New therapeutics – Cannabidiol

The psychopharmacological treatment of psychoses of the schizophrenia spectrum is sincerely affected by unsatisfactory efficacy for some patients. Beyond that, the existing pharmaceuticals show a large number of side effects. Therefore, developing more effective and/ or less side-effect-prone alternatives is essential.

In recent years we have conducted several studies based on our findings regarding the role of the endogenous cannabinoid system in schizophrenia. We have completed the first controlled, double-blind randomised exploratory clinical trial on the safety and efficacy of cannabidiol in acute episodes of schizophrenia, and we have performed a placebo-controlled double-blind study in first-episode patients with acute schizophrenia. In both studies, cannabidiol led to a significant decrease in psychotic symptoms in the acute stage of this disorder. In addition, cannabidiol displayed a markedly superior side effect profile compared to the standard antipsychotic. The mentioned side effect profile was even comparable to a placebo.

Although these initial results seem very promising, the existing data is insufficient to designate cannabidiol as a proven antipsychotic. Several larger clinical trials are necessary to do so, and we are about to conduct the first of them already. As more results concerning the efficacy of cannabidiol in the treatment of psychosis and schizophrenia will become available, we will let you know here.

At the present stage of its development, we strictly do NOT recommend using cannabidiol as an antipsychotic under any circumstances other than in controlled clinical trial conditions. In particular, no data is available for the safety and efficacy of maintenance treatment using cannabidiol yet. In addition, no drug-drug-interaction data proving the safety of combined treatment with cannabidiol and existing antipsychotics have been reported so far in humans.

Funding:
This research was supported by the Stanley Medical Research Institute of the Theodore and Vada Stanley Foundation, USA (Grant IDs 00-093, 05T-678 and 08TGF-1257 to FML), the European Commission (EU FP7 HEALTH-F2-2010-242114 - OPTiMiSE) and is supported by the German Federal Ministry of Education and Research (BMBF – ESPRIT Network, FKZ: 01EE1407A).

Publications:

D. Koethe, C. Rohleder, L. Kracht, F. M. Leweke: Cannabidiol enhances cerebral glucose utilisation and ameliorates psychopathology and cognition: a case report in a clinically high-risk mental state. Front Psychiatry (2023) 14:1088459

F. M. Leweke, C. Rohleder, C. W. Gerth, M. Hellmich, R. Pukrop, D. Koethe: Cannabidiol and amisulpride improve cognition in acute schizophrenia in an explorative, double-blind, active-controlled randomized clinical trial. Front Pharmacol (2021) 12:614811

J. Schoevers, J. E. Leweke, F. M. Leweke: Cannabidiol as a treatment option for schizophrenia: recent evidence and current studies. Curr Opin Psychiatry (2020) 33:185-191

F. M. Leweke*, J. K. Mueller*, B. Lange, S. Fritze, C. E. Topor, D. Koethe, C. Rohleder: Role of the endocannabinoid system in the pathophysiology of schizophrenia: Implications for pharmacological interventions. CNS Drugs (2018) 32:605-619

F. M. Leweke, J. K. Mueller, B. Lange, C. Rohleder: Therapeutic potential of cannabinoids in psychosis. Biol Psychiatry (2016) 79:604-612

C. Rohleder, J. K. Müller, B. Lange, F. M. Leweke: Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence. Front Pharmacol (2016) 7:422

F. M. Leweke, D. Piomelli, F. Pahlisch, D. Muhl, C. W. Gerth, C. Hoyer, J. Klosterkötter, M. Hellmich, D. Koethe: Cannabidiol enhances anandamide signalling and alleviates psychotic symptoms in schizophrenia. Transl Psychiatry (2012) 2, e94

F. M. Leweke, U. Schneider, M. Radwan, E. Schmidt, H. M. Emrich: Different effects of nabilone and cannabidiol on binocular depth inversion in man. Pharmacology, Biochemistry and Behavior (2000) 66:175-181.