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How THC and CBD affect the brain's reward system, and what that means for psychosis

Narrative ReviewModerate evidence
The takeaway

THC appears to disrupt reward-related brain regions in ways that correlate with psychotic symptoms, while CBD may push those same regions in the opposite direction.

Neuroscience researchers, clinicians treating psychosis, and anyone interested in the biological basis of cannabis-related psychosis risk.

THC and CBD modulated the same reward and salience brain regions in opposite directions

What the researchers found

THC modulated activity in the striatum, midbrain, insula, and anterior cingulate during reward processing, with some effects correlating with the severity of THC-induced psychotic symptoms. CBD appeared to modulate the same reward and salience regions in the opposite direction.

Why it matters

Both psychosis and THC use involve altered dopamine signaling in the striatum. Understanding whether cannabinoid effects on reward processing underlie psychotic symptoms could clarify why some cannabis users develop psychosis while others do not.

The numbers in context

People with psychosis show increased striatal presynaptic dopamine synthesis and release. Cannabis users generally show impaired presynaptic dopaminergic function, though acute THC challenges produced only modest effects on striatal dopamine.

How the study worked

Narrative review combining preclinical and human neuroimaging evidence. A systematic search identified acute cannabinoid drug-challenge studies using neuroimaging in healthy subjects and people with psychosis.

What this study cannot tell us

Narrative review rather than systematic meta-analysis. Acute THC challenge studies may not reflect chronic cannabis use. The relationship between reward processing changes and psychotomimetic effects remains correlational.

How to read the evidence

Narrative review synthesizing preclinical and human imaging data with some systematic search elements.

When this study was published

Published in 2022, reviewing literature up to that point.

The bigger picture

The overlap between cannabinoid effects on reward circuitry and the neurobiology of psychosis raises the question of whether endocannabinoid dysfunction and reward processing abnormalities are mechanistically linked in psychotic disorders.

Questions still open

  • Does CBD's opposing effect on reward regions explain its potential antipsychotic properties? Could individual differences in reward circuitry predict psychosis risk from cannabis use?

Common questions

Does THC cause psychosis through the reward system?
The review found overlap between THC's effects on reward circuitry and the neurobiology of psychosis, but whether reward processing changes actually cause psychotic symptoms remains unclear.
Can CBD counteract THC's effects on the brain?
Imaging evidence suggests CBD modulates reward and salience regions in the opposite direction to THC, though the clinical significance of this opposition needs further study.

Read the original research

Cannabinoids, reward processing, and psychosis.

Psychopharmacology, 239(5), 1157-1177

Citation

Gunasekera, Brandon; Diederen, Kelly; Bhattacharyya, Sagnik. (2022). Cannabinoids, reward processing, and psychosis.. Psychopharmacology, 239(5), 1157-1177. https://doi.org/10.1007/s00213-021-05801-2

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