Ketamine rapidly reverses fentanyl withdrawal symptoms, study finds
Posted on February 23, 2026 by Marketing and Communications
Drug overdoses caused an estimated 73,000 U.S. deaths last year, with the synthetic
opioid fentanyl causing the majority of fatal overdoses.
Buprenorphine, a medication for treating opioid-use disorder, is effective and saves
lives, but people often avoid it for fear of painful opioid withdrawal symptoms that
can occur when starting the medication.
This is particularly true among fentanyl-dependent individuals, many of whom report
that buprenorphine initially makes their symptoms worse before abating. Withdrawal
symptoms of muscle aches, vomiting, diarrhea, sweating, chills, restlessness and anxiety
can increase in severity for up to five days.
Findings published Feb. 11 in the journal Addiction Science and Clinical Practice
showed that a new strategy of using an extremely low intramuscular dose of the anesthetic
ketamine before starting buprenorphine led to a rapid, large reduction of fentanyl
withdrawal symptoms in nearly all patients, without any side effects. Most patients
could then immediately start buprenorphine without a return of withdrawal symptoms.
“It has been a challenge helping individuals dependent on opioids in the fentanyl
era, and this simple, inexpensive and highly effective treatment strategy has a lot
of promise in helping people transition to buprenorphine safely and comfortably. The
hope is that this will be another opportunity to make a dent in the ongoing opioid
overdose epidemic ,” said Luke Engeriser, M.D., first author of the study, deputy
chief medical officer for AltaPointe Health, and an associate professor of psychiatry
at the University of South Alabama Frederick P. Whiddon College of Medicine.
Engeriser, who also serves as director of the psychiatry residency program and the
addiction medicine fellowship, designed the study, which followed 50 patients experiencing
fentanyl withdrawal at a 24-hour crisis center in Mobile, Alabama. Over half of the
patients were completely free of withdrawal symptoms within an hour of starting the
ketamine-assisted buprenorphine therapy, and the average length of stay at the facility
dropped from 66 hours to seven hours. Almost all patients were stable enough for discharge
from the crisis center within hours after the first buprenorphine dose. The ketamine
treatment costs 44 cents per patient.
In emergency departments, a high dose of ketamine, causing intense drowsiness, has
been shown to reverse withdrawal symptoms after starting buprenorphine. This study
was the first demonstration that a low dose of ketamine could both relieve fentanyl
withdrawal and prevent renewed symptoms after starting buprenorphine.
The researchers think this strategy could be adapted for use in many settings where
buprenorphine treatment is offered, including inpatient, emergency department, residential
treatment, withdrawal management, crisis center, outpatient, prison/jail or mobile
clinics, and warrants further study in these settings. Importantly, since ketamine
is a controlled substance, injection by a healthcare provider is safer than self-administration
as it avoids the risk of misuse by patients.
“I have seen the impact this protocol has had in quickly and relatively comfortably
transitioning patients from dangerous use patterns onto a path to recovery and stability.
It has been very gratifying to provide such a benefit to the person in front of me
while contributing to a shift in how many others receive care,” said Evan Chavers,
M.D., a co-author of the study and chief resident of the psychiatry residency program.
This report of the use of sub-dissociative dose ketamine to block withdrawal symptoms
affirms and greatly strengthens findings from a previously published pilot study from
the senior author of this week's report, Dr. Lucinda Grande, a primary care doctor
in Lacey, Washington and a clinical associate professor of family medicine at the
University of Washington School of Medicine, who specializes in chronic pain and addiction
treatment.
The paper is available at https://rdcu.be/e3Brj.