Hydrocodone

4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one

Overview

Hydrocodone belongs to Opioids.

Key safety note: Hydrocodone can cause fatal respiratory depression, especially combined with alcohol, benzodiazepines, gabapentinoids or other CNS depressants: the main mechanism of opioid-overdose death.[4][3]
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.
  • At therapeutic doses: relief of moderate-to-severe pain and suppression of cough, commonly with drowsiness, nausea, constipation and pinpoint pupils.
  • At higher (recreational) doses: opioid euphoria, warmth and relaxation, with pronounced sedation, itching and slowed breathing.
  • Effects begin ~10–30 minutes after an oral dose and last around 4–8 hours. Combination products cap the safe dose because of their paracetamol/acetaminophen or ibuprofen content.
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.

Oral (tablets, capsules or solution). Medical use is oral, usually as a combination product.. The figures below are commonly cited recreational oral reference ranges, not a recommendation or a 'safe' dose. The critical harm-reduction point is that hydrocodone is almost always sold combined with paracetamol/acetaminophen (or ibuprofen): taking extra tablets to increase the opioid effect delivers a toxic dose of paracetamol that can cause fatal liver failure long before the opioid dose itself would. Tolerance, physical dependence and, with alcohol or other depressants, fatal respiratory depression are the other key risks, and effect varies with CYP2D6 genotype.

Dose ranges

Threshold

3 mg

Light

5–10 mg

Common

10–25 mg

Strong

25–40 mg

Heavy

40 mg +

Duration

onset

10–30 minutes (up to ~60)

total

4–8 hours

after effects

Sedation and constipation. Tolerance and physical dependence with repeated use

Chemical & Physical Properties
FormulaC18H21NO3
Molar mass299.36 g/mol
StateSolid
Melting point198 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKa8.23
LogP1.2
SolubilitySoluble in acetone, ethyl acetate, chloroform, Soluble in ethanol, 7.97×10⁻¹ g/L
Refractive indexNot reported
Identifiers & Synonyms
CAS125-29-1
CAS (enantiomer)
PubChem CID5284569
InChIKeyLLPOLZWFYMWNKH-CMKMFDCUSA-N
InChIInChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-12,17H,4-5,7-9H2,1-2H3/t11-,12+,17-,18-/m0/s1
SMILESCN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)OC)O[C@H]3C(=O)CC4

Synonyms

  • Dihydrocodeinone
  • Vicodin (with paracetamol)
  • Norco
  • Hydrocodone
Pharmacodynamics & Biochemistry

Hydrocodone is a semi-synthetic opioid derived from codeine/thebaine, used as an oral analgesic and cough suppressant. It was one of the most widely prescribed opioids in the United States and central to the prescription-opioid crisis. It is almost always sold as a combination product: most commonly with paracetamol/acetaminophen (Vicodin, Norco) or ibuprofen, and as an antitussive with homatropine. It is a moderately potent agonist at the μ-opioid receptor (MOR), roughly comparable to oral morphine. MOR activation in the CNS produces analgesia, sedation, euphoria and cough suppression and depresses the brainstem respiratory drive (the mechanism of overdose death), while peripheral MOR activation slows gut motility and causes constipation. Hydrocodone is metabolised by two hepatic pathways: CYP3A4 converts most of a dose to the inactive metabolite norhydrocodone, while CYP2D6 converts a smaller fraction to hydromorphone, a far more potent MOR agonist. Because hydrocodone itself is active, this conversion matters less than codeine's conversion to morphine, but CYP2D6 ultra-rapid metabolizers can still form more hydromorphone (greater effect and risk), while CYP2D6 inhibitors or poor-metabolizer status reduce it. In vitro it binds MOR with roughly nanomolar affinity and the κ-opioid receptor far more weakly, so its effects are essentially μ-mediated.

Biological targets

  • MOR

Binding & functional measurements

TargetMeasurementSpecies
μ-opioid receptorKi 42 nMHuman
κ-opioid receptorKi 260 ± 9.7 nMHuman
Pharmacokinetics
BioavailabilityOral ≈25–70%
TmaxNot reported
Half-life≈3.8 h
VdNot reported
Protein bindingNot reported
MetabolismHepatic CYP2D6 to hydromorphone and CYP3A4 to norhydrocodone
ExcretionRenal
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

Hydrocodone can cause fatal respiratory depression, especially combined with alcohol, benzodiazepines, gabapentinoids or other CNS depressants: the main mechanism of opioid-overdose death. It produces tolerance and physical dependence and was a major driver of the US prescription-opioid epidemic. A distinct hazard comes from the combination products: taking extra tablets to chase the opioid effect delivers toxic doses of the co-formulated paracetamol/acetaminophen (or ibuprofen), which can cause fatal liver failure. Effect and risk also vary with CYP2D6 genotype.[4][3]

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

Alcohol, Benzodiazepines, Opioids, Gabapentinoids (gabapentin, pregabalin) Additive respiratory depression, the main mechanism of opioid-overdose death.[4][3]
CYP3A4 inhibitors (ritonavir, azole antifungals, macrolides, grapefruit) Ritonavir, ketoconazole or clarithromycin raise hydrocodone exposure.[3]
CYP3A4 inducers (rifampicin, carbamazepine) Rifampicin or carbamazepine lower hydrocodone exposure.[3]
Strong CYP2D6 inhibitors (e.g. paroxetine, fluoxetine) Fluoxetine, paroxetine, bupropion or quinidine reduce conversion to hydromorphone, while ultra-rapid metabolisers form more.[4][3]
MAOIs, SSRIs, SNRIs Risk of serotonin syndrome and severe opioid potentiation.[4][3]
Co-formulated paracetamol/acetaminophen or ibuprofen (combination analgesics) Co-formulated paracetamol/acetaminophen or ibuprofen has its own dose ceiling, and exceeding it to chase the opioid risks hepatotoxicity or GI/renal harm.[4]

Contraindications

Significant respiratory depression or acute severe asthma or acute/severe bronchial asthma in an unmonitored setting.[4][3]
Paralytic ileus or gastrointestinal obstruction[3]
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent MAOI use.[3]
Children (age-restricted; respiratory-depression risk)[4]
Kidney or liver impairment hepatic impairment, given the combination-product paracetamol/acetaminophen.[4]
Usage & Context
  • Widely prescribed oral opioid for moderate-to-severe pain and, in some formulations, as a cough suppressant: almost always dispensed as a combination product (with paracetamol/acetaminophen or ibuprofen).
  • Extensively misused: one of the most diverted and misused prescription opioids, especially in North America, and a common entry point to opioid dependence.
  • A central drug in the US prescription-opioid crisis before the later shift toward illicit fentanyl.
Sources & Evidence

Further Information