Cannabis users had significant differences in brain structure and function, most markedly for markers of lower white matter microstructure integrity. Other subcortical assessments found that cannabis users had similar (60,62) or larger cerebellar volumes (44,58) than nonusers. Finally, there is some evidence for damage to white matter in specific brain regions of cannabis users as compared with controls, possibly reflecting demyelination or axonal damage resulting in altered brain connectivity and functional impairment (65–68). We did not replicate previously observed associations between cannabis use and grey matter volume in the hippocampus.
Increasing usage rates by people in every age range in the United States (74,75) highlight the need to address unanswered questions about the effects of cannabis on the brain (see Table 1). Legalization has enhanced public awareness of questions about the effects of cannabis, and may also facilitate the recruitment of participants for observational studies to answer these questions. Rapidly advancing data collection supported by funding for large-scale longitudinal studies, such as the Adolescent Brain Cognitive Development Longitudinal Study, will be addressing many of these questions (Collaborative Research on Addiction at NIH). Several reports found no group differences in amygdala volume (43,58–62), but according to one report, the amygdala was 7.1% smaller in users than in controls (47). Recent findings indicate that changes to hippocampal structure due to heavy cannabis use, starting in adolescence, persist well into adulthood even following abstinence for several decades (45).
What this study adds
Yet some formulations of cannabinoid compounds are FDA-approved for medical uses, including applications in children. People who use both cannabis and tobacco show distinct brain changes compared to those who use cannabis alone, according to a new study led by McGill University researchers at the Douglas Research Center. However, Gowin mentions their research also suggests that abstaining from using cannabis before doing a cognitive task could help to improve performance. “People need to be aware of their relationship with cannabis since abstaining cold turkey could disrupt their cognition as well.
- Although evidence suggests that heavy, recreational cannabis use is linked to cognitive deficits and potentially untoward neural changes as outlined above, findings from studies of recreational cannabis use may not be applicable to medical marijuana (178).
- Another study found differences in resting state connectivity of the middle frontal gyrus, precentral gyrus, superior frontal gyrus, posterior cingulate cortex, cerebellum and some other regions of male heavy cannabis users compared with controls (94).
- Yet some formulations of cannabinoid compounds are FDA-approved for medical uses, including applications in children.
- Aside from studies evaluating effects of THC on brain activity and various functions, such as memory retrieval and emotional processing, potential effects are being evaluated in chronic pain, bipolar disorder, and improvement of sleep.
- As of February 2017, ClinicalTrials.gov listed 108 ongoing clinical trials with “cannabis” as the intervention.
These changes are regionally specific to hippocampal subregions with high densities of CB1 receptors, and are not seen in parietal cortex, where the density of CB1 receptors is relatively low. Although obtained in a retrospective assessment, these results argue for more long-term prospective studies to examine the effects of adolescent use in late life, to help clarify how changes resulting from heavy cannabis use interact with brain aging. Decades of research have suggested that recreational cannabis use confers risk for cognitive impairment across various domains, and structural and functional differences in the brain have been linked to early and heavy cannabis use. As of February 2017, ClinicalTrials.gov listed 108 ongoing clinical trials with “cannabis” as the intervention. A recent meta-analysis examined 79 clinical trials and concluded that cannabinoids may be beneficial for nausea and vomiting, pain reduction, and reduced spasticity (Whiting, Wolff, Deshpande, & et al., 2015). These included dizziness, dry mouth, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucinations.
Review of Longitudinal Studies on Cannabis Use and Neuropsychological Functioning
In Canada, about one in 20 people who used cannabis in the past year are considered at risk for cannabis use disorder. “What surprised us was how strong the effect was, and how different it was from those who only used cannabis, compared to those Cannabis and Brain who used both tobacco and cannabis,” said co-author Romina Mizrahi, Professor of Psychiatry and director of the McGill Research Centre for Cannabis. In Canada, about one in 20 people who used cannabis in the past year are considered at risk for cannabis use disorder. “Identifying this mechanism is an important step toward finding targets for future medications to treat cannabis use disorder, especially among those that co-use tobacco. Right now, the only available treatments are behavioral therapies such as counseling,” she said. The University of Colorado Anschutz Medical Campus is a world-class medical destination at the forefront of transformative science, medicine, education and patient care. Evidence demonstrates that low levels of anandamide, a prominent endocannabinoid, correlate with worse clinical outcomes.
- These changes are regionally specific to hippocampal subregions with high densities of CB1 receptors, and are not seen in parietal cortex, where the density of CB1 receptors is relatively low.
- The results suggested that these patients experienced improvement in measures of executive functioning, in addition to positive changes in some aspects of quality of life.
- Whether the current findings generalize to individuals using such formulations, which were not likely represented in the reported cohort studies, will need to be determined with future research.
- The findings uncover a potential biological target for treating cannabis use disorder, especially in those who co-use tobacco.
