Not yet reviewed — this article is pending editorial review by Lyrea.

WARNINGDANGER OF DEATH

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

O-Desmethyltramadol

Psychoactive Class

Opioid Depressant

Chemical Class

Phenylpropylamine

O-Desmethyltramadol is an opioid analgesic and the primary active metabolite of tramadol.¹ Since the 2010s, it has been available through the research chemical market as a standalone substance. It acts as a full agonist at the mu-opioid receptor² with additional affinity for delta and kappa receptors, producing more typical opioid-like effects than its parent compound. It also exhibits some influence on monoaminergic systems.²

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~10 mg

Light10-25 mg

Moderate25-50 mg

Strong50-100 mg

Heavy100+ mg

Duration

Onset30-60 minutes

After Effects1-8 hours

Total3-6 hours

Half-life

6.7-9 hours

Subjective Effects

Effects vary widely by individual, dose, and context.

Physical

The cognitive effects of O-Desmethyltramadol can be broken down into several components which progressively intensify proportional to dosage. The general head space of codeine is described by many as one of intense euphoria, relaxation, anxiety suppression and pain relief.

Constipation Cough suppression Difficulty urinating Nausea Sedation Pupil constriction

Cognitive

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

Anxiety suppression Compulsive redosing

Forked from Subjective Effect Documentation

by Josie KinsJuly 2015.

Pharmacology

Pharmacodynamics

O-Desmethyltramadol acts primarily as a μ-opioid receptor full agonist with substantial affinity (Ki of 19 nM for the racemic mixture), with the (+)-enantiomer exhibiting G-protein biased signaling² and considerably higher affinity (Ki of 3 nM). The substance also binds δ- and κ-opioid receptors, though with comparatively much lower affinity. O-DSMT acts as a competitive antagonist at serotonin 5-HT2C receptors at pharmacologically relevant concentrations.³ The (−)-enantiomer retains some norepinephrine reuptake inhibitor activity, though the potency gap between opioid and monoaminergic activity is substantial enough that this property is functionally minimal for the racemic mixture. Additional in vitro findings include inhibition of muscarinic M1 receptor activity and inhibition of Substance P.

Pharmacokinetics

O-Desmethyltramadol is pharmacologically active without requiring metabolic activation.² It is metabolized in the liver into the active metabolite N,O-didesmethyltramadol via CYP3A4 and CYP2B6. The organic cation transporter OCT1, expressed on hepatocyte membranes, mediates uptake of the substance into the liver; individuals with reduced OCT1 activity metabolize it more slowly. Reported elimination half-life values range from approximately 6.7 to 9 hours, with oral peak plasma concentrations reached around 3 hours.⁴

Interactions

Interactions not written up yet

An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.

Check

TripSit

Tolerance

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

Full Tolerance

Tolerance develops very rapidly with daily use, particularly when dosing multiple times per day. The most desirable effects may become difficult to obtain after just a few days of heavy use. This rapid tolerance development is identified as a major driver of dependence, as users continue attempting to achieve progressively harder to obtain positive effects.

Cross Tolerance

Opioids

Harm Potential

Addiction & Dependence

Psychological

Moderate

Moderate psychological addiction potential with risk of compulsive redosing. Tolerance develops rapidly with daily use, particularly with multiple daily doses, leading users to chase progressively harder to obtain positive effects, which is identified as a major driver of dependence.

Physical

Moderate

Physical dependence develops within a week of heavy daily use. Withdrawal effects match those of other opioids, including sweating, vomiting, flu-like symptoms, runny nose, chills, lethargy, and headache, though reportedly milder in intensity compared to stronger opioids like diamorphine. At least 3-5 days of moderate to strong flu-like illness should be expected upon cessation.

Toxicity

Hepatic

Long-term chronic use may be associated with elevated hepatic damage markers including α-GST, ALT, AST, ALP, and GGT, particularly in individuals who are CYP2D6 extensive or ultrarapid metabolizers; however, decades of tramadol use in humans has not produced clear evidence of severe hepatotoxicity when used moderately.

Respiratory

Respiratory depression is the primary life-threatening effect in overdose⁵; a sensation of labored breathing may occur at strong doses and represents a danger sign in overdose situations.

Seizure Risk

Seizure risk may be lower than with tramadol, though this has not been definitively confirmed. The (S) enantiomer demonstrated seizure-inducing capability in rats at doses that also caused significant respiratory depression. Studies of tramadol intoxication found O-DSMT plasma levels correlated with seizure onset, though co-ingestion of benzodiazepines or other opioids appeared to reduce seizure risk.

History & Culture

Emergence as a Research Chemical

O-Desmethyltramadol has a limited independent history because it has never been marketed by pharmaceutical companies as a standalone medication, instead being encountered primarily as the principal active metabolite of the analgesic tramadol. Comparatively little research has been conducted on the…

Legality

By Country

United StatesIllegalTemporary Schedule I

21 CFR § 1308.11(h)(88); DEA Temporary Scheduling Order, 91 FR 52013 (August 12, 2026)^33343536

O-Desmethyltramadol (O-DSMT; desmetramadol) is expressly listed in federal Schedule I at 21 CFR § 1308.11(h)(88), DEA code 9667. DEA's temporary scheduling order took effect on August 12, 2026 and runs through August 12, 2028 unless extended or made permanent. Unauthorized handling is subject to Schedule I controls. The former suggestion that O-DSMT might be covered as an analogue merely because it is structurally related to tramadol is not a valid federal analogue analysis: tramadol is Schedule IV, whereas 21 U.S.C. § 802(32)(A) requires a Schedule I or II comparator. No alternate qualifying comparator was established here, and during direct scheduling O-DSMT is excluded from the analogue definition because it is itself a controlled substance.

