|Summary sheet: Diphenhydramine|
|Molecular structure of diphenhydramine|
|Common names||DPH, Benadryl, Nytol, Sominex, Unisom, ZzzQuil|
|Routes of Administration|
Diphenhydramine (also known as DPH, and by its trade name Benadryl, among many others) is a first-generation antihistamine used to treat a number of conditions including allergic symptoms, itchiness, insomnia, motion sickness, Parkinson's disease and extra-pyramidal symptoms. When taken in “recreational” doses (many times the recommended or safe dose), DPH becomes a notoriously powerful deliriant.
Diphenhydramine is an over the counter medicine. It was one of the first known antihistamines, first synthesized in 1943 by Dr. George Rieveschl and became usually sold under the brand name of Benadryl and Dramamine. This substance is available in many forms of generic or store brand medication. It is also sometimes marketed in dimenhydrinate, which is a mixture of roughly 55% diphenhydramine and 45% 8-chlorotheophylline, which is included to counteract the drowsiness.
Due to its extremely uncomfortable effects and very uncomfortable body load, this substance may be overly challenging for those who are not already extensively experienced with hallucinogens. Therefore, it is highly advised to approach this very powerful hallucinogenic substance with the proper amount of precaution, preparation, and harm reduction practices if one chooses to use it.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Available forms
- 5 Toxicity and harm potential
- 6 Legal issues
- 7 See also
- 8 External links
- 9 References
Diphenhydramine, 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.
Diphenhydramine is an inverse agonist of the peripheral histamine H1 receptor and a central histamine H1 receptor. The peripheral inverse agonism induces the allergy reducing effects. Like many first-generation antihistamines, it is also a competitive antagonist at mACH receptors.
This substance works mainly via its antagonistic action on acetylcholine receptors, but has also been shown to block sodium channels and inhibit the reuptake of serotonin. It is not known how significant this property is. However, the boxes of diphenhydramine-containing products do not warn users of diphenhydramine and SSRI interaction. Diphenhydramine 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. 
|Receptor Site||Binding Affinity (Lower = Stronger)|
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 that this substance can produce.
Regarding its subjective effects, DPH has a non-linear dose-response unlike anything found within other psychoactive substances. It is not like other substances in that a light dose does not necessarily equal a light trip. Doses under 300mg tend to induce more of a restless feeling, body high, and relaxation. Dosages above 500mg are typically what make the user enter a state of delirium and begin to see and hear fully-formed, extremely convincing hallucinations. Anything in between these two extremes is often reported to be a disappointing and extremely uncomfortable experience characterized by an extreme body high and sometimes terrifying hallucinations, depending on the lighting conditions and other contextual factors.
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 physical effects of DPH are usually described as extremely uncomfortable. They can be broken down into several components which progressively intensify proportional to dosage. These are described below and include:
- Abnormal heartbeat
- Dehydration - Diphenhydramine can be extremely dehydrating, which often leads to dry mouth and skin, chapped lips and nose bleeds. Users should drink plenty of water before and after an experience.
- Frequent urination and Difficulty urinating - This can be described as a feeling of concrete blocking the urethra, painfully conflicting with a frequent need to urinate.
- Gustatory hallucinations - A foul metallic-like taste is present throughout the entire trip, which in combination with a dry mouth can be a very uncomfortable effect which can last for days after the experience. Eating or drinking flavored drinks will only make the taste go away temporarily. It can also appear as a sign of addiction, where it is commonly felt as a result of cravings.
- Increased blood pressure and Increased heart rate - This often results in feelings of a beating chest and, with a high heart rate can lead to hyperventilation if excess stress is applied to the body.
- Increased bodily temperature
- Increased perspiration
- Motor control loss
- Muscle cramps and Muscle spasms - Sudden muscle cramps and spasms can form unexpectedly. This is common at the beginning of the trip and usually passes quickly.
- Nausea - High doses can cause nausea while lower doses suppress it.
- Nausea suppression - Diphenhydramine can suppress nausea, which is why it is marketed and sold as a motion sickness suppressant.
