Dextromethorphan

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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 75 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.

Interactions
Benzodiazepines
DOx
25x-NBOMe
2C-T-x
5-MeO-xxT
Amphetamines
Cocaine
ΑMT
PCP
MDMA
Alcohol
GHB
GBL
Opioids
Tramadol
MAOIs
SSRIs


Dextromethorphan (also known as robo, dex, DM, and DXM) is a dissociative substance of the morphinan class. DXM is the primary active ingredient 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]

Subjective effects include dissociation, time distortion, bodily hallucinations, immersion enhancement, motor control loss, euphoria, and ego loss. Users commonly describe low doses as producing an alcohol-like intoxication while higher doses produce effects similar to ketamine or PCP. 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, neutral, or dull, while others report mystical-like psychedelic experiences.

It should be noted that DXM in freebase form (as found in Robocough RoboTablets) is around 27-37% more potent than its hydrobromide form due to a higher concentration of DXM by weight. One should take this into account when calculating their dose so as to avoid a potential overdose.

The toxicity of DXM in recreational 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-opioid 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]

Variations of how individual persons metabolize DXM may significantly alter the nature of the experience. Poor metabolizers clear less DXM than the average person, leading to a higher ratio of DXM to DXO in the bloodstream[18], as well as overall increased potency and duration, due to less lost to the largely inactive metabolites 3MM and 3HM. CYP2D6 and CYP3A4 inhibitors have a similar effect.

Dextrorphan

Dextrorphan is produced by O-demethylation of dextromethorphan through the CYP2D6 enzyme and contributes to the psychoactive effects of dextromethorphan.[19] 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[20] 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.[21] It has local anaesthetic effects.[22]

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[23]. 3-Hydroxymorphinan exhibits neuroprotective and neurotrophic effects.[24][25][26]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a literature based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses are more likely to induce the full spectrum of effects. Likewise, adverse effects become much more likely with higher doses and may include serious injury or death.

Physical effects
Child.svg

    • Stimulation[27] & Sedation - At lower, recreational doses, DXM is predominantly stimulating. However, it can produce waves of tiredness, or the desire to lay down with the eyes closed in a sleep-like state. As higher dosages are approached, the experience generally turns very sedating and lethargic, sometimes resulting in the user not moving at all.
    • Perception of bodily lightness - This creates the sensation that the body is floating and has become entirely weightless. This effect is strangely stimulating and encourages physical activities at low to moderate dosages by making the body feel light and effortless to move.
    • Spontaneous bodily sensations - The DXM "body high" is a sharp, pleasurable and warm tingling sensation which can be localized to the hands, feet, and head. In lower doses, it can produce an empowering stimulated sensation, at higher dosages a slight to heavy body load.
      • Physical euphoria - This results in feelings of physical euphoria which range between mild pleasure to powerful, all-encompassing bliss.
    • Appetite suppression - Appetite suppression on DXM is very strong and may persist through the next day.
    • Changes in felt bodily form - This becomes quite prominent at moderate or high doses.
    • Motor control loss[27] - A loss of gross and fine motor control alongside balance and coordination is prominent within DXM and becomes especially strong at higher dosages. One should be sitting down before the onset to prevent falling over and becoming injured.
    • Spatial disorientation[27] - A spinning sensation is commonly felt that can result in mild disorientation as if one were falling through a hole.
    • Nausea[27] - DXM can sometimes produce extreme nausea and vomiting, typically during the come up phase of the experience. This is more intense and consistent than the nausea produced by ketamine and MXE. This is likely not caused just by DXM itself, but rather by the medium which contains the DXM, which is usually syrup or gelatin capules. When pure DXM is consumed it is rare to experience nausea.
    • Temperature regulation suppression
      • Increased bodily temperature- Since Dextromethorphan is a moderate serotonergic substance, it increases body temperature slightly at moderate to high doses.
    • Increased blood pressure[27]
    • Increased heart rate[27]
    • Increased perspiration - This is the result of a combination of increased bodily temperature and temperature regulation suppression.
    • Muscle spasms
    • Orgasm suppression
    • Decreased libido
    • Itchiness - This effect is colloquially known as "robo-itch". Many users never experience this effect while some individuals can experience it quite intensely. It is caused by histamine release.[citation needed]
    • Cough suppression - Since dextromethorphan is a commonly sold cough medicine, it will have the same effect in recreational doses.
    • Pain relief
    • Optical sliding
    • Dizziness - At higher dosages this can result in incapability to willingly stand up.
    • Gustatory hallucination
    • Physical autonomy - At very high dosages some may find to awake in strange locations, sometimes while standing or performing actions with no recollection of events or how they got there.
    • Tactile suppression - This partially to entirely suppresses sense of touch, creating feelings of numbness within the extremities. It is responsible for the anesthetic properties of this substance.
    • Pupil dilation- Pupil dilation is very noticeable at moderate to high doses but is less prevalent at low doses in the 1st plateau.
    • Gait alteration - This is a common effect on DXM and is commonly referred to as "robo walking". As with itchiness, some users may never experience this effect while others may experience it quite intensely.

