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Hydromorphone

Hydromorphone molecule structureHydromorphone molecule structure
Hydromorphone
Dilaudid, Dihydromorphinone, Palladone, Exalgo, Jurnista
Psychoactive Class
Chemical Class
Morphinan

Hydromorphone is a semisynthetic opioid of the morphinan class, derived as a hydrogenated ketone of morphine. First introduced to the mass market in 1926 under the brand name Dilaudid,citation needed it is prescribed for the management of moderate to severe pain. Hydromorphone is notably more potent than morphine and carries a high potential for addiction and dependence. It has low oral bioavailability1 and is most commonly administered intravenously in clinical settings.

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~0.5 mg
Light0.5-2 mg
Moderate2-4 mg
Strong4-8 mg
Heavy8+ mg

Duration

Onset5-15 minutes
Come Up60-120 minutes
Peak15-20 minutes
Offset30-60 minutes
After Effects1-12 hours
Total4-6 hours

Subjective Effects

Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.

The hydromorphone experience is dominated by profound pain relief, mood lift, and a warm, sedated body state characteristic of potent opioids. As a semi-synthetic morphinan roughly 5-7 times more potent than morphine with a shorter duration, its effects arrive with considerable intensity but resolve comparatively quickly. Compared to morphine, it is associated with a lower incidence of itching and nausea, though both still occur. Sensory and cognitive alteration beyond sedation and mental clouding is minimal, making the experience primarily physical and emotional in character.

Physical

The body experience is one of deep relaxation, analgesia, and sedation, accompanied by a side effect load that can include itching, constipation, nausea, dry mouth, and sweating. Respiratory depression, low blood pressure, and slowed heart rate become dangerous at high doses, where drowsiness can progress to unresponsiveness.

Analgesia

Cardiovascular

Sedation

Uncomfortable

Dry mouthIncreased perspirationHeadaches

Cognitive

The headspace centers on euphoria and an elevated mood accompanied by mental clouding and slowed thought. Mood changes can also tilt toward dysphoria in some individuals, and prolonged high-dose use has been associated with agitation and cognitive dysfunction.

Emotional

Suppressions

Reagent Testing

Expected colorimetric results for common reagent tests. Colors show reaction change over 1–2 minutes.

Marquis(MQ)
white → yellow2 → red2 → purple2 → brown2
Mecke(ME)
white → yellow2 → orange2 → brown2
Froe(FR)
white → blue2 → purple2 → black2
Mandelin(MD)
No reaction
No reaction
Powered by PROtestkit.eu

Pharmacology

Pharmacodynamics

Hydromorphone is a semi-synthetic opioid that acts primarily as a μ-opioid receptor agonist, with approximately five to seven times the potency of morphine on a per milligram basis.citation needed It also binds to kappa-opioid receptors as an agonist and to delta-opioid receptors as a partial agonist, though with minor affinity at both. As a hydrogenated ketone of morphine, it possesses higher lipid solubility, enabling more rapid and complete penetration of the blood-brain barrier.

Pharmacokinetics

When taken orally, hydromorphone is absorbed primarily in the upper small intestine and undergoes extensive first-pass hepatic metabolism, resulting in an oral bioavailability of approximately 60%.citation needed The primary metabolic pathway is glucuronidation by UDP-glucuronosyltransferase-2B7 (UGT2B7), producing hydromorphone-3-glucuronide as the principal urinary metabolite. Unlike many other opioids in its class, hydromorphone is not primarily metabolized through CYP450 enzymes, though minor CYP3A4- and CYP2C9-mediated pathways produce norhydromorphone. Protein binding is low (8 to 19%) and the elimination half-life of the immediate-release formulation is approximately 2 to 3 hours. Parenteral administration yields a higher bioavailability of approximately 78%, with near-immediate peak plasma levels. In patients with renal impairment, the half-life may increase to as much as 40 hours.2

Interactions

Dangerous

Highest risk

These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.

AlcoholBenzodiazepinesCocaineDXMGHB/GBLKetamineMXEPregabalinTramadol

Unsafe

Avoid

There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

AmphetaminesMAOIsMephedroneNitrous oxidePCP
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Tolerance

Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.

Full Tolerance
Prolonged repeated hydromorphone use can produce tolerance to many effects, including therapeutic benefits. Once tolerance develops, comparable effects may require larger doses. The pace is effect-specific, and constipation-related tolerance tends to appear more slowly than tolerance to other opioid effects.
Cross Tolerance

All other opioids

Baseline Reset
After a period without opioid use, fatal overdose risk rises sharply because physical tolerance to respiratory and other depressant effects is reduced. For someone resuming use after extended abstinence, a much smaller fraction of the previous usual dose is safer. Environmental context may also influence tolerance, as studies suggest familiar drug-associated settings can provide some conditioned tolerance.

Harm Potential

Addiction & Dependence

Psychological

High

Hydromorphone is considered extremely addictive with high abuse potential, classified under Schedule II.citation needed Compulsive redosing is commonly reported, and the intense physical and cognitive euphoria contribute to its reinforcing properties.

Physical

High

Physical dependence develops with chronic use, and withdrawal symptoms may occur if the drug is suddenly stopped.1 Withdrawal effects include abdominal pain, anxiety, panic attacks, depression, muscle and joint pain, nausea, vomiting, sweating, and piloerection. Some users cannot tolerate the withdrawal symptoms, resulting in continued drug use.

