Recreational use of DXM has more or less dangerous side effects, especially if DXM is combined with other drugs (including many pharmaceuticals), if too much is taken or if DXM is used chronically. DXM can also cause psychological addiction (habituation).
The following information is based on anecdotal reports from DXM users and on articles, reviews, and letters published in the medical literature.
[top]Short-term (acute) dangers
Short-term dangers and side effects of DXM occur during the DXM experience and usually wear off with it or shortly after it.
These may pose a serious risk to the user. Some may require medical care.
Dizziness, imbalance, ataxia, vertigo: Common [1-2,7,10-11]. In extreme cases, users may lose coordination and accidentally injure themselves. May induce nausea in persons with motion sickness.
Acute cognitive impairment (inattention, confusion; impaired memory, judgment, reflexes and reaction speed): Common [4,7-8,10-11,13-15]. May lead users to potentially dangerous activities and impair the ability to react and make decisions in critical situations.
Users should be in a controlled environment with few potential dangers. Driving or otherwise partaking in traffic, operating machinery, and any other activities which expose the user and others to danger should be avoided. DXM is known to impair driving abilities [13]. A fatal car accident in which DXM was involved has been recently reported [49].
Tachycardia (fast heart rate), hypertension (high blood pressure), hyperthermia (overheating): Common but not particularly serious in most cases [7,9,11-12,16-17]. May cause serious reactions (hypertensive crisis, myocardial infarction, cerebrovascular accident, etc.) in susceptible individuals (high blood pressure, cardiovascular disease, etc.), or when stimulants are concomitantly used with DXM Activities which raise blood pressure and heart rate (dancing, sex, sports, etc.) should not be overdone while on DXM (overexertion is possible).
These effects could be limited with low quantities of sedatives (benzodiazepines, kava, valerian, etc.). Because of the risk of increasing respiratory depression, these should not be used in high doses.
Respiratory depression (slow and shallow breathing): Common effect of high doses but not measurable with amounts up to 480 mg [8]. May be more pronounced and possibly life-threatening at high doses or when DXM is combined with other depressants.
Urticaria (hives), fixed drug eruption, rash: Rare [4,50-51]. While usually not serious by themselves, these and other cutaneous allergic reactions may predict a more serious allergic reaction and therefore warrant discontinuing DXM.
Facial edema (swelling of face through accumulation of fluids): Rare. May warrant discontinuing DXM. May be prevented by antihistamines.
Anxiety, paranoia: Occasional [8,11,52]. While usually not serious, may trigger panic attacks in certain individuals.
Unconsciousness: Being an effect of full dissociation, it is common at upper plateau doses, especially at fourth and Sigma plateaus. Usually not dangerous per se, but the unresponsive user needs to be watched by a sober trip assistant in order to prevent possible accidents (choking on vomit, etc).
Panic attacks, bad trips: Uncommon. May be caused by unfavorable set and setting. High doses of DXM may make the user believe he or she is going to die or become insane, which may lead to panic attacks, especially in inexperienced users. Read about preventing and controlling panic attacks and bad trips here.
Convulsions (seizures): Rare [18,53-54]. Seizures are more likely to develop in susceptible individuals such as epileptics or if the seizure threshold is reduced by other drugs or non-drug factors (see factors reducing the seizure threshold).
Data on this topic is conflicting. In most trials on rodents, DXM was shown to have anticonvulsant effects [55-58], although proconvulsant (seizure-potentiating) effects were observed in two trials (on rats) [59-60]. In another trial on rats, DXM was shown to be anticonvulsant at low doses, but induced seizures at high doses [ 61]. In humans, daily doses of 160-200 mg DXM were shown to have anticonvulsant effects which were more pronounced in intermediate and poor metabolizers at CYP2D6 [54]. However, a moderate amount of DXM (two doses of 300 mg, taken several hours apart) in a CYP2D6 poor metabolizer was reported to cause seizures [18]. In a human trial, DXM in daily doses of 120 mg increased the frequency of complex partial seizures by 25% [53]. In another trial on brain-damaged children suffering from seizures, doses of 20-42 mg/kg DXM (with assisted respiration) had anticonvulsant effects [62].
