Mescaline

{{Short description|Naturally occurring psychedelic compound}} {{Distinguish|mezcal|mesclun|mexamine}} {{Use dmy dates|date=October 2020}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Watchedfields = verified | verifiedrevid = 477169864 | drug_name = | image = Mescaline Structural Formulae bondline.svg | image_class = skin-invert-image | width = 225px | image2 = Mescaline-3D-xray-ballstick.png | image_class2 = bg-transparent | width2 = 165px

| Drugs.com = {{drugs.com|parent|mescaline}} | pregnancy_US = C | MedlinePlus = | licence_EU = | licence_US = | pregnancy_AU = | pregnancy_category = | class = Serotonin receptor agonist; Serotonergic psychedelic; Hallucinogen | routes_of_administration = Oral, smoking, insufflation, intravenous<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /> | ATC_prefix = None | ATC_suffix =

| legal_AU = Schedule 9 | legal_BR = F2 | legal_BR_comment = <ref>{{cite web | author = Anvisa | date = 2023-07-24 | title = RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial | language = pt-BR | publisher = Diário Oficial da União | url = https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | access-date = 2023-08-27 | archive-date = 2023-08-27 | archive-url = https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 | author-link = Brazilian Health Regulatory Agency | trans-title = Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control | url-status = live | publication-date = 2023-07-25 }}</ref> | legal_CA = Schedule III | legal_CA_comment = , except peyote | legal_DE = Anlage I | legal_UK = Class A | legal_UK_comment = (Plants containing mescaline legal) | legal_US = Schedule I (with religious use exceptions) | legal_UN = P I (psychoactive cactus like peyote or san pedro uncontrolled) | legal_status =

| bioavailability = Unknown (but ≥53%)<ref name="MuellerKlaiberLey2025" /><ref name="DrugBank">{{cite web | title=Mescaline: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=3 July 2024 | url=https://go.drugbank.com/drugs/DB19083 | access-date=19 May 2025}}</ref> | protein_bound = Unknown<ref name="DrugBank" /> | metabolism = Oxidative deamination, ''N''-acetylation, ''O''-demethylation, conjugation, other pathways<ref name="CasselsSáez-Briones2018" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> | metabolites = • 3,4,5-Trimethoxyphenyl-acetaldehyde<ref name="CasselsSáez-Briones2018" /><ref name="VamvakopoulouNarineCampbell2023" /> • 3,4,5-Trimethoxyphenylacetic acid<ref name="VamvakopoulouNarineCampbell2023" /> • 3,4,5-Trimethoxyphenylethanol<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> • Others<ref name="CasselsSáez-Briones2018" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /> | onset = Oral: 0.5–0.9{{nbsp}}hours (range 0.1–2.7{{nbsp}}hours)<ref name="HolzeSinghLiechti2024" /><ref name="KlaiberSchmidBecker2024" /><ref name="VamvakopoulouNarineCampbell2023" /> | elimination_half-life = 3.6{{nbsp}}hours (range 2.6–5.3{{nbsp}}hours)<ref name="HolzeSinghLiechti2024" /><ref name="LeyHolzeArikci2023" /><ref name="KlaiberSchmidBecker2024" /><ref name="MuellerKlaiberLey2025" /> | duration_of_action = 6.4–14{{nbsp}}hours (range 3.0–22{{nbsp}}hours)<ref name="HolzeSinghLiechti2024" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="KlaiberSchmidBecker2024" /> | excretion = Urine (≥92%; 28–60% unchanged, ≥27–31% as {{Abbr|TMPAA|3,4,5-trimethoxyphenylacetic acid}}, 5% as {{Abbr|''N''-Ac-3,4-DiMeO-5-OH-PEA|''N''-acetyl-3,4-dimethoxy-5-hydroxyphenylethylamine}}, <0.1% as {{Abbrlink|NAM|N-acetylmescaline}})<ref name="VamvakopoulouNarineCampbell2023" /><ref name="MuellerKlaiberLey2025" /><ref name="Patel1968" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="CasselsSáez-Briones2018" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="CharalampousWalkerKinross-Wright1966" />

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 54-04-6 | PubChem = 4076 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | DrugBank = DB19083 | ChemSpiderID = 3934 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = RHO99102VC | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C06546 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 28346 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 26687 | PDB_ligand = A1AFW | synonyms = Mescalin; Mezcalin; Mezcaline; 3,4,5-Trimethoxyphenethylamine; 3,4,5-TMPEA; TMPEA; ''O'',''O''-Dimethyl-5-methoxydopamine

| IUPAC_name = 2-(3,4,5-trimethoxyphenyl)ethanamine | C = 11 | H = 17 | N = 1 | O = 3 | SMILES = O(c1cc(cc(OC)c1OC)CCN)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C11H17NO3/c1-13-9-6-8(4-5-12)7-10(14-2)11(9)15-3/h6-7H,4-5,12H2,1-3H3 | StdInChIKey_Ref = {{Stdinchicite|correct|chemspider}} | StdInChIKey = RHCSKNNOAZULRK-UHFFFAOYSA-N

| density = 1.067 | melting_point = 35 | melting_high = 36 | boiling_point = 180 | boiling_notes = at 12 mmHg | solubility = moderately soluble in water }}

'''Mescaline''', also known as '''mescalin''' or '''mezcalin''',<ref>{{cite web | title = Mescaline | work = PubChem | publisher = U.S. National Library of Medicine | url = https://pubchem.ncbi.nlm.nih.gov/compound/Mescaline#section=Depositor-Supplied-Synonyms | access-date = 2024-10-22 }}</ref> and in chemical terms '''3,4,5-trimethoxyphenethylamine''', is a naturally occurring classical psychedelic protoalkaloid of the substituted phenethylamine class, found in cacti like peyote (''Lophophora williamsii'') and San Pedro (certain species of the genus ''Echinopsis'').<ref name="CasselsSáez-Briones2018">{{cite journal | vauthors = Cassels BK, Sáez-Briones P | title = Dark Classics in Chemical Neuroscience: Mescaline | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2448–2458 | date = October 2018 | pmid = 29847089 | doi = 10.1021/acschemneuro.8b00215 | url = https://repositorio.uchile.cl/handle/2250/155746}}</ref><ref name="VamvakopoulouNarineCampbell2023">{{cite journal | vauthors = Vamvakopoulou IA, Narine KA, Campbell I, Dyck JR, Nutt DJ | title = Mescaline: The forgotten psychedelic | journal = Neuropharmacology | volume = 222 | article-number = 109294 | date = January 2023 | pmid = 36252614 | doi = 10.1016/j.neuropharm.2022.109294 | doi-access = free }}</ref><ref name="HolzeSinghLiechti2024">{{cite journal | vauthors = Holze F, Singh N, Liechti ME, D'Souza DC | title = Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile | journal = Biological Psychiatry. Cognitive Neuroscience and Neuroimaging | volume = 9 | issue = 5 | pages = 472–489 | date = May 2024 | pmid = 38301886 | doi = 10.1016/j.bpsc.2024.01.007 | url = | doi-access = free }}</ref>

Mescaline is used recreationally, spiritually, and medically, with psychedelic effects occurring at doses from 100 to 1,000{{nbsp}}mg and it can be used in pure crystalline form or via the crude extract of mescaline-containing cacti. Mescaline induces a psychedelic experience characterized by vivid visual patterns, altered perception of time and self, synesthesia, and spiritual effects, with an onset of 0.5 to 0.9{{nbsp}}hours and a duration that increases with dose, ranging from about 6 to 14{{nbsp}}hours. Ketanserin blocks mescaline’s psychoactive effects, and while it's unclear if mescaline is metabolized by monoamine oxidase enzymes, preliminary evidence suggests harmala alkaloids may potentiate effects.

Mescaline primarily acts as a partial agonist at serotonin 5-HT2A receptors, with varying affinity and efficacy across multiple serotonin, adrenergic, dopamine, histamine, muscarinic, and trace amine receptors. It is a relatively hydrophilic psychedelic compound structurally related to dopamine, first synthesized in 1919, with numerous synthetic methods and potent analogues developed since. Mescaline occurs naturally in various cacti species, with concentrations varying widely, and is biosynthesized in plants from phenylalanine via biochemical pathways likely linked to stress responses.

The practice of ingesting mescaline-containing cacti extracts dates back over 6,000 years.<ref name="CasselsSáez-Briones2018"/>

Peyote cacti were studied scientifically in the 19th and 20th centuries, culminating in the isolation of mescaline as the primary psychoactive compound in cacti, legal recognition of religious use, and ongoing exploration of the therapeutic potential of mescaline analogues. Mescaline and the cacti that produce it are largely illegal worldwide, though exceptions exist for religious, scientific, or ornamental use, and the compound has influenced many notable cultural figures. Very few studies concerning mescaline's activity and potential therapeutic effects in people have been conducted since the early 1970s.

==Use and effects== {{See also|Psychedelic drug#Dosing|Psychedelic experience}}

Mescaline is used recreationally, spiritually, and medically.<ref name="CasselsSáez-Briones2018" /><ref name="VamvakopoulouNarineCampbell2023" /> It is typically taken orally.<ref name="Dinis-OliveiraPereiradaSilva2019" /> The drug is used as a psychedelic at doses of 100 to 1,000{{nbsp}}mg orally.<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022">{{cite book | vauthors = Liechti ME, Holze F | date = 2022 | chapter = Dosing Psychedelics and MDMA | title = Disruptive Psychopharmacology | volume = 56 | pages = 3–21 | isbn = 978-3-031-12183-8 | doi = 10.1007/7854_2021_270 | pmid = 34734392 | series = Curr Top Behav Neurosci | chapter-url = https://www.researchgate.net/publication/355943062 }}</ref><ref name="LuethiLiechti2018">{{cite journal | vauthors = Luethi D, Liechti ME | title = Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics | journal = The International Journal of Neuropsychopharmacology | volume = 21 | issue = 10 | pages = 926–931 | date = October 2018 | pmid = 29850881 | pmc = 6165951 | doi = 10.1093/ijnp/pyy047 }}</ref> Low doses are 100 to 200{{nbsp}}mg, an intermediate or "good effect" dose is 500{{nbsp}}mg, and a high (ego-dissolution) dose is 1,000{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022" /> Microdosing involves the use of daily mescaline doses of less than 75{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022" /> In addition to pure form, mescaline is used in the form of mescaline containing crude extracts from cacti such as peyote and San Pedro.<ref name="CasselsSáez-Briones2018" />

The onset of the effects of mescaline given orally is 0.5 to 0.9{{nbsp}}hours on average with a range of 0.1 to 2.7{{nbsp}}hours.<ref name="HolzeSinghLiechti2024" /><ref name="KlaiberSchmidBecker2024" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /> Its effects peak after 1.9 to 4.0{{nbsp}}hours with a range of 0.5 to 8.0{{nbsp}}hours.<ref name="HolzeSinghLiechti2024" /><ref name="HolzeLiechtiMüller2024">{{cite book | vauthors = Holze F, Liechti ME, Müller F | chapter = Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms | title = Psychedelic Harm Reduction | journal = Current Topics in Behavioral Neurosciences | series = Curr Top Behav Neurosci | volume = 77| pages = 25–42| date = July 2024 | pmid = 39080236 | doi = 10.1007/7854_2024_510 | isbn = 978-3-032-21106-4 | chapter-url = https://www.researchgate.net/publication/382715259}}</ref><ref name="LeyHolzeArikci2023" /><ref name="KlaiberSchmidBecker2024" /> The duration of mescaline appears to be dose-dependent, varying from 6.4{{nbsp}}hours on average (range 3.0–10{{nbsp}}hours) at a dose of 100{{nbsp}}mg, 9.7 to 11{{nbsp}}hours on average (range 5.6–22{{nbsp}}hours) at moderate doses of 300 to 500{{nbsp}}mg, and 14{{nbsp}}hours on average (range 7.2–22{{nbsp}}hours) at a dose of 800{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="KlaiberSchmidBecker2024" /> Cases of mescaline having unusually prolonged or delayed effects have also been described.<ref name="NeffRossi1963" />

Mescaline induces a psychedelic state comparable to those produced by LSD and psilocybin, but with unique characteristics.<ref name="Bender_2022" /> Subjective effects may include altered thinking processes, an altered sense of time and self-awareness, and closed- and open-eye visual phenomena.<ref name="Kovacic_2009">{{cite journal |vauthors=Kovacic P, Somanathan R |date=1 January 2009 |title=Novel, unifying mechanism for mescaline in the central nervous system: electrochemistry, catechol redox metabolite, receptor, cell signaling and structure activity relationships |journal=Oxidative Medicine and Cellular Longevity |volume=2 |issue=4 |pages=181–190 |doi=10.4161/oxim.2.4.9380 |pmc=2763256 |pmid=20716904}}</ref> In his book ''PiHKAL'' (''Phenethylamines I Have Known and Loved''), Alexander Shulgin comprehensively described the effects of mescaline based on a collection of experience reports.<ref name="PiHKAL" /> Its effects included brightened colors, increased visual contrast, open-eye visuals like colors and patterns, pareidolia, increased significance of objects, enhanced music appreciation, feeling intoxicated, self-analysis, insights, increased body awareness, feelings of joy, happiness, and peacefulness, feeling hyper and energized, feelings of empathy, things feeling ridiculous, humor and laughter, religious feelings, restlessness, social discomfort and avoidance, and nausea, among others.<ref name="PiHKAL">{{CitePiHKAL}} https://erowid.org/library/books_online/pihkal/pihkal096.shtml</ref> Mescaline was one of Shulgin's "magical half-dozen" psychedelic compounds in ''PiHKAL''.<ref name="PiHKAL" />

