Avaliação do componente ansiedade em pacientes com disfunção temporomandibular muscular submetidos à tratamento com um óleo de cannabis full spectrum: ensaio clínico, randomizado, duplo-cego, controlado por placebo e estudo in sílico

Abstract

Temporomandibular dysfunction (TMD) is the second most common chronic musculoskeletal pain disorder worldwide, impacting quality of life and frequently associated with anxiety. Current pharmacological treatments have limited efficacy and significant adverse effects. Cannabis has emerged as a promising therapeutic alternative with a more favorable safety profile. This study evaluated the effects of a full-spectrum Cannabis oil on anxiety in patients with TMD and orofacial pain. A randomized, double-blind, placebo-controlled clinical trial was conducted, involving 10 women aged 26 to 53 years, divided into experimental and placebo groups. The intervention lasted 60 days, with data collection including anthropometric measurements, vital signs, and anxiety assessment using the IDATE questionnaire and self-reported emotional evaluation. Additionally, molecular docking simulations were performed to investigate the anxiolytic mechanisms of THC and CBD by analyzing their binding affinity to CB1, CB2, GPR55, and 5HT1A receptors. The results indicated that 60% of participants in the experimental group reported no pain at the end of the study, while 40% experienced a reduction from intense to mild pain. The average dose used was 10.4 drops/day. In the placebo group, 60% still reported intense pain even with the maximum dose (20 drops/day), while 40% reported no pain. The average consumption in this group was 16 drops/day. Phytochemical analysis revealed THC and CBD concentrations of 22.49% and 21.28%, respectively. There were no statistically significant changes in anthropometric measurements or vital signs. In the IDATE assessment, trait anxiety significantly decreased in the placebo group (p<0.02). However, 40% of participants in the experimental group reported reduced anxiety, and 60% felt calmer after using Cannabis oil. Adverse effects were present in both groups but were more frequent in the experimental group, with drowsiness being the most common. The molecular docking study demonstrated that THC and CBD interact with cannabinoid and 5HT1A receptors. THC showed higher affinity for CB1, CB2, and 5HT1A, while CBD exhibited stronger binding to GPR55. In conclusion, full-spectrum Cannabis oil, administered for 60 days at moderate doses, reduced pain in 80% of participants without affecting anthropometric parameters or vital signs. Although anxiety measured by IDATE was not significantly influenced, self-assessments indicated a greater sense of calm in the experimental group. The potential use of Cannabis oil for sleep disorders should be highlighted, given that drowsiness was the most common adverse effect. Further clinical trials are needed to better investigate the anxiolytic effects of phytocannabinoids, particularly at different concentrations and THC:CBD ratios. In silico modeling suggests that, in addition to cannabinoid receptors CB1 and CB2, the 5-HT1A receptor is also involved in the effects produced by the tested product.