Early-onset cannabis users showed altered hippocampal volumes in specific subregions, and a dopamine transporter gene variant modified how cannabis affected overall hippocampal size.
Read this if you started using cannabis as a teenager and are interested in how genetics might influence the brain effects.
Cannabis disrupted the normal relationship between dopamine genes and hippocampal structure
What the researchers found
Researchers examined hippocampal brain structure in 59 young men aged 18-30, including 30 chronic cannabis users who started regular use before age 16 and 29 controls. They combined high-resolution brain imaging with genetic testing for three dopamine-related genes: COMT, DAT1, and BDNF.
Cannabis users showed emerging alterations in total hippocampal volume and in specific subregions (CA1, CA2/3, and CA4), with associations between the amount of cannabis use and the degree of volume changes.
The most novel finding was an interaction between cannabis use and the DAT1 dopamine transporter gene. Normally, different variants of DAT1 (associated with higher or lower dopamine availability) relate to hippocampal size in a predictable pattern. Cannabis exposure disrupted this normal gene-brain relationship, suggesting that cannabis interferes with how dopamine gene variants shape hippocampal development.
Why it matters
The hippocampus is critical for memory and learning, and its development during adolescence makes it potentially vulnerable to cannabis exposure. This study shows that the effects of cannabis on hippocampal structure are not uniform but depend on an individual's genetic makeup, particularly genes controlling dopamine signaling. This could help explain why some young cannabis users develop cognitive problems while others do not.
The numbers in context
59 young men (30 cannabis users, 29 controls). Ages 18-30. Cannabis users started regular use before age 16. Altered subregions: CA1, CA2/3, CA4. Cannabis x DAT1 interaction significant for total hippocampal volume and fissure subregion. DAT1 variants: 9/9R (high dopamine) and 10/10R (low dopamine).
How the study worked
This was a cross-sectional neuroimaging-genetics study of 59 male Caucasian young adults aged 18-30. Hippocampal volumes were manually traced and automatically segmented into subregions using high-resolution MRI. Participants were genotyped for COMT, DAT1, and BDNF polymorphisms. Cannabis users had begun regular use before age 16.
What this study cannot tell us
The sample was small (59 participants) and restricted to male Caucasians, limiting generalizability. The cross-sectional design cannot determine whether hippocampal differences preceded or followed cannabis use. Cannabis use was measured retrospectively. Multiple genetic comparisons increase the risk of false-positive findings. Only three candidate genes were tested.
How to read the evidence
This is a small neuroimaging-genetics study providing preliminary evidence of gene-environment interactions affecting hippocampal structure.
When this study was published
Published in 2018. Neuroimaging-genetics approaches to cannabis research have continued to develop.
The bigger picture
This study exemplifies the gene-environment interaction approach to understanding cannabis effects. Rather than asking whether cannabis damages the brain in general, it asks which brains are most affected and why. The dopamine system is particularly relevant because it mediates both the rewarding effects of cannabis and is critical for hippocampal function.
Questions still open
- Could DAT1 genotyping identify adolescents at higher risk for cannabis-related hippocampal effects? Do these structural changes correspond to measurable memory or learning deficits? Are the hippocampal alterations reversible with cannabis cessation?
Common questions
Does cannabis affect the hippocampus?
Do genetics determine who is affected?
Read the original research
The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users.
Cannabis and cannabinoid research, 3(1), 1-10
Citation
Batalla, Albert; Lorenzetti, Valentina; Chye, Yann; Yücel, Murat; Soriano-Mas, Carles; Bhattacharyya, Sagnik; Torrens, Marta; Crippa, José A S; Martín-Santos, Rocío. (2018). The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users.. Cannabis and cannabinoid research, 3(1), 1-10. https://doi.org/10.1089/can.2017.0021
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