PM287. Mixtures of opioid receptor agonists and cannabinoid receptor agonists: enhanced antinociception without abuse liability
Year: 2016
Type: conference-abstract
Abstract: Mu opioid receptor agonists remain the drugs of choice for treating moderate-severe pain despite their well-documented adverse effects (constipation, respiratory depression, abuse). Kappa opioid receptor agonists also have antinociceptive effects although adverse effects (dysphoria, hallucinations) have precluded their use in the clinic. One strategy for reducing or avoiding the adverse effects of opioid receptor agonists (mu and possibly kappa) is to combine them with drugs that exert antinociceptive effects through nonopioid mechanisms. The need for much smaller doses of each drug in a drug mixture, to achieve the desired therapeutic effect, has the potential to avoid the adverse effects that occur with larger doses of either drug administered alone, thereby increasing the therapeutic window of both drugs. These studies used adult male rats to examine the antinociceptive effects of mu and kappa opioid receptor agonists, each administered alone and in combination with a cannabinoid receptor agonist. When administered alone (intraperitoneally), morphine (mu receptor agonist; 1.78–17.8 mg/kg), spiradoline (kappa receptor agonist; 1–32 mg/kg), Δ9-tetrahydrocannabinol (THC; cannabinoid receptor agonist; 3.2–32 mg/kg), and CP55940 (cannabinoid receptor agonist; 0.032–1 mg/kg) increased tail withdrawal latency from 50oC water in a dose-related manner. Mixtures of an opioid and a cannabinoid, in ratios of 3:1, 1:1, and 1:3, also increased tail withdrawal latency in a dose-related manner. The interaction for both mu (morphine) and kappa (spiradoline) receptor agonists with a cannabinoid receptor agonist was at least additive for all mixtures and greater than additive (synergistic) for some ratios of some mixtures. Together these results support the view that mixtures of opioids and nonopioids could provide significant therapeutic effects (for treating pain) in the absence of adverse effects that currently limit the use of opioids in the clinic. Supported by USPHS Grant K05DA017918
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,693
OpenAlex ID: W2807852162