Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 43; no. 10; pp. 2046 - 2055
• Main Authors: Cooper, Ziva D., Bedi, Gillinder, Ramesh, Divya, Balter, Rebecca, Comer, Sandra D., Haney, Margaret
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2018; Springer International Publishing
• Subjects: Abuse; Adult; Analgesia; Analgesics; Analgesics, Opioid - pharmacology; Blindness; Cannabinoids; Cannabis; Double-Blind Method; Dronabinol - pharmacology; Drug Synergism; Drug tolerance; Female; Humans; Laboratory animals; Liability; Male; Marijuana; Marijuana Smoking - psychology; Middle Aged; Narcotics; Opioid-Related Disorders - psychology; Opioids; Oxycodone; Oxycodone - pharmacology; Pain; Pain Measurement - drug effects; Pain perception; Self-administration; Tetrahydrocannabinol; Young Adult
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/s41386-018-0011-2

Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5, and 5.0 mg, PO) with smoked cannabis (0.0, 5.6% Δ tetrahydrocannabinol [THC]) and analgesia was assessed using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4 °C); times to report pain (pain threshold) and withdraw the hand from the water (pain tolerance) were recorded. Abuse-related effects were measured and effects of oxycodone on cannabis self-administration were determined. Alone, 5.0 mg oxycodone increased pain threshold and tolerance (p ≤ 0.05). Although active cannabis and 2.5 mg oxycodone alone failed to elicit analgesia, combined they increased pain threshold and tolerance (p ≤ 0.05). Oxycodone did not increase subjective ratings associated with cannabis abuse, nor did it increase cannabis self-administration. However, the combination of 2.5 mg oxycodone and active cannabis produced small, yet significant, increases in oxycodone abuse liability (p ≤ 0.05). Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis's abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.