Toxicity

Respiratory

Heavy dosages cause respiratory depression that can progress to fatal or dangerous levels of oxygen deprivation; this effect is dose-related and represents the primary cause of opioid overdose deaths.citation needed

Central Nervous System

Prolonged use, high dosage, or kidney dysfunction may cause neuroexcitatory symptoms including tremor, myoclonus, agitation, and cognitive dysfunction; this neurotoxicity is less pronounced than with some other opioid classes such as pethidine derivatives.citation needed

Endocrine

Heavy chronic use often causes temporary hypogonadism or hormone imbalance, consistent with other opioids in this class.citation needed

Gastrointestinal

Chronic use commonly causes constipation, with tolerance to this effect developing particularly slowly compared to other opioid effects; this is one of the few long-term complications from unadulterated hydromorphone aside from dependence.citation needed

Urinary

Urinary retention is recognized as a major hazard of hydromorphone use, occurring as an acute effect during intoxication.citation needed

Psychosis Risk

Hallucinations may occur as a side effect, listed among more common adverse effects particularly in ambulatory patients and those not experiencing severe pain.citation needed

Seizure Risk

Seizures are listed among serious potential side effects, though they are not commonly reported with hydromorphone alone and appear to be a relatively rare occurrence.citation needed

History & Culture

Discovery and Commercial Introduction

Hydromorphone is a semi-synthetic opioid derived from morphine through hydrogenation, producing a more potent hydrogenated ketone derivative. The compound has been available for clinical use since approximately 1920 and was patented in 1923.

Legality

International

Hydromorphone is listed in Schedule I of the 1961 Single Convention on Narcotic Drugs. It is not listed under the 1971 Convention on Psychotropic Substances. It is not listed under the 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.

By Country

Illegal5
United States flagUnited StatesIllegal
Canada flagCanadaIllegal
Netherlands flagNetherlandsIllegal
Singapore flagSingaporeIllegal
United Kingdom flagUnited KingdomIllegal
Controlled / restricted4
Colombia flagColombiaRestricted
Russia flagRussiaRestricted
South Korea flagSouth KoreaRestricted
Turkey flagTurkeyRestricted
Prescription17
Australia flagAustraliaPrescription only
Austria flagAustriaPrescription only
Brazil flagBrazilPrescription only
Chile flagChilePrescription only
Czech Republic flagCzech RepublicPrescription only
Denmark flagDenmarkPrescription only
Germany flagGermanyPrescription only
Ireland flagIrelandPrescription only
Italy flagItalyPrescription only
Japan flagJapanPrescription only
Mexico flagMexicoPrescription only
New Zealand flagNew ZealandPrescription only
Philippines flagPhilippinesPrescription only
Poland flagPolandPrescription only
Sweden flagSwedenPrescription only
Switzerland flagSwitzerlandPrescription only
Ukraine flagUkrainePrescription only

References

Source Pages

  1. DrugBank
  2. DrugBank: Clinical Trials - Hydromorphone
  3. DrugBank: Hydromorphone Salt
  4. Erowid
  5. Erowid: Hydromorphone Vault
  6. Isomer Design (TiHKAL/PiHKAL)
  7. PsychonautWiki
  8. TripSit Factsheets
  9. TripSit Wiki
  10. TripSit: Hydromorphone Factsheet
  11. Wikipedia

Citations

  1. DILAUDID (hydromorphone hydrochloride) Oral Solution and Tablets — Full Prescribing Information. FDA / DailyMed (n.d.). https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d6b40e39-a57e-402c-b4f6-7041e832f837&type=display12
  2. DILAUDID INJECTION (hydromorphone hydrochloride) — Full Prescribing Information. FDA / DailyMed (n.d.). https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=9eebd88a-5632-460f-b7b6-26c8a180540d&type=display12
  3. State of Ohio Department of Rehabilitation and Correction — Execution Policy 01-COM-11. (November 30, 2009). https://files.deathpenaltyinfo.org/legacy/OhioProtocol11.30.2009.pdf12
  4. Hydromorphone Drug Usage Statistics, United States, 2013 – 2022. ClinCalc (n.d.). https://clincalc.com/DrugStats/Drugs/Hydromorphone1
  5. Therapeutic Goods (Poisons Standard—February 2026) Instrument 2026, Schedule 8. legislation.gov.au (n.d.). https://www.legislation.gov.au/F2026L000601
  6. Suchtgiftverordnung, Anhang I. ris.bka.gv.at (n.d.). https://www.ris.bka.gv.at/Dokumente/Bundesnormen/NOR40267454/NOR40267454.html1
  7. Suchtmittelgesetz (SMG) — Austrian Narcotic Substances Act. Bundeskanzleramt Österreich / RIS (current). https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=100110401
  8. Suchtgiftverordnung (SGV) — Anlage 1, Abschnitt I.1.b. Bundeskanzleramt Österreich / RIS (current). https://www.ris.bka.gv.at/NormDokument.wxe?Abfrage=Bundesnormen&Gesetzesnummer=10011053&FassungVom=2021-12-29&Anlage=11
  9. ANVISA RDC No. 985 of 29 July 2025. gov.br (n.d.). https://www.gov.br/anvisa/pt-br/assuntos/medicamentos/controlados/copy4_of_ResoluodaDiretoriaColegiadaRDCn985de29072025.pdf1
  10. Schedule I, Controlled Drugs and Substances Act. laws-lois.justice.gc.ca (n.d.). https://laws-lois.justice.gc.ca/eng/acts/C-38.8/FullText.html1

Further Reading

  1. Davis et al. 2004 - Bioavailability of Intranasal Hydromorphone in Rhinitis Patients

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