The Dextromethorphan reference article from the English Wikipedia on 24-Apr-2004
(provided by Fixed Reference: snapshots of Wikipedia from wikipedia.org)

Dextromethorphan

Videos show Africa through the eyes of children
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 first plateau dose of dextromethorphan, which extends to a 2.5 mg/kg dose (up to ten times maximal recommended dose for a 200 pound adult).

The effects of dextromethorphan tend to be nonlinear with respect to dosage. DXM users soon developed unique terminology describing the unique effects of dextromethorphan. Unlike most substances, the effects of dextromethorphan tend to be described as four discrete sets of effects, commonly called plateaus. The first plateau, often described in terms of dextromethorphan dosage per body weight, is characterized by a noticeable "speedy" effect. 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 is possibly unaware of his physical surroundings. The dosages associated with the various plateaus have been described extensively in the DXM FAQ (see external links.)

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.

Low quantities of dextromethorphan can cause euphoria of a sort, though most would not suggest that DXM be used as a substitute for marijuana or ecstasy, both of which can--unlike large quantities of DXM--be used alone in relative safety. It is for all practical purposes simply not possible for a person under the influence of upper plateau quantities of DXM to appear sober offline, 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.

At and above the second plateau (see below) the user generally feels "disconnected" from reality, or disoriented. 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. Also, high-dose use of DXM brings a separation from reality which has much in common with forms of psychosis.

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 coloquailly 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.

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 casually 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 (high possibility of liver damage with as few as eight pills) and the anticholinergic drug contained in Coricidin. Cough supressents 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 lingering death over several 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.

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 used together because DXM gives stimulant effects itself.

Coricidin Cough and Cold in particular, known as CCC in the 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 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. 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 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.

Most drugs have an effect that, essentially, 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 grouped into "plateaus", of which there are typically regarded to be four. The first plateau is mildly euphoric, and tends to allow physical activity. The second plateau can result in delusion, and those encountering the user will be likely to realize they are high. The third and fourth plateaus, which according to most should not be explored without a sober trip sitter, are partially to fully dissociative. For more info, see the DXM FAQ, available by searching the web, or from several of the links below. This resource was last officially maintained in the 20th century, but is still extremely useful for anyone considering use of DXM.

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, and 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 are quite frightening, and are largely used for spiritual self-improvement. Psychotic breaks are more common in the upper two plateaus.

While DXM is not a safe drug (and some would argue that there are no safe drugs) by any means, and has a truly horrific taste (in its pure form, or as cough syrup), it is recommended that users do not smoke it, since this creates toxic materials. Additionally, users should not inject DXM, since injection, even with sterile equipment, can be quite hazardous in the hands of the inexperienced. In addition, the high recreational dose of DXM compared to some illegal drugs, coupled with its marginal solubility in water, require injecting a large quantity of material, a good recipe for a sterile abcess. Swallowing may not be pleasant, but it is the safest option.

There is speculation that high doses of DXM may cause brain damage. John Olney demonstrated that high doses of NMDA antagonists, the class of drugs to which DXM belongs, caused brain cell death in animal studies. 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 not be taken by those taking either prescribed prescription or OTC medications, particularly antidepressants. The reason is two-fold: many medications are either substrates or inhibitors by the liver enzyme used in the metabolism of dextromethorphan, and with antidepressants there is risk of developing serotonin syndrome.

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 with milkweed sap.

External links