4   General Information About DXM

This section covers general information about dextromethorphan, herein referred to as DXM. IUPAC chemical names are in a sans serif font, in square brackets.

1. PLEASE NOTE that the UK (and European?) name of acetaminophen is paracetamol. It is also known as APAP. They all refer to the same substance.
2. Erowid Correction of Canada's Contac CoughCaps, March 31, 2001

If you get nothing else out of this FAQ, let it be this: Remember that DXM is a powerful psychedelic which can be used safely, but must be used with care and respect for your own body and mind. DXM is not a safe drug, and it has not been well studied at recreational levels; whenever you use it you are taking a risk, possibly a big one. Please read and follow these basic guidelines:

	Not everyone likes DXM, and your experiences with it may be very unpleasant. A very few have had such intense side effects from DXM that their first trip lands them in the hospital. DXM is not a quick and easy buzz, and getting good results with it can be hard, sometimes unpleasant work.
	Do not use DXM on a constant or frequent basis! Like alcohol (and unlike marijuana), constant or frequent (more than once or twice a week) use may be dangerous. Although not everyone seems susceptible, a very few daily high-dose users may have seriously and permanently fried their brains.
	Do not use DXM if you have a any of the following medical conditions: mental illness, epilepsy, seizures, liver or kidney disorders, hypertension, heart problems, or ulcers.
	Do not use DXM if you are pregnant or nursing. All dissociatives adversely affect fetal development, and may lead to birth defects and mental retardation.
	Because some people can have severely adverse reactions to DXM, never rush into a high dose. Instead, take no more than twice your last dose, and wait at least one week between doses. Yes, it may take you a month before you get to interesting territory, but that's better than ending up in the hospital. Yes it can happen to you!
	Never exceed 20mg/kg (or 2000mg, whichever is lower) of DXM under any circumstances, and never exceed 15mg/kg (or 1500mg) unless you have a trip-sitter who is experienced and capable in the event of a medical emergency.
	Because of the potential for allergic or other adverse reactions to inert ingredients, always try a low dose first when taking a DXM product (syrup, gelcap, capsule, whatever) you haven't taken before.
	Never experiment with hallucinogens without a sober person around to help you in case you get into trouble. This goes doubly for DXM, which is much more likely to induce abnormal and dangerous behaviour than LSD.
	NEVER, EVER, EVER drive under the influence of any intoxicating drug including DXM!
	Never use a product containing acetaminophen (also called paracetamol or APAP, and known by the brand name TylenolTM). Large doses of acetaminophen can cause liver damage or death. Many cough syrups contain acetaminophen so always read the label.
	Never take DXM with yohimbine (YoconTM)! To do so may be risking permanent brain damage!
	Never take DXM if you are taking a monoamine oxidase inhibitor (MAOI). This also applies for one week before and two weeks after taking a MAOI. MAOIs include some (rarely used) prescription drugs for depression and Parkinson's disease, a few recreational ethnobotanicals (harmine and harmaline), and yohimbe bark. Mixing DXM and a MAOI has regularly been fatal.
	Do not take DXM with phentermine, fenfluramine, or the combination (phen-fen), all of which are used as prescription diet pills. This combination can cause serotonin syndrome.
	Never take DXM if you are taking, will take, or have taken within six weeks, the prescription antihistamine terfenadine (SeldaneTM), or any other prescription, non-drowsy antihistamine (e.g., ClaritinTM or HisminalTM).
	Never take DXM with the SSRI antidepressants Desyrel (trazodone) or Serzone (nefazodone); these combinations have resulted in liver damage.
	Be very careful combining DXM with SSRI and tricyclic antidepressants (i.e., those in common use), and never use DXM when taking more than one drug at a time for depression, due to the potential for serotonin syndrome.
	Avoid all products containing DXM and other active ingredients.
	Avoid BenylinTM brand products which seem to cause severe nausea. Avoid any product with castor oil. Avoid Coricidin Cough and ColdTM at upper plateau doses due to the potentially dangerous effects of antihistamine overdose.
	Remember that DXM can sometimes trigger panic attacks in susceptible individuals, especially those inexperienced with DXM. This is a major cause (if not the major cause) of tachycardia (high heart rate) from DXM. All the more reason not to rush in to anything.
	Always remember: recreational use of DXM is still a great unknown. The brain you are risking is your own.

Dextromethorphan (decks-tro-meth-OR-fan), or DXM, is a cough suppressant found in over-the-counter medications. It has also been used recreationally for at least 30 years, without much harm or publicity. Although chemically related to opiates, its effects are closest to ketamine's. In addition to suppressing coughs, DXM is used medically for diagnostic purposes, and may be useful for a variety of conditions from seizures to heroin addiction. In the brain, DXM blocks the dopamine reuptake site, activates the sigma receptor, and blocks the open NMDA channel. (None of these effects are permanent). Occasional recreational use of DXM is probably safe, though side effects and risks have been noted (I hereby tell you not to use any recreational drug including DXM). Many cough medicines contain ingredients other than DXM; some, like acetaminophen (paracetamol) can be fatal when an overdose is taken. The commercial preparations which can be used recreationally are those containing DXM only In the USA this includes mostly "Maximum Strength" cough formulas and Drixoral Cough Liquid CapsTM, and generic equivalents. All should list ONLY dextromethorphan hydrobromide under active ingredients. Avoid Benylin DMTM. The above cough syrups have 3mg/ml (15mg per teaspoon), for 360mg per 4oz bottle and 720mg per 8oz bottle; the cough gelcaps have 30mg each. Preparations like Robitussin DMTM contain guaifenesin and may cause vomiting. Never take DXM with, or up to two weeks before or six weeks after, the prescription "non-drowsy" antihistamines (allergy medications) SeldaneTM, ClaritinTM, or HisminalTM. Never take DXM with, or up to two weeks before or three weeks after, a MAOI (Monoamine Oxidase Inhibitor) - certain drugs for depression; you will probably be told by your doctor if your drug is a MAOI (ProzacTM isn't). Never drive under the influence of DXM. Don't take DXM more than once or twice a week. Don't take DXM if you have a history of mental illness, panic attacks, seizures, liver, kidney, or heart disease. Some people react very badly to DXM; others don't experience anything at all, partly from inherited lack of an enzyme. ProzacTM blocks this enzyme and may lengthen or change the DXM trip. Recreational DXM use may be illegal. DXM may cause false positives on drug tests. DXM trips vary depending on dosage, and can be lumped into four very different plateaus, or types of trips, depending on the amount taken. Dosages are given in milligrams per kilogram, so multiply the figure by your mass in kg (or pounds divided by 2.2). The first plateau, 1.5 to 2.5 mg/kg, is like a slightly intoxicating stimulant; music and movement are often pleasurable. The second plateau, 2.5 to 7.5 mg/kg, is intoxicating, with a "stoning" a bit like that of nitrous oxide or marijuana; sounds and sights seem to be on strobe-effect ("flanging"), short-term memory is somewhat disrupted, and there are occasional mild hallucinations. The third plateau, at 7.5 to 15mg/kg, consists of strong intoxication, hallucinations, and overall disturbances in thinking, senses, and memory; third plateau trips can be unpleasant. The fourth plateau, above 15mg/kg, is similar to a sub-anesthetic dose of ketamine, with dissociation of the mind from the body, and may be dangerous physically and psychologically. Most recreational use of DXM happens at the first and second plateau. DXM starts to become toxic around 20 to 30mg/kg. While occasional recreational use of DXM is probably safe, some people react very badly to dissociatives, especially at high doses, and may panic. Frequent DXM use, like frequent alcohol use, is probably dangerous and should be avoided. Please be safe, sensible, and use your brain; it's the only one you'll ever have.

