The vast majority of people who consume cannabis will never experience psychosis, but to those who do, the experience is often terrifying and life-altering. Many emerging research studies suggest that the mind-altering effects of cannabis may have a significant influence on the immune system, and in some cases, may cause psychotic disorders. In the January 2015 issue of the journal Schizophrenia Bulletin, the authors analyzed a recent study that examined the relationship between cannabis use and psychosis. Through a series of questionnaires and interviews, the researchers identified a group of people who had used cannabis within the past six months, and then followed them for an additional 16 months, to see if their psychosis would progress.

The link between cannabis and psychosis has been long-debated, and the recent increase in new users in Colorado (and the rise in the number of cannabis-related hospitalizations) has led to calls for a more scientific understanding of the link.

The combination of pro-inflammatory cytokines in the blood and regular cannabis use or use at an early age may increase the risk of developing psychiatric disorders, researchers have shown.

A landmark study by researchers at the Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP) in Brazil found that people exposed to a combination of these two factors – the presence of pro-inflammatory cytokines in the blood and cannabis use (daily or during puberty) – were more likely to develop psychosis than those exposed to neither or only one of these factors. According to the authors, the study is the first clinical evidence that a disruption of the immune system modifies the link between cannabis and psychosis.

The study was part of a project by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI), a consortium of research centers from 13 countries, including Brazil. A consortium paper published in The Lancet Psychiatry in 2019 found that daily cannabis use triples the risk of developing a psychotic disorder.

The article was published in the journal Psychological Medicine.

Cannabis use and bodily functions

In a recent study, researchers analyzed data from 409 people between the ages of 16 and 64, including first-time psychotic patients and community controls. The sample was drawn from the population of Ribeirão Preto and 25 other cities in the region. Variables analysed included the frequency of cannabis use (daily, non-daily or never), the duration (five years or less) and the age at which use began (in adolescence or later).

In addition to the questionnaire on cannabis use, the researchers measured plasma levels of various cytokines in the subjects and calculated scores reflecting their systemic inflammatory profile. They also collected clinical and socio-demographic data, specifically so-called influencing variables such as age, sex, education, ethnicity, body mass index, smoking and substance use. The results obtained were independent of the associated factors.

Fabiana Corsi-Zuelli, lead author of the article, said: Not everyone who uses cannabis develops psychosis. This suggests that the relationship may be modified by other factors, which may be biological, genetic or environmental.

In a previous study I did for my master’s thesis, we found a correlation between plasma cytokines and first episode psychosis. Following this finding and a recent consortium publication showing that psychosis is more common in individuals who use cannabis daily, our next step was to investigate whether a biological factor [inflammation profile] influences the association between cannabis use and psychosis.

We found a statistically significant correlation between inflammation profile and daily or adolescent cannabis use. Overall, the results showed that immune system dysfunction may alter the association between cannabis use and psychosis, and that the combination of these two factors increases the likelihood of developing a psychotic disorder.

The principal investigator of the project is Cristina Marta Del Ben, professor in the Department of Neuroscience and Behavioral Sciences at the FMRP-USP. Risk factors for developing psychosis can be both biological, including genetic predisposition and problems during pregnancy, and environmental, including traumatic experiences in childhood and adolescence and exposure to psychoactive substances, especially cannabis, Del-Ben said.

Professor Del Ben said: The mechanisms of this disorder are poorly understood. Our results suggest that frequent cannabis use or use of the drug during adolescence is a risk factor for the development of psychosis. We did not find the same correlation with episodic or recreational use. In a multicenter study in European cities with varying cannabis availability, we also found that the risk of psychosis was higher among users of stronger variants of cannabis containing THC or 10%. THC is the main psychoactive component of cannabis or marijuana.


Once these data are available, researchers plan to study genetic variants associated with the immune system and use neuroimaging data to examine the link to environmental risk factors.

By focusing on the interaction between genetics and environment, we will better understand the neurobiology of psychosis, including the role played by the immune system.

This is important for finding alternative treatments for these disorders and for answering often overlooked questions about the physical health of psychiatric patients, Corsi-Zuelli said.

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