Study of the effects of chronic treatment with cannabidiol orally administered on the microbiota profile in mice

• Grant number: 24/03720-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Sayuri Higa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders, AP.TEM

Abstract

Cannabidiol (CBD) is the most abundant non-psychoactive phytocannabinoid in C. sativa, and there is an extensive bibliography on its mechanisms of action in the body and its effects on neuropsychiatric disorders, such as anxiety and obsessive-compulsive disorder. In clinical studies with CBD, most have identified therapeutic effects at high doses and have been conducted with intraperitoneal administration. On the other hand, there is currently a growing use of Cannabis products or its derivatives, such as Cannabidiol, at low doses over long periods and with oral administration of these phytocannabinoids, and there are reports of symptom improvement, such as anxiety. However, such results are often attributed to the placebo effect. Nonetheless, recently, the antimicrobial action of CBD has been discovered, which, when consumed orally, could alter the intestinal microbiota. On the other hand, there are several studies showing that the gut microbiota has an effect on behavior through the Microbiota-Gut-Brain (MGB) communication axis. The composition of this bacterial community has been linked to various comorbidities and neuropsychiatric disorders, such as stereotyped behavior and autism. Thus, we raised the question whether the reported effects of CBD use at low doses orally might not be related to the antimicrobial action of CBD, which could lead to alterations in the intestinal microbiota, influencing behavior. Therefore, this project aims to investigate changes in the intestinal microbiota caused by chronic oral use of cannabidiol at different doses (3, 10, and 30 mg/kg) and its effects on repetitive and compulsive behavior in mice through the Marble Burying test.