Dextromethorphan & Diphenhydramine
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.
|Summary sheet: Dextromethorphan & Diphenhydramine|
|Dextromethorphan & Diphenhydramine|
|The molecular structure of Dextromethorphan.|
|The molecular structure of Diphenhydramine.|
|Psychoactive class||Dissociative and Deliriant|
|Chemical class||Morphinan and Antihistamine|
|Routes of Administration|
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.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Toxicity and harm potential
- 5 Legal status
- 6 See also
- 7 References
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.
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.”
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.
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.
The subjective physical effects of DXM and DPH can be broken down into several components which progressively intensify proportional to dosage. These components generally include:
- Sedation & Stimulation - Sedation is generally more prevalent during the trip but at the very beginning slight stimulation may come which encourages simple activities like walking or socializing.
- Cough suppression
- Frequent urination and Difficulty urinating - These effects aren't as pronounced as they are when diphenhydramine is taken alonecitation needed
- Increased bodily temperature
- Increased blood pressure[Controversial]
- Increased heart rate[Controversial]
- Increased perspiration
- Motor control loss - A loss of gross and fine motor control alongside balance and coordination is prominent within this combination and becomes especially strong at higher dosages. This means that one should be sitting down before the onset to prevent falling over and becoming injured.
- Nausea - Extremely high doses can cause nausea.
- Nausea suppression - Diphenhydramine can suppress nausea, which is why it is marketed and sold as a motion sickness suppressant.
- Pain relief
- Physical autonomy
- Physical fatigue
- Spontaneous tactile sensations - The "body high" is a sharp, pleasurable tingling sensation which is location specific to the hands, feet and head. The second is a warm euphoric glow which emanates outwards from the centre of the body's torso.
- Perception of bodily heaviness - A powerful increase in the body's overall weight and sense of gravity is felt.
- Pupil dilation
- Tactile disconnection
- Temporary erectile dysfunction
This combination does not enhance the perception of visual stimuli in the way that psychedelics do. Instead, they tend to degrade and decrease visual acuity while increasing the instances of hallucinations as a result. These are described below and generally include:
The Visual distortions seem to be much more apparent than when DXM or DPH are taken alone and also have a slight psychedelic feel to them. The effects experienced are detailed below:
- Drifting (melting, breathing, morphing and flowing) - In comparison to other hallucinogens, this effect can be described as intricate in complexity; jittery, slow, and rigid in motion; static in permanence; blurry in detail; realistic in believability; and interactive in plasticity.
- Object alterations
- Brightness alteration - It is not uncommon during DPH/DXM experiences for one's vision to become dark and gloomy in its brightness.
In terms of the specific style of geometry present within this combination, it can be described as intricate in complexity, slow in movement, dark in colour scheme and ominous in emotional tone. It manifests itself in a traditional psychedelic manner when the eyes are closed, but appears as static, unmoving shapes and geometry which the external environment morphs into when the eyes are open and looking at any single point, always resetting once the person double takes. This is an unusual visual effect because both dissociative and psychedelic visuals do not do this, preferring to manifest themselves as a fast-moving and flat translucent veil across the visual field which cannot be interacted with.
The effects of this combination are extremely efficient at inducing delirious hallucinations which can be broken into the categories described below:
- External hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots) - In comparison to other classes of hallucinogen, this effect occurs more frequently than that of any other at moderate to heavy doses and is the defining feature of the experience. It can be comprehensively described through its variations as delirious in believability, autonomous in controllability and solid in style. The most common themes for these hallucinations include those of both everyday occurrences such as smoking phantom cigarettes, talking to people who are not there, insects and sinister, nightmarish experiences.
- Internal hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots) - In comparison to other classes of hallucinogens, this effect occurs briefly and spontaneously at moderate doses, but becomes progressively extended in its occurrence and duration proportional to dose before eventually becoming all-encompassing. It can be comprehensively described through its variations as delirious in believability, interactive in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style. While the internal hallucinations do seem real, objects are commonly made up of simple jittery lines and swirls comparable to the distortions on diphenhydramine and they are usually only colored grey or black.
- Peripheral information misinterpretation
- Shadow people
- Unspeakable horrors
- Object activation
The emotional dysphoria, paranoia, anxiety, depression and feelings of impending doom usually found within DPH do not always seem to present when taken in combination with DXM. This could be attributed to DXM's euphoric and calming effects. In total, the subjective cognitive effects of DXM and DPH can be broken down into several components which progressively intensify proportional to dosage. These components generally include:
- Sleepiness and Wakefulness
- Amnesia - Total amnesia usually occurs at higher dosages.
- Analysis suppression
- Confusion - The confusion experienced can result in a complete inability to understand others' intentions, emotions, humor and even simple sentences.
- Consciousness disconnection
- Creativity suppression
- Déjà vu
- Delirium - Delirium may be experienced with high doses.
- Delusions - These are commonly caused due to external hallucinations and are more delirious than with diphenhydramine alone.
- Dream potentiation
- Emotion suppression
- Focus suppression
- Increased music appreciation - At higher dosages however music may sound quiet and muffled.
- Language suppression
- Memory suppression
- Motivation suppression
- Simultaneous emotions
- Sleep disorders - Especially at higher dosages, one may temporarly be unable to wake up when falling asleep despite external stimulation.
- Thought deceleration
- Thought disorganization
- Time distortion
Anecdotal reports which describe the effects of this compound within our experience index include:
- Experience:100/100/100mg, first time with it
- Experience:400mg DXM + 300mg DPH – Bacterial friends
- Experience:DXM & DPH in combination
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 upon or correcting it.
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.
Although many psychoactive substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
- Stimulants - This combination can potentiate the anxiety-inducing, manic, delusional and disinhibiting aspects of dissociatives, particularly those without pronounced motor and consciousness-suppression components like ketamine as this can increase the likelihood of a panic event or psychotic episode.
- 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.[Controversial] 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 in the list below may increase the amount of neurotransmitters such as serotonin and dopamine to dangerous or even fatal levels.
- MAOIs such as syrian rue, banisteriopsis caapi, 2C-T-2, 2C-T-7, αMT, and some antidepressants
- Serotonin releasers such as MDMA, 4-FA, MDAI and αMT
- Selective serotonin re-uptake inhibitors (SSRIs)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
- Dextromethorphan-induced serotonin syndrome (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19238739
- Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats | http://linkinghub.elsevier.com/retrieve/pii/S0197-0186(07)00038-1
- Dextromethorphan attenuates trimethyltin-induced neurotoxicity via σ1 receptor activation in rats (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0197018607000381
- Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210