From PsychonautWiki
(Redirected from Dextromethorphan)
Jump to: navigation, search
Summary sheet: DXM
Chemical Nomenclature
Common names DXM, DMO, DM, Dex, Robitussin, Delsym, DexAlone, Duract
Substitutive name Dextromethorphan
Systematic name (4bS,8aR,9S)-3-Methoxy-11-methyl-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthrene
Class Membership
Psychoactive class Dissociative
Chemical class Morphinan
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.

Threshold Common Heavy
100 - 100 - 200 - 400 - 700 mg
Light Strong
Threshold 100 mg
Light 100 - 200 mg
Common 200 - 400 mg
Strong 400 - 700 mg
Heavy 700 mg +
Total 8 - 12 hours
Onset 30 - 120 minutes
Come up 60 - 120 minutes
Peak 3 - 6 hours
Offset 2 - 4 hours
After effects 4 - 24 hours

DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Dextromethorphan (also known as DXM and Dex) is a dissociative substance of the morphinan class that produces long-lived dissociative and antitussive (cough suppressant) effects when administered.

DXM is the primary active ingredients in many common over-the-counter (OTC) cold and cough medicines, including generic drug labels and store brands. It is also used in other areas of medicine, ranging from pain relief to psychological applications.[citation needed] In its pure form, DXM occurs as a white powder,[1] although it is most commonly consumed in tablet, capsule, or syrup forms.

In the United States and elsewhere, DXM has been noted for having a culture of recreational consumption as a legal, commonly-available, "OTC high." When exceeding label-specified maximum dosages, it acts as a serotonergic dissociative that produces potent and long-lived hallucinogenic effects with a strong "body load" that can range from pleasant to intolerable. In high doses, this produces effects similar to, yet distinct from, the dissociative states produced by other common dissociatives such as ketamine and phencyclidine (PCP).[2]

Due to its powerful hallucinogenic and potential dependence-producing effects, it is strongly advised to take appropriate precautions and use harm reduction practices if using this substance.

History and culture

History icon.svg

This History and Culture section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

DXM was first discovered in 1954 as part of US Navy and CIA-funded research on possible substitutes for codeine and dihydrocodeine. The purpose was to find a less sedating antitussive (cough suppressant) agent with a lower potential for dependence.[3] Shortly after its approval by the FDA in 1958 as an over-the-counter antitussive,[3] anecdotal reports of recreational use began to spread.[4][2]

During the 1960s and 1970s, a tablet form preparation named "Romilar" was sold over-the-counter as a DXM-containing antitussive. DXM was excluded from the Controlled Substances Act of 1970 which allowed its sale to continue.[3]

Romilar was taken off the OTC-market in 1975, as its rising popularity as a legal dissociative drug was recognized. After its removal many companies began to sell DXM preparations in syrup form, which created an unpleasant taste if consumed in large quantities, so as to make them unappealing for recreational use.[3]


Generic structure of morphinan molecule.

Dextromorphan is a dextrorotatory molecule of the morphinan class. It contains a phenanthrene core structure with one aromatic ring (benzene) bound to two saturated rings (cyclohexane). Additionally, it contains a saturated piperidine ring attached to R9 and R13 of the core structure. DXM is substituted at RN with a methyl group and at R3 with a methoxy group.


Further information: NMDA receptor antagonist

DXM acts as an NMDA receptor antagonist. NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually what is known as the “hole”.

The mechanism of action behind DXM is via multiple effects, including actions as a nonselective serotonin reuptake inhibitor[5], alpha-3 beta-4 nicotinic receptor antagonist[6] and a sigma-1 receptor agonist.[7][8]

At high doses, DXM can cause an increase in systolic and diastolic blood pressure along with an increase in heart rate.[9] DXM also increases blood plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone.[10]

Binding Sites Binding Affinity Ki (nM)[11]
NMDA 8945
Sigma-1 138
NET 240
μ-opioid 1280
κ-opioid 7000
δ-opioid 11500