Psychotic break: Rare [63-64]. More likely to develop at very high doses of DXM, in individuals with underlying mental health disorders, in CYP2D6 poor metabolizers, etc.
[top]Long-term (chronic) dangers and side effects
Chronic dangers of DXM generally become apparent after DXM is consumed regularly for more than several days. These can be more or less serious, greatly varying between individuals.
[top]Chronic cognitive impairment
Excessive use of DXM can cause chronic cognitive impairment [7,15], ranging from slightly impaired memory and concentration to inability to form proper sentences or severe cognitive decline. This is not to be confused with the acute cognitive impairment during a DXM experience, which can be similar but is short-lived.
The intensity of chronic cognitive impairment caused by excessive DXM use can vary significantly, depending on frequency of use, the length of the period over which DXM was used, individual susceptibility, etc. In most cases, chronic cognitive impairment caused by DXM usually subsides if the user is abstinent. However, there have been reported confirmed and anecdotal cases of persisting cognitive impairment caused by long-term DXM abuse [15].
Chronic DXM abuse has been associated with depression [7]. Many anecdotal reports have also described depression following long-term DXM abuse. It is possible that depression may be a symptom of DXM withdrawal, although this is unproven.
[top]Psychological and physical dependence
Several cases describing psychological addiction to DXM have been described in the medical literature [1,7,15,52]. Psychologically addicted users often experience dysphoria and craving after ceasing DXM use.
As it often happens with psychological addiction to other drugs, DXM addiction tends to cause the addict to become very self-centered and neglect relationships, school, work, etc [15,52].
Two cases of physical withdrawal following cessation of chronic DXM abuse have been described in the medical literature. The symptoms consisted of severe nausea and vomiting, night sweats, tremor, muscle aches, abdominal pain, diarrhea, anxiety, restlessness and insomnia. Most symptoms subsided after several days [12,52].
Anecdotal reports of DXM withdrawal also include severe lethargy and headache.
It should be pointed out that the withdrawal symptoms caused by DXM are generally very mild and not comparable in intensity with those caused by opiates, alcohol, benzodiazepines, etc.
Long-term use of DXM can cause significant tolerance to its effects, some individuals being reported to use daily doses as high as 2000-3600 mg [7,52] to achieve effects.
When DXM is used regularly, the nature of effects also changes – the ‘magic’ gets lost. The positive effects DXM tend to diminish in time, while tolerance builds up and adverse effects are more pronounced. Overall, the DXM experience loses its appeal for many users (although not all). While this may be interpreted as purely physical tolerance, raising the dose doesn’t usually bring the magic back and the loss of magic is permanent in many cases.
In extreme cases (if DXM use is continued for a long time despite loss of magic), only few effects remain, the experience degrading to a state of dizziness, confusion, and discomfort.
Loss of magic can be prevented by limiting the frequency of DXM use to occasionally or rare.
[top]Hypothetical and unconfirmed chronic side effects
Because DXM is usually supplied in the form of its hydrobromide salt, its use elevates blood bromide (Br-). Long-term heavy use may raise bromide serum concentrations to toxic levels, causing bromism. The symptoms of bromism include fatigue, ataxia, cognitive impairment, psychosis, coma, bromoderma (an acne-like skin rash), etc. The threshold of bromide toxicity is a serum concentration of about 50 mg/dL.
In a human trial of DXM HBr in doses of 120/240/480 mg/day for 4 days each, consecutively, the mean bromide serum concentration was 3.2 mg/dL at the last day of administration. The total amount of consumed bromide was 740 mg [8].
An individual who consumed approximately 1500 mg DXM HBr per week for about one year had a bromide serum concentration of 27.2 mg/dL, which is still well below the threshold of toxicity [15].