Prominence of color with mescaline is distinctive, appearing brilliant and intense.<ref name="CasselsSáez-Briones2018" /> Recurring visual patterns observed during the mescaline experience include stripes, checkerboards, angular spikes, multicolor dots, and very simple fractals that can turn very complex.<ref name="Freye2009" /> The English writer Aldous Huxley described these self-transforming amorphous shapes as like animated stained glass illuminated from light coming through the eyelids in his autobiographical book ''The Doors of Perception'' (1954).<ref name="Huxley1954">{{cite book | vauthors = Huxley A | date = 2020 | title = The Doors of Perception | publisher = Otbebookpublishing | isbn = 978-3-96537-009-8 | url = https://books.google.com/books?id=ziNdEQAAQBAJ | access-date = 26 November 2025 | series = Classics To Go | orig-date = 1954 }}</ref> Like LSD, mescaline induces distortions of form and kaleidoscopic experiences but they manifest more clearly with eyes closed and under low lighting conditions.<ref name="Freye2009">{{cite book | vauthors = Freye E | date = 2009 | chapter = Peyote, a Mescaline-Containing Cactus | title = Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs | publisher = Springer Netherlands | pages = 227–228 | isbn = 978-90-481-2447-3 | doi = 10.1007/978-90-481-2448-0_38 | publication-place = Dordrecht | chapter-url = http://link.springer.com/10.1007/978-90-481-2448-0_38 }}</ref> Heinrich Klüver coined the term "cobweb figure" in the 1920s to describe one of the four form constant geometric visual hallucinations experienced in the early stage of a mescaline trip: "Colored threads running together in a revolving center, the whole similar to a cobweb".<ref name="Blom2010" /> The other three are the chessboard design, tunnel, and spiral.<ref name="Blom2010" /> Klüver wrote that "many 'atypical' visions are upon close inspection nothing but variations of these form-constants."<ref name="Blom2010">{{cite book | vauthors = Blom JD | date = 2010 | chapter = C | title = A Dictionary of Hallucinations | publisher = Springer New York | pages = 81–123 | isbn = 978-1-4419-1222-0 | doi = 10.1007/978-1-4419-1223-7_3 | access-date = 26 November 2025 | publication-place = New York, NY | chapter-url = http://link.springer.com/10.1007/978-1-4419-1223-7_3 }}</ref> An unusual but unique characteristic of mescaline use is the "geometrization" of three-dimensional objects.<ref name="Freye2009" /><ref name="GianniniSlaby1989" /> The object can appear flattened and distorted, similar to the presentation of a Cubist painting.<ref name="Freye2009" /><ref name="GianniniSlaby1989">{{cite book | vauthors = Giannini AJ, Slaby AE | year = 1989 | title = Drugs of Abuse | publisher = Medical Economics Books | pages = 207–239 | isbn = 978-0-87489-499-8 | location = Oradell, NJ. }}</ref>

According to a study in the Netherlands, ceremonial San Pedro use seems to be characterized by relatively strong spiritual experiences, and low incidence of challenging experiences.<ref>{{cite journal | vauthors = Bohn A, Kiggen MH, Uthaug MV, van Oorsouw KI, Ramaekers JG, van Schie HT | date = 2022-12-05 | title = Altered States of Consciousness During Ceremonial San Pedro Use | journal = The International Journal for the Psychology of Religion | volume = 33 | issue = 4 | pages = 309–331 | doi = 10.1080/10508619.2022.2139502 | doi-access = free | issn = 1050-8619 | hdl-access = free | hdl = 2066/285968 }}</ref>

==Contraindications== {{See also|Psilocybin#Contraindications}}

==Adverse effects== Side effects of mescaline include fatigue, weakness, impaired concentration, restlessness, tension, anxiety, panic, and social discomfort and avoidance, headache, pupil dilation, nausea, vomiting, sweating, trembling, discomfort, feeling hot or cold, palpitations, chest and neck pains, shortness of breath, increased heart rate and blood pressure, and increased body temperature, among others.<ref name="PiHKAL" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="HolzeSinghLiechti2024" /> In addition to its psychoactive effects, mescaline elicits a pattern of sympathetic arousal, with the peripheral nervous system being a major target for this substance.<ref name="Diaz">{{cite book | vauthors = Diaz J | year = 1996 | title = How Drugs Influence Behavior | publisher = Prentice Hall | isbn = 978-0-02-328764-0 | location = Englewood Cliffs }}</ref> Rarely, in susceptible individuals such as people with a family history of schizophrenia, mescaline may cause psychosis.<ref name="SchlagAdaySalam2022">{{cite journal | vauthors = Schlag AK, Aday J, Salam I, Neill JC, Nutt DJ | title = Adverse effects of psychedelics: From anecdotes and misinformation to systematic science | journal = Journal of Psychopharmacology | volume = 36 | issue = 3 | pages = 258–272 | date = March 2022 | pmid = 35107059 | pmc = 8905125 | doi = 10.1177/02698811211069100 | url = }}</ref>

===Tolerance=== Mescaline is associated with rapid tolerance development, including cross-tolerance with other psychedelics like LSD and psilocybin.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /> This tolerance is apparent within a few days and resets after 3 or 4{{nbsp}}days of abstinence.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" />

==Overdose== In terms of extrapolated human lethal dose based on animal studies and human case reports, the lethal dose of mescaline relative to a typical recreational dose is estimated to be 24-fold.<ref name="Thomas2024">{{cite book | vauthors = Thomas K | title = Psychedelic Harm Reduction | date = 2024 | chapter = Toxicology and Pharmacological Interactions of Classic Psychedelics | publisher = Springer Berlin Heidelberg | doi = 10.1007/7854_2024_508 | pmid = 39042251 | series = Current Topics in Behavioral Neurosciences | volume = 77 | pages = 43–62 | publication-place = Berlin, Heidelberg | isbn = 978-3-032-21106-4 }}</ref> The LD50 of mescaline has also been determined in various animal species, with the values including 212 to 315{{nbsp}}mg/kg i.p. in mice, 132 to 410{{nbsp}}mg/kg i.p. in rats, 328{{nbsp}}mg/kg i.p. in guinea pigs, 54{{nbsp}}mg/kg in dogs, and 130{{nbsp}}mg/kg i.v. in rhesus macaques.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Buckingham2014">{{cite journal|vauthors=Buckingham J|title=Mescaline|journal=Dictionary of Natural Products|pages=254–260|date=2014 }}</ref> It has been said based on the animal data that it would be very difficult to consume enough mescaline to cause death in humans.<ref name="Dinis-OliveiraPereiradaSilva2019" />

==Interactions== {{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

The serotonin 5-HT2A receptor antagonist ketanserin has been found to block the psychoactive effects of mescaline.<ref name="KlaiberSchmidBecker2024" /><ref name="KlaiberBeckerStraumann2024">{{cite journal | vauthors = Klaiber A, Becker AM, Straumann I, Thomann J, Luethi D, Schmid Y, Liechti ME | date = 21 May 2024 | title = Supplementum 276: Abstracts of the 8th Annual Spring Congress of the Swiss Society of General Internal Medicine: P162. Acute subjective effects and pharmacokinetics of different doses of mescaline | journal = Swiss Medical Weekly | volume = 154 | issue = 5 | page = 126S | doi = 10.57187/s.3896 | doi-access = free | pmid = 38771022 | issn = 1424-3997 }}</ref>

It is unclear whether mescaline is metabolized by monoamine oxidase (MAO) enzymes<ref name="RachedCampanaFiani2026">{{cite journal | vauthors = Rached G, Campana A, Fiani D, Nguyen C, Van den Eynde V, Gillman PK, Barnett BS | title = Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data | journal = CNS Drugs | volume = 40| issue = 3| pages = 359–417| date = January 2026 | pmid = 41546846 | doi = 10.1007/s40263-025-01256-7 | url = }}</ref><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="KapadiaFayez1970" /> or whether monoamine oxidase inhibitors (MAOIs) might increase the effects of mescaline.<ref name="RachedCampanaFiani2026" /><ref name="Ott1996">{{cite journal | vauthors = Ott J | title = Pharmahuasca: On Phenethylamines and Potentiation | journal = MAPS Newsletter | volume = 6 | issue = 3 | pages = 32–35 | url = https://maps.org/wp-content/uploads/1996/04/v06n3_34-37_pharmauhsca.pdf | quote = [...] there is circumstantial evidence for traditional use of ayahuasca containing mescaline and/or other β-phenethylamines in Amazonian Peru. [...] preliminary human bioassays suggest that the β-carboline harmaline might in fact potentiate mescaline - low doses of 60 and 100 mg mescaline hydrochloride, corresponding to 51 and 86 mg base or 0.78 and 1.32 mg/kg respectively, were decidedly psychoactive. The combination of mescaline or mescaline-containing cacti with β-carbolines has been dubbed peyohuasca.(5,18)}}</ref> No clinical studies of mescaline in combination with MAOIs are known to have been published.<ref name="RachedCampanaFiani2026" /> However, there are preliminary reports that harmala alkaloids, which are reversible inhibitors of monoamine oxidase A (RIMAs), may potentiate the effects of mescaline in humans, and the combination of mescaline or mescaline-containing cacti with harmala alkaloids has been referred to as "peyohuasca".<ref name="Ott1996" /><ref name="Trout2013">{{cite book | author = Keeper Trout & friends | date = 2013 | title = Trout's Notes on The Cactus Alkaloids Nomenclature, Physical properties, Pharmacology & Occurrences (Sacred Cacti Fourth Edition, Part C: Cactus Chemistry: Section 1) | publisher = Mydriatic Productions/Better Days Publishing | pages = 118–119 | url = https://troutsnotes.com/pdf/C13_CactusAlkaloids.pdf }}</ref><ref name="RachedCampanaFiani2026" /> In accordance with these findings, the harmala alkaloid and RIMA harmine has been reported to augment the effects of mescaline in animals.<ref name="Trout2013" /><ref name="KapadiaFayez1970" /> On the other hand, Daniel Trachsel has stated that mescaline is not metabolized by MAO, instead being metabolized by semicarbazide-sensitive amine oxidase (SSAO), and hence that MAOIs should have no effect on the metabolism of mescaline.<ref name="TrachselLehmannEnzensperger2013" /> Accordingly, the MAOI iproniazid did not potentiate the behavioral effects of mescaline in rats.<ref name="TrachselLehmannEnzensperger2013" /><ref name="FriedhoffGoldstein1962" />

==Pharmacology== ===Pharmacodynamics=== {| class="wikitable floatright" style="font-size:small;" |+ {{Nowrap|Mescaline activities}} |- ! Target !! Affinity (Ki, nM) |- | 5-HT1A || 1,841–4,600 |- | 5-HT1B || >10,000 |- | 5-HT1D || >10,000 |- | 5-HT1E || 5,205 |- | 5-HT1F || {{Abbr|ND|No data}} |- | 5-HT2A || 550–17,400 (Ki) 88–30,200 ({{Abbrlink|EC50|half-maximal effective concentration}}) 33–107% ({{Abbrlink|Emax|maximal efficacy}}) |- | 5-HT2B || 793–800 (Ki) 1,100–>20,000 ({{Abbr|EC50|half-maximal effective concentration}}) 91% ({{Abbr|Emax|maximal efficacy}}) |- | 5-HT2C || 300–17,000 (Ki) 20–19,500 ({{Abbr|EC50|half-maximal effective concentration}}) 22–109% ({{Abbr|Emax|maximal efficacy}}) |- | 5-HT3 || >10,000 |- | 5-HT4 || {{Abbr|ND|No data}} |- | 5-HT5A || >10,000 |- | 5-HT6 || >10,000 |- | 5-HT7 || >10,000 |- | α1A || >15,000 |- | α1B || >10,000 |- | α1D || {{Abbr|ND|No data}} |- | α2A || 1,400–8,930 |- | α2B || >10,000 |- | α2C || 745 |- | β1–β2 || >10,000 |- | D1 || >10,000 |- | D2 || >10,000 |- | D3 || >17,000 |- | D4 || >10,000 |- | D5 || >10,000 |- | H1–H4 || >10,000 |- | M1–M5 || >10,000 |- | TAAR1 || 3,300 (Ki) (rat) 11,000 (Ki) (mouse) 3,700–4,800 ({{Abbr|EC50|half-maximal effective concentration}}) (rodent) >10,000 ({{Abbr|EC50|half-maximal effective concentration}}) (human) |- | I1 || 2,678 |- | σ1–σ2 || >10,000 |- | {{Abbrlink|SERT|Serotonin transporter}} || >30,000 (Ki) 367,000 ({{Abbrlink|IC50|half-maximal inhibitory concentration}}) |- | {{Abbrlink|NET|Norepinephrine transporter}} || >30,000 (Ki) >900,000 ({{Abbr|IC50|half-maximal inhibitory concentration}}) |- | {{Abbrlink|DAT|Dopamine transporter}} || >30,000 (Ki) 841,000 ({{Abbr|IC50|half-maximal inhibitory concentration}}) |- class="sortbottom" | colspan="2" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. '''Refs:''' <ref name="PDSPKiDatabase">{{cite web | title=PDSP Database | website=UNC | url=https://pdsp.unc.edu/databases/pdsp.php?testFreeRadio=testFreeRadio&testLigand=mescaline&kiAllRadio=all&doQuery=Submit+Query | language=zu | access-date=5 November 2024}}</ref><ref name="BindingDB">{{cite web | vauthors = Liu T | title=BindingDB BDBM50059891 1-amino-2-(3,4,5-trimethoxyphenyl)ethane::2-(3,4,5-trimethoxyphenyl)ethanamine::3,4,5-trimethoxybenzeneethanamine::3,4,5-trimethoxyphenethylamine::3,4,5-trimethoxyphenylethylamine::CHEMBL26687::Mescalin::Meskalin::TMPEA::US20240166618, Compound Mescaline::mescalina::mescaline::mezcalina | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50059891 | access-date=5 November 2024}}</ref><ref name="HolzeSinghLiechti2024" /><ref name="VamvakopoulouNarineCampbell2023" /> <ref name="Ray2010">{{cite journal | vauthors = Ray TS | title = Psychedelics and the human receptorome | journal = PLOS ONE | volume = 5 | issue = 2 |article-number=e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | doi-access = free | bibcode = 2010PLoSO...5.9019R | url = }}</ref><ref name="RickliLuethiReinisch2015">{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = http://edoc.unibas.ch/56163/1/20170921163006_59c3cceeb8e5d.pdf}}</ref><ref name="RickliMoningHoener2016">{{cite journal |vauthors=Rickli A, Moning OD, Hoener MC, Liechti ME |date=August 2016 |title=Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens |url=http://edoc.unibas.ch/53326/1/20170117174852_587e4af45b658.pdf |journal=European Neuropsychopharmacology |volume=26 |issue=8 |pages=1327–1337 |doi=10.1016/j.euroneuro.2016.05.001 |pmid=27216487 |s2cid=6685927}}</ref><ref name="WallachCaoCalkins2023">{{cite journal | vauthors = Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD | date = December 2023 | title = Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential | journal = Nature Communications | volume = 14 | issue = 1 | article-number = 8221 | doi = 10.1038/s41467-023-44016-1 | pmc = 10724237 | pmid = 38102107 | bibcode = 2023NatCo..14.8221W }}</ref><ref name="MoyaBergGutiérrez-Hernandez2007">{{cite journal | vauthors = Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP | title = Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 321 | issue = 3 | pages = 1054–1061 | date = June 2007 | pmid = 17337633 | doi = 10.1124/jpet.106.117507 | url = https://repositorio.uchile.cl/bitstream/handle/2250/119461/Moya_Pablo_R.pdf}}</ref><ref name="GainetdinovHoenerBerry2018">{{cite journal | vauthors = Gainetdinov RR, Hoener MC, Berry MD | title = Trace Amines and Their Receptors | journal = Pharmacological Reviews | volume = 70 | issue = 3 | pages = 549–620 | date = July 2018 | pmid = 29941461 | doi = 10.1124/pr.117.015305 | url = | doi-access = free }}</ref><ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA| archive-url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | archive-date = 9 May 2025 }}</ref> |}

