Cannabis exposure is not causally associated with either significant or residual detrimental effects on cognitive performance
"This pilot study assessed structural magnetic resonance imaging in older adults who were either current cannabis users (n = 28; mean age 69.8 years, 36% female) or nonusers (n = 28; mean age 66.8 years, 61% female). Recruitment targeted users who reported at least weekly use for at least the last year, although users had 23.55 years of regular cannabis use on average. ... No significant differences between groups were observed in performance on a brief computerized cognitive battery. These results suggest that cannabis use likely does not have a widespread impact on overall cortical volume while controlling for age."
This study "provides the first quantitative synthesis of the literature examining cannabis and cognitive functioning in adolescents and young adults (with a mean age of 26 years and younger). ... Sixty-nine studies of 2152 cannabis users and 6575 comparison participants with minimal cannabis exposure were included. ... Associations between cannabis use and cognitive functioning in cross-sectional studies of adolescents and young adults are small and may be of questionable clinical importance for most individuals. Furthermore, abstinence of longer than 72 hours diminishes cognitive deficits associated with cannabis use. ... [R]esults indicate that previous studies of cannabis in youth may have overstated the magnitude and persistence of cognitive deficits associated with use. Reported deficits may reflect residual effects from acute use or withdrawal."
"Participants completed a visuospatial working memory task during fMRI acquisition and multiple cognitive assessments at 12-years-old, prior to any reported cannabis use (baseline), and at 15-years-old. ... The consistency of our results from baseline to follow-up and a lack of group differences in behavioral development do not support the idea that early cannabis initiation alone predicts cognitive dysfunction by age 15. Further, the amount of reported cannabis use was not associated with behavioral performance. ... Purported neurocognitive effects of early cannabis onset may not be due to cannabis initiation alone, but also driven by limitations or late development of neurocognitive systems predictive of substance use."
"This study tested whether adolescents who used cannabis or met criteria for cannabis dependence showed neuropsychological impairment prior to cannabis initiation and neuropsychological decline from before to after cannabis initiation. ... Participants were 1989 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of twins born in England and Wales from 1994 to 1995. ... Compared with adolescents who did not use cannabis, adolescents who used cannabis had lower IQ in childhood prior to cannabis initiation and lower IQ at age 18, but there was little evidence that cannabis use was associated with IQ decline from ages 12-18. ... Moreover, adolescents who used cannabis had poorer executive functions at age 18 than adolescents who did not use cannabis, but these associations were generally not apparent within twin pairs. ... [In] conclusion: Short-term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests."
"[W]e used a prospective cohort design to test whether neurocognitive differences preceded cannabis onset and if early cannabis use was associated with poorer neurocognitive development. Participants completed a visuospatial working memory task during fMRI acquisition and multiple cognitive assessments at 12- years-old, prior to any reported cannabis use (baseline), and at 15-years-old. ...The consistency of our results from baseline to follow-up and a lack of group differences in behavioral development do not support the idea that early cannabis initiation alone predicts cognitive dysfunction by age 15. Further, the amount of reported cannabis use was not associated with behavioral performance. ... Conclusions: Purported neurocognitive effects of early cannabis onset may not be due to cannabis initiation alone."
This study "evaluates the relationship between change in cannabis use and changed cognitive performance over 8 years. ... Data were obtained from 2404 participants ... aged 20-24 years at baseline. ... At baseline, there were significant differences between cannabis groups on the California Verbal Learning Test immediate and delayed) and Symbol Digit Modality test. However, after controlling for education, gender, gender × group and gender × wave, there were no significant between-group differences. ... Cessation of cannabis use appears to be associated with an improvement in capacity for recall of information that has just been learned. No other measures of cognitive performance were related to cannabis after controlling for confounds."
"We used magnetic resonance imaging to investigate these effects in a group of 22 older, long-term cannabis users (reporting a mean of 20,100 lifetime episodes of smoking) and 26 comparison subjects with no history of cannabis abuse or dependence. When compared to control subjects, smokers displayed no significant adjusted differences in volumes of gray matter, white matter, cerebrospinal fluid, or left and right hippocampus. Moreover, hippocampal volume in cannabis users was not associated with age of onset of use not total lifetime episodes of use. These findings are consistent with recent literature suggesting that cannabis use is not associated with structural changes within the brain as a whole or the hippocampus in particular."