From The Dextromethorphan FAQ: Answers to Frequently Asked Questions about DXM, v4.0, by William White ([email protected]). Available on Usenet rec.drugs.psychedelic and on the World Wide Web at Dextromethorphan hydrobromide is the water-soluble salt of dextromethorphan (DXM) and hydrobromic acid (that is, DXM hydrobromide is what you get when you react pure DXM with hydrobromic acid). DXM is a synthetic morphine analog, similar to levorphanol, but does not have any opiate-like effects. DXM has been in use in the USA for approximately 30 years, and has replaced codeine as an OTC cough suppressant (1-3). DXM has been popular as an "underground" recreational drug for at least 30 years (3). It is probably one of the few OTC medicines with any serious recreational use potential (ephedrine might also qualify). It is both extremely safe and very effective as a cough suppressant. DXM's IUPAC name is [(+)-cis-1,3,4,9,10,10a-hexahydro-6-methoxy- 11-methyl-2H-10,4a-iminoethanophenanthrene], and is also (and more commonly) known as 3-methoxy-17-methyl-(9alpha,13alpha,14alpha)-morphinan; CAS-125-71-3 (1). Note: the 3-methoxy and 17-methyl groups are pointed out for later notes. (Oh, just as a side note, I'm proud to say that for once I actually got the IUPAC name right all by myself - the Merck Index lists the same thing). The recreational use potential of DXM has not, in general, been well known, either by drug users or by physicians. Not too long ago, many physicians denied that dextromethorphan was psychoactive at all; whether this was out of ignorance or a desire to prevent recreational use, I do not know (probably the latter). At present, there is an increasing body of knowledge about DXM's potential for recreational use (and abuse) available in medical journals (3-7,132,136,139-141). DXM is unique among recreational drugs for several reasons. First, it is pharmacologically unlike most other recreational drugs (PCP and ketamine being its nearest relatives). Second, its effects can vary considerably from individual to individual. Finally, it can cause quite different effects at different dosage levels, ranging from mild euphoria to full dissociation. 4.3   What is Dextromethorphan Polistirex? Dextromethorphan Polistirex is a time-release formulation of DXM; the "polistirex" refers to a sulfonated styrene-divinylbenzene copolymer complex -- basically, an edible plastic (1-2). It is occasionally spelled polystirex or polystyrex. Unlike the HBr salt, which is absorbed fairly quickly, this compound is intended for longer duration cough suppression. Most, but not all, people who use DXM recreationally tend to prefer the HBr form (which is also much more readily available). The polistirex preparation will probably increase the ratio of DXM to DXO (see next section). Dextromethorphan polistirex may be more toxic than the hydrobromide version, possibly due to buildup of DXM in the bloodstream (143). 4.4   What is Dextrorphan (DXO)? Dextrorphan is a metabolite of DXM (i.e., the body converts DXM to dextrorphan). The conversion from DXM to DXO occurs via removal of the methyl group at position 6, a process called "O-demethylation". DXO is very similar chemically to DXM, and reacts with the same receptors in the body, but with a very different spectrum. Whereas DXM is strongest at the PCP2 and sigma receptors, DXO primarily targets the NMDA receptor (see Section 10). The practical upshot is that the dissociative and intoxicating or "stoning" effects are stronger with DXO, whereas the stimulation, cognitive alterations, delusions, and psychotomimetic (literally, "psychosis-like") effects are stronger with DXM. Most DXM users find some balance between the two to be the most pleasurable. Too much sigma activity is usually regarded as dysphoric (strongly unpleasant) and disturbing, and if prolonged, may be dangerous (101,135). Fortunately, you don't have to worry about converting DXM to DXO; the body does it for you via an enzyme called P450-2D6 or CYP2D6 (also called debrisoquine 4-hydroxylase). However, between 5 to 10% of the Caucasian population lacks this enzyme (12-15), and in the rest of us it can vary. Many drugs can temporarily block P450-2D6 from working (10-11) and thus alter the balance between DXM and DXO. For a list of these drugs, see Section 15.1. One of DXM's metabolites, 3-methoxymorphinan, can itself block P450-2D6. As a consequence, taking a second dose some time after the first dose of DXM will probably increase the ratio of DXM to DXO in the bloodstream. Taking the dose all at once, on the other hand, will probably increase the relative amount of DXO. Generally, then, the quicker the dosing, the more DXO and less DXM, and the more NMDA blockade (like ketamine) and the less sigma and PCP2 activity. Subcutaneous injection leads to very little conversion from DXM to DXO. When discussing effects, this text usually uses "DXM" to refer to both dextromethorphan and its metabolite, DXO. A few people have used DXO specifically; one indicated that it did in fact have fewer cognitive effects than DXM. 4.5   Is DXM Enjoyable as a Recreational Drug? It depends on what you consider "enjoyable". Roughly one third of the people who try DXM like it enough to ever repeat the experience; one third hates it, and one third doesn't enjoy it enough to drink cough syrup. Among those who do enjoy it, most report that their more "profound" DXM experiences were in many ways also very unpleasant, challening, and have a strong dysphoric undertone. Experienced psychedelic users seem to enjoy DXM more than the inexperienced. Generally speaking, enjoyable DXM experiences require putting a lot of emotional and psychological energy into the experience. DXM does not provide a simple high like marijuana, and it is not a substitute for other psychedelics. Many people will not enjoy it; before considering DXM, remember that you may hate the experience. If you are looking for a cheap buzz or a gentle ride, you probably won't like DXM. 4.6   Is DXM an Opiate? No, it isn't. Sometimes people get confused because DXM's stereoisomer (basically, the mirror image molecule), called levomethorphan, is an opiate. In two dimensions the molecules look identical, but in three dimensions, they are mirror images of each other. DXM no more fits into opiate receptors than a left-hand threaded screw will fit into a right-hand threaded nut. In fact, DXM doesn't bind at any opiate receptors, doesn't have opiate painkilling effects, and isn't cross-tolerant with opiates. It is only out of sheer chance that when DXM was invented, its origins were among the opiates; DXM's cough suppressant effects are completely different in mechanism from the cough suppressant effects of opiates. 4.7   Does Everyone Like DXM? No, in fact from speaking with many people who have tried it, only about one third of the people who try it ever take it again. One third seem to absolutely hate it, and the last third couldn't care less. Among the third who do like it, the majority (around 80% of those who like DXM) take it once a month or less. Part of the problem is that not everyone gets the interesting sets of effects (see Section 5). To some, the DXM trip is just a moderate buzzing sensation and a feeling of being slightly drunk. So your mileage may vary. A few people really enjoy DXM, and use it weekly; a very few (less than 5% of those who like DXM) use it more than twice a week. Keep in mind that I have not assessed the error margin on these figures, and that they reflect a biased sample of the population. I hope to have more accurate figures after completing a survey of DXM users. 