Examining the Severity and Progression of Illicitly Manufactured Fentanyl Withdrawal: A Quasi-experimental Comparison

Illicitly manufactured fentanyl has largely replaced heroin throughout the United States. Characteristics of fentanyl-specific withdrawal are not well understood compared to traditional opioid withdrawal. This study examines opioid withdrawal severity among 2 cohorts of study participants who underwent identical morphine stabilization procedures before and after fentanyl was introduced to the local drug market.

The Non-Fentanyl study (n = 103) included participants testing positive for non-fentanyl opioids, and the Fentanyl study (n = 30) included participants testing positive for fentanyl. Both studies completed a 7-day morphine stabilization protocol (30 mg subcutaneous, 4 times daily) and multiple daily self-report and observer-rated assessments of opioid withdrawal and vital signs. Two-way repeated-measures analyses of variance (ANOVAs) examined the effects of study, time, and study × time on daily peak ratings for each outcome.

There were significant elevations in self-report and observer-rated withdrawal scores among the Fentanyl versus Non-Fentanyl study (study × time, P < 0.05) during stabilization days 2-5 and days 2-6, respectively. There was a higher rate of tachycardia among the Fentanyl group compared to the Non-Fentanyl study, and peak diastolic blood pressure was greater among the Fentanyl study compared to the Non-Fentanyl study.

Individuals with fentanyl exposure were less stabilized by morphine and experienced more severe opioid withdrawal via several metrics compared to persons with non-fentanyl opioid exposure. Withdrawal also remained elevated for several days despite morphine initiation. Adjustments to existing treatment induction protocols may be needed given the permeation of fentanyl into the heroin supply.