6 DXM Side Effects and Other Things to Avoidused at Erowid with the permission of author William White
minor update: July 11, 2002 - modified itching section.
Like all drugs, DXM has side effects and risks. While mild in most people, they cannot be ignored. DXM is not a "safe drug" or a "harmless drug" (two oxymorons if there ever were). This section details side effects that you may encounter, and is the largest section in the FAQ (other than trip experiences).
I have reported every adverse effect (side effect) that has been related to me as a part of a DXM experience, some that have never shown up but have occurred with other dissociatives, and a few that are just speculation. Many of these have been isolated events; some have occurred only when DXM was combined with other drugs. Keep in mind when reading this section that most, if not all, of these, are infrequent side effects. If you've ever read the little information sheet that comes with any prescription medicine, you'll know that pretty much any drug you take has a plethora of side effects, most of which you'll never encounter.
I have tried to organize the side effects roughly by the frequency of occurrence, but I have not performed any real statistical analysis yet, so this is very rough. Instead of trying to give percentages I break the frequency down into the following categories, with additional categories for risks that occur with other dissociatives or may occur in theory:
|Frequent||Experienced by more than 20% of DXM users|
|Occasional||Experienced by 5% to 20% of DXM users|
|Rare||Experienced by 1% to 5% of DXM users|
|Very Rare||Experienced by less than 1% of DXM users|
|Non-DXM||A known adverse effect of other dissociatives|
|Theoretical||A theoretical adverse effect of dissociatives|
Keep in mind that I may have missed some critical research, so don't think that just because I list a risk as "theoretical", that it can't happen to you.
6.1 What are Some Minor Risks of Occasional Use?
Although generally very safe, you should be aware of some of the possible adverse effects that can occur with occasional use of DXM. These are ordered roughly by frequency of reporting, but I don't have any hard figures. These are all fairly minor risks or adverse effects, and though they may contribute to a bad trip, are probably not cause for concern. However, (and I will repeat this often), if in doubt, see a doctor!
6.1.1 Nausea and Other Gastric Disturbances
Probably the most commonly reported side effect is nausea, most likely a simple result of gagging down a bottle or two of cough syrup or a bunch of big gelcaps. People who use the gelcap or capsule preparations do not, in general, experience as much nausea, although DXM itself, like peyote, can occasionally cause nausea (this is less common than nausea from syrups). DXM free base and "Agent Lemon" (see Section 11) seem to cause the least amount of nausea.
Many cough syrup preparations can cause considerable amounts of bloating and gas. Expect to pass gas for the next day. Stomach cramps and other gastric disturbances, probably from the amount of sugars and thickeners, are also common. Preparations with guaifenesin tend to induce vomiting at recreational DXM levels. Mixing DXM with large amounts of alcohol can have the same effect; one poor individual who mixed DXM with a large quantity of alcohol vomited for over two hours.
Serotonin syndrome (see Section 6.2.9) is another possible cause of nausea and diarrhea, but doesn't seem to occur except when DXM is combined with other serotonergic drugs (mainly antidepressants).
Closely related to nausea, DXM can cause dizziness in many users. If you get motion sickness this is probably a bad thing; otherwise, enjoy the free-fall sensation. Dizziness is almost certainly a result of impaired processing of vestibular sensory input (i.e., signals from the middle ear, where position and motion are sensed).
6.1.3 Mild Allergic Reactions and Histamine Release
See Also: The Itch
Ah, the "Robo Itch". Some people get it and some don't. There's evidence that at least some of the cases of Robo Itch are a psychological reaction to mild anesthesia, but many are probably a result of histamine release - not necessarily an allergic reaction per se, but a possible consequence of DXM's pharmacology. The itching tends to go away, and although scratching is pleasurable (and a loofah is wonderful), take care not to overdo it.
Actual allergic reactions have occurred, and often these are a result of the "inert" ingredients, usually one of the dyes (e.g., tartrazine). A topical antihistamine spray might be a good idea. You should always keep an oral antihistamine on-hand, at least during your first few DXM experiences (or when trying out new preparations). Just remember not to use any prescription, non-drowsy antihistamine with DXM. Diphenhydramine (BenadrylTM) is a good OTC antihistamine that is probably safe to combine with DXM (at least it hasn't caused anyone problems yet).
People who have used CoricidinTM tablets have reported that the Robo Itch seems to be completely absent. Be warned, however, that one should not use DXM+antihistamine tablets above the second plateau due to the potential for adverse anticholinergic effects (which if nothing else tend to cause bad trips).
Note that some people find the itching to be unpleasant enough to keep them from trying DXM again, and a few people have scratched themselves raw. Do take care.
6.1.4 Sexual Dysfunction
DXM commonly inhibits orgasm in males and occasionally in females. When orgasm does occur it is often accompanied by profuse sweating and muscle rigidity. Sex probably isn't a good idea due to the potential for aggravating hypertension (see Section 6.1.12). Besides, the inhibiton of tactile sense tends to make sex a less than thrilling experience.
6.1.5 Diaphoresis (sweating)
Many DXM users note sweating both while on DXM and for several hours after coming down. Some have noted a peculiar odor to the sweat, which may be metabolites of DXM or may simply be a consequence of enhanced sense of smell. In any case, just drink lots of water and you should be fine.
6.1.6 Impaired Judgement and Mental Performance
Category: Frequent (especially upper plateaus)
This one's a no-brainer. DXM inhibits normal mental functioning. That's why people take it. Whether this is fun to you is, of course, entirely up to you. Some people simply find DXM makes them feel too stupid. There is also some evidence for impairment of judgement, so a trip sitter is a good idea. Oh, and don't think for a moment that you can drive on DXM; even if you can't tell, it greatly reduces reaction time.
Category: Frequent (especially upper plateaus)
Yes, hangovers can happen. See Section 6.9.
6.1.8 Tachycardia (Increased Heart Rate)
This seems to be fairly common but not particularly serious; generally, a heart rate in the range of 90 to 120 can occur. This is probably a side effect of the stimulant qualities of DXM. Substantially higher heart rate may indicate a panic attack (see Section 6.2.1).
Two users have reported that benzodiazepines (esp. clonazepam) prevent this side effect.
6.1.9 Pupil Dilation or Constriction
Although it doesn't happen to everyone, some report substantial pupil dilation on DXM, similar to the pupil dilating effect of LSD. This is probably a dead giveaway that you're "on something", so you might want to know if it happens to you before trying to get away with being on DXM in public. And may your eyes dilate to the size of saucers and attract cops for miles around if you ever drive on DXM!
There are also a limited number of reports of pupil constriction. These seem to occur with much less frequency. In both cases, pupils remain normally responsive to light. Two people have reported to me that their pupils were significantly different in size; usually this is an indication of something Very Wrong going on in the brain (hemorrhage, stroke, or other CVA), so if this happens to you, seek medical assistance! It is possible that this may occur as a result of asymmetrical effects of dissociatives on the cerebral cortex, and isn't indicative of any damage at all.
6.1.10 Hot and Cold Flashes
Hot and cold flashes during the trip occasionally occur, and are not generally serious. One user reported frequent extreme hot flashes, which eventually got bad enough that he sought medical assistance. A few people have reported hot flashes several days after the DXM trip is over. This may simply be a phenomenon of sensory dissociation, or it may be indicative of an actual fluctuation in core temperature (see Section 6.1.13).
A few have reported that eating a small amount of food from time to time can prevent hot and cold flashes, so they may be related to rise and fall in blood glucose levels.
Two users have reported that benzodiazepines (esp. clonazepam) prevent this side effect.
6.1.11 Facial Edema
DXM occasionally induces mild facial edema (swelling and buildup of fluid). This may be due to a histaminergic effect. It does not seem serious.
6.1.12 Mild Hypertension (High Blood Pressure)
DXM, like other dissociatives, can cause mild hypertension (high blood pressure). This is not generally considered serious, as the elevated blood pressure is still within the normal range. If you have high blood pressure to begin with, stay away from DXM (or stimulants for that matter). There are cases of serious hypertension from dissociatives; see Section 6.2.6.
Two users have reported that benzodiazepines (esp. clonazepam) prevent this side effect.
6.1.13 Mild Hyperthermia (Increased Temperature)
A rise in body temperature of about 1 degree Farenheit (0.5 C) has been noted by many users of DXM, and low-grade fever is one of the hallmarks of dissociative intoxication. It doesn't seem to be a serious condition. Serious rises in body temperature have been noted with dissociatives, however; see Section 6.2.5.
Two users have reported that benzodiazepines (esp. clonazepam) prevent this side effect.
Category: Rare (more common with other dissociatives)
As DXM is a dissociative anesthetic, it will make you less aware of the normal body senses, including muscle fatigue and pain. As a result you can easily over-exert or over-stretch yourself, especially if you are out dancing or engaging in other physical activity. Pay close attention to your body if you plan on moving a lot.
On a somewhat related note, many people report that heavy exercise under the influence of DXM can cause nausea. This seems to occur mainly at the second plateau and above; in contrast, one user reported swimming on a first plateau dose to be a very pleasant experience.
6.1.15 Urticaria (skin rash/wheal)
Category: Very Rare
Urticaria, a skin rash or wheal typically consisting of white or red bumps, is rarely reported from DXM, and typically appears on the arms or less commonly the chest or face. It is probably related to histamine release. It goes away soon after the trip is over.
6.1.16 Increased Bile Secretion
Category: Very Rare
Two people have reported greatly increased bile secretion from DXM. It's possible that DXM may be released into the bile and may be subject to re- absorption, but this has never been demonstrated. In any case, although this may be a source of discomfort, it doesn't seem particularly serious.
6.1.17 Inappropriate Behaviour
Category: Very Rare (more common with other dissociatives)
Some people have reported slightly to moderately inappropriate behaviour while on DXM. The most common example of this is blurting out whatever comes to mind, i.e., avoiding those little white lies we normally hold on to for the sake of politeness. Other cases included public nudity, impaired grooming, and abnormal gestures.
There are numerous examples in the literature of inappropriate (and often dangerous) behaviour in PCP users, but to my knowledge nobody has yet done anything terribly outrageous or dangerous while on DXM.
One user with a blind spot in one eye due to a stroke reported hallucinations in the blind spot persisting for several days. This eventually went away but was not particularly enjoyable. LSD, cannabis, and alcohol all failed to induce this effect. Ketamine did, however. DXM may also interfere with the biological clock and prevent light entrainment (221,230).
6.2 What are Some Major Risks of Occasional Use?
There are also more serious adverse effects that can occur from DXM use. All of these should be taken seriously, and if at all in doubt about your health, see a physician immediately. As far as I know nobody has ever died or suffered serious injury from any of these adverse effects, but they generally aren't pleasant either.
6.2.1 Panic Attacks
Several users have reported panic attacks, and I am beginning to think some people may be susceptible to this from DXM. This seems to be worse when DXM is combined with other drugs, including marijuana (cannabis). The trouble with a panic attack is, once you realize you're having one, it can make you feel out of control of the drug experience, which makes the panic attack even worse. This is a difficult vicious circle for some people to break. Fortunately this mostly seems to happen with high doses (around 10 mg/kg and up).
If you find yourself having a panic attack, there isn't really much that you can do for yourself except relax, take deep and even breaths, and try to calm down. If you find yourself hyperventilating, breathe into a paper bag (which really does work, by raising blood CO2 levels).
Benzodiazepines (ValiumTM and related drugs) are an effective treatment for panic attacks. However, they have several drawbacks. They must be prescribed by a physician (at least in the US), and they will usually stop the DXM experience very suddenly. They are both psychologically and physically addictive, and withdrawal from regular use can cause brain damage.
Benzodiazepines, esp. clonazepam, may prevent panic attacks from DXM, but must be used with care and under the guidance of a physician.
6.2.2 Psychotic Breaks
Psychological side effects to psychedelics can be quite varied. Bad trips are certainly possible, as with any drug. As with other psychoactive drugs, especially hallucinogens, there is always the chance that a mental illness may be triggered by the experience. Keep in mind that DXM is related to PCP, and some people really don't get along well with dissociative anesthetics. The chance of experiencing a psychotic episode probably increases with dosage.
Many of the cases of DXM "abuse" in literature have concerned psychotic episodes (the same is true for LSD). This probably skews the perception of how frequent these events are, since most of the published accounts come from hospital visits. The vast majority of DXM users do not experience psychotic breaks. From personal communications I have noted nine cases of DXM-induced psychotic breaks that required hospitalization; of these, six involved regular users.
6.2.3 Impaired Judgement in Critical Situations
Category: Rare to Very Rare
I've already mentioned how DXM impairs driving ability. It also seems to impair judgement, both about one's abilities and one's susceptibility to harm. This is bad news when it comes to driving and other critical situations. So before you consider doing anything where your life may be on the line, know good and well that DXM will impair your performance.
