A recent observational study published in BMJ Mental Health indicates that lifetime cannabis use may lead to changes in brain structure and function in older adults. However, a genetic analysis of the same data suggests these associations may not be causal. Researchers caution that other unidentified factors could explain these differences and stress the need for further research on the long-term effects of cannabis use.
As cannabis legalization for medical and recreational purposes rises globally, understanding its potential long-term effects on the brain has become crucial. The study highlights that cannabis use is associated with negative impacts on cognitive performance and brain health, yet the safe usage threshold remains unclear.
Previous observational studies have struggled to establish a direct causal link between cannabis use and brain changes, particularly among older populations. To enhance the evidence, researchers employed Mendelian randomization, a method that uses genetic variants to evaluate risk factors. They analyzed data from 15,896 cannabis users from the UK Biobank, who underwent genetic profiling and brain imaging.
Participants were categorized as lifetime cannabis users if they had consumed the drug at least once. Among them, 3,641 users (average age 61) were compared to 12,225 non-users (average age 64). Users were further divided into low frequency (up to 10 times) and high frequency (11 times or more) users.
After controlling for various factors such as age, sex, socioeconomic status, and health behaviors, the study found that cannabis users exhibited reduced white matter integrity—a crucial component for cognitive function—especially in the corpus callosum, which connects the brain’s two hemispheres. Additionally, users displayed weaker connectivity in brain regions associated with the default mode network, linked to daydreaming and mind-wandering.
Notably, the effects varied by sex. Men showed significant associations in six brain regions, while women exhibited differences across 24 areas, primarily in white matter integrity. This suggests that cannabis impacts men and women differently.
The Mendelian randomization results did not reveal significant associations between genetic predictions of cannabis dependence and brain structure changes, raising questions about the validity of observational findings. Researchers speculate that unmeasured variables, such as family history or diet, could explain the differences. They also acknowledge that the UK Biobank’s sample, predominantly consisting of healthy White individuals, limits the study’s generalizability.
Moreover, the researchers were unable to pinpoint critical periods in life that may influence cannabis’s effects, relying on participants’ self-reported cannabis use, which could be inaccurate. They urge careful interpretation of their findings and call for more research to clarify the effects of heavy cannabis use, particularly regarding potency and its implications for public policy.
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