Overview

• Buprenorphine is a safe, effective medication for opioid use disorder that increases participation in treatment.
  ¹

  Nat’l Acad. of Sciences, Engineering, and Medicine (“NASEM”), Consensus Study Report: Medications for Opioid Use Disorder Save Lives, Nat’l Acad. Press, at 18 (2019) (“Large systematic reviews and randomized controlled trials have demonstrated that treatment with either methadone or buprenorphine is associated with an array of positive outcomes, including fewer fatal overdose deaths, better treatment retention rates, lower rates of other opioid use, decreased mortality, less injection drug use, reduced transmission of HIV infections, improved social functioning, decreased engagement in criminal activity, and lower rates of neonatal abstinence syndrome.”).
• Buprenorphine and medications like it cut the risk of overdose death in half.
  ²

  Nat’l Acad. of Sciences, Engineering, and Medicine (“NASEM”), Consensus Study Report: Medications for Opioid Use Disorder Save Lives, Nat’l Acad. Press, at 6 (2019) (“In fact, people with OUD are up to 50 percent less likely to die when they are being treated long term with methadone or buprenorphine.”); Marc Auriacombe et al., French field experience with buprenorphine, 13 Am. J. Addiction S17-28 (2004), https://pubmed.ncbi.nlm.nih.gov/15204673/ (noting 79% decrease in opiate overdose deaths after all registered medical doctors in France were allowed to prescribe buprenorphine without any special education or licensing).
• Buprenorphine has been FDA-approved for pain management since 1981 and for opioid use disorder since 2002.
  ³

  Congressional Research Svc. (“CRS”), Buprenorphine and the Opioid Crisis: A Primer for Congress, at 3 (2018), https://fas.org/sgp/crs/misc/R45279.pdf (noting “[b]uprenorphine was first approved by the Food and Drug Administration (FDA) as a pain reliever in 1981” and citing the FDA Approval letter in 2002).
• It stabilizes the brain chemistry of a person with opioid use disorder by partially binding to opioid receptors.
  ⁴

  The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes (“Buprenorphine is a partial agonist, meaning it does not completely bind to the mu-opioid receptor.”).
• In doing so, it prevents painful withdrawal symptoms, including vomiting, diarrhea, tremors, pain, seizures, and anxiety, stems cravings, and decreases illicit drug use by blocking the euphoric effect of opioids.
  ⁵

  U.S. Surgeon General, Facing Addiction in America: The U.S. Surgeon General’s Report on Alcohol, Drugs, and Health, at 73, 2-19, 2-20 (2016), https://www.ncbi.nlm.nih.gov/books/NBK424857/ (noting withdrawal symptoms for prescription opioids include “[r]estlessness, anxiety, muscle and bone pain, insomnia, diarrhea, vomiting, cold flashes with goose bumps, and muscle tremors…[o]pioid addiction typically involves a pattern of…withdrawal signs that include profound negative emotions and physical symptoms, such as bodily discomfort, pain, sweating, and intestinal distress and, in the most severe cases, seizures.”); The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (2020), Table: Overview of OUD Medication Effectiveness.
• It is safer and easier to manage than titrating insulin for diabetes.
  ⁶

  Sarah E. Wakeman, MD and Michael L. Bennett, MD, Primary Care and the Opioid-Overdose Crisis – Buprenorphine Myths and Realities, 379 New England J. of Med. 1-4 (2018), https://www.nejm.org/doi/full/10.1056/NEJMp1802741(“The first myth is that buprenorphine is more dangerous than other interventions physicians master during training. In fact, PCPs regularly prescribe more complicated and risky treatments. Titrating insulin, starting anticoagulants, and prescribing full-agonist opioids for pain are often more challenging and potentially harmful than prescribing buprenorphine.”).
  Because it has a ceiling effect, even at high doses, overdose is very rare.
  ⁷

  The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (2020) (“Buprenorphine is a partial agonist, meaning it does not completely bind to the mu-opioid receptor. As a result, buprenorphine has a ceiling effect—its effects will plateau, and will not increase even with repeated dosing. Because of this partial effect at the opioid receptor, even at high doses the risk for overdose from buprenorphine is very low.”); CDC, Vital Signs: Prescription Painkiller Overdoses, at 3 (2012), https://www.cdc.gov/vitalsigns/pdf/2012-07-vitalsigns.pdf (table entitled “Death rate from overdoses caused by a single prescription painkiller” showing buprenorphine has the lowest rate of overdose compared to other prescription pain medicines like oxycodone, fentanyl, and morphine).