Disturbingly, DXM also impairs judgement in sexual behaviour. While it does tend to make orgasm difficult for males, it has also been known to impair good judgement about sex. While I don't think DXM has the same ugly potential as Rohypnol or other benzodiazepines, it can make you stupid and fearless enough to not use protection, and that can be a deadly mistake.
I have actually heard from one person about DXM being used to lower inhibitions for the sake of getting someone's consent. This is an entirely detestable practice, although not limited to DXM (alcohol is used regularly for this purpose daily, but that doesn't make it right).
Let me put it simply. If you and your partner want to use DXM with the intention of having sex on it, that's your business. But if you use DXM to lower someone's inhibitions, that's an entirely different situation. Basically, it means you can't get laid without impairing someone's judgement. There's a word for that: loser. It'll also get you thrown in prison, where you can find out how much fun nonconsensual sex really is.
Besides, it's much more fun where the other person has all their mental and physical abilities.
Category: Very Rare (more frequent with regular use)
One person reported a long-lasting depression and paranoia after a single episode of DXM use. This individual was age 15 at the time; I suspect that young teens may be more susceptible to depression and other mental illnesses from DXM use than adults.
6.2.5 Serious Hyperthermia (High Temperature)
Category: Very Rare (more frequent with other dissociatives)
One user reported a case of hyperthermia (increased body temperature) which could have been dangerous, with a rise in body temperature to 103 F (38 C). The individual in question also had a cold at the time, so part of this might have been a result of existing illness.
In the case of serious hyperthermia there is an immediate need to lower body temperature. Sponge baths with cool water and drinking cold liquids are the safest way, although a few physicians have recommended ice-water baths for severe cases. ALWAYS have someone sober to make sure the person doesn't go into shock and drown. Whenever body temperature nears 105 F (40 C) you should get medical attention. Temperatures at or above 107 F (41 C) will probably cause permanent brain damage.
There is a condition that occurs sometimes with volatile anaesthetics called Malignant Hyperthermia, which is often fatal and seems to involve genetic susceptibility. Malignant Hyperthermia can raise temperature to 112 F (44 C) and is obviously a different sort of threat than the one or two degree temperature rise from dissociatives. I have never heard of it occurring with any dissociative (anaesthetic use or not).
6.2.6 Serious Hypertension (High Blood Pressure)
Category: Very Rare (DXM plus stimulants)
I have heard of only one serious case of hypertension, when DXM was used in combination with pseudoephedrine. DXM itself typically raises blood pressure slightly (although a few people experience a drop in blood pressure). This is probably due to sympathetic activation from DXM's dopamine reuptake inhibiton and from downstream effects of NMDA blockade.
Take care combining DXM with stimulants or physical exertion. There is always a chance of hypertensive crisis and hemorrhage, and it's not always easy to predict. If in doubt consult a physician, since drugs which lower blood pressure aren't commonly available, and must be used with considerable care. Avoid DXM if you have an existing high blood pressure condition.
PCP use has been cited as a cause of rhabdomyolysis, a condition where muscle cells break down, and myoglobin and other bits and pieces of muscle cells leak out into the bloodstream. To put it simply, they don't belong there, and the body doesn't know what do with them. They end up essentially clogging the kidneys, which shut down. This can also occur with a variety of stimulant drugs, including amphetamine and MDMA (ecstasy). Nobody's really quite sure why this happens, although some believe it to be a combination of repeated or excessive muscle cell activation, dehydration, and high body temperature (not surprisingly, most MDMA-induced rhabdomyolysis takes place at raves).
This is of course a serious condition, but hasn't to my knowledge ever occurred from DXM. It's not always fatal, but if enough muscle tissue is destroyed, it can be. Needless to say, medical intervention is required.
I have received anecdotal evidence from one person who complained of prolonged illness (3-4 days) following DXM use, during which she did not produce urine, followed by about three hours of bloody urine. Needless to say she didn't repeat the experience. I haven't a clue if this could have been rhabdomyolysis (and she didn't consult a physician at the time), but obviously something was amiss with the kidneys. Incidentally, this occurred after years of DXM use.
6.2.8 Respiratory Depression
One of the risks of high doses of dissociatives, and in fact the proposed mechanism for overdose fatalities, is respiratory depression (201). The two medically recorded deaths due to DXM overdose (one of which was a suicide) were attributed to this. I have never heard of any other cases of DXM-induced respiratory depression, although I suspect it is a serious threat at doses above 15 mg/kg.
The real danger of respiratory depression (other than death of course) is hypoxia (insufficient oxygen) and subsequent brain damage. DXM does, of course, protect the brain from hypoxic damage, so hypoxia with DXM is probably safer than an equivalent degree of hypoxia with opiates, but there's still no need to put your brain at risk. In the grand scheme of things hypoxia is just one risk among many for brain damage with regular use of high-dose DXM, but the actual data from DXM users shows that brain damage is extremely rare.
A lot of people worry about respiratory depression because of a feeling of shortness of breath that often accompanies DXM intoxication. This may be a consequence of the brain "taking over" breathing from conscious control, as well as impaired perception of the breathing process. If you're really worried, stop taking DXM. I suppose you could rig up an oxygen mask, but if you're enough of a hardcore psychonaut to consider that you probably don't need my help.
6.2.9 Serotonin Syndrome
Category: Theoretical (especially DXM + antidepressants)
Serotonin syndrome is a recently-identified condition that typically occurs when combining serotonergic drugs (i.e., drugs that stimulate, or mimic, serotonin activity in the brain). Most of these drugs are antidepressants (MAOIs, SSRIs such as ProzacTM or ZoloftTM, tricyclics, lithium, and atypical antidepressants); others include buspirone (BuSparTM), MDMA (ecstasy) and other phenethylamines, tryptophan, harmine and harmaline (both recreational MAOIs), and possibly serotonergic hallucinogens such as LSD, psilocybin, and DMT. Phentermine, fenfulramine, and phen-fen can also cause serotonin syndrome when combined with DXM.
DXM induces a release of serotonin, and while it has never been demonstrated to cause serotonin syndrome by itself, it has been shown to do so in combination with other serotonergics (365). In particular, combining SSRIs and DXM may be risky; one paper found serotonin syndrome from an SSRI combined with DXM with a concurrent vascular disease (364).
Serotonin syndrome is indicated by a combination of three sets of symptoms: changes in mental status, autonomic dysfunction, and neuromuscular abnormalities. Specific symptoms include:
- Changes in Mental Status
- Autonomic Dysfunction
- low-grade fever
- diaphoresis (sweating)
- Neuromuscular Abnormalities
- myoclonus (sudden, brief muscle spasms)
- hyperreflexia (exagerrated reflexes)
- ataxia (incoordination and clumsiness)
Yes, there is some overlap (e.g., shivering can considered as an autonomic dysfunction or a neuromuscular abnormality).
More serious symptoms can include rhabdomyolysis (basically, your muscle cells break open and leak muscle-cell-parts into your bloodstream, poisoning you), coma, and death. Serotonin syndrome deaths are rare, however.
Treatment of serotonin syndrome requires medical intervention, and consists of supporting measures to treat the symptoms, and possibly antiserotonergic drugs. Benzodiazepines (such as ValiumTM) have also been used with considerable success (366).
The astute among you will notice that many of these "symptoms" are characteristics of DXM intoxication. In fact, many serotonergic drugs can cause these symptoms. The question is whether or not the symptoms become severe and numerous. At least one symptom from each of the three categories is generally required for a diagnosis of serotonin syndrome.
Once again, if in doubt, see a doctor. And avoid using DXM in combination with any antidepressant. Remember, combining DXM with a MAOI has been repeatedly fatal!
6.2.10 Major Allergic Reactions and Histamine Release
It is possible to have a major allergic reaction to DXM or to one of the inert ingredients (typically tartrazine). An antihistamine is the obvious solution. If you are allergic to aspirin you may be allergic to tartrazine, and in any case it is a good idea to try DXM at a very low dosage first to rule out allergic reactions to any of the ingredients found in cough syrups. You should also repeat the low-dose test every time you try a new syrup, gelcap, or other DXM formulation.
I have never heard of a serious case of DXM-induced histamine release but it is a possibility. Again, an antihistamine should help, but if things continue to get worse, get medical help.
Even though DXM has been successfully used to prevent seizures, it may actually induce them at high dosage levels (45), especially in epileptics (142). You want to avoid this.
Some users who have taken very high dosages of DXM (above 15 mg/kg) in products containing guaifenesin have lost motor function to the point of choking on their tongues (or at least feeling like it; I've been told that this is technically impossible but I've also been told it isn't). Obviously, nobody should be experimenting at this level without a (sober) assistant. If this happens, seek medical assistance. While I cannot vouch for the efficacy or safety of this procedure, I have been told that one can maintain the airway by grabbing the person's tongue and holding it out of his or her mouth until motor function is regained (or the ambulance comes). Don't try to insert anything into the person's mouth; it could slip and make the problem worse.
6.3 What Are the Risks of Regular Use and Binges?
Prolonged, regular use of DXM has some definite risks. Generally speaking the most common is mania, which has been reported in people using large amounts of DXM (especially to self-medicate depression) (1-3,132,136,139-141). This is probably a combined effect of dopamine reuptake inhibiton, downstream effects of NMDA blockade, and possibly sigma receptors (see Section 10). One user who had formerly used the antidepressant bupropion (WellbutrinTM) reported a similar but somewhat stronger antidepressant effect from DXM, though with greater adverse side effects.
This section may also apply in the case of drug "binges" (using DXM continuously of more than one day). This is to my knowledge much more common with other drugs than DXM, since it does tend to induce a fairly significant hangover after awhile (if for no other reason than the cough syrup is hard on your stomach).
The most serious adverse effects are all related to brain damage. This is a well documented risk of PCP in humans and has been shown with all dissociatives in animal models! The good news is this doesn't happen at human recreational dosage; the bad news is the animal models may not predict the effects of regular use at lower dosages. The other bad news is that PCP may induce brain damage by other mechanisms; the other good news is PCP is unlike DXM or ketamine, and neither DXM or ketamine users have shown much impairment.
This time I have tried to organize by categories representing the degree of seriousness of the adverse effects: permanent brain damage, physical toxicity, temporary mental impairment, psychological disorders, and miscellaneous.
6.3.1 NMDA Antagonist Neurotoxicity (Olney's Lesions)
Category: Permanent brain damage
Onley's Lesions (named after a researcher named Olney, appropriately enough) are a particular type of damage observed from NMDA antagonists (dissociatives). Damage occurs primarily to the posterior cingulate and retrosplenial cortex (289), and to a lesser extent the entorhinal cortex, dentate gyrus, and olfactory regions (213). The posterior cingulate may be involved in evaluating one's own behaviour (316), verbal and auditory memory (294), spatial memory and cognition (316), and language, notably metaphor comprehension (303). The retrosplenial cortex may be involved in novelty encoding (321) and learning, memory, and emotional behaviour (324). The hippocampus and adjacent areas are well known to be deeply involved in intermediate-term memory and forming relationships between sensory data, and damage to the hippocampal formation causes amnesia both in humans and animals. Full detail on Olney's lesions is given below; see Section 6.5
If this strikes you as areas that DXM interferes with, congratulations, you've been paying attention. On the other hand, these are functions that, according to all human research, recovers after occasional use of dissociatives. There is considerable documentation of PCP users suffering deficits in language (especially finding words), memory, cognitive skills, and motor skills (which may be a result of PCP's peculiar toxic effects on the cerebellum not shared by other dissociatives). Perhaps most disturbingly, this damage also includes the ability to form emotional ties and recognize emotions in others, and an increase in flattened affect (outward emotionality). PCP's reputation for creating psychopaths is probably 99% media hype, but in this case (unlike most drugs the media demonizes) it probably has a kernel of truth.
PC has been well studied, and an on-line review is available (355). Some of the papers cited in this source are, in my opinion, a bit dated, but it provides a good starting point for understanding what can occur with long-term high-dosage use of dissociatives. Some speculate the damage is caused by hypertensive strokes or hemorrhages, although it is worth noting that this speculation was made prior to the knowledge of Olney's lesions.
Studies with PCP show that this sort of damage sometimes does resolve (though sometimes after months or years). And users of ketamine seem to show considerably less damage than users of equivalent amounts of PCP (pers. comm.). Even more skepticism is warranted since one popular method for making PCP involves a precursor chemical which, when heated, releases cyanide gas (196). Samples of street-grade PCP show that many contain a fair amount of this precursor (the sloppiness of drug chemists is probably the biggest reason to avoid synthetic drugs).
