View source for Mescaline

{{Short description|Naturally occurring psychedelic compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Distinguish|mezcal|mesclun|mexamine}}
{{Use dmy dates|date=October 2020}}
{{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

<!-- Clinical data -->
| 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 administration|Oral]], [[smoking]], [[insufflation]], [[intravenous administration|intravenous]]<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" />
| ATC_prefix = None
| ATC_suffix =

<!-- Legal status -->
| legal_AU = Schedule 9
| legal_BR = F2
| legal_BR_comment = <ref> name="Anvisa2023"{{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 =

<!-- Pharmacokinetic data -->
| 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 (but appears minimal)<ref name="DrugBank" /><ref name="Dart2004" /><ref name="OhLeitchAxelrod1967">{{cite journal | vauthors = Oh YH, Leitch WE, Axelrod S, Small SM, Winzler RJ, Sanders BE | title = Binding of biologically active amines to plasma protein fractions | journal = Biochemical Pharmacology | volume = 16 | issue = 5 | pages = 849–861 | date = May 1967 | pmid = 6036735 | doi = 10.1016/0006-2952(67)90058-5 | url = | quote = Studies have been initiated to provide information on biochemical relationships between biogenic amines and plasma proteins. The binding in vitro of several biogenic amines, i.e. 3,4-dimethoxyphenylethylamine, mescaline, tyramine, and normetanephrine, labeled with 14C or 3H to human plasma protein fractions have been studied. [...] No appreciable binding to any of the plasma protein fractions was observed with mescaline or normetanephrine. [...]}}</ref>
| metabolism = [[Oxidative deamination]], ''N''-[[acetylation]], ''O''-[[demethylation]], [[conjugation (biochemistry)|conjugation]], other [[metabolic pathway|pathway]]s<ref name="CasselsSáez-Briones2018" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" />
| metabolites = • 3,4,5-Trimethoxyphenyl-acetaldehyde<ref name="CasselsSáez-Briones2018" /><ref name="VamvakopoulouNarineCampbell2023" /><br />• 3,4,5-Trimethoxyphenylacetic acid<ref name="VamvakopoulouNarineCampbell2023" /><br />• 3,4,5-Trimethoxyphenylethanol<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><br />• Others<ref name="CasselsSáez-Briones2018" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" />
| onset = [[Oral administration|Oral]]: 0.5–0.9{{nbsp}}hours (range 0.1–2.7{{nbsp}}hours)<ref name="HolzeSinghLiechti2024" /><ref name="KlaiberSchmidBecker2024" /><ref name="VamvakopoulouNarineCampbell2023" /><br />{{Abbrlink|IV|Intravenous injection}}: <10{{nbsp}}minutes<ref name="Patel1968" /><ref name="KapadiaFayez1970" /><ref name="Denber1958">{{cite book | vauthors = Denber HC | date = 1958 | veditors = Rinkel M | chapter = The Mescaline Psychosis: II. Clinical Considerations of the Mescaline-Induced State | title = Chemical Concepts of Psychosis: Proceedings of the Symposium on Chemical Concepts of Psychosis held at the Second International Congress of Psychiatry in Zurich, Switzerland, September 1 to 7, 1957 | publisher = McDowell, Obolensky | pages = 120–126 | doi = 10.1037/11190-009 | publication-place = New York }}</ref>
| 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" />

<!-- Identifiers -->
| 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 = M; Mescalin; Mezcalin; Mezcaline; Meskalin; Mezkalin; 3,4,5-Trimethoxyphenethylamine; 3,4,5-TMPEA; TMPEA; ''O'',''O''-Dimethyl-5-methoxydopamine; 2C-TMA; EA-1306; NSC-30419; JOUR-5700; JOUR5700; BMND04; BMND06; BMND09

<!-- Chemical data -->
| 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

<!-- Physical data -->
| 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 in chemical terms as '''3,4,5-trimethoxyphenethylamine''', is a [[natural product|naturally occurring]] [[psychedelic drug]] and [[alkaloid]] of the [[substituted phenethylamine|phenethylamine]] and [[scaline]] families found in certain [[Cactus|cacti]] like [[peyote]] (''Lophophora williamsii'') and the [[San Pedro cactus]] (''[[Echinopsis pachanoi]]'', others).<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="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 |location=Basel, Switzerland |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="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>

The drug is used [[recreational drug use|recreationally]], [[entheogen|spiritually]], and [[medicine|medically]], with psychedelic effects occurring at doses of 100 to 1,000{{nbsp}}mg [[oral administration|orally]]<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022" /> and it can be used in pure form or in the form of mescaline-containing cacti.<ref name="CasselsSáez-Briones2018" /><ref name="Anderson1996" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Mescaline induces a [[psychedelic experience]] characterized by [[psychedelic visuals|visual changes]], altered perception of time, space, and self, [[synesthesia]], and [[spiritual experience]]s, with an [[onset of action|onset]] of 30 to 60{{nbsp}}minutes, a time to peak of 2 to 4{{nbsp}}hours, and a [[duration of action|duration]] that increases with dose and ranges from 6 to 14{{nbsp}}hours.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="HolzeSinghLiechti2024" /><ref name="KlaiberSchmidBecker2024" />

Mescaline primarily acts as a [[partial agonist]] at [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptors]], with varying [[affinity (pharmacology)|affinity]] and [[efficacy]] across multiple other [[receptor (biochemistry)|receptor]]s and [[biological target|target]]s.<ref name="HolzeSinghLiechti2024" /><ref name="VamvakopoulouNarineCampbell2023" /> The serotonin 5-HT<sub>2A</sub> receptor antagonist [[ketanserin]] blocks mescaline's psychoactive effects.<ref name="TabaacShinozukaFadel2026" /><ref name="KlaiberSchmidBecker2024" /> Mescaline is a relatively [[hydrophile|hydrophilic]] compound structurally related to [[dopamine]],<ref name="PiHKAL" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /> first [[chemical synthesis|synthesized]] in 1919,<ref name="Jay2019" /> with numerous synthetic methods<ref name="Trout2013" /> and [[potency (pharmacology)|potent]] [[structural analog|analogue]]s developed since.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> It occurs naturally in various cacti species, with concentrations varying widely, and is [[Biosynthesis|biosynthesized]] in plants from [[amino acid]]s like [[phenylalanine]] and [[tyrosine]].<ref name="CasselsSáez-Briones2018" /><ref name="WangWangLin2026">{{cite journal | vauthors = Wang Y, Wang H, Lin C, Wang X | title = Chemical ecology and convergent evolution of natural hallucinogens: From ecological defense to conserved neural targets | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 123 | issue = 26 | article-number = e2535785123 | date = June 2026 | pmid = 42341036 | doi = 10.1073/pnas.2535785123 | url = | pmc = 13321363 }}</ref><ref name="Trout2013" />

The practice of humans consuming mescaline-containing cacti dates back over 6,000{{nbsp}}years.<ref name="CasselsSáez-Briones2018" /><ref name="Jay2019" /> Peyote cacti were studied scientifically in the 1800s, culminating in the isolation of mescaline as the active psychedelic constituent in cacti, legal recognition of religious use, and ongoing exploration of the therapeutic potential of mescaline and other analogues.<ref name="Jay2019" /> Mescaline was the first psychedelic compound to be characterized by the Western world and has been referred to as the "first psychedelic".<ref name="Jay2019" /><ref name="Pollan2021" />

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, for instance [[Aldous Huxley]] and [[Alexander Shulgin]] among others.<ref name="Jay2019" /><ref name="Huxley1954" /><ref name="PiHKAL" /> Very few studies of mescaline in people have been conducted since the early 1970s.<ref name="Jay2019" /><ref name="Bender_2022" /> However, the drug is now being studied in terms of its effects and for potential medical use once again as of the early 2020s.<ref name="HolzeSinghLiechti2024" /><ref name="Bender_2022" /><ref name="Metzger2022" />

