Division on Substance Use Disorders, New York State Psychiatric Institute, Department of Psychiatry, Vagelos College of Physicians and Surgeons of Columbia University, 1051 Riverside Dr., Unit 66, New York, NY 10032, United States of America.
NYU Langone School of Medicine, Department of Psychiatry, New York, NY 10016, United States of America.
Pharmacol Biochem Behav. 2021 Oct;209:173241. doi: 10.1016/j.pbb.2021.173241. Epub 2021 Jul 21.
Recent data suggest that glial cells may be involved in the analgesic effects and abuse liability of opioids. Preclinical studies have demonstrated that mu-opioid-receptor-selective agonists, such as oxycodone, activate glia and increase the release of cytokines, causing a suppression of opioid-induced analgesic effects. Preclinical studies also show that certain medications, such as the broad-spectrum tetracycline antibiotic minocycline, inhibit opioid-induced glial activation and thereby enhance the analgesic effects of opioids. Importantly, minocycline reduces the rewarding effects of opioids at the same doses that it enhances opioid-induced analgesia.
The purpose of the present study was to assess the effects of acute administration of minocycline on the subjective, physiological, and analgesic effects of oxycodone in human research volunteers.
This study was a within-subject, randomized, double-blind outpatient study. Participants completed five separate sessions in which they received 0, 100, or 200 mg minocycline (MINO) simultaneously with either 0 or 40 mg oxycodone (OXY). The subjective, physiological, and analgesic effects of OXY were measured before and repeatedly after drug administration.
Participants were between 21 and 45 years of age, non-treatment seeking, non-dependent recreational opioid users (N = 12). This study was conducted between 2013 and 2014 at the New York State Psychiatric Institute in New York, NY.
MINO 100 and 200 mg were safe and well-tolerated in combination with OXY 40 mg. MINO 200 mg administered with OXY 40 mg attenuated OXY-induced positive subjective effects such as "Good Effect" and "Liking" compared to OXY alone. MINO did not alter the physiological or analgesic effects of OXY.
MINO may attenuate the abuse liability of mu-opioid-receptor-selective agonists.
最近的数据表明，神经胶质细胞可能参与了阿片类药物的镇痛作用和滥用倾向。临床前研究表明，μ-阿片受体选择性激动剂，如羟考酮，激活神经胶质细胞并增加细胞因子的释放，从而抑制阿片类药物引起的镇痛作用。临床前研究还表明，某些药物，如广谱四环素抗生素米诺环素，可抑制阿片类药物引起的神经胶质细胞激活，从而增强阿片类药物的镇痛作用。重要的是，米诺环素在增强阿片类药物诱导的镇痛作用的同时，降低了阿片类药物的奖赏作用。
本研究旨在评估米诺环素急性给药对人类研究志愿者羟考酮的主观、生理和镇痛作用的影响。
本研究为一项随机、双盲、门诊内的个体研究。参与者完成了五个单独的疗程，在每个疗程中同时给予 0、100 或 200mg 米诺环素（MINO），以及 0 或 40mg 羟考酮（OXY）。在给药前后重复测量 OXY 的主观、生理和镇痛作用。
参与者年龄在 21 至 45 岁之间，是非治疗性、非成瘾性的阿片类药物 recreational 使用者（N=12）。本研究于 2013 年至 2014 年在纽约州立精神研究所进行。
MINO 100 和 200mg 与 OXY 40mg 联合使用是安全且耐受良好的。MINO 200mg 与 OXY 40mg 联合使用可减弱 OXY 引起的正性主观效应，如“Good Effect”和“Liking”，与 OXY 单用时相比。MINO 并未改变 OXY 的生理或镇痛作用。
MINO 可能会减弱μ-阿片受体选择性激动剂的滥用倾向。