4.8   How Does One Obtain and Use DXM? DXM is available at drugstores throughout the world, chemical suppliers, and (very rarely) as a street drug. Generally, however, I wouldn't trust anyone saying he or she had DXM on the street; it's probably ketamine, PCP, or something totally unrelated. DXM is most commonly available in cough syrups, though some syrups contain other ingredients which can make you sick (or dead) if you take too much of them. It is also available in gelcaps and in some places in capsules, either alone or in combination with other ingredients. DXM can also be extracted from cough medicines, and the extract can be taken orally, injected subcutaneously, intraperitoneally, intramuscuarly, or intravenously. It can probably also be snorted or used rectally (though why one would want to I don't know). Smoking the free base is very difficult if not impossible. DXO (not DXM) free base can be smoked at 190 C (pers. comm.). Some drugstores keep track of people who frequently buy DXM-containing cough preparations, especially if they buy multiple bottles at once or tend not to buy other things at the same time. This is less common in larger supermarket/drug stores. In some cities where DXM use has become popular (and come to public attention), sales have been restricted to adults. In Utah in the 1980's, DXM was placed behind the counter due to recreational use. Finally, DXM is available from chemical suppliers, very few of which will sell to individuals. Hopefully I'll soon be finished with the "Find the DXM" page, which allows people to find out which DXM preparations are available in their areas. Don't hold your breath, though; I'm a sysadmin at a small ISP and that doesn't leave me with a lot of time. 4.8.1   Cough Syrups DXM is widely available in cough syrups, both brand-name (such as RobitussinTM or Vicks Formula 44TM) and store brands. Most DXM-containing cough syrups also contain one or more of the following other active ingredients: nasal decongestants, antihistamines, acetaminophen, or guaifenesin (see Section 4.11). As a rule, you want to avoid all of them. Generally speaking, DXM cough syrups all taste nasty. This is for two reasons: to cover up the (even nastier) taste of DXM itself, and to prevent recreational use. The generics tend to be less thick, and thus more drinkable, than the brand names. Some people prefer to mix the DXM with sodas; others find this only makes an already unpleasant task even more unpleasant. Your Mileage May Vary. Most people who have used DXM cough syrups recreationally seem to prefer to take it on a mostly empty stomach, possibly with crackers or some other source of carbohydrates. I generally feel that you should avoid slamming your kidneys and pancreas with a lot of glucose at once; thus I think some crackers or chips beforehand would be advisable. Greasy food should be avoided both before and after taking DXM. Most people report that if carbonated drinks are ingested, they should be clear (e.g., 7-UpTM). The German company "Dr Rentschler" makes a cough syrup called "tuss hustenstiller saft". 4.8.2   Gelcaps There are "gelcaps" (liquid or gel filled capsules) available that contain DXM, but they tend to be brand-name only. The most frequent (if not only) brand in the US is Drixoral Cough Liquid CapsTM. They come in boxes of 10 or 20 gel capsules, each containing 30mg of DXM. The gel capsule itself is red colored; the liquid inside is actually clear (and tastes very, very bad). The capsules are somewhat large, and difficult if not impossible to take without liquid to wash them down. This brand also comes with a $0.50 or $1.00 manufacturer's coupon inside, which some have taken to calling DrixoralTM Dollars (after Camel BucksTM, a fake currency coupon in CamelTM cigarettes which could be collected and "spent" on various stuff, unfortunately not including iron lungs and chemotherapy). Note that Drixoral also makes several other liquid and capsule products, all of which contain undesirable active ingredients besides DXM. Recently, Drixoral Cough Liquid Caps have been getting harder and harder to find. The usual story from the drugstores is that they aren't very popular; my suspicion is that they are too popular. Look around, and you will probably be able to find them. There is a rumor going around that the "new" gelcaps have something in the coating that induces nausea, but I have found no evidence for this whatsoever. The ingredient list hasn't changed, and changing ingredients without making it public is strictly Absorption from the gelcaps takes some time, and can be sped up somewhat by cracking open each gelcap in your mouth before it is swallowed. Note, however, that the liquid inside is apt to spurt out, and it tastes bad. Really, really bad - sour and bitter and cloying all at once with a stickiness that won't go away. However, if you can stand it, you can become used to it after the first few gelcaps. You can also crack open the gelcaps and try to collect the liquid, but it tends to go everywhere. Some people have claimed that gelcap DXM "feels" different from cough syrup DXM. This may be pure placebo effect, or it may be a result of the slower absorption (and thus more DXM vs. DXO) of gelcaps. It is also possible that the "inactive" ingredients in cough syrup may affect the experience by altering blood glucose levels. Most seem to prefer the gelcap "feel". 4.8.3   Tablets and Capsules (including Coricidin) A variety of DXM-only pill brands are available throughout the world; unfortunately, none are available in the US. Some of the brands include: Romilar (southeast Asia and others) Dr. Rentschler tuss hustenstiller retard kapseln (Germany) Everest (Taipei and others) [Erowid Note: Contac CoughCaps (Canada) were removed from this list because we received reports from Canadians that these contained 300mg acetaminophen per dose.] Please let me know if you learn of any others. DXM pills typically contain 15 or 30 mg of DXM, but some (such as the Dr. Rentschler brand, tuss Hustenstiller retard Kapseln) contain 60mg of DXM. In the US, a new tablet brand, Coricidin Cough & Cold, is available. Containing 30mg DXM and 4mg chlorpheniramine maleate (an antihistame), these have become popular for lower plateau dosing, but can have extremely unpleasant anticholinergic side effects (drymouth, blurred vision, confusion, etc.) with higher doses. One person had to be hospitalized for vomiting blood and entering respiratory arrest after taking a high dose of Coricidin tablets. Even low doses often have unpleasant side effects and may be very confusing. At the lower plateaus, the chlorpheniramine does seem to alleviate the "Robo Itch" (see Section 6.1.3). The box is marked "suitable for people with high blood pressure" (Coricidin has other tablets available which are unsuitable for recreational use). Furthermore, many Coricidin seem to report that frequent use leads to increasingly severe nausea triggered by taking, or even looking at, the pills. Some people have been known to puke in the drugstore from seeing the box (one user reported that 30+ people he knows suffer from this). I have no idea why this would happen. Again, remember that the antihistamine in these tablets will change the character of the DXM trip (not necessarily in a good way), potentially increasing the degree confusion. Do not use this product except at first and second plateau dosage! An overdose of antihistamine, while not typically fatal, can be extremely unpleasant and has been reported to be a frequent cause of "bad trips" from Coricidin. Most DXM users have recommended not taking more than eight Coricidin tablets; some say not to use this product at all. 4.8.4   Lozenges There are a few brands of cough drops/lozenges which contain DXM without other active ingredients. One such brand is SucretsTM (not the kind that come in the tin; these come in a bag and are labelled as containing DXM). Each lozenge contains 15mg DXM, as well as a number of inert ingredients (primarily sucrose, flavoring, coloring, magnesium silicate). Some people report the sucrets contain menthol; others don't (I suspect there may be different versions available). Other lozenges available contain from 7.5mg DXM (a South African brand) to 30mg DXM. Revco carries a DXM lozenge containing 5mg DXM each called HoldTM, which supposedly taste better than Sucrets but are fairly expensive (and contain less DXM). Since the inert ingredients present in these lozenges may cause nausea, some people have managed to get rid of most of them by placing the lozenges in a container of water and microwaving until fully dissolved, then filtering through a coffee filter, discarding the precipitate (solid), and drinking the liquid. Longer boiling seems to drive off the flavoring and menthol without affecting the DXM. Interesting side note: recently, in South Africa, cough lozenges containing an abnormally high amount of DXM were illegally diverted from disposal and resold, causing "moderately severe" toxicity in 24% of primary school pupils using these lozenges (369). 