Impact of Cannabis on Opioid Self-Administration: Determining if Cannabis Alters the Drive to Take Opioids in Individuals with Opioid Use Disorder - Abstract Opioid misuse is an international epidemic, with an estimated 60 million individuals misusing opioids worldwide. In the US in 2022, 6.1 million individuals met criteria for opioid use disorder and 81,083 people died due to opioid overdose. In the background of the opioid epidemic, global cannabis use is also at peak levels, with 219 million users worldwide. At the same time, 22% of individuals ages 12 and older (nearly 62 million individuals) reported past year cannabis use, 42.3 million reported past-month use and 19 million individuals met criteria for cannabis use disorder. Despite these high rates of opioid and cannabis use, there are no controlled data available on how cannabis impacts opioid drug taking. Although many advocates and even several US states suggest that cannabis is an appropriate therapeutic option for opioid use disorder (i.e., 5 US states list opioid use disorder as a qualifying condition for medical cannabis) – there are virtually no controlled data on this topic. Specifically, no studies to date have examined the impact of cannabis use on opioid drug taking (i.e., opioid self-administration) in those who are at the greatest risk - individuals with opioid use disorder. The current project aims to fill this gap and provide fundamental public health data by conducting two randomized, double-blind, placebo-controlled, within subject, inpatient studies enrolling individuals with moderate-to-severe opioid use disorder and opioid physical dependence. Study 1 will determine how repeated inhaled cannabis exposure (active cannabis [30 mg THC] vs. inactive cannabis [0 mg THC]) impacts intranasal oxycodone self-administration across a wide range of doses (0, 45, 90 mg). Study 2 will determine if cannabis (0, 20, 40 mg THC), when offered as an alternative drug option, can alter the choice to take an opioid (0, 45, 90 mg, IN). Both studies will include secondary outcomes of abuse potential assessments and safety/physiological measures. Exploratory outcomes include examining endocannabinoid tone and experimental pain response across the dosing conditions. These novel and timely studies will provide the first empirical data on the impact of cannabis on opioid self-administration in a vulnerable population at the highest risk for opioid-related harms. These studies will inform clinical practice, medical cannabis recommendations, risk mitigation strategies, and regulatory decisions by providing public health information immediately relevant to the opioid epidemic.