Metabolism of Dextromethorphan

DXM is O-demethylated into Dextrorphan (DXO / D-3-hydroxy-N-methylmorphinan) by the CYP2D6 enzyme.[12][13] DXM is also N-demethylated into 3-methoxymorphinan (MEM / Morphinan) by the CYP3A4 enzyme[13][14] and to a lesser extent CYP3A5.[15]

Dextrorphan and 3-methoxymorphinan are both metabolized into 3-hydroxymorphinan. Dextrorphan is N-demethylated by CYP3A4 and 3-Methoxymorphinan is O-demethylated by CYP2D6. CYP2D6 O-demethylation is more effective than CYP3A4 N-demethylation.[13]


Dextrorphan is produced by O-demethylation of dextromethorphan through the CYP2D6 enzyme and contributes to the psychoactive effects of dextromethorphan.[16] It is pharmacologically similar to that of dextromethorphan (DXM). However, dextrorphan is much more potent as an NMDA receptor antagonist[11] as well as much less active as a selective serotonin reuptake inhibitor.[10] It is also about 3-fold less potent of a α3β4 nicotinic receptor antagonist than DXM[17] and has a lower affinity for sigma-1 receptors.[7]

Binding Sites Binding Affinity Ki (nM)[11]
NMDA 486
Sigma-1 351
SERT 484
NET 340
μ-opioid 420
κ-opioid 5950
δ-opioid 34700


3-Methoxymorphinan (also known as 3MM) is produced by the N-demethylation of dextromethorphan by the CYP3A4 enzyme[13] and inhibits the CYP2D6 enzyme.[18] It has local anaesthetic effects.[19]


3-Hydroxymorphinan (also known as 3HM) is produced by O-demethylation of 3-methoxymorphinan by CYP2D6 and metabolization of dextrorphan by CYP3A4 and CYP3A5[20]. 3-Hydroxymorphinan exhibits neuroprotective and neurotrophic effects.[21][22][23]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

Visual effects

Cognitive effects

Disconnective effects

Multi-sensory effects



The online DXM community has informally divided the types of experiences that can result from oral DXM administration into five "plateaus" which are characterized by qualitatively distinct effects that vary by their body-weight adjusted doses.[citation needed]

First Plateau (1.5 - 2.5 mg/kg) - The effects felt in the first plateau are usually not very intense. They can include but are not limited to: cognitive euphoria, increased music appreciation, time distortion, pupil dilation, and stimulation. First plateau is often described as a "drunk" feeling.

Second Plateau (2.5 - 7.5 mg/kg) - Most DXM users consider this the to be the most recreational plateau. The second plateau is more sedating than stimulating, euphoria and visual disconnection are more intense. Additional effects of the second plateau can include but are not limited to: Wakefulness, physical euphoria, spatial disorientation. Many users of DXM do not proceed past the second plateau, as the desired effects are thought to be outweighed by the increasingly unpredictable adverse physical and cognitive effects as well as a more pronounced "body load".

Third Plateau (7.5 - 15 mg/kg) - The effects of the third plateau can include but are not limited to: sedation, nausea, memory suppression and ego death, auditory hallucinations, internal hallucinations, cognitive dysphoria, anxiety, delusions, and all the effects of the second plateau.

Fourth Plateau (15 - 20 mg/kg) - Doses of DXM in this range and beyond are considered to be very dangerous and are associated with a high risk of injury and overdose, and are therefore advised against. The effects of the fourth plateau can include but are not limited to external hallucinations, complete dissociation, and all the effects of the third plateau, with greater intensity.

Fifth Plateau (also known as "Plateau Sigma") - A common method to experience the so-called "Plateau Sigma" is to take second plateau dose, followed by another second plateau dose three hours later, then at the peak of the second dose, take a fourth plateau dose. Plateau Sigma may also occur unintentionally from redosing. It is nearly always a very unpleasant and unpredictable experience. The experience can last from one day to four days. Plateau Sigma usually results in delirious hallucinations, dysphoria, delirium, psychosis, and anxiety. Plateau Sigma has a high potential to cause serotonin syndrome and is therefore strongly advised against.

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:


Available forms

DXM is available in several different forms that can be found over the counter or online.