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

Mescaline is used [[recreational drug|recreationally]], [[Entheogen|spiritually]], and [[medicine|medically]].<ref name="CasselsSáez-Briones2018" /><ref name="VamvakopoulouNarineCampbell2023" /> It is typically taken [[oral administration|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 | series = Curr Top Behav Neurosci | volume = 56 | pages = 3–21 | isbn = 978-3-031-12183-8 | doi = 10.1007/7854_2021_270 | pmid = 34734392 | 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><ref name="Trout2013" /> Low doses are 100 to 200{{nbsp}}mg, an intermediate or "good effect" dose is 500{{nbsp}}mg, and a high ([[ego dissolution|ego-dissolution]]) dose is 1,000{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022" /> In his book ''[[PiHKAL]]'' (''Phenethylamines I Have Known and Loved''), [[Alexander Shulgin]] listed a dose range of 200 to 400{{nbsp}}mg as the [[sulfate]] [[salt (chemistry)|salt]] and 178 to 356{{nbsp}}mg as the [[hydrochloride]] salt.<ref name="PiHKAL" /><ref name="UthaugDavisHaas2022">{{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 | location = Oxford, England | volume = 36 | issue = 3 | pages = 309–320 | date = March 2022 | pmid = 33949246 | pmc = 8902264 | doi = 10.1177/02698811211013583 }}</ref> [[Psychedelic microdosing|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 [[cactus|cacti]] such as [[peyote]] and the [[San Pedro cactus]].<ref name="CasselsSáez-Briones2018" /><ref name="Anderson1996" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Doses when mescaline is used in the form of fresh or dried cacti have also been described.<ref name="EngelMitchell2025">{{cite journal | vauthors = Engel LB, Low M | title = The Trouble with Psychedelic Cacti: Conflicting Meanings of San Pedro and Peyote | journal = Contemporary Drug Problems | volume = 52 | issue = 1 | pages = 104–117 | year = 2025 | doi = 10.1177/00914509251318751 }}</ref><ref name="EngelThalBright2024">{{cite journal | vauthors = Engel LB, Thal S, Bright SJ, Low M | title = Psychedelic Trip Sitting, Dosages and Intensities: Supplementing Clinical Studies with Anecdotal Reports | journal = Journal of Psychedelic Studies | volume = 8 | issue = 3 | pages = 313–323 | year = 2024 | doi = 10.1556/2054.2024.00377 }}</ref><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Anderson1996" />

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 average {{convert|76|mm|in|abbr=on}} peyote button contains about 25{{nbsp}}mg mescaline.<ref name="GianniniSlabyGiannini1982">{{cite book | vauthors = Giannini AJ, Slaby AE, Giannini MC | year = 1982 | title = Handbook of Overdose and Detoxification Emergencies | location = New Hyde Park, NY. | publisher = Medical Examination Publishing Company | isbn = 978-0-87488-182-0 }}</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 name="ICEERS2019">{{cite web | vauthors = Aixalà M | date = 2019-09-20 | title = San Pedro: Basic Info | language = en-US | website = ICEERS | url = https://www.iceers.org/san-pedro-basic-info/ | access-date = 2024-06-06 }}</ref>

The [[onset of action|onset]] of the effects of mescaline given [[oral administration|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 journal | vauthors = Holze F, Liechti ME, Müller F | title = Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms | series = Psychedelic Harm Reduction | journal = Current Topics in Behavioral Neurosciences | volume = 77| pages =  25–42| date = July 2024 | pmid = 39080236 | doi = 10.1007/7854_2024_510 | isbn = 978-3-032-21106-4 | url = https://www.researchgate.net/publication/382715259}}</ref><ref name="LeyHolzeArikci2023" /><ref name="KlaiberSchmidBecker2024" /> The [[duration of action|duration]] of mescaline appears to be [[dose dependence|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 experience|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 [[time perception|sense of time]] and [[self-awareness]], and [[closed-eye visuals|closed]]- and [[open-eye visuals|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 ''PiHKAL'', Shulgin described the effects of mescaline based on a collection of [[trip report|experience report]]s.<ref name="PiHKAL" /> The effects included brightened colors, increased [[visual contrast]], [[open-eye visual]]s like colors and patterns, [[pareidolia]], increased significance of objects, enhanced [[music]] appreciation, feeling [[drug intoxication|intoxicated]], [[self-reflection|self-analysis]], [[insight]]s, increased body awareness, feelings of [[joy]], [[happiness]], and [[peacefulness]], feeling [[hyperactivity|hyper]] and [[mental energy|energized]], feelings of [[empathy]], things feeling ridiculous, [[humor]] and [[laughter]], [[religion|religious]] feelings, [[restlessness (psychology)|restlessness]], [[social discomfort]] and [[social avoidance|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 drugs 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 | series = Classics To Go | publisher = Otbebookpublishing | isbn = 978-3-96537-009-8 | url = https://books.google.com/books?id=ziNdEQAAQBAJ | access-date = 26 November 2025 | orig-date = 1954 }}</ref> Like LSD, mescaline induces distortions of form and [[Kaleidoscope|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 [[Cubism|Cubist]] painting.<ref name="Freye2009" /><ref name="GianniniSlaby1989">{{cite book | vauthors = Giannini AJ, Slaby AE | year = 1989 | title = Drugs of Abuse | location = Oradell, NJ. | publisher = Medical Economics Books | pages = 207–239 | isbn = 978-0-87489-499-8 }}</ref> Detailed descriptions of the psychedelic experience induced by mescaline have been given by many authors.<ref name="KapadiaFayez1970" /><ref name="Trout2013" /><ref name="PrentissMorgan1895" /><ref name="Beringer1927" /><ref name="Klüver1928" /><ref name="Rouhier1927" /><ref name="Huxley1954" /><ref name="PiHKAL" />

The subjective effects of mescaline are qualitatively similar to those of [[LSD]] and [[psilocybin]].<ref name="HolzeSinghLiechti2024" /><ref name="VogtLiechti2025" /><ref name="LeyHolzeArikci2023" /><ref name="Patel1968" /><ref name="KapadiaFayez1970" /> Based on [[anecdotal evidence]] however, mescaline is said to be less threatening and to produce less [[ego dissolution]] than other psychedelics like LSD.<ref name="Bender_2022" /><ref name="Pollan2021" /> This may in part be due its slow onset allowing for a more comfortable ease-in of effects.<ref name="Bender_2022" /> In addition, mescaline is typically dosed at lower doses than LSD or psilocybin in terms of doses with equivalent or comparable strength.<ref name="KlaiberSchmidBecker2024" /><ref name="LeyHolzeArikci2023" /><ref name="HolzeSinghLiechti2024" /> According to a study in the [[Netherlands]], ceremonial San Pedro use seems to be characterized by relatively strong [[spiritual experience]]s, and low incidence of [[challenging experience]]s.<ref name="BohnKiggenUthaug2022">{{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> Mescaline, LSD, and psilocybin appear to produce similar color enhancement in clinical studies, though more research is needed.<ref name="AdayWoodBloesch2021">{{cite journal | vauthors = Aday JS, Wood JR, Bloesch EK, Davoli CC | title = Psychedelic drugs and perception: a narrative review of the first era of research | journal = Reviews in the Neurosciences | volume = 32 | issue = 5 | pages = 559–571 | date = July 2021 | pmid = 33550787 | doi = 10.1515/revneuro-2020-0094 | url = | quote = Alan M. Hartman and Leo E. Hollister conducted what seemed to be the most focused studies on psychedelics' effects on color perception from this era, as they systematically compared the effects of LSD, psilocybin, and mescaline on a variety of color perception measures. [...] the authors concluded that the similarities of LSD, psilocybin, and mescaline's effects on color perception are more prominent than any differences. [...]}}</ref><ref name="KometerVollenweider2018">{{cite journal | vauthors = Kometer M, Vollenweider FX | title = Serotonergic Hallucinogen-Induced Visual Perceptual Alterations | journal = Current Topics in Behavioral Neurosciences | volume = 36 | issue =  | pages = 257–282 | date = 2018 | pmid = 27900674 | doi = 10.1007/7854_2016_461 | url = | quote = Interestingly, classical hallucinogens, including psilocybin, mescaline and LSD, frequently induced form constants of the lattice and tunnel types. Furthermore, hallucinogen-induced visual experiences were dominated by red, orange, or yellow colors, while blue colors were most commonly observed after the administration of delta-9-THC. [...] Thus, visual experiences showed marked consistency across various classical hallucinogens, not only in terms of specific form constants, but also in terms of the color and movement categories.}}</ref><ref name="HollisterHartman1962">{{cite journal | vauthors = Hollister LE, Hartman AM | title = Mescaline, lysergic acid diethylamide and psilocybin comparison of clinical syndromes, effects on color perception and biochemical measures | journal = Comprehensive Psychiatry | volume = 3 | issue =  | pages = 235–242 | date = August 1962 | pmid = 13908449 | doi = 10.1016/s0010-440x(62)80024-8 | url = }}</ref><ref name="HartmanHollister1963">{{cite journal | vauthors = Hartman AM, Hollister LE | title = Effect of Mescaline, Lysergic Acid Diethylamide and Psilocybin on Color Perception | journal = Psychopharmacologia | volume = 4 | issue =  | pages = 441–451 | date = August 1963 | pmid = 14048565 | doi = 10.1007/BF00403349 | url = }}</ref>

