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'''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.
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|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.
{{headerpanel|{{proofread}}{{Approval}}}}
{{SubstanceBox/Doxylamine}}
'''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.
==History and culture==
==History and culture==
{{historyStub}}
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==
==Chemistry==
{{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.
Doxylamine is a part of the ethanolamine class of antihistamines.
==Pharmacology==
==Pharmacology==
{{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>
Doxylamine has powerful antihistaminergic effects, more so than any other antihistamine available over the counter{{citation needed}}, except for diphenhydramine.
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.
=== '''Metabolites'''===
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>
The primary metabolites of doxylamine are-
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>
* N-desmethyldoxylamine{{citation needed}}
* N,N-didesmethyldoxylamine{{citation needed}}
* doxylamine N-oxide{{citation needed}}
==Subjective effects==
==Subjective effects==
{{EffectStub}}
{{Preamble/SubjectiveEffects}}
===Physical effects===
:<small>* = shared with diphenhydramine</small>
*'''[[Effect::Increased heart rate]]'''* - Doxylamine inhibits the action of acetylcholine. In the heart, acetylcholine functions as an ''inhibitory'' neurotransmitter, decreasing blood pressure and heart rate.
*'''[[Effect::Increased blood pressure]]'''* - Doxylamine inhibits the action of acetylcholine. In the heart, acetylcholine functions as an ''inhibitory'' neurotransmitter, decreasing blood pressure and heart rate.
{{effects/base
===Cognitive effects===
|{{effects/physical|
*'''[[Effect::Delirium]]'''* - Because of doxylamine's blocking (antagonizing) action on muscarinic acetylcholine receptors,
*'''[[Effect::Sleepiness]]'''* - In terms of its effects on the user's physical energy levels, doxylamine is most commonly considered to be extremely tiring. It is often used and sold as a sleep aid at 25 and 12.5 mg dosages.
*'''[[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.
*'''[[Effect::Cognitive euphoria]]''' - This effect is only present in low doses, in higher doses it transforms into [[Cognitive dysphoria|dysphoria]]
*'''[[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.
*'''[[Effect::Cognitive dysphoria|Dysphoria]]'''*
*'''[[Muscle relaxation]]'''
*'''[[Effect::Delusions]]'''*
*'''[[Muscle contractions]]''' At higher doses, doxylamine may cause muscle contractions.
*'''[[Effect::Delirium]]'''*
*'''[[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.
*'''[[Effect::Increased libido]]''' - This effect is only present in low doses
*'''[[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.
*'''[[Effect::Internal hallucinations]]'''*
*'''[[Nausea]]'''
*'''[[Effect::External hallucinations]]'''*
*'''[[Abnormal heartbeat]]''' Acetylcholine is responsible for a normal heartbeat, which anticholinergics like antihistamines block.
*'''[[Effect::Depth perception distortions]]'''
*'''[[Dry mouth]]''' Dry mouth is reported to be very common with all antihistamines, including doxylamine.
*'''[[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.
*'''[[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|
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]]'''
}}
|{{effects/cognitive|
*'''[[Effect::Anxiety]]''' & '''[[Effect::Paranoia]]''' - Anxiety and paranoia are common with doxylamine, however this effect is reported to be less intense than with diphenhydramine.
*'''[[Effect::Sleepiness]]''' - Doxylamine is reported to be extremely tiring. Low doses are often used and sold as a sleep aid.
*'''[[Effect::Wakefulness]]''' - This effect is less common with doxylamine than diphenhydramine as doxylamine is extremely sedating.
*'''[[Effect::Cognitive dysphoria|Dysphoria]]'''
*'''[[Effect::Cognitive euphoria|Euphoria]]''' - Doxylamine is typically extremely dysphoric, however some users report feelings of euphoria at lower dosages.
*'''[[Effect::Delirium]]''' - Delirium is common with doxylamine at higher dosages. It is generally reported to be less intense and overwhelming as compared to diphenhydramine.
*'''[[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:
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>
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]], [[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>
==Toxicity and harm potential==
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.
{{toxicity}}
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.
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.
===Lethal dosage===
===Lethal dosage===
The LD/50 is around 50-500mg/kg in humans.{{citation needed}}
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>
===Tolerance and addiction potential===
===Tolerance and addiction potential===
Doxylamine is not addictive, but insomniacs can become dependent on the use of doxylamine to fall asleep.
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.
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===
===Dangerous interactions===
{{DangerousInteractions}}
{{DangerousInteractions/Intro}}
{{DangerousInteractions/Intro}}
*'''[[Stimulants]]''' - Because doxylamine increases BPM and BP and stimulants also do this, cardiac arrest, hypertensive crisis, stroke, and heart attack all become much more likely to occur. With very high doses, delirium can be potentiated to an extremely high level.
*'''[[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]]''' - Depressants can make the sleepiness effect of doxylamine extremely pronounced, leading to a severe cognitive deficit. Therefore, any activity that must be done sober (driving, using firearms, etc.) must absolutely not be done.
*'''[[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.
*'''[[Deliriants|Antimuscarinics]]''' - Combining doxylamine with other antimuscarinics such as [[Datura]], [[diphenhydramine]], and [[nutmeg]] can severely increase BPM and BP, and as such, cardiac arrest, hypertensive crisis, stroke, and heart attack all become much more likely to occur.
*'''[[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==
==Legal status==
{{LegalStub}}
{{LegalStub}}
:'''US''': Doxylamine is OTC.
*'''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==
==See also==
*[[Responsible use]]
*[[Responsible use]]
==External links==
==External links==
*[[wikipedia:Doxylamine|Doxylamine (Wikipedia)]]
==Literature==
==Literature==
==To Brack==
I undid this because:
:1. Wikipedia, although it is based on good faith, is not an acceptable source. I tried going to the stated reference there and it brought me to a DNS error.
:2. I have found other references that dispute this.
:3. The range of 50-500 is extremely broad when referring to an LD<sub>50</sub>.
If you can find another source of numbers, please do so. I don't like redoing edits, because I find it comes off as condescending or rude, but I decided this was necessary.
--[[User:Corticosteroid|Corticosteroid]] ([[User talk:Corticosteroid|talk]]) 01:12, 15 September 2017 (CEST)
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