In a controlled trial on humans, administration of 9 mg/kg/day bromide (the equivalent of about 2860 mg DXM HBr daily) for 12 weeks raised bromide concentrations to 34 mg/dL, whereas the threshold of bromide toxicity is 50 mg/dL. The recorded side effects consisted of slightly impaired concentration and drowsiness in males, and mild hyperthyroidism in females [65].
Although some effects of heavy DXM use certainly resemble bromism, it can be concluded the actual risk of bromism from DXM use is very low and that bromide has little to no role in the adverse effects of DXM.
In 1989, it was discovered that injecting very high doses of NMDA antagonists causes neuron death and chronic learning impairment in rats. These lesions are known as NMDA antagonist neurotoxicity (NAN) or Olney’s lesions (after their discoverer, John W. Olney).
Injected into rats, DXM and its metabolite dextrorphan induce heat-shock protein, which is related to NAN. Orally administered DXM, even in lethal doses or administered chronically, was shown not to cause NAN in rats [66].
Some have suggested that recreational use of DXM (and use of NMDA antagonists in general) causes these lesions in humans. However, this was never proven and there is circumstantial evidence that NAN does not have anything to do with the cognitive impairment caused by some NMDA antagonists in humans. See NMDA antagonist neurotoxicity.
Because DXM raises blood pressure [7-9,11-12,16,67], it should be expected that DXM increases the risk of heart attack, stroke and heart failure if used chronically. This should be considered especially if other risk factors (obesity, pre-existing high blood pressure, high cholesterol, caffeine dependence, etc.) are present.
[top]Where caution or abstinence is warranted
Because DXM raises blood pressure [7-9,11-12,16,67], it should not be used recreationally by persons with atherosclerosis, cardiovascular disease, or other conditions which contraindicate use of stimulants. Caution is also advised to persons with a family history of aforementioned conditions.
Persons with psychological and neurological disorders should be very careful with DXM, due to possible exacerbation of the illness.
DXM has been reported to exacerbate schizophrenia [68]. It is believed that some depressives may self-medicate with DXM [69], which can cause addiction and exacerbate the depression in time.
Persons suffering from bipolar disorder should be cautious, because DXM can cause mania [70-71] and mood swings resembling bipolar disorder [1,15], as well as exacerbate existing bipolar disorder [71].
Because DXM can cause seizures in some individuals (see short-term dangers), extreme caution is also warranted in epileptics and persons with a history of seizures in general.
The only controlled study of the effects of DXM in pregnancy has failed to show any significant effect of therapeutic use of DXM in the first trimester of pregnancy on the rate of birth defects [72]. However, DXM was shown to be teratogenic (i.e. cause birth defects) on chicken embryos [73] and NMDA antagonists in general are possible teratogens.
DXM is most likely safe to use therapeutically in pregnancy, but due to few safety data, recreational use of DXM during pregnancy is not recommended.
Because DXM may suppress respiration, high doses may be problematic to persons suffering of conditions which impair respiration, such as COPD (emphysema, bronchitis), lung cancer, severe asthma, etc.
CYP2D6 poor metabolizers (individuals who lack the cytochrome P450 2D6 enzyme) metabolize DXM to dextrorphan at a much lower rate than normal [4,11,14]. For these persons, the effects of DXM are prolonged, psychomotor impairment is more intense, and the overall effects are significantly less enjoyable. In a published pilot study, CYP2D6 poor metabolizers could barely tolerate doses of 3 mg/kg (lower-end second plateau), while extensive metabolizers (the majority of the population) could tolerate 6 mg/kg, which was the highest tested dose [14].
People who know to be CYP2D6 deficient should be very cautious (see first time approach). 5-10% of caucasians are CYP2D6 poor metabolizers, but prevalence varies widely between different populations.
The metabolites of DXM are excreted through the kidneys. Persons with kidney failure are expected to clear DXM much more slowly than persons with normally functioning kidneys, which can cause effects of very long duration. Persons with kidney failure should not risk consuming DXM recreationally.
