O-Desmethyltramadol
Also called Desmetramadol, O-DSMT, O-Desmethyl-cis-tramadol
Part of the metabolic pathway of Tramadol and O-Desmethyltramadol. See the timeline on the metabolic highway.
Enzymes that break it down: CYP3A4 and CYP2B6. Wikipedia’s drug infobox says: “CYP3A4 and CYP2B6” (revision 1378366601).
Dosage
Oral bands as drawn from PsychonautWiki's ranges below. The table is the source of truth.
When sources disagree, both rows are shown as published. Nothing is averaged or merged.
Oral
| Source | Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|---|
| PsychonautWiki | 5 mg PW | 10–25 mg PW | 25–50 mg PW | 50–100 mg PW | 100 mg+ PW |
| TripSit | – | 10–25 mg TS | 25–50 mg TS | 50–100 mg+ TS | – |
Sublingual
| Source | Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|---|
| PsychonautWiki | 5 mg PW | 10–25 mg PW | 25–50 mg PW | 50–80 mg PW | 80 mg+ PW |
Intravenous
| Source | Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|---|
| PsychonautWiki | 5 mg PW | 5–12.5 mg PW | 12.5–25 mg PW | 25–50 mg PW | 50 mg+ PW |
Rectal
| Source | Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|---|
| PsychonautWiki | 5 mg PW | 10–25 mg PW | 25–50 mg PW | 50–80 mg PW | 80 mg+ PW |
NOTE: Insufflation considered extremely painful. TS
TripSit dose text
TripSit's factsheet also states its doses as text.
Oral Light: 10-25mg Common: 25-50mg Strong: 50-100mg+ | NOTE: Insufflation considered extremely painful. TS
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Duration
Oral, drawn at the midpoint of each PsychonautWiki range.
| Route · source | Onset | Come-up | Peak | Offset | Total | After-effects |
|---|---|---|---|---|---|---|
| Oral · PsychonautWiki | 20–40 minutes PW | 30–40 minutes PW | 2–5 hours PW | 2–4 hours PW | 6–10 hours PW | 1–3 hours PW |
| Sublingual · PsychonautWiki | 20–40 minutes PW | – | 2–5 hours PW | 2–4 hours PW | 5–10 hours PW | 1–3 hours PW |
| Intravenous · PsychonautWiki | 10–15 seconds PW | – | 2–5 hours PW | 2–4 hours PW | 5–8 hours PW | 1–3 hours PW |
| Rectal · PsychonautWiki | 3–5 minutes PW | 8–10 minutes PW⚠ The source row looks copy-pasted from another route. Check it before relying on it. | 3–5 hours PW | 1–3 hours PW | 4–8 hours PW | 1–3 minutes PW |
TripSit factsheet
Mixing
For best safety practice, don't mix this drug with other depressants.
Why: respiratory depression. PsychonautWiki says:
- “Respiratory depression (also known as hypoventilation) can be described as a reduced urge to breathe that can be fatal depending on its intensity.” (PsychonautWiki, Respiratory depression, revision 150612)
- “... otherwise safe dosages of these compounds can become fatal when combined with even small amounts of other classes of depressant. For example, benzodiazepines combined with opioids are an extremely common cause of fatal respiratory depression. It is therefore strongly discouraged to combine these depressants at any dosage range.” (PsychonautWiki, Respiratory depression, revision 150612)
- “The most common cause of substance-related deaths is the combination of depressants (such as opiates, benzodiazepines, or alcohol) with other depressants.” (PsychonautWiki, Responsible drug use, revision 168206)
- “This combination potentiates the muscle relaxation, amnesia, sedation, and respiratory depression caused by one another. At higher doses, it can lead to a sudden, unexpected loss of consciousness along with a dangerous amount of depressed respiration.” (PsychonautWiki, dangerous interactions table, "Depressants" row, revision 156847)
Quotes from PsychonautWiki, CC BY-SA 4.0.
Acute combinations: what happens when these are taken close together. Entries backed by a medical journal or agency are listed first.
Backed by medical journals
PsychonautWiki also lists dangerous combinations shared across a whole group (opioids, serotonin syndrome) in a table this page does not copy. Read that list on PsychonautWiki.
TripSit combination chart
TripSit rates each pairing. Only pairings with a number carry a citation from TripSit. See the whole chart; TripSit's own notes are on combo.tripsit.me.