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

[[Contraindication]]s of [[psychedelic drug]]s like mescaline include severe [[cardiovascular disease]], [[epilepsy]] or [[seizure]]s, [[schizophrenia]] and other [[psychotic disorder]]s, [[bipolar disorder]], and [[pregnancy]], among others.<ref name="Aragam2022">{{cite web | vauthors = Aragam G | date = 22 March 2022 | title = Medical Contraindications to "Classic" Psychedelic Use | website = Translational Psychedelic Research (TrPR) Program, UCSF | publisher = University of California, San Francisco | url = https://psychedelics.ucsf.edu/blog/medical-contraindications-to-classic-psychedelic-use | access-date = 30 June 2026 }}</ref><ref name="SabéSulstarovaGlangetas2025">{{cite journal | vauthors = Sabé M, Sulstarova A, Glangetas A, De Pieri M, Mallet L, Curtis L, Richard-Lepouriel H, Penzenstadler L, Seragnoli F, Thorens G, Zullino D, Preller K, Böge K, Leucht S, Correll CU, Solmi M, Kaiser S, Kirschner M | title = Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies | journal = Molecular Psychiatry | volume = 30 | issue = 3 | pages = 1223–1255 | date = March 2025 | pmid = 39592825 | pmc = 11835720 | doi = 10.1038/s41380-024-02800-5 | url = }}</ref> [[Serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[receptor antagonist|antagonist]]s such as [[atypical antipsychotic]]s and certain [[antidepressant]]s may block psilocybin's hallucinogenic effects and hence may be considered contraindicated in this sense.<ref name="HalmanKongSarris2024">{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=Journal of Psychopharmacology |location=Oxford, England |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}}</ref><ref name="YatesMelon2024">{{cite journal | vauthors = Yates G, Melon E | date = January 2024 | title = Trip-killers: a concerning practice associated with psychedelic drug use | journal = Emergency Medicine Journal | volume = 41 | issue = 2 | pages = 112–113 | doi = 10.1136/emermed-2023-213377 | pmid = 38123961 | url = https://isomerdesign.com/bitnest/external/10.1136/emermed-2023-213377}}</ref>

== Adverse effects ==
[[Side effect]]s of mescaline include [[fatigue (medical)|fatigue]], [[asthenia|weakness]], impaired [[concentration]], [[restlessness (psychology)|restlessness]], [[psychological tension|tension]], [[anxiety]], [[panic attack|panic]], and [[social discomfort]] and [[social avoidance|avoidance]], [[headache]], [[pupil dilation]], [[nausea]], [[vomiting]], [[sweating]], [[trembling]], discomfort, feeling hot or cold, [[palpitation]]s, [[chest pain|chest]] and [[neck pain]]s, [[shortness of breath]], increased [[heart rate]] and [[blood pressure]], and [[hyperthermia|increased body temperature]], among others.<ref name="PiHKAL" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="HolzeSinghLiechti2024" /><ref name="KlaiberHumbert-DrozLey2024">{{cite journal | vauthors = Klaiber A, Humbert-Droz M, Ley L, Schmid Y, Liechti ME | title = Safety pharmacology of acute mescaline administration in healthy participants | journal = British Journal of Clinical Pharmacology | article-number = bcp.16349 | date = November 2024 | pmid = 39587436 | doi = 10.1111/bcp.16349 }}</ref> Nausea and vomiting are important dose-limiting side effects of mescaline and occur at greater rates than with other psychedelics like [[LSD]] and [[psilocybin]].<ref name="KlaiberHumbert-DrozLey2024" /><ref name="KlaiberSchmidBecker2024" /><ref name="LeyHolzeArikci2023" /> High doses of mescaline, such as 800{{nbsp}}mg and above, are not well-tolerated due to substantial nausea and vomiting.<ref name="VogtLiechti2025" /><ref name="KlaiberSchmidBecker2024" /><ref name="KlaiberHumbert-DrozLey2024" /> On the other hand, mescaline appears to induce less [[fear]] and [[anxiety]] than LSD and psilocybin even at equivalent doses.<ref name="HolzeSinghLiechti2024" /><ref name="VogtLiechti2025">{{cite book | vauthors = Vogt SB, Liechti ME | date = 2025 | veditors = Nutt DJ, Thurgur H | chapter = Clinical Pharmacology | title = Psychedelics in Psychiatry | series = International Review of Neurobiology | location = London | publisher = Academic Press | volume = 181 | pages = 99–148 | isbn = 978-0-443-34386-5 | doi = 10.1016/bs.irn.2025.02.003 | pmid = 40541320 | chapter-url = https://books.google.com/books?id=zNcmEQAAQBAJ&pg=PA99 }}</ref><ref name="KlaiberHumbert-DrozLey2024" /> 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 | location = Oxford, England | 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 [[drug tolerance|tolerance]] development, including [[cross-tolerance]] with other psychedelics like [[LSD]] and [[psilocybin]].<ref name="Anderson1996" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="KapadiaFayez1970" /> 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" /><ref name="Anderson1996" /><ref name="KapadiaFayez1970" />

== Overdose ==
Only a single case of death due to mescaline, as [[peyote]], has been described, and was likely due to [[asphyxiation]] by [[vomit]] rather than [[overdose]] or [[toxicity]].<ref name="Thomas2024" /><ref name="Gable2004" /><ref name="Dart2004" /><ref name="NolteZumwalt1999" /><ref name="Trout2013" /> In terms of extrapolated human [[lethal dose]] based on [[animal study|animal studies]], the lethal dose of mescaline relative to a typical recreational dose has been estimated to be 24-fold or around 8,400{{nbsp}}mg.<ref name="Thomas2024">{{cite book | vauthors = Thomas K | date = 2024 | chapter = Toxicology and Pharmacological Interactions of Classic Psychedelics | title = Psychedelic Harm Reduction | series = Current Topics in Behavioral Neurosciences | publisher = Springer Berlin Heidelberg | volume = 77 | pages = 43–62 | isbn = 978-3-032-21106-4 | doi = 10.1007/7854_2024_508 | pmid = 39042251 | publication-place = Berlin, Heidelberg }}</ref><ref name="Gable2004">{{cite journal | vauthors = Gable RS | title = Comparison of acute lethal toxicity of commonly abused psychoactive substances | journal = Addiction | location = Abingdon, England | volume = 99 | issue = 6 | pages = 686–696 | date = June 2004 | pmid = 15139867 | doi = 10.1111/j.1360-0443.2004.00744.x | url = }}</ref><ref name="NolteZumwalt1999">{{cite journal | vauthors = Nolte KB, Zumwalt RE | title = Fatal peyote ingestion associated with Mallory-Weiss lacerations | journal = The Western Journal of Medicine | volume = 170 | issue = 6 | page = 328 | date = June 1999 | pmid = 10443159 | pmc = 1305682 | doi = | url = https://pmc.ncbi.nlm.nih.gov/articles/PMC1305682/pdf/westjmed00321-0010.pdf}}</ref> However, mescaline has reportedly been taken by humans at doses of up to 8,000{{nbsp}}mg without apparent [[adverse reaction|toxic reaction]]s.<ref name="Anderson1996">{{cite book | vauthors = Anderson EF | date = 1996 | title = Peyote: The Divine Cactus | publisher = University of Arizona Press | edition = 2 | isbn = 978-0-8165-1654-4 | url = https://books.google.com/books?id=p-YzEAAAQBAJ | archive-date = 22 September 2022 | archive-url = https://archive.org/details/peyotedivinecact0000ande | quote = Ruth Underhill (1952, 148) reported that humans have taken 8 grams of mescaline powder—more than ten times the usual dose—without apparent toxic reactions. }}</ref><ref name="Trout2013" /><ref name="Underhill1952">{{cite book | vauthors = Underhill RM | date = 1952 | chapter = Peyote | title = Proceedings of the Thirtieth International Congress of Americanists, Held in Cambridge, 18-23 August 1952 | location = London | publisher = Royal Anthropological Institute | pages = 143–148 | url = https://books.google.com/books?id=t4sTAAAAIAAJ&q=%22underhill%22+%22peyote%22 | archive-date = 30 June 2026 | archive-url = https://archive.org/details/peyote-underhill-1952/ | quote = [Our workers] intend to work with mescaline and not with peyote, which contains very little of it—1/10 gramme to a hundred buttons. The Indians at a meeting usually take eight buttons or 1/200 gramme. Even the greatest peyote user never boasts of more than thirty, or 1/33 gramme, while white experimenters with mescaline have taken eight whole grammes. }}</ref><ref name="Underhill1957">{{cite journal | vauthors = Underhill R | title = Religion Among American Indians | journal = The Annals of the American Academy of Political and Social Science | volume = 311 | issue = 1 | pages = 127–136 | date = 1 May 1957 | doi = 10.1177/000271625731100114 | quote = To produce any bad effects such as shortened respiration, at least 350 mgs. of mescaline are needed; white experimenters have taken as many as 700 without harm. The standard buttons (eight) taken at meetings contain only some 107 mgs. }}</ref> On the other hand, there is one unverified reported case of death due to 15,000{{nbsp}}mg [[intravenous injection|intravenously]], which would equate to about 150 to 200{{nbsp}}mg/kg.<ref name="Trout2013" /> The [[median lethal dose]] (LD<sub>50</sub>) of mescaline has 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 macaque]]s, among others.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Trout2013" /><ref name="Patel1968">{{cite journal | vauthors = Patel AR | title = Mescaline and related compounds | journal = Fortschritte Der Arzneimittelforschung. Progress in Drug Research. Progres Des Recherches Pharmaceutiques | volume = 11 | issue =  | pages = 11–47 | date = 1968 | pmid = 4873202 | doi = 10.1007/978-3-0348-7062-7_1 | url = }}</ref><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 that it would be difficult to take enough mescaline to cause death in humans.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Trout2013" /> No deaths due to peyote use have been reported aside from the asphyxiation case.<ref name="Slothower2014">{{cite book | vauthors = Slothower JD, Wiegand TJ | year = 2014 | veditors = Wexler P | chapter = Mescaline | title = Encyclopedia of Toxicology | publisher = Academic Press | edition = 3rd | pages = 221–222 | isbn = 978-0-12-386455-0 | doi = 10.1016/B978-0-12-386454-3.00747-8 | quote = There have been no reported deaths due to the physiological effects of peyote/mescaline. Traumatic deaths have occurred secondary to hallucinations. }}</ref><ref name="Trout2013" /><ref name="NolteZumwalt1999" /> The highest known dose of peyote taken is 90{{nbsp}}dried buttons.<ref name="Schultes1938">{{cite journal | vauthors = Schultes RE | title = The Appeal of Peyote (Lophophora Williamsii) as a Medicine | journal = American Anthropologist | volume = 40 | issue = 4 | pages = 698–715 | year = 1938 | doi = 10.1525/aa.1938.40.4.02a00100 | quote = In the ceremony, peyote is eaten dry, but occasionally fresh plants are consumed.16 The dried mescal buttons keep indefinitely and are stored in bags for use. They possess a very bitter taste, but in spite of this, they are chewed and swallowed in great number by peyotists. The smallest consumption by a single person is about four buttons at each meeting. It is impossible to estimate the largest, but I have seen an Indian eat more than thirty at one ceremony. Other investigators17 report doses as large as ninety buttons. An estimate of the average consumption, however, would probably be about twelve buttons by each person at a single meeting. }}</ref><ref name="Trout2013" /><ref name="Mooney1896">{{cite journal | vauthors = Mooney J | title = The Mescal Plant and Ceremony | journal = Therapeutic Gazette | date = 15 January 1896 | volume = 12 | issue = 1 | pages = 7–11 | url = https://scholar.google.com/scholar?cluster=14937694006741592826 | archive-url = https://archive.org/details/sim_therapeutic-gazette_1896-01-15_20_1/page/7/mode/1up | archive-date = 10 June 2026 | quote = The Indians say that no mental effect is produced by less than ten, which is probably true of the seasoned initiates. From twelve to twenty is a common number for one person in the course of the night, and many have eaten thirty or more on occasions. The man with the highest record among the Kiowas is said to have once eaten more than ninety at a single sitting, or nearly a pound and a half. I do not vouch for this, but believe it possible, as he is a recognized leader in the ceremony and powerfully built. The Indians themselves, however, admit that such a quantity is excessive and extraordinary. I have myself seen this man chew up ten, one after another, like so many lozenges, without pausing. I have never heard of any serious results from over-indulgence, and it may be that vomiting relieves the stomach in such cases.}}</ref>