Visual effects
Eye.svg

  • Enhancements

    Suppression

    • Double vision - This component is prevalent at moderate to heavy dosages and makes reading impossible unless one closes an eye.
    • Pattern recognition suppression - This effect generally occurs at higher dosages and makes one unable to recognize and interpret perceivable visual data. Examples can include an inability to recognize faces or motion.
    • Frame rate suppression - This is the so-called "flanging" effect, which at appropriately high doses can affect sight, sound and at higher levels phrases, faces and thinking.
    • Nystagmus - At very high dosages one may be incapable of recognizing things such as movement of objects or human faces.
    • Visual acuity suppression - Vision is reported to be very dream-like.

    Distortions

    Geometry

    The visual geometry produced by DXM can be described as very bright, colorful, psychedelic and intricate when compared to that of ketamine or MXE, but darker than psychedelics like LSD. There are moments where the perceived geometry may start to slow down, wobble or freeze, which is not usually seen with psychedelics or dissociatives. Spontaneously they can transform into a hallucinatory state with the eyes closed. It does not extend beyond level 4 and can be comprehensively described through its variations as intricate in complexity, algorithmic in style, synthetic in feel, unstructured in organization, brightly lit in lighting, multicolored in scheme, glossy in shading, soft in edges, small in size, slow in speed, equally smooth and jittery in motion, equal in rounded and angular corners, immersive in-depth and consistent in intensity.

    Hallucinatory states

    At high dosages, DXM can produce a full range of high level hallucinatory states in a fashion that is less consistent and reproducible than that of many other commonly used psychedelics. These effects include:

Cognitive effects
User.svg

Auditory effects
Volume-up.svg

Disconnective effects
Chain-broken.svg

Multi-sensory effects
Gears.svg

    • Synaesthesia - In its fullest manifestation, this is a very rare and non-reproducible effect. Increasing the dosage can increase the likelihood of this occurring, but seems only to be a prominent part of the experience among those who are already predisposed to synaesthetic states.

Transpersonal effects
Infinity4.svg

Afterglow
Afterglow-placeholder.svg

  • The afterglow is a feeling that can occur in the following day(s) after the experience. It can be described regarding its physical sensation as one of euphoria, rejuvenation, relaxation and a light bounciness. Regarding its cognitive effects, it often comes in the form as a loss of anxiety, feelings of content, and a noticeable increase in one's ability to appreciate music and other sensory stimuli that are sometimes accompanied with mild derealization or depersonalization.

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, while 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 plateau, sounding very rich, clear, and amplified. Bass is more powerful. Feelings of bodily lightness are common on this plateau.

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; however, music can also become tinny sounding, distorted, and difficult to hear. Sometimes though it can be heard clearly (often when taken alongside Cannabis), 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 yawning).

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. Amnesia can occur, leading to memory blackouts or brownouts. 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. In recent years in the United States, a DXM formulation called RoboCough (which has no other active ingredients, and comes in small bottles) has become popular.
  • 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. However, one should still test their powder to avoid ingesting toxic byproducts or if the preparation doesn't contain DXM at all.


It is important not to overdose on other active ingredients or a combination of them. Common ingredients also contained in cough syrup and pills include:

