Hydrocodone Stats & Data
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DrugBankDescription
Hydrocodone is a synthetic opioid derivative of codeine. It is commonly used in combination with acetaminophen to control moderate to severe pain. Historically, hydrocodone has been used as a cough suppressant although this has largely been replaced by dextromethorphan in current cough and cold formulations. Hydrocodone's more potent metabolite, hydromorphone has also found wide use as an analgesic and is frequently used in cases of severe pain. The FDA first approved Hydrocodone for use as part of the cough suppressant syrup Hycodan in March of 1943.
Mechanism of Action
Hydrocodone binds to the mu opioid receptor (MOR) with the highest affinity followed by the delta opioid receptors (DOR). Hydrocodone's agonist effect at the MOR is considered to contribute the most to its analgesic effects. Both MOR and DOR are Gi/o coupled and and produces its signal through activation of inward rectifier potassium (GIRK) channels, inhibition of voltage gated calcium channel opening, and decreased adenylyl cyclase activity. In the dorsal horn of the spinal cord, activation of pre-synaptic MOR on primary afferents the inhibition of calcium channel opening and increased activity of GIRK channels hyperpolarizes the neuron and prevents release of neurotransmitters. Post-synaptic MOR can also prevent activation of neurons by glutamate through the aforementioned mechanisms. Hydrocodone can also produce several actions in the brain similarly to other opioids. Activation of MOR in the periaquaductal gray (PAG) inhibits the GABAergic tone on medulo-spinal neurons. This allows these neurons, which project to the dorsal horn of the spinal cord, to suppress pain signalling in secondary afferents by activating inhibitory interneurons. MOR can also inhibit GABAergic neurons in the ventral tegmental area, removing the inhibitory tone on dopaminergic neurons in the nucleus accumbens and contributing to the activation of the brain's reward and addiction pathway.
Pharmacodynamics
Hydrocodone inhibits pain signaling in both the spinal cord and brain . Its actions in the brain also produce euphoria, respiratory depression, and sedation.
Metabolism
Hydrocodone undergoes oxidative O-demethylation to form hydromorphone, a more potent active metabolite. Though hydromorphone is active it is not present in sufficient quantities to contribute significantly to hydrocodone's therapeutic effects. Both hydrocodone and hydromorphone form 6-α- and 6-β-hydroxy metabolites through 6-ketoreduction. The hydroxy metabolites and hydromorphone can form glucuronide conjugates. Hydrocodone also undergoes oxidative N-demthylation to norhydrocodone. O-demethylation is primarily catalyzed by CYP2D6 while N-demethylation is primarily CYP3A4.
Absorption
The absolute bioavailability of hydrocodone has not been characterized due to lack of an IV formulation. The liquid formulations of hydrocodone have a Tmax of 0.83-1.33 h. The extended release tablet formulations have a Tmax of 14-16 h. The Cmax remains dose proportional over the range of 2.5-10 mg in liquid formulations and 20-120 mg in extended release formulations. Administration with food increases Cmax by about 27% while Tmax and AUC remain the same. Administration with 40% ethanol has been observed to increase Cmax 2-fold with an approximate 20% increase in AUC with no change in Tmax. 20% alcohol produces no significant effect.
Toxicity
Overdosage with hydrocodone presents as opioid intoxication including respiratory depression, somnolence, coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. In case of oversdosage the foremost priority is the maintenance of a patent and protected airway with the provision of assisted ventilation if necessary. Supportive measures such as IV fluids, supplemental oxygen, and vasopressors may be used to manage circulatory shock. Advanced life support may be necessary in the case of cardiac arrest or arrhythmias. Opioid antagonists such as naloxone may be used to reverse the respiratory and circulatory effects of hydrocodone. Emergency monitoring is still required after naloxone administration as the opioid effects may reappear. Additionally, if used in an opioid tolerant patient, naloxone may produce opioid withdrawal symptoms.
Indication
Hydrocodone is indicated for the management of acute pain, sometimes in combination with acetaminophen or ibuprofen, as well as the symptomatic treatment of the common cold and allergic rhinitis in combination with decongestants, antihistamines, and expectorants.
Half-life
The half-life of elimination reported for hydrocodone is 7-9 h.
Protein Binding
Hydrocodone is 36% bound to plasma proteins.
