Buprenorphine is a weak partial mu-opioid receptor agonist and a weak kappa-opioid receptor antagonist used for the treatment of severe pain. It is also commonly used as an alternative to methadone for the treatment of severe opioid addiction. Buprenorphine is commercially available as the brand name product Suboxone which is formulated in a 4:1 fixed-dose combination product along with naloxone, a non-selective competitive opioid receptor antagonist. Combination with naloxone is intended to reduce the abuse potential of Suboxone, as naloxone is poorly absorbed by the oral route (and has no effect when taken orally), but would reverse the opioid agonist effects of buprenorphine if injected intravenously. Buprenorphine has poor gastrointestinal absorption and is therefore formulated as a sublingual tablet. Buprenorphine has a number of unique pharmacokinetic and pharmacodynamic properties that make it a preferred agent for the treatment of conditions requiring high doses of strong opioids. For example, buprenorphine dissociates from opioid receptors very slowly, resulting in a long duration of action and relief from pain or withdrawal symptoms for upwards of 24-36 hours. Use of once-daily buprenorphine may benefit individuals who have developed tolerance to other potent opioids and who require larger and more frequent doses. Buprenorphine may also be a preferred agent over methadone (which is also commonly used to treat severe pain and opioid use disorder), as it has less effect on Qtc interval prolongation, fewer drug interactions, reduced risk of sexual side effects, and an improved safety profile with a lower risk of overdose and respiratory depression. Buprenorphine acts as a partial mu-opioid receptor agonist with a high affinity for the receptor, but lower intrinsic activity compared to other full mu-opioid agonists such as heroin, oxycodone, or methadone. This means that buprenorphine preferentially binds the opioid receptor and displaces lower affinity opioids without activating the receptor to a comparable degree. Clinically, this results in a slow onset of action and a clinical phenomenon known as the "ceiling effect" where once a certain dose is reached, buprenorphine's effects plateau. This effect can be beneficial, however, as dose-related side effects such as respiratory depression, sedation, and intoxication also plateau at around 32mg, resulting in a lower risk of overdose compared to methadone and other full agonist opioids. It also means that opioid-dependent patients do not experience sedation or euphoria at the same rate that they might experience with more potent opioids, improving quality of life for patients with severe pain and reducing the reinforcing effects of opioids which can lead to drug-seeking behaviours. Treatment of opioid addiction with buprenorphine, methadone, or slow-release oral morphine (SROM) is termed Opioid Agonist Treatment (OAT) or Opioid Substitution Therapy (OST). The intention of substitution of illicit opioids with the long-acting opioids used in OAT is to prevent withdrawal symptomns for 24-36 hours following dosing to ultimately reduce cravings and drug-seeking behaviours. Use of OAT is also intended to improved social stabilization including a reduction in crime rates, marginalization, incarceration, and use of illicit substances such as heroin or fentanyl. Illegally purchased opioids can often be injected and may be laced with other substances that increase the risk of harm or overdose. Provision of OAT is often combined with education about harm reduction including use of clean needles and injection supplies in an effort to reduce the risks associated with injection drug use which includes contraction of HIV and Hepatitis C and other complications including skin infections, abscesses, or endocarditis.