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

The [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[receptor antagonist|antagonist]] [[ketanserin]] has been found to block the psychoactive effects of mescaline.<ref name="TabaacShinozukaFadel2026">{{cite journal | vauthors = Tabaac BJ, Shinozuka K, Fadel M, Jones G, Worchel J, Muir OS | title = Psychedelic Therapy: A Primer for Primary Care Clinicians-Mescaline | journal = American Journal of Therapeutics | volume = | issue =  | pages =  | date = June 2026 | pmid = 42299720 | doi = 10.1097/MJT.0000000000002160 | url = }}</ref><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> Similarly, the [[antipsychotic]] [[chlorpromazine]], which acts as both a [[dopamine]] [[D2 receptor|D<sub>2</sub> receptor]] [[receptor antagonist|antagonist]] and to a lesser extent as a serotonin 5-HT<sub>2A</sub> receptor antagonist, has been reported to reverse the psychoactive effects of mescaline.<ref name="TabaacShinozukaFadel2026" /><ref name="DenberMerlis1955">{{cite journal | vauthors = Denber HC, Merlis S | title = Studies on mescaline. VI. Therapeutic aspects of the mescaline-chlorpromazine combination | journal = The Journal of Nervous and Mental Disease | volume = 122 | issue = 5 | pages = 463–469 | date = November 1955 | pmid = 13320144 | doi = 10.1097/00005053-195511000-00008 | url = | quote = The effects of the injection of chlorpromazine have already been reported elsewhere (3). Tension and anxiety began to subside within minutes following the injection. In most pаtients the whole mescaline-induced state disappeared in one hour. One patient required a second injection of 50 mg. of chlorpromazine to terminate the state. The intense push and flow of thought abated slowly, and many patients became lethargic, drowsy and sleepy.}}</ref><ref name="DenberMerlis1956">{{cite book | vauthors = Denber HC, Merlis S | year = 1956 | veditors = Kline NS | chapter = Studies on mescaline IV: Antagonism between mescaline and chlorpromazine | title = Psychopharmacology | series = Publication No. 42 | location = Washington | publisher = American Association for the Advancement of Science | pages = 141–144 | archive-date = 28 May 2023 | archive-url = https://archive.org/details/psychopharmacolo0000amer/page/141/mode/1up | chapter-url = https://scholar.google.com/scholar?cluster=10420705778026562690 | quote = One hour after the injection of chlorpromazine hydrochloride all the signs and symptoms of the mescaline-induced state had disappeared. [...] Chlorpromazine hydrochloride directly antagonizes the effects of mescaline sulfate in non-epileptic patients as evidenced by changes in alpha activity, pulse, blood pressure, and pupillary diameters, as well as by the reversal of the abnormal psychic state due to mescaline. }}</ref><ref name="MerlisDenber1956">{{cite journal | vauthors = Merlis S, Denber HC | title = Studies on mescaline. V. Electroencephalgraphic evidence for the antagonism between mescaline and chlorpromazine hydrochloride | journal = The Journal of Nervous and Mental Disease | volume = 123 | issue = 6 | pages = 542–545 | date = June 1956 | pmid = 13406579 | doi = 10.1097/00005053-195606000-00005 | url = }}</ref> Other [[phenothiazine]]s, such as [[promethazine]] and [[diethazine]], have also been reported to antagonize the effects of mescaline in humans, whereas [[prochlorperazine]] was much less effective and [[promazine]] was ineffective.<ref name="Patel1968" /><ref name="Denber1958" /> [[Barbiturate]]s, which are [[GABAA receptor|GABA<sub>A</sub> receptor]] [[positive allosteric modulator]]s, have been found to abolish the [[anxiety]] induced by mescaline.<ref name="Patel1968" />

It is unclear whether mescaline is [[drug metabolism|metabolized]] by [[monoamine oxidase]] (MAO) [[enzyme]]s<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 inhibitor]]s (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 study|clinical studies]] of mescaline in combination with MAOIs are known to have been published.<ref name="RachedCampanaFiani2026" /> However, there are preliminary reports that [[harmala alkaloid]]s, 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 | chapter = Chapter 2: Mescaline and Chapter 3: Pharmacology & Metabolism of Mescaline | 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 = 81–104, 105–146 | url = https://troutsnotes.com/pdf/C13_CactusAlkaloids.pdf | chapter-url = https://isomerdesign.com/bitnest/external/TCA/81-146 }}</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 that do not also inhibit SSAO 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="Patel1968" /><ref name="FriedhoffGoldstein1962" />

== Pharmacology ==
=== Pharmacodynamics ===
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|Mescaline activities}}
|-
! [[Biological target|Target]] !! Affinity (K<sub>i</sub>, nM)
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 1,841–4,600
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || >10,000
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || >10,000
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || 5,205
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 550–17,400 (K<sub>i</sub>)<br />88–30,200 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}})<br />33–107% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 793–800 (K<sub>i</sub>)<br />1,100–>20,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />91% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 300–17,000 (K<sub>i</sub>)<br />20–19,500 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />22–109% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || >10,000
|-
| [[5-HT4 receptor|5-HT<sub>4</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || >10,000
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || >10,000
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || >10,000
|-
| [[α1A-adrenergic receptor|α<sub>1A</sub>]] || >15,000
|-
| [[α1B-adrenergic receptor|α<sub>1B</sub>]] || >10,000
|-
| [[α1D-adrenergic receptor|α<sub>1D</sub>]] || {{Abbr|ND|No data}}
|-
| [[α2A-adrenergic receptor|α<sub>2A</sub>]] || 1,400–8,930
|-
| [[α2B-adrenergic receptor|α<sub>2B</sub>]] || >10,000
|-
| [[α2C-adrenergic receptor|α<sub>2C</sub>]] || 745
|-
| [[β1-adrenergic receptor|β<sub>1</sub>]]–[[β2-adrenergic receptor|β<sub>2</sub>]] || >10,000
|-
| [[D1 receptor|D<sub>1</sub>]] || >10,000
|-
| [[D2 receptor|D<sub>2</sub>]] || >10,000
|-
| [[D3 receptor|D<sub>3</sub>]] || >17,000
|-
| [[D4 receptor|D<sub>4</sub>]] || >10,000
|-
| [[D5 receptor|D<sub>5</sub>]] || >10,000
|-
| [[H1 receptor|H<sub>1</sub>]]–[[H4 receptor|H<sub>4</sub>]] || >10,000
|-
| [[Muscarinic acetylcholine M1 receptor|M<sub>1</sub>]]–[[Muscarinic acetylcholine M5 receptor|M<sub>5</sub>]] || >10,000
|-
| [[Trace amine-associated receptor 1|TAAR<sub>1</sub>]] || 3,300 (K<sub>i</sub>) (rat)<br />11,000 (K<sub>i</sub>) (mouse)<br />3,700–4,800 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) (rodent)<br />>10,000 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}}) (human)
|-
| [[Imidazoline I1 receptor|I<sub>1</sub>]] || 2,678
|-
| [[Sigma-1 receptor|σ<sub>1</sub>]]–[[Sigma-2 receptor|σ<sub>2</sub>]] || >10,000
|-
| {{Abbrlink|SERT|Serotonin transporter}} || >30,000 (K<sub>i</sub>)<br />367,000 ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}})
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || >30,000 (K<sub>i</sub>)<br />>900,000 ({{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}})
|-
| {{Abbrlink|DAT|Dopamine transporter}} || >30,000 (K<sub>i</sub>)<br />841,000 ({{Abbr|IC<sub>50</sub>|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" /><br /><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 }}</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 | title = Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential | journal = Nature Communications | volume = 14 | issue = 1 | article-number = 8221 | date = December 2023 | pmid = 38102107 | pmc = 10724237 | doi = 10.1038/s41467-023-44016-1 | 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>
|}