Elimination
Most hydrocodone appears to be eliminated via a non-renal route as renal clearance is substantially lower than total apparent clearance. Hepatic metabolism may account for a portion of this, however the slight increase in serum concentration and AUC seen in hepatic impairment indicates a different primary route of elimination.
Volume of Distribution
The apparent volume of distribution ranges widely in published literature. The official FDA labeling reports a value of 402 L. Pharmacokinetic studies report values from 210-714 L with higher values associated with higher doses or single dose studies and lower values associated with lower doses and multiple dose studies. Hydrocodone has been observed in human breast milk at levels equivalent to 1.6% of the maternal dosage. Only 12 of the 30 women studied had detectable concentrations of hydromorphone at mean levels of 0.3 mcg/kg/day.
Clearance
Official FDA labeling reports an apparent clearance of 83 L/h. Pharmacokinetic studies report values ranging from 24.5-58.8 L/h largely dependent on CYP2D6 metabolizer status.
Receptor Profile
Receptor Actions
Receptor Binding
History & Culture
1920–1943
Hydrocodone was first synthesized in Germany in 1920 by chemists Carl Mannich and Helene Löwenheim as a semi-synthetic derivative of codeine. The compound was patented in 1923 and first marketed by the pharmaceutical company Knoll under the trade name Dicodid beginning in February 1924. This naming convention followed Knoll's established pattern for their opioid product line, which included Dilaudid (hydromorphone, 1926), Dinarkon (oxycodone, 1917), Dihydrin (dihydrocodeine, 1911), and Dimorphan (dihydromorphine). The United States Food and Drug Administration approved hydrocodone on March 23, 1943, initially for use as the cough suppressant syrup Hycodan. Health Canada subsequently approved the drug under the same brand name for the Canadian market.
Hydrocodone became predominantly prescribed within the United States, with the International Narcotics Control Board reporting that 99% of the worldwide supply was consumed in the United States as of 2007, a figure that remained consistent through 2010. The drug reached its peak prevalence in 2010 when it became the most prescribed medication in the country, with 131.2 million prescriptions written for hydrocodone-paracetamol combinations that year. The most widely recognized hydrocodone formulation has been Vicodin, produced by Knoll Laboratories. The trade name reportedly derives from the Roman numeral VI, referencing hydrocodone's approximately six-fold potency relative to codeine—where 5 mg of hydrocodone produces effects comparable to 30 mg of codeine.
2006–2014
Beginning in late 2006, the FDA initiated recalls of numerous hydrocodone-containing cough formulations following reports of deaths in infants and children under six years of age. By August 2010, enforcement actions had resulted in the removal of 88% of these hydrocodone-containing medications from the market. Concurrently, the FDA began considering restrictions on hydrocodone and oxycodone fixed-combination products due to paracetamol-related liver toxicity concerns. In late 2012, Vicodin's manufacturer reformulated their hydrocodone tablets to reduce the acetaminophen content to 300 mg per tablet, addressing the risk of liver damage associated with higher paracetamol doses. A long-acting formulation was approved for medical use in the United States in 2013, with Zohydro ER becoming the only hydrocodone brand available without acetaminophen, offered in doses up to 50 mg. The US government imposed more restrictive prescribing requirements in 2014, reclassifying all hydrocodone products from Schedule III to Schedule II effective October 6, 2014. This change followed a 2013 FDA advisory panel recommendation responding to DEA concerns about abuse potential. Prior to rescheduling, products containing 15 mg or less of hydrocodone per dosage unit had been classified as Schedule III, encompassing nearly all prescribed hydrocodone formulations including Vicodin. By 2011, hydrocodone products were involved in approximately 100,000 abuse-related emergency department visits in the United States, more than double the number recorded in 2004.
