cigarette per day and generally quits using marijuana relatively early in adulthood.
      • Sidney S.
      Comparing cannabis with tobacco—again.
      Although the active ingredients are not exactly identical, exposure of marijuana is generally much lower than that to tobacco smoking, and our data do not answer the question as to whether a similar marijuana exposure to usual tobacco exposure would affect cardiovascular risk factors.
      Our study has several limitations. Marijuana use is based on self-report, which may under-represent the prevalence of drug use.
      • Harrison E.R.
      • Haaga J.
      • Richards T.
      Self-reported drug use data what do they reveal?.
      Under-reporting of marijuana use may have attenuated our results. However, several features of the CARDIA study help minimize under-reporting of illicit drug use: a self-administered questionnaire was used instead of a face-to-face or telephone interview that may underestimate drug use; the examination takes place in a clinic that is not associated with a governmental agency or employer facility; and confidentiality is assured at each examination.
      • Braun B.L.
      • Murray D.M.
      • Sidney S.
      Lifetime cocaine use and cardiovascular characteristics among young adults the CARDIA study.
      Our constructed measurement of interval marijuana use over the 15-year period provides only a proxy for the true but nonobserved interval exposure to marijuana because it is based on previous 30-day use at the 6 CARDIA examinations. However, use in the previous month has been shown to be more reliable than lifetime use,
      • Harrison E.R.
      • Haaga J.
      • Richards T.
      Self-reported drug use data what do they reveal?.
      and it enabled us to assess the effects of marijuana for heavy users, which would not be possible using the lifetime-use variable limited to ≥500 uses. Moreover, our results were not sensitive to the choice of the indicators for marijuana use. Our results may not apply to long-term, heavy drug users who are unlikely to participate in a prospective cohort over 15 years and to comply with a 4-hour examination, as shown by the low rate of participants who used marijuana for ≥20 days/month (1%) compared with about 2% in the National Survey on Drug Use and Health.

      Results from the 2002 National Survey on Drug Use and Health (NSDUH). Available at: http://oas.samhsa.gov/NHSDA/2k3NSDUH/2k3results.htm#ch2. Accessed on December 5, 2005.

      We did not prove that marijuana causally increased energy intake from our data, but that unhealthy diet was associated with marijuana use. Another possible explanation for this association is potential bias in the self-reported diet that is not a highly reliable measurement
      • Liu K.
      • Slattery M.
      • Jacobs Jr, D.
      • Cutter G.
      • McDonald A.
      • Van Horn L.
      • Hilner J.E.
      • Caan B.
      • Bragg C.
      • Dyer A.
      • et al.
      A study of the reliability and comparative validity of the cardia dietary history.
      or an over-report of food intake by marijuana users. For example, little is known about the effect of marijuana on diet recall because marijuana use may affect memory.
      • Bolla K.I.
      • Brown K.
      • Eldreth D.
      • Tate K.
      • Cadet J.L.
      Dose-related neurocognitive effects of marijuana use.
      In conclusion, marijuana use was not independently associated with BMI and cardiovascular risk factors in these relatively healthy young adults. Further studies are needed to determine whether long-term, heavy use of marijuana is associated with a higher cardiovascular risk.

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