New research published in BMJ Mental Health sheds light on the relationship between lifetime cannabis use and brain health in mid- to late-life adults. The study found that individuals with a history of cannabis use exhibited differences in brain structure and function compared to non-users, particularly in measures of white matter integrity and brain network connectivity. However, advanced genetic analyses indicated these differences are unlikely to result from a direct causal effect of cannabis use, suggesting that other factors may be at play.
The past decade has seen a sharp increase in cannabis use among older adults, driven in part by the drug’s legalization for medical and recreational purposes in many regions. Despite its growing popularity, research on cannabis’s long-term effects on brain health in aging populations is limited.
Existing studies primarily focus on younger individuals and heavy users, leaving unanswered questions about its impact on older, more casual users. Additionally, previous research has struggled to determine whether observed brain changes are directly caused by cannabis use or are influenced by other factors. The new study aimed to address these gaps by combining traditional observational methods with genetic analyses to explore the potential causal role of cannabis in brain health.
“With cannabis use rising globally due to its legalization for medical and recreational purposes, there is a growing need to understand its potential effects on the brain, particularly in older adults,” said study author Saba Ishrat, a PhD student in psychiatry at the University of Oxford. “Despite the critical importance of brain health in later life, older adults have often been underrepresented in cannabis research. Our study is the largest observational investigation to date examining the relationship between cannabis use and brain structure and function, and it is the first to incorporate genetic data to explore potential causal links.”
The researchers analyzed data from 15,896 participants in the UK Biobank, a large-scale health database. Participants, aged 40 to 69 at the start of the study, provided self-reported information about their lifetime cannabis use. Cannabis users were categorized based on frequency, with subgroups for low-frequency (1–10 uses) and high-frequency (11 or more uses) users. Brain imaging data were collected using advanced MRI techniques, measuring over 3,900 brain characteristics related to structure and function.
The study focused on white matter integrity, assessed through fractional anisotropy and mean diffusivity, as well as functional connectivity in brain networks such as the default mode and central executive networks. These measures were compared between cannabis users and non-users, controlling for potential confounding factors such as age, sex, education, and mental health.
Cannabis users showed significant differences in brain measures compared to non-users. These differences were most pronounced in white matter integrity, particularly in the genu of the corpus callosum, a structure that connects the brain’s two hemispheres. Cannabis users exhibited lower fractional anisotropy and higher mean diffusivity in this region, indicating reduced white matter integrity. Similar patterns were observed in other white matter tracts, including the cingulum bundle and anterior corona radiata.
Functional connectivity analyses revealed weaker or stronger connections between various brain networks, particularly in regions associated with the default mode and central executive networks. These networks are critical for tasks such as decision-making, memory, and attention. While some brain regions showed increased connectivity, others displayed reduced connectivity, suggesting a complex and varied impact of cannabis use on brain function.
To further investigate causality, the researchers used Mendelian randomization, a method that leverages genetic data to infer causal relationships. Despite the observed associations, the genetic analyses found no evidence of a causal relationship between cannabis use and brain structure or function. This indicates that the observed differences may result from confounding factors, such as lifestyle, socioeconomic status, or other health-related variables, rather than being a direct consequence of cannabis use.
“In our study, we found that lifetime cannabis use is associated with several measures of brain structure and function in later life, including reduced white matter integrity and weaker resting-state functional connectivity in specific brain regions,” Ishrat told PsyPost. “However, our genetic analyses did not support a causal link, suggesting that these observed associations may not directly result from cannabis use itself.”
“One surprising aspect was the lack of replication of previously reported associations between cannabis use and grey matter volume in the hippocampus, a part of the brain important for memory. This could be due to differences in the age range of subjects as earlier studies focused on adolescents and young adults, whereas our sample comprised middle- to late-life adults. Furthermore, it’s possible that white matter changes may be more sensitive to cannabis effects than the grey matter measures.”
The study, like all research, includes some limitations. The UK Biobank sample is healthier and more educated than the general population, which may limit the generalizability of the findings. Additionally, the study’s Mendelian randomization analyses may have been underpowered to detect small causal effects. Lastly, the relatively low prevalence of heavy cannabis use in the sample limited the researchers’ ability to explore dose-dependent effects in detail.
“It’s important to interpret our findings with caution,” Ishrat said. “Unaccounted variables in the observational analysis might explain the discrepancies between our observational and genetic analyses. Additional research is needed to fully understand the mechanisms underlying these associations and to examine the effects of heavy cannabis use, including considerations of potency, in older populations.”
Future research should aim to address these limitations by including more diverse populations and longitudinal designs to track brain changes over time. Studies focusing on heavy cannabis users and examining the effects of different cannabis strains and potencies could provide a more nuanced understanding of its impact. Further exploration of sex-specific differences, which this study suggested may exist, could also yield valuable insights.
“The long-term goal is to explore the impact of cannabis use in older populations, expanding our understanding beyond the previously established associations observed in younger groups,” Ishrat said. “By shedding light on the role of cannabis in brain health, this research aims to provide valuable insights that can guide public health initiatives and inform evidence-based policies.”
The study, “Association between cannabis use and brain structure and function: an observational and Mendelian randomisation study,” was authored by Saba Ishrat, Daniel F. Levey, Joel Gelernter, Klaus Ebmeier, and Anya Topiwala.
