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Diphenhydramine use is associated with highly uncomfortable and/or dangerous experiences.

Deliriants are highly unpredictable and may result in erratic behaviors, self-injury, hospitalization, or death. It should be noted that most individuals do not choose to repeat the experience due to its unpleasant 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.

Summary sheet: Diphenhydramine
Chemical Nomenclature
Common names DPH, Benadryl, Nytol, Sominex, Unisom SleepMelts, 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.

Bioavailability 40-60%
Threshold 25 mg
Light 100 - 200 mg
Common 200 - 400 mg
Strong 400 - 700 mg
Heavy 700 mg +
Total 3 - 10 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, Dimedrol, Benadryl, and many others) is a deliriant substance of the ethanolamine class. It 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]

Subjective effects include sedation, anxiety, tactile hallucinations, memory suppression, thought disorganization, dysphoria, and external hallucinations. Lower doses tend to produce a stoning, 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 points are uncomfortable and dysphoric.

Notably, it is frequently reported to produce significant nausea and bodily discomfort ("body load"). Most people who try diphenhydramine do not report positive effects and do not wish to repeat the experience.

It is generally considered to have low abuse potential due to its dysphoric effects. The toxicity of recreational use is not well-studied. Anecdotal reports suggest that chronic use (i.e. high dose, repeated administration) may cause persisting hallucinations and impairments in cognition & memory. High doses have also been linked to seizures and cardiotoxicity.[3]

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.[4][5] In 1946, it became the first prescription antihistamine approved by the United States Food and Drug Administration (FDA).[6]

In the 1960s diphenhydramine was found to inhibit reuptake of the neurotransmitter serotonin.[7] 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).[7][8]


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 to the carbon member of a methoxy group CH3O-.

DPH is produced as a hydrochloride salt.


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.[7] 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. [9]

The receptor binding affinities are listed as follows:[10][7]

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 84-229
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.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects

Visual effects

Cognitive effects

Auditory effects

Experience reports

There are currently 15 experience reports which describe the effects of this substance in our experience index.

Additional experience reports can be found here:


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, Vivinox 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.



Dimenhydrinate (DMH) is a combination drug of Diphenhydramine and 8-Chlorotheophylline[16], marketed as Draminate, Dramamine, and Gravol among others, it is used to treat nausea. It is most commonly available as tablets, although it is also available in liquid form and as a suppository. In practice, dimenhydrinate is half as potent as pure diphenhydramine, by weight, dimenhydrinate is between 53% to 55.5% diphenhydramine.[17] The addition of the caffeine-like stimulant 8-Chlorotheophylline is reported to increase the dangerous cardiovascular effects diphenhydramine already has alone. This stimulant effect is also reported to make the trip more restless and dysphoric, with the added negative of being too wakeful to sleep the trip away.

Toxicity and harm potential


This toxicity and harm potential section is a stub.

As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
Note: Always conduct independent research and use harm reduction practices if using this substance.

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

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.[18]


The overdose threshold for diphenhydramine is commonly held to be around 1000 milligrams; however, sensitive individuals, or individuals taking other drugs alongside it can overdose with less. The main effects of an overdose are similar to those of heavy doses. Effects include delirium, psychosis, anxiety, confusion, hypotension, dryness, urinary retention, dizziness, dilated pupils and increased heart rate. Some of the more serious side effects at these doses include an even higher risk of seizures, and dangerous cardiovascular effects such as arrhythmia (abnormal heartbeat).[19]

The user may be completely unable to distinguish reality from hallucinations. For this reason there is a significant risk of the user responding to a delusional environment and injuring themselves or others, as well as the possibility of engaging in too much physical activity which can further strain the heart or cause rhabdomyolysis.[20] Individuals experiencing 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, especially when combined with most stimulants, depressants and MAOIs.


Some anecdotal 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

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.

