Dextromethorphan

From PsychonautWiki
(Redirected from DXM)
Jump to: navigation, search
Summary sheet: Dextromethorphan
Dextromethorphan
DXM.svg
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.



Oral
Dosage
Threshold 100 mg
Light 100 - 200 mg
Common 200 - 400 mg
Strong 400 - 700 mg
Heavy 700 mg +
Duration
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 robo, dex, DM, and DXM) is a dissociative substance of the morphinan class. DXM is the primary active ingredients in many common over-the-counter (OTC) cold and cough medicines. When exceeding approved doses, DXM produces dissociative effects similar to those of ketamine and phencyclidine (PCP). The pharmacology of DXM is not completely understood, but it is thought to act primarily by blocking NMDA receptors in the brain.

DXM was first reported in 1953 and approved for use as a cough suppressant in the United States in 1958.[1] After its approval, it was introduced as an OTC medication under the name Romilar. As early as 1975, the popularity and extensive abuse of DXM was recognized, and Romilar was voluntarily removed from the OTC market.[2] A few years later, companies began introducing various refined DXM products designed to deter abuse, such as including ingredients with an unpleasant taste. However, recreational use of DXM has persisted and is a considered a growing trend, particularly among teenagers seeking low cost and easily available highs.[3]

Users commonly describe the experience of DXM as disorienting, bizarre, hallucinatory, and asocial. Notable effects include time distortion, bodily hallucinations, motor control loss, ego loss, and euphoria. It is often reported to produce a strong, uncomfortable body load with significant nausea. The effects and tolerability of DXM are highly variable between users which may be due to individual differences in the genes underlying metabolism. As a result, many users find the experience of DXM to be either unpleasant or neutral, while others report mystical-type experiences that facilitate self-reflection and personal growth.

The toxicity of DXM in high doses is unclear and has been the subject of controversy. There is some evidence that suggests NMDA antagonists may have neurotoxic effects when used in excess. Many cases of DXM dependence and abuse have been documented. It is strongly advised to use harm reduction practices if using this substance.

History and culture

The racemic parent compound of dextromethorphan, racemorphan, was first described in a Swiss and US patent application from Hoffmann-La Roche in 1946 and 1947, respectively. A patent was granted in 1950. A resolution of the two isomers of racemorphan with tartaric acid was published in 1952,[4] and DXM was successfully tested in 1954 as part of US Navy and CIA-funded research on nonaddictive substitutes for codeine.[5]

DXM was approved by the FDA in 1958 as an over-the-counter antitussive, or cough suppressant.[4] As had been initially hoped, DXM was a solution for some of the problems associated with the use of codeine phosphate as a cough suppressant, such as sedation and opiate dependence, but like the dissociative anesthetics phencyclidine and ketamine, DXM later became associated with nonmedical use.[2][4]

During the 1960s and 1970s, dextromethorphan became available in an over-the-counter tablet form by the brand name Romilar. In 1973, Romilar was taken off the shelves after a burst in sales because of frequent misuse, and was replaced by cough syrup in an attempt to cut down on abuse.[2] The advent of widespread internet access in the 1990s allowed users to rapidly disseminate information about DXM, and online discussion groups formed around use and acquisition of the substance.

As early as 1996, DXM HBr powder could be purchased in bulk from online retailers, allowing users to avoid consuming DXM in syrup preparations.[4] As of January 1, 2012, dextromethorphan is prohibited for sale to minors in the state of California, except with a doctor's prescription.[6]

Chemistry

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.

Pharmacology

Further information: NMDA receptor antagonist

The pharmacology of DXM is not completely understood. In vitro studies suggest that the primary mechanism of action of DXM is blockade of N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are a type of glutamate receptor; glutamate is the primary excitatory neurotransmitter. Blockade of NMDA receptors therefore interferes with excitatory signaling in the central nervous system. This mechanism of action is similar to ketamine and PCP. Rather than acting as a direct NMDA receptor antagonist itself, dextromethorphan acts as a prodrug of its much more potent metabolite dextrorphan, and this is the actual mediator of its dissociative effects.