Still, I have received a few anecdotal reports of DXM-induced degradation of mental performance that are consistent with this type of damage. To be precise, I have received eight first-hand reports of this over the past five years, and have read about one other. Three of the eight seemed to show permanent damage; in the other five, it resolved after several months and may have been due to depression. There have been numerous second-hand stories ("I heard from this ex-girlfriend about this guy who drank a bottle of cough syrup and his brain melted and ran out his nose"), but I don't necessarily consider them accurate.
The published account (136) involved a 39-year-old insurance salesman who consumed 1500 mg DXM, 5000 mg guaifenesin, and 3 mg alcohol, about once per week. A SPECT scan showed widespread dysfunction of the cerebral hemispheres, and EEG mapping showed excessive right central alpha activity. The researchers suggested a concurrent diagnosis of temporal lobe epilepsy on the basis of extreme religiosity andexcessive note-writing (although I've known more than one who experienced this from DXM). His condition continued to deteriorate after ceasing DXM use.
One former user told me of his experiences following use of 720 mg DXM twice to three times a week for 3 months, and then four to five times a week for another three months. After quitting DXM, he experienced uncontrolled shaking of muscles and severe muscle fatigue for three years, and permanent difficulties in forming complex thoughts into words. He described the latter as "trying to make a complicated sentence out of alphabet soup".
Of the first-hand accounts, three involved concurrent use of other drugs, in all cases stimulants (pseudoephedrine in one, amphetamines in the other two), and in one case (DXM and amphetamine) also PCP, ketamine, and MDMA. Of the four cases not involving other drugs, all four used in excess of 1000 mg per week, three using over 2000 mg per week, and all four for a period of at least six months.
To make matters even more complicated, I've also spoken to at least twelve other people who have used in excess of 1000 mg per week for a period of one year or more, without obvious evidence of lasting impairment. One was formally tested and showed no significant impairment. A few of them remarked that there was a recovery period of several months to two years during which they felt "burned out".
So how do you avoid this sort of damage? Well, the obvious way is, don't do DXM. However, people regularly use drugs which can and often do cause brain damage (including alcohol, cocaine, amphetamines, and depressants), so I have a sneaking suspicion not everyone is going to drop that bottle of Tussin and walk away from the medicine cabinet.
The best advice I can give you, other than Just Say No, is Just Stay Low. Keep doses as low as necessary to meet your objectives, using meditation, sensory deprivation, theta stimulation, etc., to boost the effects (see Section 7.4). And since I mentioned it, don't use DXM without a set objective and goal. It is not a casual psychedelic which should be taken just to relieve boredom; that's why the Goddess gave is marijuana and mushrooms (wait, I can't say that ... strike that.) Okay, fly to somewhere where it's legal and then smoke marijuana. Don't break the law. But more importantly, don't use DXM so often that it becomes damaging. Besides, like any other psychedelic it loses its magick when used too often.
If you have already spent the last five years drinking gallons of cough syrup, maybe now is the time to stop, wait a year or so, and then decide whether you want to continue. More practical advice for psychonauts and the hardcore is given below, in Section 6.5.
6.3.2 Cerebral Hemorrhage and Stroke
Category: Permanent brain damage
PCP has been repeatedly blamed for causing cerebro-vascular accidents (CVAs) such as hemorrhages and strokes, with numerous papers referring to this (a good review is provided in (355)). In conversation (pers. comm.) and "off the record" one researcher into dissociative neurotoxicity told me that this mechanism may be less established than it seemed, for the following reasons:
- Most of the research suggesting CVA damage from PCP came out during the initial PCP epidemic, when it was obvious that people were being hurt but there wasn't much time to figure out why, and the research was somewhat rushed.
- Nobody at the time knew any mechanism for NMDA antagonist neurotoxicity and it wasn't considered as a possible culprit.
- Many people who used PCP were polydrug abusers and mixed it with amphetamines, cocaine, or other stimulants, a practice which is much more likely to result in hypertensive CVAs
- Much of this research was funded during the early years of the War on Drugs, and other research from this time is known to be biased.
The symptoms of a CVA can include sudden (often intense) headaches, slurred speech, ataxia, confusion, numbness or loss of muscle control to parts of the body, and abnormal pupil responses. That some of these are also symptoms of DXM intoxication complicates matters for physicians, so make sure if you do see a doctor you tell her or him about your DXM use (and what it does).
There is, I think, enough data to show that PCP is possible of inducing CVAs, at least in those with underlying hypertension and who go on "binges". It's never been demonstrated with DXM, but there hasn't been nearly as much use of DXM as PCP either. Perhaps with increasing recreational use of ketamine the issue will be resolved. If you use any drug regularly you should seriously consider donating your body to science when you die, since it really will help us in our understanding of the actual dangers of drugs. Not that a solid knowledge of the dangers of alcohol and tobacco stop anyone from using them, mind you.
I know of one person who developed a severe headache during an extended DXM trip, which lasted for several days. This person experienced no loss of mental ability, but hasn't had an MRI (a type of brain scan) either (and isn't likely to since they don't come cheap). So who knows, it could have happened. If it makes you any happier, a DXM-induced CVA is probably healthier than one induced by stimulants, since the secondary quinolinic acid induced damage (see Section 4.15.2) is blocked by DXM. Still, that's small comfort when you risk irreversible brain damage.
6.3.3 Other Neurotoxicity Mechanisms
Category: Permanent Brain Damage
Some have suggested that chronic NMDA blockade may be a mechanism for Alzheimer's disease (100), though this could be due to advanced stages of Olney's lesions. There is also a remote possibility of toxicity to 5HT (serotonin) neurons due to induced overactivity, similar to that resulting from MDMA (52). This has, however, never been observed with any dissociative.
Excitotoxic rebound is a process by which brain cells, accustomed to a lower level of activity, essentially "burn themselves out" when a depressant drug is removed. Alcohol, benzodiazepines (tranquilizers, e.g., ValiumTM), and barbiturates (sedative-hypnotics or "downers") are well known for causing severe excitotoxic rebound. It is possible that regular use of DXM could lead to an upregulation (i.e., increase in number) of NMDA receptors as the body tries to compensate for the blocking effect of DXM. Recent research suggests that NMDA receptors do not upregulate with blockade, so excitotoxic rebound probably isn't a major factor to worry about.
Category: Psychological disorder
As stated above, mania has been documented from regular use of DXM (1-3,132,136,139-141). There may be biological susceptibility to it. One of the problems with mania is that, unlike depression, manic patients are often unaware that they are suffering from a psychological disorder. In all recorded cases, mania went away when DXM use was discontinued.
Category: Psychological disorder
In addition to mania, DXM can also induce depression, although depression is more often associated with DXM withdrawal. In a few cases, depression can occur even during DXM intoxication. This can range from mild dysphoria to suicide attempts, and there have been a few anecdotal reports (unverified, at least by me) of actual suicides among heavy DXM users. These stories were one of the reasons that one group of DXM users discontinued using DXM. There is also a published case of a successful suicide attempt by DXM, although it is not known if DXM-induced depression had anything to do with it.
There is some research right now indicating that dissociatives may actually have antidepressant effects (208,212,223,245,250), but other research casts doubt on this (225,229). It seems that in animal models, dissociatives can act like antidepressants on some tests, but not necessarily others. What may be happening is that, by inhibiting memory and overall cognitive function, the dissociative is producing identical results in the test models but for a completely different reason. Others suggest that dissociative depression occurs primarily when tolerance is reached and as a result of withdrawal, or because of a perception of significant mental impairment and the fear that it might be permanent. Withdrawal does improve cognitive abilities (355).
Whatever the reason, it does seem to be a real risk of long-term use. If you start finding yourself hostile or depressed, or your friends start mentioning it, lay off the DXM for a few months and see a mental health professional.
6.3.6 Violent Ideations, Antisocial Behaviour, and Paranoia
Category: Psychological disorder
A few regular users of DXM have reported to me that, after a year or so of constant use, they developed regular, violent ideations, and would tend to respond in anger to any perceived threat. A few others have noticed a paranoia while using DXM regularly. Two may have exhibited antisocial behaviour but to my knowledge no formal tests have been done (and in one of these cases I suspect the individual wasn't terribly social to begin with).
My hunch is DXM may actually be more pleasant to antisocial personalities because it seems to impair perception of social cues, reduce stress related to social situations, and generally reduce inhibitions. It may be that antisocial personalities just happen to like DXM more than others, who don't enjoy being cut off from interpersonal interactions and social behaviour (or who find such interaction to be more unpleasant than most).
It is possible that violent ideations coupled with psychotic breaks could result in violent behaviour; this is a well known side effect of PCP, and can have such extreme consequences as parents trying to kill their children (199). However, these cases are not nearly so common as they are made out to be (192). Also, one paper on PCP found that violence was correlated with personality and background, and not everyone was susceptible (193).
The only person who reported this with whom I've communicated after he stopped using DXM told me that these symptoms went away after about three months.
6.3.7 Memory Impairment
Category: Temporary Mental Impairment
DXM inhibits memory. If you use it regularly, your memory will be impaired. No big secret here; if you smoke weed all the time you probably won't have much of an attention span either. Still, don't forget that it can take awhile (up to a month or so) for memory to come back to normal after discontinuing DXM. And since DXM inhibits encoding of memories, keep in mind that you may not have coherent memories from times when you used DXM, even for days after the experience. This is nothing new to alcoholics, of course, but it isn't exactly fun in either case, and years from now you may find yourself regretting not having remembered the times when you regularly used DXM.
6.3.8 Language Impairment
Category: Temporary Mental Impairment
While on high doses of DXM most people remark on impaired language skills, especially being unable to find the correct word. With regular use of DXM, many people have noticed that their "inner narratives" become more and more abstract and pre-linguistic, and that they find it more and more difficult to convert concepts into language. Some of this may be due to the fact that the mental states induced by DXM don't really have terms, but I have little doubt that there is some transient (and possibly permanent) inhibition of language skills. Although in all cases I've known of (except for those listed above under Section 6.3.1) this has been a temporary phenomenon, it's possible that language skills have to be re-acquired after loss of brain cells. Unproven, but possible.
One person remarked that it felt as if the skills had been somewhat forgotten due to lack of use, since DXM tended to make him think in terms of pure concepts rather than language, and that as soon as he started using language in his inner narratives, the skills came back. Perhaps like muscles, mental skills must be used regularly to stay in shape.
6.3.9 Weight Loss
Category: Physical Toxicity
Before you get any stupid ideas, the weight comes back after you stop using DXM and typically you end up worse off than before (similar to speed in this respect). I wouldn't mention it, but I've spoken with someone who used heroin for the weight loss (somehow I think this person's going to get the Darwin Award). Now that I've hopefully dissuaded everyone, here's the skinny (so to speak). Regular use of DXM can induce weight loss, typically about 10 to 20 pounds (4.5 to 9 kg), and although I don't know how much is fat and how much muscle, I suspect it's not all fat, since one regular user noted a significant decrease in strength.
Part of this weight loss is probably due to a drop in appetite, since it inhibits appetite for food (as well as most other physical appetites) and since one is often nauseous from drinking cough syrup. Part of it may be due to a stimulant effect, or an increase in metabolic rate. Regardless of the reason, it is temporary.
6.3.10 Loss of Muscle Control
At high enough doses, DXM, like any other dissociative, can cause loss of muscle control, but that's not what I'm referring to. With regular use of DXM, some people have noticed extreme weakness and muscle tremor, like that found during exhaustion with weightlifting. Exactly is going on is beyond my knowledge; it may be related to blood glucose (everyone who mentioned this was a regular user of cough syrup), it may be neuromuscular in nature, or it may be a result of exhaustion from muscle rigidity.
It's worth noting that DXM (more so than DXO) blocks calcium channels, and that regular use of DXM may lead to a buildup of DXM in the bloodstream which could eventually affect calcium channels. This is idle speculation, however. Regardless of the cause, this sort of problem is probably your body's way of telling you to lay off the drugs.
6.3.11 Habituation and Psychological Addiction
Anything can become psychologically addictive: drugs, television, shopping, gambling, sex, masturbation, thumb-sucking, whatever. Generally speaking though one can distinguish a point at which one's habits become self- destructive, and at this point it's generally safe to say psychological addiction has occurred.
There is much talk when discussing any drug about the difference between psychological and physical addictions. At the extremes, this isn't so difficult to understand. Rats won't self-administer LSD, and people who take LSD compulsively are psychologically addicted. People who use alcohol regularly eventually require alcohol for their brains to function normally, and are considered to be physically addicted.
In the middle is a grey area. Is caffeine physically addictive? With regular use, the brain does adjust to it, and there is a well-defined set of withdrawal symptoms, but people don't generally think of caffeine as being physically addictive. The same holds true for nicotine, which some rate as the most addictive drug known to man.