[top]Dangerous and otherwise undesirable interactions with DXM
Because it inhibits serotonin reuptake [74-76] and stimulates its release [77], DXM may cause serotonin syndrome when combined with other serotonergic drugs (drugs which increase brain serotonin activity). Although serotonin syndrome is rare, it is a serious and potentially lethal condition. Cases of serotonin syndrome in which DXM played a role also involved:- Serotonin reuptake inhibitors: chlorpheniramine [78], fluoxetine (Prozac) [79] and paroxetine (Paxil) [80]
- Serotonin releasers: MDMA (Ecstasy)
- Monoamine oxidase (MAO) inhibitors: phenelzine (Nardil) [81] and linezolid (Zyvox, Zyvoxid) [82]
Generally, serotonin reuptake inhibitors and releasers only cause death (due to serotonin syndrome) when combined with MAO inhibitors; therefore, combinations of DXM and MAO inhibitors should be avoided. Although generally not resulting in death, combining DXM with other serotonin reuptake inhibitors (SSRI antidepressants, venlafaxine, tramadol, pethidine, etc) and serotonin releasers (MDMA, MBDB, methylone, amphetamines, etc) can cause serotonin syndrome and should be avoided or approached with great caution (testing at low doses, etc). See serotonergic drugs.
Although data on DXM and seizures is conflicting (see acute adverse effects), caution is advised when combining DXM with seizure threshold-reducing drugs or when other seizure threshold-reducing factors are present (see seizure threshold-reducing factors).
Inhibitors of the enzyme cytochrome P450 2D6 (CYP2D6) slow down the conversion of DXM to dextrorphan. Commonly used CYP2D6 inhibitors include bupropion (Wellbutrin, Zyban), citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), etc.
Using DXM in combination with CYP2D6 inhibitors resembles the effects of DXM in CYP2D6 poor metabolizers, which are generally characterized by much more potent and less pleasant effects (see where caution or abstinence is warranted).
Note that after chronic use of a CYP2D6 inhibitor, some time is required for CYP2D6 activity to return to normal. Small amounts of DXM, such as low first plateau doses, may be used to determine individual response. See CYP2D6 inhibitors.
When combined with DXM, stimulants can amplify the tachycardia and hypertension caused by DXM and also increase the possibility of seizures (see acute adverse effects). Such combinations are capable of causing hypertensive crisis, hyperthermia, and possibly cerebrovascular addicent (stroke) and myocardial infarction (heart attack). The seriousness of such interactions is proportional with the intensity of the stimulant taken and the consumed doses of both substances (consuming large amounts of cocaine after third plateau DXM is likely much worse than first plateau DXM with a cup of coffee). Preexisting risk factors also play an important role – see where abstinence or caution is warranted.
Alcohol can significantly amplify the nausea and vomiting caused by DXM. Respiratory depression may also be a potentially lethal problem when both DXM and alcohol are consumed in large doses (see below). Large amounts of alcohol should not be combined with DXM.
Using depressant drugs (alcohol, benzodiazepines, barbiturates, opiates, kava, etc) with DXM may depress respiration to life-threatening levels.
DXM in large amounts (upper plateau doses) causes respiratory depression by itself, and other depressants add to this effect. Concomitantly consuming low doses of both DXM and a depressant is most likely safe. Three recorded deaths have been caused by DXM in combination with other depressants (two from DXM+diphenhydramine, one from DXM+diphenhydramine+alcohol).
Because DXM is a mild competitive cytochrome P450 3A (CYP3A) inhibitor in high doses, it should not be used with the antihistamines terfenadine and astemizole. These can cause cardiac arrhythmias (heart irregularities), especially when used with CYP3A inhibitors or when overdosed upon. One reported death has been attributed to a combination of high-dose DXM and terfenadine [83].
It should be noted that some internet sources warn against using DXM with nonsedating (non-drowsy) antihistamines in general. However, cardiotoxicity is not a class effect of nonsedating antihistamines but believed to be unique to terfenadine and astemizole. Both terfenadine and astemizole have been withdrawn from the market in most countries.
