Diphenhydramine is typically reported to produce highly uncomfortable or potentially dangerous experiences. The deliriant effects of high dose diphenhydramine are highly unpredictable and may result in erratic behaviors, self injury or death. It should be noted that most people do not choose to repeat the experience due to its uncomfortable nature. Please use harm reduction practices if using this substance (e.g. starting with a low dose and always having a trip sitter). Refer to this section for more details.



Diphenhydramine (also known as DPH, Benadryl, and many others) is a deliriant substance of the ethanolamine class. Diphenhydramine is a first-generation H 1 antihistamine that is widely used as a generic, over-the-counter medication to treat allergies. When exceeding approved doses, diphenhydramine produces powerful deliriant effects.

Diphenhydramine was first synthesized in 1943. In 1946, it became the first prescription antihistamine approved by the U.S. Food and Drug Administration. It was approved for over-the-counter use in the 1980s.[1] Today, it is typically used to treat allergies, but it may also be used for a number of conditions including itchiness, insomnia, motion sickness, nausea and the symptoms of Parkinson's disease.[2]

According to user reports, diphenhydramine has a non-linear dose-response, meaning the effects do not correspond directly with the dose. Lower doses produce a body high effect, while higher doses produce a state of delirium in which the user sees and hears fully-formed, extremely convincing hallucinations. Doses between these two extremes are uncomfortable and dysphoric. Diphenhydramine is frequently reported to produce significant nausea and bodily discomfort ("body load"). Most users who try diphenhydramine typically do not report positive effects and do not wish to repeat the experience.

The toxicity of recreational diphenhydramine use has not been studied. Anecdotal reports suggest that heavy use may cause persisting hallucinations and cognitive and memory impairments. It is highly advised to use harm reduction practices if using this substance.

History and culture

Diphenhydramine was discovered in 1943 by George Rieveschl, a former professor at the University of Cincinnati.[3][4] In 1946, it became the first prescription antihistamine approved by the United States Food and Drug Administration (FDA).[5]

In the 1960s diphenhydramine was found to inhibit reuptake of the neurotransmitter serotonin.[6] This discovery led to a search for viable antidepressants with similar structures and fewer side effects, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI).[6][7]

Chemistry

Diphenhydramine, or 2-(diphenylmethoxy)-N,N-dimethylethanamine, is an organic compound belonging to the ethanolamine class. The chemical structure of diphenhydramine consists of an ethylamine chain with two methyl groups bonded to the terminal nitrogen group R N . Additionally, this ethylamine chain is substituted at R 2 with a diphenylmethoxy group, forming an ether. The diphenylmethoxy group consists of two aromatic phenyl rings bonded the carbon member of a methoxy group CH 3 O-.

DPH is produced as a hydrochloride salt.

Pharmacology

Diphenhydramine is an inverse agonist of the peripheral histamine H 1 receptor and a central histamine H 1 receptor.[citation needed] The peripheral inverse agonism induces the allergy reducing effects.[citation needed] Like many first-generation antihistamines, it is also a competitive antagonist at mACH receptors.[citation needed]

Diphenhydramine is an acetylcholine receptor antagonist. Although the precise mechanism is not understood, the inhibition of the action of acetylcholine is thought to be primarily responsible for the delirium, sedation and intensely realistic hallucinations alongside the extremely uncomfortable and dysphoric physical side effects.

Diphenhydramine has been shown to block sodium channels and inhibit the reuptake of serotonin.[8][9] It also blocks voltage-gated potassium channels (VGKCs), meaning it has the potential to cause or lead to torsades de points, a potentially dangerous cardiac condition that can lead to sudden cardiac death. [10]

The receptor binding affinities are listed as follows:[11][12]

Receptor Site Binding Affinity (nM, Lower = Stronger) H 1 9.6-16 H 2 missing data H 3 >10,000 H 4 >10,000 M 1 80-100 M 2 120-490 M 3 84-299 M 4 53-112 M 5 30-260 SERT ≥3,800

Subjective effects

According to user reports, diphenhydramine displays a non-linear dose-response, meaning the effects don't correspond directly with the dose. Doses under 300 mg are reported to produce restlessness, muscle relaxation, and a body high while doses above 500 mg begin to produce a state of delirium in which the user sees and hears fully-formed, extremely convincing hallucinations. Doses in between these two extremes are said to be uncomfortable and dysphoric. Nausea and bodily discomfort ("body load") is reported almost universally.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a literature which relies on collected anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be taken with a healthy amount of skepticism. It is worth noting that these effects will not necessarily occur in a consistent or reliable manner, although higher doses (common+) are more likely to induce the full spectrum of reported effects. Likewise, adverse effects become much more likely with higher doses and may include serious injury or death.

Experience reports

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

Additional experience reports can be found here:

Forms

Diphenhydramine is available in several different forms over the counter and online.

