This is an unofficial archive of PsychonautWiki as of 2025-08-11T15:14:44Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
Doxylamine is a first-generation antihistamine. It can be used by itself as a short-term sedative and in combination with other drugs to provide night-time allergy and cold relief. Doxylamine is also used in combination with the analgesics paracetamol (acetaminophen) and codeine as an analgesic/calmative preparation, and is prescribed in combination with vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women. Its fetal safety is "A" in Briggs’ Reference Guide to Foetal and Neonatal Risk.
{{headerpanel|{{Approval}}}}
{{SummarySheet}}
{{Talk:SubstanceBox/Doxylamine}}
In addition, doxylamine is a very powerful hypnotic- even outclassing some prescription medicines. It's capable of causing very severe parasomnia with long-term usage.
'''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 B<sub>6</sub>. 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 [[Histamine|H<sub>1</sub>-histamine receptor]] and a mild [[antagonist]] of the [[Anticholinergics|muscarinic acetylcholine M<sub>1-5</sub> 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<ref name=":0">Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 546. ISBN 9783527607495.</ref> and was put on the market in a morning sickness formula combining doxylamine, vitamin B<sub>6</sub>, 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 effect index|Subjective effects]] are similar to that of other generation 1 antihistamines, which include [[Dry mouth|dry mouth]], [[External hallucination|life-like external hallucinations]], [[Tachycardia|fast heart rate]], dysphoria, [[sedation]], [[amnesia]], [[anxiety]], and [[Memory suppression|memory suppression.]] Lower doses can induce a hypnotic-sedative state similar to [[Ethanol|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.
'''Medical Uses'''
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.
It is used in the combination drug Pyridoxine/doxylamine to treat nausea and vomiting of pregnancy.
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|LD<sub>50</sub>]] 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.
As of 2004, doxylamine and diphenhydramine were the agents most commonly used to treat short term insomnia. As of 2008, antihistamines were not recommended by the American Academy of Sleep Medicine for treatment of chronic insomnia "due to the relative lack of efficacy and safety data.".
==History and culture==
It was first described in 1948 or 1949<ref name=":0" /> by Nathan Sperber and colleagues. In 1956 it was put on the market in a morning sickness formula combining doxylamine, vitamin B<sub>6</sub>, 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 on 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 in the syrup, though doxylamine could synergize the experience. This form of tripping is uncommon due to the toxicity of acetaminophen as well as the revolting taste of the syrup, and the doxylamine doesn't end up being the main factor in the trip, as it is often covered by the effects of dextromethorphan.
<br />
==Chemistry==
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.
'''Metabolites'''
==Pharmacology==
Doxylamine acts primarily as an inverse agonist of the H<sub>1</sub>-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.<ref>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.</ref>
The main metabolites are N-desmethyldoxylamine, N,N-didesmethyldoxylamine, and doxylamine N-oxide.
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.<ref>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 https://www.ncbi.nlm.nih.gov/pubmed/21686586. DOI Link: https://doi.org/10.1136/bcr.09.2008.0879</ref>
'''Side Effects'''
The bioavailability of doxylamine is 24.7% for oral administration and 70.8% for intranasal administration.<ref>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.</ref>
Doxylamine succinate is a potent anticholinergic and has a side-effect profile common to such drugs, including dry mouth, ataxia, urinary retention, drowsiness, memory problems, inability to concentrate, hallucinations, psychosis, and a marked increased sensitivity to external stimuli. Like many hypnotics, it should not be combined with other antihistamines,[citation needed] such as cetirizine (Zyrtec) or diphenhydramine (Benadryl), as this combination can increase the risk of serious side effects. Using doxylamine over a long period of time is not recommended. However, the drug is not addictive, and withdrawal effects are unlikely to be experienced with prolonged use.
==Subjective effects==
{{Preamble/SubjectiveEffects}}
'''Toxicity'''
{{effects/base
|{{effects/physical|
Doxylamine succinate is generally safe for administration to healthy adults. The median lethal dose (LD50) is estimated to be 50–500 mg/kg in humans. Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysis, and death. Fatalities have been reported from doxylamine overdose. These have been characterized by coma, tonic-clonic (or grand mal) seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3-year old child died 18 hours after ingesting 1,000 mg doxylamine succinate. Rarely, an overdose results in rhabdomyolysis and acute renal failure.
*'''[[Sedation]]''' In terms of energy level alterations, this drug is extremely sedating and often results in an overwhelmingly lethargic state. Low doses are used as a sleep aid. Doxylamine is typically more sedating than diphenhydramine.
