Global cannabis use is on the rise, with about 147 million people — roughly 2.5 percent of the world’s population — using the drug, per the World Health Organization. Cannabis is used for both recreational and medical purposes; however, experts still lack a thorough understanding of its potential long-term effects on the brain. Now, two data sets — an observational study, and a genetic analysis of the study data — may suggest a link between long-term cannabis use and changes in brain structure and function. Published in the journal BMJ Mental Health, the genetic analysis suggests that the observations may not be entirely causal. Still, the results raise important questions about the health implications of long-term cannabis use.
Evaluating Cannabis Use Using Mendelian Randomization
Previously published observational studies have not been able to confirm the link between regular cannabis use and cognitive changes among long-term users of the drug. Thus, in a bid to strengthen the evidence base, the researchers cited above used a technique known as Mendelian randomization. This technique uses genetic variants as proxies for a particular risk factor — cannabis use, in this case — to obtain evidence in support of a specific outcome. The outcome for this study involved brain structure among older lifetime cannabis users.
The researchers utilized data from 15,896 cannabis users, all of whom were participating in the UK Biobank, a large-scale biomedical database. They only used data from subjects for whom both genetic profiling and brain imaging data were available. Cannabis users were identified within the database and then further divided into low-frequency users and high-frequency users. In addition to certain genetic elements, the researchers worked to account for a range of potentially influential lifestyle factors, including employment status and mental state.
Cannabis Use Associated with Poor White Matter Integrity
The researchers ultimately concluded that individuals who used cannabis generally had poorer white matter integrity, which can play a substantial role in cognitive function. Specifically, the corpus callosum, connecting the left and right brain hemispheres, was affected.
Cannabis users also exhibited a weaker resting state of neuronal connectivity in brain regions that make up the brain’s underlying “default mode network,” which is thought to be active when the brain is at rest or engaged in self-referential thinking, including mind wandering and daydreaming. These areas of the brain are, notably, packed with cannabinoid receptors that respond to cannabis.
The study did not reveal a strong association between the frequency of cannabis use and changes in brain structure and function. There were, however, some notable differences between the sexes. For example, the researchers observed significant associations in six specific brain regions among male participants; the observations seen in women were instead spread across 24 brain structures and functional regions. This information could help determine the long-term effects of cannabis use on either sex.
Researchers Urge Cautious Interpretation of Study Results
Though the study seems to suggest a notable correlation between cannabis use and brain structure, the research team self-reported several notable flaws in the data.
First, numerous unmeasured variables, such as medication use, might have influenced the observational findings. The researchers also acknowledge the limitations of their subject pool, which was predominantly made up of healthy white participants. Finally, the study relied on participants’ recollections of their own substance use, which may have been inaccurate. “Our results need to be interpreted with careful consideration,” cautioned the team. “Additional research is needed to understand the effects of heavy cannabis use in this population, including considerations of potency and related information to inform public policy.”
Experts emphasize that further research is needed to fully understand the effects of cannabis on the brain; however, this study is an important first step. As cannabis use continues to increase around the globe, potential effects on cognition cannot be ignored.
To evaluate the effects of drugs on the brain, Scantox offers a wide range of in vitro and in vivo models. Neuronal cells and brain tissue can be evaluated for pathological changes and biomarkers by analyzing mRNA, DNA, and protein levels of the target protein using several biochemical and histological labeling methods. Drug effects can further be evaluated using different assays, e.g., measuring toxicity or enzyme activity.
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