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

Abstract

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.

Cannabis for Chronic Pain: Challenges and Considerations

“…This body of evidence suggests that the concomitant use of cannabis with opioids could result in a reduction of cannabis and opiate concentrations for pain relief . According to a recent meta‐analysis, cannabinoids produce an opioid‐sparing effect in preclinical studies; however, more high‐quality clinical studies are needed to confirm these results . Interestingly, a recent randomized, double blind, placebo‐controlled study has shown that low doses of oxycodone (2.5 mg orally but not 5 mg orally) plus low THC concentration cannabis (5.6% smoked) increased tolerance to experimental cold pain in healthy individuals, compared to a lack of effect with either drug alone, which suggests synergistic analgesic effects .…”

Diverse TRPV1 responses to cannabinoids

“…The secondary metabolome of the Cannabis plant has been suggested as sources of new analgesics [14][15][16][17]. Pain is a primary use of medicinal Cannabis and substitution for prescription opioids is common [18,19], and demonstrably opioid sparing [20][21][22]. Unregulated "medical marijuana" use for pain covers multiple demographics and disorders, even reaching historically underserved groups such as seniors facing undertreatment of pain at end-oflife [23].…”

Δ9-tetrahydrocannabinol Attenuates Oxycodone Self-Administration Under Extended Access Conditions

“…Opioid overdose mortality is lower in states with medical marijuana legalization (Bachhuber et al, 2014) and an experimental study found that inhalation of cannabis (via Volcano® vaporizer) decreased pain in chronic pain patients that were being maintained on extended release oxycodone or morphine without changing the plasma concentration-time curves for either medication (Abrams et al, 2011). A recent clinical study found that smoked cannabis enhanced the analgesic effects of oxycodone and produced modest increases in positive subjective ratings related to oxycodone when administered in combination (Cooper et al, 2018). These findings suggest that psychoactive cannabinoids may interact with the effects of opioids, both to enhance therapeutic impact and to potentially reduce nonmedical use.…”