- Olfactory hallucinations - It is common for people to smell a mild, thick and dull smell in the air that can easily be ignored most of the time. Some users also notice a smell enhancement
- Perception of increased weight - One of the most apparent effects is having a massive body as if the gravity has been multiplied tenfold. This makes it extremely tough and uncomfortable to move.
- Physical fatigue
- Pupil constriction or *Pupil dilation - While it it shown that diphenhydramine constricts pupils minimally, many people also report that their pupils dilate, especially at high dosages when anti-cholinergic effects take place similar to drugs like atropine or scopolamine.
- Rapid breathing
- Restless leg syndrome - This is arguably one of the most uncomfortable effects experienced during the trip. It can also last for days after the experience and can even be chronic when this drug is abused repeatedly.
- Sedation - This compound is considered extremely sedating in a way that is stronger than alcohol or benzodiazepines, but different in a fashion that is similar to a stimulant high. There is usually a heavy body load which can become overwhelmingly uncomfortable.
- Shivers - At the beginning of a trip, one may start to feel cold and shiver.
- Skin flushing - This happens mostly around one's eyes, but can also be seen all over the body.
- Spontaneous tactile sensations - Users commonly report all-encompassing, sharp and painful jolts of electricity that spontaneously manifest themselves uncontrollably in a similar rhythm to hiccups.
- Tactile enhancement - This results in increased feelings of touch, pain, warmth and orgasms. It is usually only present at the peak and not during the come up or come down.
- Tactile hallucinations - This is often a direct result of visual hallucinations and they commonly feel and look as if insects are crawling on one's skin.
- Tactile suppression - Due to sodium channel blockage within the nerves, a feeling of numbness can be felt throughout the entire body.
- Temporary erectile dysfunction
DPH does not enhance visual stimuli (input) in the way that psychedelics do. Instead, they tend to degrade and decrease visual acuity and processing that results in increased hallucinations and degraded vision. This becomes more apparent in darker areas than in well-lit areas. These components are detailed below.
- Double vision
- Pattern recognition suppression
- Visual acuity suppression - This effect can result in blurry vision to the point of blindness. It sometimes can last for days after the trip itself.
- Drifting (melting, breathing, morphing and flowing) - In comparison to other hallucinogens, this effect can be described as intricate in complexity, jittery and flexible in motion, static in their permanence, realistic in believability, and interactive in plasticity. It is also reported to be very faint.
- Object alterations - The textures seen are described as transparent whirling lines and swirls which move at changing speeds and jitter uncontrollably. They only appear slightly above surfaces, walls and ceilings and can not be felt.
- Brightness alteration - It is not uncommon during DPH experiences for one's vision to become dark and gloomy in its brightness.
- Visual haze
- 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 dosages and is the defining feature of the experience. It can be comprehensively described through its variations as delirious in believability, controllable or 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 or nightmarish experiences.
- Internal hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots) - In comparison to other classes of hallucinogen, this effect occurs briefly and spontaneously at moderate dosages but becomes progressively extended in its occurrence and duration proportional to dosage 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. Internal hallucinations may occur at lighter dosages than needed to cause external hallucinations and delirium.
- Peripheral information misinterpretation
- Shadow people
- Unspeakable horrors
- Object activation
The head space of DPH is described by many as generally negative and dysphoric throughout the trip, often consisting of extreme paranoia and feelings of impending doom. It is extremely confusing and disorienting often leading to a complete inability to communicate or understand normal language.
The most prominent of these effects include:
- Sleepiness - In terms of its effects on the user's physical energy levels, diphenhydramine is most commonly considered to be extremely tiring. It is often used and sold as a sleep aid at low dosages (commonly 25 or 50 mg). Dosages of 12.5 mg are usually sold as anti-nausea medications.
- Wakefulness - Even though diphenhydramine is a depressant overall and causes sleepiness, it has stimulant effects on the body, which can also keep the user awake. This effect predominates sleepiness at higher dosages. With Dimenhydrinate, this effect is significantly more pronounced.
- Dysphoria - The levels of dysphoria experienced, however, vary between people with a very small percentage of users reporting that they do not seem to experience them at all.