More recently, psychological addiction has come to be understood as the desire or need to take a drug (especially when there are serious consequences to doing so), whether out of enjoyment of the drug (primary psychological addiction) or out of a desire to avoid the negative effects of withdrawal (secondary psychological addiction).
There are documented accounts of DXM users who continued to use DXM in spite of adverse consequences (136), and I have received about two dozen reports of people whose use of DXM caused them significant trouble. Everyone I was able to follow up on had discontinued use, although some experienced relapses into use. This follows the patterns of PCP users (195,202-203).
Based on this I would say that DXM is habit-forming or psychologically addictive. How much? Well, it's hard to tell; any rating of addictiveness is definitely subject to bias. Personally, I'd say it's more addictive than marijuana, and probably about as addictive as (or slightly less than) alcohol, in those susceptible to dissociative addiction. There does seem to be some sort of factor (or factors) which are involved, since many people can use large amounts of DXM without ever developing a habit. Whether these factors are a part of personality or biology is beyond my knowledge.
Psychological addiction is not itself a threat, although there can be economic and social consequences to it. After all, not everyone likes being around someone who is high all the time, and it does impair your ability to hold down a job, go to school, and interact with your loved ones when used to excess. More importantly, however, regular DXM use may bring about long-lasting or even permanent mental impairment.
6.3.12 Tolerance and Physical Addiction
Tolerance and physical addiction are two different things, although some would argue that the first is a necessary condition for the second. Tolerance occurs where increasing doses of a drug are required to maintain a given level of a drug's effect. One can become tolerant to many drugs, whether they affect the mind or not; some examples are caffeine, alcohol, stimulants, depressants, opiates, nicotine, nasal decongestant sprays, and aspirin and related NSAIDs.
Physical addiction is generally viewed as a condition where the drug is needed for normal function of the body or brain. Tolerance to the effects of drugs can occur without physical addiction, e.g., when tolerance occurs as the body becomes more effecient at metabolizing the drug. However, in the case of psychoactive drugs, tolerance and physical addiction usually go hand in hand.
The big exception to this is the psychedelics. Any LSD user will tell you that tolerance to LSD builds quickly; however, there doesn't seem to be any "LSD withdrawal" when one stops using it that requires one to take LSD to maintain normal function. Though I had formerly worried about rebound excitotoxicity at NMDA receptors, it seems that NDMA receptors do not upregulate with use of DXM; it also doesn't appear that dissociatives are physically addictive (194). They do induce tolerance, some would argue extremely rapid tolerance (called tachyphylaxis), since a second dose of a dissociative a few hours after coming down off the first doesn't seem to induce the same level of effects. This may be related to alcohol tachyphylaxis, since many of the behavioural effects of alcohol may be a result of (direct or indirect) NMDA blockade.
To sum it up, DXM does seem to induce tolerance (and I would guess it is cross-tolerant with PCP and ketamine, but nobody's ever tested that), but there does not seem to be an appreciable withdrawal symptom beyond drug craving (194). Some might disagree, pointing out a definite set of withdrawal symptoms from dissociatives including restlessness, dysphoria, depression, and flattened affect, but these may just be an effect of long-term use itself that persists for some time after discontinuing the drug.
Category: Psychological Disorder
DXM, like other psychedelics (and for that matter any intense experience) can induce psychotic breaks which can be long-lasting. Personal susceptibility seems to be involved here, and some people may have latent mental problems which are triggered by DXM. I definitely would advise against DXM use if you have a history or family history of mental illness, especially schizophrenia, depressive disorders, or antisocial personality traits.
The threat for this sort of thing goes up as use becomes more regular, and some have noted that DXM made them a little bit crazy when they were using it regularly. One person with whom I spoke didn't think this was such a bad thing, but none of the others enjoyed it much. This isn't a particularly common problem, but shouldn't be ignored either. You never know if you're susceptible to a psychotic break until you have one, and coming to your senses in a padded room probably isn't the best trip in the world. Treatment includes antipsychotic drugs and in rare cases electroshock (200).
Some research has linked sigma receptors to schizophrenia (46-49), and chronic use of NMDA antagonists has been shown to upregulate (increase the number or activity of) dopamine receptors (50). This could theoretically mean that DXM could trigger schizophrenia or mania in susceptible individuals. Some researchers have suggested that chronic NMDA blockade and/or sigma activity may be responsible for schizophrenia (100).
6.3.14 Liver, Kidney, and Pancreas Damage
Category: Physical Toxicity
I have found no evidence of damage to the liver, kidney, or pancreas from DXM in medical research, however, there are potential mechanisms for it. DXM itself is metabolized fairly easily; it's the inactive ingredients and some of the more unlikely side effects one has to worry about.
Drinking cough syrup dumps glucose into your bloodstream, and doing this repeatedly on an empty stomach probably puts a load on your pancreas (and stomach, adrenal glands, and probably other parts of your body as well). True, that's their job, but one can overwork any organ. A few long-term users of DXM have reported that after years of use they became intolerant to any amount of sugar on an empty stomach.
There's also the possibility of damage to the liver, especially if the enzymes inhibited by DXM (cytochromes P450-2D6, 3A4, and 3A5) are also involved in metabolizing something else, and that something else ends up being metabolized by another enzyme into something dangerous. This is the sort of thing one has to worry about when inhibiting liver enzymes, and it does occasionally cause problems; as an example, DXM will compete for the enzyme which degrades the prescription antihistamine terfenadine (SeldaneTM). It may happen that the new metabolite of something is a cell toxin and will wreck your liver; this is a proposed mechanism for acetaminophen toxicity. If you are worried, there are blood tests which can assess liver function.
Finally, I received anecdotal evidence from one person about potential kidney damage. This person had used DXM numerous times without problem until once (after a year of regular use) when, while using during a flu, experienced kidney dysfunction and bloody urine. Years later when trying DXM again, the effect repeated itself, with kidney pain, lack of urine production, and (a few days later when her kidneys started to produce urine again), blood in the urine.
Needless to say if this happens to you, it's a good sign you should stop.
6.3.15 Bromide Poisoning
Category: Physical Toxicity
Although some authors have suggested the possibility of DXM-induced bromism (144), actual blood tests have revealed little danger to occasional users, even with large doses of DXM (136). Daily use might lead to a dangerous buildup. Notable symptoms of bromide poisoning include headache, irritation, slurred speech, psychosis, weight loss, hallucinations, and an acne-like rash. Bromism can cause irreversible brain damage. In addition to directly testing bromide ion content of the blood, bromism can be detected by increased anion gap.
DXM may decrease immune function due to sigma activity (51). Chronic use of NMDA antagonists seems to modify alcohol tolerance; this is based mostly on anecdotal evidence and theory, but it appears to be a very real phenomenon. If true, then it is important to note that the GABA receptor effects of alcohol may NOT be changed; in practical terms, you might be a lot drunker than you feel, and this could possibly lead to alcohol poisoning. Be careful, and limit yourself to as little alcohol as possible when using DXM. A recent paper supports the ability of DXM to affect alcohol tolerance (53) although this paper was concerned with a different effect, i.e., prevention of learned tolerance by NMDA antagonists.
At least one user has reported that very long-term regular use of DXM (recreationally) can lead to a constant hacking dry cough. I have not been able either to confirm or to disprove this.
6.3.17 Summary: Regular Use Considered
There are obvious societal consequences to regularly using a drug which can significantly alter or impair function, and though I shouldn't need to bring this up, I'd better do so anyway. One user of DXM who sent me email reported that he had lost his job, his wife, and his friends because his regular use of DXM made him unable to function in society. He seemed happy, and perhaps he found his own curious form of nirvana, but if he had been given the choice before using DXM with foreknowledge of the consequences he might have chosen differently.
I realize that most people go through irresponsible phases where they don't really care about the consequences of their actions. Now, I truly believe that, as long as those consequences don't involve the physical harm to others, that's your business. Someone who cares about you has every right to try to talk you out of it, but ultimately, it's your life, and all too often people see any behaviour they don't understand (or like) as self-destructive. I've known racists who believed that associating with members of other races was self-destructive, and that certainly doesn't make it true.
However, before doing anything that may change your outlook on life significantly, ask yourself if you are ready for the changes that may occur, for the loss of those things you now consider significant. Ideally one would consider this before making any big decision in life, regardless of whether it is marraige, divorce, taking a new job, becoming a Tibetan monk, joining the French Foreign Legion, or doing too many drugs.
Remember though, that regular use of DXM may cause long-lasting, even permanent changes in consciousness, mental ability, and personality. Don't jump into the deep end without knowing how to swim and knowing what's waiting for you down there.
6.4 DXM and Pregnancy
One word: don't. Dissociatives seriously affect fetal brain development (198), and reduce the number of axons pruned during brain development (up to and including early childhood) (237). This results in disrupted network formation (242), which leads to impaired spatial learning (246) and may increase the chance of seizures. To sum this up in non-scientific terms, kids whose parents used dissociatives during pregnancy run a high chance of brain damage and possibly epilepsy.
6.5 What is NMDA Antagonist Neurotoxicity and How do I Prevent It?
When NMDA antagonists were first studied they seemed like a dream come true: here were drugs which could block from part to all of the damage from strokes, head injury, hypoxia, polio, and a variety of other conditions. However, it seems that nature never gives something for nothing, and here too there was another side to the coin.
The dream ended when Olney et al. demonstrated that animals given huge doses of dizocilpine (MK-801), a new dissociative used in research, showed curious vacuoles (essentially, tiny holes) in tissue samples in the posterior cingulate cortex and retrosplenial cortex of lab animals (174,177,180-182,217,307-308,323,329). Further research showed that other indicators of damage were present, such as proliferation of microglia and induction of a protein called HSP70 (Heat-Shock Protein 70) (173,325).
Since then, Onley's lesions, also known as NMDA Antagonist Neurotoxicity or NAN, have been discovered with ketamine (325), PCP (302), and dextrorphan (177), all noncompetitive NMDA antagonists. Competitive NMDA antagonists have also been shown to cause Olney's lesions (213,312). PCP causes additional damage to the cerebellum and other areas, possibly due to its unique pharmacology (302). Drugs which bind to the polyamine site on the NMDA receptor evidently do not cause Olney's lesions (318), although nobody is quite sure why. Curiously, NAN may be worse in females than in males (290).
6.5.1 Overview and Mechanism of Olney's Lesions
The mechanism for Olney's damage is still being sorted out, and is somewhat perplexing, since NMDA antagonists generally protect neural tissue from damage rather than causing it. Trying to tie everything together is a little like trying to solve a crime with only circumstantial evidence; there are clues, but nobody's been able to watch the criminal in action. Here is what current research seems to indicate, pieced together into a coherent whole. A simplified explanation is given below.
- Dissociative anaesthetics activate neurons in the posterior cingulate
cortex (PC) and retrosplenial cortex (RC) in lab animals (and
presumably humans) (289,310,322). There is also secondary, "downstream"
activation of neurons in the entorhinal cortex, dentate gyrus of the
hippocampus, and olfactory regions (213).
There are two theories for why this happens; either one, both, or neither could be true. One theory is that NMDA receptors are found on inhibitory GABA interneurons, and that when these receptors are bocked, these interneurons secrete less GABA, and thus excitatory pyramidal neurons that normally receive a lot of GABA inhibition are overexcited.
The other theory is that the PC and RC are less affected by NMDA blockade than the hippocampus (and related areas), and that these formations serve as feedback to the hippocampus and surrounding networks. As these limbic networks are inhibited, the PC and RC increase their output to compensate, resulting in overactivity (300).
- The overactive cells begin to heat up, use up their energy supply generate toxic waste products, and/or let in too many calcium ions (182,217,300,308).
- Regardless of the mechanism, or whether the mechanism is none of the above, the overactivity seems to cause intracellular organelles (notably mitochondria and endoplasmic reticulum) to malfunction (174,182,217).
- The mitochondria probably lose their proton gradient and allow their innards to spill into the surrounding cell material, where they cause all sorts of trouble, possibly including forming free radicals which cause further damage to the cell. Another possibility is that the free radicals come first, and they cause damage to the mitochondria and other organelles. Mitochondrial damage can occur within 15 minutes of the drug dose, the endoplasmic reticulum is damaged 30 minutes, and in both cases gets worse as time progresses (308).
- The cell responds to this damage with a protein called HSP70. This "heat shock" protein is made and activated when something (such as overheating, thus the name "heat shock protein" or HSP) is causing a cell to malfunction so badly as to be in danger of self-destructing, and its job is to turn the cell off until repairs can be made (325). Hopefully, the cell will get a lot of rest (about 24 hours (322)) until it goes back to normal. At this point the problem is still reversible and the brain cells have not been permanently damaged (177).
