Pharmacology Biochemistry and Behavior | 2021
Minocycline attenuates oxycodone-induced positive subjective responses in non-dependent, recreational opioid users
Abstract
BACKGROUND\nRecent 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.\n\n\nAIMS\nThe 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.\n\n\nDESIGN\nThis study was a within-subject, randomized, double-blind outpatient study. Participants completed five separate sessions in which they received 0, 100, or 200\u202fmg minocycline (MINO) simultaneously with either 0 or 40\u202fmg oxycodone (OXY). The subjective, physiological, and analgesic effects of OXY were measured before and repeatedly after drug administration.\n\n\nSETTINGS AND PARTICIPANTS\nParticipants were between 21 and 45\u202fyears of age, non-treatment seeking, non-dependent recreational opioid users (N\u202f=\u202f12). This study was conducted between 2013 and 2014 at the New York State Psychiatric Institute in New York, NY.\n\n\nFINDINGS\nMINO 100 and 200\u202fmg were safe and well-tolerated in combination with OXY 40\u202fmg. MINO 200\u202fmg administered with OXY 40\u202fmg 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.\n\n\nCONCLUSIONS\nMINO may attenuate the abuse liability of mu-opioid-receptor-selective agonists.