Risks and toxicity
O-DSMT has a moderate potential toxicity relative to its dose due to its potency. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines. PW
O-DSMT has recently been marketed as a currently legal substitute for illegal opioid drugs, either in powder form or mixed into various other preparations. One such blend was sold under the brand Krypton and contains powdered kratom leaf (Mitragyna speciosa) laced with O-DSMT and was reportedly linked to at least 9 accidental deaths from overdose during 2010–2011.[4]
It is strongly recommended that one use harm reduction practices when using this drug. PW
Tolerance and addiction potential
As with other opioids, the chronic use of O-DSMT can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage. PW
Tolerance to many of the effects of O-DSMT develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). O-DSMT presents cross-tolerance with all other opioids, meaning that after the consumption of O-DSMT all opioids will have a reduced effect. PW
TripSit factsheet
- Avoid
- All other CNS depressants. TS
Testing
Effects
EuphoriaDry MouthMood liftItchinessRelaxantConstipationPupil constrictionAnalgesia TS
Overview
O-Desmethyltramadol (also known as O-DSMT and desmetramadol) is an opioid substance of the phenylpropylamine class. It is an active metabolite of tramadol.[1] PW
A opioid analgesic which is the main active metabolite of Tramadol. Alone, it is a few times more potent than Tramadol and has additional affinity for δ and κ-opioid receptors. Has proven popular when sold, but these occasions have been rare due to patent rights. TS
Desmetramadol (INN (International Nonproprietary Name)), also known as O-desmethyltramadol (O-DSMT), is an opioid analgesic and the main active metabolite of tramadol. Tramadol is demethylated by the liver enzyme CYP2D6 to desmetramadol in the same way as codeine, and so similarly to the variation in effects seen with codeine, individuals who have a less active form of CYP2D6 will tend to have reduced analgesic effects from tramadol. Because desmetramadol itself does not need to be metabolized to induce an analgesic effect, it can be used in individuals with CYP2D6 inactivating mutations.[1]
Desmetramadol is commonly encountered as a designer drug online in powder form or as an ingredient in pressed pills due to being unscheduled in many jurisdictions. Outside of its role as a metabolite, a chemical used in research, and as a recreational drug, desmetramadol has a very limited history of human usage and is not approved for medicinal use in any country as of 2025.[3] WP
History
Legal status
- There is little information online regarding the international legalities of O-Desmethyltramadol possession but it is confirmed as a controlled substance within the United Kingdom.[7] PW
- Germany: O-DSMT is not a controlled substance under the BtMG. It is legal, as long as it is not sold for human consumption, according to §2 AMG.[8]
[9] PW - Sweden: O-DSMT is a controlled substance and considered a narcotic by law. PW
- Switzerland: O-DSMT is not controlled under Buchstabe A, B, C and D. It could be considered legal.[10] PW
- United Kingdom: It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.[11] PW
United kingdom
Desmetramadol was made a Class B drug in the United Kingdom on 26 February 2013.[12] WP
United states of america
The U.S. Drug Enforcement Administration issued a temporary order for the classification of desmetramadol in schedule 1 of the Controlled Substances Act for the period of August 12, 2026 through August 12, 2028.[13] WP
Germany
Pharmacology
Pharmacodynamics
(+)-Desmetramadol is a G-protein biased μ-opioid receptor full agonist. It shows comparatively far lower affinity for the δ- and κ-opioid receptors. The two enantiomers of desmetramadol show quite distinct pharmacological profiles; both (+) and (−)-desmetramadol are inactive as serotonin reuptake inhibitors, but (−)-desmetramadol retains activity as a norepinephrine reuptake inhibitor, and so the mix of both the parent compound and metabolites contributes significantly to the complex pharmacological profile of tramadol. While the multiple receptor targets can be beneficial in the treatment of pain (especially complex pain syndromes such as neuropathic pain), they increase the potential for drug interactions compared to other opioids, and may also contribute to side effects. Desmetramadol is also an antagonist of the serotonin 5-HT2C receptor, at pharmacologically relevant concentrations, via competitive inhibition. This suggests that the apparent anti-depressant properties of tramadol may be at least partially mediated by desmetramadol, thus prolonging the duration of therapeutic benefit. Inhibition of the 5-HT2C receptor is a suggested factor in the mechanism of anti-depressant effects of agomelatine and maprotiline. The potential selectivity and favorable side effect profile of desmetramadol compared to tramadol, makes it more suitable for use as antidepressant, although clinical development appears to have stopped. Upon inhibition of the receptor, downstream signaling causes dopamine and norepinephrine release, and the receptor is thought to significantly regulate mood, anxiety, feeding, and reproductive behavior. 5-HT2C receptors regulate dopamine release in the striatum, prefrontal cortex, nucleus accumbens, hippocampus, hypothalamus, and amygdala, among others. Research indicates that some suicide victims have an abnormally high number of 5-HT2C receptors in the prefrontal cortex. There is some mixed evidence that agomelatine, a 5-HT2C antagonist, is an effective antidepressant. Antagonism of 5-HT2C receptors by agomelatine results in an increase of dopamine and norepinephrine activity in the frontal cortex.[15–23] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.