- If the cell continues to be overexcited, it eventually burns out completely as the increased temperature, disrupted ion gradient, hypoxia, calcium ions, free radicals, and/or buildup of waste products kill it. At this point, surrounding support cells called microglia are activated and come in and eat the cell (probably under the theory that if an infectious organism caused the cell death, it'd better be destroyed before the infection can spread) (173,325).
- Then, scientists come along, freeze the brain, and slice it up into thin slivers. During the fixing process (307), the disrupted intracellular organelles expand to form vacuoles, the HSP70 shows up with tests designed to look for it, and the dead cells and proliferating microglia show up on microscope slides.
- The scientists take pictures, publish papers, thank their lucky stars that they aren't the rats who just took ten times the human anaesthetic dose of dizocilpine, and go home and fix martinis, smoke cigarettes, eat fast food, and engage in other sanctioned risk-taking behaviour (that's a joke ... yes I know there's a difference between a behaviour that kills you in twenty years and one which causes immediate brain damage).
A layman's explanation of the above: when you take too high a dose of dissociatives, a few parts of your brain become wildly overexcited, the brain cells get damaged, try to shut down, and (if damaged beyond repair) die. Support cells come in to clean up the mess, and you're left with permanent brain damage.
6.5.2 Dosages at Which NAN Occurs
According to most current research the dosages at which Olney's lesions become relevant is far in excess of human recreational doses. Here are some of the reported dosages applicable for different dissociatives.
|Drug||Dosage||Type of Damage||Ref|
|Ketamine||40 mg/kg||HSP70 (no cell death?)||(325)|
|Ketamine||80 mg/kg||Microglial activation (cell death)||(325)|
|PCP||8.6 mg/kg||increased glucose metabolism (no cell death?)||(322)|
|PCP||0.86 mg/kg||normal glucose metabolism (no cell death?)||(322)|
|Dizocilpine||5 mg/kg||Vacuolation w/ cell death||(307)|
|Dizocilpine||1 mg/kg||Vacuolation w/o cell death||(308,323)|
6.5.3 Balancing the Risks: Is Olney's Research Relevant to DXM Use?
Obviously there are still a lot of questions to be answered. The most important for human users of dissociatives is whether this type of damage can occur at recreational levels, and if so, what can be done about it.
Let's review the evidence both for and against Olney's lesions in human users of dissociatives. First, the evidence for. The posterior cingulate and retrosplenial cortex (PC and RC) are involved in skills which seem to be impaired in regular users of dissociatives. Olney's lesions occur at doses several times the recreational dose, but that's at one dose of the drug; repeated doses of lower amounts may cause the same damage. Olney's lesions are also only generally visible when large numbers of cells are destroyed, and they're significant enough to be visible under the microscope. Finally, conditions which increase the likelihood of Olney's lesions, such as less than ideal blood circulation to the brain, large amounts of glucose (like that found in cough syrup), concurrent use of stimulants, physical stress, hypertension, and the like, are all commonly found in drug users, who don't tend to be the healthiest lot (this is a generalization, of course).
On the other hand, Onley's lesions have never been found at human recreational levels, and DXM has received little attention. Ketamine users, some of whom have used ketamine for many years, don't typically show mental impairment. Even the few DXM users who do show impairment typically return to normal after staying off DXM for several months, and at least one paper suggests the mental impairment from dissociatives may be caused by depression, not brain damage (355). DXM is typically found in hydrobromide form, and bromide is a CNS depressant and may prevent damage to the PC/RC (incidentally, that's not the reason DXM HBr is used; DXM HBr just happens to be more water-soluble than any other form). DXM syrups usually contain alcohol, which also depresses the CNS. And, the lower plateaus of DXM are equivalent to doses of ketamine and PCP lower than commonly used recreationally.
Weighing the two sides I personally believe that moderate use of dissociatives is probably no harder on your brain cells than moderate use of alcohol or amphetamines (I said moderate use, not some five day fry-yer-brain speedfreak binge), and that if you use DXM sparingly (e.g., once or twice a month at lower plateaus, maybe once or twice a year at upper plateaus), you'll be just fine. In fact, I've never known anyone to suffer lasting impairment even after going through a few months of weekly DXM use at upper plateaus. But I could be wrong! Mild brain damage has a nasty way of showing up years later when you've forgotten about the stupid things you did when you were young.
6.5.4 A Look at the Areas Involved
Nobody's totally sure exactly what most parts of the brain do, but there is some evidence which may indicate possible functions for the posterior cingulate and retrosplenial cortex. Although our understanding is far from complete, and mine is considerably worse than that, I'll try to put together the published results into a coherent whole.
The posterior cingulate cortex is the posterior (rear) part of the cingulate cortex, a section of the cerebral cortex interconnected with the limbic areas. The front part of the cingulate cortex is called, appropriately enough, the anterior cingulate cortex. Like most areas of the brain, the boundaries of the cingulate cortex are somewhat indistinct. There are differences between the posterior and anterior cingulate cortex (beyond the obvious one of location); notably, the anterior cingulate cortex has fewer pyramidal neurons than the posterior cingulate, and in the anterior cingulate these neurons have more complex connections (310). This entire area may relay information between the hippocampus (and other limbic systems) and other areas of the brain (298).
There is a lot of disconnected research that points towards possible purposes for the posterior cingulate cortex. It may be one of the components of verbal and auditory memory (294), multisensory perception (315), visuospatial cognition and/or evaluation of emotional behaviour (316). The right hemisphere posterior cingulate is activated in comprehension of metaphors (303), and the left in associative learning (304). Story comprehension seems to use the posterior cingulate (292). In late Alzheimer's disease the posterior cingulate may be subject to atrophy (314,317). It is activated during anxiety (313) and in OCD (Obsessive-Compulsive Disorder) (305) but deactivated during phobic fear (299).
It has been suggested that the cingulate cortex in general may be involved in evaluating (posterior) and acting on (anterior) one's own behaviour and spatial orientation (316). This is, in my opinion, the most comprehensive view of the existing research. To put it simply, the job of the posterior cingulate cortex might be to evaluate and consider where you are and what you're doing. Since dissociatives tend to interfere with the ability to evaluate one's own behaviour, it may be that the posterior cingulate is a part of a self-evaluation system.
Another paper (311) analyzed the network properties of the posterior cingulate, and suggested that neural output from the hippocampus that was in sync with the theta rhythm would pass through the posterior cingulate cortex in preference to other routes. What makes this so interesting is that the flanging or strobing effects of DXM seem to occur at theta rhythm, which may be a consequence of DXM's effects on the posterior cingulate.
There was considerably less information published on the retrosplenial cortex. One paper found that it was activated during the encoding of novel situations (321). Another (324) suggests that the circuitry between the retrosplenial cortex and hippocampus is an important path by which the hippocampus affects learning, memory, and emotional behaviour. Numerous papers suggest it has a role in visual processing.
Hopefully I'll be able to fill this area in with more information as my knowledge of (and the amount of published information on) these two areas of the brain increase. Until then, make what you will of the rather sparse information I have provided.
6.5.5 Preventing and Limiting NMDA Antagonist Neurotoxicity
So what can you do about this? Well the best thing I can tell you is, stay away from drugs that might give you brain damage, whether it's DXM, alcohol, stimulants, benzodiazepines, PCP, or glue. If marijuana were legal I'd say smoke as much as you want (keep in mind that the smoke isn't terribly good for your lungs though), since there have been numerous studies which have shown no neurotoxic effect from marijuana. But since marijuana ain't legal, ... well, there's always caffeine I guess (until that's made illegal too).
Realistically, I know many of you are going to keep using DXM, especially since it obviously doesn't impair everyone who uses it (even in large amounts). People regularly make choices to engage in risk-taking behaviour, whether it's rock climbing, driving too fast (or without a seat belt), eating red meat, not exercising, or taking drugs. Ultimately that's your choice. Society has made many drugs illegal, and many argue that if drugs were legalized that would give them an aura of legitimacy and safety, but it's legal to sit around and watch TV all day, eat nothing but cheeseburgers, bathe only once a month, and hit yourself on the head with a hammer, and even as a child I never believed that legality made any of these a good idea.
So here are some practical suggestions based on research into Olney's lesions, which may work, may do nothing at all, or may make it worse. It's up to you to decide, but keep in mind that tomorrow it may turn out that any one of these is helping to fry your brain.
- Avoid stimulants of any kind with DXM, especially yohimbine. Alpha2 agonists seem to prevent Olney's lesions (175); yohimbine, an alpha2 antagonist, could instead make the problem much, much worse.
- Make sure you are in good physical condition, with low blood pressure and low cholesterol. The ability of brain cells to recover from metabolic insults is vastly improved if cerebral blood circulation is in good shape.
- Consider Coenzyme Q10 supplementation. One paper suggested that Q10 might be useful in some types of neural lesions (216). It has been suggested that, as a mitochondrial energy substrate, it may prevent brain cells from "running out of fuel".
- Consider a very mild CNS depressant, like a glass of wine or a beer. I wouldn't go much beyond this, since combining DXM with too much alcohol can lead to severe nausea. A benzodiazepine is probably overkill.
- Use gelcaps or capsules instead of syrups, which contain glucose; the presence of high glucose levels seems to make things worse.
- Limit use of DXM extract, which doesn't contain bromide ions, or use it in conjunction with a little alcohol.
- Limit frequency and dosage of DXM
- Give your brain a rest of at least 48 hours after using DXM
- Eat healthily before, during, and after DXM use
- Consider an alpha2 agonist (175). Or maybe not; the research isn't conclusive on this yet.
- Regularly monitor your mental skills and have others monitor them as well.
- Make each DXM trip count so you don't feel the urge to reattempt an unfulfilling trip experience.
6.6 Is DXM Addictive?
From one viewpoint, of course, anything can be addictive -- television, chocolate, masturbation, self-mutilation, etc. So in that sense, yes, DXM can be addictive. Somewhat more relevant are the degree to which DXM is addictive, and how such addiction manifests itself. The quick answer is, DXM can be addictive if you use too much, too often.
The traditional distinction made with respect to addiction is between physical addiction and psychological addiction. As examples, alcohol is physically addictive, whereas marijuana is psychologically addictive. Unfortunately this distinction has its problems - not the least of which is that since the brain is a physical construct, any addiction is in some sense "physical."
As physical addiction is a somewhat nebulous concept at best, I prefer to use the concrete ideas of tolerance and serious withdrawal symptoms. Tolerance is a process by which the body and brain adjust to a drug so that the dosage must be increased to achieve the same effect (some drugs, such as nitrous oxide, exhibit reverse tolerance, becoming more potent the more often they are used). "Serious" withdrawal symptoms is somewhat less clear, unfortunately. Note that it is possible to become tolerant to a drug without being psychologically addicted; in fact, some people lose the desire to use a drug when tolerance takes away its more interesting effects.
There is considerable evidence based on personal reports that tolerance to DXM's more interesting dissociative effects builds quickly. This is a result of upregulation or sensitization of NMDA receptors, as well as possible changes in other receptors and systems indirectly affected by DXM. Cross-tolerance exists between DXM, PCP and ketamine, naturally. Some people seem to be immune to tolerance to dissociatives including DXM (lucky them).
Usually it takes several doses before tolerance is noticeable, although a few people have noted tolerance after just one dose. Larger doses will lead to quicker tolerance. Once tolerance has built, it takes at least three weeks before receptors will reregulate to normal levels. To avoid this problem, it is probably best to dose only once a week at most. Also, some people believe that receptors which are upregulated (or downregulated) for long periods of time may tend to stay that way. The practical upshot is you should take a month off every now and then (a good idea with any drug, incidentally).
Interestingly, the first plateau music euphoria effect also seems to disappear with repeated use of DXM. It's also one of the last effects to come back. This may be due to downregulation of dopamine receptors rather than upregulation of NMDA receptors. The practical upshot is, don't do DXM all the time. Again, some people are luckily immune to this tolerance effect.
For information on withdrawal and withdrawal symptoms, refer to the next section.
Psychological addiction to DXM has been noted a few times, and can theoretically lead to physical addiction. Generally, though, dissociatives aren't considered particularly habit-forming, since they tend to have such "heavy" effects. Low-dose DXM might be an exception due to its moderate to strong stimulant effect; in practicality, it's probably too hard to consistently hit the first plateau.
There are exceptions, some of them notable. One case report (132) involved a 23-year old male who maintained an incredible daily dose of 30 mg/kg to 40 mg/kg DXM (plus a six-pack of beer)! Needless to say, after maintaining this dose long enough, he had become addicted, although the authors consider it a "psychological" addiction, with withdrawal symptoms such as dysphoria, depression, and anxiety.
