Several investigations have compared differences between cannabis users and nonusers in functional brain networks, both during task performance and in the resting state, when fMRI was used in the absence of a task. Adult cannabis users generally differed from controls in resting-state functional connectivity (for review see (93)). Cheng et al. (94) used a two-level multi-voxel pattern analysis of resting state fMRI data to classify cannabis users from control participants with an accuracy rate of 84–88% in predicting whether a single participant was a cannabis user. 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). 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). Also, psychophysiological interaction analysis indicated that functional connectivity (but not regional activation) in the reward network differentiated dependent from non-dependent cannabis users in a cannabis cue paradigm (76).
- 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.
- Changes in this structure might have widespread, yet varied effects on brain function, affecting different networks and regions differently.
- There is increasing interest in cannabinoids, especially CBD as add-on treatment for the core symptoms and comorbidities of autism spectrum disorder (ASD).
- We use the term Effect Size (ES) to refer to various different measures of standardized mean differences (e.g., Cohen’s d, Hedge’s g).
- 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.
CB1 are located throughout the cortex and densely concentrated in numerous brain regions important for cognition and psychomotor functioning (Glass, Dragunow, & Faull, 1997). Not surprisingly, the effects of cannabis on neuropsychological functioning have been a topic of considerable interest for many decades. Despite numerous studies, the onset, magnitude, and duration of the effects of cannabis on neuropsychological function, and the conditions under which adverse effects are exacerbated, continue to be debated. Understanding its adverse effects on neuropsychological functioning continues to be critically important.
Links to NCBI Databases
In contrast, schizophrenic patients with cannabis abuse had better emotional memory than schizophrenic patients who did not use cannabis, possibly by reducing negative symptoms (91). In adolescents, heavy cannabis use was most commonly linked with abnormal frontoparietal network activity, but these findings may reflect a compensatory mechanism, particularly in prefrontal cortex (97–103), to maintain behavioral performance. Studies of memory (84,104,105), attention (106), decision-making (107), and inhibitory control (108) in adolescents all demonstrate abnormal functional activation patterns. Similar to studies in adults, many task-based fMRI studies also found intact behavioral performance (88,89,106,109,110) in adolescent cannabis users compared to controls. Thus, the adolescent brain apparently achieves some level of reorganization, engaging regions not typically involved in performing a particular task (71,105).
Acute effects
Finally, functional connectivity of the ventral striatum and midbrain, key brain areas for reward circuitry, as well as the brainstem and lateral thalamus was stronger in cannabis users than in controls (38,71,96). T2-weighted flair identified white matter hyperintensities and periventricular white matter hyperintensities. Diffusion MRI derived measures of white matter volume and white matter microstructure (such as FA, MD, axial diffusivity (L1), radial diffusivities (L2, L3) and mode of anisotropy from DTI, and intracellular volume fraction, isotropic volume fraction, and orientation dispersion).
Studies without Neuropsychological Data Prior to Cannabis Use Initiation
Additionally, the raw MRI data that had the wrong dimensions, were corrupted, missing, or otherwise unusable were not processed any further. Neuroscience News is an online science magazine offering free to read research articles about neuroscience, neurology, psychology, artificial intelligence, neurotechnology, robotics, deep learning, neurosurgery, mental health and more.
In our study, the observed disparity between regions with structural and functional alterations is noteworthy. Structural and functional changes in the brain might occur at different time scales, potentially leading to disparities in imaging results. The most significant association observed in our study was in the corpus callosum microstructure, which plays a crucial role in interhemispheric communication.
There is accumulating evidence that regular cannabis use can alter brain function, especially in networks that support working memory, attention, and cognitive control processing (76). Several prior reviews have addressed the functional impact of chronic cannabis use in both adults and adolescents (38,71,77,78). Functional MRI (fMRI) paired with cognitive testing typically has demonstrated abnormalities in brain activity, although the results have varied with study parameters (77), inter-subject variation (79), and amount of cannabis use (80). In comparisons of adult chronic cannabis users with healthy controls, neural activation Cannabis and Brain was measured in paradigms including tests of attention (81), cognitive control (78,80), memory (82–84), decision-making (85–88), motor performance (89) and affective processing (90). Most of these studies have revealed changes in brain function, often without notable performance deficits, suggesting that performance may be maintained through recruitment of brain regions not typically engaged in a particular cognitive function.
