Publication details

Kanabinoidy, endokanabinoidní systém a terapie vybraných poruch úzko stného spektra

Title in English Cannabinoids, endocannabinoid system and therapy of anxiety disorders
Authors

JOHN Petr JUŘICA Jan

Year of publication 2024
Type Article in Periodical
Magazine / Source Česká a slovenská Psychiatrie
MU Faculty or unit

Faculty of Medicine

Citation
web http://www.cspsychiatr.cz/detail.php?stat=1594
Keywords cannabidiol; cannabinoids; endocannabinoids; generalized anxiety disorder; nabilon; posttraumatic stress disorder; social anxiety disorder; tetrahydrocannabinol
Description Abstract: In the development of novel anxiolytics, the endocannabinoid system (ECS) is a promising therapeutic target primarily due to its ability to modulate synaptic plasticity and to act as a retrograde regulator of several neurotransmitter systems. Pharmacologically, it can target at CB1 and CB2 receptors (agonistitic or antagonistic activity) or by inhibiting FAAH and MAGL enzymes, which are involved in endocannabinoid degradation. The aim of this article is to provide a comprehensive systematic review of the clinical use of the endocannabinoid system as a pharmacotherapeutic target in anxiety spectrum disorders (posttraumatic stress disorder, generalized anxiety disorder, social phobia, and panic disorder). Method: In May 2023, a systematic search through the Medline (PubMed) and Web of Science (WOS) databases was performed. The keywords used were "(cannabinoid* OR endocannabinoid* OR cannabidiol* OR tetrahydrocannabinol*) AND ((PTSD OR posttraumatic stress disorder) OR (GAD OR generalized anxiety disorder) OR (PA OR panic attack) OR (SAD OR social anxiety disorder))" in the "Title OR Abstract" fields. Exclusion criteria included non-English language records, case reports, conference abstracts, and preclinical studies. Thus, only prospective, retrospective, randomized controlled trials using fixed doses of cannabinoids or combinations of cannabinoid receptor ligands compared with placebo were included in the review article. Results: Using the Medline and Web of Science databases, 420 and 458 publications respectively were retrieved, of which 410 and 454 were excluded from the review for not meeting the inclusion criteria. Thus, ten publications that were relevant to the topic were included in the review. There were six studies dealing with cannabinoids in the treatment of PTSD and further four studies referring to the use of cannabinoids in the treatment of SAD and GAD. Clinical trials in the treatment of panic disorder have not yet been conducted. Conclusion: Based on the results of clinical trials published to date, it appears that endocannabinoids have been tested in recent years as an alternative or complementary therapy in the indications of anxiety disorders, particularly PTSD, GAD and SAD. Four randomised clinical trials, which investigated the effect of cannabinoids in the treatment of SAD, found cannabidiol to be effective. Out of the six open-label or retrospective studies evaluating the effect of cannabinoids in the treatment of PTSD, nabilone or tetrahydrocannabinol have demonstrated efficacy in three studies. The remaining three studies showed clinical effect however not statistically significant or assessable. The favourable results of the studies may be affected by the low number of subjects and, in some studies, the absence of a control group. In addition, some studies have drawn conclusions based on the dose-response relationship with the use of measures such as neuroimaging and subjective scores on anxiety assessments, without assessing plasma levels of administered cannabinoids. Thus, although the available data suggest a promising potential for cannabinoids in the treatment of anxiety disorders, we should interpret the results with caution for the reasons mentioned above. Thus to draw evidence-based conclusions for clinical practice, it will be necessary to wait for the results of well-designed prospective, randomized, controlled trials to confirm the findings definitively.
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