The Dextromethorphan reference article from the English Wikipedia on 24-Jul-2004
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Dextromethorphan

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Dextromethorphan hydrobromide (DXM for short) is a cough suppressant drug with chemical formula C18H25NO HBr, found also in certain over-the-counter cold remedies and cough syrups. Less common names of this substance include d-Form hydrobromide of Racemethorphan and demorphan hydrobromide. Dextromethorphan is also designated as (+)-3-methoxy-17-methyl-(9alpha,13alpha,14alpha)-morphinan.

Table of contents
1 History
2 Pharmacology
3 Effects
4 Legality
5 Safety
6 Dangers
7 External links

History

Dextromethorphan was first patented with U.S. Patent 2,676,177. In the 1960's, a tablet form of dextromethorphan was marketed in the United States and abroad as Romilar. As Romilar was marketed as an alternative to codeine, it was soon discovered that high doses of dextromethorphan had psychedelic effects by those who used codeine. For some time, many doctors denied that the drug was psychoactive; indeed, it for all intents and purposes is not in the recommended dose.

Pharmacology

Molecular structure of dextromethorphanEnlarge

Molecular structure of dextromethorphan

Dextromethorphan is the d-isomer of the opioid agonist levomethorphan. It has practically no analgesic or opioid-like dependence-producing properties. Being a potent antitussive it largely replaced codeine in this indication and is available in numerous antitussive drugs or formulations. Dextromethorphan has been shown to be an antagonist at the N-methyl-d-aspartate (NMDA) receptor in the brain.

An active metabolite of dextromethorphan is dextrorphan, the 3-hydroxy derivative of dextromethorphan. The effects of dextromethorphan are believed to be caused by both dextromethorphan and dextrorphan. Dextromethorphan is predominantly metabolized by the liver, by the liver enzyme known as CYP2D6. However, a small percentage of humans are deficient in this enzyme. As CYP2D6 is the primary metabolic pathway in breaking down dextromethorphan, the duration and effects of dextromethorphan are significantly intensified in those who are poor CYP2D6 metabolizers. A significant proportion of recreational deaths and hospitalizations result from users with that condition taking the same doses their friends may have recommended. Several antidepressant medications are potent inhibitors of CYP2D6. Dextromethorphan should not be taken at recreational dosages by those taking prescribed medications, particularly antidepressants. MAOI antidepressants are especially dangerous; death has resulted from combining dextromethorphan with a MAOI. Do not take dextromethorphan, even at therapeutic doses, within 2 weeks of taking a MAOI or vice versa. One of the MAOI deaths resulted from taking two ounces of cough syrup - which is equivalent only to 2-6 times the labeled dose.

Once dextromethorphan penetrates the blood-brain barrier, it demonstrates affinity towards several sites in the brain. Specifically, it:

Effects

The advantages of dextromethorphan over
codeine are the absence of constipation and (physical) addiction; it is also less sedative, and has little to no psychological effect in the doses used medically (typically no more than 30 mg, or slightly more, spread over several hours; 10-15 mg is a common dose in cough syrups). It is safe to assume that addiction is impossible, or phenomenally improbable, for use as recommended; the medical dose of dextromethorphan likely has less psychological effect than the alcohol in mouthwash, and definitely less than the caffeine in some headache remedies. Addiction has not been reported with a first plateau dose recreational dose of dextromethorphan, which extends to a 2.5 mg/kg dose (up to ten times maximal recommended dose for a 200 pound adult). A somewhat overweight adult man might have to take 15 pills to reach the top of that range.

The FDA approved dose of dextromethorphan is 30mg. In significantly higher doses of 150 mg to 2 g, dextromethorphan is recreationally used as a psychedelic drug that can cause dissociation and dreamlike mental effects, as well as visual and aural hallucinations that can last eight hours or longer in sufficiently high dosage, and can even include "out of body experiences" at very high doses, though this is uncommon; some use high doses for attempts at spirituality or self-knowledge.

Slang terms for DXM include tussin (generic and store-brand cough syrup is often sold under the name Tussin). Use of DXM for its psychoactive effects is often referred to coloquially as "dexing," "tussing," or "robotripping" (the latter term appears to be derived from Robitussin, a brand name of a popular line of over-the-counter products containing the drug). DXM is not one of the most commonly abused drugs, at least deliberately; see mention of MDMA below.

Most drugs have an effect that is proportional to the dose — drinking twice as much coffee will make one more alert and restless, but will not have significantly different effects. DXM, however, is unusual in that its effects are nonlinear with respect to dose, and are grouped into "plateaus", of which there are typically regarded to be four. DXM users soon developed unique terminology describing the unique effects of dextromethorphan. Plateaus are usually described in terms of dextromethorphan dosage per body weight (i.e. mg/kg). The dosages associated with the various plateaus have been described extensively in the DXM FAQ (see external links).

