Dextromethorphan & Diphenhydramine

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This combination may result in severe injury.

Both of these substances have known toxic properties that may dangerously potentiate each other when combined. Please see this section for more details.


This page has not been approved by the PsychonautWiki administrators.

It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks.

Summary sheet: Dextromethorphan & Diphenhydramine
Dextromethorphan & Diphenhydramine
The molecular structure of Dextromethorphan.
The molecular structure of Diphenhydramine.
Class Membership
Psychoactive class Dissociative and Deliriant
Chemical class Morphinan and Antihistamine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.

Threshold Common Heavy
- - - -
Light Strong
Threshold 100 / 100 mg
Light 200 / 200 mg
Common 300 / 300 mg
Strong 400 / 400 mg
Heavy 500 / 500 mg
Total 6 - 8 hours
Onset 20 - 60 minutes
Peak 3 - 6 hours
Offset 3 - 5 hours
After effects 2 - 5 hours

DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

This article is designed to serve as a complete breakdown and categorization for the consistent subjective effects that are produced when dextromethorphan (DXM) and diphenhydramine (DPH) are taken in combination.

Although there are thousands of possible substance combinations, the majority of them just induce the effects of the two separate substances on top of each other in a very predictable manner.

In contrast, these two substances do the opposite by producing a unique synergy when taken together and potentiate the positive aspects of the other substance whilst simultaneously suppressing their uncomfortable effects. These effects include distinct visual and hallucinatory effects.

It is recommended to take the DXM about 20 minutes beforehand the DPH due to its effects which can be felt way before the DXM kicks in.


Diphenhydramine (DPH), or 2-(diphenylmethoxy)-N,N-dimethylethanamine, is a first generation antihistamine originally synthesized in 1943. The chemical structure of DPH contains an ethylamine chain with two methyl groups bonded to the terminal nitrogen group RN. Additionally, this ethylamine chain is substituted at R2 with a diphenylmethoxy group, forming an ether. The diphenylmethoxy group consists of two aromatic phenyl rings bonded the carbon member of a methoxy group CH3O-. DPH is produced as a hydrochloride salt.

Dextromorphan (DXM) is a dextrorotatory molecule of the morphinan class. It contains a phenanthrene core structure with one aromatic ring (benzene) bound to two saturated rings (cyclohexane). Additionally it contains a saturated piperidine ring attached to R9 and R13 of the core structure. DXM is substituted at RN with a methyl group and at R3 with a methoxy group.



Further information: NMDA receptor antagonist

DXM acts as an NMDA receptor antagonist. NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the “hole.”

The mechanism of action behind DXM is via multiple effects, including actions as a nonselective serotonin reuptake inhibitor[1] and a sigma-1 receptor agonist.[2][3]


Further information: Antihistamine

DPH is an inverse agonist of the histamine H1 receptor, and is also a competitive antagonist at mACH receptors. This substance works via its antagonistic action on acetylcholine receptors. It is this inhibition of acetylcholine which leads to delirium, sedation and intensely realistic hallucinations alongside of some extremely uncomfortable and dysphoric physical side effects.

Subjective effects

When taken in combination, DXM and DPH both lessen the physically uncomfortable effects of the other substance. For example, due to DPH’s nausea suppressing properties, the nausea that is typically produced by DXM is almost entirely absent. In return, DXM’s dissociating and anesthetic properties have a strong positive effect on the sometimes unbearable physical dysphoria produced by DPH.

The net effect is a reduction or elimination of the DPH body load such as nausea, dizziness, drowsiness, restless leg syndrome, and extreme dehydration (although it should be noted that the opposite can also occur). This allows the unique delirium, hallucinations and visual effects of the DPH experience to become much more accessible.

It should be noted that the delirium producing effects of DPH may become masked so that the user loses awareness in such a way that puts them at risk for dangerous, potentially life-threatening fever or a psychotic state. This is way more likely in combination with DXM than it is with DPH alone. It is highly advised to never attempt this combination without a sober and experienced trip sitter.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

Visual effects

Cognitive effects

Auditory effects

After effects
Aftereffects (3).svg

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Toxicity and harm potential


This toxicity and harm potential section is a stub.

As such, it may contain incomplete or even dangerously wrong information. You can help by expanding or correcting it.
We also recommend that you conduct independent research and use harm reduction practices when using this substance.


DPH has been reported to cause psychosis and delirium at a significantly higher rate than other hallucinogens like LSD, DMT, or ketamine. There are a large number of experience reports online which describe states of psychotic delirium, amnesia, and other serious consequences after abusing the substance. In many cases, it has resulted in hospitalization and death. These harmful physical side effects may become more pronounced when taken in conjunction with DXM.

It is generally recommended that one avoid this combination or at least uses extreme caution and harm reduction practices, such as having a sober trip sitter.

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

Prominent examples include PCP and its analogs 3-MeO-PCP, MXE, and the diarylethylamine dissociatives like diphenidine or ephenidine. There is also evidence that suggests that combining these two increases their neurotoxicity.[citation needed] Anecdotally, worsened comedowns are also commonly reported when these two classes of substances are combined.
  • Depressants - Because both depress the respiratory system, this combination can result in an increased risk of suddenly falling unconscious, vomiting and choking to death from the resulting suffocation. If nausea or vomiting occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it. Also, this combination will produce a combined depressant effect which can cause dangerous levels of respiratory depression.
  • Stimulants - A dangerous rise in blood pressure and heart rate can occur when DXM is combined with a stimulant such as amphetamine and/or cocaine.

Serotonin syndrome risk

Combinations with the following substances may increase the level of neurotransmitters such as serotonin and dopamine to dangerous or even fatal levels.

Legal status

See also


  1. Dextromethorphan-induced serotonin syndrome ( / NCBI) |
  2. Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats |
  3. Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 receptor activation in rats (ScienceDirect) |
  4. Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441.