  • Cough syrup is the most common form online and over the counter. Well-known brands include Benylin, DayQuil, Delsym, NyQuil, Robitussin, and Siltussin. Many of these products contain other medicines, including aspirin, acetaminophen, caffeine, guaifenesin or pseudoephedrine. Care should be taken when using these products to ensure that there is no overdose on other medicines in the DXM-containing product. Within the UK, Benylin dry coughs 7.5mg/5ml syrup (225mg dosage per 150ml bottle) is available behind the counter at every pharmacy. Generic brands are also available within these shops for a consistently lower price.
  • Gel capsules and pills are available online and over the counter. Well-known brands include Benylin, Comtrex, Coricidin, DayQuil, Mucinex, NyQuil, and Robitussin. Many of these products contain other medicines, including aspirin, acetaminophen, caffeine, guaifenesin or pseudoephedrine. Care should be taken when using these products to ensure that there is no overdose on other medicines in the DXM-containing product.
  • Pure powder is available online. This is the safest way to use DXM, as there is no danger of overdose from secondary chemicals.


Grapefruit juice is reported to be effective at potentiating and enhancing the effects of DXM. If one drinks approximately one glass of white grapefruit juice hourly the day before the trip, the effects will be considerably stronger and more intense. For users who are drinking store bought syrup, this is useful as it means drinking less syrup.

The grapefruit juice acts on DXM by inhibiting the activity of cytochrome P450 enzymes of the 3A and 1A groups.[citation needed] DXM is converted to DXO by this same enzyme, only with different groups.[citation needed] Therefore, with enough grapefruit juice, the overall trip should be significantly more intense, as the DXM is converted into DXO at a faster rate.

Preparation methods

Preparation methods for this compound within our tutorial index include:

Toxicity and harm potential

The toxicity and long-term health effects of recreational DXM use in humans do not seem to have been studied in any scientific context and the exact toxic dosage is unknown. This is because DXM has very little history of human usage.

Anecdotal evidence from people who have tried DXM within the community suggests that there do not seem to be any negative health effects attributed to simply trying this substance at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Despite early speculation that DXM (due to similarities with PCP) may cause neurotoxicity and Olney's lesions, it has not been shown to cause this effect in animals [24], However, many chronic users report significant issues with memory, attention, and mood that persist for many months after stopping usage. In rats,[25] oral administration of dextromethorphan did not cause neurotoxic effects in laboratory tests.[26] Oral administration of dextromethorphan repeatedly during adolescence, however, has been shown to impair learning in those rats during adulthood.[27]

It is strongly recommended that one use harm reduction practices when using this substance.

Tolerance and addiction potential

As with other NMDA receptor antagonists, the chronic use of DXM 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 effects may occur if a person suddenly stops their usage.

Tolerance to many of the effects of DXM develops with prolonged and repeated use. 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). DXM presents cross-tolerance with all dissociatives, meaning that after the consumption of DXM all dissociatives will have a reduced effect.

Additionally, some users report an irreversible, permanent tolerance to DXM, which develops over a long period of time and is thought to correlate with the number of doses a person has ingested throughout their lifetime. There is a supposed "50 trip limit", after which the rewarding and unique effects of DXM disappear permanently. The pharmacological mechanism for this is unknown, although it may be indicative of neurotoxicity.

A formal survey of dextromethorphan users[28] showed that more than half of users reported experience of the following withdrawal symptoms individually for the first week after long-term/addictive dextromethorphan use: fatigue, apathy, flashbacks, and constipation. Over a quarter reported insomnia, nightmares, inability to feel pleasure, impaired memory, attention deficit and decreased libido. Rarer side effects included panic attacks, impaired learning, tremor, yellowing of the skin, hives and muscle pain. Frequent and long-term usage at very high doses could lead to toxic psychosis and other permanent psychological problems.[29]

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

Prominent examples include PCP and its analogs 3-MeO-PCP, MXE, and the diarylethylamine dissociatives like diphenidine or ephenidine. There is also evidence that suggests that combining these two increases their neurotoxicity.[citation needed] Anecdotally, worsened comedowns are also commonly reported when these two classes of substances are combined.
  • Depressants - Because both depress the respiratory system, this combination can result in an increased risk of suddenly falling unconscious, vomiting and choking to death from the resulting suffocation. If nausea or vomiting occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it. Also, this combination will produce a combined depressant effect which can cause dangerous levels of respiratory depression.
  • Stimulants - A dangerous rise in blood pressure and heart rate can occur when DXM is combined with a stimulant such as amphetamine or cocaine.

