Buprenorphine is a semi-synthetic opioid derived from the opioid thebaine. [1] Buprenorphine was originally developed to provide analgesia but is much more commonly used for the management of opioid dependence. [2] It functions as a partial agonist for the mu receptor, to which addictive opioids bind, and can thus manage opioid addiction by decreasing the physiological responses typically associated with opioid tolerance. It produces effects such as euphoria and respiratory depression at low to moderate doses, but the effects are much less significant than those produced by opioids such as heroin. [3]
Buprenorphine may be better known for its use in treating opioid overuse disorder, but it is also effective at providing analgesia. In 2018, Aiyer et al. reviewed the literature on the efficacy of five different buprenorphine formulations in patients with chronic pain. [4] The researchers found that 14 of the 25 studies they reviewed showed a clinically significant benefit in the treatment of chronic pain by buprenorphine. Transdermal (application through the skin) buprenorphine was the most effective form of treatment, producing greater pain relief than intravenous, sublingual (applied under the tongue), and buccal (cheek) buprenorphine. According to Leffler et al., transdermal buprenorphine is ideal due to the drug’s low molecular weight, high lipophilicity, and high potency: these characteristics facilitate transdermal absorption. [5]
Buprenorphine is the first medication to treat opioid overuse disorder that can be prescribed in physicians’ offices, as per the Drug Addiction Treatment Act of 2000. [3] Physicians must receive approval from the Substance Abuse and Mental Health Services Administration before administering buprenorphine and must undergo training should they wish to simultaneously treat more than 30 patients with the opioid, but the fact that it can be administered in settings other than opioid treatment programs greatly increases access to treatment. [3]
Prior to the introduction of buprenorphine, methadone was commonly used to treat opioid overuse disorder. Unlike buprenorphine, methadone is a full agonist for the mu opioid receptor and causes higher levels of euphoria and analgesia, increasing the likelihood that patients treated with methadone will experience severe withdrawal when treatment stops. [6] Buprenorphine has a “ceiling effect,” which means that its effects plateau at higher concentrations.
Like virtually any opioid, buprenorphine can be abused, which may lead to the development of tolerance and withdrawal. The data on buprenorphine abuse, however, have been thus far encouraging. In 2019, nearly three-fourths of American adults using buprenorphine did not misuse the drug in the past 12 months. [7] Additionally, buprenorphine abuse decreased during 2015-2019, despite an increase in the number of people receiving buprenorphine treatment.
Patients presenting to the emergency room with untreated opioid overuse disorder often require high doses of buprenorphine. Herring et al. recently found that buprenorphine doses exceeding 12 mg very rarely caused respiratory depression, excessive sedation, or withdrawal. [8] Buprenorphine is also used in emergency medicine to treat opioid withdrawal. While rarely life-threatening, withdrawal can be extremely uncomfortable, and buprenorphine can provide relief by inducing mild and long-lasting euphoric effects. [9] Emergency departments, as well as general physicians and opioid treatment programs, have used buprenorphine extensively in the past two decades, to the great benefit of their patients.
References
- Jasinski, D. R., Pevnick, J. S. & Griffith, J. D. Human Pharmacology and Abuse Potential of the Analgesic Buprenorphine: A Potential Agent for Treating Narcotic Addiction. Arch. Gen. Psychiatry 35, 501–516 (1978).
- Welsh, C. & Valadez-Meltzer, A. Buprenorphine. Psychiatry Edgmont2, 29–39 (2005).
- Buprenorphine. https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine.
- Aiyer, R., Gulati, A., Gungor, S., Bhatia, A. & Mehta, N. Treatment of Chronic Pain With Various Buprenorphine Formulations: A Systematic Review of Clinical Studies. Anesth. Analg.127, 529–538 (2018).
- Leffler, A.et al.Local Anesthetic-like Inhibition of Voltage-gated Na+Channels by the Partial μ-opioid Receptor Agonist Buprenorphine. Anesthesiology 116, 1335–1346 (2012).
- Whelan, P. J. & Remski, K. Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds. J. Neurosci. Rural Pract.3, 45–50 (2012).
- Abuse, N. I. on D. Buprenorphine misuse decreased among U.S. adults with opioid use disorder from 2015-2019. National Institute on Drug Abuse. https://www.drugabuse.gov/news-events/news-releases/2021/10/buprenorphine-misuse-decreased-among-us-adults-with-opioid-use-disorder-from-2015-2019 (2021).
- Herring, A. A.et al.High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder. JAMA Netw. Open 4, e2117128 (2021).
- Herring, A. A., Perrone, J. & Nelson, L. S. Managing Opioid Withdrawal in the Emergency Department With Buprenorphine. Ann. Emerg. Med.73, 481–487 (2019).