  • Acetaminophen: Also named Paracetamol or APAP, it is a non-steroidal anti-inflammatory drug. The recommended dose of acetaminophen in adults is 650 to 1,000 mg every 4 to 6 hours, not to exceed 4,000 mg in a 24-hour period. Single doses of more than 150 mg/kg or 7.5 g in adults have been considered potentially toxic, although the minimal dose associated with liver injury can range anywhere from 4 to 10 g. This dose will be substantially lower for younger adults.[28]
  • Guaifenesin: The maximum recommended daily dose for Guaifenesin is 2.4 grams. Guaifenesin overdose up to 4 grams or more have not been associated with overdose symptoms, besides causing nausea and vomiting.[29] This should however not be taken as a lead and guaifenesin overdose should be avoided if possible.
  • Chlorphenamine: Known as an active ingredient in Coricidin, chlorphenamine acts as a blood pressure stabilizer. Chlorphenamine overdose has led to a number of circulatory complications and in combination with dextromethophan has resulted in many overdoses and death.[citation needed] Chlorphenamine should be avoided when taken in combination with DXM.
  • Phenylephrine: The maximum daily dose should be under 60 milligrams. Phenylephrine overdose has been associated with a range of dangerous cardiovascular problems which may be amplified further by dextromethorphan.[citation needed] Phenylephrine should be avoided when taken in combination with DXM.
  • Pseudoephedrine: Overdose can result in cardiovascular problems.[citation needed] Pseudoephedrine should be avoided when taken in combination with DXM.
  • Caffeine: Caffeine overdose can result from as few as 400 to 600 milligrams. May increase cardiovascular side effects of DXM, but the extent to this is unknown.[citation needed] Caffeine should be avoided when taken in combination with DXM.
  • Diphenhydramine: Diphenhydramine in combination with dextromethorphan has a very low threshold for delirium and a complete detachment of reality. May also strain the circulatory system and heart in high doses.[citation needed]
  • Aspirin: Aspirin overdose starts below 300mg/kg and can become deadly at 500mg/kg.[citation needed] Higher doses of aspirin should be avoided in combination with DXM.
  • Dextromethorphan polistirex: This type of Dextromethorphan is used in the common brand Desylum for long cough and cold relive. The polistirex around the dextromethorphan causes the high of DXM to last much longer than intended with some reports of the high lasting 18-24 hours instead of normal DXM lasting around 8-12 hours, which for some users could be very unpleasant. On top of that, you need more DXM polistirex to get the same high as regular DXM. This could lead to someone using too much DXM polistirex and overdosing to get the same effects as a moderate too high dose of normal DXM without the polistirex.
  • Doxylamine: This drug is found in NyQuil and is used as a sleep aid so the user has an easier time sleeping. Doxylamine's median lethal dose (LD 50) is estimated to be 50–500 mg/kg in humans and when ingested with DXM will have a very low threshold for delirium and complete detachment of reality due to the fact that it is a generation one antihistamine just like Diphenhydramine. Doxylamine in combination with DXM can also cause strong sedation and ataxia when combined with each other which would lead to impaired thinking and possibly unconsciousness.

Potentiation

Grapefruit juice is reported to be effective at potentiating the effects of DXM. For users who are drinking store bought syrup, this is useful as it means drinking less syrup.

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).[30] 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).[23] 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.

Near maximal pharmacokinetic interaction of grapefruit juice remains for 4 hours after the ingestion of a modest quantity (200–250 mL), and ingesting an amount beyond that doesn't increase effects significantly. On the other hand, frequent consumption of a modest quantity at least three times for a day or more augments the pharmacokinetic effect moreso than a lone (even if greater) quantity. The enzyme inhibition effect also takes longer to wear off, suggesting a cumulative effect when consumed frequently.[31]

Preparation methods

Preparation methods for this compound within our tutorial index include:

Toxicity and harm potential

Further information: Responsible use § Hallucinogens

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 [32], However, many chronic users report significant issues with memory, attention, and mood that persist for many months after stopping usage. In rats,[33] oral administration of dextromethorphan did not cause neurotoxic effects in laboratory tests.[34] Oral administration of dextromethorphan repeatedly during adolescence, however, has been shown to impair learning in those rats during adulthood.[35]

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[36] 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.[37]

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], dangerously high fever, risk of accidental injury, self-harm and seizures. Seizures are created possibly due to hyponatremia and a general lowering of the seizure threshold.[citation needed] They are reported above the 900-1000mg dose range[citation needed]. It is possible that DXM may also affect other levels like potassium, vitamins or blood sugar further contributing to seizues and other health problems in a linear fashion in terms of severity and duration.

It is also believed that extremely high and repeated doses lead to serotonin syndrome.[citation needed]

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, or at the very least, medical surveillance should be sought to prevent severe respiratory depression, choking or organ damahe. Death from DXM toxicity is rare, although most overdose cases do cite life-threatening complications, typically extremely elevated heart rate and blood pressure, urinary retention and rhabdomylosis. Fever and seizures can lead to brain cell death.[38]

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.