Most people who use DXM have noticed little or no addiction, and only mild tolerance (don't let that scare you; remember that coffee produces both tolerance and withdrawal symptoms). A few unfortunate people have developed problems with DXM. Prolonged, heavy use of DXM seems to induce dysphoria, anxiety, and/or depression in some people; as the dosage is increased, the problem gets worse. Unfortunately, at this point, there may be withdrawal problems (see the next section). If this happens to you, seek medical assistance.
6.7 Is DXM Withdrawal Dangerous?
Withdrawal from occasional DXM use is almost certainly not dangerous, and in fact any "symptoms" felt are probably just "jonesing" - the same sort of withdrawal "symptoms" felt with marijuana, television, sex, etc. At this point it's a matter of willpower more than anything else.
Once tolerance has built, withdrawal has the potential to cause more serious problems. Mild tolerance to DXM is probably no more dangerous than mild tolerance to alcohol (tolerance at the level of "being able to hold your liquor"). Withdrawal may produce boredom and mild anxiety, but rarely anything more troubling than that.
One person reported a curious withdrawal effect which has also been noted upon cessation of SSRI antidepressant therapy. Whenever moving his eyes, or upon any sudden change in sensory input, he experienced a sudden, momentary dizziness and altered consciousness. Ginkgo biloba, exercise, and sleep were reported to all help with this.
Beyond the mild tolerance level, things could get rapidly worse. There is evidence that significant NMDA upregulation can lead to (100) and many of the symptoms of opiate withdrawal may occur via a similar mechanism (109,133). The good news is, studies generally haven't found any significant evidence of brain damage from heroin withdrawal, so withdrawal from DXM probably wouldn't be much trouble. The bad news is, heroin withdrawal isn't particularly enjoyable.
Interestingly, one person who developed addiction and tolerance to DXM also compared the withdrawal symptoms to those of heroin (although DXM never produced any of the positive effects of opiates in this individual). These symptoms included watery eyes, stuffy nose, gooseflesh, muscle spasms, increased pain sensitivity, nausea, anxiety, and depression. Furthermore, the individual eventually began to develop some of these symptoms even while using DXM. This is definitely something to avoid.
If you happen to develop a significant degree of tolerance to DXM, it might be a good idea not to quit "cold turkey" (all at once). Build down slowly over a few weeks, and avoid all other drugs in the mean time. One person who had been using DXM twice daily reported no withdrawal symptoms after decreasing the dosage 10% per day, and stopping at 180 mg. This should prevent any excitotoxic rebound.
On the other hand, given the research from Olney et al (see Section 6.3.1, it may be better to go ahead and quit cold turkey after all. Some research casts doubt upon upregulation of NMDA receptors with blockade, and if so, then there may be no danger to quitting DXM completely without tapering down. To be honest, there is evidence on both sides, and the best advice I can give you is not to get into this situation in the first place. If you do manage to develop a DXM addiction, I wish you the best of luck, and I think your best course of action would be to see a physician. Since most medical authorities are ignorant of DXM's psychoactive potential, it would probably be advisable to treat it as an addiction to any other dissociative (ketamine or PCP).
6.8 Kicking the DXM Habit: What to Do If You are Addicted
The first thing to understand about DXM addiction is that most people who find themselves addicted use DXM on a very regular basis -- weekly, or (more frequently) daily. This is very dangerous!. It is vital that you quit using DXM as quickly as possible if you are using it on a daily basis.
If you have access to mental health services I strongly suggest you seek them out. Many areas provide financial assistance for uninsured or low-income patients. DXM addiction can be treated like addiction to any other dissociative, i.e., PCP or ketamine. Unfortunately, many physicians and psychiatrists are not generally up-to-date on dissociative addiction, so you may need to look around.
The biggest problem with DXM addiction is rebound depression. Many casual DXM users have noticed a slight depression during the hangover phase. With regular use, however, the brain becomes tolerant to certain aspects of the DXM experience (probably a reregulation of serotonin receptors due to the DXM-induced serotonin release). To compensate for the depression (which can be severe) many people turn back to DXM. Unfortunately, dissociatives make poor antidepressants, since they have numerous side effects.
Incidentally, keep in mind that dissociative-induced depression is often severe enough to result in impaired mental functioning. Many cases of dissociative "brain damage" turn out not to be permanent after all, but only the consequences of major depression.
If you choose to kick the habit on your own, or if you have no other choice, you have two options: build-down and cold turkey. Build-down means that you slowly taper off DXM use in the hope that your brain will readjust as you do so, and thus avoid the potentially severe depression of sudden withdrawal. Cold turkey withdrawal (the term comes from the gooseflesh of heroin withdrawal) means stopping suddenly.
6.8.1 Preparing to Quit
The first and most important step in either case is wanting to quit. Not merely knowing you should, but actually wanting to. Take a good, hard look at your life. Talk to your friends about your problem -- I know it can be hard to do, but they probably already know it anyway. Examine your performance at work or school. And look at your own use patterns -- are you using DXM as a group activity, or are you using it alone? Take stock of your finances. All of these factors can help to contribute towards the desire to quit DXM.
Keep in mind that you may have to quit DXM permanently, and never use it again. By the time most people has become addicted to DXM, however, they tend to derive little or no pleasure from the experience anyway. So you must be prepared for the thought of never using DXM again, or at least waiting a year or two and before trying it again. Remember, though, there are other psychedelics out there, and many of the more interesting effects of DXM can be achieved through transcendental meditation, yoga, and other spiritual work.
In preparation for quitting any drug, get rid of anything and everything that acts as a "trigger" for DXM use. Let your friends who use DXM know you are trying to quit. You don't have to shun them completely, but you might be well-advised to avoid them while they are using or discussing DXM. Discard any supplies of DXM you have (if you are quitting cold- turkey). Don't go to the drugstore without someone else to watch over you. Don't go to places where you traditionally used DXM (this is hard if you used it at home). If you will be moving soon, you can use the move as an opportunity to leave behind all the sensory triggers that made you think about DXM.
6.8.2 Quitting "Cold Turkey"
The safest way to quit from a neurological standpoint is to quit cold turkey -- completely and suddenly. This is also the most difficult. The depression stage can last for several weeks, even months. Fortunately, it is treatable with drugs; SSRIs such as fluoxetine (Prozac) have been used with great success in treating PCP addiction, although there is some evidence that serotonin/dopamine reuptake inhibitors, or combining a SSRI with a dopamine reuptake inhibitor such as bupropion (Wellbutrin), may be preferrable. In drug-resistant cases, electroconvulsive therapy (ECT), or the newer (and safer) variant, left-prefrontal transcranial magnetic stimulation, have been used as well. In any event, it is important to see a psychiatrist who can assist you, give you a neurological evaluation, and prescribe any necessary drugs. DO NOT use DXM after you are placed on antidepressants of any kind.
If you do not have access to psychiatric medicine, you still have other options. Try to vary your daily routine to expose yourself to new and interesting stimuli. As corny as it seems, taking long walks in the woods and, especially, getting a lot of sunlight, has helped many people (and there may be some evidence that DXM-induced depression may be in part due to a disruption of the circadian rhythm, similar to Seasonal Affective Disorder). Keep a regular, rigid schedule of getting up and going to bed at the same time. Some people have had success using melatonin to help them stay on schedule but there is some evidence that melatonin may worsen depression in susceptible individuals. And the most important thing you can do is to get regular physical exercise! Not only does it help with depression, it also helps to get your body and brain back in top working order.
Build-down is a controversial method for dealing with addiction. Many people with whom I've spoken have used build-down successfully, but many others tried it and failed. At the very least you can try it first and then, if that doesn't work, try cold-turkey withdrawal (which may be easier after you have cut down DXM use).
There are two conflicting issues here. On the one hand, maintaining a regular, even dose of any drug can prevent the "rush" that so many people find contributes to the addictiveness of the drug. On the other hand, regular use of DXM can become dangerous to the brain. Weighing these issues, and on the basis of those who have used build-down successfully, I believe that a regular low dose of DXM may be appropriate for build-down. Fortunately, even a lower dose of DXM seems to help fight off dissociative depression.
I do not claim to be a physician and I can only relay to you what others have told me. Before attempting build-down you must consult a medical authority, and at the very least have your serum bromide level checked (or check anion gap, which amounts to the same thing) to see if you are already in danger or bromide poisoning. Assuming you check out OK, and your physician is willing to let you try build-down, here is what I have been told from successful build-down attempts. THIS IS NOT INTENDED AS MEDICAL ADVICE, ONLY ANECDOTAL EVIDENCE FROM FORMER DXM USERS.
First off, get someone else to help you -- a friend, spouse, whatever. You want to make sure they will keep you on the rigorous schedule and not let you go back to using large amounts of DXM.
The key to this method, according to those who have used it successfully, is to place yourself on a regular, low dose of DXM -- just enough to keep the depression from becoming severe. First off, wait at least three days from your last DXM dose before starting the build-down; this should allow your body to clear out any DXM and metabolites. Also, make sure you are not on any drug which can alter DXM metabolism -- including antidepressants.
The build-down dose is taken three times per day at rigid six hour intervals, and an individual dose should not be enough to get you high. One person successfully used 30 mg 3/day; most however have used 60 mg 3/day. It would probably be better to start at 30 mg 3/day and then move up, if that isn't working, after two or thee days.
After establishing the maintenance dose, build-down users continued this dose for one to two weeks, before halving the dose. Again, after another one to two weeks, the dose was halved again; finally, when the total daily dose was less than 45 mg, they went to twice a day for one week, then once a day for one week, and then quit completely.
All of the people who built down experienced mild depression, although most found it manageable, and some told me that the ideas suggested above in Section 6.8.2 (exercise, walks in the woods, sunlight, regular sleep habits, etc.) helped to make them feel better.
Again, remember, I'm only conveying anecdotal information here; you absolutely must work with a physician or counselor who can give you the professional help you need. For all I know, these people who told me their successes could be unique in some way (or for that matter they could be lying to me).
6.8.4 After Quitting: When Can I Use DXM Again?
Possibly never. Like any other severe addiction, there is always the risk of a relapse. If you choose to throw caution to the wind, that's your choice and you do it with the understanding of the risks involved. The only suggestion I can give you is to limit DXM use to one particular environment, and make sure it's an environment you do not encounter when not using DXM. Basically, by making it into an isolated ritual, you lessen the chances of normal sensory cues leading you back into addiction. One former DXM addict managed to use DXM again without becoming addicted after two years of being drug-free; he did so by only using it with a select group of people, in one particular place, and then one of his friends was responsible for giving him his dose in a particular cup (thus avoiding the sensory cue of the cough syrup bottle).
Still, it's better to find other ways of feeling good. Yoga and meditation are probably the two best means of achieving altered states of consciousness that are similar to DXM (unfortunately, unlike DXM, they require hard work and patience). If you live somewhere where serotonergic psychedelics (mushrooms, LSD, 2CB, etc) are legal, you may find that these can give you the psychedelic consciousness without the addictiveness (or danger of neurological damage) that come with DXM.
Best of luck, and remember, above all, seek professional help. I am not a physician, only a researcher, and I cannot and will not claim to give advice for your particular case. There are too many other factors which I do not know, and cannot understand, as I have limited medical knowledge in areas other than neuroscience.
6.9 DXM Hangovers -- Avoiding and Alleviating
Hangovers from DXM trips are not common at lower dosage ranges (first and second plateau). Instead, many people report feeling energetic and refreshed the next day, although it seems that getting enough sleep is important here.
At higher dosage levels (third and fourth plateau), hangovers are more frequent. Hangover effects reported consist of lethargy, sleepiness, amotivation, mild sensory dissociation, muscle rigidity, muscle tics (especially in the jaw and hands), dizziness, loss of balance, headache, photophobia, and sharply diminished sense of taste. Some people say that everything tastes like slightly salty tepid water, or like MSG (monosodium glutamate, the flavor enhancer). Note that you're very unlikely to get all, or even most, of these symptoms.
Some of the hangover effect from high dosage trips is probably due to residual DXM or dextrorphan, especially in individuals who lack P450-2D6, or in whom it is inhibited (e.g., by fluoxetine). To my knowledge there doesn't seem to be any way to speed up the metabolism; the best I can suggest is to exercise, drink plenty of water, take a multivitamin every day (don't overdo it, one is plenty) and possibly a small iron supplement (which just might increase cytochrome turnover), get enough sleep, and eat right. Don't take too much iron; iron is very toxic.
Other hangover effects may be due to neurotransmitter depletion (due to induction of 5HT and dopamine release), temporary inactivation of NMDA receptors (I doubt it, but there's been speculation), or just plain lack of sleep. Again, treating your body well is probably the best you can do.
Finally, there is evidence that, for 24 to 48 hours following use of a dissociative, certain parts of the brain are underactive (probably due to neurotransmitter depletion) (322). There's not much you can do except tough it out. Obviously, you shouldn't use DXM unless you have a day to recover.