Additional pharmacological mechanisms include actions as a nonselective serotonin reuptake inhibitor[7], alpha-3 beta-4 nicotinic receptor antagonist[8] and a sigma-1 receptor agonist.[9][10]

At high doses, DXM can cause an increase in systolic and diastolic blood pressure along with an increase in heart rate.[11] DXM also increases blood plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone.[12]

Although it is structurally similar to opioids, DXM does not act as a mu-opiod like heroin or codeine.

Binding Sites Binding Affinity Ki (nM)[13]
NMDA 8945
Sigma-1 138
SERT 40
NET 240
μ-opioid 1280
κ-opioid 7000
δ-opioid 11500

Metabolism

Metabolism of Dextromethorphan

DXM is O-demethylated into Dextrorphan (DXO / D-3-hydroxy-N-methylmorphinan) by the CYP2D6 enzyme.[14][15] DXM is also N-demethylated into 3-methoxymorphinan (MEM / Morphinan) by the CYP3A4 enzyme[15][16] and to a lesser extent CYP3A5.[17]

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.[15]

Some people may be very fast metabolizers and others slow or even have this enzyme missing due to genetic variation. This contributes to the wide array of effects as this is the main factor for the levels of mainly DXM and DXO in the body. Enzyme disruption as well as CYP2D6 inhibitors also contribute to this effect.[citation needed]

Dextrorphan

Dextrorphan is produced by O-demethylation of dextromethorphan through the CYP2D6 enzyme and contributes to the psychoactive effects of dextromethorphan.[18] It is pharmacologically similar to that of dextromethorphan (DXM). However, dextrorphan is much more potent as an NMDA receptor antagonist[13] as well as much less active as a selective serotonin reuptake inhibitor.[12] It is also about 3-fold less potent of a α3β4 nicotinic receptor antagonist than DXM[19] and has a lower affinity for sigma-1 receptors.[9]

Binding Sites Binding Affinity Ki (nM)[13]
NMDA 486
Sigma-1 351
SERT 484
NET 340
μ-opioid 420
κ-opioid 5950
δ-opioid 34700

3-Methoxymorphinan

3-Methoxymorphinan (also known as 3MM) is produced by the N-demethylation of dextromethorphan by the CYP3A4 enzyme[15] and inhibits the CYP2D6 enzyme.[20] It has local anaesthetic effects.[21]

3-Hydroxymorphinan

3-Hydroxymorphinan (also known as 3HM) is produced by O-demethylation of 3-methoxymorphinan by CYP2D6 and metabolization of dextrorphan by CYP3A4 and CYP3A5[22]. 3-Hydroxymorphinan exhibits neuroprotective and neurotrophic effects.[23][24][25]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These 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 of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
Child.svg

Visual effects
Eye.svg

Cognitive effects
User.svg

Disconnective effects
Chain-broken.svg

Multi-sensory effects
Gears.svg

Afterglow
Afterglow-placeholder.svg

Plateaus

The online DXM community categorizes the types of experiences that can result from oral DXM use into five "plateaus" which are characterized by qualitatively distinct effects.

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) - Many 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, Frame rate suppression, Music Enhancement. 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". Music is greatly enhanced at this plat, sounding very rich, clear, and amplified as if you are in a gigantic concert hall with music coming from all around you. Bass is more powerful.

Third Plateau (7.5 - 15 mg/kg) - The Third Plateau is much more intense than the second. One should gradually work up to it. The effects of the third plateau can include but are not limited to: dissociation, sedation, nausea (during comeup), memory suppression and ego death, auditory hallucinations, internal hallucinations, cognitive dysphoria, Cognitive and Physical Euphoria, anxiety, delusions, and all the effects of the second plateau. Third Plateau trips are capable of inducing euphoric, introspective, and profound experiences. You may feel an omnipotent feeling that you are in control of the entire universe, accompanied with CEVs. Closed eye visuals are often present at this plateau consisting of usually darker colored geometric patterns, vast landscapes and scenes. Music can greatly enhance this. Music however can become tinny sounding, distorted, and difficult to hear. Sometimes though it can be heard clearly (cannabis helps), and it will take on a bizzare and alien sound. You may be able to break down every single fragment of a song and visualize all of it in your mind. You may also relive past memories. Third plat is often extremely introspective. Many users report these introspective trips to help them grow as a person and improve their lives. While bad trips can leave you shaken for a few days. The afterglow from this plateau is sedating and you feel very groggy yet slightly euphoric the next day (especially when you yawn).

