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Diphenhydramine (Benadryl, Dimedrol, Daedalon, and Nytol) is used to treat sneezing, runny nose, watery eyes, hives, skin rash, itching, and other cold or allergy symptoms. It is a first generation antihistamine which has anticholinergenic, antitussive, antiemetic, and sedative properties. An injectable solution of Diphenhydramine may be used for immediate control of life threatening allergens such as bee stings, exposure to peanuts or latex, in addition to epinephrine.[1]

Diphenhydramine is an antihistamine, meaning that it blocks the effect of histamine at the H1 receptor sites, and is used for a wide range of effects, ranging from allergy and itching relief, to sleep aids, to nausea relief. However, in addition to its antihistamine effect, it also has powerful, anticholinergic effects. This is accomplished by the antagonization of the neurotransmitter Acetylcholine - specifically, the muscarinic acetylcholine receptors - mAChR). Acetylcholine is associated with numerous, important, bodily functions (such as heartbeat, secretion of saliva and sweat, regulation of motor control, and regulation of Electrolytes).

At high doses - Antagonization of Acetylcholine can cause an interesting delirium that some find enjoyable. However, there are also numerous side effects associated with this state that will deter many people from using the drug. Anticholinergic toxicity can occur from the use of Diphenhydramine. Cases of Diphenhydramine causing anticholinergic toxicity have been reported at doses as low as 400 mgs. The overuse of Diphenhydramine is therefore deterred by most clinicians.

This article will go into depth on the recreational uses and dangers of diphenhydramine, but note that the information here will also apply to the commonly used drug dimenhydrinate. See the “Different forms of...” section to learn more about the differences between these drugs. However, apart from dosages, all the information about diphenhydramine will translate to dimenhydrinate.


[top]Using Diphenhydramine


Before one should even consider the use of diphenhydramine, they should read these recommendations:

1. Start with low dosages and work up. People often have drastically different reactions to the same dosages. While reading experience reports may give an idea of what dosages produce what effects, there is no guarantee they will translate to you.

2. Use a sober trip sitter if possible. At high dosages, the delirium produced by this drug may make it impossible to differentiate between hallucinations and reality. People have been known to reach into a burning fire, thinking they were grabbing a pencil off of their desk.

3. An extremely unpleasant hangover effect is to be expected for the day after. Expect dry mouth, nausea, vomiting, dry eyes, bad taste in mouth, jaundice (yellowing of skin), sensitivity to light and sound, burning or itching sensation in brain, lethargy, loss of motor control, and possible dehydration. Drink plenty of water and plan to do nothing but lay in bed the next day or two. Many users say that the hangover is not worth the experience. DO NOT DRIVE, OPERATE HEAVY MACHINERY, SWIM, CLIMB LADDERS, OR DO ANY OTHER LABOR INTENSIVE TASK THE FOLLOWING DAY!

[top]Dosages and Timeline

Diphenhydramine and its counterpart, dimenhydrinate (see the “Different Forms of...” section) can be bought over-the-counter at a pharmacy or grocery store almost worldwide in pill form. These dosages should give one a rough estimate of how much to take.

Note that it is possible one may have an allergy to this drug. One should never take a large dose before having tried a very small dose on its own previously.

Diphenhydramine usually comes in 25 or 50mg dosages. The following table should give an idea of how many pills one should take depending on the effect they are looking for.

Diphenhydramine Dosages
Light: 25 - 150 mg
Medium: 150 - 350 mg
Strong: 250 - 500 mg
Very Strong: 400 - 800 mg
Dangerous: 800+ mg

As far as dosing and effects go,
100mg: sleepiness, maybe some audio hallucinations. It'll be tough to stay awake.

200mg: sedation and mild delirium, mild hallucinations like bugs flying across visual field and things of the like. They'll pop up and be gone before you really catch whats going on.

300mg: Same as 200mg except more intense. Definite delirium and difficulty motivating yourself to stay awake. Visuals are more present. You might see bugs crawling in your skin and be able to comprehend some things like bugs before you fall asleep. Things that are really there might have different facial expressions. Audio hallucinations. Intense drymouth and uncomfortable.

400mg: Intense delirium. Symptoms are very similar to schizophrenia. You'll see people pass by that don't exist. If you close your eyes you'll think you're in a different place. Difficulty speaking and restlessness occurs. Heart rate increases and it's difficult to get comfortable. Staggering and depth perception will occur.