Serotonin syndrome risk

Combinations with the following substances may increase the level of neurotransmitters such as serotonin and dopamine to dangerous or even fatal levels.

Other interactions

  • Modafinil induces the CYP3A4 enzyme that DXM, and its metabolite DXO, are metabolized by.[31]
  • DXM has been shown to prevent and reverse morphine tolerance while also increasing analgesic effects[32][33][34] as well as potentiating the analgesic activity of NSAIDs, naproxen, piroxicam, etodolac, diclofenac, and ketorolac.[35]

Legal status

DXM is available either over the counter or by prescription in most countries. Some countries require the purchaser to be over 16, 18 or 21. However, it is easily accessible to legally purchase in a variety of forms online.[citation needed]

  • Austria: Dextromethorphan is not listed in the "Suchtmittelgesetz" (Federal Law on Narcotics). Sales of DXM containing medications are restricted to pharmacies. DXM containing preparations are available at pharmacies without a prescription.
  • Canada: Dextromethorphan is listed as specifically exempt from the Controlled Drugs and Substances Act[36]. It is available OTC in Canada and can legally be obtained in powder form.
  • Germany: Dextromethorphan is not listed in the "Betäubungsmittelgesetz" (Federal Law on Narcotics).[37] Sales of DXM containing medications are restricted to pharmacies.[38] DXM containing preparations are available at pharmacies without a prescription.
  • Mexico: Dextromethorphan is not listed in the General Health Law (Ley General de Salud)[39], which specifies which substances represent a risk to public health. It is also listed in the Reference Medicine Listing[40] as a General Health Law article 226 fraction VI drug, which means it can be freely sold even in businesses that weren't legally registered as pharmacies. In practice, this translates into DXM-only syrups being available off-the-shelf and without prescription at any supermarket with a pharmacy section.
  • Russia: Dextromethorphan is a schedule III controlled substance.[41]
  • Switzerland: Dextromethorphan is listed as a "Abgabekategorie C" pharmaceutical, which is sold exclusively in pharmacies without a prescription but needs approval of a medicinal.