Recent reports indicate that massive doses of cetirizine (Zyrtec), another nonsedating antihistamine, can also cause arrhythmias. As a precaution, concomitant use of cetirizine and DXM should be avoided.
Because of being a competitive CYP2D6 inhibitor, DXM can cause potentially severe interactions with a number of medications:- Amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin), imipramine (Tofranil). CYP2D6 inhibitors increase the toxicity of these tricyclic antidepressants. Combination should be avoided.
- Risperidone (Risperdal): CYP2D6 inhibitors increase extrapyramidal side effects. Combination should be avoided.
- Codeine, tramadol (Ultram): CYP2D6 inhibitors decrease analgesic efficacy.
- Flecainide, mexiletine (Mexitil), propafenone (Rythmol). CYP2D6 inhibitors increase the potential for arrhytmias. Combination should be avoided.
- Haloperidol (Haldol): CYP2D6 inhibitors may increase side effects.
- Propranolol: CYP2D6 inhibitors may increase hypotensive effects. Combination should be avoided.
- Trazodone (Desyrel): CYP2D6 inhibitors increase side effects. Combination should be avoided.
[top]Dangerous ingredients in DXM products
DXM is most commonly used in the form of a pharmaceutical. Depending on the product, this may pose a significant risk to the user.
[top]Multiple active ingredients
Combination (multi-symptom) products which contain other active ingredients besides DXM are common in some countries. When consumed in recreational doses, combination products can be dangerous because of the toxicity of the other active substances.
Information on the most common active ingredients found in combination products containing DXM is listed below.
Guaifenesin
Guaifenesin is a mucolytic agent which aids in coughing up mucus. High amounts can cause nausea and vomiting. Chronic high-dose abuse can result in kidney stones.
Acetaminophen (paracetamol, APAP)
Acetaminophen is a non-steroidal anti-inflammatory drug commonly used to relieve minor pain and to reduce fever. In high doses, it can cause liver damage, which can be fatal.
Antihistamines
Anticholinergic antihistamines such as chlorpheniramine and diphenhydramine are often present in combination cold preparations. Overdose generally manifests itself in dry mucosa, urinary retention, tachycardia, dysphoria and delirium.
Chlorpheniramine maleate is an antihistamine used in combination with DXM in Coricidin HBP Cough & Cold and some generics. Besides the risks of overdose, chlorpheniramine is especially dangerous because it is a potent inhibitor of CYP2D6 (which potentiates DXM, prolongs toxicity and may cause toxic chlorpheniramine buildup when used repeatedly), a serotonin reuptake inhibitor (a case of serotonin syndrome has been reported [78]), and a respiratory depressant. Coricidin HBP Cough & Cold is notorious for causing adverse reactions and deaths at relatively low doses, having a significantly higher risk profile than DXM alone [84-85].
Diphenhydramine also causes typical anticholinergic symptoms in overdose, causes respiratory depression and is a possible serotonin reuptake inhibitor and CYP2D6 inhibitor. Products containing diphenhydramine and DXM should not be used recreationally.
Systemic nasal decongestants
Pseudoephedrine is a sympathomimetic and psychostimulant mostly used to relieve nasal congestion. High doses can cause tachycardia, hyperthermia, and hypertension. Products containing pseudoephedrine besides DXM should not be used recreationally.
Phenylephrine (neosynephrine) is growing increasingly popular as a decongestant and is found besides DXM in some combination products. Phenylephrine is a potent vasopressor (causes hypertension), being potentially dangerous when used in high doses with DXM.
[top]Potentially dangerous inactive ingredients
While generally posing a less significant health risk to users, some inactive ingredients (excipients) in certain pharmaceuticals may be dangerous for some persons or if they are consumed in high doses.
Sugars & other sweeteners
Most cough syrups contain sugars (sucrose, glucose, high-fructose corn syrup, etc.) and other sweeteners, mostly sugar alcohols (sorbitol, glycerine, mannitol, etc).
Sorbitol is commonly used as a sweetener in chewing gum, cough syrups, low-calorie foods, etc. In large amounts, it can cause abdominal pain, bloating and diarrhea.
