Further information: Responsible use § Hallucinogens
The toxicity and long-term health effects of recreational DXM use in humans has not been studied in any scientific context and the exact toxic dosage is unknown.
Anecdotal evidence suggests that there do not seem to be any negative health effects attributed to simply trying DXM at low to moderate doses by itself and using it sparingly, however, many DXM users report that waiting a week between their respective plateaus before doing DXM again (one week after first plat., two weeks after 2nd plat., etc.) can potentially prevent or minimize severe damage to the kidneys and many other organs including the heart and liver due to an excess of assorted toxic chemicals in the blood stream after DXM use. This 1-4 week period gives your body time to filter out these chemicals and help get you back to baseline levels to where its safe to do again. Some more heavy users of DXM report that these chemicals can build up heavily over time if you do not follow these guidelines, which could mean waiting longer to do again after more heavy use between short periods.
Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
Despite early speculation that DXM may cause neurotoxicity and Olney's lesions, it has not been shown to cause this effect in animals , However, many chronic users report significant issues with memory, attention, and mood that persist for many months after stopping usage.
In rats, oral administration of dextromethorphan did not cause neurotoxic effects in laboratory tests. Oral administration of dextromethorphan repeatedly during adolescence, however, has been shown to impair learning in those rats during adulthood.
It is strongly advised to use harm reduction practices if using this substance.
Dependence and abuse potential
As with other dissociatives, DXM produces dependence with chronic use and has moderate abuse potential.
When dependence has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
A formal survey of dextromethorphan users showed that more than half of users reported experience of the following withdrawal symptoms individually for the first week after long-term/addictive dextromethorphan use: fatigue, apathy, flashbacks, and constipation.
Over a quarter reported insomnia, nightmares, inability to feel pleasure, impaired memory, attention deficit and decreased libido.
Rarer side effects included panic attacks, impaired learning, tremor, yellowing of the skin, hives and muscle pain. Frequent and long-term usage at very high doses could lead to toxic psychosis and other permanent psychological problems.
Tolerance to many of the effects of DXM develops with prolonged and repeated use.
This results in users having to administer increasingly large doses to achieve the same effects.
After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption).
DXM produces cross-tolerance with all dissociatives, meaning that after the consumption of DXM all dissociatives will have a reduced effect.
Additionally, some users report an irreversible, permanent tolerance to DXM, which develops over a long period of time and is thought to correlate with the number of doses a person has ingested throughout their lifetime.
Some users claim that there is a "50 trip limit", after which the rewarding and unique effects of DXM are said to disappear permanently. The reason for this is unknown, although it may be indicative of neurotoxicity.
Tolerance
Long-term dextromethorphan (DXM) abuse may result in a permanent irreversible tolerance due to several different mechanisms.
DXM is an NMDA receptor antagonist that blocks the inhibitory effects of glutamate in the brain. With repeated use, the body compensates for this blockade by increasing glutamate production. This leads to the rapid development of tolerance to DXM.
Chronic DXM abuse leads to neuroadaptations, including changes in neurons and synapses. These adaptive changes result in altered brain function that reduces the effects of DXM.
DXM exerts its effects by blocking NMDA receptors. Long-term abuse can lead to the downregulation of these receptors, meaning they are decreased in number. Reduced receptors result in diminished responsiveness to DXM.
DXM is metabolized in the liver. Chronic abuse can induce metabolic enzymes, which accelerate DXM breakdown.
Overdose
Anecdotal evidence suggests that the risk of DXM overdose becomes significant at roughly 15mg/kg to 20mg/kg, or roughly 1000mg - 1500mg in a 70kg person. DXM overdose can have a wide range of effects, including delusions, hallucinations, psychosis, confusion, panic attacks, mania, sedation and severe balance issues, sometimes very inappropriate or violent behavior, increased heart rate, nystagmus and amnesia.
More serious side effects include anesthesia, respiratory depression, dangerously high fever, risk of accidental injury, self-harm and seizures. Seizures are created possibly due to hyponatremia and a general lowering of the seizure threshold. They are reported above the 900-1000mg dose range. It is possible that DXM may also affect other levels like potassium, vitamins or blood sugar further contributing to seizures and other health problems in a linear fashion in terms of severity and duration.
It is also believed that extremely high and repeated doses lead to serotonin syndrome.
One should not disrupt a person undergoing this experience as their delusions may cause them to respond with violence. Care should be taken as to not let the user get injured, and medical attention, or at the very least, medical surveillance should be sought to prevent severe respiratory depression, choking or organ damage.
Death from DXM toxicity is rare, although most overdose cases do cite life-threatening complications, typically extremely elevated heart rate and blood pressure, urinary retention and rhabdomylosis. Fever and seizures can lead to brain cell death.
Dangerous interactions
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Benzodiazepines - Small doses of benzodiazepines can end a bad trip, however, both substances potentiate the ataxia and sedation caused by the other. This can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position.
Cannabis - CBD is known to be an inhibitor of the CYP2D6 enzyme, which normally breaks down DXM to Dextorphan. This can lead to unexpected effects.
DOx - The DOx class as psychedelic stimulants have the potential to mask the effects of DXM and could lead to redosing to an unsafe level. DXM can also potentiate DOx resulting in an unpleasantly intense experience. DOx are also very physically stimulating and can cause heart rate and blood pressure problems especially since both substances have a very long duration.
25x-NBOMe
2C-T-x - As most 2C-T-x's are MAOIs this can potentially lead to serotonin syndrome, among other dangerous effects.
5-MeO-xxT - Little information exists about this combination.
Amphetamines - Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues.
Bupropion - Bupropion is a potent inhibitor of CYP2D6, the enzyme primarily responsible for breaking down DXM. This can lead to different and prolonged effects due to excessive accumulation of DXM in the bloodstream. Recreationally mixing Bupropion with DXM can lower the seizure threshold, heighten anxiety/paranoia and increase the potential of tachycardia among other symptoms. Information on this interaction within recreational doses is overall lesser-known and is to be advised against.
Cocaine - Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues.
ΑMT
PCP - Due to PCP's unique pharmacology affecting dopamine levels this may cause cardiovascular complications.
MDMA - High risk of serotonin syndrome due to the fact that both MDMA and DXM are both serotonergic substances.
Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Additionally CNS depression can lead to difficulty breathing. Avoid on anything higher than 1st plateau.
GHB - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the patient falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. This combination is hard to predict
GBL - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the patient falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. This combination is hard to predict
Opioids - Both substances can, with heavy doses, cause respiratory depression, and additionally, extremely heavy doses of both may be hepatotoxic. Additionally, use of NMDA antagonists such as dextromethorphan can lower tolerance to and potentiate opioids, increasing their effects.
Tramadol- Both substances can, with heavy doses, cause respiratory depression and if heavy doses are taken both may be hepatotoxic. Additionally, if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
MAOIs - High risk of serotonin syndrome.
SSRIs - High risk of serotonin syndrome.
Antihistamines - Many H1 antagonists, including antihistamines such Benadryl or terfenadine, as well as many antipsychotics, can slow down the metabolism of DXM due to their inhibition of CYP2D6, leading to possible death.
Other interactions
- DXM has been shown to prevent and reverse morphine tolerance while also increasing analgesic effects as well as potentiating the analgesic activity of NSAIDs, naproxen, piroxicam, etodolac, diclofenac, and ketorolac.