See also

External links



  1. Reference Tables: Description and Solubility - D | http://www.pharmacopeia.cn/v29240/usp29nf24s0_alpha-2-13.html
  2. 2.0 2.1 Dextromethorphan | http://web-beta.archive.org/web/20121016221008/http://www.deadiversion.usdoj.gov/drugs_concern/dextro_m/dextro_m.pdf
  3. 3.0 3.1 3.2 3.3 Dextromethorphan (DXM) | http://www.cesar.umd.edu/cesar/drugs/dxm.asp
  4. Morris H, Wallach J. From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. | https://www.ncbi.nlm.nih.gov/pubmed/24678061
  5. Dextromethorphan-induced serotonin syndrome (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19238739
  6. Dextromethorphan and Its Metabolite Dextrorphan Block α3β4 Neuronal Nicotinic Receptors | http://jpet.aspetjournals.org/content/293/3/962.long
  7. 7.0 7.1 Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 receptor activation in rats (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0197018607000381
  8. A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: treatment of involuntary emotional expression disorder. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17689532
  9. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652430/
  10. 10.0 10.1 Comparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-Pituitary-Adrenal Axis | http://jpet.aspetjournals.org/content/309/2/515
  11. 11.0 11.1 11.2 Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders - 3. Pharmacodynamics (January 2016) - Linda Nguyen et al. | https://www.researchgate.net/publication/292212463_Dextromethorphan_An_update_on_its_utility_for_neurological_and_neuropsychiatric_disorders
  12. Cytochrome P450-dependent metabolism of dextromethorphan: fetal and adult studies. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/1306804
  13. 13.0 13.1 13.2 13.3 Comparative Contribution to Dextromethorphan Metabolism by Cytochrome P450 Isoforms in Vitro: Can Dextromethorphan Be Used as a Dual Probe for Both CYP2D6 and CYP3A Activities? (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11602530
  14. Effect of black seed on dextromethorphan O- and N-demethylation in human liver microsomes and healthy human subjects. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/20201775
  15. Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8043020
  16. Psychotropic Effects of Dextromethorphan Are Altered by the CYP2D6 Polymorphism: A Pilot Study | http://journals.lww.com/psychopharmacology/pages/articleviewer.aspx?year=1998&issue=08000&article=00014&type=abstract
  17. Dextromethorphan and Its Metabolite Dextrorphan Block α3β4 Neuronal Nicotinic Receptors | http://jpet.aspetjournals.org/content/293/3/962.long
  18. The role of CYP2D6 in primary and secondary oxidative metabolism of dextromethorphan: in vitro studies using human liver microsomes. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/7826826
  19. Dextromethorphan, 3-methoxymorphinan, and dextrorphan have local anaesthetic effect on sciatic nerve blockade in rats - Chia-Hui Hou et al. | http://www.sciencedirect.com/science/article/pii/S0014299906006285
  20. Gorski JC, Jones DR, et al. Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. Biochem. Pharmacol.. 1994;48:173-182
  21. 3-Hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity - Zhang W, Shin EJ, Wang T, et al. (December 2006) | http://www.fasebj.org/content/early/2005/03/04/fj.04-1586fje.long
  22. Neuropsychotoxicity of Abused Drugs: Potential of Dextromethorphan and Novel Neuroprotective Analogs of Dextromethorphan With Improved Safety Profiles in Terms of Abuse and Neuroprotective Effects - Eun-Joo Shin et al. (June 2011) | https://www.jstage.jst.go.jp/article/jphs/106/1/106_FM0070177/_article
  23. Neuropsychotoxic and Neuroprotective Potentials of Dextromethorphan and Its Analogs - Eun-Joo Shin et al. (January 2008) | https://www.jstage.jst.go.jp/article/jphs/116/2/116_11R02CR/_article
  24. https://www.erowid.org/chemicals/dxm/dxm_health2.shtml
  25. Induction of heat shock protein HSP-70 in rat retrosplenial cortex following administration of dextromethorphan | Induction of heat shock protein HSP-70 in rat retrosplenial cortex following administration of dextromethorphan
  26. Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17573115
  27. Impairments in water maze learning of aged rats that received dextromethorphan repeatedly during adolescent period | http://en.wikipedia.org/wiki/Recreational_use_of_dextromethorphan#Risks_associated_with_use
  28. Side effects of dextromethorphan abuse, a case series (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16122622
  29. Center for Substance Abuse Research - DXM | http://www.cesar.umd.edu/cesar/drugs/dxm.asp
  30. Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210
  31. Clinical pharmacokinetic profile of modafinil. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/12537513
  32. Dextromethorphan attenuates and reverses analgesic tolerance to morphine. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/7708410
  33. Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8951930
  34. Evaluation the effects of dextromethorphan and midazolam on morphine induced tolerance and dependence in mice. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18819620
  35. Effects of the combined oral administration of NSAIDs and dextromethorphan on behavioral symptoms indicative of arthritic pain in rats. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9252006
  36. Controlled Drugs and Substances Act (S.C. 1996, c. 19) | http://laws-lois.justice.gc.ca/PDF/C-38.8.pdf
  37. "Anlage I-III", BTMG | http://www.gesetze-im-internet.de/btmg_1981/
  38. § 43 AMG | http://www.gesetze-im-internet.de/amg_1976/
  39. http://www.diputados.gob.mx/LeyesBiblio/pdf/142_220617.pdf
  40. https://www.gob.mx/cms/uploads/attachment/file/178695/LMR_2017-07_V001.pdf
  41. Russian controlled substances lists | http://base.garant.ru/12112176/