Fourth Plateau (15 - 20 mg/kg) - 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. Doses of DXM in this range are very dangerous and have a high risk of injury and overdose, and are therefore advised against.

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:

Common usage

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.

Potentiation

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] including cytochrome P450 3A4 (CYP3A4).[27] DXM is mostly (up to 90%) O-demethylated into dextrorphan (DXO) by cytochrome P450 2D6 (CYP2D6)[14][15] and to a lesser extent (10%) N-demethylated into the non-psychoactive metabolite 3-methoxymorphinan (3MM) by CYP3A4.[15][16] DXO is further metabolized into the inactive metabolite 3-hydroxy-morphinan (3HM).[22] Inhibition of CYP3A4 leads to less DXM being metabolized into 3MM and therefore more DXM being metabolized through the pathway of DXO, leading to higher plasma concentrations and slower degradation of DXO. Therefore, with enough grapefruit juice, the overall trip should be significantly more intense.

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 has not been studied in any scientific context and the exact toxic dosage is unknown.

Anecdotal evidence suggests that there do not seem to be any negative health effects attributed to simply trying DXM 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 may cause neurotoxicity and Olney's lesions, it has not been shown to cause this effect in animals [28], However, many chronic users report significant issues with memory, attention, and mood that persist for many months after stopping usage. In rats,[29] oral administration of dextromethorphan did not cause neurotoxic effects in laboratory tests.[30] Oral administration of dextromethorphan repeatedly during adolescence, however, has been shown to impair learning in those rats during adulthood.[31]

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

Dependence and abuse potential

As with other dissociatives, DXM produces dependence with chronic use and has moderate abuse potential. When dependence has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

A formal survey of dextromethorphan users[32] 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.[33]

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 produces 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. Some users claim that there is a "50 trip limit", after which the rewarding and unique effects of DXM are said to disappear permanently. The reason for this is unknown, although it may be indicative of neurotoxicity.

Overdose

Anecdotal evidence suggests that the risk of DXM overdose becomes significant at roughly 15mg/kg to 20mg/kg, or roughly 1000mg - 1500mg in a 70kg person.[citation needed] DXM overdose can have a wide range of effects, including delusions, hallucinations, psychosis, confusion, panic attacks, mania, sedation and severe balance issues, sometimes very inappropriate or violent behavior, increased heart rate, nystagmus and amnesia.[citation needed] The more serious side effects include anesthesia, respiratory depression[citation needed] and risk of accidental injury or self-harm. One should not disrupt a person undergoing this experience as their delusions may cause them to respond with violence. Care should be taken as to not let the user get injured, and medical attention should be sought to prevent severe respiratory depression and choking. Death from DXM toxicity is rare.

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The following lists some known dangerous combinations, but may not include all of them. A combination that appears to be safe in low doses can still increase the risk of injury or death. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume.

  • Stimulants - Combining stimulants with DXM is very dangerous and elevates the risk of high blood pressure problems, strokes, and brain hemorrhages.
  • 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.

Serotonin syndrome risk

Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.

Other interactions

  • Modafinil induces the CYP3A4 enzyme that DXM, and its metabolite DXO, are metabolized by.[35]
  • DXM has been shown to prevent and reverse morphine tolerance while also increasing analgesic effects[36][37][38] as well as potentiating the analgesic activity of NSAIDs, naproxen, piroxicam, etodolac, diclofenac, and ketorolac.[39]

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. It is available for legal 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.[citation needed]
  • Canada: Dextromethorphan is listed as specifically exempt from the Controlled Drugs and Substances Act.[40] 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).[41] Sales of DXM containing medications are restricted to pharmacies.[42] DXM containing preparations are available at pharmacies without a prescription.
  • Mexico: Dextromethorphan is not listed in the General Health Law (Ley General de Salud),[43] which specifies which substances represent a risk to public health. It is also listed in the Reference Medicine Listing[44] as a General Health Law article 226 fraction VI drug, which means it can be freely sold even in businesses that are not 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.[45]
  • Switzerland: Dextromethorphan is listed as a "Abgabekategorie C" pharmaceutical, which is sold exclusively in pharmacies without a prescription but needs approval of a medicinal.[citation needed]

