Evaluating dynamic associations between pain catastrophizing and the effect of cannabinoids

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Project Summary This NRSA F32 proposal includes a coordinated training plan and research project that will facilitate the candidate's transition to becoming a productive, independent investigator. Specifically, the applicant proposes three training goals: (1) develop expertise in psychophysical pain assessment; (2) acquire comprehensive knowledge of the methodology, safety, and ethics of conducting human behavioral pharmacological research; and (3) deepen knowledge of cannabis/cannabinoids, their mechanisms of action, and risk. Learned skills will be applied to conducting a research project that will examine how the effect of an FDA-approved cannabinoid (i.e., dronabinol) is dynamically associated with pain catastrophizing, a potent predictor of negative pain-related outcomes and a crucial psychological factor in pain management. Although chronic pain is a debilitating condition that affects millions of individuals, current treatment options for pain still largely rely on opioids, which have substantial safety concerns. Thus, investigating safer and more effective pharmacological pain management strategies is imperative for public health. Pre-clinical studies suggest considerable promise of cannabinoids as an effective analgesic agent. However, findings on the efficacy of cannabinoid analgesia have been widely mixed across human clinical studies. Furthermore, despite the fact that effective pain management involves addressing various factors beyond pain reduction, previous studies on cannabinoids have only focused on evaluating pain intensity as their primary endpoint. The applicant proposes that pain catastrophizing (PC), a maladaptive state and trait cognitive-affective response to pain, can play an important role in expanding our nascent understanding of cannabinoids’ potential utility in pain management. The proposed study builds upon the applicant’s knowledge and experience in pain-related cognition and individual differences in pain regulation. This project will be based upon sponsors’ NIH-funded parent R01 (DA042751) that is a within-subject, randomized, double-blind, and placebo-controlled human laboratory experiment with chronic pain patients. The applicant’s proposed study aims to investigate cannabinoids’ potential to reduce state PC and the influence of trait PC on analgesic efficacy of cannabinoids. It is expected that cannabinoid administration will result in a greater reduction in state PC than a placebo. It is also hypothesized that individuals with higher trait PC will exhibit significantly lower cannabinoid analgesia relative to those with lower trait PC. The training and mentorship that the applicant will receive from pursing the present study will help him attain his long-term goal of unraveling the bio-behavioral mechanisms of pain regulation and developing personalized integrative pain management programs. Furthermore, the present study will contribute to a nuanced evaluation of cannabinoids’ therapeutic potential in pain management, as well as precision pain medicine, which are important public health goals.