4.8.5   Pharmaceutical and Chemical Suppliers DXM is not DEA scheduled in the USA (or most other parts of the world), and consequently should be available via pharmaceutical chemical suppliers. For example, Sigma Chemical Company (1-800-325-3010) lists DXM hydrobromide (product D2531) for US $18.20 for 5 grams, US $128.45 for 50 grams. Note that I have no affiliation with Sigma in any way; I just happened to have a copy of their catalog handy when writing this. In theory, it would be fantastically cheap and easy to order DXM this way; in practice, it's possibly difficult, and probably a Very Bad Idea. First off, most chemical companies are wary about selling to individuals (and if you're not a legal adult, forget it). Secondly, there's a significant chance that your order will be reported to the DEA, and although it's not technically illegal, if enough people do this, that may change very quickly. Still, though, if you have the (possibly foolish) courage to try, there's no reason why this shouldn't be a reasonable source. Just use your head. And don't mention the FAQ. Recently, a few chemical resale companies have popped up, relying upon the fact that many potentially useful chemicals can be sold legally to researchers (for which there doesn't seem to be a legal definition). Please remember that it is your responsibility to make sure that ordering and using DXM from a chemical supplier is legal in your area. Also, to my knowledge no chemical supplier (at least, none you're likely to run across) warrants its product for human consumption. Buyer beware! Currently I know of two companies selling DXM (other than Sigma and the like, which won't sell to individuals): Chemical Resale of Santa Barbara and WANMAN Enterprises. 4.8.5.1   Chemical Resale of Santa Barbara September 2001: CRSB is no longer in business according to its founder, Tom Kaspar. He recommends http://www.ltkresearchproducts.com/ as a reliable commercial provider. CRSB was in limbo while Tom Kasper was in jail for a couple years for acting freaky and scaring people on an airplane. He and CRSB returned to business in the spring of 2001 and is once again selling DXM, among other chemicals. CRSB's products are not for human consumption and are for research only. CRSB can be contacted at [email protected] 4.8.5.2   WANMAN Enterprises Another company which offers USP grade DXM is WANMAN Enterprises. I know next to nothing about them except they gave me their address and prices for inclusion in the FAQ. Current prices are 10g for $50, 100g for $300, and 1kg for $1000 (US dollars). Orders are shipped via private carrier (UPS, FedEx, etc). They have a special of 50g for $100 to readers of the FAQ (mention you saw them there). Certified check or money order should be made out to WANMAN Enterprises. Their address: WANMAN Enterprises 7620 Vance Rd. Kernersville NC 27284 [email protected] 4.8.5.3   Other I have also heard of a company in Texas that sells small quantities of DXM (again, for research purposes I suppose), but do not know anything else about them. 4.8.6   Extracted DXM DXM can be extracted (see Section 11) and the extracted DXM can be taken orally, either as free base or as salt (the free base should convert to the hydrochloride salt in your stomach). DXM is commercially available as the hydrobromide salt (as well as polistirex), but DXM extraction typically results in DXM citrate (see Section 11.1.3). The free base tends to be somewhat alkaline and should be avoided unless combined with food and/or juice (or other acidic beverage). When taken on a mostly empty stomach, the extract is generally (but not always) absorbed faster than cough syrups, gelcaps, or capsules. Some extraction processes may convert some or all of the DXM into dextrorphan (DXO). Extracted DXM, unlike cough syrups and gelcaps, has no bromide toxicity (see Section 4.11.7). 4.8.7   Injection and Other Routes DXM hydrobromide is reasonably soluble in saline, and I see no reason why other acid salts shouldn't be - though their long-term stability may be doubtful. However, injection is a very dangerous way of using recreational drugs, especially if the substance in question is not prepared specifically to be injected. Some of the potential risks include: sterile abscesses, torn or collapsed veins, bruising, muscle fiber damage, histamine release, infection (hepatitis B, HIV, etc.), embolism (and possible resulting stroke or cardiac arrest), increased chance of addiction, overdose, and people mistaking you for a junky. True, most of these are unlikely, and if done correctly injection is generally very safe. However, the key word is correctly. If you're still interested, consult a medical text; I'm not going to teach you how to shoot up. A few notes for those brave or stupid enough to still be interested. Intravenous (IV) and intramuscular (IM) injection both seem to produce similar results in animals, and IM injection is almost always safer. DXM can also be injected intraperitoneally (IP), but that evidently requires some skill. Subcutaneous (SC) injection ("skin popping") leads to slower absorption and a great increase in the amount of DXM relative to DXO. All injected drugs should be completely pure, dissolved in the appropriate physiological saline. In the case of SC (and possibly IM) injection, injecting too large a volume of material can lead to a sterile abscess. DXM can also theoretically be snorted although I don't generally think this is a very smart route; the nasal lining is very tender. DXM free base is probably too alkaline to try this with. It can also probably be used rectally, but somehow the thought of a cough syrup enema doesn't thrill me. Smoking DXM free base has been attempted several times by various people without much success. DXM itself seems to vaporize at a fairly high temperature, and is extremely harsh. To make matters worse, in typical DXM extractions, some of the flavoring agents end up surviving the extraction and they lend a definite unpleasant taste to the smoke. I have received one report of a successful DXM freebasing experiment. The person said that while it was nice to know it was possible, it was just too much trouble to be worth it. Another person reported making the attempt and suffering from a severe burning sensation in his lungs which ended up as an asthma attack. 4.9   What are Some Typical DXM-Containing Preparations? OK, I finally gave up on even trying to list commercial DXM preparations because there are too many (not to mention they differ from place to place even within the US). Instead, I list here the typical DXM formulas and preparations you are likely to encounter. Pediatric Syrups (1-1.5mg/ml DXM) There are several brands and generics of "Pediatric" formulation DXM preparations. Intended for children, they contain very little DXM; on the other hand, they usually taste better. In general though it's a waste of money and time to try and use pediatric DXM formulas for recreational purposes. Regular Strength Syrups (2mg/ml DXM) Many "regular strength" cough syrups contain 2mg/ml DXM. In the US, the most notable example is Vicks Formula 44TM (which formerly contained 3mg/ml). These are of course quite usable for recreational purposes, although 3mg/ml syrups are preferred. "DM" Cough Syrups (2mg/ml DXM) Most of the "DM" cough syrups (of which the notable brand is Robitussin DMTM) contain 2mg/ml DXM as well as gauifenesin. During the 1980's, many of these syrups contained 3mg/ml DXM but were reduced in strength in response to recreational use. These syrups can also be used recreationally, but note that the guaifenesin can cause nausea or vomiting (see Section 4.11.3). Maximum Strength Cough Syrups (3mg/ml DXM) The strongest syrups regularly available in the US are 3mg/ml and are typically marked "Maximum Strength Cough" (of which RobitussinTM is the most notable example). The generics are almost always called "Tussin Maximum Strength Cough". These are the most commonly used syrups for recreational purposes. Concentrate Syrups (6mg/ml DXM) There are a very few brands of "concentrate" syrups, which are intended for institutions (or large families) who buy the concentrate and dilute it, possibly adding flavoring. The only brand I've ever heard of is PinexTM. Good luck trying to find these. Gelcaps (30mg DXM) Drixoral Cough Liquid CapsTM are available in the US (and possibly other places), and contain 30mg DXM in a gel capsule. These are sporadically available; if you can't find them in your area, try elsewhere. Lozenges (7.5mg - 30mg DXM) A few lozenges are available which contain DXM. In the US, the only brand I'm aware of is SucretsTM, which contain 15mg of DXM (see above notes on Section 4.8.4). Another brand containing 7.5mg DXM is available in South Africa. Capsules and Tablets (15mg - 60mg DXM) Various capsules and tablets are available throughout the world containing only DXM (to my knowledge, none are available in the US). These range from 15mg to 60mg per pill, with 15mg and 30mg being the most common. DXM + Chlorpheniramine Capsules (30mg DXM) Coricidin Cough and ColdTM tablets are available in the US with 30mg DXM and 4mg chlorpheniramine maleate (an antihistamine). These are suitable only for first and second plateau dosing (generally, ten pills or less) due to the adverse effects (possibly dangerous) of antihistamines at high doses. Be advised that some people react very poorly to antihistamines. On the other hand, the antihistamine evidently can prevent the dreaded "Robo Itch" (see Section 6.1.3). Coricidin has other formulas which contain undesirable or dangerous ingredients; the correct one is marked "suitable for people with high blood pressure". Miscellaneous I have heard rumors of DXM available on the street in 240mg, 300mg, and 600mg doses, but I cannot verify these rumors. The "DXM" may actually be PCP, ketamine, or anything for that matter (but is probably just extracted or purchaed DXM). "Agent Lemon" (see Section 11.1.3) has also been made available in some locations. Again, be advised that you are relying upon someone else's chemistry skills. 