500mg: Very intense delirium. Walking is increasingly difficult. Walls will have patterns, random things will pop up and fake people will be seen and will converse with you. Speech and motor function is extremely difficult, and not much more than mumbling will come out at most. You will think you're in one place at a different time of day, then quickly flash to another place. Staying at one place at a time for roughly a minute. It becomes very uncomfortable and falling asleep will be difficult. You won't know if you're awake or dreaming, and if not lying in bed "sleepwalking" may occur, but you'll be bumping into walls and cannot comprehend where you're going. Drymouth seems uncurable, no matter how much water. Possible sickness.

Anything over 600mg may cause blackouts and dangerous for the heart, especially without a tolerance. Although people have taken over 1g and have survived, but remember very little of their trip, and cannot recall what was reality or hallucinations.

Note: The aforementioned list are general effects. Everyone reacts differently to diphenhydramine, but after reading multiple trip reports these are the most common effects.

Effective dosages vary greatly from person to person, based on factors such as body weight, tolerance, and other unknowns. There have been people taking doses higher than 800 mg and have been fine, but once someone gets to dosages that high, it begins to put strain on his or her heart. Some may take 500mg one night and not reach the desired effects, and then on a different night take the same dose and become overwhelmed. This chemical tends to be on the darker side and extremely random and is part of the reason why its popularity is low.

Tolerance develops extremely fast for diphenhydramine and seems to disappear slowly, so it is a good idea to space out diphenhydramine trips rather than increasing one's dosage to compensate for this tolerance. Compensation can become dangerous, because it is impossible to tell at exactly what dose diphenhydramine will become dangerous to one's health.

Dimenhydrinate dosages are roughly twice those of diphenhydramine dosages, as there are 29 mg of diphenhydramine per 50 mg of dimenhydrinate.

Dimenhydrinate Dosages
Light: 50 - 300 mg
Medium: 250 - 650 mg
Strong: 450 - 900 mg
Very Strong: 700 - 1400 mg
Dangerous: 1400+ mg

The timeline of diphenhydramine can vary greatly depending on the same factors as dosage. It can take anywhere from 30 minutes to two hours to completely come up, so one should be very hesitant to redose if they are not getting the effects they desire. The full experience usually lasts 4 to 8 hours, but in cases of tolerance, drastically different effects can occur. For some users, they may find themselves back at baseline within two hours. There has also been a case where a subject took 600 mg of diphenhydramine, felt nothing for a few hours, redosed another 600 mg, and then woke up to find themselves in the hospital, having almost died of heart failure. It is clear that this is not a drug to be taken lightly.

Also note that dimenhydrinate has a slightly slower timeline than diphenhydramine, as one's body has to separate the two parts of the molecule (diphenhydramine and the weak stimulant).

While a user may feel at baseline after five or so hours, very subtle effects often persist for as long as 24 hours, and in rare cases even for a few days.

[top]Effects of Diphenhydramine

Positive Effects
- Muscle relaxation
- Music appreciation - This effect varies widely from person to person, but it is generally agreed that diphenhydramine does enhance music. Some various comments include "listening to any song sounds like you are listening to it for the first time, it is never boring," "it smooths out music and makes it more enjoyable." Some people say it gives a darker and creepier edge to music.
- Mixture of dreaming and reality - Perhaps the most interesting effect of diphenhydramine is that it causes people to dream while they are awake. This can be a very positive experience, but also a very negative as dreams are well known to be. Users can often have much more vivid dreams after the intoxication is over. Here is how one user described the dream-reality blending: "All of his thought patterns would turn into conversations with himself, or other people. Some conversations were actually reproductions of real conversations he had had in the past week. These thought-conversations would slowly get more and more real. Eventually, he would always feel compelled to say something out loud. He would struggle for a while, not sure if he really wanted to, but would always eventually say it. This would suddenly bring him back to reality, he would realize that there was no one in the room he was talking to, and his voice would sound foreign and distant."

Neutral Effects
- Time dilation (one minute may feel like 20)
- Extreme short-term memory impairment (at higher doses it becomes difficult to even finish sentences)
- Extreme sedation at higher doses, difficulty staying awake
- Flushed skin
- Feelings of intense gravity or extreme heaviness, feeling like one weighs thousands of pounds
- Unusual thoughts, speech, and behavior
- Visual and auditory hallucinations - This is one of the most sought after effects, and it can range from seeing simple patterns on the walls, to having conversations with people that are not there. This can be pleasant, interesting, terrifying, or even dangerous, because at high enough doses it becomes impossible to distinguish hallucinations from reality. A very common hallucination is seeing small insects that do not exist. Perhaps a small speck on the wall will be interpreted as a small fly. Many people see realistic spiders everywhere and proceed to get extremely terrified. Some have scratched nonexistent bugs on their skin to the point of bleeding. Because what someone will see is so unpredictable, one should be extremely careful using this drug.

