This is an unofficial archive of PsychonautWiki as of 2025-08-08T03:33:20Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
Talk:Hydroxyzine
Revision as of 07:30, 6 December 2023 by >Sugar(Capitalized "culture" in the title)
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.
Hydroxyzine is a first-generation antihistamine substance of the diphenylmethylpiperazine/ethano-piperidine class.[1] It acts primarily as a potent and selective histamine H1 receptor antagonist,[2][3] with anxiolytic effects likely attributable to weak antiserotonergic effects.[4]
Hydroxyzine is often used in the treatment of itchiness, anxiety, insomnia, and nausea from motion sickness.[5] Unlike many other first-generation antihistamines, hydroxyzine has low affinity for muscarinic acetylcholine receptors, and thus does not produce strong anticholinergic side effects responsible for the deliriant properties of drugs such as diphenhydramine.[6]
Hydroxyzine sees little recreational use, limited mostly to where stronger anxiolytics, such as benzodiazepines or alcohol, are not available.[citation needed] Unlike more commonly abused depressants, it does not impact the neurotransmitterGABA, instead acting via potent inverse agonism of the histamine H1 receptor, which is responsible for its antihistamine and sedative effects.[7][8] In addition to its antihistamine activity, it has been shown to act as a weak antagonist towards the serotonin 5-HT2A receptor, the dopamine D2 receptor, and the α1-adrenergic receptor. It is prescribed for the treatment of generalized anxiety disorder, short-term treatment of insomnia, and allergic reactions .[9] Like other antihistamines, high doses of hydroxyzine can prolong the QT interval, which may lead to the development of torsades de pointes, a potentially fatal arrhythmia.[10] Combining hydroxyzine with other depressants such as benzodiazepines or alcohol can cause extreme symptoms such as dizziness or drowsiness, and as such it is recommended to use harm reduction practices if using this substance.
Tolerance to the CNS effects of hydroxyzine develops rapidly, often in as few as 3-7 days.[11] Tolerance to its sedative effects builds faster than tolerance to its anxiolytic effects. Such, it is indicated for use in short-term or as-needed insomnia treatment.
As a result, it may contain incomplete or wrong information. You can help by expanding it.
Hydroxyzine was first synthesized by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year.[12][13] Originally mostly given for nausea and allergies, it later began to be used in medicine for its anxiolytic properties. It is sometimes given as a substitute to benzodiazepines in surgeries to decrease anxiety and act as an anesthetic. In the United Kingdom 28 doses cost less than a pound.[14] In the United States the wholesale cost in 2018 was about 0.05 USD per dose.[15] In the United States about 8 million prescriptions were written for hydroxyzine in 2016.[16]
Hydroxyzine is a member of the diphenylmethylpiperazine and ethano-piperidine class of drugs. Analogues of hydroxyzine include buclizine, cetirizine, cinnarizine, cyclizine, etodroxizine, meclizine, and pipoxizine among others. It is synthesized by the alkylation of 1-(4-chlorobenzhydryl)piperazine with 2-(2-Chloroethoxy)ethanopiperidine[17]
Hydroxyzine acts primarily as a potent histamine H1 receptor antagonist.[18][19] Hydroxyzine is notable for having lower affinity for muscarinic acetylcholine receptor relative to other first-generation antihistamines, like diphenhydramine - subsequently, hydroxyzine is less liable to cause hallucinatory states or delirium. In addition to antihistamine activity, hydroxyzine acts as an antagonist towards [[5-HT2A]] receptors (likely responsible for its anxiolytic effects), dopamine D2 receptors, and α1-adrenergic receptors. Hydroxyzine is unique among first-generation antihistamines with regards to its anxiolytic properties.
Hydroxyzine is metabolized rapidly and crosses the blood-brain barrier with ease. When taken orally, it is rapidly absorbed through the gastrointestinal tract and is metabolized in the liver. Effects typically begin within 15-30 minutes. Peak concentration of hydroxyzine occurs at approximatively two hours after administration. Hydroxyzine and its metabolites have long half-lives, but the sedative effects typically at around 4-6 hours. In adults, the elimination half-life of hydroxyzine is 20 hours. Low doses of hydroxyzine (where less than 20% of H1 receptors are bound) are not associated with somnolence, but high doses (where 50% or more of H1 receptors are bound) cause sedation.[20]
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 - Hydroxyzine has milder sedative effects than other first-generation antihistamines, such as diphenhydramine. Tolerance to its sedative effects builds rapidly.
Tactile hallucinations - This effect only occurs at dangerously high doses, such as intentional overdoses.
Visual effects
Visual acuity suppression - Like many depressants, hydroxyzine is known to cause blurred or otherwise suppressed visual acuity in high doses. This is less likely to occur than other depressants, however it can still present itself at higher doses, or if the user has a low tolerance.
Paradoxical reactions to hydroxyzine occur mostly in high doses and can include nausea, itchiness, agitation, restlessness, and muscle spasms. Extremely high doses can result in seizures, vomiting, uncontrollable shaking, and other effects typical of an antihistamine overdose.
Cognitive effects
The general head space of hydroxyzine is described by many as one of mild to moderate sedation.
The most prominent of these cognitive effects generally include:
Amnesia - This only occurs in very high doses and is less pronounced than other depressants.