In humans, mescaline acts similarly to other psychedelic agents.<ref name="pmid14761703">{{cite journal |vauthors=Nichols DE |date=February 2004 |title=Hallucinogens |journal=Pharmacology & Therapeutics |volume=101 |issue=2 |pages=131–181 |doi=10.1016/j.pharmthera.2003.11.002 |pmid=14761703}}</ref> It acts as an agonist,<ref name="pmid2707301">{{cite journal |vauthors=Appel JB, Callahan PM |date=January 1989 |title=Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline |journal=European Journal of Pharmacology |volume=159 |issue=1 |pages=41–46 |doi=10.1016/0014-2999(89)90041-1 |pmid=2707301}}</ref> binding to and activating the serotonin 5-HT2A receptor.<ref name="pmid9301661">{{cite journal |vauthors=Monte AP, Waldman SR, Marona-Lewicka D, Wainscott DB, Nelson DL, Sanders-Bush E, Nichols DE |date=September 1997 |title=Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives |journal=Journal of Medicinal Chemistry |volume=40 |issue=19 |pages=2997–3008 |citeseerx=10.1.1.690.9370 |doi=10.1021/jm970219x |pmid=9301661}}</ref><ref name="KlaiberSchmidBecker2024">{{cite journal | vauthors = Klaiber A, Schmid Y, Becker AM, Straumann I, Erne L, Jelusic A, Thomann J, Luethi D, Liechti ME | date = September 2024 | title = Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects | journal = Translational Psychiatry | volume = 14 | issue = 1 | article-number = 395 | doi = 10.1038/s41398-024-03116-2 | pmc = 11442856 | pmid = 39349427 }}</ref> Its {{Abbrlink|EC50|half-maximal effective concentration}} at the serotonin 5-HT2A receptor is approximately 10,000{{nbsp}}nM and at the serotonin 5-HT2B receptor is greater than 20,000{{nbsp}}nM.<ref name="VamvakopoulouNarineCampbell2023" /> How activating the 5-HT2A receptor leads to psychedelic effects is still unknown, but it is likely that somehow it involves excitation of neurons in the prefrontal cortex.<ref name="pmid17535909">{{cite journal |vauthors=Béïque JC, Imad M, Mladenovic L, Gingrich JA, Andrade R |date=June 2007 |title=Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=104 |issue=23 |pages=9870–9875 |bibcode=2007PNAS..104.9870B |doi=10.1073/pnas.0700436104 |pmc=1887564 |pmid=17535909 |doi-access=free}}</ref> In addition to the serotonin 5-HT2A and 5-HT2B receptors, mescaline is also known to bind to the serotonin 5-HT2C receptor and a number of other targets.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="RickliMoningHoener2016" /><ref name="Ray2010" /><ref>{{Cite web |date=27 March 2009 |title=Neuropharmacology of Hallucinogens |url=http://www.erowid.org/psychoactives/pharmacology/pharmacology_article1.shtml |access-date=7 September 2011 |publisher=Erowid.org}}</ref> The drug shows pronounced biased agonism at the serotonin 5-HT2C receptor.<ref name="BonniwellAlabadaliHennessey2025">{{cite journal | vauthors = Bonniwell EM, Alabdali R, Hennessey JJ, McKee JL, Cavalco NG, Lammers JC, Moore EJ, Franchini L, Orlandi C, McCorvy JD | title = Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism | journal = ACS Chemical Neuroscience | volume = 16 | issue = 19 | pages = 3899–3914 | date = October 2025 | pmid = 40944639 | doi = 10.1021/acschemneuro.5c00647 | pmc = 12629614 | url = }}</ref>

Mescaline lacks affinity for the monoamine transporters, including the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) (Ki > 30,000{{nbsp}}nM).<ref name="VamvakopoulouNarineCampbell2023" /> However, it has been found to increase levels of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) at high doses in rodents.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023">{{cite journal |vauthors=Doesburg-van Kleffens M, Zimmermann-Klemd AM, Gründemann C |date=December 2023 |title=An Overview on the Hallucinogenic Peyote and Its Alkaloid Mescaline: The Importance of Context, Ceremony and Culture |url= |journal=Molecules |volume=28 |issue=24 |page=7942 |doi=10.3390/molecules28247942 |pmc=10746114 |pmid=38138432 |doi-access=free}}</ref><ref name="Dinis-OliveiraPereiradaSilva2019">{{cite journal | vauthors = Dinis-Oliveira RJ, Pereira CL, da Silva DD | title = Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions | journal = Current Molecular Pharmacology | volume = 12 | issue = 3 | pages = 184–194 | date = 2019 | pmid = 30318013 | pmc = 6864602 | doi = 10.2174/1874467211666181010154139 | url = }}</ref><ref name="FreedmanGottliebLovell1970">{{cite journal | vauthors = Freedman DX, Gottlieb R, Lovell RA | title=Psychotomimetic drugs and brain 5-hydroxytryptamine metabolism | journal=Biochemical Pharmacology | publisher=Elsevier BV | volume=19 | year=1970 | issn=0006-2952 | doi=10.1016/0006-2952(70)90378-3 | pages=1181–1188}}</ref> This finding suggests that mescaline might inhibit the reuptake and/or induce the release of serotonin at such doses.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="TilsonSparber1972">{{cite journal | vauthors = Tilson HA, Sparber SB | title = Studies on the concurrent behavioral and neurochemical effects of psychoactive drugs using the push-pull cannula | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 181 | issue = 3 | pages = 387–398 | date = June 1972 | pmid = 5033008 | doi = 10.1016/S0022-3565(25)29220-5| url = https://jpet.aspetjournals.org/content/181/3/387.long| url-access = subscription }}</ref> In any case, this possibility has not yet been further assessed or demonstrated.<ref name="VamvakopoulouNarineCampbell2023" /> Besides serotonin, mescaline might also weakly induce the release of dopamine, but this is probably of modest significance, if it occurs.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="TrulsonCrispHenderson1983">{{cite journal | vauthors = Trulson ME, Crisp T, Henderson LJ | title = Mescaline elicits behavioral effects in cats by an action at both serotonin and dopamine receptors | journal = European Journal of Pharmacology | volume = 96 | issue = 1–2 | pages = 151–154 | date = December 1983 | pmid = 6581976 | doi = 10.1016/0014-2999(83)90544-7 | url = }}</ref> In accordance, there is no evidence of the drug showing addiction or dependence.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Mescaline appears to be inactive in terms of norepinephrine release induction and indirect sympathomimetic activity.<ref name="NeumannAzatsianHühm2023">{{cite journal | vauthors = Neumann J, Azatsian K, Höhm C, Hofmann B, Gergs U | title = Cardiac effects of ephedrine, norephedrine, mescaline, and 3,4-methylenedioxymethamphetamine (MDMA) in mouse and human atrial preparations | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 396 | issue = 2 | pages = 275–287 | date = February 2023 | pmid = 36319858 | pmc = 9831963 | doi = 10.1007/s00210-022-02315-2 | url = }}</ref> Other psychedelic phenethylamines, including the closely related 2C, DOx, and TMA drugs, are inactive as monoamine releasing agents and reuptake inhibitors.<ref name="NagaiNonakaKamimura2007">{{cite journal | vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K | title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain | journal = European Journal of Pharmacology | volume = 559 | issue = 2–3 | pages = 132–137 | date = March 2007 | pmid = 17223101 | doi = 10.1016/j.ejphar.2006.11.075 }}</ref><ref name="EshlemanForsterWolfrum2014">{{cite journal | vauthors = Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB | title = Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function | journal = Psychopharmacology | volume = 231 | issue = 5 | pages = 875–888 | date = March 2014 | pmid = 24142203 | pmc = 3945162 | doi = 10.1007/s00213-013-3303-6 | url = }}</ref> However, an exception is trimethoxyamphetamine (TMA), the amphetamine analogue of mescaline, which is a very low-potency serotonin releasing agent ({{Abbrlink|EC50|half-maximal effective concentration}} = 16,000{{nbsp}}nM).<ref name="NagaiNonakaKamimura2007" /> The possible monoamine-releasing effects of mescaline would likely be related to the compound's phenethylamine backbone<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" />

Mescaline is a relatively low-potency psychedelic, with active doses in the hundreds of milligrams and micromolar affinities for the serotonin 5-HT2A receptor.<ref name="CasselsSáez-Briones2018" /><ref name="VamvakopoulouNarineCampbell2023" /> For comparison, psilocybin is approximately 20-fold more potent (doses in the tens of milligrams) and lysergic acid diethylamide (LSD) is approximately 2,000-fold more potent (doses in the tens to hundreds of micrograms).<ref name="VamvakopoulouNarineCampbell2023" /> There have been efforts to develop more potent analogues of mescaline.<ref name="CasselsSáez-Briones2018" /> Difluoromescaline and trifluoromescaline are more potent than mescaline, as is its amphetamine homologue TMA.<ref>{{cite journal |vauthors=Trachsel D |year=2012 |title=Fluorine in psychedelic phenethylamines |url=http://bitnest.ca/external.php?id=%257DbxUgXXCNAUj%257E%257E%2507 |url-status=dead |journal=Drug Testing and Analysis |volume=4 |issue=7–8 |pages=577–590 |doi=10.1002/dta.413 |pmid=22374819 |archive-url=https://web.archive.org/web/20130603150127/http://bitnest.ca/external.php?id=%257DbxUgXXCNAUj%257E%257E%2507 |archive-date=2013-06-03|url-access=subscription }}</ref><ref name="PiHKAL-TMA">{{Cite web |title=#157 TMA - 3,4,5-TRIMETHOXYAMPHETAMINE |url=https://www.erowid.org/library/books_online/pihkal/pihkal157.shtml |access-date=9 January 2013 |work=PiHKAL: A Chemical Love Story |publisher=Erowid.org |vauthors=Shulgin A}}</ref> Escaline and proscaline are also both more potent than mescaline, showing the importance of the 4-position substituent with regard to receptor binding.<ref name="pmid3952123">{{cite journal |vauthors=Nichols DE |date=February 1986 |title=Studies of the relationship between molecular structure and hallucinogenic activity |journal=Pharmacology, Biochemistry, and Behavior |volume=24 |issue=2 |pages=335–340 |doi=10.1016/0091-3057(86)90362-x |pmid=3952123 |s2cid=30796368}}</ref>

There is no evidence of acute tolerance with mescaline.<ref name="MuellerKlaiberLey2025" /> However, tolerance to mescaline builds with repeated use, lasting for a few days. The drug causes cross-tolerance with other serotonergic psychedelics such as LSD and psilocybin.<ref>{{Cite web |url=http://www.erowid.org/archive/rhodium/chemistry/psychedelicchemistry/chapter1.html |title=Psychedelics and Society | vauthors = Smith MV |publisher=Erowid.org |access-date=6 April 2012 }}</ref>

