A highly purified form of cannabidiol (CBD) demonstrated antipsychotic-like effects in a new animal study published by the Journal of Psychopharmacology.
The study compared highly purified CBD, known as hpCBD and sold as Epidiolex, with two newer non-dopamine-blocking psychosis medications: pimavanserin, approved for psychosis associated with Parkinson’s disease, and xanomeline, approved for schizophrenia psychosis when paired with trospium.
Researchers noted that psychosis can occur alongside several neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. Current treatments often rely on dopamine D2 receptor antagonists, which may worsen symptoms in some patients with these conditions. Because of this, the study says there is a need for new treatment approaches that do not work through D2 receptor antagonism.
For the study, researchers tested the three compounds in male C57BL/6J mice using two standard preclinical models relevant to psychosis: MK-801-induced hyperlocomotion and prepulse inhibition deficits. MK-801 is commonly used in animal studies to produce behavioral changes associated with psychosis-like states.
Pimavanserin was tested at doses of 0.1, 0.3 and 1 mg/kg, while xanomeline was tested at 1, 3 and 10 mg/kg. Highly purified CBD was tested at 50, 100 and 200 mg/kg.
According to the study, pimavanserin and xanomeline reduced MK-801-induced hyperlocomotion at all tested doses. Highly purified CBD also reduced hyperlocomotion, but only at the highest dose tested, 200 mg/kg.
Researchers also found that prepulse inhibition deficits were improved by all doses of pimavanserin, by the highest dose of xanomeline, and by the highest dose of highly purified CBD.
The study concludes that highly purified CBD, similar to pimavanserin and xanomeline, showed “putative antipsychotic-like activity” in classic mouse assays relevant to psychosis. Researchers said the findings are consistent with previous clinical data showing antipsychotic effects of CBD in patients with psychosis.
The results are preclinical, meaning the findings come from animal testing and do not establish that CBD can treat psychosis in humans. However, the study adds to a growing body of research examining CBD’s potential role in psychiatric and neurological conditions, particularly through mechanisms that do not involve dopamine D2 receptor blockade.