4.10   How am I Supposed to Drink Cough Syrup? Good question. Part of the reason DXM isn't terribly popular is that drinking cough syrup is, well, disgusting. However, here is a suggested method courtesy of "JR": Materials: 2 glasses A sink with COLD water cough syrup toothpaste Procedure: Fill one glass with water, the other with Robo. Keep the water running (it makes the sensation less gross for some reason). Do not allow Robo to be smelled under any circumstances! Pinch nose shut with one hand Sip water Take 5-6 deep hyperventilative breaths Slam the entire 8oz bottle of Robo at one time. While still holding nose, drink remainder of water Refill glass with water and drink the entire glass of water. Repeat again, for a third glass of water. Still holding your nose, spread toothpaste in your mouth, thoroughly coating the inside of your mouth. Release your nose, and exhale through both nose and mouth. Minty fresh! 4.11   What Should I Know About Other Drug Ingredients? There are five main classes of active ingredients that are present in OTC DXM-containing products: decongestants, antihistamines, guaifenesin, analgesics, and alcohol. Each will be discussed in turn, followed by "inactive" ingredients. With the possible exception of alcohol, all should be avoided, although for differing reasons. Some of these other active ingredients will make your experience unpleasant; others can kill you. Additionally, some of the dyes and other "inactive" ingredients may cause some people trouble. 4.11.1   Decongestants There are three nasal decongestants that are used in OTC cough formulas in the USA: PPA, pseudoephedrine, and phenyleprine (the latter is almost always found with antihistamines). PPA is also known as phenylpropanolamine (from which the acronym PPA is derived), norephedrine, and the IUPAC name [alpha-(1-aminoethyl)benzyl alcohol]. Pseudoephedrine, known as the brand name SudafedTM, has the IUPAC name [(+)alpha-(1-methylamino)benzyl alcohol]. Phenyleprine is [(-)-3-hydroxy-alpha-(methylaminomethyl)benzyl alcohol] (1-2). These decongestants belong to a class of chemicals known as the phenethylamines; this class also includes methamphetamine, MDMA (ecstasy), MDA, etc., and tend to be DEA scheduled. Decongestants are not scheduled by the DEA (this is USA laws) because they do not have significant psychostimulant activity. Ephedrine, which is similar to pseudoephedrine, and is (or was, depending on your state) available throughout truck stops and mail-order pharmaceutical companies in the USA, does have mild stimulant properties; thus its popularity as a form of "legal speed". All of these drugs stimulate the sympathetic nervous system (the "fight or flight" system) and are thus called sympathomimetics. What nasal decongestants do share with the more potent amphetamines is the peripheral activity common to sympathomimetics, such as vasoconstriction (constriction of blood vessels) and decreased nasal secretions (the good side), and - with larger doses - insomnia, hypertension, heart rhythm abnormalities, hemorrhaging, stroke, or death (the bad side) (8). Note that these are extreme reactions, and that individual tolerance to sympathomimetics tends to vary considerably. Tolerance can build quickly, and a fatal dose for one person may have only a mild effect on another person. Because of the potential danger of hypertension, exceeding the recommended dose of DXM and decongestant containing preparations may be asking for trouble. Most people can probably handle it in smaller recreational doses, but the peripheral "speediness" can be distinctly unpleasant. Anyone with high blood pressure or the like has no business taking large quantities of decongestants. Finally, more recent research suggests that many of DXM's potentially disturbing side effects (see Section 6) might be potentiated by any stimulant. Panic attacks, hyperthermia, hypertensive crisis, and the like are notable examples. In extreme cases, stroke or brain hemorrhage may be possible. Conclusion: Possibly suitable for first plateau use only; otherwise avoid these drugs! 4.11.2   Antihistamines The antihistamines operate by blocking histamine receptors (see Section 10.1 for an explanation of receptors). Peripherally, this has the effect of reducing the symptoms of histamine activity (stuffy and runny nose, itchy eyes, hives, rashes, etc.) associated with infections and allergies. In the brain, histamine is partially responsible for wakefulness, and antihistamines that cross the blood-brain barrier will cause sleepiness. In fact, most OTC "sleeping pills" in the USA are really just antihistamines (although melatonin is making inroads as an alternative). There are antihistamines that do not cross the blood-brain barrier (e.g., SeldaneTM) but these are prescription in the USA. High doses of antihistamines can result in dizziness, impairment of concentration, extreme sedation (or, paradoxically, insomnia), headache, heart palpitations, dry mouth, gastric discomfort, delusions, and abnormally high blood pressure. Doses of 30-60mg/kg have been fatal in very young children; most adults, however, are very unlikely to overdose on antihistamines. Death, when it does occur, is from cardiovascular collapse or respiratory arrest (8). High doses of prescription antihistamines are much more dangerous; do not mix DXM with prescription antihistamines! The danger of an antihistamine overdose is very low when using a DXM-containing product recreationally. However, you will most likely experience some unpleasant symptoms, such as sleepiness, dry mouth, heart palpitations, etc. These side effects increase as the dosage increases. A very small amount of antihistamines might be useful in preventing DXM-induced histamine release. Conclusion: Traditional antihistamines may be suitable for first and second plateau dosage levels, but should not be used at the upper plateaus. NEVER use DXM with prescription, non-drowsy antihistamines! 4.11.3   Guaifenesin Guaifenesin (gwye-FEN-a-sin) [3-(2-methoxyphenoxy)-1,2-propanediol] is an expectorant; it increases the production of respiratory tract fluids, thus making phlegm less viscous and easier to cough up. Guaifenesin has been shown effective as an expectorant, but is of no use as a cough suppressant. It is often combined with dextromethorphan. Guaifenesin should not be used for chronic coughs or coughs accompanied by excessive phlegm (1-2). High doses of guaifenesin tend to induce emesis (i.e., you puke). Other effects from high guaifenesin doses are not well known, but probably not serious. Some suggest that guaifenesin may act as a muscle relaxant at high doses (an effect for which it is used in veterinary medicine). Conclusion: as most people do not enjoy vomiting, I would recommend avoiding guaifenesin-containing products. 