*'''[[Spontaneous bodily sensations]]''' The “body high” of doxylamine can be described as similar to diphenhydramine, though it is less uncomfortable and dysphoric. Some users might even describe it as mildly euphoric.
*'''[[Muscle relaxation]]'''
*'''[[Muscle contractions]]''' At higher doses, doxylamine may cause muscle contractions.
*'''[[Perception of bodily heaviness]]''' One of the most apparent effects is having a very heavy body, or gravity being increased. This makes moving very difficult.
*'''[[Restless leg syndrome]]''' This effect is far less pronounced than with diphenhydramine, with some users not experiencing it at all.
*'''[[Tactile hallucination]]''' This is often a direct result of visual hallucinations and they commonly feel and look as if insects are crawling on one's skin.
*'''[[Nausea]]'''
*'''[[Abnormal heartbeat]]''' Acetylcholine is responsible for a normal heartbeat, which anticholinergics like antihistamines block.
*'''[[Dry mouth]]''' Dry mouth is reported to be very common with all antihistamines, including doxylamine.
*'''[[Dizziness]]'''
*'''[[Frequent urination]]''' & '''[[Difficulty urinating]]''' Doxylamine has the strange effect of making the user want to frequently urinate while making actual urination extremely difficult. This sensation is described as very uncomfortable.
*'''[[Gustatory hallucination]]'''
*'''[[Increased heart rate]]''' Acetylcholine is responsible for a normal heartbeat, which anticholinergics like antihistamines block.
*'''[[Increased bodily temperature]]'''
*'''[[Temperature regulation suppression]]'''
*'''[[Increased perspiration]]'''
*'''[[Motor control loss]]'''
*'''[[Physical fatigue]]'''
*'''[[Pupil dilation]]''' Common amongst all hallucinogens
*'''[[Skin flushing]]'''
*'''[[Temporary erectile dysfunction]]'''
}}
{{effects/visual|
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".
The threshold for doxylamine's hallucinations seems to be higher than diphenhydramine, with hallucinations only appearing at higher dosages.
====Suppression====
*'''[[Effect::Double vision]]''' - Double vision begins to manifest itself at moderate doses, with some users reporting that the effects can be quite intense.
*'''[[Effect::Peripheral information misinterpretation]]'''
*'''[[Effect::Shadow people]]'''
*'''[[Effect::Transformations]]'''
*'''[[Effect::Unspeakable horrors]]'''
*'''[[Effect::Object activation]]'''
Doxylamine is primarily used as the succinic acid salt, doxylamine succinate.
}}
|{{effects/cognitive|
It is the sedating ingredient of NyQuil (generally in combination with dextromethorphan and acetaminophen)
*'''[[Effect::Anxiety]]''' & '''[[Effect::Paranoia]]''' - Anxiety and paranoia are common with doxylamine, however this effect is reported to be less intense than with diphenhydramine.
In Commonwealth countries, such as Australia, Canada, South Africa and the United Kingdom, doxylamine is available prepared with paracetamol (acetaminophen) and codeine under the brand name Dolased, Propain Plus, Syndol (UK version no longer contains doxylamine as of 2015), or Mersyndol, as treatment for tension headache and other types of pain.
*'''[[Effect::Sleepiness]]''' - Doxylamine is reported to be extremely tiring. Low doses are often used and sold as a sleep aid.
Doxylamine succinate is used in general over-the-counter sleep-aids branded as Somnil (South Africa), Dozile, Donormyl (France, Russian Federation), Dormidina (Spain, Portugal), Restavit, Unisom-2 and Sleep Aid (generic, Australia).
*'''[[Effect::Wakefulness]]''' - This effect is less common with doxylamine than diphenhydramine as doxylamine is extremely sedating.
In the United States:
*'''[[Effect::Cognitive dysphoria|Dysphoria]]'''
doxylamine succinate is the active ingredient in the over-the-counter sleep-aid tablets branded as Unisom SleepTabs; however, all other Unisom products contain diphenhydramine hydrochloride instead.
*'''[[Effect::Cognitive euphoria|Euphoria]]''' - Doxylamine is typically extremely dysphoric, however some users report feelings of euphoria at lower dosages.
doxylamine succinate and pyridoxine (Vitamin B6) are the ingredients of Diclegis, approved by the FDA in April 2013 as the only drug for morning sickness with a class A safety rating for pregnancy.
