WARNINGDANGER OF DEATH

High doses alone or ordinary doses in combination with other depressants can fatally stop breathing.

Dihydrocodeine

DHC, Drocode, Paracodeine, Parzone, DF-118

Psychoactive Class

Opioid Sedative Depressant

Chemical Class

Morphinan (substituted)

Dihydrocodeine is a semi-synthetic opioid analgesic¹ of the morphinan class. Developed in Germany in 1908 and first marketed in 1911, it was originally created during efforts to find more effective antitussive medications to curb the spread of airborne diseases like tuberculosis. Slightly more potent than codeine, it is prescribed for moderate to severe pain¹, dyspnea, and cough suppression. It is commonly sold in combination formulations containing paracetamol¹ or aspirin², which pose additional overdose risks¹² if not accounted for.

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~50 mg

Light50-100 mg

Moderate100-150 mg

Strong150-200 mg

Heavy200+ mg

Bioavailability

~20%

When using combination products that contain dihydrocodeine alongside paracetamol (acetaminophen) or other active ingredients, cold water extraction may be employed to separate the opioid component and reduce exposure to potentially hepatotoxic doses of the additional substances.

Duration

Onset30-45 minutes

After Effects1-8 hours

Total3-4 hours

Half-life

~4 hours

Subjective Effects

Effects vary widely by individual, dose, and context.

Physical

The physical effects of dihydrocodeine can be broken down into several components which progressively intensify proportional to dosage.

Constipation Cough suppression Difficulty urinating Pupil constriction

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.

Anxiety suppression Compulsive redosing

Forked from Subjective Effect Documentation

by Josie KinsSeptember 2015.

Reagent Testing

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

Marquis(MQ)

Mandelin(MD)

PROtestkit.eu

Pharmacology

Pharmacodynamics

Dihydrocodeine exerts its analgesic effects primarily through agonist activity at μ-opioid receptors, with lesser contributions from κ-opioid and δ-opioid receptors. Its affinity at the δ-opioid receptor is approximately 5 to 50 times weaker than at the μ-opioid receptor,³ while its κ-opioid affinity is comparable to that of codeine and morphine. The parent compound is itself pharmacologically active and is considered the primary contributor to analgesia.

Pharmacokinetics

Dihydrocodeine has low oral bioavailability (approximately 20%)⁴, attributable to poor gastrointestinal absorption and extensive first-pass metabolism by the liver and intestinal wall. It is metabolized hepatically via CYP2D6 (O-demethylation to dihydromorphine)⁵ and CYP3A4 (N-demethylation to nordihydrocodeine),⁵ with additional glucuronide conjugation producing dihydrocodeine-6-glucuronide (DHC-6-G),⁵ which itself contributes to the overall analgesic effect. Due to this multidirectional metabolic pathway, CYP2D6 metabolizer status does not appear to significantly influence analgesia, as pain threshold and pupillary responses do not differ between poor and extensive metabolizers. The mean elimination half-life is approximately 4 hours,⁴ with linear pharmacokinetics and plasma clearance of roughly 300 mL/min.

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.

Diphenhydramine

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

TripSit

Tolerance

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

Full Tolerance

Tolerance develops with repeated use, as is characteristic of opioids. Physical dependence has been demonstrated to develop with continued administration.⁶

Cross Tolerance

Opioids (dihydrocodeine has demonstrated cross-tolerance with other opioids and has historically been used to manage morphine withdrawal)

Harm Potential

Addiction & Dependence

Psychological

Moderate

Dihydrocodeine produces euphoria at higher-than-therapeutic doses and is commonly used recreationally. Psychological dependence develops with repeated use, as is characteristic of opioids.¹

Physical

High

Physical dependence develops with repeated use.¹ Dihydrocodeine has demonstrated cross-tolerance with other opioids and has historically been used to manage morphine withdrawal.

History & Culture

Discovery and Development

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,…

Legality

By Country

JapanLegal (regulated)Dihydrocodeine, its esters and salts are expressly listed as narcotics in Narcotics and Psychotropics Control Act Appendix 1 item 23.⁹ A qualifying preparation containing no more than 10/1000 (1%) dihydrocodeine or its salts and no other Appendix 1 substance or cannabis is excluded from the narcotic definition under item 78(i) and is a 家庭麻薬 (household narcotic) under Article 2(5).⁹ Qualifying OTC cough/cold medicines may therefore be non-prescription, but the active substance is not generally unscheduled; from 1 May 2026 non-external oral OTC products containing dihydrocodeine are also 指定濫用防止医薬品 subject to pharmacist/registered-seller information and purchase checks.¹³¹⁴

麻薬及び向精神薬取締法 (Narcotics and Psychotropics Control Act), Articles 2(1), 2(5), 3, 20-24, 26-28 and Appendix 1 items 23 and 78(i); 医薬品、医療機器等の品質、有効性及び安全性の確保等に関する法律 (PMD Act), Article 36-11; MHLW Notification 医薬発0213第1号 (13 February 2026) implementing the current 指定濫用防止医薬品 designation effective 1 May 2026; MHLW cough-medicine approval notice 薬食審査発0325第5号 (25 March 2015).^910111213

The legacy status Unscheduled (OTC available) is corrected because Japanese primary law expressly schedules dihydrocodeine, its esters and salts as narcotics in Appendix 1 item 23.⁹ The legacy OTC observation is only conditionally true: a preparation at or below 1% DHC (10/1000) with no other Appendix 1 substance or cannabis falls under the item 78(i) household-narcotic exception, and MHLW approval guidance permits DHC phosphate in qualifying cold medicines only within the 10/1000 product-mass limit.⁹¹⁰ Those product-level exceptions do not make dihydrocodeine generally unscheduled, and pure or higher-strength DHC remains subject to the narcotics licensing, possession, transfer and medical-channel controls. Since 1 May 2026, qualifying non-external OTC products containing DHC are also designated abuse-prevention medicines, requiring the strengthened pharmacist/registered-seller information and purchase checks.¹³¹⁴ The appropriate canonical disposition is legal_regulated: ordinary DHC is a controlled narcotic, while qualifying authorized OTC cough/cold preparations can be legally supplied without a prescription under formulation-specific medicine approval and the current abuse-prevention sales regime. No claim is made that every Japanese cough syrup, every DHC salt, or every product presentation is OTC; the exact product's concentration, ingredients, authorization and dosage form remain decisive.

References

Source Pages

Citations

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