The legalization of cannabis for recreational and medical purposes has expanded in various states and countries, with a corresponding rise in the potency of cannabis products and the rates of cannabis use. Despite known risks, cannabis is often perceived as harmless, and short-term use may impair episodic memory, with effects that typically fade within 72 hours. Tetrahydrocannabinol (THC) affects brain regions with high densities of cannabinoid 1 (CB1) receptors that may potentially alter brain structure and function.
Research shows prefrontal cortex thinning in adolescents with abnormal neural activity related to reward processing, executive function, and memory. However, small sample sizes lack comprehensive analysis of the effects of cannabis on brain function.
The data for the study were obtained from the Human Connectome Project (HCP) through MRI scans of 1,005 adults aged 22-37 years, where urine toxicology assessed the lifetime cannabis use, dependence, age at first use, and recent use. This study evaluates cognitive performance in seven domains: logical reasoning, relational, language, working memory, motor function, reward, and emotion. The study received ethical approval from Washington University and was preregistered in the Open Science Framework.
The total subjects of 1,003 adults with an average age of 28.7 years (SD = 3.7) comprised 533 women (53.1%) and 470 men (46.9%). Among the participants, 63 (6.3%) were Asian, 137 (13.7%) were Black, and 762 (76.0%) were White. Based on lifetime cannabis use, 88 individuals (8.8%) were classified as heavy users, 179 (17.8%) moderate users, and 736 (73.4%) non-users. Heavy cannabis use over a lifetime (Cohen’s d = −0.28 [95% CI, −0.50 to −0.06] with false discovery rate corrected to P = 0.02) was linked to reduced activation during working memory tasks.
Regions associated with a history of heavy cannabis use included the dorsolateral prefrontal cortex, medial prefrontal cortex, and anterior insula. Recent cannabis use has been associated with reduced performance and low brain activation for working memory and motor tasks. However, the link between recent use and brain activation was no longer significant after controlling for the false discovery rate. No other tasks were related to lifetime heavy use, recent use, or a diagnosis of dependence.
The results highlighted that lifetime heavy cannabis use was significantly associated with lower brain activation during the working memory task, even after excluding recent users. This suggests a potential long-term impact on cannabis for cognitive function. Furthermore, working memory task activation correlated with verbal memory, intelligence, and education, making it relevant to cognitive markers.
Although recent cannabis use initially appeared to be linked to decreased brain activation in working memory and motor tasks, these associations did not hold after statistical correction. Interestingly, no significant relationship was found between cannabis dependence and brain function, suggesting that the consequences of dependence, such as social and legal issues, may not directly translate into neurological impairment. Instead, cumulative exposure to cannabis constituents like THC is a more relevant factor in brain function changes.
Heavy lifetime cannabis use was associated with a small to medium reduction in brain activation in areas of the brain responsible for working memory. Early results also suggested that the poor performance of the theory-of-mind tasks needs further investigation. However, recent cannabis use showed some links to reduced brain activation, but the effects were insignificant after adjustments. Further long-term studies are required to establish whether cannabis use leads to changes in brain function.
Reference: Gowin JL, Ellingson JM, Karoly HC, et al. Brain function outcomes of recent and lifetime cannabis use. JAMA Netw Open. 2025;8(1):e2457069. doi:10.1001/jamanetworkopen.2024.57069