Pills are available over the counter and online. Well-known brands include Benadryl, Benylin, Dramamine, Nytol, Sominex and ZzzQuil. Rarely, some of these products may contain other medicines, including dextromethorphan, guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose on other medicines in these DPH-containing products.

are available over the counter and online. Well-known brands include Benadryl, Benylin, Dramamine, Nytol, Sominex and ZzzQuil. Rarely, some of these products may contain other medicines, including dextromethorphan, guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose on other medicines in these DPH-containing products. Liquid is available over the counter and online. Diphenhydramine in liquid form can be taken orally or injected. Well-known brands include Benadryl and ZzzQuil. Rarely, some of these products may contain other medicines, including dextromethorphan, guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose on other medicines in DPH-containing products.

is available over the counter and online. Diphenhydramine in liquid form can be taken orally or injected. Well-known brands include Benadryl and ZzzQuil. Rarely, some of these products may contain other medicines, including dextromethorphan, guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose on other medicines in DPH-containing products. Powder is available online. Diphenhydramine in powdered form can be taken orally as well as via injection. Any other routes of administration other than oral are not recommended because diphenhydramine burns and dehydrates skin tissue, which leads to extremely painful burns and bleeding.

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.

The toxicity and long-term health effects of recreational diphenhydramine use have not been studied extensively.

User should note that diphenhydramine can be extremely unpredictable and the mechanism by which it produces hallucinations has the potential to result in serious injury, hospitalization or death. Additionally, diphenhydramine puts users in a state where they have little control over their actions. Diphenhydramine can provoke bizarre and nonsensical behavior which may put the user at risk.

Anecdotal reports suggest that regular use of diphenhydramine can have serious effects on one's kidney and bladder with the potential to result in issues similar to that of ketamine cystitis.

Cumulative diphenhydramine use has been tentatively linked to an increased risk of developing dementia.[17]

Overdose

The overdose threshold for diphenhydramine is commonly held to be around 1000 milligrams; however, sensitive individuals can overdose with less. The main effects of an overdose are similar to those of heavy doses. Effects include delirium, psychosis, anxiety, confusion as well as an increased heart rate,[citation needed] increased blood pressure[citation needed], dryness, urinary retention, dizziness and dilated pupils. Some of the more serious side effects at very high doses include the risk of seizures,[citation needed] and dangerous cardiovascular effects such as arrhythmia (abnormal heartbeat).[citation needed]

The user may completely not be able to distinguish reality from hallucinations. There is also a significant risk of responding to a delusional environment and possibly injuring themselves or others and also too much physical activity which can further strain the heart or cause rhabdomyolysis.[citation needed] Individuals undergoing delusions should, if possible, not be agitated. The first lines of treatment for overdose should be benzodiazepines, although medical attention should always be sought.

Diphenhydramine can become fatal at amounts close to or exceeding 2 grams.[citation needed] This can result in death when combined with most stimulants, depressants and MAOIs.

Psychosis

User reports suggest that diphenhydramine causes psychosis and delirium at a significantly higher rate than other hallucinogens (i.e. psychedelics and dissociatives).[citation needed] 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.[citation needed]

The recreational use of diphenhydramine is generally not advised. If deciding to use this substance, one should use extreme caution and harm reduction practices, such as having a sober trip sitter.

Dependence and abuse potential

Diphenhydramine produces dependence with chronic use. In comparison to other hallucinogens, DPH has been reported to have significantly less abuse potential than other hallucinogens. This is simply because the vast majority of people who try it do not wish to repeat the experience.

Tolerance to many of the effects of DPH develops with repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 1 - 2 weeks for tolerance to return to baseline (in the absence of further consumption). DPH presents cross-tolerance with all deliriants, meaning that after the consumption of DPH, all deliriants will have a reduced effect.

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The list below includes some known dangerous combinations (although it cannot be guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from TripSit.

Selective serotonin re-uptake inhibitors (SSRIs) - SSRIs can suppress the visual effects of diphenhydramine. However, this combination may elevate the risk of serotonin syndrome due to diphenhydramine's serotonergic effects. [ citation needed ]

- SSRIs can suppress the visual effects of diphenhydramine. However, this combination may elevate the risk of serotonin syndrome due to diphenhydramine's serotonergic effects. Stimulants - Due to diphenhydramine's excitatory cardiac effect, combining it with stimulants poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack as well as other cardiovascular events.

- Due to diphenhydramine's excitatory cardiac effect, combining it with stimulants poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack as well as other cardiovascular events. Benzodiazepines - Benzodiazepines can suppress the visual effects of diphenhydramine. However, this can combination can produce a dangerous amount of sedation and respiratory depression. [ citation needed ]

- Benzodiazepines can suppress the visual effects of diphenhydramine. However, this can combination can produce a dangerous amount of sedation and respiratory depression. Anticholinergics - Due to diphenhydramine's excitatory cardiac effect, combining it with other anticholinergics poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack as well as other cardiovascular events (inhibition of acetylcholine causes increased heart rate).

Legal status

Diphenhydramine is available either over the counter or by prescription in most countries. However, some countries require the purchaser to be over 16, 18 or 21.

Zambia: Diphenhydramine is illegal to possess and sell in Zambia; foreigners have been detained for possession. [ citation needed ]

Diphenhydramine is illegal to possess and sell in Zambia; foreigners have been detained for possession. United States: Diphenhydramine is widely available over-the-counter in the United States. It is an approved drug and is legal to buy, possess, and ingest without a license or prescription.[18]

See also

References



