The researchers then studied the neural response of participants during a magnetic resonance imaging (MRI) session and gave them seven cognitive tasks to complete. The tasks tested working memory, reward, emotion, language, motor skills – such as tapping a finger to map brain control, relational assessment and theory of mind. In the study, heavy users are considered young adults who’ve used cannabis more than 1000 times over their lifetime. Whereas, using 10 to 999 times was considered a moderate user and less than 10 times was considered a nonuser.
Studies with Neuropsychological Data Prior to Cannabis Use Initiation
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.
Cannabis effects on brain function
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.
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).
- A total of 3921 brain measures of structural and functional connectivity were used in the analysis (online supplemental table 1).
- In another study, adult cannabis users showed stronger functional connectivity compared to controls within the default mode network, and this difference persisted after 1 month of abstinence (95).
- It may be that the relatively small effects observed in the reviewed studies contribute to some of these outcomes.
- Our conclusions may not generalize to neurologically (or otherwise) vulnerable populations that may be at greater risk for neuropsychological decline nor do they suggest an absence of more subtle effects on brain structure and function.
- More FAAH means less anandamide, a pattern previously linked to anxiety, depression and relapse when trying to quit cannabis.
- Individuals who use both cannabis and tobacco exhibit higher brain levels of FAAH, the enzyme that degrades anandamide, compared to those using cannabis alone.
Scope of the Current Review and Literature Search Process
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.
What are the short-term effects of cannabis use on the brain?
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.
For example, additional research is needed to clarify the impact of moderate cannabis use, short- and long-term consequences of using high-potency products and novel delivery methods, effects of cannabis use in older adults, and the efficacy and safety of existing products as well as those in development. Additionally, considerations for preclinical models of cannabis inhalation (instead of injection) may facilitate translation of results in the human population. Mounting evidence points to cognitive impairment after chronic, heavy cannabis use (133–135), enduring beyond the acute effects, although there is also a large body of evidence with negative findings in cannabis users (136–138).
- While tobacco-smoking rates are declining overall, most people who use cannabis also use tobacco, the researchers note.
- This results in reduced anandamide, a molecule involved in mood regulation, potentially contributing to increased anxiety, depression, and difficulty quitting cannabis among co-users.
- In the past decade cannabis use has increased worldwide following its legalisation for medical and recreational purposes.
- 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).
CB1 receptors, which mediate many of the psychoactive effects of cannabinoids, are found in high densities in several brain regions and the eye, and in lower densities throughout the body (6,7). Among the most abundant G protein-coupled receptors in the brain (5), they are localized primarily to neurons but also are expressed in glia (8). The endocannabinoid system comprises these receptors, the endocannabinoids anandamide and 2-AG, and the enzymes that regulate their production and degradation (9,10). Using cannabis before age 18 may affect how the brain builds connections for functions like attention, memory, and learning.10 Cannabis’s effects on attention, memory, and learning may last a long time or even be permanent,11 but more research is needed to fully understand these effects. Research to date has suggested that acute and chronic use of cannabis leads to cognitive impairments (111,112). With substantial evidence for the role of the endocannabinoid system in neural development and understanding that brain development continues into early adulthood, the rising use of cannabis in adolescents and young adults raises major concerns.
What are the 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.
This legalisation has occurred without a comprehensive understanding of the potential effect of cannabis on the brain. Between 2006 and 2013, there was a 250% increase in reported past-year cannabis use among adults aged 65 and older in the United States.1 While cannabis use has increased in older adults, studies on health-related outcomes in this group are still limited. There are reports of adverse cannabis effects on neurocognitive performance, brain structure and function.2 Whether there is a safe threshold of cannabis use is unknown. It is worth noting that a recent evidence-based consensus report from the National Academy of Sciences (2017) concluded there was moderate evidence for acute effects of cannabis on cognitive abilities, but limited evidence for associations under abstinence. When considering the aforementioned results, it is important to keep in mind that the majority of the current literature on cannabis use and neuropsychological functioning consists predominantly of cross-sectional studies and convenience samples of modest size. Although such studies have been valuable in advancing research in this area, they have an important limitation – they preclude making strong causal inferences between use of cannabis and declines in neuropsychological functioning.
Historically, this remains much lower than estimates from 1977 to 1980, when it hovered near 50% (Johnston et al., 2016). Despite a Cannabis and Brain 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).
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).
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).
