Opioid Withdrawal and Opioid Antagonists

"For people with opioid tolerance, withdrawal symptoms begin within 6 hours after the last use of short-acting opioids such as fentanyl or heroin or within 1 to 3 days after long-acting opioids such as methadone or buprenorphine. Withdrawal effects, which last days to weeks, include autonomic hyperactivity (tachycardia, hypertension, hyperthermia, hyperhidrosis, mydriasis, and piloerection), neuropsychiatric symptoms (anxiety, restlessness), and gastrointestinal symptoms (nausea, abdominal cramping, diarrhea; Figure 1).¹¹ The COWS (Clinical Opioid Withdrawal Scale) is a standardized tool that assesses and quantifies 11 signs and symptoms of opioid withdrawal and is scored from 0 to 47 (5-12 mild, 13-24 moderate, and >24 severe).¹² Some people experiencing opioid withdrawal have symptoms of dysphoria, disrupted sleep, and cravings for months.¹³

"For people with opioid tolerance, use of opioid antagonists displaces opioid agonists from μ-opioid receptors, causing precipitated withdrawal, a condition of intense withdrawal symptoms that develops within minutes of taking an opioid antagonist. Similarly, buprenorphine, a partial agonist, can acutely precipitate withdrawal symptoms in the presence of full opioid agonists (eg, fentanyl or methadone) by competitively binding the μ-opioid receptor and rapidly displacing full agonists.¹⁴"