Koseli Eda, Buzzi Belle, Honaker Torin, Rakholia Yogesh, Lewis Melissa, Gaines-Smith Maya, Jaster Alaina M, Gonzalez-Maeso Javier, Damaj M Imad
Department of Pharmacology and Toxicology, Virginia Commonwealth University, USA.
Department of Physiology & Biophysics, Virginia Commonwealth University, Richmond, VA, USA.
Pharmacol Res. 2025 May;215:107699. doi: 10.1016/j.phrs.2025.107699. Epub 2025 Mar 17.
Chronic pain is a debilitating disease with current treatments lacking efficacy and safety, therefore discovery of new treatments is crucial. Initial studies suggest that psychedelics may be feasible for targeting pain, however clinical and preclinical controlled studies are necessary to further investigate that possibility. In this study we assessed the effects of two classical psychedelics psilocybin and 2,5-Dimethoxy-4-iodoamphetamine (DOI) in two models of chronic pain after systemic administration in male and female mice. Psilocybin and DOI dose-dependently reversed mechanical and cold hypersensitivity in the chemotherapy-induced peripheral neuropathy (CIPN) mouse model with different time-course of action. Similarly, psilocybin and DOI dose-dependently reversed thermal hypersensitivity in the chronic inflammatory mouse model of Complete Freud's Adjuvant (CFA). The effects of Psilocybin and DOI in both models were mediated by activation of 5-HT receptors (5-HTR). Overall, the present study suggests that classical psychedelics psilocybin and DOI are effective in reducing pain-like behaviors via 5-HTR activation in two mouse models of chronic pain.
慢性疼痛是一种使人衰弱的疾病，目前的治疗方法缺乏疗效和安全性，因此发现新的治疗方法至关重要。初步研究表明，迷幻剂可能对治疗疼痛可行，然而，需要进行临床和临床前对照研究来进一步探究这种可能性。在本研究中，我们评估了两种经典迷幻剂——裸盖菇素和2,5-二甲氧基-4-碘苯丙胺（DOI）——在雄性和雌性小鼠全身给药后对两种慢性疼痛模型的影响。裸盖菇素和DOI在化疗诱导的周围神经病变（CIPN）小鼠模型中剂量依赖性地逆转了机械性和冷超敏反应，且作用时间过程不同。同样，裸盖菇素和DOI在完全弗氏佐剂（CFA）慢性炎症小鼠模型中剂量依赖性地逆转了热超敏反应。裸盖菇素和DOI在两种模型中的作用均由5-羟色胺受体（5-HTR）的激活介导。总体而言，本研究表明，经典迷幻剂裸盖菇素和DOI在两种慢性疼痛小鼠模型中通过激活5-HTR有效减轻了疼痛样行为。
