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Methods
A potential pool of 74 young adults with urinalysis results, self-reports of marijuana use and a broad measure of IQ obtained at both a preteen (9–12 years) and a young adult (17–20 years) assessment was available. Two subjects with inconsistencies between the self- report of marijuana use and the urine screening results were excluded, as were one subject who tested positive for cocaine and another who was taking methylphenidate. Consequently, the final sample comprised 70 subjects whose self-report of marijuana use and absence of hard drug use had been validated by urinalysis results.
During the preteen period and before initiation of marijuana use, IQ was measured by means of the Wechsler Intelligence Scale for Children-III (WISC).23 When the subjects were young adults, IQ was evaluated with the Wechsler Adult Intelligence Scale-III (WAIS).24 The outcome variable for the examination of potential marijuana effects was an IQ difference score, derived by subtracting the preteen WISC IQ score from the young adult WAIS IQ score. Thus a positive difference score reflects an increase in IQ over the approximately 10-year period, whereas a negative score reflects a decrease.
Marijuana use was determined by 2 procedures that were part of an extensive neuropsychologic battery given to the 17– to 20-year-olds. The first consisted of a questionnaire completed by the subject, which asked for details of current and past marijuana use, as well as other drug use. The second was a urine sample analyzed for the presence of cannabinoids, amphetamines, opiates, cocaine and cotinine (a metabolite of nicotine). All metabolite concentrations were adjusted for creatinine to control for urine dilution. Although these procedures did not assess the strength of the marijuana used by the OPPS subjects, an estimate was suggested by Health Canada's analysis of marijuana seized by police between 1996 and 1999, which revealed an average of 5% to 6% tetrahydrocannabinol (THC).
Marijuana measures treated as continuous variables were self-report of mean number of joints currently smoked per week, self-report of length of time (months) that marijuana had been smoked and total estimated number of joints smoked (mean number of joints smoked per week multiplied by number of weeks of use). The mean number of joints currently smoked per week was also treated as a categorical variable, as follows: the subjects were grouped as light current regular users, heavy current regular users, former regular users or non-users.
Categorization of the current marijuana users as light or heavy users was based on both the self-report and the urinalysis data. The urinalysis data were bimodally distributed: 11 subjects had cannabinoid to creatinine ratios between 4 and 54 ng/mg, and 13 subjects had ratios between 147 and 705 ng/mg. These 2 groups of subjects were used to validate the categorization based on self-reports. Defining heavy regular use as at least 5 joints per week (n = 15) and light regular use of any amount less than 5 joints at least once a week (n = 9) optimized concordance with the bimodal urine division as indicated by 𝛘2 analysis. Eight (73%) of the 11 subjects with the lower metabolite values smoked fewer than 5 joints per week, and 12 (92%) of the 13 subjects with the higher metabolite values smoked an average of 5 or more joints per week (p = 0.001).
Of the 70 subjects, 37 were non-users who had never used marijuana regularly (where regular use was defined as at least once a week) and who had not used any marijuana in the past 2 weeks; 9 were former users who had smoked marijuana regularly in the past but had not smoked for at least 3 months before the young adult assessment; 9 were light current users; and 15 were heavy current users.
The assessments were conducted in laboratories at Carleton University, Ottawa. Given that the testing sessions commenced in the early morning and that all subjects reported no use of marijuana on the day of testing, it is unlikely that the subjects were assessed while in an acute state of intoxication.
The validity of self-reporting for current marijuana use was examined with 2 approaches. The initial selection of the 70 subjects involved a criterion of concordance between self-reports of marijuana use and urine screening results (see above). The second measure of concordance was a high correlation between reported current marijuana use and the cannabinoid to creatinine ratio found with urinalysis (r = 0.70, p < 0.001). Although self-reports of earlier use could not be directly confirmed pharmacologically, their reliability is enhanced by the validity of the self-reporting for current marijuana use.
In examining the relation between marijuana use and IQ difference scores, we considered a variety of potentially confounding variables, including variables related to socioeconomic status, such as family income and parental education; the subject's education level (number of years of education at the time of the young adult assessment); age and sex of the subject; mother's age at the time of the subject's birth; maternal use of cigarettes, marijuana and alcohol during pregnancy; and the subject's use of tobacco and alcohol and exposure to secondhand marijuana smoke. In the subsequent analyses, we controlled for any potential confounding factor that was related to both the marijuana independent variable (at ? = 0.1) and the IQ difference score (at ? = 0.05).25
Hierarchical regression (a statistical approach to measure the impact of marijuana use after considering potential confounders) was used to examine the predictive relation of quantity (both mean number of joints per week and total joints over lifetime) and duration (period of use) of current marijuana use to the IQ difference score. Differential effects on the IQ difference score of light current use, heavy current use and former use as contrasted to non-use were examined with Dunnett's 2-sided multiple comparison procedure26 with analysis of variance (ANOVA) and analysis of covariance (ANCOVA) when required to control for confounding variables.

https://www.cmaj.ca/content/166/7/887.long

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