Endocannabinoid System as Potential Target for Opioid Withdrawal Treatment

Finding new medications to effectively alleviate opioid withdrawal is an important step in enabling transition to medication protocols to treat opioid use disorders. Many patients drop out of treatment early if they cannot tolerate the withdrawal period and are then unable to start medications.

The endocannabinoid system is a potential novel target for opioid withdrawal treatment. Scientists supported by the National Institute on Drug Abuse conducted a proof-of-concept study examining the potential efficacy of a cannabinoid receptor (CB1) partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. (An agonist means it activates the cannabinoid receptors). Dronabinol is a synthetic form of cannabis approved by the Food and Drug Administration to treat loss of appetite that causes weight loss in people with AIDS.

Twelve opioid dependent adults participated in this five-week, inpatient, double-blind, randomized, placebo-controlled study. Results suggest that lower doses of dronabinol (i.e., 5 and 10 mg) produced effects similar to placebo, while higher doses (i.e., 20 and 30 mg) modestly suppressed withdrawal, but also produced sedation and impairment, a feeling of being high, and unpleasant sensations like a racing heart.

The authors conclude that while CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal, it is not a likely candidate given its modest withdrawal suppression effects and concerning effects on heart rate. Instead, they suggest exploring other CB1 agents or medications with different mechanisms of action on the endocannabinoid system to treat opioid withdrawal.


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