Preventing hangovers may be possible to some degree. Certainly, make sure you are in good physical condition to start with, and don't try to stay up too late during your trip. Drink plenty of fluids (it is possible to get dehydrated; this can slow down the kidneys), and don't mix DXM with anything that could further deplete neurotransmitters (e.g., amphetamines, MDMA, etc.). Try to avoid going to sleep while still tripping hard - it seems to reduce the quality of sleep. Eat something before you go to sleep; usually DXM kills the appetite, so you may not know your body needs food.
Another possibility is the use of nootropics ("Smart Drugs") to help prevent and alleviate hangovers. A good place to start for information is alt.psychoactives (although, like any source on the Internet, take any information with a grain of salt and ask for medical journal references); another good place is Dean and Morganthaler's text on the subject. A healthy dose of skepticism is probably a good idea here; some of it might be placebo effect. There's evidence for and against; check Medline if you're interested. Note that unless otherwise specified, everything I mention should be available at health-food or mail-order vitamin suppliers (this is USA; I don't know about other countries).
Several people have reported beneficial effects from cholinergics, specifically choline (the precursor to acetylcholine), and DMAE (also a precursor, and a choline oxidase inhibitor). In both cases the bitartrate salt seems to be the usual (there is a liquid DMAE para-aminobenzoic acid formulation that tastes nasty and evidently doesn't work). Note that some people with depression, primarily endogenous, react very poorly to cholinergics. Also note that they can make you really, really irritable if you're susceptible. Regular use of DMAE seems to be the most effective, although that's something that you have to build up for a couple of weeks (Dean and Morganthaler suggest around 800 mg per day in divided doses).
One-time use of DMAE or choline immediately before, during, or after the trip has also been reported to work, (in that order of preference), although not as well. Recommendations given to me have been 800 mg DMAE, or 1500 mg choline; in either case with 350 mg vitamin B-5 (pantothenic acid) which acts as the relevant cofactor here. Don't go much above that.
There is some preliminary evidence that supplementary tyrosine (the precursor to dopamine and noradrenaline) may actually be useful in the case of dopamine depletion. Normally, the rate-limiting enzyme in the process is nearly saturated, so boosting tyrosine doesn't work. It's hypothesized that more enzyme may be produced in response to dopamine depletion. Furthermore, sigma activity may enhance synthesis of dopamine (114), so taking supplemental tyrosine is even more likely to be a good idea.
A side note ... for whatever reason, nootropics fans seem to be abnormally fond of using phenylalanine instead of tyrosine. Phenylalanine does convert to tyrosine, but it's a very slow, limited conversion, and there's no good reason for choosing phenylalanine over tyrosine.
Vasopressin might also be useful; it seems to have a fair amount of success in combating intoxicants, possibly by affecting long-term potentiation (how I don't know). It's prescription in the USA, and it does have side effects.
One final note - do not take tryptophan! Although this isn't established, it's possible that NMDA receptors may be upregulated after a DXM trip (especially in chronic users). Tryptophan, in addition to leading to 5HT, also leads (along a much more efficient pathway) to a substance called quinolinic acid, which is very toxic to neurons, and acts via NMDA receptors.
6.10 How Toxic is DXM, and What is the Lethal Dose?
The LD50 (dose at which 50% of animals die) of DXM doesn't seem to be well known. For a variety of reasons, animal assays of the lethal dose of psychoactives aren't always accurate. Nor have I ever found a published LD50 for DXM. So instead, I've decided to go on the basis of the few deaths that have occurred from DXM use, keeping in mind the amount of DXM people regularly consume for recreational purposes.
In searching medical literature, I found only two cases of death associated with DXM use, both in Sweden. In one case, a girl was found dead in a public bathroom with two bottles of 30 mg DXM tablets (the number of tablets is believed to be 50/bottle, but may be 15 or 25). She had previously tried to commit suicide using a bottle of 50 tablets (this leads me to believe that she had, in fact, taken 100 tablets, for a total dose of 3000 mg).
The other case involved a 27 year old man, and few details were specified. In both cases, death was apparently due to inhibition of respiration. Plasma levels of DXM were 9.2 and 3.3 micrograms per gram (cases 1 and 2); plasma levels of dextrorphan were 2.9 and 1.5 micrograms per gram. Liver levels of DXM were about an order of magnitude higher. In both cases, the ratio of DXM to dextrorphan was about 3 (9).
On the other hand, a dosage of 42 mg/kg/day has been used (with respiratory support) in children (33), which would be 2500 to 3000 mg for a 60-70 kg adult. There is also a very low incidence of death associated with DXM use. Since a 42 mg/kg dose in an adult may be stronger than the equivalent dose in a child (I have no reason to believe this, but it is possible), caution is advisable in taking this as an indication of safety.
The highest daily dose of DXM I've come across is from a case study of a 23-year old male (132). His daily dose was 3 to 4 12oz bottles of Robitussin DMTM, for a total of 2160 mg (31 mg/kg) to 2880 mg (41 mg/kg). He was, of course, considerably addicted to DXM, and had built up this dose over a long period of time.
It is reasonable to expect, given the data, and the available data on the effects of high DXM doses, that DXM starts becoming toxic around 25 to 30 mg/kg (about 1700-2000 mg for adult of 150 lb). This corresponds to between 5 and 6 4oz bottles of 3 mg/ml cough syrup, i.e., a fairly large amount, but still within the realm of hardcore experimenters. Keep this in mind before you consider large doses. IV naloxone is considered the antidote for DXM overdose (54), even though DXM isn't an opiate.
Note that since publishing the FAQ, I have heard anecdotally (but have not verified) of a few recent (non-fatal) overdoses in Australia, and one fatality in the United States. The latter involved long-term regular use and may have involved a buildup of DXM in the bloodstream. Nine additional fatalities involving combined use of DXM and zipeprol in Korea have been documented (367).
6.11 Do You Recommend DXM for Recreational Use?
No. Definitely not. Use of medicine, OTC or not, contrary to instructions may be a violation of local, state, and/or federal law. I hereby specifically tell you not to use any DXM-containing product (or any other product) in a manner inconsistent with its labeling.
Even if DXM were legal for recreational use, I still wouldn't recommend it for frequent use, nor for high-dosage use. Frequent use may bring about undesirable changes as mentioned above. High-dosage use carries with it all the risks of any hallucinogen, and can be distinctly unpleasant. Very little is known about sigma, PCP, or NMDA receptors. You dork with them at your own risk, and that risk may be considerable.
To be honest, part of my answer is covering my ass, and part is genuine caution. DXM probably isn't quite as friendly as I used to think it was, and there's no need to place onesself in harm's way for the sake of a buzz. If you're just looking to get generically "high", there are better highs out there (unless you really happen to be drawn to dissociatives, and if so, believe me, you have my sympathies). So make sure you really want to do DXM before you do it. It's not a substitute for LSD or marijauana and shouldn't be used as one.
Once more, I officially instruct you not to do DXM, or any other drug, unless under the guidance of a physician. Right now, in the USA, there are many people with nothing better to do than support legal paternalism and legal moralism. For whatever reason, some people feel that they have the right to tell a legal adult what she or he can and cannot do that involves only her/his body. And as long as this goes on, I'm going to make sure I'm not thrown into prison so they can free murderers and rapists to make room for me. So, I'm telling you - don't break the law.
6.12 Help! What do I do if ...
This section covers suggestions for undesirable, unexpected, and unplanned situations. Always remember, though, if you feel there is a real emergency, get to a hospital. While DXM-related deaths are very, very rare (two published, three anecdotal), they have occurred. Nobody wants to see any more happen. None of this is intended to be medical advice or replace the judgment of a physician, nor should it be taken as such. These are general guidelines only, compiled from reports of DXM users. Neither I nor anyone else take responsibility for any injury, death, or other misfortune, resulting from this advice. There, have I covered my ass well enough? Probably not. Just remember, please use common sense and be careful!
6.12.1 Itching (the "Robo Itch")
See Also: Allergic Reactions & Histamine Release
Some people get the itch, some don't. Among those who do, some seem to get it from the DXM itself, some from the dyes in cough syrups (in particular tartrazine), and some just as a consequence of losing tactile sensation.
In any case, from all reports the best thing seems to be to wait for it to go away, and try to think about something else. Scratching is OK, so long as you don't injure yourself in the process (remember, you many not be feeling pain as you normally would). A loofah can be quite enjoyable, actually, should you feel the urge to take a bath (which evidently can itself be enjoyable on DXM. Just be careful!) You can try a topical antihistamine spray, but I doubt it will do any good. An oral antihistamine (remember, never take non-drowsy antihistamines like SeldaneTM with DXM!) is also reported to work without adverse effects.
If the itch is accompanied by a rash, swelling, or other symptoms of an allergic reaction, you can consider taking a small dose of an oral antihistamine such as Chlorpheniramine Maleate (CPM) (not a prescription one), and make sure there is someone with you. Redness with itching often results from unconscious scratching or rubbing the skin, but some DXM users report redness appears with the onset of the itching reaction.
If the allergic reaction continues, or you feel you may be going into shock, get to a hospital. To my knowledge this type of allergic reaction has never occurred on DXM.
6.12.2 Fast Heartbeat
Many times this is more a problem of perception than anything else. Still, it does happen. As far as I have been able to determine, DXM itself can raise the heart rate somewhat, about as much as a mild to moderate stimulant (e.g. a few cups of coffee to a "coffee virgin"). Reports have indicated a range of 90 to 120 beats per minute as the relevant range.
Try to have someone sober take your pulse, since you may be getting sensory echoes. If your heart rate is truly high (as a general but probably inadequate guideline, above 120 beats per minute), do your best to relax, stay calm, and see if it goes down with relaxation (and see Section 6.12.3 below if relevant). If you continue to have an abnormally fast heartbeat, by all means see a doctor. You probably aren't in much danger, but there's no need to take the risk.
Prolonged very fast heartbeat, or fast heartbeat accompanied by chest pain or tightness, should be taken seriously and may be cause for medical attention (note that a panic attack can also cause a feeling of chest tightness). If in doubt, go to the hospital. People with existing heart problems should avoid recreational DXM use. Incidentally, neither of the recorded deaths due to DXM overdose were attributed to heart failure (respiratory failure was considered the cause).
6.12.3 Panic Attacks
Panic attacks can occur on DXM, especially in naive users or users rushing in to higher doses. A panic attack can increase the heart rate significantly, sometimes as high as 200 beats per minute! Unfortunately, panic attacks can be hard to control; the best thing to do seems to be to try to relax, go somewhere you feel comfortable, and focus on your environment. A panic attack is a positive feedback situation; once you start having one, the symptoms themselves can feed the fear. Breaking this vicious cycle can be difficult. If you are predisposed to panic attacks you should probably avoid DXM in the first place.
6.12.4 Irregular or Skipped Heartbeats
An irregular heartbeat, like a fast heartbeat, may be a problem of perception more than anything else. Remember that, especially at higher doses, there can be a "sensory echo" effect which may influence your measurements.
An occasional feeling that your heart "skipped a beat" is usually not cause for worry. Sometimes it is due to spasms of the esophagus, stomach, or bronchial tubes and has nothing to do with the heart; it's hard to distinguish sensations among internal organs. More frequent heart irregularity, or irregularity with chest pain, may require medical attention. Go to the hospital if in doubt.
6.12.5 Nausea, Vomiting, Gas, and Diarrhea
Ah, the joys of ingesting large amounts of thickening agents. Nausea is to be expected, especially with cough syrups. It usually goes away. A few people have reported that meclizine (available in several brands of over-the-counter anti-nausea medicine) can help without adversely affecting the DXM experience. In general, though, most anti-nausea drugs are anticholinergics and/or CNS depressants, neither one of which you want to mix with DXM. The best response seems to be to tough it out, or switch to gel-caps. Incidentally, avoid taking DXM with greasy or heavy foods.
Vomiting occasionally occurs, usually for the same reason as nausea. Again, not much to worry about. If you do vomit, just make sure to drink lots of water to replace what you just lost. Both guaifenesin and large amounts of alcohol tend to contribute to the tendency to vomit.
Gas and diarrhea, especially after the trip, are also fairly common with syrups. Not much to do, unfortunately; just tough it out and drink water. Loperamide (ImmodiumTM) can help with intestinal cramps and diarrhea, and from all reports doesn't affect the brain at all.
This is mostly advice for the designated sober person; obviously it won't do you much good if you're unconscious. Unconsciousness with DXM is to my knowledge extremely rare (I've heard of it happening once). Please keep in mind that it is possible to achieve a fully anaesthetic dose of DXM, but if you do so you risk serious injury, and probably won't remember much of the experience. There are probably a few psychonauts out there with the experience (and the assistance of physicians) to handle voluntary anaesthesia, but let's leave that to the professionals and the truly insane.