  • Benzodiazepines - Small doses of benzodiazepines can end a bad trip, however, both substances potentiate the ataxia and sedation caused by the other. This can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position.
  • DOx - The DOx class as psychedelic stimulants have the potential to mask the effects of DXM and could lead to redosing to an unsafe level. DXM can also potentiate DOx resulting in an unpleasantly intense experience. DOx are also very physically stimulating and can cause heart rate and blood pressure problems especially since both substances have a very long duration.
  • 25x-NBOMe
  • 2C-T-x - As most 2C-T-x's are MAOIs this can potentially lead to serotonin syndrome, among other dangerous effects.
  • 5-MeO-xxT - Little information exists about this combination.
  • Amphetamines - Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues.
  • Cocaine - Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues
  • ΑMT
  • PCP - Due to PCP's unique pharmacology affecting dopamine levels this may cause cardiovascular complications.
  • MDMA - High risk of serotonin syndrome due to the fact that both MDMA and DXM are both serotonergic substances.
  • Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Additionally CNS depression can lead to difficulty breathing. Avoid on anything higher than 1st plateau.
  • GHB - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the patient falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. This combination is hard to predict
  • GBL - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the patient falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. This combination is hard to predict
  • Opioids - Both substances can, with heavy doses, cause respiratory depression, and additionally, extremely heavy doses of both may be hepatotoxic. Additionally, use of NMDA antagonists such as dextromethorphan can lower tolerance to and potentiate opioids, increasing their effects.
  • Tramadol- Both substances can, with heavy doses, cause respiratory depression and if heavy doses are taken both may be hepatotoxic. Additionally, if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
  • MAOIs - High risk of serotonin syndrome.
  • SSRIs - High risk of serotonin syndrome.

Other interactions

  • Modafinil induces the CYP3A4 enzyme that DXM, and its metabolite DXO, are metabolized by. This means that mixing DXM and Modafinil together would potentiate the effects of DXM[39]
  • DXM has been shown to prevent and reverse morphine tolerance while also increasing analgesic effects[40][41][42] as well as potentiating the analgesic activity of NSAIDs, naproxen, piroxicam, etodolac, diclofenac, and ketorolac.[43]

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.[44] 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).[45] Sales of DXM containing medications are restricted to pharmacies.[46] DXM containing preparations are available at pharmacies without a prescription.
  • Mexico: Dextromethorphan is not listed in the General Health Law (Ley General de Salud),[47] which specifies which substances represent a risk to public health. It is also listed in the Reference Medicine Listing[48] 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.[49]
  • Sweden: Dextromethorphan is no longer marketed in Sweden due to drug abuse and associated risks. The cough medicine Tussidyl, with DXM as active ingredient, was withdrawn from Swedish sales in 1999.[citation needed]
  • Switzerland: Dextromethorphan is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a prescription.[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. ↑ The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: The role of gut CYP3A and P-glycoprotein | https://doi.org/10.1016/S0024-3205(02)01799-X
  19. ↑ 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
  20. ↑ Dextromethorphan and Its Metabolite Dextrorphan Block α3β4 Neuronal Nicotinic Receptors | http://jpet.aspetjournals.org/content/293/3/962.long
  21. ↑ 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
  22. ↑ 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
  23. ↑ 23.0 23.1 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
  24. ↑ 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
  25. ↑ 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
  26. ↑ 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
  27. ↑ 27.00 27.01 27.02 27.03 27.04 27.05 27.06 27.07 27.08 27.09 27.10 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
  28. ↑ https://www.uspharmacist.com/article/acetaminophen-toxicity-what-pharmacists-need-to-know
  29. ↑ https://www.medsafe.govt.nz/Consumers/cmi/CoughandCold/Guaifenesin1.pdf
  30. ↑ 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
  31. ↑ https://dx.doi.org/10.1503%2Fcmaj.120951 | Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?
  32. ↑ https://www.erowid.org/chemicals/dxm/dxm_health2.shtml
  33. ↑ 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
  34. ↑ Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17573115
  35. ↑ 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
  36. ↑ Side effects of dextromethorphan abuse, a case series (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16122622
  37. ↑ Center for Substance Abuse Research - DXM | http://www.cesar.umd.edu/cesar/drugs/dxm.asp
  38. ↑ https://www.erowid.org/experiences/exp.php?ID=3547
  39. ↑ Clinical pharmacokinetic profile of modafinil. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/12537513
  40. ↑ Dextromethorphan attenuates and reverses analgesic tolerance to morphine. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/7708410
  41. ↑ 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
  42. ↑ 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
  43. ↑ 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
  44. ↑ Controlled Drugs and Substances Act (S.C. 1996, c. 19) | http://laws-lois.justice.gc.ca/PDF/C-38.8.pdf
  45. ↑ "Anlage I-III", BTMG | http://www.gesetze-im-internet.de/btmg_1981/
  46. ↑ § 43 AMG | http://www.gesetze-im-internet.de/amg_1976/
  47. ↑ http://www.diputados.gob.mx/LeyesBiblio/pdf/142_220617.pdf
  48. ↑ https://www.gob.mx/cms/uploads/attachment/file/178695/LMR_2017-07_V001.pdf
  49. ↑ Russian controlled substances lists | http://base.garant.ru/12112176/


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