Metabolites
Desmetramadol is metabolized in the liver into the active metabolite N,O-didesmethyltramadol via CYP3A4 and CYP2B6. The inactive tramadol metabolite N-desmethyltramadol is metabolized into the active metabolite N,O-didesmethyltramadol by CYP2D6.[24] WP
Chemistry
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References
- Journal / agency Sevcik, J., Nieber, K., Driessen, B., Illes, P. Effects of the central analgesic tramadol and its main metabolite, O-desmethyltramadol, on rat locus coeruleus neurones. British Journal of Pharmacology. September 1993. doi:10.1111/j.1476-5381.1993.tb13788.x
- Journal / agency Borlak J, Hermann R, Erb K, Thum T. A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadol. Metabolism. November 2003. doi:10.1016/s0026-0495(03)00256-7 · PMID 14624403
- Harm reduction site Erowid, DrugsData. org. (n.d.). Drugsdata.org: Test results - “O-DSMT” (Desmetramadol)
- Journal / agency Arndt, T., Claussen, U., Güssregen, B., Schröfel, S., Stürzer, B., Werle, A., Wolf, G. Kratom alkaloids and O-desmethyltramadol in urine of a “Krypton” herbal mixture consumer. Forensic Science International. 20 May 2011. doi:10.1016/j.forsciint.2010.10.025
- Journal / agency Bäckstrom, B. G., Classon, G., Löwenhielm, P., Thelander, G. Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden. Lakartidningen. 15 December 2010
- Journal / agency Kronstrand, R., Roman, M., Thelander, G., Eriksson, A. Unintentional Fatal Intoxications with Mitragynine and O-Desmethyltramadol from the Herbal Blend Krypton. Journal of Analytical Toxicology. 1 May 2011. doi:10.1093/anatox/35.4.242
- Other http://www.legislation.gov.uk/ukdsi/2013/9780111532980/pdfs/ukdsi_9780111532980_en.pdf
- Other Anlage I BtMG - Einzelnorm
- Other § 2 AMG - Einzelnorm
- Other Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien
- Other Psychoactive Substances Act 2016
- Other The Misuse of Drugs (Designation) (Amendment) (England, Wales and Scotland) Order 2013. 31 January 2013
- Other Schedules of Controlled Substances: Temporary Placement of O-Desmethyltramadol in Schedule I. August 12, 2026
- Other Sechste Verordnung zur Änderung der Anlage des Neue-psychoaktive-Stoffe-Gesetzes
- Journal / agency Zebala JA, Schuler AD, Kahn SJ, Maeda DY. Desmetramadol Is Identified as a G-Protein Biased µ Opioid Receptor Agonist. Frontiers in Pharmacology. 2019. doi:10.3389/fphar.2019.01680 · PMID 32116679 · PMC7025522
- Journal / agency Potschka H, Friderichs E, Löscher W. Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. British Journal of Pharmacology. September 2000. doi:10.1038/sj.bjp.0703562 · PMID 10991912 · PMC1572317
- Journal / agency Garrido MJ, Valle M, Campanero MA, Calvo R, Trocóniz IF. Modeling of the in vivo antinociceptive interaction between an opioid agonist, (+)-O-desmethyltramadol, and a monoamine reuptake inhibitor, (-)-O-desmethyltramadol, in rats. The Journal of Pharmacology and Experimental Therapeutics. October 2000. doi:10.1016/S0022-3565(24)38909-8 · PMID 10992001
- Journal / agency Bamigbade TA, Davidson C, Langford RM, Stamford JA. Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus. British Journal of Anaesthesia. September 1997. doi:10.1093/bja/79.3.352 · PMID 9389855
- Journal / agency Driessen B, Reimann W, Giertz H. Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro. British Journal of Pharmacology. March 1993. doi:10.1111/j.1476-5381.1993.tb12882.x · PMID 8467366 · PMC1908052
- Journal / agency Horishita T, Minami K, Uezono Y, Shiraishi M, Ogata J, Okamoto T, Shigematsu A. The tramadol metabolite, O-desmethyl tramadol, inhibits 5-hydroxytryptamine type 2C receptors expressed in Xenopus Oocytes. Pharmacology. 2006. doi:10.1159/000093179 · PMID 16679816
- Journal / agency Heisler LK, Zhou L, Bajwa P, Hsu J, Tecott LH. Serotonin 5-HT(2C) receptors regulate anxiety-like behavior. Genes, Brain and Behavior. July 2007. doi:10.1111/j.1601-183X.2007.00316.x · PMID 17451451
- Journal / agency Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E. RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology. May 2001. doi:10.1016/S0893-133X(00)00223-2 · PMID 11282248
- Journal / agency Eser D, Baghai TC, Möller HJ. Agomelatine: The evidence for its place in the treatment of depression. Core Evidence. June 2010. doi:10.2147/CE.S6005 · PMID 20694073 · PMC2899775
- Other Figure 7. Tramadol and desmetramadol metabolism catalyzed by CYPs in vitro
Text and values on this page are quoted from PsychonautWiki (CC BY-SA 4.0), Wikipedia (CC BY-SA 4.0), TripSit factsheets, PubChem (public domain). Each value links to the exact revision it came from.