The cryo-EM structures of the serotonin 5-HT2A receptor with mescaline, as well as with various other psychedelics and serotonin 5-HT2A receptor agonists, have been solved and published by Bryan L. Roth and colleagues.<ref name="GumpperJainKim2025">{{cite journal | vauthors = Gumpper RH, Jain MK, Kim K, Sun R, Sun N, Xu Z, DiBerto JF, Krumm BE, Kapolka NJ, Kaniskan HÜ, Nichols DE, Jin J, Fay JF, Roth BL | date = March 2025 | title = The structural diversity of psychedelic drug actions revealed | journal = Nature Communications | volume = 16 | issue = 1 | article-number = 2734 | doi = 10.1038/s41467-025-57956-7 | pmc = 11923220 | pmid = 40108183 | bibcode = 2025NatCo..16.2734G }}</ref><ref name="GumpperDiBertoJain2022">{{cite conference | vauthors = Gumpper RH, DiBerto J, Jain M, Kim K, Fay J, Roth BL | title = Structures of Hallucinogenic and Non-Hallucinogenic Analogues of the 5-HT2A Receptor Reveals Molecular Insights into Signaling Bias | conference = University of North Carolina at Chapel Hill Department of Pharmacology Research Retreat September 16th, 2022 – William and Ida Friday Center | date = September 2022 | url = https://www.med.unc.edu/pharm/wp-content/uploads/sites/930/2022/07/COMPLETE-PHARM-RETREAT-PROGRAM-2022-UPDATE.pdf#page=37}}</ref>

===Pharmacokinetics=== ====Absorption==== Mescaline is usually taken orally, although it may also be insufflated, smoked, or given intravenously.<ref name="Dinis-OliveiraPereiradaSilva2019" /> Taken orally, it is rapidly absorbed from the gastrointestinal tract.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Patel1968" /> The oral bioavailability of mescaline is unknown.<ref name="DrugBank" /> However, since at least 53% of orally administered mescaline is excreted in urine unchanged, the bioavailability appears to be at least 53%.<ref name="MuellerKlaiberLey2025" /> Peak concentrations of mescaline occur after approximately 1.6 to 2.3{{nbsp}}hours on average (range 1.0–6.0{{nbsp}}hours).<ref name="HolzeSinghLiechti2024" /><ref name="LeyHolzeArikci2023" /><ref name="KlaiberSchmidBecker2024" /> However, there is a delay of 1 to 2{{nbsp}}hours following peak levels in terms of the drug producing maximal psychoactive and behavioral effects.<ref name="TrachselLehmannEnzensperger2013" /> The pharmacokinetics of mescaline are dose-proportional over an oral dose range of 100 to 800{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="KlaiberSchmidBecker2024" />

====Distribution==== Mescaline is distributed to the liver, spleen, and kidneys at many times higher levels than blood or brain based on animal studies.<ref name="Patel1968" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="VamvakopoulouNarineCampbell2023" /> It is said that a great proportion of mescaline is combined with hepatic proteins, which is said to delay its onset and elimination half-life.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="VamvakopoulouNarineCampbell2023" /> The exact portion bound to plasma proteins appears to be unknown.<ref name="DrugBank" />

Mescaline appears to have relatively poor blood–brain barrier permeability due to its low lipophilicity.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="MuellerKlaiberLey2025">{{cite journal | vauthors = Mueller L, Klaiber A, Ley L, Becker AM, Thomann J, Luethi D, Schmid Y, Liechti ME | title = Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants | journal = Clinical Pharmacokinetics | volume = 64| issue = 10| pages = 1495–1506| date = July 2025 | pmid = 40658345 | doi = 10.1007/s40262-025-01544-x | pmc = 12479620 | url = | quote = The low affinity of mescaline for 5-HT2A receptors [3] and poor blood–brain barrier permeability [20] contribute to the comparatively high oral doses of 300–800 mg of mescaline hydrochloride (HCl) that are typically required to induce a full psychedelic experience in humans compared with psilocybin dihydrate (20–40 mg) and LSD base (100–200 µg) [5, 21]. [...] We found that acute subjective efects of mescaline were closely linked to the plasma mescaline concentrations but occurred with a delay as seen in the counterclockwise hysteresis. Accordingly, our modeling approach that used an efect compartment that was connected to the plasma mescaline concentration using a frst-order equilibrium rate constant (ke0) adequately described the observed acute efects. This finding is consistent with a delayed central distribution of mescaline.}}</ref> However, it is still able to cross into the central nervous system and produce psychoactive effects at sufficiently high doses.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="MuellerKlaiberLey2025" /> The poor central permeability of mescaline appears to be responsible for its delayed onset of effects and is also thought to contribute to its low potency.<ref name="MuellerKlaiberLey2025" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="PálenícekBalíkováBubeníková-Valesová2008">{{cite journal | vauthors = Pálenícek T, Balíková M, Bubeníková-Valesová V, Horácek J | title = Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose | journal = Psychopharmacology | volume = 196 | issue = 1 | pages = 51–62 | date = January 2008 | pmid = 17922234 | doi = 10.1007/s00213-007-0926-5 | url = }}</ref>

Mescaline given orally appears to be subject to first-pass metabolism of about 50%.<ref name="MuellerKlaiberLey2025" /> Following the first pass, mescaline appears to be subject to relatively limited metabolism.<ref name="MuellerKlaiberLey2025" />

The primary metabolic pathway of mescaline is oxidative deamination.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="RachedCampanaFiani2026" /><ref name="CasselsSáez-Briones2018" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="KapadiaFayez1970">{{cite journal | vauthors = Kapadia GJ, Fayez MB | title = Peyote constituents: chemistry, biogenesis, and biological effects | journal = Journal of Pharmaceutical Sciences | volume = 59 | issue = 12 | pages = 1699–1727 | date = December 1970 | pmid = 5499699 | doi = 10.1002/jps.2600591202 | bibcode = 1970JPhmS..59.1699K | url = | quote = Some authors (398) postulated that mescaline oxidase is identical with diamine oxidase, while others (399-401) believe that the oxidative deamination of mescaline can be effected by monoamine oxidase or diamine oxidase or both. However, mescaline was found to be a poor substrate for highly purified human plasma monoamine oxidase (402) and for dopamine-β-oxidase (403). According to Seiler (404), who treated mescaline with mouse brain homogenates, the oxidation is not caused by diamine oxidase but by a monoamine oxidase leading to 3,4,5-trimethoxyphenylacetic acid (LXXIII). [...] rabbit liver preparations caused O-demethylation to VII and LX along with oxidation to LXXIII (407). The formation of this acid (LXXIII) was inhibited by iproniazid, semicarbazide, nicotinamide, and triphosphopyridine nucleotide. [...] Harmine was found to augment the effect of mescaline (260). [...] (260) H. Hoshikawa, Nippon Yakurigaku Zasshi, 58, 241, 261 (1962); through Chem. Abstr., 60, 7338(1964).}}</ref> The specific enzymes mediating the deamination of mescaline are controversial however.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="RachedCampanaFiani2026" /><ref name="KapadiaFayez1970" /><ref name="SmythiesJohnstonBradley1967" /> Monoamine oxidase (MAO), diamine oxidase (DAO; histamine oxidase), semicarbazide-sensitive amine oxidase (SSAO), and/or other enzymes may be responsible.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="KapadiaFayez1970" /><ref name="SmythiesJohnstonBradley1967">{{cite journal | vauthors = Smythies JR, Johnston VS, Bradley RJ | title = Alteration by pretreatment with iproniazid and an inactive mescaline analogue of a behaviour change induced by mescaline | journal = Nature | volume = 216 | issue = 5111 | pages = 196–197 | date = October 1967 | pmid = 6057240 | doi = 10.1038/216196a0 | bibcode = 1967Natur.216..196S | url = }}</ref> Preclinical studies of mescaline given in combination with inhibitors of MAO and/or DAO, such as iproniazid, pargyline, and semicarbazide, have been conducted, but findings have been conflicting.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="RachedCampanaFiani2026" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="KapadiaFayez1970" /><ref name="Patel1968" /><ref name="MusacchioGoldstein1967">{{cite journal | vauthors = Musacchio JM, Goldstein M | title = The metabolism of mescaline-14-C in rats | journal = Biochemical Pharmacology | volume = 16 | issue = 6 | pages = 963–970 | date = June 1967 | pmid = 6040403 | doi = 10.1016/0006-2952(67)90268-7 | url = }}</ref><ref name="SmythiesJohnstonBradley1967" /> Mescaline has been reported to be a poor or negligible substrate of highly purified human MAO ''in-vitro''.<ref name="KapadiaFayez1970" /><ref name="Patel1968" /><ref name="McEwen1965">{{cite journal | vauthors = McEwen CM | title = Human plasma monoamine oxidase. 1. Purification and identification | journal = The Journal of Biological Chemistry | volume = 240 | issue = 5 | pages = 2003–2010 | date = May 1965 | pmid = 5888801 | doi = 10.1016/S0021-9258(18)97417-X| doi-access = free | url = }}</ref> Mescaline is converted via deamination into 3,4,5-trimethoxyphenylacetaldehyde (TMPA) as an intermediate and then into 3,4,5-trimethoxyphenylacetic acid (TMPAA) or 3,4,5-trimethoxyphenylethanol (TMPE).<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="NeffRossi1963">{{cite journal | vauthors = Neff N, Rossi GV | title = Mescaline | journal = Am J Pharm Sci Support Public Health | volume = 135 | issue = 9 | pages = 319–327 | date = September 1963 | pmid = 14061276 | doi = | url = https://archive.org/details/mescaline-neff-rossi-1963}}</ref>

Mescaline appears not to be subject to metabolism by CYP2D6 based on ''in-vitro'' studies with human liver microsomes.<ref name="pmid9264312">{{cite journal | vauthors = Wu D, Otton SV, Inaba T, Kalow W, Sellers EM | title = Interactions of amphetamine analogs with human liver CYP2D6 | journal = Biochemical Pharmacology | volume = 53 | issue = 11 | pages = 1605–1612 | date = June 1997 | pmid = 9264312 | doi = 10.1016/S0006-2952(97)00014-2 }}</ref> Similarly, the ''in-vitro'' cytotoxicity of mescaline does not appear to be affected by cytochrome P450 (CYP450) enzyme inhibitors.<ref name="MartinsGil-MartinsCagide2023">{{cite journal | vauthors = Martins D, Gil-Martins E, Cagide F, da Fonseca C, Benfeito S, Fernandes C, Chavarria D, Remião F, Silva R, Borges F | title = Unraveling the In Vitro Toxicity Profile of Psychedelic 2C Phenethylamines and Their N-Benzylphenethylamine (NBOMe) Analogues | journal = Pharmaceuticals | volume = 16 | issue = 8 | date = August 2023 | page = 1158 | pmid = 37631071 | pmc = 10458253 | doi = 10.3390/ph16081158 | doi-access = free | url = }}</ref> Conversely, it was potentiated by the MAO-A inhibitor clorgiline but not by the MAO-B inhibitor rasagiline.<ref name="MartinsGil-MartinsCagide2023" /> These findings were in contrast to those with the related compound 2C-B, which was potentiated by rasagiline but not by clorgiline.<ref name="MartinsGil-MartinsCagide2023" />

Circulating peak and area-under-the-curve concentrations of mescaline and TMPAA are similar with oral administration of mescaline.<ref name="KlaiberSchmidBecker2024" /><ref name="MuellerKlaiberLey2025" /> Conversely, levels of ''N''-acetylmescaline (NAM) are far lower than those of mescaline or TMPAA and are thought not to be of clinical relevance.<ref name="KlaiberSchmidBecker2024" /><ref name="MuellerKlaiberLey2025" /> Intravenous injection of mescaline may result in less hepatic deamination than with oral administration.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="MuellerKlaiberLey2025" />

It has been theorized that active metabolites of mescaline might contribute to its psychoactive effects.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="CasselsSáez-Briones2018" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="Nichols1981" /><ref name="WatanabeKayanoMatsunaga1995">{{cite journal | vauthors = Watanabe K, Kayano Y, Matsunaga T, Yamamoto I, Yoshimura H | title = 3,4,5-Trimethoxyphenylacetaldehyde, an intermediate metabolite of mescaline, is a substrate for microsomal aldehyde oxygenase in the mouse liver | journal = Biol Pharm Bull | volume = 18 | issue = 5 | pages = 696–699 | date = May 1995 | pmid = 7492985 | doi = 10.1248/bpb.18.696 | url = }}</ref><ref name="NeffRossi1963" /><ref name="FriedhoffGoldstein1962">{{cite journal | vauthors = Friedhoff AJ, Goldstein M | title = New developments in metabolism of mescaline and related amines | journal = Ann N Y Acad Sci | volume = 96 | issue = | pages = 5–13 | date = January 1962 | pmid = 13895218 | doi = 10.1111/j.1749-6632.1962.tb50097.x | url = }}</ref> Relatedly, TMPA and TMPE were reported in early research to show pharmacological effects in rats and rabbits with greater potency than mescaline.<ref name="NeffRossi1963" /><ref name="FriedhoffGoldstein1962" /> In addition, co-administration of mescaline with the aldehyde dehydrogenase inhibitor (ALDHI) calcium carbimide, which elevates TMPA and/or TMPE levels, has been reported to produce extreme reactions in rabbits at doses at which mescaline alone was inactive.<ref name="NeffRossi1963" /> Similarly, co-administration of TMPE with calcium carbimide markedly potentiated the effects of TMPE.<ref name="FriedhoffGoldstein1962" /> However, subsequent research found that TMPA, TMPE, and NAM all failed to produce mescaline-like effects in rodent drug discrimination tests, and this was the case even when they were co-administered with calcium carbimide.<ref name="CasselsSáez-Briones2018" /><ref name="Nichols1981" /><ref name="BrowneHo1975">{{cite journal | vauthors = Browne RG, Ho BT | title = Discriminative stimulus properties of mescaline: mescaline or metabolite? | journal = Pharmacology, Biochemistry, and Behavior | volume = 3 | issue = 1 | pages = 109–114 | date = 1975 | pmid = 1129346 | doi = 10.1016/0091-3057(75)90088-x | url = }}</ref> Likewise, another subsequent study found that TMPE and TMPAA were both inactive in producing behavioral effects in rodents, while TMPA was much less potent than mescaline.<ref name="WatanabeKayanoMatsunaga1995" /> Another study found TMPAA to be inactive in animals as well.<ref name="NeffRossi1963" /><ref name="SlottaMuller1936">Slotta, K. H., & Muller, J. (1936). On the catabolism of mescaline and mescaline-like substances in the organism. Hoppe-Seyler’s Z., 238, 14–22. https://scholar.google.com/scholar?cluster=12893490063723146887 https://scholar.google.com/scholar?cluster=12713934913707858633</ref> As with animal findings, both TMPAA and NAM have been said to be inactive based on human tests.<ref name="CharalampousWalkerKinross-Wright1966" /> It has also been noted that metabolites like TMPA and TMPE are rapidly metabolized.<ref name="WatanabeKayanoMatsunaga1995" /> As such, metabolites of mescaline like TMPA, TMPE, TMPAA, and NAM do not appear to be involved in the drug's psychedelic-related effects.<ref name="Nichols1981" /><ref name="BrowneHo1975" /><ref name="CharalampousWalkerKinross-Wright1966" />