- Analysis suppression - At higher dosages, a person could experience a complete halt of external information processing, which can make the user unable to perform simple tasks or make decisions.
- Anxiety - This is universal and more common on diphenhydramine than almost any other substance, although at extremely high dosages this effect isn't apparent.
- Cognitive fatigue
- Confusion - The confusion experienced can result in a complete inability to understand others' intentions, emotions, humor and even simple sentences.
- Creativity suppression
- Decreased libido - Interestingly, one's sex drive seems to have diminished, although sex and masturbation are considered more enjoyable in a unique way and often come with powerful orgasms.
- Delirium - Delirium may be experienced with extremely high doses.
- Delusions - These are commonly caused due to external hallucinations.
- Disinhibition - This effect is different from substances like alcohol, as it may not even be present in certain situations and is heavily influenced by anxiety and paranoia.
- Dream potentiation - Diphenhydramine is extremely efficient at potentiating dreams. This can result in not just the potentiation of dreams but a change in the content of them as well, occasionally leading to dreams that are both vivid and extremely bizarre.
- Dysarthria - Slurred speech and speaking with a different voice is common on DPH.
- Emotion suppression
- Feelings of impending doom
- Focus suppression
- Increased music appreciation
- Language suppression
- Memory suppression - There is extremely strong and apparent short-term memory loss, similar to cannabis.
- Motivation suppression - DPH can cause a complete loss of motivation to do almost anything. This is often accompanied by depression and can make the user extremely bored.
- Thought deceleration
- Thought disorganization
- Time distortion - Although not extreme, time dilation is definitely felt and can be overwhelming if the user is having a difficult trip.
Anecdotal reports which describe the effects of this compound within our experience index include:
- Experience: 550mg DPH - My First Time on DPH
- Experience:700mg - Joining the 700 club
- Experience:700mg Diphenhydramine trip
- Experience:Results of Experiment by Isopropanol
Additional experience reports can be found here:
DPH 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. DPH 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. DPH in powdered form can be taken orally as well as via injection. Any other routes of administration other than oral are not recommended because DPH burns and dehydrates skin tissue, which leads to extremely painful burns and bleeding.
Toxicity and harm potential
It is critical to note that a single dose of DPH can be extremely unpredictable and has the potential to result in severe consequences, hospitalization or death. The toxicity and long-term health effects of regular DPH usage do not seem to have been studied in any scientific context. This is because long-term DPH usage is very rare and the vast majority of people who try this compound do not wish to repeat the experience.
If taken on a regular basis, anecdotal reports suggest that DPH can have some serious effects on one's kidneys with the potential to result in bladder issues similar to that of ketamine cystitis.
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.
Diphenhydramine can become fatal at amounts close to or exceeding 2 grams. This can result in death when combined with most stimulants, depressants and MAOIs. It is worth noting, however, that a dosage of 1 gram is considered extreme in its strength and could potentially result in a fatal overdose if a person happened to be particularly sensitive to this substance.
It is strongly recommended that one use harm reduction practices when using this drug.
Tolerance and addiction potential
The use of DPH can be considered mildly addictive with a high potential for adverse side effects such as psychosis. In comparison to other hallucinogens, DPH has been reported to be significantly less addictive than that of MXE, ketamine, 2C-B or LSD. This is simply because the vast majority of people who try this substance 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 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at 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.
- Selective serotonin re-uptake inhibitors (SSRIs) - This combination can suppress the visual effects of diphenhydramine, however it may be dangerous to combine them due to diphenhydramine also being a weak SSRI, and may cause serotonin syndrome.
- Benzodiazepines - This combination can suppress the visual effects of diphenhydramine, however it may be dangerous due to being a sedative.
- Stimulants - Because of 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.
- Other anticholinergics - Because of 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.)
DPH 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: Possession and sale is illegal; foreigners have been detained for posession.
- Domino, E. F. (1999). History of modern psychopharmacology: a personal view with an emphasis on antidepressants. Psychosomatic medicine, 61(5), 591-598.
- 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.
- 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.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885114/ | Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine
- Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine | http://www.sciencedirect.com/science/article/pii/S0006899300028602?via%3Dihub