Effect Profile
Curated + 307 ReportsStrong euphoria, itching/nausea, pain relief, and sedation
Tolerance & Pharmacokinetics
drugs.wikiCross-Tolerances
Demographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
Erowid + BluelightEffects aggregated from 307 experience reports (266 Erowid + 41 Bluelight)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 43
Adverse Effects 33
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Light (n=25) | Common (n=94) | Strong (n=21) | Heavy (n=20) |
|---|---|---|---|---|
| Euphoria | 44.0% | 42.6% | 52.4% | 65.0% |
| Nausea | 20.0% | 30.9% | 38.1% | 50.0% |
| Stimulation | 16.0% | 27.7% | 42.9% | 35.0% |
| Anxiety Suppression | 36.0% | 24.5% | 28.6% | 40.0% |
| Sedation | 24.0% | 39.4% | 38.1% | 25.0% |
| Music Enhancement | 16.0% | 34.0% | 28.6% | 20.0% |
| Focus Enhancement | 28.0% | 14.9% | 0% | 25.0% |
| Confusion | 28.0% | 14.9% | 0% | 15.0% |
| Empathy | 24.0% | 26.6% | 19.0% | 20.0% |
| Body High | 16.0% | 20.2% | 0% | 15.0% |
| Dissociation | 20.0% | 10.6% | 14.3% | 10.0% |
| Visual Distortions | 12.0% | 8.5% | 9.5% | 20.0% |
| Tactile Enhancement | 12.0% | 16.0% | 9.5% | 20.0% |
| Headache | 0% | 17.0% | 0% | 10.0% |
| Introspection | 16.0% | 3.2% | 0% | 0% |
Subjective Effect Ontology
Experience ReportsStructured effect tags extracted from 307 Erowid & Bluelight experience reports using a controlled vocabulary of 220+ canonical effects across 15 domains.
Emotional
Motor
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 266 experience reports.
| Effect | Light (n=25) | Common (n=94) | Strong (n=21) | Heavy (n=20) | |
|---|---|---|---|---|---|
| euphoria | ↑ | ||||
| nausea | ↑ | ||||
| stimulation | ↑ | ||||
| anxiety suppression | → | ||||
| sedation | → | ||||
| music enhancement | ↑ | ||||
| focus enhancement | — | → | |||
| confusion | — | ↓ | |||
| empathy | ↓ | ||||
| body high | — | → | |||
| dissociation | ↓ | ||||
| visual distortions | ↑ | ||||
| tactile enhancement | ↑ | ||||
| headache | — | — | ↓ | ||
| introspection | — | — | ↓ | ||
| auditory effects | — | ↑ | |||
| motor impairment | — | — | ↑ | ||
| color enhancement | ↑ | ||||
| closed-eye visuals | — | — | → | ||
| hospital | — | — | ↑ |
Showing top 20 of 33 effects
Risk Escalation
Sentiment AnalysisAverage frequency of positive vs adverse effects across dose tiers
View effect breakdown
Adverse Effects
| Effect | Light (n=25) | Common (n=94) | Strong (n=21) | Heavy (n=20) | Change |
|---|---|---|---|---|---|
| Nausea | +150% | ||||
| Anxiety Suppression | +11% | ||||
| Confusion | — | -46% | |||
| Headache | — | — | -41% | ||
| Motor Impairment | — | — | +24% | ||
| Sweating | — | +88% | |||
| Memory Suppression | — | — | -33% | ||
| Muscle Tension | — | — | — | 0% | |
| Increased Heart Rate | — | — | — | 0% | |
| Pupil Dilation | — | — | — | 0% | |
| Jaw Clenching | — | — | — | 0% | |
| Seizure | — | — | — | 0% | |
| Appetite Suppression | — | — | — | 0% |
Positive Effects
| Effect | Light (n=25) | Common (n=94) | Strong (n=21) | Heavy (n=20) | Change |
|---|---|---|---|---|---|
| Euphoria | +47% | ||||
| Stimulation | +118% | ||||
| Music Enhancement | +25% | ||||
| Focus Enhancement | — | -10% | |||
| Empathy | -16% | ||||
| Body High | — | -6% | |||
| Tactile Enhancement | +66% | ||||
| Introspection | — | — | -80% | ||
| Color Enhancement | +25% | ||||
| Creativity Enhancement | — | — | -73% | ||
| Pain Relief | — | — | — | 0% |
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 465 individual dose entries
Oral (n=358)
Insufflated (n=17)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Oral
Insufflated
Redose Patterns
Redosing behavior across 231 reports
Opioid Equivalence (MME)
NIH HEAL 2024 & CDC 2022Hydrocodone 10 mg oral ≈ 10 mg Morphine oral
Legal Status
| Country | Status | Notes |
|---|---|---|
| Australia | Schedule 8 (S8) | Classified as a controlled drug requiring a prescription. Schedule 8 substances are considered drugs of addiction with recognized therapeutic use. |
| Austria | Controlled (Suchtmittelgesetz) | Regulated under the Austrian Suchtmittelgesetz (SMG) in a similar manner to Germany. Since 2002, hydrocodone products from Germany and elsewhere in the European Union have been available under Article 76 of the Schengen Treaty. |
