Hydromorphone

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

Overview

Hydromorphone belongs to Opioids.

Key safety note: Hydromorphone is a high-potency opioid with a narrow margin between an effective and a lethal dose: respiratory depression is the principal hazard, and the risk is especially high in opioid-naïve people and when it is injected.[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: strong relief of moderate-to-severe pain, with drowsiness, nausea, constipation and pinpoint pupils.
  • At higher (recreational) doses: intense opioid euphoria, warmth and relaxation, particularly rapid and pronounced when injected, alongside heavy sedation, itching and slowed breathing.
  • Effects begin within minutes when injected (about 15–30 minutes orally) and last roughly 4–6 hours. The fast, intense onset of injected hydromorphone drives both its abuse liability and its overdose risk.
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/solution) and parenteral (IV/IM/subcutaneous). Also rectal. Medical injectable use is common. Non-medical use is oral, insufflated or injected.. Hydromorphone is highly potent, active in single-milligram amounts and roughly 5× morphine, so small dosing errors matter and it is very dangerous to opioid-naïve users. The oral figures below are commonly cited recreational reference ranges, not a recommendation or a 'safe' dose. Injected, the same amount acts far faster and more intensely, sharply raising overdose risk. Never combine with alcohol or other depressants, and remember that tolerance to euphoria outpaces tolerance to respiratory depression.

Dose ranges

Threshold

0.5 mg

Light

1–2 mg

Common

2–4 mg

Strong

4–8 mg

Heavy

8 mg +

Duration

onset

Injected: within minutes, oral: 15–30 minutes

total

4–6 hours

after effects

Sedation and constipation. Tolerance and physical dependence with repeated use

Chemical & Physical Properties
FormulaC17H19NO3
Molar mass285.34 g/mol
StateSolid
Melting point266–267 °C
Boiling pointDecomposes at 305 °C
DensityNot reported
Vapor pressureNot reported
pKa8.2
LogP1.06
SolubilityHighly soluble, In water, 1,931 mg/L at 25 °C, Freely soluble in alcohol. Very soluble in chloroform
Refractive indexNot reported
Identifiers & Synonyms
CAS466-99-9
CAS (enantiomer)
PubChem CID5284570
InChIKeyWVLOADHCBXTIJK-YNHQPCIGSA-N
InChIInChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,16,19H,3,5-8H2,1H3/t10-,11+,16-,17-/m0/s1
SMILESCN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)O)O[C@H]3C(=O)CC4

Synonyms

  • Dihydromorphinone
  • Dilaudid
  • Palladone
  • Hydromorphone
Pharmacodynamics & Biochemistry

Hydromorphone (Dilaudid) is a potent semi-synthetic opioid derived from morphine, used for moderate-to-severe pain. It is roughly 5–7 times more potent than morphine and is also the active metabolite formed when hydrocodone is broken down by CYP2D6. It is available orally and, importantly, as an injectable widely used in hospital and palliative care. It is a strong, full agonist at the μ-opioid receptor (MOR), with weaker activity at the κ- and δ-opioid receptors. MOR activation in the CNS produces analgesia, sedation, euphoria and pupillary constriction and depresses the brainstem respiratory centres (the mechanism of fatal overdose), while peripheral MOR activation slows gut motility and causes constipation. Unlike many opioids, hydromorphone is not metabolised by the cytochrome-P450 system: it is cleared mainly by hepatic glucuronidation to hydromorphone-3-glucuronide (H3G). H3G has no opioid analgesic activity but is neuro-excitatory and accumulates in kidney impairment, where it can cause agitation, myoclonus and seizures. Its high potency means active doses are small, giving a narrow margin for error. Parenteral (injected) use produces a rapid, intense onset that carries high overdose and dependence risk.

Biological targets

  • MOR

Binding & functional measurements

TargetMeasurementSpecies
μ-opioid receptorKi 0.37 nMHuman
κ receptorpKi 8.6Human
δ receptorpKi 7.4Human
Pharmacokinetics
BioavailabilityOral ≈30–55%
TmaxNot reported
Half-life≈2–3 h
VdNot reported
Protein bindingNot reported
MetabolismHepatic glucuronidation to hydromorphone-3-glucuronide
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

Hydromorphone is a high-potency opioid with a narrow margin between an effective and a lethal dose: respiratory depression is the principal hazard, and the risk is especially high in opioid-naïve people and when it is injected. It is greatly amplified by alcohol, benzodiazepines and other CNS depressants. Because active doses are only a few milligrams, dosing errors and unfamiliarity with its potency are dangerous. It produces tolerance and physical dependence, is widely diverted and misused (including by injection, with associated infection risks), and in kidney impairment its metabolite H3G can accumulate and cause agitation, myoclonus and seizures. Naloxone reverses overdose.[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]
MAOIs, SSRIs, SNRIs Risk of serotonin syndrome and severe opioid potentiation.[4]
General anaesthetics and other sedatives Other sedatives, anaesthetics and muscle relaxants add sedation and respiratory depression.[3]

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]
Opioid-naive (no tolerance) high-potency and long-acting forms.[4][3]
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent MAOI use.[4][3]
Kidney or liver impairment caution in renal impairment (neuro-excitatory H3G accumulation causing agitation, myoclonus and seizures).[4]
Usage & Context
  • A hospital and palliative-care mainstay for severe acute and chronic pain (brand name Dilaudid), given orally or by injection, and useful when high opioid potency in a small volume is needed.
  • Widely diverted and misused for its strong euphoria, frequently by injection, which adds risks of infection and vein damage.
  • The active metabolite of hydrocodone, and one of the more sought-after prescription opioids on the illicit market.
Sources & Evidence

Further Information