Buprenorphine
Buprenorphine, is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue, in the cheek, by injection, as a skin patch, or as an implant.
In the United States, the combination formulation of buprenorphine/naloxone is usually prescribed to discourage misuse by injection. Maximum pain relief is generally within an hour with effects up to 24 hours. Buprenorphine affects different types of opioid receptors in different ways. Depending on the type of opioid receptor, it may be an agonist, partial agonist, or antagonist. Buprenorphine's activity as an agonist/antagonist is important in the treatment of opioid use disorder: it relieves withdrawal symptoms from other opioids and induces some euphoria, but also blocks the ability for many other opioids, including heroin, to cause an effect. Unlike full agonists like heroin or methadone, buprenorphine has a ceiling effect, such that taking more medicine past a certain point will not increase the effects of the drug.
Being a partial MOR agonist, buprenorphine offers flexibility to prescribers treating opioid use disorder as the dosage can be easily adjusted.
Side effects may include respiratory depression, sleepiness, adrenal insufficiency, QT prolongation, low blood pressure, allergic reactions, constipation, and opioid addiction. Among those with a history of seizures, a risk exists of further seizures. Opioid withdrawal following stopping buprenorphine is generally less severe than with other opioids. Whether use during pregnancy is safe is unclear, but use while breastfeeding is probably safe, since the dose the infant receives is 1–2% that of the maternal dose, on a weight basis.
Buprenorphine was patented in 1965, FDA approved for medical use as an analgesic in 1981, and FDA approved for treating opioid use disorder in 2002. It is on the World Health Organization's List of Essential Medicines. Despite originally being marketed as an analgesic it is far more commonly prescribed and used to treat opioid use disorders, such as addiction to heroin. In 2020, it was the 186th most commonly prescribed medication in the United States, with more than 2.8million prescriptions. Buprenorphine provides virtually no euphoria or "high" for opioid tolerant individuals, making it ideal as a medication for treating opioid use disorder. Buprenorphine has reduced euphoric potential compared with full opioid agonists thanks to its partial-agonist ceiling effect. In many patients with opioid use disorder it does not produce a noticeable ‘high’, which supports its use in maintenance therapy. However, in opioid-naïve individuals it may still produce euphoria, so the risk is not zero. In the United States, buprenorphine, alone and as a combination drug, is a schedule III controlled substance.
Medical uses
Opioid use disorder
Buprenorphine is used to treat people with opioid use disorder. In the U.S., the combination formulation of buprenorphine/naloxone is generally prescribed to deter injection, since naloxone, an opioid antagonist, is believed to cause acute withdrawal if the formulation is crushed and injected. Taken orally, the naloxone has virtually no effect, due to the drug's extremely high first-pass metabolism and low bioavailability.Before starting buprenorphine, individuals are generally advised to wait long enough after their last dose of opioid until they have some withdrawal symptoms to allow for the medication to bind the receptors, since if taken too soon, buprenorphine can displace other opioids bound to the receptors and precipitate an acute withdrawal. The dose of buprenorphine is then adjusted until symptoms improve, and individuals remain on a maintenance dose of 8–16 mg.
Because withdrawal is uncomfortable and a deterrent for many patients, users have called for different means of treatment initiation. The Bernese method, also known as micro dosing was described in 2016, where very small doses of buprenorphine are given while patients are still using street opioids, and without precipitating withdrawal, with medicine levels slowly titrated upward. This method has been used by some providers as of the 2020s. Many of the publications on the Bernese method are case reports, case series, or clinical guidance rather than large randomized controlled trials. For example, a CMAJ article noted that only two case reports and one small case series existed at the time of writing, and guidance documents typically state that micro-dosing is not yet a fully evidence-based alternative compared with standard induction. Furthermore, the phrase “without precipitating withdrawal” should be understood as "typically less likely to precipitate withdrawal" rather than guaranteed to avoid it. Clinicians adopting this method must do so with caution, informed consent, and close monitoring — particularly because many of the studies are small, heterogeneous, and variable in protocol.
Buprenorphine versus methadone
Both buprenorphine and methadone are medications used for detoxification and opioid replacement therapy, and appear to have similar effectiveness based on limited data. Both are safe for pregnant women with opioid use disorder, although preliminary evidence suggests that methadone is more likely to cause neonatal abstinence syndrome. In the US and European Union, only designated clinics can prescribe methadone for opioid use disorder, requiring patients to travel to the clinic daily. If patients are drug-free for a period they may be permitted to receive "take-home doses," reducing their visits to as little as once a week. Alternatively, up to a month's supply of buprenorphine has been able to be prescribed by clinicians in the US or Europe who have completed basic training and received a waiver/licence allowing the prescription of the medicine. In France, buprenorphine prescription for opioid use disorder has been permitted without any special training or restrictions since 1995, resulting in treatment of approximately ten times more patients per year with buprenorphine than with methadone in the following decade. In 2021, seeking to address record levels of opioid overdose, the United States also removed the requirement for a special waiver for prescribing physicians. Whether this change will be sufficient to impact prescription is unclear, since even before the change as many as half of physicians with a waiver permitting them to prescribe buprenorphine did not do so, and one-third of non-waivered physicians reported that nothing would induce them to prescribe buprenorphine for opioid use disorder.Buprenorphine versus naltrexone
Naltrexone is a full antagonist, meaning it fully blocks the opioid receptor from binding with other opioids and any feelings of euphoria if opioids are ingested. Buprenorphine has a higher affinity than most opioids and can bind to opioid receptors to have some effects - the mechanism that treats withdrawal symptoms. However, like naltrexone, buprenorphine can also block other opioids from binding to the receptors.