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Hydrocodone

Hydrocodone molecule structureHydrocodone molecule structure
Dihydrocodeinone
Vicodin, Norco, Lortab, Lorcet, Zohydro ER
Psychoactive Class
Chemical Class

Hydrocodone is a semi-synthetic opioid of the morphinan class, derived from codeine.citation needed First synthesized in Germany in 1920 by Carl Mannich and Helene Löwenheim,1 it is used primarily as an analgesic and cough suppressant.2 Hydrocodone is almost exclusively prescribed within the United States, where it is most commonly formulated in combination with acetaminophen or ibuprofen.citation needed The presence of acetaminophen in most preparations poses a significant risk of liver toxicity at high doses.

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~3 mg
Light3-10 mg
Moderate10-25 mg
Strong25-40 mg
Heavy40+ mg
Bioavailability
~25%

Duration

Onset10-30 minutes
After Effects1-12 hours
Total4-6 hours
Half-life
3.3-4.4 hours

Subjective Effects

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

The hydrocodone experience is dominated by classic opioid effects: pain relief, mood elevation, and a warm, relaxed euphoria accompanied by sedation. Sensory alteration is minimal; instead, the experience centers on physical comfort and an emotionally contented, mentally clouded state. At higher doses, sedation deepens into drowsiness and respiratory depression becomes a serious risk.

Physical

Pronounced analgesia and muscle relaxation form the core of the body experience, accompanied by sedation and itchiness. Uncomfortable effects such as nausea, vomiting, constipation, dizziness, light-headedness, and dry mouth are common.

Pupil constriction

Cardiovascular

Decreased blood pressure

Sedation

Muscle relaxation

Uncomfortable

Cognitive

The headspace is characterized by an improved and abnormally happy mood alongside mental clouding, with noticeable changes in focus and attention. Some users instead experience anxiety or a shift toward a low mood.

Emotional

Mood elevation is a defining feature, though anxiety and abnormal sadness are also reported.

Anxiety

Suppressions

Thought deceleration

Reagent Testing

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

Marquis(MQ)
white → purple2
Mecke(ME)
white → green2 → blue2
Froe(FR)
white → yellow1 → orange1
Mandelin(MD)
No reaction
No reaction
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Pharmacology

Pharmacodynamics

Hydrocodone is a highly selective full agonist of the μ-opioid receptor (MOR), which constitutes its primary pharmacological target.citation needed It also acts as an agonist at the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), though with substantially lower affinity; its affinity at DOR is approximately six-fold less than at MOR. Through these receptor interactions, hydrocodone inhibits pain signaling in both the spinal cord and brain. It is reported to be approximately one-tenth as potent as morphine at binding to opioid receptors.

Pharmacokinetics

Hydrocodone is available only as an oral medication, with an estimated oral bioavailability of approximately 25%.citation needed It is metabolized in the liver through multiple pathways: CYP2D6 catalyzes O-demethylation to hydromorphone (a more potent active metabolite with approximately 5-fold higher MOR binding affinity), while CYP3A4 catalyzes N-demethylation to norhydrocodone, the major metabolite. Despite its higher receptor affinity, hydromorphone is not generally present in sufficient quantities to contribute significantly to the effects of hydrocodone. Norhydrocodone is a MOR agonist with similar receptor potency to hydrocodone but appears to produce minimal analgesia due to poor penetration of the blood-brain barrier. Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome P450-catalyzed reactions.3 Hydrocodone and its metabolites also undergo 6-ketoreduction and glucuronide conjugation, with urinary excretion (primarily as conjugates) representing the main elimination route.citation needed The average plasma elimination half-life is reported as 3.8 hours (range 3.3–4.4 hours), though values of 7–9 hours have also been reported. Plasma protein binding ranges from 20 to 50%.

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
With prolonged and repeated use, tolerance can develop to many hydrocodone effects, including therapeutic ones. As tolerance increases, larger doses may be required to obtain comparable effects. The timeline varies by effect, with constipation-related tolerance emerging especially slowly compared with analgesic and euphoric effects.
Baseline Reset
1-2 weeks
Half Tolerance
3-7 days
Cross Tolerance

Opioids (all opioid receptor agonists)

Harm Potential

Addiction & Dependence

Psychological

High

Hydrocodone has significant abuse potential with abuse liability similar to morphine.citation needed Compulsive redosing is commonly reported, and chronic use is considered moderately to highly addictive with capability of causing psychological dependence.

Physical

High

Physical dependence develops with chronic use,citation needed and withdrawal symptoms occur upon sudden cessation.4 Newborns of mothers taking opioid medications regularly will be physically dependent at birth.citation needed Tolerance develops to many effects with prolonged use, requiring increasingly large doses.

Toxicity

Respiratory

Dose-related respiratory depression is the primary life-threatening toxicity;citation needed at high doses or overdose this can progress to shallow or stopped breathing, anoxia, and death, particularly when combined with other CNS depressants.