3,4,5-Trimethoxyamphetamine (TMA), the α-methyl analogue of mescaline and an MAO-resistant psychedelic, is only about twice as potent as mescaline as a psychedelic in humans despite having similar serotonin receptor affinity.<ref name="TrachselLehmannEnzensperger2013" /><ref name="Nichols1981">{{cite journal | vauthors = Nichols DE | title = Structure-activity relationships of phenethylamine hallucinogens | journal = Journal of Pharmaceutical Sciences | volume = 70 | issue = 8 | pages = 839–849 | date = August 1981 | pmid = 7031221 | doi = 10.1002/jps.2600700802 | bibcode = 1981JPhmS..70..839N | url = https://bitnest.netfirms.com/external/10.1002/jps.2600700802}}</ref> This suggests that the deamination of mescaline has a relatively limited impact on its potency, compared to for example the 2C series of psychedelics.<ref name="Nichols1981" /> Another analogue of mescaline, the deuterated isotopologue Alpha-D (α,α-dideuteromescaline), has been reported to be roughly one-third more potent than mescaline as a psychedelic in humans, albeit based on limited testing.<ref name="TrachselLehmannEnzensperger2013">{{cite book | vauthors = Trachsel D, Lehmann D, Enzensperger C | year = 2013 | title = Phenethylamine: von der Struktur zur Funktion | language = de | publisher = Nachtschatten-Verlag | edition = 1 | pages = 677–705 | isbn = 978-3-03788-700-4 | url = https://books.google.com/books?id=-Us1kgEACAAJ | archive-date = 21 August 2025 | archive-url = https://archive.org/details/phenethylamine-von-der-struktur-zur-funktion-trachsel-lehmann-enzensperger-2013 | trans-title = Phenethylamines: From Structure to Function | location = Solothurn | series = Nachtschatten-Science | oclc = 858805226 }}</ref> This is consistent with findings of about one-third of a dose of mescaline being metabolized via deamination.<ref name="TrachselLehmannEnzensperger2013" />

====Elimination==== Mescaline given orally is excreted 87% in urine within 24{{nbsp}}hours and 92% in urine within 48{{nbsp}}hours.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Patel1968" /><ref name="Leth-PetersenBundgaardHansen2014">{{cite journal | vauthors = Leth-Petersen S, Bundgaard C, Hansen M, Carnerup MA, Kehler J, Kristensen JL | title = Correlating the metabolic stability of psychedelic 5-HT₂A agonists with anecdotal reports of human oral bioavailability | journal = Neurochemical Research | volume = 39 | issue = 10 | pages = 2018–2023 | date = October 2014 | pmid = 24519542 | doi = 10.1007/s11064-014-1253-y | url = | quote = Mescaline (11a in Fig. 4) is known to be metabolized very slowly in humans, with more than 87 % of the ingested dose being excreted [...] with the urine within 24 h [36].}}</ref><ref name="CharalampousWalkerKinross-Wright1966">{{cite journal | vauthors = Charalampous KD, Walker KE, Kinross-Wright J | title = Metabolic fate of mescaline in man | journal = Psychopharmacologia | volume = 9 | issue = 1 | pages = 48–63 | date = 1966 | pmid = 5989103 | doi = 10.1007/BF00427703 | url = }}</ref> During the first hour after administration, 81.4% of mescaline is excreted unchanged while 13.2% is excreted as its deaminated metabolite 3,4,5-trimethoxyphenylacetic acid (TMPAA).<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="CharalampousWalkerKinross-Wright1966" /> However, after the first hour, the percentage excreted as unchanged mescaline declines and the percentage excreted as TMPAA rises.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="CharalampousWalkerKinross-Wright1966" /> Ultimately, mescaline is excreted in urine 28 to 60% unchanged, 27 to 30% or more as TMPAA, 5% as ''N''-acetyl-3,4-dimethoxy-5-hydroxyphenylethylamine, and less than 0.1% as ''N''-acetylmescaline.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Patel1968" /><ref name="CharalampousWalkerKinross-Wright1966" /> Other minor or trace excreted metabolites have also been observed.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="CharalampousWalkerKinross-Wright1966" /> In a more modern study published in 2025, mescaline was eliminated in urine 53% as unchanged mescaline and 31% as TMPAA.<ref name="MuellerKlaiberLey2025" />

Mescaline was originally reported to have an elimination half-life of 6{{nbsp}}hours based on a study conducted in the 1960s.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="LeyHolzeArikci2023" /><ref name="CharalampousWalkerKinross-Wright1966" /> However, subsequent research published in the 2020s found that its half-life is actually about 3.6{{nbsp}}hours (range 2.6–5.3{{nbsp}}hours).<ref name="HolzeSinghLiechti2024" /><ref name="LeyHolzeArikci2023">{{cite journal | vauthors = Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, Coviello F, Dierbach S, Thomann J, Duthaler U, Luethi D, Varghese N, Eckert A, Liechti ME | title = Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants | journal = Neuropsychopharmacology | volume = 48 | issue = 11 | pages = 1659–1667 | date = October 2023 | pmid = 37231080 | doi = 10.1038/s41386-023-01607-2 | pmc = 10517157 }}</ref><ref name="KlaiberSchmidBecker2024" /><ref name="MuellerKlaiberLey2025" /> The previous higher estimate is believed to have been due to small sample numbers and collective measurement of mescaline metabolites.<ref name="LeyHolzeArikci2023" /> The elimination half-life of mescaline does not appear to be dose-dependent.<ref name="HolzeSinghLiechti2024" /><ref name="LeyHolzeArikci2023" /> TMPAA has a half-life of about 3.7 to 4.1{{nbsp}}hours, similar to that of mescaline.<ref name="MuellerKlaiberLey2025" /> Mescaline has a similar half-life as LSD yet has a longer duration.<ref name="HolzeSinghLiechti2024" /> This is due to mescaline having slower absorption and onset rather than a longer half-life.<ref name="HolzeSinghLiechti2024" /><ref name="LeyHolzeArikci2023" />

==Chemistry== Mescaline, also known as 3,4,5-trimethoxyphenethylamine (3,4,5-TMPEA), is a substituted phenethylamine derivative.<ref name="PubChem">{{cite web | title=Mescaline | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/4076 | access-date=6 November 2024}}</ref><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> It is closely structurally related to the dopamine (3,4-dihydroxyphenethylamine), norepinephrine (3,4,β-trihydroxyphenethylamine), and epinephrine (3,4,β-trihydroxy-''N''-methylphenethylamine).<ref name="PubChem" /> In contrast to the catecholamine neurotransmitters however, mescaline acts on the serotonergic system rather than on the dopaminergic or adrenergic systems.

===Properties=== The physical properties and general chemistry of mescaline have been reviewed.<ref name="Patel1968">{{cite book | vauthors = Patel AR | date = 1968 | chapter = Mescaline and Related Compounds | title = Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques | volume = 11 | pages = 11–47 | isbn = 978-3-0348-7064-1 | doi = 10.1007/978-3-0348-7062-7_1 | pmid = 4873202 | chapter-url = }}</ref> The compound is relatively hydrophilic with low fat solubility.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Its predicted log P (XLogP3) is 0.7.<ref name="PubChem" />

===Synthesis=== right|thumb|A sample of pure mescaline thumb|250px|Dried Peyote (''Lophophora williamsii''), containing around 5-6% mescaline by weight

Mescaline was first ever psychedelic drug synthesized by chemists. Ernst Späth's 1919 total synthesis started from 3,4,5-trimethoxy{{shy}}benzoyl chloride.<ref name="Späth_1919" /> Several approaches using different starting materials have been developed since, including the following:

* Hofmann rearrangement of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}propionamide.<ref>{{cite journal | vauthors = Slotta KH, Heller H |title=Über β-Phenyl-äthylamine, I. Mitteil.: Mezcalin und mezcalin-ähnliche Substanzen |journal= Berichte der Deutschen Chemischen Gesellschaft (A and B Series) |year=1930 |volume=63 |issue=11 |pages=3029–3044 |doi=10.1002/cber.19300631117 }}</ref> * Cyanohydrin reaction between potassium cyanide and 3,4,5-trimethoxy{{shy}}benz{{shy}}aldehyde followed by acetylation and reduction.<ref>{{cite journal| vauthors = Amos D |title= Preparation of Mescaline from Eucalypt Lignin|journal=Australian Journal of Pharmacy |date=1964 |volume=49 |page=529 |url=https://www.erowid.org/archive/rhodium/chemistry/mescalyptus.html}}</ref><ref>{{cite journal| vauthors = Kindler K, Peschke W |title=Über neue und über verbesserte Wege zum Aufbau von pharmakologisch wichtigen Aminen VI. Über Synthesen des Meskalins|journal=Archiv der Pharmazie|year=1932|volume=270|issue=7|pages=410–413|doi=10.1002/ardp.19322700709|s2cid=93188741 }}</ref> * Henry reaction of 3,4,5-trimethoxy{{shy}}benz{{shy}}aldehyde with nitromethane followed by nitro compound reduction of ��-nitro{{shy}}trimethoxy{{shy}}styrene.<ref>{{cite journal | vauthors = Benington F, Morin R | year = 1951 | title = An Improved Synthesis of Mescaline | journal = Journal of the American Chemical Society | volume = 73 | issue = 3 | page = 1353 | doi = 10.1021/ja01147a505 | bibcode = 1951JAChS..73Q1353B }}</ref><ref name="PiHKAL" /><ref>{{cite journal| vauthors = Hahn G, Rumpf F |title=Über β-[Oxy-phenyl]-äthylamine und ihre Umwandlungen, V. Mitteil.: Kondensation von Oxyphenyl-äthylaminen mit α-Ketonsäuren|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|year=1938|volume=71|issue=10|pages=2141–2153|doi=10.1002/cber.19380711022}}</ref><ref>{{cite journal| vauthors = Toshitaka O, Hiroaka A |title=Synthesis of Phenethylamine Derivatives as Hallucinogen|journal=Japanese Journal of Toxicology and Environmental Health|date=1992|volume=38|issue=6|pages=571–580|doi=10.1248/jhs1956.38.571 |url=https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_ohshita1992.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_ohshita1992.pdf |archive-date=2022-10-09 |url-status=live|access-date=20 June 2014|doi-access=free}}</ref><ref>{{cite journal| vauthors = Ramirez F, Erne M |title=Über die Reduktion von β-Nitrostyrolen mit Lithiumaluminiumhydrid|journal=Helvetica Chimica Acta|date=1950|volume=33|issue=4|pages=912–916|doi=10.1002/hlca.19500330420 |bibcode=1950HChAc..33..912E }}</ref><ref>{{cite journal| vauthors = Szyszka G, Slotta KH |title=Über β-Phenyl-äthylamine.III. Mitteilung: Neue Darstellung von Mescalin|journal=Journal für Praktische Chemie|date=1933|volume=137|issue=9–12|pages=339–350|doi=10.1002/prac.19331370907}}</ref><ref>{{cite journal| vauthors = Burger A, Ramirez FA |title=The Reduction of Phenolic β-Nitrostyrenes by Lithium Aluminum Hydride|journal=Journal of the American Chemical Society|date=1950|volume=72|issue=6|pages=2781–2782|doi=10.1021/ja01162a521|bibcode=1950JAChS..72.2781R }}</ref> This was the method used by Alexander Shulgin in his 1991 book ''PiHKAL'' (''Phenethylamines I Have Known and Loved'').<ref name="PiHKAL" /> * Ozonolysis of elemicin followed by reductive amination.<ref>{{cite journal| vauthors = Hahn G, Wassmuth H |title=Über β-[Oxyphenyl]-äthylamine und ihre Umwandlungen, I. Mitteil.: Synthese des Mezcalins|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|year=1934|volume=67|issue=4|pages=696–708|doi=10.1002/cber.19340670430}}</ref> * Ester reduction of Eudesmic acid's methyl ester followed by halogenation, Kolbe nitrile synthesis, and nitrile reduction.<ref name="Makepeace, Tsao 1951 5495–5496">{{cite journal| vauthors = Makepeace T |title=A New Synthesis of Mescaline|journal=Journal of the American Chemical Society|year=1951|volume=71|issue=11|pages=5495–5496|doi=10.1021/ja01155a562|bibcode=1951JAChS..73.5495T }}</ref><ref>{{cite journal| vauthors = Dornow A, Petsch G |title=Über die Darstellung des Oxymezcalins und Mezcalins 2. Mitteilung|journal=Archiv der Pharmazie|year=1952|volume=285|issue=7|pages=323–326|doi=10.1002/ardp.19522850704|s2cid=97553172 }}</ref><ref>{{cite book | vauthors = Ikan R | year = 1991 | title = Natural Products: A Laboratory Guide 2nd Ed | publisher = Academic Press, Inc. | pages = 232–235 | isbn = 978-0-12-370551-8 | url = https://books.google.com/books?id=B7P8HQimBAIC&pg=PA243 | location = San Diego }}</ref> * Amide reduction of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}acetamide.<ref>{{cite journal| vauthors = Banholzer K, Campbell TW, Schmid H |title=Notiz über eine neue Synthese von Mezcalin, N-Methyl- und N-Dimethylmezcalin|journal=Helvetica Chimica Acta|date=1952|volume=35|issue=5|pages=1577–1581|doi=10.1002/hlca.19520350519}}</ref> *Reduction of 3,4,5-trimethoxy{{shy}}(2-nitrovinyl)benzene with lithium aluminum hydride.<ref name="Kovacic_2009" /> * Treatment of tricarbonyl-(η6-1,2,3-trimethoxy{{shy}}benzene) chromium complex with acetonitrile carbanion in THF and iodine, followed by reduction of the nitrile with lithium aluminum hydride.<ref name="Makepeace, Tsao 1951 5495–5496" />

