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Dextromethorphan

From Academic Kids

Much information has been taken almost directly from the DXM FAQ. While this is a public domain work, and has been linked to below, the origin of much text on this page is unclear.
Missing image
Dextromethorphan.png
Molecular structure of dextromethorphan


Dextromethorphan
D-(+)-3-methoxy-17-methyl-
(9α,13α,14α)-morphinan
CAS number
125-71-3
ATC code
R05DA09
Chemical formula C18H25NO
Molecular weight 271.4
Bioavailability  ?
Metabolism hepatic
Elimination half-life  ?
Excretion  ?
Pregnancy category C (United States)
A (Australia)
Legal status Schedule 2 (Australia)
Route of administration Oral
Indicated for:

Recreational uses:

Dextromethorphan hydrobromide (DXM for short) is an antitussive drug that is found in many over-the-counter cold remedies and cough syrups. In considerably higher doses, DXM is a powerful psychedelic drug. (Specifically, it is a dissociative drug. The dissociatives are a major subclass of the psychedelic drugs.) It is not physically addictive, but may be psychologically addictive (see below).

Contents

History

Dextromethorphan was first patented with U.S. Patent 2,676,177 (http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=/netahtml/srchnum.htm&r=1&f=G&l=50&s1=2,676,177.WKU.&OS=PN/2,676,177&RS=PN/2,676,177).

In 1958 the FDA approved the use of dextromethorphan as an anti-tussive, in response to the rampant recreational use of, and addition to, the now government-regulated codeine that was present in cough medicines at the time. The perceived advantages of dextromethorphan in comparison to codeine were the lack of physical addiction and the absence of a sedative-like effect from a normal dosage. Two years after its approval, dextromethorphan was finally marketed in the United States as Romilar, a dextromethorphan-only pill, which touted itself as the safe cough medicine alternative to the heavily abused codeine. While it did not take recreational codeine users long to unlock the abuse potential of dextromethorphan, it took thirteen years from Romilar’s initial debut for it to be withdrawn from the shelves.

The removal of Romilar from shelves in 1973 left many wondering if dextromethorphan would be phased out in favor of a new compound less susceptible to abuse that could alleviate coughs as well as codeine and dextromethorphan. Manufacturers instead re-released dextromethorphan to the public in syrup form, which was harder to abuse in quantity. While some allege that reports of abuse went down mainly because of the unattractive delivery agent, William White, a dextromethorphan researcher, suggests the plunge in DXM abuse cases was mainly due to the availability of more appealing hallucinogens such as LSD, and psilocybin (White, 1997).

The 1980s saw Dextromethorphan abuse remain localized in small communities of users as the War on Drugs began to ramp up its presence in a drug drenched United States. While many now regard DXM's potential for abuse as common knowledge, in the 1980s due to the lack of widespread Internet access and sources for reputable information on drugs, many were left in the dark about its dissociative properties.

The early 90s trend of DXM use followed closely to the 80s due to the War on Drugs, and the lack of information about dextromethorphan. The Internet began to take shape around the world at this time allowing many to communicate with a defined topic at hand. Much of the early dissemination of knowledge on DXM was conducted on Usenet, calling attention to an obscure recreational drug. As the availability of access to the Internet became more common, dedicated websites with more accurate (and more scientific) information concerning DXM appeared, and were easily found by many. This flow of information has only increased with time. The growth of the Internet and the ease of spreading information also led to deaths from DXM coming to light. There are now websites largely focusing on documenting the circumstances of these deaths.

The unique plateau model of DXM effects seems to have emerged largely from the Internet drug culture of the late 1990s, especially William White's comprehensive, book-length DXM FAQ. This document, which was little known outside the online drug community, details DXM's effects, chemistry and dangers in lengthy detail. Using science, history and hands-on reports from individual users, White's manual acted as a virtual how-to guide for the interested psychonaut or scholar. While originally presenting DXM as generally benign, White, receiving various reports from users reporting apparent long-term effects, changed his introduction to warn recreational users more vigorously.

Chemistry and Pharmacology

Dextromethorphan is the dextrorotary-enantiomer of the opioid-receptor agonist levomethorphan. Unlike most opioids, it has not been reported to possess significant analgesic properties or dependence-liability. It is, however, a potent antitussive and has largely replaced codeine in this indication. It is perhaps the most widely available and used antitussive currently marketed.

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 hepatic cytochrome P450 enzyme known as CYP2D6. There is a significant proportion of the population who have a functional deficiency in this enzyme (CYP2D6 poor metabolizers). As CYP2D6 is the primary metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan are significantly increased in such poor metabolizers. Deaths and hospitalizations have been reported in poor metabolizer recreational users.

A large number of medications (including antidepressants) are potent inhibitors of CYP2D6 (see CYP2D6 article). There exists, therefore, the potential of drug-drug interactions between dextromethorphan and concomitant medications. There have been reports of fatal consequences arising from such interactions.

Dextromethorphan crosses the blood-brain barrier, and the following pharmacological actions have been reported:

Effects

The advantages of dextromethorphan over codeine are the absence of constipation and physical dependence; 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 30 mg. 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. Some users also report an increased ability to understand abstract concepts.

Slang terms for DXM include tussin and robomax (generic and store-brand cough syrup is often sold under the name Tussin). Use of DXM for its psychoactive effects is often referred to colloquially as "dexing", "tussing", "robotripping" (based on Robitussin), or "skittling"and "triple C's" (based on Coricidin HBP Cough and Cold.) Both are brand names of a popular lines of over-the-counter products containing the drug).

