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Summary sheet: Doxylamine
Chemical Nomenclature
Common names Unisom, Doxylamine, Doxylamine succinate, Doxyl
Systematic name N,N-dimethyl-2-(1-phenyl-1-pyridin-2-ylethoxy)ethanamine
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 24.7% [1]
Threshold 10 mg
Light 75 - 200 mg
Common 200 - 350 mg
Strong 350 - 600 mg
Heavy 600 mg +
Total 4 - 8 hours
Onset 20 - 60 minutes
Come up 30 - 90 minutes
Peak 1 - 4 hours
Offset 2 - 3 hours
After effects 2 - 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.


Doxylamine (brand names Unisom, Vicks, Robitussin, and Coricidin) is a deliriant of the ethanolamine class. It is an alternative active antihistamine to diphenhydramine used in over-the-counter (OTC) cold medicines, as well as a morning sickness medication in combination with vitamin B6. In therapeutic doses, it's used as a hypnotic and allergy medication but when taken in excess acts as a delirant similar to diphenhydramine and datura. It is a reverse agonist of the H1-histamine receptor and a mild antagonist of the muscarinic acetylcholine M1-5 receptors. Doxylamine is often times found as the succinic acid salt, doxylamine succinate, in the form of a 25mg pill.

It was first described in 1948 or 1949[2] and was put on the market in a morning sickness formula combining doxylamine, vitamin B6, and dicyclomine called Bendectin. Today, it is used as an OTC medication used to treat short-term insomnia and allergies, but can also treat nausea and morning sickness in pregnant women.

Subjective effects are similar to that of other generation 1 antihistamines, which include dry mouth, life-like external hallucinations, fast heart rate, dysphoria, sedation, amnesia, anxiety, and memory suppression. Lower doses can induce a hypnotic-sedative state similar to ethanol, and a state of delirium at higher doses, though weaker than diphenhydramine. Doxylamine is described by many as being soft, cozy, and dreamy compared to diphenhydramine.

Doxylamine is a deliriant which is typically not an enjoyable experience. It is common for someone to avoid using deliriants after their first time as the effects of the substance are dysphoric in nature.

The abuse potential of doxylamine has not been extensively studied, but is inferred that due to its dysphoric nature that it has a low abuse potential. The measured LD50 of doxylamine is 500mg/kg in adults. It has not been shown to be carcinogenic or teratogenic. A tolerance is built up after repeated use over long periods of time, taking more of the substance to feel the same level of effects.

History and culture

It was first described in 1948 or 1949[2] by Nathan Sperber and colleagues. In 1956 it was put on the market in a morning sickness formula combining doxylamine, vitamin B6, and dicyclomine called Bendectin. It was then reformulated to remove dicyclomine in 1976, and taken off the market in 1983 due to concerns over causing congenital limb defects, though no study has been conducted over this matter. In 2013, the formula was approved again in the U.S. for morning sickness under the brand name Diclegis

Doxylamine succinate has been used in Vicks cold formulas since 1966 as the sedating agent, along side other drugs such as dextromethorphan, acetaminophen, and phenylephrine. Drinking NyQuil or Vicks for its intoxicating effects is due mostly to the dextromethorphan, though doxylamine could synergize the experience. This form of tripping is uncommon due to the toxicity of acetaminophen and the revolting taste of the syrup.


Doxylamine, or N,N-dimethyl-2-(1-phenyl-1-pyridin-2-ylethoxy)ethanamine is a ethanolamine antihistamine. It's similar to diphenhydramine, differentiating by having a pyridin and a phenyl group instead of two phenyls, and an extra methyl group attached to the carbon connecting the aromatic rings. It is a clear and colorless liquid at standard conditions as the freebase, and a white powder in standard conditions as the succinate salt.


Doxylamine acts primarily as an inverse agonist of the H1-histamine receptor. This action is responsible for its antihistamine and sedative properties. To a lesser extent, doxylamine acts as an antagonist of the muscarinic acetylcholine receptors, an action responsible for its deliriant effects.[3]

Doxylamine is broken down in the liver by cytochrome P450 enzymes CYP2D6, CYP1A2, and CYP2C9. The primary metabolites of doxylamine are N-desmethyldoxylamine, N,N-didesmethyldoxylamine, and doxylamine N-oxide. The highest blood levels of doxylamine are reached 1.5-2.5 hours after administration, and has a half life of 10-12 hours.

