New therapeutics – Cannabidiol (CBD)

We acknowledge that the current psychopharmacological treatments for psychoses of the schizophrenia spectrum may not work for some patients and can cause numerous side effects. Therefore, it is vital to develop more efficient and less side-effect-prone alternatives.

In recent years, we have conducted several studies on the role of the endogenous cannabinoid system in schizophrenia. We have performed the first controlled, double-blind randomized exploratory clinical trial to assess the safety and effectiveness of cannabidiol in acute episodes of schizophrenia. Additionally, we have conducted a placebo-controlled double-blind study with cannabidiol in first-episode patients with acute schizophrenia. Both studies have shown that cannabidiol significantly reduced psychotic symptoms during the acute stage of the disorder and had a notably superior side effect profile compared to the standard antipsychotic. The side effect profile was even comparable to a placebo.

Although these initial results are promising, we strictly do NOT recommend using cannabidiol as an antipsychotic outside of controlled clinical trial conditions. Several more extensive clinical trials are necessary to confirm cannabidiol as a proven antipsychotic. We are currently conducting a maintenance clinical trial (CBD-ESPRIT) to investigate the longer-term effects of CBD in schizophrenia. We will keep you updated as more results become available.

At this stage of development, the data supporting the safety and efficacy of cannabidiol is insufficient, both for acute or maintenance treatment of psychosis and schizophrenia. Additionally, no 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.