- In the study, heavy users are considered young adults who’ve used cannabis more than 1000 times over their lifetime.
- These side effects, as well as the recreational and medical effects of cannabis on the central nervous system, occur primarily through activity at cannabinoid receptor type 1 (CB1) (Pertwee, 2006; Pertwee, 2008).
The data from adverse events was not amenable to meta-analysis and suggests that further work is needed to better understand the circumstances under which they emerge (e.g., formulation, route of administration, dosing, disorder treated). Cannabis users showed a higher surface area of the left frontal pole and higher tissue intensity in the right pallidum. In view of previously observed associations with hippocampal volume, we examined this region as a region of interest in a hypothesis-driven approach. We assessed whether the duration of abstinence or dose had an impact on the relationships between cannabis use and brain IDPs that survived the FDR correction in the main analysis. Neither the duration of cannabis abstinence nor the frequency of cannabis dosage (as assessed through low- and high-frequency use) significantly moderated the associations between cannabis use and brain measures. Objective To explore observational and genetic associations between cannabis use and brain structure and function.
CU Anschutz Medical Campus
Historically, this remains much lower than estimates from 1977 to 1980, when it hovered near 50% (Johnston et al., 2016). Despite a higher prevalence of use during the late 1970s, public opinion toward legalization of cannabis has become more favorable. When the Pew Research Center began surveying public opinion toward cannabis legalization during 1969, 12% supported legalization, whereas 84% did not (Pew Research Center, 2016).
MRI acquisition and data processing
“As cannabis use continues to grow globally, studying its effects on human health has become increasingly important. While tobacco-smoking rates are declining overall, most people who use cannabis also use tobacco, the researchers note. Most studies have looked at cannabis and tobacco in isolation, Rabin added, leaving a gap that this preliminary study begins to address. People who use both cannabis and tobacco show distinct brain changes compared to those who use cannabis alone, according to a new study led by McGill University researchers at the Douglas Research Centre.
Short and long-term effects of cannabis use on the brain
Nonetheless, several review articles in the past decade (53–55) have concluded that chronic cannabis use has a significant effect on hippocampal structure in adolescents and suggested that such effects reflect interactions with cannabinoid CB1 receptors, which are densely expressed in the hippocampus. Finally, we performed two-sample MR analyses by using the TwoSampleMR in an R package to investigate whether significant observed associations between cannabis use and brain IDPs were causal. To test for the presence of horizontal pleiotropy, a violation of a key MR assumption, we used the MR-Egger intercept test. Conclusions Associations between lifetime cannabis use and brain structure and function in later life are probably not causal in nature and might represent residual confounding.
Whether such a compensation extends into adulthood after prolonged usage is questionable, and a mechanistic clarification of how long-term usage and prolonged functional brain alterations transform behavioral or cognitive output will require further investigation. After FDR correction, while significant associations were observed in six brain regions among men, women exhibited a more widespread effect across 24 brain structures and functional regions. Among male cannabis users, most associations were observed in functional connectivity, whereas in women, associations were primarily seen in diffusion MRI measures of white matter, with the genu and body of corpus callosum showing the most significant association (online supplemental tables 9 and 10). These changes are most evident among adolescent users or those with early onset of cannabis use, as adolescence represents a critical period of neurodevelopment, making youth more vulnerable to exogenous influences, including cannabis. Accordingly, frequency and magnitude of use, product choice/potency, mode of use, and age of the consumer are all likely to influence the effects of cannabis on the brain. It is important, however, to recognize that cannabis is a complex plant comprising numerous constituents, which exhibit unique effects when studied alone as well as in the presence of other cannabinoids.
It may be that the relatively small effects observed in the reviewed studies contribute to some of these outcomes. Alternatively, the relationship between neurocognitive functioning and academic performance is likely more complex and may be bi-directional. For example, adverse consequences on academic performance, school engagement, and psychosocial functioning that are experienced as a result of cannabis use may, at least in part, influence later neuropsychological outcomes. Although evidence suggests that heavy, recreational cannabis use is linked to cognitive deficits and potentially untoward neural changes as outlined above, findings from studies of recreational cannabis use may not be applicable to medical marijuana (178).
Statistical analyses
FAAH is the enzyme that breaks down anandamide, a naturally occurring molecule sometimes called the “bliss molecule” for its role in mood and stress regulation. The endocannabinoid system is phylogenetically old, having been identified in the most primitive animals with a neuronal network. In animals, N-arachidonoylethanolamine (anandamide) and 2-arachidonoyl glycerol (2-AG) are the major endocannabinoids. Many of their effects and those of phytocannabinoids are mediated by CB1 and CB2 receptors, which primarily couple to G proteins of the Gi and G0 classes, although some cannabinoids engage other receptors (i.e., transient receptor potential channels and peroxisome proliferator-activated receptors) (5,6).