The first plateau is characterized by a slight but noticeable "speedy" stimulant effect, a feeling of inebriation, and an altered sense of movement and position. The second plateau is an extension of the first plateau. The third plateau has a set of effects that are significantly "darker" than the earlier plateaus, and lead to a significantly dissociated effect. The fourth plateau is an extremely dissociative effect, to the point that the user becomes totally unaware of their physical surroundings.

The first plateau can be mildly euphoric, and tends to allow somewhat normal physical activity. Movement can feel pleasurable (motion euphoria). Music may sound incredible, or totally wrong. The second plateau results in a noticeably different shuffling gait (the so-called robo-walk), and can occasionally result in mild delusions of reference. Intermediate-term and working memory is more impaired, and time distortion becomes apparent. Some users have a wide-eyed staring expression (though they may not realize it) at and above these dose levels. Those encountering a user at or above the second plateau will likely realize they are high. Starting at higher second plateau dosages, the user generally feels "disconnected" from reality.

The third and fourth plateaus — which according to most should not be explored without a sober trip sitter — are partially to fully dissociative. At these very high doses, the user may not want to move around, or may not be consciously capable of movement. However, due to confusion, disconnection from reality, and delusions, the presence of an experienced sitter is recommended.

While low doses of dextromethorphan can cause euphoria of sorts, most would not suggest that DXM be used as a cheap, quasilegal substitute for marijuana or ecstasy, both of which can — unlike large quantities of DXM — be used alone in relative safety, albeit with possibly decreased enjoyment.

It is for all practical purposes simply not possible for a person under the influence of upper plateau quantities of DXM to appear sober in person or on the phone due to confusion and very slow reaction time (multiple seconds). Do not drive on DXM, or swim either alone or on more than first plateau quantities.

DXM can also cause vomiting, fever and death. There is also the possibility of psychological addiction. Two deaths are in the medical literature for use of DXM alone, one of which was a suicide. This should be contrasted with almost all other drugs, legal and otherwise. However abuse of DXM bears risks such as brain damage and psychotic breaks which have not occurred with many drugs (and are probably impossible with marijuana, ecstasy, and sane doses of LSD, among others). Also, high-dose use of DXM brings a separation from reality which has much in common with forms of psychosis. Extreme schizophrenic hallucinations (hearing voices, seeing entities with eyes open, experiencing a breakdown of reality) are the hallmark of Plateau Sigma. Over half the people who had a Plateau Sigma experience have said it was extremely unpleasant and that they would never repeat it.

For more information, see William White's DXM FAQ, available by searching the web, or from several of the links below. This resource is considered one of the most useful for anyone considering use of DXM. It should be noted that the FAQ was last updated in the Clinton administration, and does not include recent deaths, particularly due to Coricidin Cough and Cold (CCC).

Legality

Unlike ketamine and PCP, DXM is legal in most places. The dissociative experiences associated with DXM are similar to those of ketamine. Dextromethorphan has a longer biological half life than ketamine, and the unpleasant side effects are considered by some to be worse. Since DXM is legal, it is available in pure form from several online sources, typically for "research purposes only". The price for a high dose of two grams is typically under five dollars; this kind of dose will typically lead to a completely dissociative experience, or can be broken up for more casual recreational use; see below.

In 2004, bills were introduced in several state legislatures in the United States to prohibit the sale of products containing DXM to those under 18 years of age, and other proposed legislation would set a limit on the quantity of DXM that may be purchased at one time by any individual regardless of age.

Safety

Most over-the-counter cough medicines contain other drugs besides dextromethorphan and can be quite dangerous when taken in high doses. These ingredients include acetaminophen, also known as paracetamol or APAP (very high possibility of fatal liver damage with as few as eight acetaminophen-containing pills) and chlorpheniramine maleate (a deleriant antihistamine which can cause severe allergic reactions and death) contained in Coricidin. Coricidin has been linked to at least twelve deaths in the United States from chlorpheniramine maleate overdose. DO NOT use Coricidin recreationally! Some cough suppressants also often contain guaifenesin which contributes to the nausea and vomiting that some experience when taking this drug.

Acetaminophen in particular deserves more detailed discussion. There are three enzymatic pathways used in the liver to break it down, and the two typically found are safe for the body. When these two become overwhelmed, the third pathway processes acetaminophen into a chemical that is quite toxic to the liver. Fatal liver damage can occur before any symptoms become evident, causing a painful, lingering death over several days to weeks; additionally, a user who is in a hangover from significant quantities of DXM may not notice that anything is wrong even once symptoms begin to occur. To put it simply, acetaminophen-containing preparations are not safe for recreational use, and in high recreational quantities death is the more probable outcome. Liver toxicity can occur at doses as low as 8-10 pills, at the bottom of the first plateau. Acetaminophen overdoses can be corrected without much permanent harm as long as the individual gets to an emergency room within about eight hours. After that, toxic effects become apparent.