Mescaline acts as an [[agonist]] of the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] to produce its [[psychedelic drug|psychedelic]] effects.<ref name="Nichols_2004">{{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><ref name="Monte_1997">{{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="Appel_1989">{{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><ref name="KlaiberSchmidBecker2024">{{cite journal | vauthors = Klaiber A, Schmid Y, Becker AM, Straumann I, Erne L, Jelusic A, Thomann J, Luethi D, Liechti ME | 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 | date = September 2024 | pmid = 39349427 | pmc = 11442856 | doi = 10.1038/s41398-024-03116-2 | quote = [...] a 500 mg dose of mescaline hydrochloride produced comparable effects to 100 µg LSD base or 20 mg psilocybin dihydrate when they were compared within the same study and subjects [14]; [...] Dosages ranging from 178 to 356 mg of mescaline hydrochloride are considered moderate [36]. }}</ref> Its {{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} at the serotonin 5-HT<sub>2A</sub> receptor is approximately 10,000{{nbsp}}nM and at the serotonin [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]] is greater than 20,000{{nbsp}}nM.<ref name="VamvakopoulouNarineCampbell2023" /> How activating the 5-HT<sub>2A</sub> 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="Béïque_2007">{{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-HT<sub>2A</sub> and 5-HT<sub>2B</sub> receptors, mescaline is also known to bind to the serotonin [[5-HT2C receptor|5-HT<sub>2C</sub> receptor]] and a number of other [[biological target|target]]s.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="RickliMoningHoener2016" /><ref name="Ray2010" /> The drug shows pronounced [[biased agonism]] at the serotonin 5-HT<sub>2C</sub> 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 transporter]]s, including the [[serotonin transporter]] (SERT), [[norepinephrine transporter]] (NET), and [[dopamine transporter]] (DAT) (K<sub>i</sub> > 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" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><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 [[serotonin reuptake inhibitor|inhibit the reuptake]] and/or [[serotonin releasing agent|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 [[dopamine releasing agent|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 [[drug addiction|addiction]] or [[drug dependence|dependence]].<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Mescaline appears to be inactive in terms of [[norepinephrine releasing agent|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 (psychedelics)|2C]], [[DOx]], and [[trimethoxyamphetamine|TMA]] drugs, are inactive as [[monoamine releasing agent]]s and [[monoamine reuptake inhibitor|reuptake inhibitor]]s.<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 | location = Berl | 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 [[structural analog|analogue]] of mescaline, which is a very low-[[potency (pharmacology)|potency]] [[serotonin releasing agent]] ({{Abbrlink|EC<sub>50</sub>|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 [[Substituted phenethylamine|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-HT<sub>2A</sub> receptor.<ref name="CasselsSáez-Briones2018" /><ref name="VamvakopoulouNarineCampbell2023" /> For comparison, [[psilocybin]] is approximately 25-fold more potent (doses in the tens of milligrams) and [[lysergic acid diethylamide]] (LSD) is approximately 5,000-fold more potent (doses in the tens to hundreds of micrograms).<ref name="VogtLiechti2025" /><ref name="VamvakopoulouNarineCampbell2023" /> There have been efforts to develop more potent [[structural analogue|analogue]]s of mescaline.<ref name="CasselsSáez-Briones2018" /><ref name="PiHKAL" /><ref name="Trachsel2012" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="StoeckmannOstertagTrachsel2026">{{cite journal | vauthors = Stoeckmann OV, Ostertag S, Trachsel D, Liechti ME, Rudin D | title = Scalines: novel mescaline analogues targeting 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors | journal = Neuroscience Applied | volume = 5 | article-number = 106565 | date = 2026 | doi = 10.1016/j.nsa.2025.106565 | doi-access = free }}</ref> [[Difluoromescaline]] and [[trifluoromescaline]] are more potent than mescaline, as is its amphetamine [[homologous series|homologue]] TMA.<ref name="Trachsel2012">{{cite journal |vauthors=Trachsel D |year=2012 |title=Fluorine in psychedelic phenethylamines |url=http://bitnest.ca/external.php?id=%257DbxUgXXCNAUj%257E%257E%2507 |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="TrachselLehmannEnzensperger2013" /><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="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="Nichols1986">{{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>

It is unclear why mescaline produces more [[nausea]] and [[vomiting]] than other psychedelics like LSD and psilocybin.<ref name="KlaiberHumbert-DrozLey2024" /> In any case, the serotonin 5-HT<sub>2A</sub> receptor antagonist [[ketanserin]] blocked not only the psychoactive but also the physical side effects of mescaline including nausea and vomiting, suggesting that these effects may be mediated by serotonin 5-HT<sub>2A</sub> receptor activation.<ref name="KlaiberSchmidBecker2024" />

There is no evidence of acute [[drug tolerance|tolerance]] with mescaline.<ref name="MuellerKlaiberLey2025" /> However, tolerance to mescaline builds with repeated use, lasting for a few days.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Anderson1996" /><ref name="KapadiaFayez1970" /> The drug causes [[cross-tolerance]] with other psychedelics like LSD and psilocybin.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Anderson1996" /><ref name="KapadiaFayez1970" />

The [[cryo-EM]] [[protein–ligand complex|structure]]s of the serotonin 5-HT<sub>2A</sub> receptor with mescaline, as well as with various other psychedelics and serotonin 5-HT<sub>2A</sub> 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 | title = The structural diversity of psychedelic drug actions revealed | journal = Nature Communications | volume = 16 | issue = 1 | article-number = 2734 | date = March 2025 | pmid = 40108183 | pmc = 11923220 | doi = 10.1038/s41467-025-57956-7 | 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 [[oral administration|orally]], although it may also be [[insufflation|insufflated]], [[inhalational administration|smoked]], or given [[intravenous injection|intravenously]].<ref name="Dinis-OliveiraPereiradaSilva2019" /> Taken orally, it is rapidly [[absorption (pharmacokinetics)|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" /> [[Cmax (pharmacology)|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 administration|oral]] dose range of 100 to 800{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="KlaiberSchmidBecker2024" />

==== Distribution ====
Mescaline is [[distribution (pharmacology)|distributed]] to the [[liver]], [[spleen]], and [[kidney]]s 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 of action|onset]] and [[elimination half-life]].<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="VamvakopoulouNarineCampbell2023" /> The exact portion [[plasma protein binding|bound to plasma proteins]] seems to be unknown, but appears to be minimal.<ref name="DrugBank" /><ref name="Dart2004">{{cite book | vauthors = Dart RC | date = 2004 | title = Medical Toxicology | publisher = Lippincott Williams & Wilkins | edition = 3 | page = 1706 | isbn = 978-0-7817-2845-4 | url = https://books.google.com/books?id=BfdighlyGiwC&pg=PA1706 | archive-date = 29 March 2022 | archive-url = https://archive.org/details/medicaltoxicolog0000unse/page/1706/ | quote = Mescaline binds to liver proteins but not to plasma proteins. It is rapidly and widely distributed into the peripheral tissues. The volume of distribution is not specifically known but is believed to be on the order of several L/kg. }}</ref><ref name="OhLeitchAxelrod1967" />

Mescaline appears to have relatively poor [[blood–brain barrier]] [[drug permeability|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><ref name="VogtLiechti2025" /> 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 (pharmacology)|potency]].<ref name="MuellerKlaiberLey2025" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="VogtLiechti2025" /><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 | location = Berl | volume = 196 | issue = 1 | pages = 51–62 | date = January 2008 | pmid = 17922234 | doi = 10.1007/s00213-007-0926-5 | url = }}</ref>