Generally if someone passes out, the first thing to do is make sure they don't fall and hit their head. Yes, DXM may protect brain cells somewhat from the effects of head trauma, but let's not try out that theory ourselves. Make sure the unconscious person is lying down with their feet elevated, and that someone (sober) is with them. If you feel there is any danger of vomiting, roll the person onto his or her side.
There are several reasons why a person on DXM might be, or appear, unconscious. Most commonly, he or she may be in an imaginary dream world, unresponsive to the physical world. He or she may have fainted due to postural hypotension (which I've heard of happening with DXM). Or they may just be ignoring you.
Whatever the reason, try and get a response from the unconscious person. If you can't get any response after a minute or so, it's time to call an ambulance. See Section 6.12.7.
The first thing to do in the case of a suspected overdose is to call an ambulance. Don't argue, don't hesitate, and don't worry about the legal implications; you can work that out later. Remain calm; freaking out won't help anyone. If they are unfamiliar with DXM overdoses, tell them to bring a syringe of naloxone. If you receive instructions from the medical authorities, follow them.
Check the individual's breathing and pulse. You may need to apply CPR if the heart has stopped (again, follow any instructions the emergency personnel give you). Try to find out exactly how much DXM he or she took, and at what time. Also find out if he or she was taking any other drugs (legal or not), notably including antidepressants, prescription antihistamines, sedatives, or alcohol.
Really, at this point, you need competent medical advice, and I'm not a physician. Unfortunately, as more than one physician has told me, the medical community is generally ignorant about DXM. Given this, I'm going to try to outline below as much as I can that might be relevant about DXM in an emergency, with the understanding that someone with medical knowledge will evaluate the situation.
When dealing with a DXM overdose it is important to remember that there are really two drugs at work: DXM and its metabolite, dextorphan. At overdose levels, the conversion enzyme (CYP-2D6) will probably be saturated, so even after gastric lavage and activated charcoal, DXM will continue to be converted to dextrorphan (DXO), probably raising serum DXO levels. Also, since DXM is usually found as the hydrobromide, you may have to worry about acute bromide toxicity.
DXO is in the same class as ketamine and PCP, and from all accounts can be treated as such. DXM has additional pharmacological activity; it is a calcium (and possibly sodium) channel blocker and a mild noncompetative dopamine reuptake inhibitor. Like PCP, DXM may cause hypertension and CVAs (though if it's any consolation the NMDA blockade should minimize the damage). There is also the possibility for serotonin syndrome if DXM has been combined with a serotonergic. Rhabdomyolysis has never been observed with DXM but is possible.
I have no data on whether acidifying the urine will hasten DXM clearance. Nor do I know whether DXM (or DXO) may reappear in bile, though I have heard several anecdotal reports of increased bile secretion during DXM use.
Finally, remember that, like PCP, DXM can cause emergence phenomena. Once the individual regains consciousness he or she will probably be confused, and possibly paranoid and hostile. Also like PCP, DXM can impair perception of pain. Although I've never heard of it happening, it's possible that someone coming out of a DXM overdose could become violent.
Remember, if there is any indication or suspicion of an overdose, get medical assistance immediately!
6.12.8 High Temperature / Fever
First, make sure you actually have a fever. DXM can mess with your sense of temperature. On the other hand, I have received one report of DXM-induced hyperthermia that could have been dangerous. A temperature at or above 102 F (39 C) is entering the danger zone. If this happens to you (or someone you are with), the best way to cool down is by taking a cool bath or shower (make sure it feels cool to a normal person!), and drinking cold water. Incidentally, speaking from personal experience (with the flu, not DXM), the "cool" water will feel damn cold.
In the case of a fever at or above 105 F (40.5 C) you've got a real emergency on your hands. Immediately contact a doctor or hospital, and try to reduce the body temperature as quickly as possible. Ice-water baths are acceptable providing there is someone (sober) there to make sure the person doesn't go into shock and drown. Expect to hear a lot of screaming; this is a significantly unpleasant experience even without a fever.
6.12.9 Shortness of Breath / Breathing Problems
Again this is usually a perception problem, and sometimes is related to panic attacks. There is also evidence that dissociative anesthetics in general cause a transient feeling of shortness of breath, possibly because the body is beginning to "take over" breathing from conscious control. Take deep, even, and slow breaths; hyperventilating won't help, and can make you feel even worse. It should clear up by itself. In the case of hyperventilation, the "breathing into a paper bag" trick really does work, by increasing blood CO2 levels.
6.12.10 Choking On Your Tongue
If you start feeling like you are choking on your tongue, make sure someone can assist you, or call a doctor if you believe you really are choking. There is actually very little danger of choking on your tongue; it's pretty much physically impossible. Nonetheless it can seem frightening.
If you are in the position of trying to assist someone in this situation, open the person's mouth, tilt their head back slightly, and grasp and hold their tongue out of the way of their airway until they feel better. Avoid putting anything in their mouth; this could easily fall in and make things much worse.
DXM can occasionally dry out your sinuses (an anticholinergic effect), so check first to see if your nosebleed is a result of nasal irritation. If so, treat it like you'd treat any other nosebleed.
If in doubt, or if you notice a prolonged nosebleed, burst capillaries in the eyes or face, headache, or a sudden impairment of mental or motor skills (hard to determine on DXM, I know), get medical help. I'm not familiar with any cases of DXM-induced hypertensive CVAs, although it might be possible, especially when mixed with stimulants or MAOIs.
A suggestion was made to me from a physician that I'm going to pass along. If you're going to be doing any sort of recreational drugs which carry a risk of hypertension, you may wish to purchase a sphygmomanometer (that blood pressure measuring gadget). They aren't terribly expensive, and they can warn you when you're starting to get into dangerous territory.
6.12.12 Feeling "dead" / losing one's body
Remember, DXM at high levels can be very dissociative. You're not dead, you just can't feel your body right now. This state can have a lot in common with certain lucid dream states. A feeling of "being dead" is common with third and fourth plateau DXM doses. The best thing seems to be to try to make contact with some part of your body (this can take a lot of effort), to reassure you that you're still there. Then, relax and enjoy your trip.
This is another reason why you should have a sober person with you. If you are in any real danger, he or she should take care of you.
6.12.13 Hangovers (lethargy and feeling "not all there")
Hangovers can occur from higher doses. Usually you can expect to feel very relaxed if not lethargic for the next day after a heavy trip. You may also might experience dizziness, muscle rigidity, loss of balance, slight double-vision, and a general feeling of being "not all there". Again, it goes away. Sleep seems to improve things a great deal. Make sure to drink a lot of liquids, get plenty of rest, take a multivitamin, and exercise. As DXM is metabolized differently in different people, some may experience hangovers (and trips) a lot longer than others; some have had three-day trips and week-long hangovers. For more details, see Section 6.1.7.
6.12.14 Prolonged Dissociation From the Real World
Very rarely, someone will come out of a DXM trip and seem to be very dissociated from the real world, behaving a little like a robot. Whenever this has been reported to me, the person in question had always taken a high (third to fourth plateau) dose, and in most cases had tried to achieve an out-of-body state (draw your own conclusions). Make sure the person is relaxed, and try to engage him or her in a familiar activity. Familiar environmental cues should go a long way towards bringing him or her back to the "real world". Also keep in mind that the person may be slow to metabolize DXM and thus still be tripping.
If, after a couple of days, the person still hasn't returned to normal, it's time to get worried. Contact your nearest psychologist, priest, shaman, or other equivalent. Note that I don't think there's any biological reason for this to happen.
Some papers on PCP have suggested that PCP can cause transient psychotic breaks in susceptible individuals which can last up to ten days. Hospitalization is recommended for the safety both of the patient and of others. I've never heard of anything like this with DXM but it could happen. This problem seems to resolve itself with or without psychiatric intervention. After returning to normal, the person may not remember the trip or a few days after it (355).
6.12.15 Serotonin Syndrome
It's not generally a good idea to diagnose yourself, and I'm hesitant to list in this section a diagnosis rather than symptoms. On the other hand, serotonin syndrome is, at least at the time I'm writing this, relatively unknown and probably underreported. And with increasing numbers of people taking SSRIs like ProzacTM, the potential for serotonin syndrome among users of DXM is rising.
The symptoms of serotonin syndrome are specified above (see Section 6.2.9). Keep in mind that generally speaking anyone on DXM will experience some of those symptoms, so don't freak out. The point is, if you start noticing said symptoms when you aren't on DXM, or if they are considerably stronger than usual, you might have a problem.
Don't panic. Serotonin syndrome is rarely fatal; usually it's just an indication that you need to stop taking so many serotonergic drugs. There are specific treatments for it (antiserotonergic drugs, appropriately enough), and most of the symptoms respond adequately to benzodiazepines.
6.12.16 Bad Trips
First off, let me distinguish between a bad trip and a true psychotic break. Here's an example. If you feel like your ego is dissolving into a puddle of jelly and you're suddenly confronted with frightening memories and images, that's a bad trip. If you believe the aliens have implanted a homing beacon in your brain and you have to drill a hole in your skull to let it out, that's a psychotic break. Generally speaking if you're having a bad trip, you still know you're on drugs. If you have a psychotic break, you probably don't.
The most important thing, and it seems trivial, is to remember that it's all in your mind. Your own mind is generating your experiences, and nothing in there can truly harm you. Make sure you are in a quiet, calm place, with limited sensory stimuli. If you find yourself having severe Lilliputian hallucinations (i.e., everything seems the wrong size, either too big or too small, or both), keep your eyes open and focus on a familiar object that will give you a size reference.
If things seem to be getting worse, consider a light sedative, such as as beer or two. Clinically, benzodiazepines have shown great utility in terminating dissociative trips, but I do not recommend using them except under the guidance of a physician. If you do use them, prepare to slam into a "psychic wall" since the experience of suddenly stopping the trip can be unpleasant, to say the least. Incidentally, by "psychic" I mean the effects of psychedelics on the psyche (mind and consciousness), not anything paranormal or spiritual.
Finally, try to keep a sense of humor about the whole thing. You aren't generally in any danger from DXM (unless you've taken way too much, in which case you should get yourself to the hospital), and it will end.
6.12.17 Psychotic Breaks
This section is probably of no use to you if you're the one experiencing the psychotic break, and is primarily intended for trip-sitters. First verify that the tripper is actually out of his gourd and not just playing games (incidentally, this is a good reason to use a "safeword" when tripping; when the safeword is spoken, take everything seriously until further notice). Delusions on DXM, especially upper plateaus, are common and not usually something to worry about since people aren't usually motivated to act upon them.
If you've got a real problem on your hands, call the hospital and explain the situation. Again, since DXM isn't a commonly known drug, you can tell them it's similar to ketamine and PCP (an oversimplification, I know). Be very careful in trying to restrain the tripper, since she or he may perceive this as a threat, and will probably be mostly immune to pain. Unless you can safely restrain someone (and unless you've had training in this sort of thing, you probably can't), the tripper, like a cornered animal, could beat the living shit out of you without thinking twice.
Instead of restraint, try talking him or her down. Be calm, soothing, and repeatedly remind the tripper that they have taken a drug which has critically impaired their perceptions. Remind them of who they are and how they got here, and that the experience will end.
6.13 How to Know When You've Done Too Much DXM
I always try to keep a sense of humor in life ... after all, it's only a temporary stop between incarnations anyhow. In view of that, I offer some suggestions from readers on how to know when to stop.
- You can identify a dozen different brands of cough syrup ... by the smell alone
- The local pharmacist starts asking about your tuberculosis problem
- The checkout clerk calls you "that Robitussin junkie"
- When you take out your recycling it's all brown glass bottles
- You ran out of excuses at the supermarket and now just tell people you like that cherry taste
- If Drixoral Dollars were real you'd own a Ferrari
- You haven't slept in two weeks, haven't eaten solid food in days, and you've just told your parents that you're marrying an alien from the desert planet Zolgar
- You've gotten so used to your eyes moving independently that you think you're actually a cleverly disguised lizard
- You just made your fifth Christmas ornament out of those little plastic shotglasses
- People ask you why you're walking around in shorts and a T-shirt sweating like a horse ... in the dead of winter.
- Your native language now consists of grunts and bizarre gestures
- Sophia Loren, Sean Connery, etc., come knocking at your door offering a night of passion and you tell them you aren't into "meat pleasures"
- You think you're on the Internet ... physically.
- You're sure you're actually a Jedi Master, but for some reason your Jedi Mind Powers don't seem to work on the cop that just arrested you for walking naked down Main Street.
On a more serious note, if you do start finding reality breaking down, your friends avoiding you, or your grades or work performance dropping, it's time to stop. DXM may be a lot of fun, but it just isn't worth losing something truly important over.