How are the brains of cannabis users different? Insights from positron emission tomography

Xu, H., Owens, M. M., Farncombe, T., Noseworthy, M., & MacKillop, J. (2023). Molecular brain differences and cannabis involvement: A systematic review of positron emission tomography studies. Journal of psychiatric research, 162, 44–56. https://doi.org/10.1016/j.jpsychires.2023.03.045

Why was this research conducted?

This article synthesized the current findings on molecular brain differences in individuals who use cannabis based on positron emission tomography (PET) scans. This form of neuroimaging uses radioactive chemicals to bind to specific molecular targets to characterize the number or activity of the target.

The focus of the review was on findings relating to three biological systems, namely:

• dopaminergic function (e.g., how the brain synthesizes and metabolizes dopamine, a neurotransmitter associated with learning and reward),
• endocannabinoid function (e.g., differences in the endocannabinoid system, the biological system that chemicals in cannabis, like tetrahydrocannabinol [THC], affect directly)
• overall brain metabolism (e.g., how much glucose the brain uses)

What does this article add?

The review found that, compared to control participants, cannabis users appear to have:

• a reduction in dopamine synthesis (reduced activity in the dopamine system).
• a reduction in cannabinoid 1 (CB1) receptors availability in the endocannabinoid system; CB1 receptors are the primary molecular target for THC.
• a reduction in fatty acid amide hydrolase (FAAH) binding in the endocannabinoid system; FAAH is an enzyme that breaks down innate and external substances that are responsible for endocannabinoid signaling.
• lower glucose metabolism (lower overall brain activity).

These findings are thought to potentially explain why heavy cannabis use is associated with cognitive consequences, such as poorer working memory; development of cravings and physiological dependence; and generally lower cognitive function.

Is there anything else I should know?

Most of these results were correlational, meaning we can’t definitively know if cannabis was the cause of these differences. In other words, in many of the studies, we know that the groups differed significantly, but we don’t know if cannabis caused those differences or whether people with those differences are more likely to seek out cannabis. (A ‘chicken and egg’ problem.)

Another consideration is that PET imaging is very expensive so many of the studies had relatively small sample sizes.

This review found that two studies that are using newer radioactive tracers, [¹¹C]UCB-J and [¹⁸F]FEPPA respectively, in order to look at brain synaptic density and inflammatory blood biomarkers. These novel approaches may yield new insights in the near future.

Overall, PET studies reveal significant differences in the molecular neurobiology of individuals who use cannabis. The results are promising and suggest there may be potential for PET scans to ultimately be used to help diagnose cannabis use disorder or even predict clinical trajectories.