Doxylamine can cause false-positives for methadone in high enough doses.[4]

The bioavailability of doxylamine is 24.7% for oral administration and 70.8% for intranasal administration.[5]

Subjective effects

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

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Medical Uses

Doxylamine is commonly used as an over-the-counter sleep aid for alleviating short-term insomnia. Doxylamine could also serve as a cough suppressant by suppressing histaminic reactions that promote coughing; however its efficacy varies depending on where the cough derives from. Some doxylamine products are concomitant with pyridoxine to prevent morning sickness for those undergoing pregnancy.[6]

Toxicity and harm potential

For healthy adults, doxylamine is usually safe. The IARC has concluded that carcinogenic effects in humans are not a high-risk factor. Anticholinergic effects can pile up with other anticholinergics such as DPH, atropine, hyoscine, and hyoscyamine, tricyclic antidepressants, and some antipsychotics like promethazine and quetiapine. This can cause greatly increased delirium and heart rate/blood pressure. Additionally, doxylamine in high doses can cause rhabdomyolysis (the breakdown of skeletal muscle tissue), making it quite dangerous to frequently use or use large quantities.[7][8]

User should note that doxylamine can be extremely unpredictable and the mechanism by which it produces hallucinations has the potential to result in serious injury, hospitalization or death. Additionally, doxylamine puts users in a state where they have little control over their actions. Doxylamine can provoke bizarre and nonsensical behavior which may put the user at risk. It is strongly recommended that one use harm reduction practices when using this substance.

Lethal dosage

The LD50 is around 470mg/kg in mice.[9]

Tolerance and addiction potential

Doxylamine produces dependence with chronic use. In comparison to other hallucinogens, doxylamine 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 doxylamine 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). Doxylamine presents cross-tolerance with all deliriants, meaning that after the consumption of doxylamine, 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.

  • Stimulants - Due to doxylamine'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.
  • Depressants - As doxylamine is sedating, this combination can result in dangerous or even fatal levels of respiratory depression. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Benzodiazepines - Benzodiazepines can suppress the visual effects of doxylamine. However, this can combination can produce a dangerous amount of sedation and respiratory depression.
  • Anticholinergics - Due to doxylamine'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).
  • Selective serotonin re-uptake inhibitors (SSRIs) - SSRIs can suppress the visual effects of doxylamine. However, this combination may elevate the risk of serotonin syndrome due to doxylamine's serotonergic effects.

Legal status


This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

  • US: Doxylamine is available over the counter and is commonly sold as a sleep aid.
  • Russia: Doxylamine is only available through a prescription.[citation needed]

See also

External links



  1. Andries Pelser, Douw G. Müller, Jeanetta du Plessis, Jan L. du Preez, Colleen Goosen. "Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats".
  2. 2.0 2.1 Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 546. ISBN 9783527607495.
  3. Krystal AD, Richelson E, Roth T (2013). "Review of the histamine system and the clinical effects of H1 antagonists: basis for a new model for understanding the effects of insomnia medications". Sleep Med Rev. 17 (4): 263–72. doi:10.1016/j.smrv.2012.08.001. PMID 23357028.
  4. Syed, H., Som, S., Khan, N., & Faltas, W. (2009). Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone. - PubMed - NCBI. Retrieved from DOI Link:
  5. Pelser A, Müller DG, du Plessis J, du Preez JL, Goosen C (2002). "Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats". Biopharm Drug Dispos. 23 (6): 239–44. doi:10.1002/bdd.314. PMID 12214324. S2CID 32126626.
  7. Syed, H., Som, S., Khan, N., & Faltas, W. (2009). Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone. - PubMed - NCBI. Retrieved from DOI Link:
  8. Leybishkis, B., Fasseas, P., & Ryan, K. F. (2001). Doxylamine overdose as a potential cause of rhabdomyolysis. - PubMed - NCBI. Retrieved from
  9. ScienceLab - Material Safety Data Sheet Doxylamine succinate MSDS |