==== Metabolism ====
[[File:Metabolism of mescaline.png|thumb|right|500px|class=skin-invert-image|[[Drug metabolism|Metabolism]] of mescaline in humans and/or animals.<ref name="Dinis-OliveiraPereiradaSilva2019" />]]

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 [[drug metabolism|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 [[enzyme]]s 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 research|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 (biochemistry)|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 [[metabolic intermediate|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 = American Journal of Pharmacy and the Sciences Supporting 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> [[β-Hydroxymescaline]] may also be a minor [[metabolite]] of mescaline formed by [[dopamine β-hydroxylase]] (DBH), though this remains unclear.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="TangXuGuo2025">{{cite journal | vauthors = Tang Y, Xu L, Guo Z, Zhao J, Xiao Y, Xiang P, Xu L, Yan H | title = Metabolism study of two phenethylamine - derived new psychoactive substances using in silico, in vivo, and in vitro approaches | journal = Archives of Toxicology | volume = 99 | issue = 6 | pages = 2367–2378 | date = June 2025 | pmid = 40064698 | doi = 10.1007/s00204-025-04010-6 | url = | quote = Previous studies have suggested that mescaline could be bioactivated by dopamine-β-hydroxylase, similar to the activation of some biogenic amines, which would lead to the formation of β-hydroxymescaline (Goldstein and Contrera 1962). Taking both the literature results and the actual results from this study into consideration, the reaction position of monohydroxylation of proscaline and methallylescaline was concluded to be on the β-carbon, which was consistent with the fragment ion analysis.}}</ref><ref name="CrevelingDalyWitkop1962">{{cite journal | vauthors = Creveling CR, Daly JW, Witkop B, Undenfriend S | title = Substrates and inhibitors of dopamine-beta-oxidase | journal = Biochimica et Biophysica Acta | volume = 64 | pages = 125–134 | date = October 1962 | pmid = 14023834 | doi = 10.1016/0006-3002(62)90765-5 }}</ref>

Mescaline appears not to be subject to metabolism by [[CYP2D6]] based on ''in-vitro'' studies with human liver microsomes.<ref name="Wu_1997">{{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 inhibitor]]s.<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 | location = Basel, Switzerland | 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 [[Cmax (pharmacology)|peak]] and [[area-under-the-curve (pharmacokinetics)|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|''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 metabolite]]s 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 = Biological & Pharmaceutical Bulletin | 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 = Annals of the New York Academy of Sciences | 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="PiHKAL" /><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 group|methyl]] [[structural analog|analogue]] of mescaline and an MAO-resistant psychedelic, is only about twice as [[potency (pharmacology)|potent]] as mescaline as a psychedelic in humans despite having similar [[serotonin receptor]] [[affinity (pharmacology)|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 (psychedelics)|2C]] series of psychedelics.<ref name="Nichols1981" /> Another analogue of mescaline, the [[deuterated drug|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 | series = Nachtschatten-Science | location = Solothurn | 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 | 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 [[excretion|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|''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 | quote = As for its limitations; we failed to achieve instant dose equivalence, leading to a subsequent increase in the mescaline dose from 300 to 500 mg. The study thus tested two doses of mescaline against LSD and psilocybin.}}</ref><ref name="KlaiberSchmidBecker2024" /><ref name="MuellerKlaiberLey2025" /> The previous higher estimate is believed to have been due to small [[sample size|sample numbers]] and collective measurement of mescaline metabolites.<ref name="LeyHolzeArikci2023" /> The elimination half-life of mescaline does not appear to be [[dose dependence|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 of action|duration]].<ref name="HolzeSinghLiechti2024" /> This is due to mescaline having slower [[absorption (pharmacokinetics)|absorption]] and [[onset of action|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]] [[chemical derivative|derivative]].<ref name="PubChem">{{cite web | author = PubChem | 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 [[structural analog|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 primarily on the [[serotonin|serotonergic]] system rather than on the [[dopaminergic]] or [[adrenergic]] systems.<ref name="CasselsSáez-Briones2018" />

=== Properties ===
[[File:Synthetic mescaline powder i2001e0151 ccby3.jpg|thumb|right|200px|A sample of pure mescaline.]]

The physical properties and general chemistry of mescaline have been reviewed.<ref name="Patel1968" /> The compound is relatively [[hydrophilic]] with low [[lipophilicity|fat solubility]].<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Its predicted [[partition coefficient|log P]] ([[XLogP3]]) is 0.7.<ref name="PubChem" />

=== Synthesis ===
Mescaline was first ever psychedelic drug synthesized by chemists.<ref name="Jay2019" /> [[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:<ref name="Trout2013" /><ref name="KapadiaFayez1970" />

* [[Hofmann rearrangement]] of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}propionamide.<ref name="SlottaHeller1930">{{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-trimethoxybenzaldehyde|3,4,5-trimethoxy{{shy}}benz{{shy}}aldehyde]] followed by [[acetylation]] and [[Organic redox reaction|reduction]].<ref name="Amos1964">{{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 name="KindlerPeschke1932">{{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 [[Reduction of nitro compounds|nitro compound reduction]] of ω-nitro{{shy}}trimethoxy{{shy}}styrene.<ref name="BeningtonMorin1951">{{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 name="HahnRumpf1938">{{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 name="ToshitakaHiroaka1992">{{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 name="RamirezErne1950">{{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 name="SzyszkaSlotta1933">{{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 name="BurgerRamirez1950">{{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 name="HahnWassmuth1934">{{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>
* [[Carbonyl reduction#Ester reduction|Ester reduction]] of [[Eudesmic acid]]'s [[methyl group|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 name="DornowPetsch1952">{{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 name="Ikan1991">{{cite book | vauthors = Ikan R | year = 1991 | title = Natural Products: A Laboratory Guide 2nd Ed | location = San Diego | publisher = Academic Press, Inc. | pages = 232–235 | isbn = 978-0-12-370551-8 | url = https://books.google.com/books?id=B7P8HQimBAIC&pg=PA243 }}</ref>
* [[Amide reduction]] of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}acetamide.<ref name="BanholzerCampbellSchmid1952">{{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 [[Tetrahydrofuran|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 analogue]]s of mescaline that act as psychedelics have been developed.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> These drugs often have far greater [[potency (pharmacology)|potency]] than mescaline itself.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> Examples include [[scaline]]s like [[escaline]], [[3C (psychedelics)|3C]]s like [[3,4,5-trimethoxyamphetamine]] (TMA or TMA-1; α-methylmescaline), [[2C (psychedelics)|2Cs]] like [[2C-B]], and [[DOx]] drugs like [[DOM (drug)|DOM]], among others.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> Other notable analogues of mescaline include [[N-methylmescaline|''N''-methylmescaline]] (found in ''[[Pachycereus pringlei]]''), [[trichocereine]] (''N'',''N''-dimethylmescaline), [[mescaline-FLY]], and [[NBOMe-mescaline]], among others.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" /> [[Deuterated drug|Deuterated]] [[isotopologue]]s of mescaline include [[α-D]] (α,α-dideuteromescaline), [[β-D]] (β,β-dideuteromescaline), [[α,β-D]] (α,β-dideuteromescaline), and [[4-D (drug)|4-D]] (4-trideuteromescaline), among others.<ref name="PiHKAL" /><ref name="TrachselLehmannEnzensperger2013" />

== Natural occurrence ==
[[File:Troncos de cactus Echinopsis pachanoi.jpg|thumb|''[[Trichocereus pachanoi]]'' (San Pedro cactus) in [[Peru]].]]
[[File:Dried Peyote.jpg|thumb|250px|Dried [[peyote]] (''Lophophora williamsii''), containing ~5 to 6% mescaline by weight.]]

Mescaline has been [[chemical isolation|isolated]] from numerous [[cactus]] species, including ''[[Echinopsis]]'' (''Trichocereus''), ''[[Gymnocalycium]]'', ''[[Lophophora]]'', ''[[Opuntia]]'', ''[[Stenocereus]]'', and ''[[Turbinicarpus]]'' species, among others.<ref name="Trout2013" /> It occurs at the highest known concentrations in ''[[Lophophora williamsii]]'' (peyote), where it is highly variable but makes up 0.1 to 0.255% fresh weight and 0.9 to 6.3% of dry weight.<ref name="Trout2013" /> Levels of mescaline are much lower in other ''Lophophora'' species.<ref name="Trout2013" /> The compound also occurs in relatively high concentrations in various ''Echinopsis'' species, for instance ''[[Echinopsis pachanoi]]'' ([[San Pedro cactus]]), ranging from 0.02 to 0.12% fresh weight and 0.331 to 2.0% dry weight in this species.<ref name="Trout2013" /> Mescaline occurs in only small or trace amounts in most other cactus species in which it has been detected.<ref name="Trout2013" />