Scheduling and Formulations

Buprenorphine is one of three FDA-approved medications for opioid use disorder, which are proven to be the most effective treatments for the condition.

⁸

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes (“The most effective treatments for opioid use disorder (OUD) are three medications approved by the Food and Drug Administration (FDA): methadone, buprenorphine, and naltrexone.”).

It is listed as a Schedule III medication.

⁹

DEA, Controlled Substances By CSA Schedule, at 12 (2020) https://www.deadiversion.usdoj.gov/schedules/orangebook/e_cs_sched.pdf.

Buprenorphine comes in four formulations: tablets and film (which are placed under the tongue or inside the cheek) and implants and injections (which are inserted beneath the skin). Buprenorphine is available in generic form.

How Buprenorphine Works

Buprenorphine evens out brain chemistry changes caused by opioid use much like insulin evens out blood chemistry for a person with diabetes. The medication is known as a “partial agonist” because it partially binds to opioid receptors in the brain.

¹⁰

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes (“Buprenorphine is a partial agonist, meaning it does not completely bind to the mu-opioid receptor.”).

Through this mechanism, buprenorphine significantly reduces painful withdrawal symptoms, cravings, and illicit drug use.

¹¹

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes, Table: Overview of OUD Medication Effectiveness (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes.

Because it is a partial agonist, there is a limit on its euphoric effects.

¹²

U.S. Surgeon General, Facing Addiction in America: The U.S. Surgeon General’s Report on Alcohol, Drugs, and Health, at 4-23 (2016), https://www.ncbi.nlm.nih.gov/books/NBK424857/ (“Buprenorphine is a partial opioid agonist, meaning that it binds to and activates opioid receptors but with less intensity than full agonists. As a result, there is an upper limit to how much euphoria, pain relief, or respiratory depression buprenorphine can produce.”).

People who take buprenorphine “feel normal, not high.”

¹³

Substance Abuse and Mental Health Svcs. Admin. (“SAMHSA”), The Facts About Buprenorphine for Treatment of Opioid Addiction, at 3 (2014), https://store.samhsa.gov/system/files/sma14-4442.pdf (“The person who takes buprenorphine feels normal, not high.”).

Just like chemotherapy will not work for every person with cancer, buprenorphine won’t work for every person with opioid use disorder. But the science is clear that it can save lives and it can help people achieve long-term recovery.

Side Effects and Risks

Buprenorphine has very few side effects. The most common include constipation, vomiting, headaches, sweating, insomnia, and blurred vision.

¹⁴

SAMHSA, Treatment Improvement Protocol (TIP) 63: Medications for Opioid Use Disorder, at 2-20 (2020), https://store.samhsa.gov/product/TIP-63-Medications-for-Opioid-Use-Disorder-Full-Document/PEP20-02-01-006.

The risks associated with buprenorphine are low. Even at high doses, overdose is very rare when taking buprenorphine.

¹⁵

SAMHSA, Treatment Improvement Protocol (TIP) 63: Medications for Opioid Use Disorder, at 2-20 (2020), https://store.samhsa.gov/product/TIP-63-Medications-for-Opioid-Use-Disorder-Full-Document/PEP20-02-01-006 (noting risk of medication-induced respiratory depression is “very rare”).

According to the National Academy of Sciences, Engineering and Medicine, “[t]he risk of opioid overdose death declines immediately when patients with [opioid use disorder] initiate buprenorphine.”

¹⁸

Nat’l Acad. of Sciences, Engineering, and Medicine (“NASEM”), Consensus Study Report: Medications for Opioid Use Disorder Save Lives, Nat’l Acad. Press, at 36-7 (2019) https://www.nap.edu/catalog/25310/medications-for-opioid-use-disorder-save-lives

Other Opioid Use Disorder Treatments

Other medications for opioid use disorder include methadone and naltrexone (commonly known as “Vivitrol”), but they are limited in their ability to reach or stabilize significant numbers of people.

