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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%[citation needed]
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 is a first generation antihistamine affecting histamine at H1 receptors. In addition, it has powerful anticholinergic effects. It is very closely related to diphenhydramine, an agent with the same properties and OTC status. It is used as a short-term sedative and hypnotic (sleep aid) or in combination formulations to provide night-time allergy and cold relief. It is prescribed in combination with vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women.

It was first described in 1948.[1]



This chemistry section is incomplete.

You can help by adding to it.

Doxylamine is a part of the ethanolamine class of antihistamines.


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This pharmacology section is incomplete.

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Doxylamine succinate is generally safe for administration to healthy adults. The median lethal dose (LD50) is estimated to be ~500 mg/kg in humans.[2] Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysis, and death. [3] Rarely, an overdose results in rhabdomyolysis and acute kidney injury.[4]

Studies of doxylamine's carcinogenicity in mice and rats have produced positive results for both liver and thyroid cancer, especially in the mouse. The carcinogenicity of the drug in humans is not well studied, and the IARC lists the drug as "not classifiable as to its carcinogenicity to humans".[5]

The primary metabolites of doxylamine are:

Doxylamine can cause false-positives for methadone in high enough doses.[6]

Doxylamine acts primarily as an antagonist or inverse agonist of the histamine H1 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 anticholinergic and (at high doses) deliriant effects.[7]

The bioavailability of doxylamine is 24.7% for oral administration and 70.8% for intranasal administration.[8]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a research literature based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be regarded with a healthy degree of skepticism. It is 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 much more likely with higher doses and may include addiction, serious 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 used with pyridoxine to prevent morning sickness. It's also used as an over-the-counter sleep aid useful for alleviating short-term insomnia. Doxylamine is also a useful cough suppressant.[citation needed]

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.[9][10]

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.[11]

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

Although many psychoactive substances are reasonably safe to use on their own, they can suddenly become dangerous or even life-threatening when combined with other substances. The following list includes some known dangerous combinations (although it is not guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted 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. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 546. ISBN 9783527607495.
  3. Syed, Husnain; Sumit Som; Nazia Khan; Wael Faltas (17 March 2009). "Doxylamine toxicity: seizure, rhabdomyolysis and false positive urine drug screen for methadone". BMJ Case Reports. 2009 (90): 845. doi:10.1136/bcr.09.2008.0879. PMC 3028279. PMID 21686586.
  4. Leybishkis, B.; Fasseas, P.; Ryan, K. F. (2001). "Doxylamine overdose as a potential cause of rhabdomyolysis". American Journal of the Medical Sciences. 322 (1): 48–9. doi:10.1097/00000441-200107000-00009. PMID 11465247.
  5. DOXYLAMINE SUCCINATE. International Agency for Research on Cancer (IARC) – Summaries & Evaluations.
  6. 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:
  7. 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.
  8. 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.
  9. 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:
  10. Leybishkis, B., Fasseas, P., & Ryan, K. F. (2001). Doxylamine overdose as a potential cause of rhabdomyolysis. - PubMed - NCBI. Retrieved from
  11. ScienceLab - Material Safety Data Sheet Doxylamine succinate MSDS |