United KingdomIllegalClass B / Schedule 1

Misuse of Drugs Act 1971, Schedule 2, Part II; Misuse of Drugs Regulations 2001, Schedule 1; Misuse of Drugs Regulations (Northern Ireland) 2002, Schedule 1^{242526232728293031}

O-Desmethyltramadol is expressly listed under its chemical name, 2-((dimethylamino)methyl)-1-(3-hydroxyphenyl)cyclohexanol, as a Class B drug in Part II of Schedule 2 to the Misuse of Drugs Act 1971. It is not Class A and its control is not inferred from its relationship to tramadol. The 2013 Order exact-listed O-DSMT separately from the structural phenylcyclohexylamine provision, and the current Class A 2-benzyl-benzimidazole generic does not provide O-DSMT's classification. O-DSMT is in Schedule 1 of the Misuse of Drugs Regulations in Great Britain and, since 24 February 2014, in the parallel Schedule 1 in Northern Ireland. As a controlled drug, it is an exempted substance under the Psychoactive Substances Act 2016; unauthorized possession, production and supply are controlled under the Misuse of Drugs Act 1971, subject to statutory regulations and defences.

CanadaIllegalSchedule I / NCR narcotic

Controlled Drugs and Substances Act, Schedule I, item 27(1); Narcotic Control Regulations, Schedule, item 19(1)^{101112131415161718192021}

O-Desmethyltramadol is not federally uncontrolled. It is expressly listed in Schedule I to the Controlled Drugs and Substances Act at item 27(1) as O-desmethyltramadol (3-[2-[(dimethylamino)methyl]-1-hydroxycyclohexyl]-phenol), including the salts, isomers and salts of isomers specified by item 27. The official amendment materials also identify it as tramadol's M1 metabolite. It is separately listed as a narcotic in the schedule to the Narcotic Control Regulations at item 19(1). Both entries took effect on March 31, 2022. The CDSA prohibits unauthorized possession, trafficking, possession for trafficking, import, export, possession for export, and production; regulatory authorizations and section 56 medical, scientific, or public-interest exemptions remain available, and the NCR provides controlled prescription and dispensing pathways. This does not establish Canadian market authorization for an O-desmethyltramadol product. The NCR remains current on the access date but will be repealed on October 1, 2026; the replacement Controlled Substances Regulations retain the exact substance in Schedule 1, Narcotics.

References

Citations

Automated synthesis
Information aggregated and synthesized using an autonomous workflow built by Josie Kins.

Suggest an edit

Spotted a mistake, an outdated claim, or something missing from the O-Desmethyltramadol article? Send the editors a private note. Feedback lands in a moderation queue and is never shown on the site.

Wish to give generalised feedback? You can do so here.

Not yet reviewed — this article is pending editorial review by Lyrea.

WARNINGDANGER OF DEATH

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

O-Desmethyltramadol

Psychoactive Class

Opioid Depressant

Chemical Class

Phenylpropylamine

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~10 mg

Light10-25 mg

Moderate25-50 mg

Strong50-100 mg

Heavy100+ mg

Duration

Onset30-60 minutes

After Effects1-8 hours

Total3-6 hours

Half-life

6.7-9 hours

Subjective Effects

Effects vary widely by individual, dose, and context.

Physical

Constipation Cough suppression Difficulty urinating Nausea Sedation Pupil constriction

Cognitive

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

Anxiety suppression Compulsive redosing

Forked from Subjective Effect Documentation

by Josie KinsJuly 2015.

Pharmacology

Pharmacodynamics

Pharmacokinetics

Interactions

Interactions not written up yet

An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.

Check

TripSit

Tolerance

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

Full Tolerance

Cross Tolerance

Opioids

Harm Potential

Addiction & Dependence

Psychological

Moderate

Physical

Moderate

Toxicity

Hepatic

Respiratory

Respiratory depression is the primary life-threatening effect in overdose⁵; a sensation of labored breathing may occur at strong doses and represents a danger sign in overdose situations.

Seizure Risk

History & Culture

Emergence as a Research Chemical

Legality

By Country

United StatesIllegalTemporary Schedule I

21 CFR § 1308.11(h)(88); DEA Temporary Scheduling Order, 91 FR 52013 (August 12, 2026)^33343536

United KingdomIllegalClass B / Schedule 1

Misuse of Drugs Act 1971, Schedule 2, Part II; Misuse of Drugs Regulations 2001, Schedule 1; Misuse of Drugs Regulations (Northern Ireland) 2002, Schedule 1^{242526232728293031}

CanadaIllegalSchedule I / NCR narcotic

Controlled Drugs and Substances Act, Schedule I, item 27(1); Narcotic Control Regulations, Schedule, item 19(1)^{101112131415161718192021}

References

Citations

Automated synthesis
Information aggregated and synthesized using an autonomous workflow built by Josie Kins.

Suggest an edit

Spotted a mistake, an outdated claim, or something missing from the O-Desmethyltramadol article? Send the editors a private note. Feedback lands in a moderation queue and is never shown on the site.

Wish to give generalised feedback? You can do so here.