*'''[[Effect::Cognitive fatigue]]'''
In Canada:
*'''[[Effect::Confusion]]'''
doxylamine succinate was the active ingredient in the over-the-counter sleep-aid marketed as Unisom-2 tablets (no longer available). Unisom now solely markets products containing diphenhydramine hydrochloride as the active ingredient.
*'''[[Effect::Creativity suppression]]'''
doxylamine succinate and pyridoxine (vitamin B6) are the ingredients of Diclectin, which is used to prevent morning sickness.
It is also available in combination with vitamin B6 and folic acid under the brand name Evanorm (marketed by Ion Healthcare)[where?].
*'''[[Effect::Delirium]]''' - Delirium is common with doxylamine at higher dosages. It is generally reported to be less intense and overwhelming as compared to diphenhydramine.
It is marketed under the names Restavit and Dozile), Russia (Valocordin-Doxylamine) and India (Vomentin).
*'''[[Effect::Delusion]]'''
*'''[[Effect::Depression]]'''
*'''[[Effect::Derealization]]'''
*'''[[Effect::Disinhibition]]'''
*'''[[Effect::Dysarthria]]''' - Dysarthria from doxylamine is reported to be notably intense.
*'''[[Effect::Emotion suppression]]'''
*'''[[Effect::Feelings of impending doom]]'''
*'''[[Effect::Focus suppression]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Language suppression]]'''
*'''[[Effect::Memory suppression]]'''
*'''[[Effect::Thought deceleration]]'''
*'''[[Effect::Thought disorganization]]'''
*'''[[Effect::Time distortion]]'''
}}
{{effects/auditory|
*'''[[Effect::Auditory hallucinations|Hallucinations]]''' - Auditory hallucinations on doxylamine are reported to be stronger than diphenhydramine.
There are currently no anecdotal reports which describe the effects of this compound within our [[experience index]]. Additional experience reports can be found here:
Pelser, Andries; Müller, Douw G.; du Plessis, Jeanetta; du Preez, Jan L.; Goosen, Colleen (2002). "Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats". Biopharmaceutics & Drug Disposition. 23 (6): 239–244. doi:10.1002/bdd.314. PMID 12214324.
^ Jump up to: a b "New Zealand Datasheet: Doxylamine Succinate" (PDF). Medsafe, New Zealand Medicines and Medical Devices Safety Authority. 16 July 2008. Archived from the original on 22 March 2016.
Jump up ^ Briggs, Gerald G.; Freeman, Roger K.; Yaffe, Sumner J. (2008). Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Lippincott Williams & Wilkins. doi:10.1258/om.2009.090002. ISBN 978-0-7817-7876-3.
==Medical Uses==
Jump up ^ Madjunkova, S; Maltepe, C; Koren, G (June 2014). "The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin ®) for the treatment of nausea and vomiting of pregnancy.". Paediatric drugs. 16 (3): 199–211. doi:10.1007/s40272-014-0065-5. PMC 4030125Freely accessible. PMID 24574047.
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 [https://en.wikipedia.org/wiki/Pyridoxine pyridoxine] to prevent morning sickness for those undergoing pregnancy.<ref>https://www.drugs.com/mtm/doxylamine-and-pyridoxine.html</ref>
Jump up ^ Ringdahl, EN; Pereira, SL; Delzell JE, Jr (2004). "Treatment of primary insomnia.". The Journal of the American Board of Family Practice. 17 (3): 212–9. doi:10.3122/jabfm.17.3.212. PMID 15226287.
==Toxicity and harm potential==
Jump up ^ Schutte-Rodin, S; Broch, L; Buysse, D; Dorsey, C; Sateia, M (15 October 2008). "Clinical guideline for the evaluation and management of chronic insomnia in adults." (PDF). Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 4 (5): 487–504. PMID 18853708.
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]], [[Datura|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.<ref>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 https://www.ncbi.nlm.nih.gov/pubmed/21686586. DOI Link: https://doi.org/10.1136/bcr.09.2008.0879</ref><ref>Leybishkis, B., Fasseas, P., & Ryan, K. F. (2001). Doxylamine overdose as a potential cause of rhabdomyolysis. - PubMed - NCBI. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11465247</ref>
Jump up ^ Holder, C. L.; Korfmacher, W. A.; Slikker Jr, W.; Thompson Jr, H. C.; Gosnell, A. B. (1985). "Mass spectral characterization of doxylamine and its rhesus monkey urinary metabolites". Biomedical Mass Spectrometry. 12 (4): 151–158. doi:10.1002/bms.1200120403. PMID 2861861.