Cough syrups containing large amounts of sugars should not be used chronically. Sugar is linked to tooth decay, obesity, insulin resistance, etc. Because sugar-containing cough syrup can have a very high caloric value, chronic abuse may also result in malnutrition, as it often occurs in alcoholics. For obvious reasons, diabetics should avoid any cough syrups containing sugar. Syrups formulated for diabetics are available, although these may contain sorbitol as a sweetener.
Colorings
Food colorings such as tartrazine (E102, FD&C Yellow 5), Allura Red AC (E129, FD&C Red 40), Brilliant Blue FCF (E133, FD&C Blue 1) and others are often used in pharmaceuticals. These may cause allergic reactions in a minority of users, as well as hyperactivity. Effects of chronic high doses of these colorings are generally unknown in humans.
Two deaths resulting from overdose on DXM alone have been reported in the medical literature. Both took place in Sweden. One case was a suicide of an 18-year-old girl who most likely ingested 3000 mg. The other case involved uncertain amounts of DXM and suspected chronic abuse, in a 27-year-old man [86].
Several other fatalities caused by DXM have been reported by the media and websites about DXM [dextromethorphan.ws, indexed 6 Feb 2006]. Most of these involved use of unknown amounts of DXM HBr powder. Most victims used or intended to use DXM recreationally, but at least two cases were intentional suicides. Most deaths occurred in the US, while one was reported from Sweden.
Several deaths have been caused by concomitant use of DXM and other drugs. One death thought to be caused by an interaction between DXM and terfenadine was reported in the medical literature [83]. Another case is thought to be caused by an interaction between DXM and the monoamine oxidase inhibitor phenelzine [81]. Two teenagers died in February 2005 after overdosing on DXM powder and diphenhydramine. Another reported death involved alcohol and a product containing DXM and diphenhydramine. From 1993 to 1996, nine deaths caused by concomitant recreational use of DXM and zipeprol (another opioid antitussive which is used recreationally) have been reported in Korea [87].
Most fatalities caused by DXM alone share a common point: consumption of very large amounts of pure DXM HBr in powder form, in most cases without weighing the doses.
Any purified form of DXM (hydrobromide or free base) should not be consumed without weighing each dose with a scale of at least 10 mg accuracy. Estimating (eyeballing) the right amount of powder is generally not possible, which can result in overdose.
Although chronic users can build up a massive tolerance to DXM and may be resistant to doses that would kill any beginner, continuing use with a high tolerance should be avoided.
Anything above the third plateau (doses higher than 15 mg/kg) should be considered very risky and preferably avoided.
[top]DXM as an antitussive - side effects and risks
Medicinal use of DXM as an antitussive (in maximal doses of 30 mg every 4 hours, not exceeding 120 mg/day) is generally safe but may have side effects.
DXM should not be used to treat productive cough (accompanied by mucus). It should only be used to treat nonproductive (dry) or slightly productive cough.
DXM should be used for a limited period of time. If cough persists for more than several days, a health care professional should be contacted, as persistent cough may indicate serious underlying conditions.
Possible adverse effects include drowsiness, dizziness, nausea, vomiting, agitation, and allergic reactions (skin rash, bronchospasm, etc).
Using DXM in conjunction with central nervous system depressants (alcohol, sedative antihistamines, anxiolytics, hypnotics, etc) can increase drowsiness.
DXM should not be used with MAO inhibitors (nonselective MAO inhibitors and selective MAO-A inhibitors), because of the possibility of serotonin syndrome.
DXM can cause drowsiness and dizziness, which can impair the ability to drive and operate machinery. The individual response to therapeutic doses of DXM should be assessed before planning to drive or operate machinery.
Because of inconclusive data on its safety in pregnancy, DXM should be avoided during pregnancy and lactation unless necessary.
Therapeutic use of DXM in toddlers has repeatedly resulted in death. DXM should not be administered to anyone under 4 years of age unless directed by a physician.
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