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November 12, 2024 — BMJ Mental Health
A new study has revealed that lifetime cannabis use is associated with notable changes in brain structure and function, particularly in older adults. However, the research raises questions about whether these effects are truly causal, suggesting that other factors could be at play.
The observational study, published in BMJ Mental Health, examined the impact of cannabis use on brain health in a large cohort from the UK Biobank. While cannabis use was linked to poorer brain function, especially in areas critical for cognition, genetic analysis failed to support a direct causal relationship. This suggests that the observed brain changes may be due to other unidentified factors.
The Global Shift Toward Legalization
As cannabis use increases globally due to its legalization for medical and recreational purposes, understanding its long-term effects on the brain has become more crucial. Researchers are particularly concerned about the lack of evidence regarding a “safe” level of cannabis use and how it may differ by sex, especially considering the sex-based differences observed in the study.
Study Overview and Methodology
The study included data from 15,896 cannabis users participating in the UK Biobank, who were subjected to genetic profiling and brain imaging. The participants were categorized into lifetime users (those who reported any cannabis use) and non-users, with further subgrouping based on frequency of use.
Cannabis users were also classified as low-frequency users (those who used cannabis up to 10 times) and high-frequency users (those who used it 11 or more times). The study examined various factors such as age, sex, mental health, smoking, alcohol consumption, and socioeconomic status, alongside brain structure and function data from MRI scans.
Key Findings on Brain Changes
The study found that cannabis use was associated with significant changes in brain structure and function. Cannabis users exhibited poorer white matter integrity, which is critical for cognitive function. These effects were especially pronounced in the corpus callosum, the brain’s main communication pathway between the left and right hemispheres.
Additionally, cannabis users showed weaker neuronal connectivity in areas of the brain responsible for the default mode network, which is active during mind-wandering and daydreaming. These regions are rich in cannabinoid receptors, which are thought to be involved in the drug’s effects on the brain.
Notable Sex-Based Differences
The study also revealed sex-based differences in how cannabis affects the brain. In men, cannabis use was linked to changes in functional connectivity, while women exhibited changes primarily in white matter integrity across 24 brain regions. This suggests that the effects of cannabis on the brain may differ between the sexes.
Genetic Analysis and the Question of Causality
To strengthen their findings, the researchers employed Mendelian randomization, a genetic method that helps assess whether observed associations are likely to be causal. Surprisingly, no genetic evidence supported a causal relationship between cannabis use and brain changes, despite the strong observational associations.
The researchers acknowledge that genetic analyses may have lacked the statistical power to detect small effects, and they suggest that the long-term impact of cannabis use might not have been captured fully by the Mendelian randomization approach.
Discrepancies and Future Research
The study’s authors point to several possible reasons for the discrepancy between observational and genetic findings. It’s possible that other factors, such as family history, diet, or medication use, contributed to the observed brain changes. They also note the limitations of using a predominantly healthy, White population from the UK Biobank, which may not fully reflect the experiences of other demographic groups or individuals with cannabis use disorders.
Furthermore, the study was unable to pinpoint critical time points during a person’s life when cannabis use might have the most profound effects on brain health. The reliance on participants’ recall of their cannabis use over a lifetime also introduces the possibility of inaccuracies.
Conclusion and Policy Implications
While the findings suggest a link between cannabis use and brain changes, the researchers caution that more research is needed before drawing firm conclusions about causality. They emphasize the importance of investigating the effects of heavy cannabis use and its potency, particularly in light of global legalization trends. Further studies could help inform public health policy and provide clearer guidance on safe usage thresholds.
“As cannabis use continues to rise globally, understanding its long-term impact on the brain is more important than ever,” the authors conclude. “Our results highlight the need for ongoing research to assess the full range of potential effects, especially in older adults and women.”
Reference:
Ishrat, S., Levey, D. F., Gelernter, J., Ebmeier, K., & Topiwala, A. (2024). Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study. BMJ Mental Health, 30 October 2024. DOI: 10.1136/bmjment-2024-301065
