Cannabinoids, reward processing, and psychosis

Abstract

Background: Evidence suggests that an overlap exists between the neurobiology of psychotic disorders and the effects of cannabinoids on neurocognitive and neurochemical substrates involved in reward processing.

Aims: We investigate whether the psychotomimetic effects of delta-9-tetrahydrocannabinol (THC) and the antipsychotic potential of cannabidiol (CBD) are underpinned by their effects on the reward system and dopamine.

Methods: This narrative review focuses on the overlap between altered dopamine signalling and reward processing induced by cannabinoids, pre-clinically and in humans. A systematic search was conducted of acute cannabinoid drug-challenge studies using neuroimaging in healthy subjects and those with psychosis RESULTS: There is evidence of increased striatal presynaptic dopamine synthesis and release in psychosis, as well as abnormal engagement of the striatum during reward processing. Although, acute THC challenges have elicited a modest effect on striatal dopamine, cannabis users generally indicate impaired presynaptic dopaminergic function. Functional MRI studies have identified that a single dose of THC may modulate regions involved in reward and salience processing such as the striatum, midbrain, insular, and anterior cingulate, with some effects correlating with the severity of THC-induced psychotic symptoms. CBD may modulate brain regions involved in reward/salience processing in an opposite direction to that of THC.

Conclusions: There is evidence to suggest modulation of reward processing and its neural substrates by THC and CBD. Whether such effects underlie the psychotomimetic/antipsychotic effects of these cannabinoids remains unclear. Future research should address these unanswered questions to understand the relationship between endocannabinoid dysfunction, reward processing abnormalities, and psychosis.

Keywords: Aberrant salience; CBD; Cannabidiol; Cannabis; Dopamine; PET; Psychosis; Reward processing; Schizophrenia; THC; fMRI.

Fig. 1

Proposed schematic diagram of the molecular action of delta-9-tetrahydrocannabinol on reward circuitry leading to the induction of psychotic symptoms

Fig. 2

Conceptual schematic diagram of the molecular action of cannabidiol on reward circuitry leading to the attenuation of psychotic symptoms. Four different hypothesised modes of action have been proposed. (a) Laprairie et al. . (b) Seeman (2016). (c) Bisogno et al. (2001). (d) Sartim et al. (2016)