Behavioral health treatments maybe used in conjunction with medications for opioid use disorder, but the medications are effective on their own.

Detox and abstinence-only treatment are not recommended by public health officials due to the significantly higher risk of overdose death.

Methadone

Methadone is a full agonist, which completely binds to the opioid receptors in the brain. Like buprenorphine, it decreases painful withdrawal symptoms and the risk of overdose.

¹⁹

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes (“Methadone is a full agonist, meaning that it fully occupies the mu-opioid receptor. In doing so, methadone lessens the painful symptoms of opiate withdrawal and blocks the euphoric effects of other opioid drugs… Methadone and buprenorphine have also been shown to reduce the risk of death from opioid overdose.”).

While all doctors can prescribe methadone for pain, the use of methadone to treat opioid use disorder is available only through highly regulated clinics.

²⁰

U.S. Surgeon General, Facing Addiction in America: The U.S. Surgeon General’s Report on Alcohol, Drugs, and Health, at 4-22 (2016), https://www.ncbi.nlm.nih.gov/books/NBK424857/ (“Any licensed physician can prescribe methadone for the treatment of pain, but methadone may only be dispensed for treatment of an opioid use disorder within licensed methadone treatment programs.”).

Many patients consequently cannot access and stay on methadone due to the regulatory restrictions of these clinics, which mandate daily visits at locations that can be hours from a person’s home.

²¹

Rebecca Haffajee et al., Policy Pathways to Address Provider Workforce Barriers to Buprenorphine Treatment, 54 Am. J. Prev. Med. S230-42 (2019), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330240/ (“Barriers to methadone treatment provision and access are numerous, however, and include: a shortage of providers, waitlists for treatment, stigma and patient costs of treatment (daily time, transportation), drug-drug interaction risks, and stringent regulatory requirements.”).

Naltrexone

Naltrexone (Vivitrol) is an opioid antagonist that blocks the opioid receptors in the brain and the effect of any opioids taken.

²²

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes (“Naltrexone is an opioid antagonist, meaning that it blocks, rather than activates, the mu-opioid receptor, preventing a biological response to block the effects of opioids if they are used.”).

It is not as effective as buprenorphine and methadone because it is harder to initiate patients on naltrexone,

²³

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes) (“[N]altrexone requires that patients detoxify before starting treatment, meaning they must abstain from opioids for seven to 14 days to rid their body of the drug. This can make it more difficult for patients to initiate treatment, and leads to lower rates of treatment initiation compared with other medications. Neither methadone nor buprenorphine requires detoxification, thus they are more accessible to people who are unable to stop using opioids long enough to begin naltrexone treatment. In fact, some physicians cite patient lack of interest in naltrexone, and specifically detoxification from opioids, as a barrier to prescribing the drug.”).

has a higher likelihood of a return to use,

²⁴

Nat’l Acad. of Sciences, Engineering, and Medicine (“NASEM”), Consensus Study Report: Medications for Opioid Use Disorder Save Lives, Nat’l Acad. Press, at 41 (2019) https://www.nap.edu/catalog/25310/medications-for-opioid-use-disorder-save-lives (“In real-world community treatment settings, only 10.5 percent of patients were adherent to extended-release naltrexone at 6 months. The only controlled trial from the United States comparing extended-release naltrexone to buprenorphine found that ‘in the intention-to-treat population of all patients who were randomly assigned, XR-NTX [extended-release naltrexone] had lower relapse-free survival than BUP-NX [buprenorphine-naloxone]’.”).

and is not proven to reduce the risk of overdose.

²⁵

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes) (“[R]ecent evidence indicates that unlike methadone and buprenorphine, naltrexone may not reduce the risk of overdose.”).

Buprenorphine and methadone are on the World Health Organization’s list of essential medicines for opioid use disorder, while naltrexone is not.

²⁶

World Health Organization, Model List of Essential Medicines (2019), https://www.who.int/publications/i/item/WHOMVPEMPIAU2019.06.

