Vaped Marijuana to Attenuate Naloxone-Precipitated Withdrawal

The goal of the proposed, proof-of-concept study is to test the combined effects of vaporized marijuana \[Delta-9-tetrahydracannabinol (THC)\] with NLX as a proof of concept towards the possible development of a combined overdose reversal agent with improved tolerability. Marijuana plant material will be obtained from the National Institutes on Drug Abuse (NIDA). In clinical studies, oral synthetic THC reduced the severity of opioid withdrawal during opioid detoxification. Clinically, cannabinoid drugs like Marinol® (oral synthetic THC), Sativex ® (nabixomols), and Cesamet® (nabilone) are used to treat nausea and vomiting, common symptoms of opioid withdrawal. This study will investigate the ability of vaporized marijuana (V-MJ) (0.00, 12.5, and 25 mg: concentration= 11.7% THC + 0.04% CBD) to reduce the severity of opioid withdrawal precipitated by intranasal (IN) NLX (0.0 and 4.0 mg). This trial will recruit healthy participants with opioid use disorder (N=16, completers). Testing will begin following stabilization on oral morphine (120 mg/day), which will continue throughout the trial. During each testing session, a single V-MJ + naloxone dose combination will be assessed (in randomized order), with 48 hours between testing sessions. Laboratory testing sessions will consist of a modified naloxone challenge procedure, which quantifies the severity of naloxone-precipitated opioid withdrawal.