Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys

Area of Science:

• Pharmacology
• Neuroscience
• Pain Management

Background:

• Opioids are primary treatments for severe pain but have limiting adverse effects.
• Combining opioids with other analgesics could improve efficacy if side effects are not increased.
• Cannabinoids enhance opioid antinociception without increasing other effects.

Purpose of the Study:

• To investigate if cannabinoid effectiveness is altered in morphine-dependent monkeys.
• To assess the development of cross-tolerance between opioids and cannabinoids.

Main Methods:

• Four monkeys received daily morphine doses.
• Antinociceptive effects of opioid and cannabinoid agonists were measured using tail-withdrawal latency from warm water.
• Tolerance was assessed by changes in drug potency during chronic morphine treatment.

Main Results:

• Chronic morphine treatment decreased the antinociceptive potency of morphine and cannabinoids (WIN 55,212, CP 55,940).
• The greatest potency decrease was observed for morphine, WIN 55,212, and CP 55,940, with at least sixfold shifts.
• Morphine discontinuation caused withdrawal signs, including increased heart rate and decreased activity.

Conclusions:

• Tolerance to antinociceptive effects of morphine and cross-tolerance to cannabinoids developed with modest physical dependence.
• Lower opioid doses may be effective with cannabinoids, potentially preventing tolerance.
• Opioid-cannabinoid mixtures may offer a strategy for improved chronic pain management.