Negative Effects
- Dry mouth
- Frequent urination, or possible urinary retention
- Sexual dysfunction (though there have been a few cases of sexual enhancement reported in low to moderate doses)
- Feelings of impending doom
- Blurred vision
- Confusion
- Discomfort, dizziness, loss of coordination
- Uncontrollable muscle twitches or cramps, restless leg syndrome (less common)
- Nervousness, anxiety
- Nausea (at higher doses, less common)
- Vomiting (very rare, in fact most users would have trouble vomiting if they tried due to diphenhydramine's antiemitic effects)
- Amnesia, loss of memory of the experience afterwards

[top]Combinations with Diphenhydramine

Diphenhydramine has been combined with other drugs by many users, this article will try to cover most of the combinations and point out which are dangerous.

Marijuana - Anecdotally, marijuana seems to alleviate some of the unpleasant side effects of diphenhydramine (although certainly not dry mouth) while slightly enhancing the visual and auditory hallucinations. It is possible that marijuana could increase one's heart rate further than what diphenhydramine does, but unless a very large dose of diphenhydramine was taken, this will probably not be dangerous. Most agree that this is a good drug to combine with diphenhydramine.

Stimulants - Many people have turned to stimulants to attempt to combat the strong sedation caused by diphenhydramine. This is generally not recommended, because it may stress the heart to dangerous levels, however something mild like caffeine will probably be fine. Avoid stronger stimulants like cocaine or amphetamines.

Alcohol or other sedatives - Generally not recommended, the sedative effects of each drug will compound the other, being possibly dangerous, and most likely very unpleasant (excessive dizziness is a likely effect).

Opiates - Small doses of diphenhydramine combine very well with opiates, as they reduce the side effects of opiates such as itching and nausea, as well as potentiating the opiates somewhat. Bad reactions can occur taking more than about 125 mg of diphenhydramine, or 200 mg of dimenhydrinate.

DXM - Medium or high doses of diphenhydramine should never be combined with DXM, as diphenhydramine has weak SSRI activity and this could lead to the unpleasant and potentially deadly serotonin syndrome. Also, combining these two drugs would likely create an extremely terrifying and unpleasant trip mentally, with the user begging to come down. Very small doses of diphenhydramine might alleviate some of the side effects of DXM, however, such as the robo-itch.

Psychedelics - Not recommended, the possibility of a scary trip is almost assured. One user took just 50 mg of diphenhydramine during a mushroom trip and very quickly descended into a confused and scared mental state. However a smaller dose, perhaps just 25 mg could relieve the nausea caused by some psychedelics.

[top]Different Uses for Diphenhydramine

[top]Pharmacology of Diphenhydramine

Binding profile of Diphenhydramine. All action is inhibition unless otherwise specified.
  • Histamine H1 (Ki = 0.3nM) [1]
  • Muscarnic Receptors (Ki = 0.6nM - Value is estimated from pA2. Subject to change) [1]
  • Na+ (Sodium Channel) Inhibitor (Ki = Unknown)
  • SERT Inhibitor (Ki = Unknown)

Diphenhydramine is an inverse agonist at peripheral H1 histamine receptors. These receptors are located outside of the central nervous system and are the prime target of second-generation antihistamines. However, Diphenhydramine is a first-generation antihistamine. Due to it's polarity, it's able to cross the blood-brain barrier and have a direct effect on the H1 histamine receptors as an antagonist.

Like most other first-generation antihistamines, Diphenhydramine also possesses potent anticholinergic effects by blocking the antimuscarinic acetylcholine receptors. Diphenhydramine is a competitive antagonist at all muscarinic subtypes. By acting as a muscarinic antagonist, Diphenhydramine is able to reduce the effects of parkinsons disease. This same action is also responsible for Diphenhydramines antiemetic effects.

By antagonizing the H1 histamine receptors, Diphenhydramine is able to reduce the effects of Histamine at these receptors. By stopping Histamine from being able to modulate H1 receptors, Diphenhydramine can reverse the effects of histamine on the capillaries, which reduce symptoms of allergies.

By antagonizing Histamine H1 and Muscarinic receptors centrally, Diphenhydramine is able to inhibit the exciting effects of Histaminergic & Cholinergic activity. This cause immense sedation and hypnosis. Because Histamine and Acetylcholine cannot excite neurons, you will feel tired, groggy, and "brain-fogged."