"The aim of this study is to assess brain function in frequent but relatively moderate cannabis users in the domains of working memory and selective attention. ... Functional magnetic resonance imaging was used to examine verbal working memory and visuo-auditory selective attention in ten frequent cannabis users (after 1 week of abstinence) and ten non-using healthy controls. Groups were similar in age, gender and estimated IQ. Cannabis users and controls performed equally well during the working memory task and the selective attention task. Furthermore, cannabis users did not differ from controls in terms of overall patterns of brain activity in the regions involved in these cognitive functions. ... No evidence was found for long-term deficits in working memory and selective attention in frequent cannabis users after 1 week of abstinence."
"Fifty-four monozygotic male twin pairs, discordant for regular marijuana use in which neither twin used any other illicit drug regularly, were recruited from the Vietnam Era Twin Registry. ... Twins were administered a comprehensive neuropsychological test battery to assess general intelligence, executive functioning, attention, memory and motor skills. Differences in performance between marijuana-using twins and their non-using co-twins were compared using a multivariate analysis of specific cognitive domains and univariate analyses of individual test scores. Dose response relationships were explored within the marijuana-using group. ... Out of the numerous measures that were administered, only one significant difference was noted between marijuana-using twins and their non-using co-twins on cognitive functioning. The results indicate an absence of marked long-term residual effects of marijuana use on cognitive abilities."
Cannabis exposure, even among young people, is not associated with causal, long-term changes in brain morphology
"Data came from the Pittsburgh Youth Study – a longitudinal study of 1000 boys. Boys completed self- reports of cannabis use annually from age 13–19, and latent class growth analysis was used to identify different trajectories of adolescent cannabis use A subset of boys (n = 181) subsequently underwent structural neuroimaging in adulthood, when they were between 30–36 years old on average. For this subset, we grouped participants according to their classified adolescent cannabis trajectory and tested whether these groups showed differences in adult brain structure in 14 a priori regions of interest, including six subcortical (volume only: amygdala, hippocampus, nucleus accumbens, caudate, putamen, and pallidum) and eight cortical regions (volume and thickness: superior frontal gyrus; caudal and rostral middle frontal gyrus; inferior frontal gyrus, separated into pars opercularis, pars triangularis, and pars orbitalis; lateral and medial orbitofrontal gyrus).
We found that adolescent cannabis use was not associated with adult brain structure in a sample of boys followed prospectively to adulthood. Boys were classified into one of four prototypical adolescent cannabis trajectory subgroups based on prospective assessments of cannabis use frequency from age 13–19: infrequent use/no use, desisting use, escalating use, or chronic-relatively frequent use. These subgroups showed different patterns of cannabis use across adolescence and differed in terms of their overall cumulative exposure to cannabis. For example, the infrequent/no use subgroup had used cannabis, on average, on four total days from age 13–19, whereas the chronic-relatively frequent subgroup had used cannabis, on average, on 782 total days from age 13–19. We found no differences in adult brain structure for boys in the different adolescent cannabis trajectory subgroups. Even boys with the highest level of cannabis exposure in adolescence showed subcortical brain volumes and cortical brain volumes and thickness in adulthood that were similar to boys with almost no exposure to cannabis throughout adolescence."
"In this study, high-resolution T1-weighted MRIs were obtained from 781 youth aged 14-22 years who were studied as part of the Philadelphia Neurodevelopmental Cohort. This sample included 147 cannabis users (109 occasional [≤1-2 times per week] and 38 frequent [≥3 times per week] users) and 634 cannabis non-users. Several structural neuroimaging measures were examined in whole brain analyses, including gray and white matter volumes, cortical thickness, and gray matter density. Established procedures for stringent quality control were conducted, and two automated neuroimaging software processing packages were used to ensure robustness of results. There were no significant differences by cannabis group in global or regional brain volumes, cortical thickness, or gray matter density, and no significant group by age interactions were found. Follow-up analyses indicated that values of structural neuroimaging measures by cannabis group were similar across regions, and any differences among groups were likely of a small magnitude. In sum, structural brain metrics were largely similar among adolescent and young adult cannabis users and non-users."
"In a large, multisite dataset of 120 controls and 141 cannabis users, we examined whether differences in key characteristics of the cortical surface -- including cortical thickness, surface area, and gyrification index were related to cannabis use characteristics, including (i) cannabis use vs. non-use, (ii) cannabis dependence vs. non-dependence vs. non-use, and (iii) early adolescent vs. late adolescent onset of cannabis use vs. non-use. Our results revealed that cortical morphology was not associated with cannabis use, dependence, or onset age. ... We additionally found no association between cortical surface area and gyrification index in relation to cannabis use. ... Our lack of finding in a well-powered study suggests that cortical surface morphology may be less associated with cannabis use than previously assumed."