| Belgium | Not available | Hydrocodone is no longer available for medical use in Belgium. |
| Canada | Schedule I (CDSA) | Controlled under the Controlled Drugs and Substances Act. Available only by prescription, both as a single-ingredient formulation and in proprietary combinations with NSAIDs or paracetamol. |
| France | Prohibited narcotic | Classified as a prohibited narcotic substance. Hydrocodone is no longer available for medical use in France. |
| Germany | Anlage III BtMG | Listed under Anlage III of the Betäubungsmittelgesetz (Narcotics Act) as a Suchtgift. Can only be prescribed using a special narcotic prescription form (Betäubungsmittelrezept). |
| Luxembourg | Prescription only | Available by prescription under the trade name Biocodone. Prescriptions are more commonly issued for use as a cough suppressant (antitussive) rather than for pain relief. |
| Mexico | Prescription only | Requires a valid prescription for legal acquisition. Not available over-the-counter despite contrary rumors. |
| Netherlands | List I (Opiumwet) | Classified as a List I substance under the Opium Law (Opiumwet). Hydrocodone is not available for medical use and possession without a prescription or license is illegal. |
| Russia | Schedule I | Classified as a Schedule I controlled substance under Russian drug control legislation. |
| Sweden | Not available | Hydrocodone is no longer available for medical use in Sweden. The last remaining formulation was deregistered in 1967. |
| Switzerland | Controlled (Verzeichnis A) | Listed as a controlled substance under Verzeichnis A of Swiss narcotics legislation. Medicinal use is permitted with appropriate authorization. |
| United Kingdom | Class A (Schedule 2) | Listed as a Class A drug under the Misuse of Drugs Act 1971 and Schedule 2 under the Misuse of Drugs Regulations. Hydrocodone is not available for medical use in the UK; dihydrocodeine formulations are commonly used as alternatives. |
| United States | Schedule II | As of October 6, 2014, all hydrocodone products are designated Schedule II controlled substances under the Controlled Substances Act. Prior to this date, combination products containing 15 mg or less per dosage unit were classified as Schedule III. Prescriptions cannot be refilled and require a new written prescription for each fill. |
Harm Reduction
drugs.wikiMost hydrocodone IR products are co‑formulated with acetaminophen (APAP); keep total APAP from all sources ≤ 4,000 mg in 24 h (lower in hepatic disease or chronic alcohol use) to reduce risk of severe liver injury. Dose‑dumping and fatal overdose can occur if extended‑release hydrocodone (e.g., Hysingla ER, Zohydro ER) is crushed, chewed, or dissolved—swallow whole only. Respiratory depression risk is highest during initiation, after dose increases, or when combined with other CNS depressants; avoid mixing with alcohol, benzodiazepines, Z‑drugs, barbiturates, or GHB/GBL. Hydrocodone is metabolized by CYP2D6 to hydromorphone (active) and by CYP3A4 to norhydrocodone (inactive); strong CYP3A4 inhibitors (including ritonavir in Paxlovid) can dangerously raise hydrocodone levels, while inducers can reduce analgesia and precipitate withdrawal; CYP2D6 inhibitors can blunt hydromorphone formation and alter response. Combination with serotonergic drugs (e.g., SSRIs/SNRIs/TCAs, some muscle relaxants, tramadol) has produced serotonin‑toxicity cases; monitor or avoid high‑risk combinations. Counterfeit opioid tablets adulterated with potent synthetic opioids (e.g., nitazenes/fentanils) have been reported in Europe; avoid non‑pharmacy pills and consider carrying naloxone; do not use alone. Opioid‑naïve individuals and those with reduced tolerance after a break are at particularly high overdose risk—start low, go slow, and space doses ≥ 4–6 h. Common adverse effects include sedation, miosis, pruritus, nausea, and constipation; maintain bowel regimen (hydration, fiber, stimulant + stool softener as needed). Avoid driving or hazardous tasks while sedated; impairment can persist beyond subjective effects. Seek urgent care for severe drowsiness, slowed or irregular breathing, cyanosis, or unresponsiveness; naloxone is the first‑line reversal for life‑threatening respiratory depression.