  • 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 weak serotonergic effects.[21]
  • 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 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.[22]
  • 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.[23]
  • Poland: Diphenhydramine is not a controlled substance under Polish law, but is only available over the counter in medicine that contains paracetamol.<ref>[1]

See also

External links


  1. Emanuel, M. B. (July 1999). "Histamine and the antiallergic antihistamines: a history of their discoveries: History of antiallergic antihistamines". Clinical & Experimental Allergy. 29: 1–11. doi:10.1046/j.1365-2222.1999.00004.x-i1. ISSN 0954-7894. 
  2. http://www.drugs.com/monograph/diphenhydramine-hydrochloride.html
  3. Jang, D. H., Manini, A. F., Trueger, N. S., Duque, D., Nestor, N. B., Nelson, L. S., Hoffman, R. S. (November 2010). "Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose". Clinical Toxicology. 48 (9): 945–948. doi:10.3109/15563650.2010.527850. ISSN 1556-3650. 
  4. 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. 
  5. "Benadryl". Ohio History Central. Archived from the original on 5 September 2015. Retrieved 13 August 2015. 
  6. 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. 
  7. 7.0 7.1 7.2 7.3 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. 
  8. 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. 
  9. Khalifa, M., Drolet, B., Daleau, P., Lefez, C., Gilbert, M., Plante, S., O’Hara, G. E., Gleeton, O., Hamelin, B. A., Turgeon, J. (February 1999). "Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine". The Journal of Pharmacology and Experimental Therapeutics. 288 (2): 858–865. ISSN 0022-3565. 
  10. 10.0 10.1 Kim, Y. S., Shin, Y. K., Lee, C., Song, J. (27 October 2000). "Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine". Brain Research. 881 (2): 190–198. doi:10.1016/s0006-8993(00)02860-2. ISSN 0006-8993. 
  11. Thakur, A. C., Aslam, A. K., Aslam, A. F., Vasavada, B. C., Sacchi, T. J., Khan, I. A. (15 February 2005). "QT interval prolongation in diphenhydramine toxicity". International Journal of Cardiology. 98 (2): 341–343. doi:10.1016/j.ijcard.2003.10.051. ISSN 0167-5273. 
  12. Lilienfield, L. S., Rose, J. C., Princiotto, J. V. (April 1976). "Antitussive activity of diphenhydramine in chronic cough". Clinical Pharmacology and Therapeutics. 19 (4): 421–425. doi:10.1002/cpt1976194421. ISSN 0009-9236. 
  13. Huynh, David A.; Abbas, Malak; Dabaja, Ali (29 April 2023). "Diphenhydramine Toxicity". StatPearls. OCLC 1021256616. 
  14. Huynh, David A.; Abbas, Malak; Dabaja, Ali (29 April 2023). "Diphenhydramine Toxicity". StatPearls. OCLC 1021256616. 
  15. Hou, R. H., Scaife, J., Freeman, C., Langley, R. W., Szabadi, E., Bradshaw, C. M. (June 2006). "Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine". British Journal of Clinical Pharmacology. 61 (6): 752–760. doi:10.1111/j.1365-2125.2006.02632.x. ISSN 0306-5251. 
  16. Putra, Okky Dwichandra; Yoshida, Tomomi; Umeda, Daiki; Higashi, Kenjirou; Uekusa, Hidehiro; Yonemochi, Etsuo (29 July 2016). "Crystal Structure Determination of Dimenhydrinate after More than 60 Years: Solving Salt–Cocrystal Ambiguity via Solid-State Characterizations and Solubility Study". Crystal Growth & Design. 16 (9): 5223–5229. doi:10.1021/acs.cgd.6b00771. 
  17. "Dimenhydrinate injection, solution". Daily Med. U.S. National Library of Medicine. Archived from the original on 13 October 2014. Retrieved 19 July 2014. 
  18. Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., Yu, O., Crane, P. K., Larson, E. B. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA internal medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. ISSN 2168-6114. 
  19. Huynh, David A.; Abbas, Malak; Dabaja, Ali (29 April 2023). "Diphenhydramine Toxicity". StatPearls. OCLC 1021256616. 
  20. Emadian, S. M., Caravati, E. M., Herr, R. D. (October 1996). "Rhabdomyolysis: a rare adverse effect of diphenhydramine overdose". The American Journal of Emergency Medicine. 14 (6): 574–576. doi:10.1016/S0735-6757(96)90103-5. ISSN 0735-6757. 
  21. Khan, Salman; Saud, Shakir; Khan, Imran; Asif, Muhammad; Ismail, Osama; Salam, Arqam; Yang, Tsu Jung; Norville, Kim J (April 04 2018). "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect". Cureus. 10 (4). doi:10.7759/cureus.2421. PMC 5985917Freely accessible. PMID 29872601. 
  22. "The Pharmacy and Poisons Act" (PDF). Ministry of Legal Affairs, Government of the Republic of Zambia. 
  23. Erowid Diphenhydramine (Benadryl) Vault : Legal Status