4.11.4   Analgesics, Acetaminophen/Paracetamol Acetaminophen, also known as paracetamol and APAP, is the most common analgesic (painkiller) present in cough suppressant formulas. It is closely related to the NSAIDs (non-steroidal anti-inflammatory drugs) of which aspirin and ibuprofen are the two most common examples. Unlike the OTC NSAIDs, however, acetaminophen/paracetamol does not tend to irritate the stomach, and thus its inclusion in cough syrups. An acetaminophen overdose is very dangerous. Normally, acetaminophen is metabolized (broken down) in the body by two separate pathways, both of which lead to harmless metabolites. However, these two pathways can only handle so much before saturating. At that point, the remaining acetaminophen is metabolized by a cytochrome P450 liver enzyme. The metabolite via the P450 pathway is toxic to the liver (2,8). Furthermore, this doesn't happen right away; it can take 16 hours before any signs of liver damage show up. This delayed toxic effect has been responsible for the rather painful deaths of some people who (accidentally or not) overdose on acetaminophen, and then think they are fine when no immediate problems occur. There is an antidote (acetylcystine), but it must be administered within the first 12 to 16 hours. The toxic dose of acetaminophen can be as low as 50mg/kg; for a 60kg person this is only six acetaminophen tablets. This is unlikely but possible. DO NOT UNDER ANY CIRCUMSTANCES USE RECREATIONALLY ANY DXM PRODUCT WHICH ALSO CONTAINS ACETAMINOPHEN / PARACETAMOL! As for aspirin and ibuprofen, the other two most common OTC painkillers, both tend to irritate the stomach at high doses. I recommend against them, especially if you have an irritable stomach. Never take large doses of aspirin or ibuprofen if you have an ulcer. Conclusion: avoid any product containing an analgeisc. 4.11.5   Alcohol Most cough syrups contain some alcohol, to help dissolve the DXM (and other drugs) and to numb the throat. With a few exceptions (such as NyquilTM), the amount of alcohol is not usually very great. While alcohol does not, in general, mix well with DXM as a recreational drug, the amount in cough syrups should not cause trouble unless you are specifically sensitive to, or attempting to avoid, alcohol. There are alcohol-free preparations available; gelcaps and tablets are alcohol-free. 4.11.6   Food Coloring and Dyes Some of the dyes used in cough formulas may give some people allergic reactions. Most notable among these is tartrazine (FD&C Yellow #5). Generally, these dyes are not a problem unless you take a lot of them (which recreational DXM use may involve). If you think you may be allergic to a dye, switch to a different brand (or more accurately, a different color). It is also a good idea to keep an antihistamine (not a prescription or non-drowsy one!) nearby in case an allergic reaction does occur. 4.11.7   Bromide Ions DXM is usually ingested as a hydrobromide salt. Large amounts of bromide ions can cause sedation and eventually lead to bromism (bromide poisoning), which affects (among other things) the skin and nervous system (see Section 6.3.15. I don't think this is terribly relevant for users of DXM (recreational or not); however it is one more reason to avoid prolonged high-dose use. You can avoid bromide ions by converting the DXM to free base and/or hydrochloride salt (see Section 11.1). Some physicians do believe that prolonged heavy use of DXM may lead to bromism (144). 4.11.8   Other "Inactive" Ingredients Cough syrups tend to contain several thickening and sweetening agents. Glucose, sucrose, invert sugar, and fructose are all commonly used as sweetening agents. Obviously, a person with blood sugar problems (diabetes or hypoglycemia) should not take large amounts of these syrups. "Diabetic" syrups are available. Thickening agents don't generally cause problems other than nausea. Occasionally people will look on cough syrup labels and see propylene glycol or polyethylene glycol, and (thinking about ethylene glycol, i.e., antifreeze) worry about toxicity. Propylene glycol is not toxic, even though ethylene glycol is. The same goes for polyethylene glycol (PEG) - it's also nontoxic. About the worst you will get from any of these is an upset stomach. One general note - keep in mind that your body does eventually have to use or excrete whatever you eat and drink. Drinking huge amounts of sugars and thickening agents can put a fair amount of load on the pancreas and kidneys and should definitely be avoided if you have kidney problems already. There is anecdotal evidence that regular high-dose use of DXM cough syrups (without eating much) has led to kidney damage due to the glucose load (though I suspect rhabdoymolysis may be the cause -- see Section 6.2.7. I cannot confirm this but I can't disprove it either. I've also heard of people having blood sugar problems after repeated use of DXM cough syrups, but again I can't verify this. 4.12   Why are So Many DXM Preparations in Liquid Form? Cough preparations are in liquid form for two reasons. First and foremost, most people have the (mistaken) belief that in order for a cough suppressant formula to work, it must coat the throat. While this may be true for local anaesthetics, in the case of DXM (or codeine for that matter), it's complete bunk. If consumers were a bit smarter, maybe we wouldn't have to gag down cough syrup. There are, in fact, gel-capsule cough suppressants on the market, and I expect that tablet or capsule dextromethorphan will eventually be more common. Second, tablet-form DXM preparations have been kept from the market in an attempt to prevent their recreational use. RomilarTM tablets used to be available in the US, but were removed from the market due to concerns about their abuse. Other DXM formulas have been reduced in strength, or combined with other ingredients, in an attempt to prevent or reduce recreational use potential. 4.13   Is Recreational Use of DXM Illegal? Possibly. There may be laws making it a crime to use OTC medicines in any way other than directed on the label. Not that this stops people from using ephedrine (a bronchodilator) as a stimulant. Nor are you likely to get caught and/or prosecuted; the authorities are much too busy infringing upon our civil rights looking for the illegal drugs. But, remember - I SPECIFICALLY instruct you NOT to use any medicine in a manner inconsistent with its labeling. Furthermore, suggesting to someone that they use DXM as a recreational drug could also be violating a law - against prescribing drugs as a layperson. Again, it's not likely to happen, but it is possible. DXM is a prescription drug in Sweden (9). It is prescription and scheduled in Australia unless combined with other active ingredients. It may become prescription in other countries. In drug stores in some areas it is kept behind the counter, must be requested, and is only sold to adults. 4.14   If DXM is Legal Why Isn't Everyone Doing It? A lot of reasons, actually. Beyond the obvious one that not everyone knows about it are a number of reasons which may be more relevant. First and foremost, DXM doesn't appeal to everyone; in fact, it seems to follow a "rule of thirds". One third of people who try DXM like it, one third hate it, and one third could care less. Secondly, doing DXM is either disgusting or a time-consuming process for most people. Cough syrup tastes bad, and is unpleasant to drink; even the gelcaps become unpleasant to take after a few times due to their rather large size. DXM can of course be extracted, but it is a time-consuming process that requires enough effort to discourage those only casually interested. Third, DXM is to a certain extent "anti-addictive", at least when used occasionally. Because DXM blocks NMDA receptors (see Section 9 and Section 10.3), it prevents associating any pleasant effects of the drug with the taking of the drug. Instead, the memories of taking the drug are associated with sensations before the DXM kicks in, e.g., nausea. Fourth, DXM trips can be extremely confusing, especially if the user doesn't have experience with psychedelics. The DXM trip is so unlike an LSD or mushroom trip that people who take it expecting the latter are often discouraged and do not repeat the experience. Finally, DXM has a reputation as a "loser drug", something people take when nothing else is available. While it's true that DXM is legal, and thus can in fact be taken when nothing else is available, this doesn't make it any less powerful (or any safer) than illegal drugs. 