Jump up ^ DOXYLAMINE SUCCINATE. hazard.com
User should note that doxylamine can be extremely unpredictable and the mechanism by which it produces [[hallucination]]s 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.
Jump up ^ 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. BMJ Group. 2003 (90): 845. doi:10.1136/bcr.09.2008.0879. PMID 21686586.
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.
Jump up ^ Leybishkis B, B; Fasseas P; Ryan KF. (2001). "Doxylamine overdose as a potential cause of rhabdomyolysis". American Journal of the Medical Sciences. Lippincott Williams & Wilkins. 322 (1): 48–9. doi:10.1097/00000441-200107000-00009. PMID 11465247.
Jump up ^ Doxylamine succinate (CAS 562-10-7). berkeley.edu
===Lethal dosage===
Jump up ^ DOXYLAMINE SUCCINATE. International Agency for Research on Cancer (IARC) - Summaries & Evaluations
The LD<sub>50</sub> is around 470mg/kg in mice.<ref>ScienceLab - Material Safety Data Sheet Doxylamine succinate MSDS | http://www.sciencelab.com/msds.php?msdsId=9923890</ref>
Jump up ^ Sperber, Nathan.; Papa, Domenick.; Schwenk, Erwin.; Sherlock, Margaret. (1949). "Pyridyl-Substituted Alkamine Ethers as Antihistaminic Agents". Journal of the American Chemical Society. 71 (3): 887–890. doi:10.1021/ja01171a034. PMID 18113525.
Jump up ^ chattem.com, UNISOM Drug facts
===Tolerance and addiction potential===
Jump up ^ Slaughter, Shelley R.; Hearns-Stokes, Rhonda; van der Vlugt, Theresa; Joffe, Hylton V. (2014). "FDA Approval of Doxylamine–Pyridoxine Therapy for Use in Pregnancy". New England Journal of Medicine. 370 (12): 1081–1083. doi:10.1056/NEJMp1316042. PMID 24645939.
Doxylamine [[Addiction potential::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.
Jump up ^ unisom.ca product page
Tolerance to many of the effects of doxylamine develops [[Time to full tolerance::with repeated use]]. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to zero tolerance::1 - 2 weeks]] for tolerance to return to baseline (in the absence of further consumption). Doxylamine presents cross-tolerance with [[Cross-tolerance::all [[deliriant]]s]], meaning that after the consumption of doxylamine, all [[deliriant]]s will have a reduced effect.
===Dangerous interactions===
{{DangerousInteractions/Intro}}
*'''[[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==
{{LegalStub}}
*'''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}}
It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks. It may also not meet PW style and grammar standards.
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
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.
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.
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 on 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 in the syrup, though doxylamine could synergize the experience. This form of tripping is uncommon due to the toxicity of acetaminophen as well as the revolting taste of the syrup, and the doxylamine doesn't end up being the main factor in the trip, as it is often covered by the effects of dextromethorphan.
Chemistry
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.
Pharmacology
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 PsychonautWikicontributors. 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
Sedation In terms of energy level alterations, this drug is extremely sedating and often results in an overwhelmingly lethargic state. Low doses are used as a sleep aid. Doxylamine is typically more sedating than diphenhydramine.
Spontaneous bodily sensations The “body high” of doxylamine can be described as similar to diphenhydramine, though it is less uncomfortable and dysphoric. Some users might even describe it as mildly euphoric.
Muscle contractions At higher doses, doxylamine may cause muscle contractions.
Perception of bodily heaviness One of the most apparent effects is having a very heavy body, or gravity being increased. This makes moving very difficult.
Restless leg syndrome This effect is far less pronounced than with diphenhydramine, with some users not experiencing it at all.
Frequent urination & Difficulty urinating Doxylamine has the strange effect of making the user want to frequently urinate while making actual urination extremely difficult. This sensation is described as very uncomfortable.
Delirium - Delirium is common with doxylamine at higher dosages. It is generally reported to be less intense and overwhelming as compared to diphenhydramine.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
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.
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 [[Cross-tolerance::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).
↑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". https://onlinelibrary.wiley.com/doi/10.1002/bdd.314
↑ 2.02.1Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 546. ISBN 9783527607495.
↑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.
↑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.
↑Leybishkis, B., Fasseas, P., & Ryan, K. F. (2001). Doxylamine overdose as a potential cause of rhabdomyolysis. - PubMed - NCBI. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11465247