Behavioral Health Treatments

Behavioral therapy, including counseling and contingency management, may be pursued in conjunction with medications for opioid use disorder. Medications, however, are effective on their own.

²⁷

The Pew Charitable Trusts, Medications for Opioid Use Disorder Improve Patient Outcomes (Dec. 17, 2020) https://www.pewtrusts.org/en/research-and-analysis/fact-sheets/2020/12/medications-for-opioid-use-disorder-improve-patient-outcomes (“While the American Society of Addiction Medicine recommends [behavioral health treatments] in conjunction with all drug therapies for OUD, medications are effective in treating OUD even in the absence of counseling.”)..

Every person has the right to choose their pathway to recovery, and they should make that decision with full information. People with opioid use disorder who pursue only behavioral health treatments have twice the death rate of people who take opioid agonist medications like buprenorphine.

²⁸

Matthias Pierce et al. Impact of treatment for opioid dependence on fatal related drug poisoning: a national cohort study in England, 111 Addiction, at 301 (2016), https://doi: 10.1111/add.13193 (“The [drug-related poisoning] risk associated with psychological support was twice that for [opioid-agonist pharmacotherapy] and was comparable to the risk when not in treatment. This is consistent with an earlier observation that ‘drugfree’ treatment is associated with a higher all-cause mortality risk.”).

Detox and Abstinence-Only Treatment

Detox and abstinence-only treatment are not recommended by public health officials because they increase the risk of overdose death. As few as 1 in 10 people who undergo detox (medically supervised withdrawal) will remain in recovery.

²⁹

Nat’l Acad. of Sciences, Engineering, and Medicine (“NASEM”), Consensus Study Report: Medications for Opioid Use Disorder Save Lives, Nat’l Acad. Press, at 98 (2019) https://www.nap.edu/catalog/25310/medications-for-opioid-use-disorder-save-lives (“Return-to-use rates following medically supervised withdrawal (also known as ‘detox’) have been reported to be as high as 65 to 91 percent; this approach also carries a high risk of overdose due to a reduced tolerance for opioids if patients return to use.”).

Those who do undergo medically supervised withdrawal experience a higher risk of overdose because they have a reduced tolerance for opioids.

³⁰

Nat’l Acad. of Sciences, Engineering, and Medicine (“NASEM”), Consensus Study Report: Medications for Opioid Use Disorder Save Lives, Nat’l Acad. Press, at 98 (2019) https://www.nap.edu/catalog/25310/medications-for-opioid-use-disorder-save-lives (“Return-to-use rates following medically supervised withdrawal (also known as ‘detox’) have been reported to be as high as 65 to 91 percent; this approach also carries a high risk of overdose due to a reduced tolerance for opioids if patients return to use.”).

Despite these risks, the vast majority of treatment facilities across the country still offer only abstinent-based treatment.

³¹

Nat’l Acad. of Sciences, Engineering, and Medicine (“NASEM”), Consensus Study Report: Medications for Opioid Use Disorder Save Lives, Nat’l Acad. Press, at 91-92 (2019) https://www.nap.edu/catalog/25310/medications-for-opioid-use-disorder-save-lives (“Withholding or failing to have available all classes of U.S. Food and Drug Administration–approved medication for the treatment of opioid use disorder in any care or criminal justice setting is denying appropriate medical treatment… Although overall roughly 36 percent of SUD treatment facilities offer medication to patients…only about 6 percent provide patients with a choice of all three U.S. Food and Drug Administration (FDA)-approved medications.”).

Many treatment providers believe that taking medication like buprenorphine and methadone is “substituting one substance for another.” As the U.S. Surgeon General notes, “[s]uch views are not scientifically supported; the research clearly demonstrates that MAT leads to better treatment outcomes compared to behavioral treatments alone. Moreover, withholding medications greatly increases the risk of relapse to illicit opioid use and overdose death.”

³²

U.S. Surgeon General, Facing Addiction in America: The U.S. Surgeon General’s Report on Alcohol, Drugs, and Health, at 4-22 (2016), https://www.ncbi.nlm.nih.gov/books/NBK424857/.

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