4.15   New Medical Uses for DXM In the past five years, research, especially research centered on NMDA receptors, has uncovered more and more medical uses for DXM. Some of these include: 4.15.1   Diagnostic Uses Cytochrome P450-2D6, also known as CYP2D6 or debrisoquine hydroxylase, is a liver enyme which is extensively involved in metabolizing drugs. Many drugs are metabolized by P450-2D6, and many drugs also inhibit it. Some people are genetically lacking in the normal P450-2D6 variant, and physicians will use DXM to determine which variant of P450-2D6 a patient has (10-11). About 5-10% of Caucasians and 0.5% of Asians seem to lack P450-2D6 entirely, or have a very inactive mutation (12-15). In remaining individuals, its activity can vary significantly due to genetic factors (15-18). Between 0.5% and 2% of the population has multiple copies of the P450-2D6 gene and will metabolize 2D6-dependent drugs much more quickly than most people (155). Since many drugs become toxic at high doses, it is important to give the proper amount to those people who will metabolize it differently than the normal population. DXM is used to test metabolism by CYP2D6. The patient is given a specific amount of DXM, and then the relative concentrations of DXM and its metabolites are determined. Some recent research suggests that susceptibility to lung cancer may be related to P450 variant, and DXM may be an effective diagnostic tool for predicting lung cancer susceptibility (376). 4.15.2   Neuroprotectant Uses One area in which DXM (as well as other NMDA blockers; see Section 10.3) shows great promise is in the prevention of brain damage resulting from excitotoxicity (over-stimulation of nerve cells to the point of cell death) and other types of nerve cell damage (19). DXM may reduce or eliminate the brain damage resulting from conditions such as fever, hypoxia (lack of oxygen) (20), ischemia (cutoff of blood to brain cells) (21-22), physical injury (23), infection (such as poliomyelitis, encephalitis, and meningitis), stroke, seizure, drug toxicity (24-25), electrical shock (231), hypoglycaemia (243), and withdrawal from long-term dependence upon certain drugs (notably alcohol, barbiturates, and benzodiazepines such as ValiumTM) (26-29). In the case of infection (and in particular poliomyelitis), it has been demonstrated that the damage to the CNS often occurs not from the infection, but from the body's own defenses, and notably from a chemical called quinolinic acid (a metabolite of tryptophan) (30,31). Quinolinic acid is a very potent agonist (activator) at excitatory amino acid receptors, of which NMDA is one type; DXM prevents quinolinic acid from activating NMDA receptors. (Incidentally, the function of quinolinic acid - if it has any - is not currently known; it may be involved in the immune response). As for physical trauma, hypoxia, seizure, stroke, etc., there are several experiments which indicate that the majority of the damage again comes from excitotoxicity at excitatory amino acid receptors. While DXM has shown somewhat less success there (possibly due to other factors being involved), it still has potential. DXM is currently being evaluated as an anticonvulsant (32,33). The animal data are somewhat conflicting, but the most accurate model of epileptic seizures (called kindling) responds well to DXM. Preliminary studies in humans indicates that even very low levels of DXM may help prevent seizures. This effect is not, as was originally thought, due to NMDA receptors; instead, it is probably due to sigma receptors or voltage-gated ion channels (32). Interestingly, DXM produces different side-effects in kindled (seizure-susceptible) animals than in non-kindled animals (this may be due to uncoupling of NMDA receptors). It is possible that humans susceptible to seizure may experience different effects from recreational DXM use. 4.15.3   DXM for Chronic Pain DXM seems to enhance the painkilling ability of opiates without adding to the side effects, and in practice the patient can lower the dose of opiates while maintaining analgesic effect (37). As an added bonus, DXM seems to prevent opiate tolerance (see next section). DXM by itself has only marginal analgesic effect if any (373,375). 4.15.4   DXM for Drug Addiction DXM, as well as other dissociatives, seems to prevent and even reverse tolerance to (and thus physical addiction to) many drugs. In the case of opiates, DXM has been used to treat withdrawal symptoms (169). DXM plus diazepam (ValiumTM) was tested and found to be more effective at combating the symptoms of heroin withdrawal (goose flesh, tremors, pupil dilation, joint pains, etc.) than chlorpromazine (ThorazineTM) plus diazepam (34). A further study verified this and found that adding tizanidine (an alpha-2 adrenergic agonist) to the DXM+diazepam cocktail was even more effective (133). Dissociatives have also been found to reverse or prevent tolerance to cocaine (247), nicotine (249), and alcohol (232), and some researchers have suggested that DXM (and other NMDA antagonists) may be universally useful in most if not all drug addictions. 4.15.5   DXM for Disease and Miscellaneous Conditions DXM is being investigated as a treatment for various diseases due mostly to its NMDA antagonist effects. The most promising results have been in treating shingles, a disease which primarily affects the elderly wherein a dormant viral infection flares up and attacks peripheral nerves. DXM can block the (often excruciating) pain from this flareup, and may prevent peripheral nerve damage (370). It may also be effective at treating herpes pain (368). Some chronic neurodegenerative diseases may be treatable with DXM. Notable among these include ALS (Lou Gehrig's Disease) (168), although more recent research seems to show that DXM may not be a useful treatment for ALS (363). Even "Mad Cow" disease (and other prion diseases) may respond to treatment with DXM (362). DXM has also been used to treat mental retardation (35), and Parkinson's disease (36). DXM may even have be useful in treating lung and other cancers (38) and preventing tissue rejection in transplants (263) due to the (poorly understood) effects of sigma ligands on tumor cells and the immune system (see Section 10.2). Some papers have suggested that dissociatives have antidepressant effects (208,212,223,245,250), while others dispute this (225,229). Finally, the dissociative qualities of DXM may be of use; ketamine has been used to calm children in order to perform genital exam in cases of suspected sexual abuse (184-186). 4.16   Drug Interactions Please read through this section if you are taking (or have or will be taking) other drugs in addition to DXM. 4.16.1   Fatal or Dangerous Interactions DXM should not be used (either recreationally or at normal dosage levels) by people who are taking a monoamine oxidase inhibitor (MAOI, rhymes with "wowee") - either a prescription MAOI or a recreational one such as harmaline. Note that there is considerable confusion among drug users about what is and isn't a MAOI. MAOIs include a few drugs prescribed for depression and Parkinson's disease, and a few rare recreational drugs derived from exotic plant sources (harmine and harmaline, from Syrian Rue and Yagé, for example). ProzacTM, MDMA, cheese, beer, SeldaneTM, etc., are not MAOIs - they are things to avoid when taking a MAOI. If you are taking a prescription MAOI you will almost certainly know, as your physician will have (hopefully!) told you to avoid eating aged cheeses. Combining DXM and a MAOI has been fatal (3)! Fluoxetine (ProzacTM) is a cytochrome P450-2D6 inhibitor (39) and will change the characteristics of a DXM trip somewhat, increasing the ratio of DXM to DXO. Other P450-2D6 inhibiting drugs, which include many antidepressants, will probably do the same; see Section 15.1. The duration of the trip may be greatly extended by P450-2D6 inhibitors; some users have reported effects lasting 12 to 24 hours past the normal duration. The potency of DXM may also be enhanced via other mechanisms by fluoxetine (40). Combining DXM with the antidepressants Desyrel (trazodone) or Serzone (nefazodone) has been reported to cause liver damage! One user reported that combining DXM with bupropion (Wellbutrin[tm]) resulted in a prolonged (3+ day) hangover and an increase in adverse side effects. Fluoxetine and other SSRI antidepressants, as well as tricyclics and lithium (and of course MAOIs) may interact with DXM to cause serotonin syndrome (see Section 6.2.9). This condition, although rarely fatal, is not terribly pleasant. Vascular disease may increase the chance for serotonin syndrome with DXM + antidepressants (364), and other disease conditions may do so as well. Some DXM users who have taken DXM while on antidepressants have reported unpleasant reactions that sound a lot like serotonin syndrome, so you might want to watch out. Some of the symptoms of