Impact of Repeatedly-Administered THC-cannabis on Experimental Pain and Abuse Liability in Humans

Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication, and they report experiencing minimal psychoactive effects. However, there are few well-controlled human laboratory studies assessing cannabis' efficacy for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability. Carefully controlled research is needed. The proposed randomized, within-subjects, placebo-controlled 16-day crossover inpatient human laboratory study (N = 20 healthy cannabis users; 10 men, 10 women) will address three important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) Does tolerance develop to repeated, daily smoked cannabis administration on measures of experimental pain and abuse liability; 2) If so, is tolerance reversed during the 7 days of abstinence from active-THC cannabis; 3) Does abrupt abstinence from active cannabis increase experimental pain sensitivity, i.e. hyperalgesia, relative to baseline, and do these effects parallel measures of cannabis withdrawal such as disrupted mood and sleep? Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS). Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.