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.
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.
- Cotwin designs are very effective at controlling for measured and unmeasured confounds given that twins share genetic and environmental factors (e.g., comparing twins that differ on their history of cannabis use when trying to link cannabis use to neuropsychological functioning).
- Cannabis is the most widely used illicit substance worldwide, with an estimated 183 million past-year users in 2017 (4).
- Among 12th graders, 45% have used cannabis and 23% have used in the past month (Johnston, Miech, O’Malley, Bachman, & Schulenberg, 2016).
- To reconcile these seemingly contradictory results, it has been suggested that THC modulates memory and cognition in an age- and dose-dependent manner (155).
Clinical implications
This results in reduced anandamide, a molecule involved in mood regulation, potentially contributing to increased anxiety, depression, and difficulty quitting cannabis among co-users. PET brain scans revealed that people who used both tobacco and cannabis had higher levels of FAAH, relative to people who only used cannabis. 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. More FAAH means less anandamide, a pattern previously linked to anxiety, depression and relapse when trying to quit cannabis.
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).
Cannabis and Brain Health
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 Cannabis and Brain for another study, the research did not include a tobacco-only group.
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).
Study sample
Early, heavy use may then interfere with educational and vocational training, leading to long-term consequences in adulthood. From a more biological perspective, use of cannabis during critical developmental periods may cause persistent, long-term alterations in brain structure and brain function. Some studies suggest that the effects of cannabis use during adolescence could be more serious than during adulthood (57) because it may alter the trajectory of brain development (24). AURORA, Colo. (Jan. 28, 2025) – A new study published today in JAMA Network Open explores the effects of both recent and lifetime cannabis use on brain function during cognitive tasks. Self-report questionnaires and laboratory risk-taking tasks have demonstrated differences between cannabis users and non-users, possibly related to the severity of cannabis use.
Statistical analyses
These regions of the brain are involved in important cognitive functions such as decision-making, memory, attention and emotional processing. Increased risk for substance use, abuse or dependence of many illicit substances has been well-documented in adolescents and adults with a childhood diagnosis of ADHD, further clouding investigations of the effects of cannabis per se on the brain in this patient population (201–203). Among illicit substances used by people with ADHD, cannabis is the most commonly used (203,204), providing opportunities for researchers to design cohort studies on the effects of cannabis in patients with ADHD. Although it is crucial to understand how cannabis use interacts with the neurocognitive vulnerabilities related to ADHD, ethical considerations would preclude assigning pediatric patients with ADHD to receive cannabis in the absence of previous use.
- 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).
- Through studies such as these, we will continue to come closer to understanding who, and under what conditions, is most vulnerable to neuropsychological declines from cannabis use.
- These regions of the brain are involved in important cognitive functions such as decision-making, memory, attention and emotional processing.
- Fatty acid amide hydrolase (FAAH) degrades anandamide, and greater FAAH levels may underlie poorer clinical outcomes in people who co-use relative to those who use only cannabis.
- Alternatively, the relationship between neurocognitive functioning and academic performance is likely more complex and may be bi-directional.
Studies with Neuropsychological Data Prior to Cannabis Use Initiation
“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).
Acute effects
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.
Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study
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).
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.