See also

External links

Discussion

References

  1. Dicpinigaitis, P. V., Morice, A. H., Birring, S. S., McGarvey, L., Smith, J. A., Canning, B. J., & Page, C. P. (2014). Antitussive drugs—past, present, and future. Pharmacological Reviews, 66(2), 468-512.
  2. 2.0 2.1 2.2 "Dextromethorphan (DXM)". Cesar.umd.edu. Retrieved 2018-07-31.
  3. https://www.pharmacytimes.com/publications/issue/2008/2008-11/2008-11-8747
  4. 4.0 4.1 4.2 4.3 Morris, Hamilton; Wallach, Jason (2014). "From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs". Drug Testing and Analysis. 6 (7–8): 614–32. https://doi.org/10.1002/dta.1620. PMID 24678061.
  5. "Memorandum for the Secretary of Defense" (PDF). Archived (PDF) from the original on 2017-09-15. Retrieved 2013-07-28.
  6. "Senate Bill No. 514" (PDF). An act to add Sections 11110 and 11111 to the Health and Safety Code, relating to nonprescription drugs. State of California, Legislative Counsel. Archived (PDF) from the original on 2018-03-08.
  7. Dextromethorphan-induced serotonin syndrome (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19238739
  8. Dextromethorphan and Its Metabolite Dextrorphan Block α3β4 Neuronal Nicotinic Receptors | http://jpet.aspetjournals.org/content/293/3/962.long
  9. 9.0 9.1 Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 receptor activation in rats (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0197018607000381
  10. 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
  11. 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/
  12. 12.0 12.1 Comparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-Pituitary-Adrenal Axis | http://jpet.aspetjournals.org/content/309/2/515
  13. 13.0 13.1 13.2 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
  14. 14.0 14.1 Cytochrome P450-dependent metabolism of dextromethorphan: fetal and adult studies. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/1306804
  15. 15.0 15.1 15.2 15.3 15.4 15.5 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
  16. 16.0 16.1 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
  17. 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
  18. 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
  19. Dextromethorphan and Its Metabolite Dextrorphan Block α3β4 Neuronal Nicotinic Receptors | http://jpet.aspetjournals.org/content/293/3/962.long
  20. 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
  21. 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
  22. 22.0 22.1 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
  23. 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
  24. 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
  25. 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
  26. 26.00 26.01 26.02 26.03 26.04 26.05 26.06 26.07 26.08 26.09 26.10 Reissig, C. J., Carter, L. P., Johnson, M. W., Mintzer, M. Z., Klinedinst, M. A., & Griffiths, R. R. (2012). High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens. Psychopharmacology, 223(1), 1-15. https://doi.org/10.1007/s00213-012-2680-6
  27. Bailey, D., Malcolm, J., Arnold, O. & Spence, J. D. 1998. Grapefruit juice–drug interactions. Br J Clin Pharmacol; 46: 101–110. https://doi.org/10.1046/j.1365-2125.1998.00764.x
  28. https://www.erowid.org/chemicals/dxm/dxm_health2.shtml
  29. 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
  30. Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17573115
  31. 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
  32. Side effects of dextromethorphan abuse, a case series (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16122622
  33. Center for Substance Abuse Research - DXM | http://www.cesar.umd.edu/cesar/drugs/dxm.asp
  34. 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
  35. Clinical pharmacokinetic profile of modafinil. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/12537513
  36. Dextromethorphan attenuates and reverses analgesic tolerance to morphine. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/7708410
  37. 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
  38. 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
  39. 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
  40. Controlled Drugs and Substances Act (S.C. 1996, c. 19) | http://laws-lois.justice.gc.ca/PDF/C-38.8.pdf
  41. "Anlage I-III", BTMG | http://www.gesetze-im-internet.de/btmg_1981/
  42. § 43 AMG | http://www.gesetze-im-internet.de/amg_1976/
  43. http://www.diputados.gob.mx/LeyesBiblio/pdf/142_220617.pdf
  44. https://www.gob.mx/cms/uploads/attachment/file/178695/LMR_2017-07_V001.pdf
  45. Russian controlled substances lists | http://base.garant.ru/12112176/