Cannabidiol (CBD) may have therapeutic potential for treating psychosis associated with schizophrenia, according to a new scientific review examining how the cannabinoid interacts with brain receptors and neurotransmitter systems.
The review, published August 27 in Neurochemical Research, was conducted by researchers from Hyogo Medical University, Kagoshima University, the University of Toledo, the VA Maryland Healthcare System and the University of Maryland School of Medicine.
Researchers examined the molecular mechanisms that distinguish CBD from delta-9 tetrahydrocannabinol (THC), particularly their interactions with cannabinoid and serotonin receptors. While THC activates CB1 and CB2 receptors, CBD acts differently, including as a negative allosteric modulator of CB1 receptors and an antagonist of some THC-related effects.
The authors said these differences may help explain why THC and CBD have substantially different pharmacological profiles and potential for dependence. CBD has limited abuse potential and is itself being investigated as a possible treatment for cannabis use disorder and other conditions.
CBD also interacts with several targets outside the traditional cannabinoid receptors, including GPR55, TRPV1 and ENT1. These systems have been linked to anticonvulsant, anti-inflammatory, pain-relieving and neuroprotective effects.
Of particular interest for schizophrenia is CBD’s interaction with serotonin signaling. The researchers noted that excessive activation of serotonin receptors including 5-HT1A and 5-HT2A is believed to contribute to some symptoms of psychosis. Previous research cited in the review has also examined CBD’s effects on brain activity in people experiencing schizophrenia or early psychosis.
Researchers said CBD’s multiple molecular actions provide a “mechanistic rationale for exploring CBD as a treatment option” for psychosis associated with schizophrenia, as well as psychotic states induced by stimulant drugs.
The paper is a review of existing evidence rather than a new clinical trial, meaning the findings support continued research into CBD as a potential treatment rather than demonstrating that it is an established therapy for schizophrenia.