Hepatic

Hydrocodone alone does not cause significant hepatotoxicity, but pharmaceutical preparations commonly contain acetaminophen which can cause serious liver damage or acute liver failure at high doses or with repeated use, particularly when combined with alcohol.citation needed

Auditory

Progressive bilateral hearing loss unresponsive to steroid therapy has been described as an infrequent adverse reaction to hydrocodone/acetaminophen misuse.citation needed

Cardiovascular

Serious cardiovascular effects including bradycardia, hypotension, and QT prolongation may occur, primarily in overdose situations or at heavy doses.citation needed

Gastrointestinal

Constipation is a consistent effect that occurs even at therapeutic doses; tolerance to this effect develops particularly slowly compared to other opioid effects.

Seizure Risk

Seizures are listed as a serious side effect and symptom of overdose;citation needed they are not commonly reported at typical doses but may occur in overdose situations.

History & Culture

Synthesis and Early Development

Hydrocodone was first synthesized in Germany in 1920 by chemists Carl Mannich and Helene Löwenheim as a semi-synthetic derivative of codeine.citation needed The compound was patented in 1923 and first marketed by the pharmaceutical company Knoll under the trade name Dicodid beginning in February

Legality

International

Hydrocodone 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

Illegal11
United States flagUnited StatesIllegal
Austria flagAustriaIllegal
Canada flagCanadaIllegal
Finland flagFinlandIllegal
France flagFranceIllegal
Germany flagGermanyIllegal
Netherlands flagNetherlandsIllegal
New Zealand flagNew ZealandIllegal
Russia flagRussiaSchedule I
South Korea flagSouth KoreaIllegal
United Kingdom flagUnited KingdomIllegal
Controlled / restricted3
Indonesia flagIndonesiaRestricted
Sweden flagSwedenRestricted
Ukraine flagUkraineRestricted
Prescription13
Belgium flagBelgiumPrescription only
Brazil flagBrazilPrescription only
Chile flagChilePrescription only
China flagChinaPrescription only
Denmark flagDenmarkPrescription only
Ireland flagIrelandPrescription only
Japan flagJapanPrescription only
Luxembourg flagLuxembourgPrescription only
Mexico flagMexicoPrescription only
Philippines flagPhilippinesPrescription only
Spain flagSpainPrescription only
Switzerland flagSwitzerlandPrescription only
Turkey flagTurkeyPrescription only
Legal / decriminalized2
Australia flagAustraliaLegal (regulated)
Portugal flagPortugalDecriminalized

References

Source Pages

  1. DrugBank
  2. DrugUsersBible: Hydrocodone
  3. Erowid
  4. Erowid: Hydrocodone Dosage
  5. Erowid: Hydrocodone Effects
  6. Erowid: Hydrocodone Vault
  7. Isomer Design (TiHKAL/PiHKAL)
  8. PsychonautWiki
  9. PsychonautWiki: Dangerous Combinations
  10. TripSit Factsheets
  11. TripSit Wiki
  12. TripSit Wiki: Drug Combinations
  13. Wikipedia

Citations

  1. Hydrocodone - EBSCO Research Starters: Health and Medicine. (n.d.). https://www.ebsco.com/research-starters/health-and-medicine/hydrocodone1
  2. Hydrocodone - LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. (n.d.). https://www.ncbi.nlm.nih.gov/books/NBK548700/1
  3. Hutchinson MR, Menelaou A, Foster DJ, Coller JK, & Somogyi AA. (2004). CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. https://doi.org/10.1046/j.1365-2125.2003.02002.x1
  4. HYDROCODONE BITARTRATE AND ACETAMINOPHEN tablet (label). National Institutes of Health DailyMed (10 March 2021). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=73c1059b-0c7d-42ef-9827-f018858fc447123
  5. Therapeutic Goods (Poisons Standard—June 2026) Instrument 2026. legislation.gov.au (n.d.). https://www.legislation.gov.au/F2026L00633/latest/text1
  6. Suchtgiftverordnung, Anhang I. ris.bka.gv.at (n.d.). https://www.ris.bka.gv.at/Dokumente/Bundesnormen/NOR40267454/NOR40267454.html1
  7. Suchtgiftverordnung — Österreich (Ärztliche Verschreibungshöchstmengen § 15). Bundeskanzleramt Österreich / ris.bka.gv.at (n.d.). https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=100110531
  8. Arrêté royal du 6 septembre 2017 réglementant les substances stupéfiantes et psychotropes. ejustice.just.fgov.be (n.d.). https://www.ejustice.just.fgov.be/eli/arrete/2017/09/06/2017031231/justel1
  9. Arrêté royal du 6 septembre 2017 réglementant les substances stupéfiantes et psychotropes. afmps.be (n.d.). https://www.afmps.be/fr/humain/produits_particuliers/subst_specialement_reglementees/stupefiants_et_psychotropes/substances1
  10. Arrêté royal du 6 septembre 2017 réglementant les substances stupéfiantes et psychotropes. afmps.be (n.d.). https://www.afmps.be/sites/default/files/content/INSP/NARC/annex%20I_non%20official%20consolidated%20version.pdf1

Article Status

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Recent changes8 human edits · latest

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16 August 2026

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