Buprenorphine

(2S)-2-[(5R,6R,7R,14S)-9α-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylbutan-2-ol

Overview

Buprenorphine belongs to Opioids.

Key safety note: Buprenorphine's partial μ-agonism gives a ceiling on respiratory depression, so taken alone it is much safer in overdose than full-agonist opioids and is a first-line medication for opioid use disorder.[5][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • As an opioid it produces analgesia, warmth, relaxation and mild euphoria, with the typical opioid signs: pupil constriction, drowsiness, itching, nausea and constipation.
  • Because μ-activation is only partial, the euphoria and respiratory depression plateau at higher doses (a 'ceiling'), so it feels less intensely rewarding than heroin or oxycodone: helpful for maintenance, and also why it can 'block' other opioids.
  • In a person already dependent on a full agonist, taking buprenorphine too early triggers precipitated withdrawal: a rapid, intense onset of sweating, cramps, anxiety and flu-like symptoms.
  • Effects are long-lasting (up to ~24 h from a dose), supporting once-daily or even alternate-day maintenance dosing.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Sublingual, Transdermal patch, Buccal, Injection (incl. long-acting depot). Prescription-only, dosed by clinicians. These are medical reference ranges, not recreational guidance. For opioid use disorder buprenorphine is started only once the patient is in mild–moderate withdrawal (or via a low-dose 'Bernese' micro-induction) to avoid precipitated withdrawal. It is far more potent than morphine by weight, so analgesic doses are in micrograms–milligrams.

Dose ranges

Opioid-use disorder (sublingual maintenance)

Typically 8–16 mg/day (induction from ~2–4 mg, up to ~24 mg)

Chronic pain (transdermal patch)

5–20 µg/hour

Acute pain (sublingual / injection)

≈0.2–0.4 mg

Duration

onset

≈30–60 min

total

Up to ~24 h (long-acting, monthly depot injections exist)

Chemical & Physical Properties
FormulaC29H41NO4
Molar mass467.64 g/mol
StateSolid
Melting pointNot reported
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKa8.31 (25 °C)
LogP4.98
Solubility1.68×10⁻² g/L
Refractive indexNot reported
Identifiers & Synonyms
CAS52485-79-7
CAS (enantiomer)
PubChem CID644073
InChIKeyRMRJXGBAOAMLHD-IHFGGWKQSA-N
InChIInChI=1S/C29H41NO4/c1-25(2,3)26(4,32)20-15-27-10-11-29(20,33-5)24-28(27)12-13-30(16-17-6-7-17)21(27)14-18-8-9-19(31)23(34-24)22(18)28/h8-9,17,20-21,24,31-32H,6-7,10-16H2,1-5H3/t20-,21-,24-,26+,27-,28+,29-/m1/s1
SMILESC[C@]([C@H]1C[C@@]23CC[C@@]1([C@H]4[C@@]25CCN([C@@H]3CC6=C5C(=C(C=C6)O)O4)CC7CC7)OC)(C(C)(C)C)O

Synonyms

  • Subutex
  • Suboxone (with naloxone)
  • Temgesic
  • Buprenorphine
  • Bupe
Pharmacodynamics & Biochemistry

Buprenorphine is a semi-synthetic opioid derived from thebaine with an unusually complex receptor profile. Its defining action is high-affinity partial agonism at the μ-opioid receptor (MOR): it binds very tightly and dissociates slowly but only partially activates the receptor. This partial character produces a ceiling effect on respiratory depression, beyond a certain dose breathing is suppressed no further, which makes buprenorphine markedly safer in overdose than full agonists such as heroin or methadone when taken alone. Its very high MOR affinity and slow off-rate mean buprenorphine out-competes and displaces other opioids from the receptor while only partly activating it. Given to someone dependent on a full agonist it can therefore precipitate acute withdrawal, and it blunts the effect of additional opioids taken on top: the basis of both its withdrawal-management use and the rule that it is started only once a patient is already in mild withdrawal. Beyond MOR it is an antagonist at the κ- and δ-opioid receptors and a partial agonist at the nociceptin/ORL-1 (NOP) receptor (relevant mainly at higher doses). The κ-antagonism may contribute anti-craving/antidepressant effects. Only the μ (partial agonist) and κ (antagonist) constants are quantified in the binding table (sub-nM to low-nM). The δ and NOP actions are described qualitatively. It is metabolised to norbuprenorphine, itself a MOR full agonist but poorly brain-penetrant (extruded by P-glycoprotein), so it adds little central effect. In opioid-use-disorder products buprenorphine is often combined with naloxone (Suboxone): naloxone is nearly inactive when the film is taken sublingually but precipitates withdrawal if the product is dissolved and injected: an abuse deterrent.