"The aim of this report is to determine the size of associations between cannabis use and the volumes of seven subcortical regions of interest (ROIs) in two independent population-based samples. ... Sample 1 comprised 622 young male and female adult twins from the ongoing population- based Brisbane Longitudinal Twin Study. ... Sample 2 comprised 474 middle-age male twins from the population-based Harvard Drug Study. ... Magnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus; caudate nucleus; putamen; pallidum; hippocampus; amygdala; and nucleus accumbens."
... This is the largest exploratory analysis integrating brain imaging with self-report cannabis and comorbid substance use data. After correcting for multiple testing, there was no effect of cannabis use on the volume at any subcortical region of interest in young adults or middle-aged males. ... In the context of expanding medicalization and decriminalization and the concerns surrounding the consequences of increased cannabis availability, our findings suggest that normal variation in cannabis use is statistically unrelated to brain morphology as measured by subcortical volumes in non-clinical samples."
"The current study aimed to test the strength of association between (1) alcohol use and grey matter (GM) volume; (2) alcohol use and white matter (WM) integrity; (3) cannabis use and GM volume; and (4) cannabis use and WM integrity among adults and adolescents. ... The current analysis included adults aged 18-55 years (n = 853) and adolescents aged 14-18 years (n = 439) with a range of alcohol and cannabis use. ... Alcohol use severity is associated with widespread lower gray matter volume and white matter integrity in adults, and with lower gray matter volume in adolescents. ... No associations were observed between structural measures and past 30-day cannabis use in adults or adolescents."
"To our knowledge, this is the largest study to date examining the association between cannabis exposure (ever vs never used) and brain volumes. ... Despite speculation regarding the neurotoxic effects of tetrahydrocannabinol based on preclinical research, the observed cannabis-related volumetric differences were well within the range of normal variation. [D]ifferences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences."
"[T]his retrospective study examined brain morphology in a sample of adult daily marijuana users versus nonusers and a sample of adolescent daily users versus nonusers. Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter ... in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures. ... "[I]t seems unlikely that marijuana use has the same level of long-term deleterious effects on brain morphology as other drugs like alcohol."
After adjusting for potential confounders, the cumulative use of cannabis -- even among young people -- is not associated with either a significant or long-term adverse impact on intelligence quotient
"In the largest longitudinal examination of marijuana use and IQ change, ... we find little evidence to suggest that adolescent marijuana use has a direct effect on intellectual decline. ... [T]he lack of a dose-response relationship, and an absence of meaningful differences between discordant siblings lead us to conclude that the deficits observed in marijuana users are attributable to confounding factors that influence both substance initiation and IQ rather than a neurotoxic effect of marijuana."
"We ... test[ed] for associations between marijuana use and changes in intelligence scores from adolescence (ages 12-21) to adulthood (ages 18-26) using data drawn from the National Longitudinal Study of Adolescent to Adult Health. ... [O]ur findings did not reveal a significant association between cumulative marijuana use and changes in intelligence scores."
"We investigated associations between adolescent cannabis use and IQ and educational attainment in a sample of 2235 teenagers from the Avon Longitudinal Study of Parents and Children. ... After full adjustment, those who had used cannabis ≥50 times did not differ from never-users on either IQ or educational performance. ... These findings suggest that adolescent cannabis use is not associated with IQ or educational performance once adjustment is made for potential confounds, in particular adolescent cigarette use. Modest cannabis use in teenagers may have less cognitive impact than epidemiological surveys of older cohorts have previously suggested."
"Does cannabis use have substantial and permanent effects on neuropsychological functioning? Renewed and intense attention to the issue has followed recent research on the Dunedin cohort, which found a positive association between, on the one hand, adolescent-onset cannabis use and dependence and, on the other hand, a decline in IQ from childhood to adulthood [Meier et al. (2012) Proc Natl Acad Sci USA 109(40):E2657-E2664]. The association is given a causal interpretation by the authors, but existing research suggests an alternative confounding model based on time-varying effects of socioeconomic status on IQ. A simulation of the confounding model reproduces the reported associations from the Dunedin cohort, suggesting that the causal effects estimated in Meier et al. are likely to be overestimates, and that the true effect could be zero."
"Assessing marijuana's impact on intelligence quotient (IQ) has been hampered by a lack of evaluation of subjects before they begin to use this substance. Using data from a group of young people whom we have been following since birth, we examined IQ scores before, during and after cessation of regular marijuana use to determine any impact of the drug on this measure of cognitive function. ... Current marijuana use had a negative effect on global IQ score only in subjects who smoked 5 or more joints per week. A negative effect was not observed among subjects who had previously been heavy users but were no longer using the substance. We conclude that marijuana does not have a long-term negative impact on global intelligence."