{|class="wikitable"
|+ Mescaline content in selected cactus species<ref name="Trout2013" />
|-
! 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="OgunMcCoTrouDale10" />
|-
| ''[[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}}</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>
|-
| ''[[Lophophora williamsii]]'' (peyote)<ref name="Bib">{{cite book | year = 2007 | title = Drug Identification Bible | location = Grand Junction, CO | publisher = Amera-Chem, Inc. | isbn = 978-0-9635626-9-2 }}</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}}</ref> 0.24–0.81%<ref name="OgunMcCoTrouDale10" /> 
|-
| [[Trichocereus macrogonus var. pachanoi|''Trichocereus macrogonus'' var. ''pachanoi'']] (San Pedro cactus, syns ''Echinopsis pachanoi'', ''Echinopsis santaensis'', ''Trichocereus pachanoi'')<ref name="CrosbyMcLaughlin1973">{{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="OgunMcCoTrouDale10" /> 0.32% under its synonym ''Echinopsis santaensis''<ref name="OgunMcCoTrouDale10" />
|-
| ''[[Trichocereus uyupampensis]]'' (syn. ''Echinopsis uyupampensis'') || 0.05%<ref name="OgunMcCoTrouDale10" />
|-
| ''[[Echinopsis tacaquirensis|Trichocereus tacaquirensis]] (subsp. taquimbalensis syn. Trichocereus taquimbalensis)''
| 0.005–2.7%<ref name="TheMescalinGarden">{{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 }}</ref>
|}

As shown in the accompanying table, the concentration of mescaline in different specimens can vary largely within a single species.<ref name="Trout2013" /> Moreover, the concentration of mescaline within a single specimen varies as well.<ref name="VanDerSypt2022">{{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 peyote, mescaline constitutes about 30% of total alkaloid content.<ref name="KapadiaFayez1973">{{cite journal | vauthors = Kapadia GJ, Fayez MB | title = The chemistry of peyote alkaloids | journal = Lloydia | volume = 36 | issue = 1 | pages = 9–35 | date = March 1973 | pmid = 4593882 | url = https://bibliography.maps.org/resources/download/13922 | archive-date = 27 June 2026 | archive-url = https://web.archive.org/web/20260627045833/https://bibliography.maps.org/resources/download/13922 }}</ref><ref name="BruhnHolmstedt1973" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Lundström1971" /> For comparison, the alkaloid contents of other major constitutes include [[pellotine]] 17%, [[anhalonidine]] 14%, [[anhalamine]] 8%, [[hordenine]] 8%, and [[lophophorine]] 5%.<ref name="KapadiaFayez1973" /><ref name="BruhnHolmstedt1973" /><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Lundström1971">{{cite journal | vauthors = Lundström J | title = Biosynthetic studies on mescaline and related cactus alkaloids | journal = Acta Pharmaceutica Suecica | volume = 8 | issue = 3 | pages = 275–302 | date = June 1971 | pmid = 5560272 | doi = | url = }}</ref> 

It has also reported to be found in small amounts in certain members of the bean family, [[Fabaceae]], including ''[[Senegalia berlandieri]]'' (syn. ''Acacia berlandieri''),<ref name="ForbesClement">{{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 }}</ref> although these reports have been challenged and have been unsupported in any additional analyses.<ref name="Trout2013" /><ref name="Trout2015">{{cite web | author = [[Keeper Trout]] | date = 16 January 2015 | title = Acacia species with data conflicts | publisher = sacredcacti.com | url = https://sacredcacti.com/blog/acacia/ | access-date = 13 March 2021 }}</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 [[antioxidant]]s, 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" />

=== Biosynthesis ===
[[File:Mescaline biosynthetic pathways.svg|class=skin-invert-image|thumb|right|400px|[[Biosynthesis]] of mescaline.]]

Mescaline is [[biosynthesis|biosynthesized]] from [[tyrosine]], which, in turn, is derived from [[phenylalanine]] by the [[enzyme]] [[phenylalanine hydroxylase]].<ref name="CasselsSáez-Briones2018" /><ref name="WangWangLin2026" /><ref name="Trout2013" /> In ''[[Lophophora williamsii]]'' (peyote), [[dopamine]] converts into mescaline in a [[biosynthetic pathway]] involving ''m''-''O''-[[methylation]] and [[aromatic compound|aromatic]] [[hydroxylation]].<ref name="Dewick2009">{{cite book | vauthors = Dewick PM | year = 2009 | title = Medicinal Natural Products: A Biosynthetic Approach | location = United Kingdom | publisher = John Wiley & Sons | pages = 335–336 | isbn = 978-0-471-49641-0 }}</ref>

Tyrosine and phenylalanine serve as [[metabolic precursor]]s 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 [[phenol|monophenol]] [[hydroxylase]] or first be hydroxylated by [[tyrosine hydroxylase]] to form [[L-DOPA|<small>L</small>-DOPA]] and decarboxylated by [[DOPA decarboxylase]]. These create dopamine, which then experiences methylation by a [[catechol-O-methyltransferase|catechol-''O''-methyltransferase]] (COMT) by an [[S-Adenosyl methionine|''S''-adenosyl methionine]] (SAM)-dependent mechanism. The resulting [[metabolic intermediate|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 <small>L</small>-tyrosine by [[L-amino acid hydroxylase|<small>L</small>-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}}

[[File:Estela Wachumero en Chavin.jpg|thumb|right|200px|The [[stela of the cactus bearer]], a piece of [[ancient Peru|ancient Peruvian]] art depicting the [[San Pedro cactus]].]]

[[Archaeological evidence]] from sites in the [[United States]], [[Mexico]], and [[Peru]] indicates that mescaline-containing [[cactus|cacti]] have been used for over 6,000{{nbsp}}years.<ref name="CasselsSáez-Briones2018" /> [[European people|European]]s recorded use of [[peyote]] in [[Native American]] [[religious ceremony|religious ceremonies]] upon early contact with the [[Huichol people]] in Mexico.<ref name="RuizdeAlarcón1984">{{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 cactus]] have a long history of use in [[South America]], from Peru to [[Ecuador]].<ref name="SochaSykuteraOrefici2022">{{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 name="BussmannSharon2006">{{cite journal | vauthors = Bussmann RW, Sharon D | 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 | date = November 2006 | pmid = 17090303 | pmc = 1637095 | doi = 10.1186/1746-4269-2-47 | doi-access = free }}</ref><ref name="Armijos_2014">{{cite journal | vauthors = Armijos C, Cota I, González S | 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 | date = February 2014 | pmid = 24565054 | pmc = 3975971 | doi = 10.1186/1746-4269-10-26 | doi-access = free }}</ref><ref name="Samorini2019">{{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 people|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>

[[File:Arthur Carl Wilhelm Heffter.jpg|thumb|left|175px|[[Arthur Heffter]], the chemist who isolated mescaline and discovered its effects.]]

Peyote was first described by [[Bernardino de Sahagún]] in 1560.<ref name="Patel1968" /><ref name="KapadiaFayez1970" /> It was first scientifically named as ''Peyotl zacatensis'' by [[Francisco Hernández]] in 1638.<ref name="KapadiaFayez1970" /> 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" /><ref name="BruhnHolmstedt1973" /><ref name="Briggs1887">{{cite journal | vauthors = Briggs JR | title = "Muscale Buttons"—Physiological Effects—Personal Experience | journal = The Medical Register | volume = 1 | issue =   | date = 8 April 1887 | pages = 267–268 | url = https://bibliography.maps.org/resources/download/12878| archive-url = https://web.archive.org/web/20250405031456/https://bibliography.maps.org/resources/download/12878 | archive-date = 5 April 2025 }}</ref> However, he took a very low dose of the drug, and in the modern literature, the symptoms he experienced have been attributed to a severe [[panic attack]] in response to the drug.<ref name="Perrine2001" /><ref name="Briggs1887" /> 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 name="Anderson1996" /> The effects of mescaline in humans were first properly described by D. W. Prentiss and Francis P. Morgan in 1895.<ref name="BruhnHolmstedt1973">{{cite journal | vauthors = Bruhn JG, Holmstedt B | date = 1973 | title = Early peyote research an interdisciplinary study | journal = Economic Botany | volume = 28 | issue = 4 | pages = 353–390 | doi = 10.1007/BF02862854 | issn = 0013-0001 | quote = The spark that was to ignite the "peyote boom" was not lit until 1887 when Briggs published the first study of the effects of "muscale buttons". [...] Early peyote research is closely connected with the name of Louis Lewin. However, he was not the discoverer of the drug. Credit for having brought peyote to the attention of the medical world of the 1880's must go to Dr. John Raleigh Briggs of Dallas, Texas. An instrumental role was also played by the pharmaceutical manufacturers Parke, Davis & Company of Detroit. [...] Mrs. Nickels was long considered to be the first supplier of "mescal buttons" for scientific study, but Slotkin (1955, p. 222, note 7) rejected this and pointed out that Briggs was the pioneer (cf. Bender, 1968). [...] In 1894, however, Prentiss and Morgan (1895) of the Medical Department of Columbian University in Washington obtained a large supply of mescal buttons through James Mooney, "agent among the Indians". They described six experiments in man with the crude drug. "The production of visions" was the most interesting effect found, and the authors concluded that the action of Anhalonium lewinii was not identical with that of any other drug. Except for Briggs' early (and somewhat dubious) self-experiment, these were the first reported studies of the drug in man. [...] The first person to draw the attention of the scientific world to peyote was doubtless Dr. J. R. Briggs, and not Mrs. A. B. Nickels as is often stated. }}</ref><ref name="PrentissMorgan1895">{{cite journal | vauthors = Prentiss DW, Morgan FP | title = Anhalonium Lewinii (Mescal Buttons). A Study of the Drug, With Especial Reference to its Physiological Action Upon Man, With Report of Experiments | journal = Therapeutic Gazette | volume = 19 | issue =   | pages = 577–585 | date = 16 September 1895 | url = https://collections.nlm.nih.gov/catalog/nlm:nlmuid-101751140-bk | archive-url = https://web.archive.org/web/20260610035248/https://bibliography.maps.org/resources/download/14843 | archive-date = 10 June 2026}}</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 [[pharmacological activity|active]].<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Mescaline was first [[chemical synthesis|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>