serotonin syndrome include muscle rigidity, confusion, diarrhea, incoordination, low-grade fever, sweating, muscle tremor, mania, agitation, exaggerated reflexes, and nausea. Do not take DXM with the diet drugs phentermine, fenfluramine, or phen-fen; this combination can also cause serotonin syndrome. DXM should not be taken (recreationally or at normal dosage levels) with the prescription antihistamine terfenadine (SeldaneTM). This combination has been fatal (41). Terfenadine has been implicated in other drug interactions, incidentally. The reason for this interaction seems to be that terfenadine, which is normally metabolized by a P450 enzyme, induces heart irregularities when it builds up. DXM may saturate the P450 enzymes that normally metabolize terfenadine. Incidentally, this probably applies to other non-drowsy antihistamines, such as ClaritinTM and HisminalTM as well; avoid combining them with DXM. Some people find that nicotine (cigarettes) causes severe nausea when combined with DXM. Others have noticed a general increase in physical discomfort and "bad trips" from combining the two. Some research has suggested that cigarette smoke inhibits monoamine oxidase (378,379) in which case cigarettes could greatly increase the chance of unpleasant side effects. 4.16.2   Beneficial Drug Interactions Both opiates and dissociatives have strong side effects which can limit their usefulness in pain treatment. When the two are combined, however, a synergistic effect occurs, and patients can lower the dose of both drugs to the point where side effects are minimalized (236,267,278). Dissociatives prevent tolerance to opiates (248) and can alleviate opiate withdrawal (254). On the other hand, combining the two may increase the chance for respiratory depression and fatal overdose. 4.16.3   Recreational Drug Interactions Marijauna and DXM is a frequently used combination, albeit one which has seen little research. Competitive NMDA blockade enhances marijuana catalepsy (210), and conceivably noncompetitive blockade would as well. Dizocilpine, a dissociative used in research, decreases the analgesic effects of marijuana (214), and causes downregulation of anandamide receptors (THC receptors) (218). Dissociatives may block the depletion of 5HT (serotonin) caused by MDMA (ecstasy) (241). However, there is also the potential for hypertensive problems, so I wouldn't advise this combination. Methamphetamine produces vacuolation of neuron terminals due to a collapsed vesicular proton gradient (181) (translated into English, this means that speed damages brain cells by breaking open the little bubbles of neurotransmitters inside the cells). However, dizocilpine (and presumably other dissociatives) may prevent this (219). It also seems to block methamphetamine induced 5HT depletion (241). Antidepressants and dissociatives seem to interact as well, not necessarily in a good way. Both desipramine and dissociatives increase prefrontal lobe dopamine activity; the combination is highly synergistic (277). Even worse, dissociatives may actually reverse the antidepressant effect (229). Dizocilpine reduces 5HT2 receptor density (212), and increases 5HT binding in the hippocampus and striatum (252). On the other hand, one paper found that dizocilpine helped antidepressants in some tests (245,250). Finally, dissociatives block tolerance to many drugs, including alcohol (232), cocaine (247), nicotine (249), and morphine (248). 4.17   General Warnings Probably the most important warning about DXM is that, like other dissociatives, it may cause brain damage when used to excess (see Section 6.3.1. What exactly constitutes "excess" is anyone's guess, although in animal models, Olney's lesions (the type of brain damage caused by dissociatives) only occur at many times the anaesthetic dose, which is itself higher than the recreational dose. Of the people I've interviewed who have used DXM regularly, about 1% have reported long-term cognitive impairment (although some of these people were continuing to use DXM when they reported it, so it may have been due to chronic intoxication rather than any permanent damage). Everyone who did report impairment were very heavy users, i.e., 720mg or more (upper plateau doses) twice per week or more often extended use over at least one year On the other hand, many people seem to be able to use DXM very heavily for years without adverse effects, though. So in any case, be careful!. Like other psychoactive drugs, DXM should not be used by people who are mentally or emotionally unstable. I tend to believe that NO recreational drug (legal or not) should be used unless the user is in a calm, rational mood, free from anxiety or negative emotions, and is in a controlled setting where s/he will not have to drive. Speaking of which, as DXM is an intoxicating drug, don't drive under the influence. Ever. But I shouldn't have to tell you that, right? High doses of DXM can be very dissociative. While this is not necessarily bad, you should know what you are getting into first. A high-dose DXM trip is not like an LSD trip; it more closely resembles ketamine. You will most likely encounter experiences that you didn't expect, and possibly didn't want. While this is OK for the more committed psychonaut, casual users of hallucinogens might want to think twice before taking a high dose. Prolonged use of DXM, or extended doses of DXM (including the polistirex formulation), may cause problems due to the buildup of DXM (as opposed to DXO), and the resulting activity at sigma receptors (see Section 10.2). Sigma receptors seem to have a potent modulatory role on neurons, possibly inducing permanent or semi-permanent changes when they are activated for long periods of time (most studies so far indicate over 3 days of high DXM concentrations are required before such changes occur). Furthermore, sigma activity seems to be correlated with delusional thinking, which should probably be avoided, especially in the inexperienced. Some people are allergic to tartrazine (FD&C Yellow #5), which is present in several cough syrups. Sensitivity to tartrazine is rare, but is frequent in people sensitive to aspirin. Avoid tartrazine if you are, or think you might be, allergic to it or to aspirin. Note that, based on anecdotal evidence, I believe that sensitivity to other dyes may develop from chronic use. The large amount of glycerine, glucose syrup, and sugars present in cough syrups can give some people problems ranging from stomach ache to sugar shock. Obviously anyone with diabetes or a family history of blood sugar problems should avoid cough syrups. 4.18   What About Other Cough Suppressants? There are other cough suppressants available, of course, but none of them are likely to take the place of DXM. 4.18.1   Noscapine Noscapine is a natural ingredient in opium, and is related to papaverine. It doesn't seem to have any opiate-like effects (other than cough suppression) and is not constipating. It may be a NMDA/sigma ligand like DXM. Adverse effects and effects of overdose include drowsiness, dizziness, headache, nausea, allergic rhinitis, conjunctivitis, and skin rashes. I have no idea whether it has recreational effects at high doses, but I wouldn't advise finding out. Oral adult dose is 25mg-50mg 3-4 times daily. 4.18.2   Opiates Opiates are of course still used as cough suppressants; the most common is codeine, which is still used for severe coughs (although some research suggests it is no better than DXM). Other opiates have been used for severe cough. As an interesting bit of trivia, heroin was first marketed for cough suppression. The recreational effects of opiates are fairly well known, and are in any case beyond the scope of the DXM FAQ. 4.18.3   Topical Anaesthetics A variety of substances have been used as topical anaesthetics to numb the throat, including phenol and methol. These have no recreational use potential (and in general are highly toxic in overdoses). 4.18.4   Can DXM be Detected on Drug Tests? As DXM itself, probably not; nobody bothers to look for it. There has been some anecdotal evidence that DXM can cause false positives for opiate tests, but one paper (374) disputes this. There may be more reliable evidence that DXM can cause false positives for PCP and possibly cocaine. So keep this in mind before using DXM if you have to take a drug test. If worse comes to worse, you can always claim you had a bad cold, and ask them to do a test which will discriminate between opiates and DXM. Good luck!