===Analogues=== {{See also|Substituted methoxyphenethylamine|Scaline}}

A large number of structural analogues of mescaline that act as psychedelics have been developed.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> These drugs often have far greater potency than mescaline itself.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> Examples include scalines like escaline, 3Cs like 3,4,5-trimethoxyamphetamine (TMA or TMA-1; α-methylmescaline), 2Cs like 2C-B, and DOx drugs like DOM, among others.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> Other notable analogues of mescaline include ''N''-methylmescaline (found in ''Pachycereus pringlei''), trichocereine (''N'',''N''-dimethylmescaline), mescaline-FLY, and NBOMe-mescaline, among others.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> Deuterated isotopologues of mescaline include α-D (α,α-dideuteromescaline), β-D (β,β-dideuteromescaline), α,β-D (α,β-dideuteromescaline), and 4-D (4-trideuteromescaline), among others.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" />

==Natural occurrence== It occurs naturally in several species of cacti. It is also reported to be found in small amounts in certain members of the bean family, Fabaceae, including ''Senegalia berlandieri'' (syn. ''Acacia berlandieri''),<ref name="chem">{{Cite web |title=Chemistry of Acacia's from South Texas |publisher=Texas A&M Agricultural Research & Extension Center at Uvalde |url=http://uvalde.tamu.edu/pdf/chemtdaf.pdf |archive-url=https://web.archive.org/web/20110515034950/http://uvalde.tamu.edu/pdf/chemtdaf.pdf |archive-date=15 May 2011 | vauthors = Forbes TD, Clement BA |url-status=dead }}</ref> although these reports have been challenged and have been unsupported in any additional analyses.<ref>{{Cite web |url=https://sacredcacti.com/blog/acacia/ |title=Acacia species with data conflicts |publisher=sacredcacti.com |date=16 January 2015 |access-date=13 March 2021 }}</ref>

{|class="wikitable" |- ! Plant source ! Amount of mescaline (% of dry weight) |- | ''Echinopsis lageniformis'' (Bolivian torch cactus, syns. ''Echinopsis scopulicola'', ''Trichocereus bridgesii'')<ref name="Bury_2021">{{Cite web | vauthors = Bury B |date=2021-08-02 |title=Could Synthetic Mescaline Protect Declining Peyote Populations? |url= https://chacruna.net/synthetic_mescaline_protect_declining_peyote_populations/ |access-date=2021-11-02 |website=Chacruna |language=en-US}}</ref>||Average 0.56; 0.85 in one cultivar of ''Echinopsis scopulicola''<ref name="Bury_2021" /><ref name="Ogunbodede McCombs Trout Daley"/> |- | ''Leucostele terscheckii'' (syns ''Echinopsis terscheckii'', ''Trichocereus terscheckii'')<ref>{{cite web|url=http://www.desert-tropicals.com/Plants/Cactaceae/Echinopsis_terscheckii.html|title=Cardon Grande (Echinopsis terscheckii)|publisher=Desert-tropicals.com|access-date=14 January 2015|archive-date=5 April 2015|archive-url=https://web.archive.org/web/20150405113718/http://www.desert-tropicals.com/Plants/Cactaceae/Echinopsis_terscheckii.html|url-status=dead}}</ref> || 0.005 - 2.375<ref name="nook2"/><ref name="netfirms">{{cite web | url = http://entheogen.netfirms.com/articles/articles/Narcotic_Cacti.html | title = Forbidden Fruit Archives | archive-url = https://web.archive.org/web/20051128031148/http://entheogen.netfirms.com/articles/articles/Narcotic_Cacti.html | archive-date=2005-11-28 }}</ref> |- | Peyote cactus (''Lophophora williamsii'')<ref name="Bib">{{cite book | year = 2007 | title = Drug Identification Bible | publisher = Amera-Chem, Inc. | isbn = 978-0-9635626-9-2 | location = Grand Junction, CO }}</ref>||0.01-5.5<ref name="Lophwilliamsii MollyT">{{cite journal | vauthors = Klein MT, Kalam M, Trout K, Fowler N, Terry M | title=Mescaline Concentrations in Three Principal Tissues of Lophophora williamsii (Cactaceae): Implications for Sustainable Harvesting Practices | journal=Haseltonia | publisher=Elsevier BV | volume=131 | issue=2 | year=2015 | issn= | doi=10.2985/026.020.0107| pages=34–42| bibcode=2015Hasel..20...34K | s2cid=32474292 }}</ref> |- | ''Trichocereus macrogonus'' var. ''macrogonus'' (Peruvian torch, syns ''Echinopsis peruviana'', ''Trichocereus peruvianus'')<ref name="OgunMcCoTrouDale10">{{cite journal | vauthors = Ogunbodede O, McCombs D, Trout K, Daley P, Terry M | title = New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) ("San Pedro") and their relevance to shamanic practice | journal = Journal of Ethnopharmacology | volume = 131 | issue = 2 | pages = 356–362 | date = September 2010 | pmid = 20637277 | doi = 10.1016/j.jep.2010.07.021 }}</ref>||0.01-0.05;<ref name="nook2">{{cite web|url=http://www.thenook.org/archives/tek/alklist.htm|title=Partial List of Alkaloids in Trichocereus Cacti|publisher=Thennok.org|access-date=22 December 2017|archive-date=11 February 2009|archive-url=https://web.archive.org/web/20090211110045/http://thenook.org/archives/tek/alklist.htm|url-status=dead}}</ref> 0.24-0.81<ref name="Ogunbodede McCombs Trout Daley"/> |- | ''Trichocereus macrogonus'' var. ''pachanoi'' (San Pedro cactus, syns ''Echinopsis pachanoi'', ''Echinopsis santaensis'', ''Trichocereus pachanoi'')<ref>{{cite journal | vauthors = Crosby DM, McLaughlin JL | title = Cactus alkaloids. XIX. Crystallization of mescaline HCl and 3-methoxytyramine HCl from Trichocereus pachanoi | journal = Lloydia | volume = 36 | issue = 4 | pages = 416–418 | date = December 1973 | pmid = 4773270 | url = http://catbull.com/alamut/Bibliothek/1973_d.m._crosby_8158_1.pdf | access-date = 13 December 2013 }}</ref> ||0.23-4.7;<ref name="Ogunbodede McCombs Trout Daley">{{cite journal | vauthors = Ogunbodede O, McCombs D, Trout K, Daley P, Terry M | title = New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) ("San Pedro") and their relevance to shamanic practice | journal = Journal of Ethnopharmacology | volume = 131 | issue = 2 | pages = 356–362 | date = September 2010 | pmid = 20637277 | doi = 10.1016/j.jep.2010.07.021 | publisher = Elsevier BV }}</ref> 0.32 under its synonym ''Echinopsis santaensis''<ref name="Ogunbodede McCombs Trout Daley"/> |- | ''Trichocereus uyupampensis'' (syn. ''Echinopsis uyupampensis'')||0.05<ref name="Ogunbodede McCombs Trout Daley"/> |- | ''Trichocereus tacaquirensis (subsp. taquimbalensis syn. Trichocereus taquimbalensis)'' |0.005-2.7<ref>{{Cite web |title=Mescaline in Trichocereus |url=https://www.themescalinegarden.com/mescaline-in-trichocereus |access-date=2024-08-09 |website=The Mescaline Garden |language=en-AU |archive-date=8 August 2024 |archive-url=https://web.archive.org/web/20240808110012/https://www.themescalinegarden.com/mescaline-in-trichocereus |url-status=dead }}</ref> |}

thumb|''Trichocereus pachanoi'' in Peru

As shown in the accompanying table, the concentration of mescaline in different specimens can vary largely within a single species. Moreover, the concentration of mescaline within a single specimen varies as well.<ref>{{Cite journal | vauthors = Van Der Sypt F |date=2022-04-03 |title=Validation and exploratory application of a simple, rapid and economical procedure (MESQ) for the quantification of mescaline in fresh cactus tissue and aqueous cactus extracts |url=https://zenodo.org/records/6409376 |journal=PhytoChem & BioSub Journal |doi=10.5281/zenodo.6409376}}</ref>

In plants, mescaline may be the end-product of a pathway utilizing catecholamines as a method of stress response, similar to how animals may release such compounds and others such as cortisol when stressed. The ''in vivo'' function of catecholamines in plants has not been investigated, but they may function as antioxidants, as developmental signals, and as integral cell wall components that resist degradation from pathogens. The deactivation of catecholamines via methylation produces alkaloids such as mescaline.<ref name="10.1016/j.plantsci.2006.10.013" />

Mescaline is biosynthesized from tyrosine, which, in turn, is derived from phenylalanine by the enzyme phenylalanine hydroxylase. In ''Lophophora williamsii'' (Peyote), dopamine converts into mescaline in a biosynthetic pathway involving ''m''-''O''-methylation and aromatic hydroxylation.<ref>{{cite book | vauthors = Dewick PM | year = 2009 | title = Medicinal Natural Products: A Biosynthetic Approach | publisher = John Wiley & Sons | pages = 335–336 | isbn = 978-0-471-49641-0 | location = United Kingdom }}</ref>

Tyrosine and phenylalanine serve as metabolic precursors towards the synthesis of mescaline. Tyrosine can either undergo a decarboxylation via tyrosine decarboxylase to generate tyramine and subsequently undergo an oxidation at carbon 3 by a monophenol hydroxylase or first be hydroxylated by tyrosine hydroxylase to form L-DOPA and decarboxylated by DOPA decarboxylase. These create dopamine, which then experiences methylation by a catechol-O-methyltransferase (COMT) by an ''S''-adenosyl methionine (SAM)-dependent mechanism. The resulting intermediate is then oxidized again by a hydroxylase enzyme, likely monophenol hydroxylase again, at carbon 5, and methylated by COMT. The product, methylated at the two meta positions with respect to the alkyl substituent, experiences a final methylation at the 4 carbon by a guaiacol-O-methyltransferase, which also operates by a SAM-dependent mechanism. This final methylation step results in the production of mescaline.

