Diphenhydramine

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Diphenhydramine is associated with extremely unpleasant, if not dangerous, experiences.

The effects of DPH are very unpredictable and may result in serious injury. Please use harm reduction practices (such as always having a trip sitter) when using this substance. See this section for more details.

Summary sheet: Diphenhydramine
Diphenhydramine
Diphenhydramine.svg
Chemical Nomenclature
Common names DPH, Benadryl, Nytol, Sominex, Unisom, ZzzQuil
Substitutive name Diphenhydramine
Systematic name 2-(diphenylmethoxy)-N,N-dimethylethanamine
Class Membership
Psychoactive class Deliriant
Chemical class Ethanolamine
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.



Oral
Dosage
Bioavailability 40-60%
Threshold 25 - 100 mg
Light 100 - 200 mg
Common 200 - 400 mg
Strong 400 - 700 mg
Heavy 700 mg +
Duration
Total 2 - 6 hours
Onset 30 - 90 minutes
Come up 45 - 90 minutes
Peak 1 - 4 hours
Offset 2 - 6 hours
After effects up to 24 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.

Diphenhydramine (also known as DPH, Benadryl, and many others) is a deliriant substance of the ethanolamine class. Diphenhydramine is a first-generation H1 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 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.

Pharmacology

Diphenhydramine is an inverse agonist of the peripheral histamine H1 receptor and a central histamine H1 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)
H1 9.6-16
H2 missing data
H3 >10,000
H4 >10,000
M1 80-100
M2 120-490
M3 84-299
M4 53-112
M5 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.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These 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 of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Visual effects
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Cognitive effects
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Auditory effects
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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.
  • 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.
  • 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

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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.

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.

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 safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The following lists some known dangerous combinations, but may not include all of them. A combination that appears to be safe in low doses can still increase the risk of injury or death. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume.

  • 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]
  • 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.
  • 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]
  • 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]

See also

External links

References

  1. Emanuel, M. B. (1999). Histamine and the antiallergic antihistamines: a history of their discoveries. Clinical & Experimental Allergy, 29(S3), 1-11. https://doi.org/10.1046/j.1365-2222.1999.00004.x-i1
  2. http://www.drugs.com/monograph/diphenhydramine-hydrochloride.html
  3. Hevesi D (29 September 2007). "George Rieveschl, 91, Allergy Reliever, Dies". The New York Times. Archived from the original on 13 December 2011. Retrieved 14 October 2008. 
  4. "Benadryl". Ohio History Central. Archived from the original on 5 September 2015. Retrieved 13 August 2015. 
  5. Ritchie J (24 September 2007). "UC prof, Benadryl inventor dies". Business Courier of Cincinnati. Archived from the original on 24 December 2008. Retrieved 14 October 2008. 
  6. 6.0 6.1 Domino EF (1999). "History of modern psychopharmacology: a personal view with an emphasis on antidepressants". Psychosomatic Medicine. 61 (5): 591–8. doi:10.1097/00006842-199909000-00002. PMID 10511010. 
  7. Awdishn RA, Whitmill M, Coba V, Killu K (October 2008). "Serotonin reuptake inhibition by diphenhydramine and concomitant linezolid use can result in serotonin syndrome". Chest. 134 (4 Meeting abstracts). doi:10.1378/chest.134.4_MeetingAbstracts.c4002. 
  8. Domino, E. F. (1999). History of modern psychopharmacology: a personal view with an emphasis on antidepressants. Psychosomatic medicine, 61(5), 591-598.
  9. Kim, Y. S., Shin, Y. K., Lee, C. S., & Song, J. H. (2000). Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine. Brain research, 881(2), 190-198.
  10. halifa, M., Drolet, B., Daleau, P., Lefez, C., Gilbert, M., Plante, S., ... & Turgeon, J. (1999). Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine. Journal of Pharmacology and Experimental Therapeutics, 288(2), 858-865.
  11. https://www.ncbi.nlm.nih.gov/pubmed/11036158
  12. https://www.ncbi.nlm.nih.gov/pubmed/10511010
  13. Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine | http://www.sciencedirect.com/science/article/pii/S0006899300028602?via%3Dihub
  14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885114/ | Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine