CBD has a complex mode of action which includes inverse agonism (functionally an antagonist) of CB1 and CB2 cannabinoid receptors, mild monoamine uptake inhibition, and 5-HT1A agonism. Additionally, reviews based on preclinical and clinical research identify CBD as an anxiolytic, antipsychotic, anti-insomnia and antidepressant agent. Furthermore, it has putative anti-inflammatory, antidiabetic, analgesic, and neuroprotective properties.
Adjunct use of CBD in schizophrenia is supported by the highest quality of evidence. A recent randomized controlled trial demonstrated superiority of adjunctive CBD to placebo in treating positive symptoms of schizophrenia, and a strong trend towards efficacy in addressing cognitive difficulties associated with this condition. A prior randomized active control study found that monotherapy with CBD had comparable effect to amisulpride (one of the most efficacious antipsychotics) on positive symptoms while demonstrating a clear advantage in treating negative symptoms of schizophrenia. Several open-label studies extend and support the benefits of CBD in psychotic disorders.
Preclinical and open-label studies have found that CBD also may be helpful in the treatment of anxiety, particularly social anxiety, using a public speaking paradigm.5 Mostly preclinical evidence from animal studies suggests there may be a reason to study CBD as an adjunct treatment for depression, while preliminary evidence points to its potential usefulness as a safer substitute for controlled substances used in treating psychiatric and pain disorders.