Dihydrocodeine Stats & Data
COc1ccc2CC3N(C)CCC45C3CCC(O)C5Oc1c24RBOXVHNMENFORY-DNJOTXNNSA-NPharmacology
DrugBankDescription
Dihydrocodeine is an opioid analgesic used as an alternative or adjunct to codeine to treat moderate to severe pain, severe dyspnea, and cough. It is semi-synthetic, and was developed in Germany in 1908 during an international search to find a more effective antitussive agent to help reduce the spread of airborne infectious diseases such as tuburculosis. It was marketed in 1911.
Mechanism of Action
Dihydrocodeine is metabolized to dihydromorphine -- a highly active metabolite with a high affinity for mu opioid receptors.
Pharmacodynamics
Possible opioid related side effects include, but are not limited to, drowsiness, nausea, headache, dry mouth, constipation, difficulty passing urine, and mild euphoria.
Metabolism
Metabolized in the liver by CYP 2D6 into an active metabolite, dihydromorphine, and by CYP 3A4 into secondary primary metabolite, nordihydrocodeine. A third primary metabolite is dihydrocodeine-6-glucuronide. The time for mean peak concentration in acid metabolites is 1.76h and 1.98h for a 30 and 60mg dose, respectively. The concentrations achieved were 563 ug/1 and 1476 ug/1, respectively.
Absorption
Bioavailability is low (approximately 20%) if administered orally. This may be due to poor gastrointestinal absorption. It is also likely due to pre-systemic metabolism by the liver and intestinal wall. The AUCs after oral and intravenous administration are similar (3203ug/l/h and 3401ug/l/h, respectively). Time to peak values are 1.6 and 1.8hours for a 30mg and 60mg dose, respectively. The concentrations achieved were 71.8 ug/1 and 146 ug/1, respectively.
Indication
Dihydrocodeine is used for the treatment of moderate to severe pain, including post-operative and dental pain . It can also be used to treat chronic pain , breathlessness and coughing. In heroin addicts, dihydrocodeine has been used as a substitute drug, in doses up to 2500mg/day to treat addiction. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014322/
Elimination
Renal elimination and urinary excretion.
Volume of Distribution
The disposition of dihydrocodeine is described as a two compartment model.
Clearance
Plasma clearance is approximately 300ml/min. The pharmacokinetics of dihydrocodeine and active metabolite dihydromorphine have been reported to be linear. The decline in plasma dihydrocodeine concentrations after intravenous administration has been described as bi-exponential, with a sleep decline in the initial 2h following administration, followed by a mono-exponential decline thereafter. Clearance was not dose dependent.
Receptor Profile
Receptor Actions
Receptor Binding
History & Culture
1908–1911
Dihydrocodeine is a semi-synthetic opioid that was developed in Germany in 1908 during a period of intensive research into more effective antitussive agents. This effort was motivated by the urgent need to limit the transmission of airborne infectious diseases, particularly tuberculosis, pertussis, and pneumonia, which were major public health concerns during the late 19th and early 20th centuries. The compound entered the market in 1911 and was later granted formal regulatory approval for medical use in 1948.
In clinical settings, dihydrocodeine has been employed as a substitution therapy for individuals with heroin dependence, with doses reaching up to 2500mg daily. Japan represents a notable exception in global drug policy, where dihydrocodeine remains available without prescription. It appears in over-the-counter cough preparations such as New Bron Solution-ACE, serving as an alternative to dextromethorphan. Japanese manufacturers typically formulate these products with caffeine to counteract sedative effects and reduce the potential for recreational misuse.
Subjective Effect Notes
physical: The physical effects of dihydrocodeine can be broken down into several components which progressively intensify proportional to dosage.
cognitive: The cognitive effects of dihydrocodeine can be broken down into several components which progressively intensify proportional to dosage. The general head space of dihydrocodeine is described by many as one of intense euphoria, relaxation, anxiety suppression and pain relief.
Effect Profile
Curated + 15 ReportsStrong euphoria with moderate itching/nausea, mild pain relief and sedation
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Tolerance develops rapidly with near‑daily use and decays over days to weeks after cessation. After a break, prior doses can overshoot—restart with markedly lower doses to reduce overdose risk. Cross‑tolerance exists across mu‑agonist opioids but is incomplete.