Biological targets

  • MOR
  • KOR
  • DOR

Binding & functional measurements

TargetMeasurementSpecies
κ-opioid receptorKi 0.11 ± 0.05 nMHuman
μ-opioid receptorKi 0.22 nMHuman
δ-opioid receptorKi 1.6 ± 0.07 nMGuinea pig
δ-opioid receptorKi 4.5 ± 0.40 nMHuman
δ-opioid receptorKi 0.42 ± 0.04 nMMouse
κ-opioid receptorKi 1.5 ± 0.25 nMGuinea pig
κ-opioid receptorEC50 0.04 ± 0.01 nM
Emax 10 ± 4%		Human
μ-opioid receptorKi 1.3 ± 0.15 nMGuinea pig
μ-opioid receptorEC50 0.08 ± 0.01 nM
Emax 38 ± 8%		Rat
μ-opioid receptorKi 0.08 ± 0.02 nMRat
Nociceptin/ORL1 receptorEC50 35 ± 8.0 nM
Emax 60 ± 10%		Human
Nociceptin/ORL1 receptorKi 285 ± 30 nMHuman
Pharmacokinetics
BioavailabilitySublingual ≈30%, oral very low
TmaxNot reported
Half-life≈24–42 h
VdNot reported
Protein binding≈96%
MetabolismHepatic CYP3A4 to norbuprenorphine. Glucuronidation
ExcretionMainly faecal
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Buprenorphine's partial μ-agonism gives a ceiling on respiratory depression, so taken alone it is much safer in overdose than full-agonist opioids and is a first-line medication for opioid use disorder. That safety does NOT hold in combination: fatal respiratory depression occurs with benzodiazepines, alcohol, gabapentinoids or other CNS depressants, and reversal can require high, repeated naloxone doses with prolonged monitoring because buprenorphine is so long-acting and tightly bound. Because of its high affinity it can precipitate withdrawal if started too soon after a full agonist. Other effects/risks: sedation, nausea, constipation, miosis, orthostatic hypotension, QT prolongation and dose-dependent adrenal insufficiency. Dependence develops and stopping causes a milder but protracted opioid withdrawal. Diversion and injection misuse occur, though the ceiling limits the achievable 'high'.[5][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Benzodiazepines, Alcohol, Gabapentinoids (gabapentin, pregabalin) Additive respiratory depression, the main cause of buprenorphine-related deaths.[5][4]
Opioids As a partial agonist, buprenorphine blocks and can displace full-agonist opioids (precipitating withdrawal) and blunts their analgesic or euphoric effect.[5]
CYP3A4 inhibitors (ritonavir, azole antifungals, macrolides, grapefruit) Ritonavir or ketoconazole raise buprenorphine exposure.[5]
CYP3A4 inducers (rifampicin, carbamazepine) Rifampicin, carbamazepine or some antiretrovirals lower buprenorphine exposure.[5]
QT-prolonging drugs (some antipsychotics, antibiotics, antiarrhythmics) Additive QT-prolongation risk at higher doses.[4]

Contraindications

Significant respiratory depression or acute severe asthma significant or acute.[5]
Kidney or liver impairment severe hepatic impairment, with liver-function monitoring.[5]
Head injury or raised intracranial pressure head injury or raised intracranial pressure.[5]
Combining with alcohol or other CNS depressants acute alcoholism, delirium tremens, or concurrent benzodiazepines or other CNS depressants without careful supervision.[5]
Known hypersensitivity to the drug known hypersensitivity to buprenorphine.[5]
Usage & Context
  • A first-line medication for opioid use disorder (maintenance and withdrawal management), as buprenorphine alone (Subutex) or with naloxone (Suboxone), including long-acting monthly depot injections (Sublocade/Brixadi).
  • An analgesic for moderate-to-severe and chronic pain via sublingual tablets (Temgesic), transdermal patches (Butrans) and buccal films (Belbuca).
  • Diverted and misused, but its μ-ceiling and (in Suboxone) the added naloxone limit the achievable 'high'. Often used non-medically to self-manage withdrawal.
Sources & Evidence

Further Information