Other preparations contain high doses of pseudoephedrine, a stimulant drug that's very closely related to ephedrine. It is unwise for high doses of these drugs to be purposefully used together because DXM gives stimulant effects itself. High doses of pseudoephedrine can raise blood pressure to dangerous levels, bringing with it the chance for a glaucoma crisis, heart attack, stroke, and death.

Coricidin Cough and Cold in particular, known as CCC in the DXM community, is a typical source of DXM for casual users, especially those in high school who may not have credit cards and so cannot buy pure DXM from online merchants, and who see it as a preferable alternative to large quantities of cough syrup. Many deaths or psychotic breaks have resulted from abuse of Coricidin in particular. It contains a drug (chlorpheniramine maleate) that is broken down by the same liver enzyme that decomposes DXM, and taking more than the recommended dose of Coricidin can be highly hazardous. Coricidin has been linked to at least twelve deaths in the United States from chlorpheniramine maleate overdose. DO NOT use Coricidin recreationally! Coricidin has a track record of causing deaths and hospitalizations in upper first plateau doses, even among those who have been abusing it for years.

Also, some young users have taken to shoplifting CCC and similar preparations to such an extent that some stores do not carry them, or make them available only by asking the pharmacist. The general opinion in the DXM community is that CCC is simply not safe for recreational use. It has caused many dozens of hospitalizations, and several deaths, and the general advice is that for those who cannot get other products is to either not use DXM, or use products (largely syrups) with no other active ingredients. CCC should not be regarded as a safe source of DXM for anyone, in any quantity beyond that recommended on its labeling.

Dangers

It should be noted that the symptoms of upper second plateau and higher DXM use are nearly impossible to conceal, and may be quite frightening, especially to those who do not know that the user has used a drug; they are similar to a temporary psychosis. At the fourth plateau the individual has little to no connection with external reality, and may have extreme difficulty moving. Most users find that use at or below the second plateau is more pleasant; the two upper plateaus can be quite disturbing or frightening, and are largely used for spiritual self-improvement. Psychotic breaks are more common in the upper two plateaus.

While DXM has a truly horrific taste (in its pure form or extract, or as cough syrup), and is not a safe drug if taken in any manner, it is considered difficult to inject and almost impossible to smoke. DXM HBr and the free base have very high vaporization points, and if the user extracted the chemical from commercial cough preparations, some of the inactives may have survived the extraction to yield a very harsh, possibly toxic smoke.

Additionally, users should not inject DXM, since injection, even with sterile equipment, can be quite hazardous in the hands of the inexperienced. One of the problems with injecting DXM HBr is its marginal solubility in water compared to other injected drugs. Due to this low solubility and high dose (into the gram range, higher than almost every drug except alcohol), injection of DXM would require injecting a large quantity of material — a good recipe for a sterile abscess. Swallowing may not be pleasant, but it is the safest option.

There is speculation that high doses of DXM may cause brain damage in the form of NAN (NMDA antagonist neurotoxicity). John Olneydemonstrated that high doses of NMDA antagonists, the class of drugs to which DXM belongs, caused brain cell death in animal studies. The characteristic brain lesions produced are thus named Olney's lesions. The doses required to instantly produce damage are far in excess of human recreational doses, but there have not been studies on long-term, lower-dose use. Since detecting the cell death requires an autopsy, it has not been studied in humans. Furthermore, DXM ingestion has been linked to several deaths, including some where only pure DXM was involved.

DXM should only be taken with extra caution and reading by those taking either prescribed prescription or OTC medications, particularly antidepressants. The reason is two-fold: with antidepressants there is risk of developing serotonin syndrome, and many medications are either substrates or inhibitors by the liver enzyme used in the metabolism of dextromethorphan. This has the effect of minimizing hallucinations but maximizing confusion, and can cause the trip to literally last for days. A first or second plateau trip is probably nothing to worry about, though you may not enjoy all the effects your non-medicated friends might.

Since DXM is legal, and a highly psychoactive dose can be purchased in bulk for the cost of a box of cereal, it is often sold as MDMA (aka Ecstasy), a practice that endangers users of MDMA.

While DXM significantly impairs judgement, and can confuse the user greatly, it is not a common drug in date rape since it has an extremely bitter taste, comparable only perhaps with milkweed sap. It would be nearly impossible to conceal an incapacitating dose of DXM in food or drink, due to its unbelievably bitter taste being noticeable in any food item.

External links