Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

Abstract

There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

Effects of non‐euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice

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Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review

“…In contrast to THC, as mentioned in the introduction, CBD may in fact provide an opposing effect to THC albeit more research into this mechanism is required. Additional effects include the inhibition of anandamide breakdown via fatty acid amide hydrolase (FAAH) blocking effects, and anti-inflammatory effects [97,98].…”

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

“…There is medical evidence showing that CBD may be effective in treatment of a wide range of disorders including epilepsy (particularly medically‐refractory pediatric epilepsy syndromes), Alzheimer's disease, Parkinson's disease, MS, ‐ , Huntington's disease, ALS, anxiety disorders including PTSD, depression, dystonia, Meige's syndrome, schizophrenia and psychosis, stroke and hypoxic‐ischemic injury, antioxidant, TBI,…”