Summary: Buprenorphine is quite effective for managing opioid addiction, including fentanyl addiction. However, many of those who transition from fentanyl to buprenorphine experience worsening withdrawal symptoms. A new pilot study shows that sub-lingual ketamine could be an answer to this problem.
Despite much effort in recent years, opioid overdose-related deaths continue to be a significant issue in the US. However, the characteristics of this epidemic have changed over the years. Fentanyl, a potent synthetic opioid, is now among the primary causes of opioid overdose-related deaths. In 2022, an estimated 83,000 individuals died due to fentanyl overdose or due to fentanyl-laced drugs.
It means that over the years, this synthetic opioid has become one of the significant issues. Hence, the focus of doctors has also shifted to treating fentanyl addiction. Since fentanyl withdrawal causes severe symptoms, those addicted to the substance are treated with safer opioids like buprenorphine. It was the first drug approved in the US for treating opioid use disorder (OUD) and can be dispensed in physicians’ offices. It has an excellent safety record.
However, things are not that simple. Some individuals develop rare complications when they are prescribed buprenorphine for fentanyl addiction. They develop a condition called buprenorphine-precipitated opioid withdrawal (BPOW). It is a condition in which patients experience significant pain, discomfort, and distress when they are given buprenorphine to manage their fentanyl addiction. Simply put, in some patients opioid withdrawal symptoms actually worsen when treatment with the drug begins.
Now, one of the new studies shows that ketamine, one of the well-known anesthetic drugs, may help such patients. It may help overcome BPOW and thus may be useful in managing fentanyl withdrawal symptoms.
Ketamine has been in clinical use for more than half a century, and interest in this drug has been reignited due to its ability to help rewire the brain and manage OUD and other kinds of addictions and mental health conditions like depression. This drug has shown some wonderful results in low dosages. Addictionology Center provides opioid addiction treatment as a part of a comprehensive care approach.
There are many strategies for giving ketamine to patients. One strategy is giving patients slow IV infusion in a physician’s office under controlled conditions. Another emerging strategy is using low-dose ketamine sub-lingually. At lower dosages, it is relatively safe and helps overcome a range of conditions. It appears the sub-lingual ketamine is especially good for those transitioning from fentanyl or even methadone to buprenorphine.
This new study that reported the benefits of sub-lingual ketamine was a small clinical trial. It enrolled 37 patients, and out of them, just 16 completed the study. Nevertheless, the results were just astonishing in this small number of patients. Almost all of them (92%) reported significant benefits with a reduction in opioid withdrawal symptoms.
Although ketamine has been in clinical use for decades, its mechanism of action is not fully understood yet. Nevertheless, it is known that it particularly affects the so-called NMDA-type glutamate receptor (NMDAr) and many other brain receptors.
However, much mystery still remains around ketamine. For example, it does not work for long, even when taken sub-lingually in small dosages. However, studies show that its benefits may last for much longer. It may reduce pain and emotional distress for much longer periods. So, it appears that ketamine causes certain brain changes.
Hence, there is a need for more extensive trials to understand its role in managing substance abuse disorder and also managing OUD. When used responsibly, it does not cause addiction and is pretty safe.
Frequently asked questions
What does precipitated withdrawal mean?
Precipitated withdrawal is withdrawal that gets worse when treatment starts. Some people switching from fentanyl to buprenorphine develop buprenorphine-precipitated opioid withdrawal (BPOW): instead of relief, the first doses bring significant pain, discomfort and distress. Buprenorphine itself has an excellent safety record; the trouble comes during the switch.
Can ketamine help with opioid withdrawal?
A small pilot study says it can. Low-dose ketamine taken under the tongue was given to patients switching from fentanyl to buprenorphine. The study enrolled 37 patients and 16 completed it, and 92% of those who finished reported a significant reduction in opioid withdrawal symptoms. Larger trials are still needed to define ketamine’s role in treating opioid use disorder.
How is ketamine given for withdrawal?
There are two main ways. One is a slow IV infusion in a physician’s office under controlled conditions. The other, newer approach is low-dose ketamine placed under the tongue (sublingual). At lower doses ketamine is relatively safe, and the sublingual form appears especially useful for people moving from fentanyl or methadone to buprenorphine.
Is ketamine like fentanyl?
They are different drugs. Fentanyl is a potent synthetic opioid and a leading cause of overdose deaths. Ketamine is an anesthetic that has been in clinical use for more than half a century. It works mainly on the NMDA-type glutamate receptor, along with other brain receptors, and when used responsibly it does not cause addiction and is quite safe.
Source:
Grande, L. A., Hutch, T., Jack, K., Mironov, W., Iwuoha, J., Muy-Rivera, M., Grillo, J., Martin, S. A., & Herring, A. (2024). Ketamine-assisted buprenorphine initiation: A pilot case series. Addiction Science & Clinical Practice, 19(1), 60. https://doi.org/10.1186/s13722-024-00494-2