- Several prior reviews have addressed the functional impact of chronic cannabis use in both adults and adolescents (38,71,77,78).
- There is little-to-no long-term outcome data on cognition or brain structure in older patients with early-life cannabis exposure for medical intervention.
- CBD does not bind to the orthosteric binding sites of CB1 and CB2 receptors with high affinity (27–29), but acts as an allosteric inhibitor of both cannabinoid receptors subtypes (27,30,31).
- Finally, numerous individual differences may influence who most is at risk for experiencing cannabis-related declines in neuropsychological functioning, which were not explored in the reviewed studies.
- CB1 receptors are expressed at high levels in the temporal lobe (olfactory system, the hippocampal formation, and amygdala), the cerebellum and neocortex, and are expressed widely at lower levels in other brain regions (6,40,41).
Cannabis effects on brain function
A reversal occurred recently, with 57% of Americans supporting and 37% opposing cannabis legalization during 2016. Support for legalization appears to be transgenerational, with the largest shift observed in generations born during or after the 1940s (i.e., Baby Boomers, Generation X, Millennials), but also observed to a lesser extent among those born from mid-1920 to mid-1940 (i.e., the Silent Generation). Consistent with these trends, 28 U.S. states have passed medical marijuana laws and 8 have legalized recreational use for adults over the age of 21. Individuals who use both cannabis and tobacco exhibit higher brain levels of FAAH, the enzyme that degrades anandamide, compared to those using cannabis alone.
Across studies, IQ and episodic memory performance were the measures most likely affected, although results varied depending on the study. Regardless of the neuropsychological ability assessed, it is important to consider the magnitude of effects observed across studies, which ranged from about 1/5 to 1/2 of a SD unit. Nonetheless, adverse consequences of cannabis use, including on psychosocial and academic outcomes, are well documented (Lynskey & Hall, 2000; National Academies of Sciences & Medicine, 2017; Volkow et al., 2014).
The study, the largest of its kind ever to be completed, examined the effects of cannabis use on over 1,000 young adults aged 22 to 36 using brain imaging technology. The researchers found that 63% of heavy lifetime cannabis users exhibited reduced brain activity during a working memory task, while 68% of recent users also demonstrated a similar impact. Current prospective studies on how cannabis exposure can impact brain structure and cognition are beginning to inform public policy, including considerations for age limits and guidelines for use. Nonetheless, additional research is needed to fully understand the impact of marijuana on the brain, especially for medical marijuana where there may be various confounding biological variables unique to individual medical conditions. Extreme care is warranted when evaluating the impact of cannabis on the still-developing adolescent brain. While recreational use among adolescents and early onset users is relatively well studied, a number of areas remain understudied and urgently need data to inform rapidly changing public policy.
Effects on brain structure
The findings uncover a potential biological target for treating cannabis use disorder, especially in those who co-use tobacco. «What surprised us was how strong the effect was, and how different it was from those who only used cannabis, compared to those who used both tobacco and cannabis,» said co-author Romina Mizrahi, Professor of Psychiatry and director of the McGill Research Center for Cannabis. Because the data was originally collected for another study, the research did not include a tobacco-only group.
Further preclinical and clinical studies are needed in order to examine the pros and cons of CBD and other cannabinoids in ASD before they are established as treatment for ASD symptoms and co-morbidities. While all of the medical uses of cannabis mentioned above for pediatric patients with epilepsy, ADHD or autism show merit, care is warranted in taking into account the use of cannabis on the developing adolescent brain. There is little-to-no long-term outcome data on cognition or brain structure in older patients with early-life cannabis exposure for medical intervention.
“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. Unlike THC, which is psychoactive and is self-administered by rats (e.g. (26),), CBD is considered non-psychotropic and inhibits drug-seeking and self-administration in animal models (26,27). CBD does not bind to the orthosteric binding sites of CB1 and CB2 receptors with high affinity (27–29), but acts as an allosteric inhibitor of both cannabinoid receptors subtypes (27,30,31).