Cannabinoid modulation of opioid analgesia and subjective drug effects in healthy humans

• Published in: Psychopharmacology Vol. 236; no. 11; pp. 3341 - 3352
• Main Authors: Babalonis, Shanna, Lofwall, Michelle R., Sloan, Paul A., Nuzzo, Paul A., Fanucchi, Laura C., Walsh, Sharon L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2019; Springer; Springer Nature B.V
• Subjects: Abuse; Adolescent; Adult; Agonists; Analgesia; Analgesia - methods; Analgesia - psychology; Analgesics; Analgesics, Opioid - pharmacology; Analgesics, Opioid - therapeutic use; Analysis; Biomedical and Life Sciences; Biomedicine; Blindness; Cannabinoid Receptor Agonists - pharmacology; Cannabinoid Receptor Agonists - therapeutic use; Cannabinoid receptors; Cold tolerance; Cross-Over Studies; Diagnostic Self Evaluation; Double-Blind Method; Drug dosages; Drug tolerance; Female; Healthy Volunteers; Humans; Hyperalgesia; Male; Middle Aged; Narcotics; Neurosciences; Opioids; Original Investigation; Oxycodone; Pain; Pain - drug therapy; Pain - psychology; Pain Measurement - drug effects; Pain Measurement - methods; Pain Measurement - psychology; Pain perception; Pharmacology/Toxicology; Pressure; Pressure tolerance; Psychiatry; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Remifentanil; Tetrahydrocannabinol; Young Adult; France; Human; Opioid; Pain; Opioid sparing; Cannabinoid; Dronabinol
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-019-05293-1

Rationale Dozens of preclinical studies have reported cannabinoid agonist potentiation of the analgesic effects of μ-opioid agonists. Objectives The aim of this study was to determine if a cannabinoid agonist could potentiate opioid analgesia in humans using several laboratory pain models. Methods Healthy participants ( n  = 10) with/out current drug use/pain conditions completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Nine 8-h sessions were completed during which dronabinol (0, 2.5, 5 mg, p.o.) was administered 1 h before oxycodone (0, 5, 10 mg, p.o.) for a total of 9 test conditions. Outcomes included sensory threshold and tolerance from four experimental pain models (cold pressor, pressure algometer, hot thermode, cold hyperalgesia), along with participant- and observer-rated, performance and physiological effects. Results Oxycodone produced miosis ( p  < 0.05) and analgesic responses (e.g., pressure algometer [ p  < 0.05]), while dronabinol did not ( p  > 0.05). Depending on the dose combination, dronabinol attenuated or did not alter oxycodone analgesia; for example, dronabinol (2.5 mg) decreased the analgesic effects of oxycodone (10 mg) on pressure tolerance. Conversely, dronabinol increased oxycodone subjective effects (e.g., drug liking) ( p  < 0.05); oxycodone (5 mg) ratings of “high” were potentiated by 5 mg dronabinol ( p  < 0.05; placebo = 1.1 [± 0.7]; 5 mg oxycodone = 4.7 [± 2.2]; 5 mg dronabinol = 9.9 [± 8.4]; 5 mg oxycodone + 5 mg dronabinol = 37.4 [± 11.3]). Conclusions This study indicates that dronabinol did not enhance the analgesic effects of oxycodone and increased abuse- and impairment-related subjective effects. These data suggest that dronabinol may not be an effective or appropriate opioid adjuvant; it could potentially increase opioid dose requirements, while increasing psychoactive opioid effects.