Emotion suppression - Antagonizing dopamine, adrenaline, and serotonin receptors, hydroxyzine exhibits similar emotional suppression to antipsychotics, but far less pronounced.
Language suppression - This only occurs in very high doses and may be indictive of an overdose.
Rebound anxiety - Rebound anxiety is a commonly observed effect with anxiety relieving substances like hydroxyzine. It typically corresponds to the total duration spent under the substance's influence along with the total amount consumed in a given period, an effect which can easily lend itself to cycles of dependence and addiction. Because hydroxyzine is a weak anxiolytic compared to benzodiazepines, addiction is extremely rare, but physical dependence is possible with frequent use.
Residual sleepiness - While hydroxyzine can be used as an effective sleep-inducing aid, its effects may persist into the morning afterward, which may lead users to feeling "groggy" or "dull" for up to a few hours.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
This toxicity and harm potential section is a stub.
As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. Note: Always conduct independent research and use harm reduction practices if using this substance.
Hydroxyzine works in multiple ways and can cause a variety of effects. It is only proven to affect histamine but has been shown to effect Acetylcholine, Glutamate, and GABA. Being a dissociative at very high doses, it can act more similarly to Ketamine and PCP (structural relative)in comparison to other antihistamines like Diphenhydramine (a deliriant). Most abuse of this drug happens at lower doses with the desired effect being sedation. Being a relaxant sedative, it can become habit forming. Its sedative effects are found to be more powerful than that of Diphenhydramine or Doxylamine, and happens to have more of an anxiolytic/anticonvulsant effect than that of those named above. Because of this, it can be a safer substitute to Benzodiazepines and GABAergics, and can provide a similar effect. Tolerance to Hydroxyzine can develop fast and psychological addiction can be common in patients treated for anxiety and insomnia with Hydroxizine. Physical addiction and dependence is present but not common - much of the addiction is psychological. Safe use is recommended with this medication.
Dangerous interactions
This medication can interact with many other substances in dangerous and even lethal ways. Being a CNS depressant, it can be potentiated by other depressant drugs. Alcohol should always be avoided as well as other GABA active drugs like Benzodiazepines (Ex. Alprazolam, Diazepam), Barbiturates (Ex. Secobarbital, Sodium Thiopental), and Anticonvulsants (Ex. Gabapentin, Pregabalin, Carisoprodol, Baclofen). Other depressant drugs that can interact with this are opiates. Opiates can be potentiated by this drug and can increase risk for overdose. Phencyclidine is a piperidine similar in structure to this drug and can basically double dose you. Be careful with any depressant when taking this medication.
Legal status
United States: Hydroxyzine is available by prescription but is not scheduled due to its low abuse concern
↑"Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.
↑Szepietowski J, Weisshaar E (2016). Itin P, Jemec GB (eds.). Itch - Management in Clinical Practice. Current Problems in Dermatology. 50. Karger Medical and Scientific Publishers. pp. 1–80. ISBN 9783318058895.
↑Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.
↑Snowman AM, Snyder SH (December 1990). "Cetirizine: actions on neurotransmitter receptors". The Journal of Allergy and Clinical Immunology. 86 (6 Pt 2): 1025–1028. doi:10.1016/S0091-6749(05)80248-9. PMID 1979798.
↑"Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.
↑Kubo N, Shirakawa O, Kuno T, Tanaka C (March 1987). "Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay". Japanese Journal of Pharmacology. 43 (3): 277–282. doi:10.1254/jjp.43.277. PMID 2884340.
↑Szepietowski J, Weisshaar E (2016). Itin P, Jemec GB (eds.). Itch - Management in Clinical Practice. Current Problems in Dermatology. 50. Karger Medical and Scientific Publishers. pp. 1–80. ISBN 9783318058895.
↑Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.
↑Rosario B. Hidalgo, David V. Sheehan, in Handbook of Clinical Neurology, 2012
↑British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.
↑ Levander S, Ståhle-Bäckdahl M, Hägermark O (1 September 1991). "Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine". European Journal of Clinical Pharmacology. 41 (5): 435–439. doi:10.1007/BF00626365. PMID 1684750. S2CID 25249362.
↑"Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.
↑Shorter E (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 9780195368741.
↑British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.
↑"NADAC as of 2018-11-21". Centers for Medicare and Medicaid Services. Retrieved 21 Nov 2018.
↑British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.
↑H. Morren, U.S. Patent 2,899,436 (1959); H. Morren, DE 1049383 (1954); H. Morren, DE 1061786 (1954); H. Morren, DE 1068262 (1954); H. Morren, DE 1072624 (1954); H. Morren, DE 1075116 (1954).
↑Szepietowski J, Weisshaar E (2016). Itin P, Jemec GB (eds.). Itch - Management in Clinical Practice. Current Problems in Dermatology. 50. Karger Medical and Scientific Publishers. pp. 1–80. ISBN 9783318058895.
↑Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.
↑Yanai K, Tashiro M (January 2007). "The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies". Pharmacology & Therapeutics. 113 (1): 1–15. doi:10.1016/j.pharmthera.2006.06.008. PMID16890992.
↑ Anderson PO, Knoben JE, Troutman WG (2002). Handbook of Clinical Drug Data. pp. 794-6. ISBN 9780071363624. PMC 1875767. PMID 20313924.