Phenylalanine serves as a precursor by first being converted to L-tyrosine by L-amino acid hydroxylase. Once converted, it follows the same pathway as described above.<ref name="10.1016/j.plantsci.2006.10.013">{{cite journal |vauthors=Kulma A, Szopa J |date=March 2007 |title=Catecholamies are active compounds in plants |journal=Plant Science |volume=172 |issue=3 |pages=433–440 |doi=10.1016/j.plantsci.2006.10.013|bibcode=2007PlnSc.172..433K }}</ref><ref name="RosengartenFriedhoff1976">{{cite journal | vauthors = Rosengarten H, Friedhoff AJ | title = A review of recent studies of the biosynthesis and excretion of hallucinogens formed by methylation of neurotransmitters or related substances | journal = Schizophrenia Bulletin | volume = 2 | issue = 1 | pages = 90–105 | year = 1976 | pmid = 779022 | doi = 10.1093/schbul/2.1.90 | doi-access =}}</ref>

==History== {{See also|Psychedelic drug#The phenethylamine psychedelic mescaline}}

Archaeological evidence from sites in the United States, Mexico, and Peru indicates that mescaline-containing cacti have been used for over 6,000 years.<ref name="CasselsSáez-Briones2018" /> Europeans recorded use of peyote in Native American religious ceremonies upon early contact with the Huichol people in Mexico.<ref>{{cite book | vauthors = Ruiz de Alarcón H | date = 1984 | title = Treatise on the Heathen Superstitions that Today Live Among the Indians Native to this New Spain, 1629 | publisher = University of Oklahoma Press | isbn = 978-0-8061-2031-7 }}</ref> Other mescaline-containing cacti such as the San Pedro have a long history of use in South America, from Peru to Ecuador.<ref>{{cite journal | vauthors = Socha DM, Sykutera M, Orefici G | date = 2022-12-01 | title = Use of psychoactive and stimulant plants on the south coast of Peru from the Early Intermediate to Late Intermediate Period | journal = Journal of Archaeological Science | volume = 148 | article-number = 105688 | doi = 10.1016/j.jas.2022.105688 | doi-access = free | bibcode = 2022JArSc.14805688S | s2cid = 252954052 | issn = 0305-4403 }}</ref><ref>{{cite journal | vauthors = Bussmann RW, Sharon D | date = November 2006 | title = Traditional medicinal plant use in Northern Peru: tracking two thousand years of healing culture | journal = Journal of Ethnobiology and Ethnomedicine | volume = 2 | article-number = 47 | doi = 10.1186/1746-4269-2-47 | doi-access = free | pmc = 1637095 | pmid = 17090303 }}</ref><ref name="Armijos_2014">{{cite journal | vauthors = Armijos C, Cota I, González S | date = February 2014 | title = Traditional medicine applied by the Saraguro yachakkuna: a preliminary approach to the use of sacred and psychoactive plant species in the southern region of Ecuador | journal = Journal of Ethnobiology and Ethnomedicine | volume = 10 | article-number = 26 | doi = 10.1186/1746-4269-10-26 | doi-access = free | pmc = 3975971 | pmid = 24565054 }}</ref><ref>{{cite journal | vauthors = Samorini G | date = 2019-06-01 | title = The oldest archeological data evidencing the relationship of Homo sapiens with psychoactive plants: A worldwide overview | journal = Journal of Psychedelic Studies | volume = 3 | issue = 2 | pages = 63–80 | doi = 10.1556/2054.2019.008 | doi-access = free | s2cid = 135116632 }}</ref> While religious and ceremonial peyote use was widespread in the Aztec Empire and northern Mexico at the time of the Spanish conquest, religious persecution confined it to areas near the Pacific coast and up to southwest Texas. However, by 1880, peyote use began to spread north of South-Central America with "a new kind of peyote ceremony" inaugurated by the Kiowa and Comanche people. These religious practices, incorporated legally in the United States in 1920 as the Native American Church, have since spread as far as Saskatchewan, Canada.<ref name="prehistoric">{{cite journal |vauthors=El-Seedi HR, De Smet PA, Beck O, Possnert G, Bruhn JG |date=October 2005 |title=Prehistoric peyote use: alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas |journal=Journal of Ethnopharmacology |volume=101 |issue=1–3 |pages=238–242 |doi=10.1016/j.jep.2005.04.022 |pmid=15990261}}</ref>

In traditional peyote preparations, the top of the cactus is cut off, leaving the large tap root along with a ring of green photosynthesizing area to grow new heads. These heads are then dried to make disc-shaped buttons. Buttons are chewed to produce the effects or soaked in water to drink. However, the taste of the cactus is bitter, so modern users will often grind it into a powder and pour it into capsules to avoid having to taste it. The typical dose is 200 to 400{{nbsp}}mg of mescaline sulfate or 178 to 356{{nbsp}}mg of mescaline hydrochloride.<ref name="PiHKAL" /><ref>{{cite journal | vauthors = Uthaug MV, Davis AK, Haas TF, Davis D, Dolan SB, Lancelotta R, Timmermann C, Ramaekers JG | title = The epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects | journal = Journal of Psychopharmacology | volume = 36 | issue = 3 | pages = 309–320 | date = March 2022 | pmid = 33949246 | pmc = 8902264 | doi = 10.1177/02698811211013583 }}</ref> The average {{convert|76|mm|in|abbr=on}} peyote button contains about 25{{nbsp}}mg mescaline.<ref>{{cite book | vauthors = Giannini AJ, Slaby AE, Giannini MC | year = 1982 | title = Handbook of Overdose and Detoxification Emergencies | publisher = Medical Examination Publishing Company | isbn = 978-0-87488-182-0 | location = New Hyde Park, NY. }}</ref> Some analyses of traditional preparations of San Pedro cactus have found doses ranging from 34{{nbsp}}mg to 159{{nbsp}}mg of total alkaloids, a relatively low and barely psychoactive amount. It appears that patients who receive traditional treatments with San Pedro ingest sub-psychoactive doses and do not experience psychedelic effects.<ref>{{Cite web |date=2019-09-20 |title=San Pedro: Basic Info |url=https://www.iceers.org/san-pedro-basic-info/ |access-date=2024-06-06 |website=ICEERS |language=en-US}}</ref>

Botanical studies of peyote began in the 1840s and the drug was listed in the Mexican pharmacopeia.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> The first use of mescal buttons was published by John Raleigh Briggs in 1887.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> In 1887, the German pharmacologist Louis Lewin received his first sample of the peyote cactus, found numerous new alkaloids and later published the first methodical analysis of it.<ref>{{Cite web |title=Botany of Peyote |url=https://www.druglibrary.org/schaffer/lsd/pbotany.htm |access-date=2025-03-03 |website=www.druglibrary.org}}</ref> Mescaline was first isolated and identified in 1897 by the German chemist Arthur Heffter.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Erowid-Heffter">{{Cite web |url=http://www.erowid.org/culture/characters/heffter_arthur/heffter_arthur.shtml |title=Arthur Heffter |work=Character Vaults |publisher=Erowid.org |access-date=9 January 2013 }}</ref> He showed that mescaline was exclusively responsible for the psychoactive or hallucinogenic effects of peyote.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> However, other components of peyote, such as hordenine, pellotine, and anhalinine, are also active.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Mescaline was first synthesized in 1919 by Ernst Späth.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name = "Späth_1919">{{cite journal| vauthors = Späth E |title=Über dieAnhalonium-Alkaloide I. Anhalin und Mezcalin|journal=Monatshefte für Chemie und Verwandte Teile Anderer Wissenschaften|date=February 1919|volume=40|issue=2|pages=129–154|doi=10.1007/BF01524590|s2cid=104408477|language=de|issn=0343-7329}}</ref>

In 1955, English politician Christopher Mayhew took part in an experiment for BBC's ''Panorama'', in which he ingested 400{{nbsp}}mg of mescaline under the supervision of psychiatrist Humphry Osmond. Though the recording was deemed too controversial and ultimately omitted from the show, Mayhew praised the experience, calling it "the most interesting thing I ever did".<ref>{{Cite web |url=http://sotcaa.net/hiddenarchive/mayhew01.html |title=Panorama: The Mescaline Experiment |date=February 2005 |archive-url=https://web.archive.org/web/20120726183523/http://sotcaa.net/hiddenarchive/mayhew01.html |archive-date=26 July 2012 }}</ref>

Studies of the potential therapeutic effects of mescaline started in the 1950s.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" />

The mechanism of action of mescaline, activation of the serotonin 5-HT2A receptors, became known in the 1990s.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" />

==Society and culture== ===Legal status=== {{See also|Legal status of psychoactive cactus by country}}

====United States==== In the United States, mescaline was made illegal in 1970 by the Comprehensive Drug Abuse Prevention and Control Act, categorized as a Schedule I hallucinogen.<ref>{{cite web | author = United States Department of Justice | title = Drug Scheduling | url = http://www.usdoj.gov/dea/pubs/scheduling.html | access-date = 2 November 2007 | archive-date = 20 October 2008 | archive-url = https://web.archive.org/web/20081020210309/http://www.usdoj.gov/dea/pubs/scheduling.html | author-link = United States Department of Justice | url-status = dead }}</ref> The drug is prohibited internationally by the 1971 Convention on Psychotropic Substances.<ref>{{cite web|url=http://www.incb.org/pdf/e/list/green.pdf |title=List of psychotropic substances under international control |publisher=International Narcotics Control Board |access-date=27 January 2008 |url-status=dead |archive-url=https://web.archive.org/web/20051205125434/http://www.incb.org/pdf/e/list/green.pdf |archive-date=5 December 2005 }}</ref> Mescaline is legal only for certain religious groups (such as the Native American Church by the American Indian Religious Freedom Act of 1978) and in scientific and medical research. In 1990, the Supreme Court ruled that the state of Oregon could ban the use of mescaline in Native American religious ceremonies. The Religious Freedom Restoration Act (RFRA) in 1993 allowed the use of peyote in religious ceremony, but in 1997, the Supreme Court ruled that the RFRA is unconstitutional when applied against states.<ref>{{cite web|url=https://www.fjc.gov/history/cases/cases-that-shaped-the-federal-courts/city-boerne-v-flores|title=City of Boerne v. Flores|work=Federal Judicial Center|access-date=March 18, 2025}}</ref> Many states, including the state of Utah, have legalized peyote usage with "sincere religious intent", or within a religious organization,{{Citation needed|date=October 2012}} regardless of race.<ref>{{cite web |url=http://www.utcourts.gov/opinions/supopin/mooney062204.htm |title=State v. Mooney |publisher=utcourts.gov |access-date=5 October 2012}}</ref> Synthetic mescaline, but not mescaline derived from cacti, was officially decriminalized in the state of Colorado by ballot measure Proposition 122 in November 2022.<ref>{{cite web | url=https://ballotpedia.org/Colorado_Proposition_122,_Decriminalization_and_Regulated_Access_Program_for_Certain_Psychedelic_Plants_and_Fungi_Initiative_(2022) | title=Colorado Proposition 122, Decriminalization and Regulated Access Program for Certain Psychedelic Plants and Fungi Initiative (2022) }}</ref>

While mescaline-containing cacti of the genus ''Echinopsis'' are technically controlled substances under the Controlled Substances Act, they are commonly sold publicly as ornamental plants.<ref>{{cite book | vauthors = Gupta RC | date = 2018 | title = Veterinary Toxicology: Basic and Clinical Principles | publisher = Academic Press | edition = Third | pages = 363–390 | isbn = 978-0-12-370467-2 }}</ref>

====United Kingdom==== In the United Kingdom, mescaline in purified powder form is a Class A drug. However, dried cactus can be bought and sold legally.<ref>{{Cite web |url=http://www.erowid.org/plants/cacti/cacti_law2.shtml |title=2007 U.K. Trichocereus Cacti Legal Case Regina v. Saul Sette |publisher=Erowid.org |date=June 2007 |access-date=6 April 2012 }}</ref>

====Australia==== Mescaline is considered a schedule 9 substance in Australia under the Poisons Standard (February 2020).<ref name="Poisons Stanrard">[https://www.legislation.gov.au/Details/F2020C00148 Poisons Standard February 2020]. comlaw.gov.au</ref> A schedule 9 substance is classified as "Substances with a high potential for causing harm at low exposure and which require special precautions during manufacture, handling or use. These poisons should be available only to specialised or authorised users who have the skills necessary to handle them safely. Special regulations restricting their availability, possession, storage or use may apply."<ref name="Poisons Stanrard" />

====Other countries==== In Canada, France, The Netherlands and Germany, mescaline in raw form and dried mescaline-containing cacti are considered illegal drugs. However, anyone may grow and use peyote, or ''Lophophora williamsii'', as well as ''Echinopsis pachanoi'' and ''Echinopsis peruviana'' without restriction, as it is specifically exempt from legislation.<ref name=Bib/> In Canada, mescaline is classified as a schedule III drug under the Controlled Drugs and Substances Act, whereas peyote is exempt.<ref>{{cite web |url=http://laws-lois.justice.gc.ca/Search/Search.aspx?txtS3archA11=mescaline&txtT1tl3=%22Controlled+Drugs+and+Substances+Act%22&h1ts0n1y=0&ddC0nt3ntTyp3=Acts. |title=Justice Laws Search |publisher=laws-lois.justice.gc.ca |access-date=5 October 2012}}</ref>

In Russia mescaline, its derivatives and mescaline-containing plants are banned as narcotic drugs (Schedule I).<ref>{{cite web|url=http://base.garant.ru/12112176/|title=Постановление Правительства РФ от 30.06.1998 N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями) - ГАРАНТ|website=base.garant.ru}}</ref>