Cross-Tolerances
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 15 experience reports (15 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 5
Adverse Effects 1
Real-World Dose Distribution
62K DosesFrom 41 individual dose entries
Oral (n=40)
Form / Preparation
Most common forms and preparations reported
Redose Patterns
Redosing behavior across 11 reports
Opioid Equivalence (MME)
NIH HEAL 2024 & CDC 2022Dihydrocodeine 40 mg oral ≈ 10 mg Morphine oral
Legal Status
| Country | Status | Notes |
|---|---|---|
| Japan | Unscheduled (OTC available) | Available without prescription in over-the-counter cough preparations such as cough syrups. Represents a notable exception in global drug policy where dihydrocodeine remains accessible for consumer purchase without a medical prescription. |
Harm Reduction
drugs.wikiLow oral bioavailability (~21%) and a delayed peak (~1.6–1.8 h) increase the risk of impatient redosing; wait at least 2 hours to assess effects before taking more. The parent drug and its metabolites (notably dihydromorphine and DHC‑6‑glucuronide) mediate effects; CYP2D6 O‑demethylation is polymorphic and inhibited by some medications, so potency can vary widely between people and with drug–drug interactions. Most non‑medical harms come from polydrug use: combining opioids with benzodiazepines and/or alcohol markedly elevates overdose risk via additive respiratory depression. Many DHC products are combined with acetaminophen; do not exceed 4,000 mg acetaminophen in 24 h from all sources to avoid potentially fatal hepatotoxicity (reduce to ≤3,000 mg/day if risk factors exist). Avoid crushing/chewing controlled‑release tablets; as with other extended‑release opioids, tampering can cause dose dumping and life‑threatening overdose. Carry naloxone if using opioids; it reverses respiratory depression within minutes but may wear off in 20–40 minutes—always call emergency services. Nasal use of tablets exposes sinuses to insoluble binders and offers little benefit; prefer oral use of known single‑ingredient products. Tolerance builds quickly; after even short breaks, tolerance drops and the prior ‘usual’ dose may cause overdose—start low again. Opioids predictably cause constipation; start prevention early (fluids, fiber, movement; consider stimulant or osmotic laxatives if needed). Avoid driving or operating machinery while sedated; opioid effects can outlast the perceived ‘high,’ and some services recommend at least 24 hours before driving after recreational use.
References
Cited References
- Ammon et al. 1999 - Pharmacokinetics of DHC and DHM (DOI)
- Kirkwood et al. 1997 - Cytochrome P450 metabolism (DOI)
- Leppert 2010 - DHC as opioid analgesic (DOI)
- PsychonautWiki: Dihydrocodeine
- Rowell et al. 1983 - Pharmacokinetics IV and oral (DOI)
- Schmidt et al. 2002 - Opioid receptor affinities (DOI)
- Schmidt et al. 2003 - Role of active metabolites (DOI)
- TripSit: Dihydrocodeine Factsheet
- TripSit: Drug Combinations Chart
Drugs.wiki References
- Erowid Dihydrocodeine Vault (brands; APAP warning)
- Rowell et al., 1983 (oral BA ~21%, Tmax 1.6–1.8 h, t1/2) via DrugBank
- DrugBank: Dihydrocodeine (PK/enzymes; CYP2D6→dihydromorphine; CYP3A4→nordihydrocodeine)
- Characterization of CYPs in DHC metabolism (CYP2D6 O‑demethylation; CYP3A N‑demethylation) via DrugBank
- Receptor affinities of DHC metabolites; CYP2D6 phenotypes and variability via DrugBank
- SAMHSA/CBHSQ: Benzo + opioid/alcohol increases serious ED outcomes
- EUDA: Non‑medical benzodiazepine co‑use with opioids—overdose risk
- EUDA mini‑guide on polydrug use (opioids+benzos/alcohol; stimulants masking sedation)
- WHO/NCBI Bookshelf: Paracetamol dosing—max 4 g/day adults (reduce with risk factors)
- StatPearls (Hydrocodone/APAP): ER opioids—do not crush/chew; acetaminophen hepatotoxicity >4 g/day
- Naloxone—mechanism and duration (20–40 min), emergency care still required
- WHO/NCBI: Naloxone (no contraindications in suspected opioid toxicity; dosing cautions)
- Hi‑Ground: Opioids harm‑reduction (carry naloxone; snorting risks; counterfeit pills; driving caution)
- NCBI: OUD text—tolerance loss after abstinence increases overdose risk
- StatPearls: Opioid‑induced constipation—prevention and management
- Bluelight community reports: DHC BA and nasal ROA limitations (anecdotal)