Chronic cannabis use downregulates CB1 receptors, which may mirror changes seen in psychosis | Research

The takeaway

The first systematic review of how cannabis affects the endocannabinoid system found chronic use downregulates CB1 receptors, a pattern that may overlap with endocannabinoid changes seen in psychosis, though the evidence in cannabis users with schizophrenia is unclear.

People interested in cannabis and psychosis mechanisms, neuroscience researchers, and anyone wanting to understand how cannabis changes the brain.

Chronic cannabis use downregulates CB1 receptors, potentially mirroring psychosis-related changes

What the researchers found

The most established finding is CB1 receptor downregulation after chronic and recent cannabis exposure. This pattern may mirror endocannabinoid system changes observed in psychosis. However, it remains uncertain whether CB1 downregulation also occurs in cannabis users who have schizophrenia.

Why it matters

If cannabis causes endocannabinoid system changes that resemble those seen in psychosis, this provides a biological mechanism linking cannabis use to psychotic disorders. Understanding this overlap could inform both prevention and treatment.

The numbers in context

CB1 receptor downregulation is the most consistently reported change after chronic cannabis use. The pattern overlaps with endocannabinoid alterations observed in psychosis. Uncertainty remains for cannabis users with schizophrenia.

How the study worked

Systematic review of studies examining the effects of exogenous cannabinoids on the endocannabinoid system in humans with and without psychotic disorders.

What this study cannot tell us

Limited number of human studies examining endocannabinoid system changes after cannabis use. Unclear whether CB1 changes are cause or effect in psychosis. Different imaging and measurement methods across studies complicate comparison.

How to read the evidence

Moderate: first systematic review on this topic, but limited by the small number of available human studies.

When this study was published

Published in 2019.

The bigger picture

The endocannabinoid system may be a convergence point where cannabis exposure and psychosis vulnerability meet. If CB1 downregulation is both a consequence of cannabis use and a feature of psychosis, it could explain why cannabis increases psychosis risk in vulnerable individuals.

Questions still open

Does CB1 downregulation recover with abstinence? Is the overlap between cannabis-induced and psychosis-related endocannabinoid changes causal or coincidental? Could measuring CB1 receptor density identify individuals at risk for cannabis-related psychosis?

Common questions

Does cannabis permanently change brain receptors?

Chronic cannabis use downregulates CB1 receptors, meaning the brain produces fewer of them. Whether this fully reverses with abstinence is still being studied. The pattern is concerning because it overlaps with receptor changes seen in psychosis.

Could this explain why cannabis triggers psychosis?

Possibly. If cannabis causes the same type of endocannabinoid system changes that are seen in psychotic disorders, it could push vulnerable individuals past a biological threshold. But the evidence is still correlational, not causal.

Read the original research

A systematic review of phytocannabinoid exposure on the endocannabinoid system: Implications for psychosis.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29(3), 330-348

View on PubMed ↗Publisher’s paper ↗

Citation

Jacobson, Maya R; Watts, Jeremy J; Boileau, Isabelle; Tong, Junchao; Mizrahi, Romina. (2019). A systematic review of phytocannabinoid exposure on the endocannabinoid system: Implications for psychosis.. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29(3), 330-348. https://doi.org/10.1016/j.euroneuro.2018.12.014