LD50 (mg/kg) :
Rat : 500 orally (hydrochloride salt)

[top]Chemistry of Diphenhydramine

Systematic (IUPAC) name:2-diphenylmethoxy-N,N-dimethylethanamine
Synonyms:2-(benzhydryloxy)-N,N-dimethylethylamine, [beta]-dimethylaminoethyl benzhydryl ether, O-benzhydryldimethylaminoethanol, [beta]-dimethylaminoethanol diphenylmethyl ether, [alpha]-(2-dimethylaminoethoxy)diphenylmethane, benzhydramine; Benadryl, Benocten, Nytol, Sedopretten, Sominex, Unisom sleepgels (hydrochloride); 1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid / 2-(diphenylmethoxy)-N,N-dimethylethanamine (2:1), diphenhydramine bis(theophyllin-7-ylacetate), bietanautine, Nautamine (di(acetyllinate))
Molecular Formula:C17H21NO
Molar mass: 255.36 g/mol, 291.82 g/mol (hydrochloride), 731.77 g/mol (di(acetyllinate))
CAS Registry Number:58-73-1, 147-24-0 (hydrochloride), 6888-11-5 (di(acetyllinate))
Melting Point:166-170°C (hydrochloride), 168-170°C (di(acetyllinate))
Boiling Point:150-165°C @ 2.0 mmHg
Flash Point:no data
Solubility:Hydrochloride (g/mL) : water 1, alcohol 0.5, chloroform 0.5, acetone 0.02; Very slightly soluble in benzene, ether. Di(acetyllynate) soluble in alcohol; sparingly soluble in water
Additionnal data:pH of 1% aqueous hydrochloride salt solution is about 5.5
Notes:hydrochloride crystallyzed from absolute ethanol/ether

[top]Dangers of Diphenhydramine

[top]Short-term Dangers

The primary danger of diphenhydramine comes from the nature of the effects. Deliriant antihistamines at high enough doses cause hallucinations that one cannot determine whether they are real or not. Confusion becomes an issue. Because of this, it is important to have a sober trip sitter who can stop one from doing anything dangerous.

At high enough doses, the drug becomes dangerous to the user's body. An overdose will result in a dangerously high heart heart rate, a possible heart attack or cardiac arrhythmias, and possible hepatotoxicity.

[top]Long-term Dangers

No one is really sure what the longterm effects of heavy diphenhydramine use are. It is not recommended due to the fast tolerance building, and there are anecdotal reports of depression, brain and/or stomach damage, and other problems. One study in older patients indicated that high diphenhydramine intake even at just therapeutic levels could raise the risk of dementia.


- Do not take if you are on MAOI's
- Do not take if you have glaucoma, enlargement of prostrate, or urinary obstructions
- Do not take if you have any breathing problems such as emphysema or particularly bad asthma
- Do not take if you a stomach ulcer

[top]Producing Diphenhydramine

[top]Different forms of diphenhydramine

Diphenhydramine and dimenhydrinate are essentially the same drug. Specifically, dimenhydrinate is the 8-chlorotheophyllinate salt of diphenhydramine. What this means is that dimenhydrinate is diphenhydramine attached to a weak stimulant similar to caffeine. Therefore, the only real differences between the two drugs is that diphenhydramine is stronger (29 mg of diphenhydramine is the same as 50 mg of dimenhydrinate), and diphenhydramine will probably start affecting the user faster. Also, a user may be less likely to fall asleep on dimenhydrinate, but the sedative properties of diphenhydramine far outweigh the stimulant properties of what is attached to it.

Some of the main brands of OTC drugs that contain dimenhydrinate are Dramamine and Gravol, while some of the main brands of OTC drugs that contain diphenhydramine are Benedryl, Nytol, and Sominex. However, no one should rely on just brand names to assume they have the proper drug. For example, Benedryl in the UK contains other chemicals that are far more toxic, so one should always check the active ingredients they have and make sure there is only diphenhydramine or dimenhydrinate. Often times these drugs are packaged with acetaminophen, which can be very toxic in high dosages, so it is also important watch out for this.

[top]Legal Status of Diphenhydramine

Diphenhydramine and dimenhydrinate are both legal, over the counter medications in most or all countries. They are sold in various allergy, sleeping, and anti-nausea formulas.


In Zambia diphenhydramine is listed as a controlled and illegal substance under article 34, PtII of chapter 96 of the Laws of Zambia.
Under the schedule listed in Regulation 2, possession of any amount of powders/tablets, containing 0.5mg or more, or liquids containing 2.5mg (or ml), of diphenhydramine is classed as trafficking.

  1. ^ https://drugs.com

[top]History of Diphenhydramine

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[1]Merck Index, fifteenth edition (2013)

Created by chrisn , 10-01-2008 at 00:11
Last edited by gonzochef, 09-01-2016 at 21:29
Last comment by SwampFox56 on 03-08-2013 at 11:11
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