A systematic review of 122 studies found that external cannabinoids generally suppress immune function, potentially creating immune conditions during adolescence that increase vulnerability to psychosis.
Read this if you want to understand the biological mechanism that might link cannabis to psychosis risk.
122 studies: external cannabinoids suppress immunity while endocannabinoids enhance it
What the researchers found
The review identified a clear dichotomy: endocannabinoids (produced naturally in the body) generally enhanced immune responses, while exogenous cannabinoids (from cannabis) had immunosuppressant effects. Both types shifted the immune response from Th1 (pro-inflammatory, antiviral) to Th2 (anti-inflammatory, allergic) patterns.
Both endogenous and synthetic cannabinoids modulated microglial function and neurotransmitter secretion. The peripheral immune effects of cannabinoids were predictable and consistent, but their effects in the central nervous system remained less clear.
The authors hypothesize that exposure to external cannabinoids during adolescence could trigger immunological dysfunctions that create latent vulnerability to psychosis, providing a biological mechanism linking cannabis use to psychotic disorders.
Why it matters
The link between cannabis use and psychosis is well-established epidemiologically, but the biological mechanism has been unclear. This review proposes that the immune system could be the missing link, offering a testable hypothesis for how cannabis exposure, particularly during adolescence, increases psychosis risk.
The numbers in context
122 articles reviewed from 446 references. Key finding: exogenous cannabinoids are immunosuppressant while endocannabinoids enhance immune response. Both shift immune balance from Th1 to Th2.
How the study worked
A comprehensive search of PubMed/MEDLINE, EMBASE, and ISI Web of Knowledge was conducted using combinations of terms related to immune function, cannabinoids, and endocannabinoid receptors. 122 articles were identified from 446 references. Studies were included if they reported quantitative or qualitative relationships between cannabinoid ligands, their receptors, and the immune system in vitro or in mammals including humans.
What this study cannot tell us
The hypothesis linking cannabis immune effects to psychosis is largely theoretical. Most evidence comes from in vitro and animal studies. The causal chain from cannabis use to immune disruption to psychosis vulnerability has not been demonstrated in prospective human studies. The review acknowledges significant uncertainty about central nervous system immune effects.
How to read the evidence
This is a systematic review synthesizing a large body of basic science evidence. The proposed mechanism linking immune effects to psychosis remains theoretical.
When this study was published
Published in 2014. The neuroimmune hypothesis of psychosis and its relationship to cannabis has been further developed since.
The bigger picture
The neuroinflammation hypothesis of psychosis has been gaining traction, with evidence that immune system alterations play a role in schizophrenia. This review connects cannabis pharmacology to immune-mediated psychosis risk, opening potential avenues for prevention and early intervention.
Questions still open
- Can immune biomarkers identify cannabis users at risk for psychosis before symptoms appear? Would anti-inflammatory interventions prevent cannabis-associated psychosis? Does the Th1-to-Th2 shift explain the specific symptom profile of cannabis-associated psychosis?
Common questions
What is the Th1/Th2 immune shift?
Why is adolescence a vulnerable period?
Read the original research
Immune system: a possible nexus between cannabinoids and psychosis.
Brain, behavior, and immunity, 40, 269-82
Citation
Suárez-Pinilla, Paula; López-Gil, José; Crespo-Facorro, Benedicto. (2014). Immune system: a possible nexus between cannabinoids and psychosis.. Brain, behavior, and immunity, 40, 269-82. https://doi.org/10.1016/j.bbi.2014.01.018
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