New therapeutics – Cannabidiol (CBD)

We acknowledge that current psychopharmacological treatments for psychoses within the schizophrenia spectrum might not be effective for some patients and can lead to numerous side effects. Therefore, developing better and safer alternatives is crucial.

In recent years, we have conducted multiple studies on the role of the endogenous cannabinoid system in schizophrenia. We completed the first controlled, double-blind, randomised exploratory clinical trial to evaluate the safety and effectiveness of cannabidiol during acute episodes of schizophrenia. Additionally, we carried out a placebo-controlled, double-blind study with cannabidiol in patients experiencing their first episode of acute schizophrenia. Both studies showed that cannabidiol significantly alleviated psychotic symptoms during the acute phase and had a notably better side effect profile compared to standard antipsychotics. In fact, its side effect profile was comparable to that of a placebo.

Although these initial findings are promising, we strictly do NOT recommend using cannabidiol as an antipsychotic outside of controlled clinical trials. Several larger clinical trials are required to establish cannabidiol as a proven antipsychotic. Currently, we are conducting a maintenance clinical trial (CBD-ESPRIT) to examine the long-term effects of CBD in schizophrenia. We will keep you updated as more results become available.

At this point, the evidence supporting the safety and efficacy of cannabidiol—both for acute and maintenance treatment of psychosis and schizophrenia—is insufficient. Moreover, there is no data confirming the safety of combined therapy with cannabidiol and existing antipsychotics in humans to date.


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 the German Federal Ministry of Education and Research (BMBF – ESPRIT Network, FKZ: 01EE1407A). Currently, we are supported by Endosane Pharmaceuticals GmbH, Berlin, Germany.

Publications:

T. A. Couttas, C. Boost, F. Pahlisch, E. B. Sykorova, J. K. Mueller, B. Jieu, J. E. Leweke, I. Dammann, A. E. Hoffmann, M. Loeffler, O. Grimm, F. Enning, H. Flor, A. Meyer-Lindenberg, D. Koethe, C. Rohleder**, F. M. Leweke** (2024) Dose-dependent effects of oral cannabidiol and delta-9-tetrahydrocannabinol on serum anandamide and related N-acylethanolamines in healthy volunteers. BMJ Mental Health 27:e301027

B. Jieu, E. B. Sykorova, C. Rohleder, E. Marcolini, A. E. Hoffmann, D. Koethe, F. M. Leweke**, T. A. Couttas** (2024) Alterations to sphingolipid metabolism from antipsychotic administration in healthy volunteers are restored following the use of cannabidiol. Psychiatry Res 229:116005

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.