===Notable individuals=== * Salvador Dalí experimented with mescaline believing it would enable him to use his subconscious to further his art potential. * Antonin Artaud wrote 1947's ''The Peyote Dance'', where he describes his peyote experiences in Mexico a decade earlier.<ref>{{cite magazine | vauthors = Doyle P | date = 2019-05-20 | title = Patti Smith Channels French Poet Antonin Artaud on Peyote | language = en-US | magazine = Rolling Stone | url = https://www.rollingstone.com/music/music-news/watch-patti-smith-channel-french-poet-antonin-artaud-on-peyote-837533/ | access-date = 2022-04-03 }}</ref> * Allen Ginsberg took peyote. Part II of his poem "Howl" was inspired by a peyote vision that he had in San Francisco.<ref>{{cite magazine | date = 1968-08-10 | title = The Father of Flower Power | language = en-US | magazine = The New Yorker | url = http://www.newyorker.com/magazine/1968/08/17/paterfamilias-i | access-date = 2022-04-03 }}</ref> * Ken Kesey took peyote prior to writing ''One Flew Over the Cuckoo's Nest''. * Jean-Paul Sartre took mescaline shortly before the publication of his book, ''L'Imaginaire'' (1940); he had a bad trip during which he imagined that he was menaced by sea creatures.<ref name="Jay2019">{{cite web | last=Jay | first=Mike | title=Sartre's Bad Trip by Mike Jay | website=The Paris Review | date=2019-08-21 | url=https://www.theparisreview.org/blog/2019/08/21/sartres-bad-trip/ | access-date=2026-05-25}}</ref><ref name="Allens-Mills2009">{{cite web | last=Allen-Mills | first=Tony | title=Mescaline left Jean Paul Sartre in the grip of lobster madness | website=The Times | date=22 November 2009 | url=https://www.thetimes.com/comment/register/article/mescaline-left-jean-paul-sartre-in-the-grip-of-lobster-madness-mkgqxxcln2k | access-date=25 May 2026}}</ref> For many years following this, he persistently imagined that he was being followed by lobster- or crab-like creatures, and became a patient of Jacques Lacan in hopes of being rid of them.<ref name="Jay2019" /><ref name="Allens-Mills2009" /> Lobsters and crabs figure in his novel ''Nausea'' (1938).<ref name="Allens-Mills2009" /><ref name="Jay2019" /> * Havelock Ellis was the author of one of the first written reports to the public about an experience with mescaline (1898).<ref>{{cite book | vauthors = Ellis H | date = 1898 | chapter = Mescal: A New Artificial Paradise | title = The Contemporary Review | volume = LXXIII | chapter-url = https://archive.org/stream/contemporaryrev23unkngoog#page/n142/mode/2up }}</ref><ref name =rudgley1993>{{cite book | author = Rudgley R | date = 1993 | chapter = VI | title = The Alchemy of Culture: Intoxicants in Society | publisher = British Museum Press | isbn = 978-0-7141-1736-2 | author-link = Richard Rudgley }}</ref><ref>{{cite book | vauthors = Giannini AJ | year = 1997 | title = Drugs of Abuse | publisher = Practice Management Information Corp | edition = Second | isbn = 978-1-57066-053-5 | location = Los Angeles }}</ref> *Stanisław Ignacy Witkiewicz, Polish writer, artist and philosopher, experimented with mescaline and described his experience in a 1932 book ''Nikotyna Alkohol Kokaina Peyotl Morfina Eter''.<ref name="Witkiewicz">{{cite book | vauthors = Witkiewicz SI, Biczysko S | date = 1932 | title = Nikotyna, alkohol, kokaina, peyotl, morfina, eter+ appendix. | publisher = Drukarnia Towarzystwa Polskiej Macierzy Szkolnej | url = https://pl.wikisource.org/wiki/Nikotyna_Alkohol_Kokaina_Peyotl_Morfina_Eter_%2B_Appendix | location = Warsaw }}</ref> * Aldous Huxley described his experience with mescaline in the essay "The Doors of Perception" (1954). * Jim Carroll in ''The Basketball Diaries'' described using peyote that a friend smuggled from Mexico. * Quanah Parker, appointed by the federal government as principal chief of the entire Comanche Nation, advocated the syncretic Native American Church alternative, and fought for the legal use of peyote in the movement's religious practices. * Hunter S. Thompson wrote an extremely detailed account of his first use of mescaline in "First Visit with Mescalito", and it appeared in his book ''Songs of the Doomed'', as well as featuring heavily in his novel ''Fear and Loathing in Las Vegas''. * Psychedelic research pioneer Alexander Shulgin said he was first inspired to explore psychedelic compounds by a mescaline experience.<ref>{{Cite web |title=Alexander Shulgin: why I discover psychedelic substances |year=1996 |work=Luc Sala interview |url=https://www.youtube.com/watch?v=QD260LPqHKA&t=3m18s |archive-url=https://ghostarchive.org/varchive/youtube/20211211/QD260LPqHKA| archive-date=2021-12-11 |url-status=live|location=Mexico }}{{cbignore}}</ref> In 1974, Shulgin synthesized 2C-B, a psychedelic phenylethylamine derivative, structurally similar to mescaline,<ref>{{cite journal | vauthors = Papaseit E, Farré M, Pérez-Mañá C, Torrens M, Ventura M, Pujadas M, de la Torre R, González D | date = 2018 | title = Acute Pharmacological Effects of 2C-B in Humans: An Observational Study | language = English | journal = Frontiers in Pharmacology | volume = 9 | article-number = 206 | doi = 10.3389/fphar.2018.00206 | doi-access = free | pmc = 5859368 | pmid = 29593537 }}</ref> and one of Shulgin's self-rated most important phenethylamine compounds together with Mescaline, 2C-E, 2C-T-7, and 2C-T-2.<ref>{{Cite web |date=2019-12-02 |title=Mescaline |url=https://psychedelicreview.com/compound/mescaline/ |access-date=2023-10-30 |website=Psychedelic Science Review |language=en-US}}</ref> * Bryan Wynter produced ''Mars Ascends'' after trying the substance for the first time.<ref>{{cite book | vauthors = Bird M | date = 2012 | title = 100 Ideas that Changed Art. | publisher = Laurence King Publishing | location = London }}</ref> * George Carlin mentioned mescaline use during his youth while being interviewed in 2008.<ref>{{cite web | vauthors = Dixit J |date=23 June 2008 |title=George Carlin's Last Interview |work=Psychology Today |url=http://www.psychologytoday.com/blog/brainstorm/200806/george-carlins-last-interview?page=4}}</ref> * Carlos Santana told about his mescaline use in a 1989 ''Rolling Stone'' interview.<ref>{{cite magazine | vauthors = Greene A | date = 1989 | title = Dazed and Confused: 10 Classic Drugged-Out Shows | magazine = Rolling Stone | url = https://www.rollingstone.com/music/pictures/10-classic-drugged-out-performances-from-santana-to-green-day-20130606/1-santana-at-woodstock-1969-mescaline-0973315 | quote = Santana at Woodstock, 1969 - Mescaline }}</ref> * Disney animator Ward Kimball described participating in a study of mescaline and peyote conducted by UCLA in the 1960s.<ref>{{cite web |url=http://cartoonician.com/ward-kimballs-final-farewell/ |title=Ward Kimball's Final Farewell |date=4 March 2016 |publisher=cartoonician.com |access-date=4 March 2016|archive-url=https://web.archive.org/web/20160306095332/http://cartoonician.com/ward-kimballs-final-farewell/|archive-date=6 March 2016|url-status=dead}}</ref> * Michael Cera used real mescaline for the movie ''Crystal Fairy & the Magical Cactus'', as expressed in an interview.<ref>{{cite news| url=http://www.huffingtonpost.com/2013/07/10/michael-cera-drugs-mescaline-crystal-fairy_n_3575056.html | work=Huffington Post | vauthors = Boardman M | title=Michael Cera Took Drugs On-Camera | date=10 July 2013}}</ref> * Philip K. Dick was inspired to write ''Flow My Tears, the Policeman Said'' after taking mescaline.<ref>{{Cite web|url=http://www.philipkdickfans.com/mirror/websites/pkdweb/FLOW%20MY%20TEARS.HTM|title=FLOW MY TEARS |publisher=www.philipkdickfans.com|access-date=2018-05-04}}</ref> * Arthur Kleps, a psychologist turned drug legalization advocate and writer whose Neo-American Church defended use of marijuana and hallucinogens such as LSD and peyote for spiritual enlightenment and exploration, bought, in 1960, by mail from Delta Chemical Company in New York 1 g of mescaline sulfate and took 500{{nbsp}}mg. He experienced a psychedelic trip that caused profound changes in his life and outlook.{{citation needed|date=October 2024}}

===Media representations=== ====Movies==== * ''Fear and Loathing in Las Vegas'' (1998) starring Johnny Depp and Benicio del Toro featured mescaline use. * ''The Matrix'' (1999) by the Wachowskis included a brief mention of mescaline.<ref name="IMDB-The-Matrix-1999">{{cite web | title=''The Matrix'' Quotes | website=imdb.com | url=https://www.imdb.com/title/tt0133093/quotes/?item=qt0324290 | quote=Neo: You ever have that feeling where you're not sure if you're awake or still dreaming? Choi: All the time. It's called mescaline, it's the only way to fly.}}</ref> * ''The Royal Tenenbaums'' (2001) features a character named Eli Cash (Owen Wilson) who regularly takes mescaline. * ''Crystal Fairy & the Magical Cactus'' (2013) starring Michael Cera and Gaby Hoffmann was about taking mescaline in the form of the San Pedro cactus.

====Documentaries==== * ''Peyote to LSD: A Psychedelic Odyssey'' (2008), a History Channel documentary, covers mescaline. * ''Hamilton's Pharmacopeia'' (2016–2021) has multiple episodes on mescaline in the form of peyote and the San Pedro cactus. * ''How to Change Your Mind'' (2022) features an episode on mescaline.

==Research== {{See also|Psychedelic therapy|List of investigational hallucinogens and entactogens}}

Mescaline has a wide array of suggested medical usage, including treatment of depression, anxiety, PTSD,<ref name="Naturalistic Use of Mescaline Is As">{{cite journal | vauthors = Agin-Liebes G, Haas TF, Lancelotta R, Uthaug MV, Ramaekers JG, Davis AK | title = Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes | journal = ACS Pharmacology & Translational Science | volume = 4 | issue = 2 | pages = 543–552 | date = April 2021 | pmid = 33860184 | pmc = 8033766 | doi = 10.1021/acsptsci.1c00018 }}</ref> nicotine dependence, and alcoholism.<ref>{{Cite web |url=https://abcnews.go.com/blogs/health/2012/03/09/could-lsd-treat-alcoholism/ |title=Could LSD treat alcoholism? |publisher=ABC News |date=9 March 2012 |access-date=5 October 2012 }}</ref><ref>{{cite journal | vauthors = Shaw J, Yong A, Lee J, Cheng J, Andricioaei A, Wang JY, Zisman-Ilani Y, Bota R | date = March 2026 | title = The Ethnopharmacological Use of Mescaline for Psychiatric Disorders: A Systematic Review | journal = International Journal of Molecular Sciences | volume = 27 | issue = 7 | page = 3081 | doi = 10.3390/ijms27073081 | doi-access = free | pmc = 13072975 | pmid = 41977267 }}</ref> However, its status as a Schedule I controlled substance in the Convention on Psychotropic Substances limits availability of the drug to researchers. Because of this, very few studies concerning mescaline's activity and potential therapeutic effects in people have been conducted since the early 1970s.<ref>{{Cite web | vauthors = Carpenter DE |date=2021-07-08 |title=Mescaline is Resurgent (Yet Again) As a Potential Medicine |url=https://www.lucid.news/mescaline-is-resurgent-yet-again-as-a-potential-medicine/ |access-date=2022-02-28 |website=Lucid News |language=en-US}}</ref><ref name="Naturalistic Use of Mescaline Is As"/><ref name="Bender_2022">{{cite journal | vauthors = Bender E | title = Finding medical value in mescaline | journal = Nature | volume = 609 | issue = 7929 | pages = S90–S91 | date = September 2022 | pmid = 36171368 | doi = 10.1038/d41586-022-02873-8 | bibcode = 2022Natur.609S..90B | s2cid = 252548055 | doi-access =}}</ref>

== See also == * Scaline * List of psychedelic plants ** Mind at Large (concept in ''The Doors of Perception'') * ''The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead'' (1964) * ''Der Meskalinrausch, seine Geschichte und Erscheinungsweise'' (1927)

== References == {{Reflist}}

== Further reading == * {{cite book | vauthors = Jay M | date = 2019 | title = Mescaline: A Global History of the First Psychedelic | publisher = Yale University Press }} * {{cite book | vauthors = Klüver H | date = 1942 | veditors = McNemar Q, Merrill MA | chapter = Mechanisms of hallucinations. | title = Studies in personality | publisher = McGraw-Hill | pages = 175–207 | author-link = Heinrich Klüver | chapter-url = https://maps.org/research-archive/psychedelicreview/n07/n07041klu.pdf }} * {{cite book | vauthors = Pollan M | date = 2021 | title = This Is Your Mind on Plants | publisher = Penguin Press | isbn = 978-0-593-29690-5 | author-link = Michael Pollan }}

== External links == {{Commons}} * [https://isomerdesign.com/pihkal/explore/96 Mescaline - Isomer Design] * [https://psychonautwiki.org/wiki/Mescaline Mescaline - PsychonautWiki] * [https://www.erowid.org/chemicals/mescaline/mescaline.shtml Mescaline - Erowid] * [https://erowid.org/library/books_online/pihkal/pihkal096.shtml Mescaline - PiHKAL - Erowid] * [https://isomerdesign.com/pihkal/read/pk/96 Mescaline - PiHKAL - Isomer Design] * [https://archive.org/details/shulgin-index-vol-1/page/212/mode/1up?view=theater Mescaline - The Shulgin Index] * [https://isomerdesign.com/bitnest/external/TCA/81-146 Mescaline - Trout's Notes] * [https://www.bluelight.org/xf/threads/377141 Archive List for The Big and Dandy Basic Mescaline/Cactus Threads - Bluelight] * [https://www.youtube.com/watch?v=Hd4rgyZzseY The Mescaline Experiment: Humphry Osmond and Christopher Mayhew - YouTube] * [http://www.houstonpress.com/2008-02-14/news/mescaline-on-the-mexican-border/ Mescaline on the Mexican Border - Houston Press]

{{Psychedelics}} {{Serotonin receptor modulators}} {{TAAR modulators}} {{Phenethylamines}} {{Chemical classes of psychoactive drugs}}

Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:Alexander Shulgin Category:Alkaloids found in Fabaceae Category:Biased ligands Category:Cacti Category:Entheogens Category:Experimental hallucinogens Category:Native American Church Category:Phenethylamine alkaloids Category:PiHKAL Category:Psychedelic-assisted therapy Category:Psychoplastogens Category:Scalines Category:Serotonin receptor agonists Category:TAAR1 modulators