Several studies have suggested that cannabis use may be related to a loss of gray matter in the hippocampus. This complex brain structure is related to memory, learning and emotional experiences, and an abnormal functioning could explain some of the most frequently observed psychological effects of cannabis abuse.
Now, a report published in the journal Psychopharmacology indicates that specific subregions of the hippocampus are vulnerable to regular cannabis use, but suggests that these effects might be restricted to users suffering from dependency. Cannabis dependence affects an estimated 13 million people worldwide and, much like any other drug addiction, is associated with severe psychological and social difficulties and, possibly, neurological abnormalities.
The breakthrough work was led by Dr. Valentina Lorenzetti and integrated researchers from three universities in the United Kingdom and Australia. Dr. Lorenzetti’s previous work at the University of Melbourne has focused on brain alterations that co-occur with psychopathologies such as depression, schizophrenia, OCD, opiate and cannabis addiction.
The study included a total of 96 adult participants, of which 35 were non-users, 22 were non-dependent regular users and 39 were dependent users. A thorough screening ensured that the participants had normal intelligence, mental and physical health, and that the three groups were evenly matched across several other factors.
Regular cannabis users were defined as those using cannabis at least twice a month for an uninterrupted period of at least two years. Dependency was assessed with resource to a standardized clinical test. Finally, a urine test confirmed self-reported use, although it was not later included in the statistical analysis due to its high variability.
Magnetic resonance imaging (MRI) was used to observe patients’ brain morphology, and a computer software located and segmented the subregions of the hippocampus for volume analysis. This analysis showed that cannabis dependent users had, on average, less gray matter in the hippocampus than either non-users or non-dependent users. These differences were observed in two subregions: CA1 and CA2/3.
The researchers then tested whether specific measures of cannabis use such as age of onset, last month use and lifetime use could explain the observed patterns. In addition, they tried to control for confounders, like IQ and tobacco use, which are known to affect hippocampal volume as well. This revealed that lifetime use in dependent users, but not in non-dependent users, was linked to the changes observed initially. Moreover, IQ in the dependent group was also linked to changes in the volumes of CA4/DG.
Areas CA1, CA2/3 and DG are deeply involved in the mental representation, encoding and retrieval of day to day experiences. They are crucial for both short-term and long-term memories, which are often impaired under heavy persistent cannabis use. In addition, area GD is also involved in adult neurogenesis, which is thought to be important for the formation of new memories. An alteration of this process could account for the smaller volumes of the hippocampal substructures observed in this study.
The finding of brain abnormalities among dependent users is not that surprising, considering the negative symptoms and life trajectories of these patients. As the authors discuss, their data does not rule out that the effects observed are due to cannabis use in specific instead of more general effects of drug abuse that could emerge with any intoxicating substance.
The fact that regular non-addicted users showed normal brain morphology was perhaps more surprising, and could denote the generally safe profile of cannabis use. The authors play with the idea that previous findings related to cannabis use could be attributed to a subset of addicted users who were not separated by researchers.
They are careful to emphasize, however, that the majority of the evidence leans on the side of there being negative psychological effects due to both dependency and heavy regular use. It is also possible that these effects are not linked to gray matter changes in the hippocampus, or that the changes are too subtle to be captured with MRI technology. Regardless, this study will force researchers to pay more attention to their participants in subsequent works.
The work described in this article was supported by grants from the National Health and Medical Research Council of Australia (link) , the Australian Research Council (link) and the David Winston Turner Endowment Fund (link).
Featured image by Chmee2.