Endocannabinoid system may help explain weight gain in patients with schizophrenia

Schizophrenia is a complex psychiatric disorder, marked by symptoms that affect thinking, behavior, and perception of reality. Although there are already effective medications, such as clozapine for resistant cases, treatment still presents challenges, including weight gain. 

A study conducted by the University of São Paulo (USP) indicates that the endocannabinoid system (ECS), a network of receptors and substances involved in functions such as appetite, memory, and mood, may play an important role in understanding this process.

The study and its participants

The work, developed by the USP Psychosis Group, analyzed 93 volunteers divided into three groups: patients with treatment-resistant schizophrenia using clozapine (29), patients using other antipsychotics (31), and healthy controls (33). Levels of anandamide (AEA), 2-AG, and peripheral CB2 receptors, all linked to the endocannabinoid system, were evaluated.

Cannabis and antipsychotics show distinct effects

The results showed that individuals who reported cannabis use at some point in their lives had lower concentrations of 2-AG (2-Arachidonoylglycerol), an endocannabinoid, a substance produced by the body that interacts with cannabinoid receptors. 

On the other hand, patients using antipsychotics other than clozapine had higher values of CB2 receptors, one of the two main receptors of the endocannabinoid system in the human body linked to pain modulation, inflammation, and immunity.

According to the researchers, after controlling for possible confounding factors, cannabis use was the only factor linked to the reduction of 2-AG, while the use of other antipsychotics was associated with an increase in CB2.

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Implications for schizophrenia

According to the study, published in 2024, these findings represent the first direct association between cannabis use, antipsychotic medications, and changes in the endocannabinoid system in patients with schizophrenia. 

Although the results still need to be further explored in new research, they may contribute to revisions in diagnosis, understanding comorbidities, and, in the future, in the search for new pharmacological targets that improve the quality of life of patients.