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 mostly an extension of the first plateau, with sensory and motor effects becoming stronger; mild dissociation also starts on this 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. Sensory input (mostly sight and sound) begins to slow. Music tempo appears to become noticeably slower and visual perception begins to get choppy. It also becomes harder for the user to focus both eyes onto one object, and vision appears as if the brain cannot keep its inner model of the world in sync with the outside. 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 using DXM at recreational doses 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 or the Erowid DXM Valut (http://www.erowid.org/chemicals/dxm/dxm.shtml), available by searching the web, or from several of the links below. These resources are considered among 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

Missing image
Robitussin_togo.gif
Over the counter robitussin.

While DXM is legal to purchase from stores, it may be illegal to purchase bulk DXM that is intended for laboratory use only from online vendors, if one intends to use it recreationally. However, such illegality would have to fall under the jurisdiction of the FDA. The DEA cannot enforce sales or use of DXM, as DXM is specifically exempted from the Controlled Substances Act. The DEA in July, 2004, made arrests on several online vendors under the Federal Analogues Act of 1986; most of these vendors were pursued for selling analogues of controlled substances as well as DXM.

2003 saw Texas and North Dakota vote against bills that would prohibit the purchase of products containing DXM to minors. In 2004 California also followed suit and voted against a bill similar to the ones proposed in Texas and North Dakota. Although these three states have been unable to pass these bills, New York in 2004 passed legislation making the distribution of 2 or more Dextromethorphan containing products to a minor a criminal misdemeanor (Bill Summary - S06244). This variation in States’ decision to restrict the availability of Dextromethorphan from minors is a hotly contested federalist matter that advocates of abuse prevention must keep in mind while formulating programs.

In 2005, the Virginia General Assembly considered HB 2045, a bill to make distribution of DXM to minors a Class 1 misdemeanor[3] (http://leg1.state.va.us/cgi-bin/legp504.exe?051+sum+HB2045).

DXM is specifically excluded from regulation under the Schedules of the Single Convention on Narcotic Drugs[4] (http://www.un.org/documents/ecosoc/docs/1999/e1999-28.htm).

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 (high possibility of fatal liver damage with as few as eight acetaminophen-containing pills) and chlorphenamine (an anticholinergic antihistamine which can cause severe allergic reactions and death) contained in Coricidin Cough and Cold. Coricidin should not be used recreationally: see the paragraph on it below. 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 is 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 and dextromethorphan 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 (CCC) in particular 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 recreational use 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 Cough & Cold can be highly hazardous, especially to those individuals with a CYP2D6 enzyme deficiency and those with a history of allergic reaction to antihistamines, clorpheniramine in particular.

Also, some young users have taken to shoplifting CCC and similar preparations to such an extent that some stores have either stopped selling them (making it less available to legitimate users) or made them available only by request to the pharmacist (making bulk purchases impossible). CCC is generally not regarded as a safe source of DXM, especially in the amount required to achieve an upper-plateau trip. Very large amounts of CCC has caused many dozens of hospitalizations, and several deaths, and the general advice is that for those who wish to use more than 500 mg of DXM but cannot get it in pure form are to either not use DXM, or use products (largely syrups) with no other active ingredients.

Also, as mentioned above, there is a significant proportion (6-10% of caucasians) of the population who have a functional deficiency in the enzyme CYP2D6, which metabolizes DXM. These people will overdose very easily, even with a small recreational dose. This can lead to hospitalization, and death.

Dangers

There have been several dextromethorphan overdose deaths documented in medical and media reports. Even when used alone, dextromethorphan overdoses have been fatal. Lethal toxicity starts at around 20mg/kg (about 2000mg for a 220lb person). Overdose is possible while redosing; a person who is already under the influence of DXM may not be able to accurately weigh the next dose, or may forget how much s/he has already taken. Some users suggest that those who plan to redose with pure DXM weigh all doses in advance, then set their supply in a place where it is inconvenient to reach.

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 is toxic to smoke. DXM HBr and the freebase 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. Either way, DXM HBr releases ammonia and other toxins and should never be smoked.

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.

William E. White published a paper on Usenet claiming that high doses of DXM may cause brain damage in the form of NMDA antagonist neurotoxicity (NAN or Olney's lesions). John Olney demonstrated 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. However, White's article has been challenged by Cliff Anderson in his paper The Bad News Isn't In (http://www.erowid.org/chemicals/dxm/dxm_health2.shtml). White has later retracted his original claims in a response (http://www.erowid.org/chemicals/dxm/dxm_health3.shtml) to Cliff Anderson's paper though he still warns of possible long term damage from DXM.

Before any use of DXM, extra caution should be taken 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 of the liver enzyme used in the metabolism of dextromethorphan. Selective serotonin reuptake inhibitors (SSRIs) are one such drug that inhibits the P450-2D6 enzyme responsible for breaking DXM down into DXO (Otton & Wu, 1993). 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. DXM should not in any case be used by people who are taking a Monoamine oxidase inhibitor (MAOI) -- either in prescription medication or from natural sources, such as harmala. This may cause serotonin syndrome, and has been fatal (Bem & Peck, 1992).

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.

See also

External links

References

  1. Bem JL, Peck R. Dextromethorphan. An overview of safety issues. Drug Saf. 1992;7:190-199.
  2. Otton SV, Wu D, et al. Inhibition by fluoxetine of cytochrome P450 2D6 activity. Clin. Pharmacol. & Therapeutics. 1993;53:401- 409.
  3. Zhou GZ, Musacchio JM. Computer-assisted modeling of multiple dextromethorphan and sigma binding sites in guinea pig brain. Eur. J. Pharmacol.. 1991;206:261-269.

Template:Dissociative hallucinogensde:Dextromethorphan fr:Dextrométhorphan nl:DXM pl:Dekstrometorfan fi:DXM

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