Three major books on mescaline and/or peyote were published in the mid-to-late 1920s.<ref name="Jay2019">{{cite book | vauthors = Jay M | date = 18 June 2019 | title = Mescaline: A Global History of the First Psychedelic | publisher = Yale University Press | isbn = 978-0-300-23107-6 | url = https://books.google.com/books?id=6IKVDwAAQBAJ }}</ref><ref name="McKenna1999">{{cite book | vauthors = McKenna T | date = 1999 | chapter = [Chapter 14:] A Brief History of Psychedelics | title = Food of the Gods: The Search for the Original Tree of Knowledge: a Radical History of Plants, Drugs and Human Evolution | publisher = Rider | pages = 223–245 | isbn = 978-0-7126-7038-8 | url = https://alquimiahealingarts.com/wp-content/uploads/2020/03/Food-Of-The-Gods-Terence-Mckenna.pdf#page=117 }}</ref> These included [[French people|French]] [[pharmacist]] [[Alexandre Rouhier]]'s ''[[Le Peyotl: La Plante Qui Fait les Yeux Émerveillés]]'' (''Peyote: The Plant That Fills the Eyes with Marvels'') in 1927,<ref name="Jay2019" /><ref name="DubusGrandgeorgeVerroust2023">{{cite journal | vauthors = Dubus Z, Grandgeorge E, Verroust V | title = History of the administration of psychedelics in France | journal = Frontiers in Psychology | volume = 14 | issue =  | article-number = 1131565 | date = 2023 | pmid = 37744588 | pmc = 10513055 | doi = 10.3389/fpsyg.2023.1131565 | doi-access = free | url = | quote = In the 1920s, the pharmacologist Alexandre Rouhier captured the attention of the French and international scientific communities, first through his important monograph on the uses of peyote, which was translated several times, and later through his pharmaceutical preparations. [...] Alexandre Rouhier: the totality of peyote's alkaloids, for a polyvalent therapeutic action: The 1927 appearance of pharmacist Alexandre Rouhier's Le Peyotl: la plante qui fait les yeux émerveillés (Peyote: The Plant That Fills the Eyes with Marvels) was a success considering its somewhat obscure subject matter (Rouhier, 1927). [...]}}</ref><ref name="Perrine2001" /><ref name="Rouhier1927">{{cite book | vauthors = Rouhier A | date = 1927 | title = Le Peyotl: La Plante Qui Fait les Yeux Émerveillés | language = fr | publisher = Doin | url = https://books.google.com/books?id=aQqJHAAACAAJ | access-date = 26 June 2026 | archive-date = 14 March 2024 | archive-url = https://archive.org/details/alexandre-rouhier-peyotl/ | trans-title = Peyote: The Plant That Fills the Eyes with Marvels }}</ref> the [[German people|German]] [[psychiatrist]] [[:de:Kurt Beringer|Kurt Beringer]]'s ''[[Der Meskalinrausch, seine Geschichte und Erscheinungsweise]]'' (''Mescaline Intoxication, its History and Manifestation'') in 1927,<ref name="Jay2019" /><ref name="McKenna1999" /><ref name="Beringer1927">{{cite book | vauthors = Beringer K | date = 1927 | title = Der Meskalinrausch, seine Geschichte und Erscheinungsweise | language = de | series = Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie | publisher = Julius Springer | volume = 49 | isbn = 978-3-540-04660-8 | doi = 10.1007/978-3-662-11451-3 | trans-title = Mescaline Intoxication, its History and Manifestation | oclc = 2536666 }}</ref> and German–[[American people|American]] [[psychologist]] [[Heinrich Klüver]]'s ''[[Mescal: The Divine Plant and Its Psychological Effects]]'' in 1928.<ref name="Jay2019" /><ref name="McKenna1999" /><ref name="Klüver1928">{{cite book | vauthors = Klüver H | date = 1928 | title = Mescal: The ʻDivine' Plant and Its Psychological Effects | publisher = K. Paul, Trench, Trubner & Company Limited | url = https://books.google.com/books?id=oZYaAAAAIAAJ | archive-date = 24 June 2026 | archive-url = https://www.samorini.it/doc1/alt_aut/ek/kluver-mescal-the-divine-plant-and-its-psychological-effects.pdf }}</ref>

Studies of the potential therapeutic effects of mescaline started in the 1950s.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> It was studied as part of [[psychedelic-assisted psychotherapy]] by Walter Frederking by 1953.<ref name="Patel1968" /><ref name="KapadiaFayez1970" /><ref name="Frederking1953">{{cite journal | vauthors = Frederking W | title = Über die Verwendung von Rauschdrogen (Meskalin und Lysergsäurediaethylamid) in der Psychotherapie | trans-title = The use of narcotics (mescaline and lysergic acid diethylamide) in psychotherapy | language = de | journal = Psyche (Stuttg) | volume = 7 | issue = 6 | pages = 342–364 | date = September 1953 | pmid = 13112311 <!-- | doi = 10.5555/ps-7-6-342 --> | url = https://elibrary.utb.de/doi/10.5555/ps-7-6-342}}</ref><ref name="Frederking1955">{{cite journal | vauthors = Frederking W | title = Intoxicant drugs (mescaline and lysergic acid diethylamide) in psychotherapy | journal = The Journal of Nervous and Mental Disease | volume = 121 | issue = 3 | pages = 262–266 | date = March 1955 | pmid = 14381913 | doi = 10.1097/00005053-195503000-00010 | url = }}</ref> [[Aldous Huxley]]'s book ''[[The Doors of Perception]]'', about his experience with mescaline, was published in 1954.<ref name="Dyck2025">{{cite journal | vauthors = Dyck E | date = 1 April 2025 | title = History of Psychedelics: An Overview | journal = South Atlantic Quarterly | volume = 124 | issue = 2 | pages = 295–305 | doi = 10.1215/00382876-11626609 | issn = 0038-2876 }}</ref> In 1955, English politician [[Christopher Mayhew]] took part in an experiment for [[BBC]]'s ''[[Panorama (TV series)|Panorama]]'', in which he ingested 400{{nbsp}}mg of mescaline under the supervision of psychiatrist [[Humphry Osmond]].<ref name="Jay2019" /><ref name="WalkerPullella2023">{{cite journal | vauthors = Walker SR, Pullella GA, Piggott MJ, Duggan PJ | title = Introduction to the chemistry and pharmacology of psychedelic drugs | journal = Australian Journal of Chemistry | volume = 76 | issue = 5 | pages = 236–257 | date = 17 July 2023 | doi = 10.1071/CH23050 | issn = 0004-9425 | quote = In 1955, mescaline (4) even gained the attention of British politician Christopher Mayhew, who participated in an 'experiment' in which he was recorded after being administered mescaline (4). The footage of Mayhew was to be televised on the BBC programme Panorama; however, the broadcaster decided against airing it. Mayhew later described the experiment as 'the most interesting thing [he has] ever done' and 'profoundly thought-provoking'.[80] }}</ref><ref name="BBC2021">{{cite web | title=The History Hour, Why a British MP was filmed taking mescaline | website=BBC | date=15 May 2021 | url=https://www.bbc.co.uk/programmes/w3ct1z6v | access-date=26 June 2026}}</ref><ref name="SOTCAA2005" /> 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" and saying that it was "profoundly thought-provoking".<ref name="Jay2019" /><ref name="WalkerPullella2023" /><ref name="BBC2021" /><ref name="SOTCAA2005">{{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>

The mechanism of action of mescaline, activation of the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]]s, became fully known in the 1990s.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> A serotonin 5-HT<sub>2A</sub> receptor antagonist, specifically [[ketanserin]], was first clearly shown to block the psychedelic effects of mescaline in humans by [[Matthias Liechti]] and colleagues in 2024.<ref name="KlaiberSchmidBecker2024" />

The [[history]] of mescaline was reviewed in the 2019 book ''[[Mescaline: A Global History of the First Psychedelic]]'' by [[cultural historian]] Mike Jay.<ref name="Daly2019">{{cite web | vauthors = Daly M | date = 15 May 2019 | title = The Fascinating History of Mescaline, the OG Psychedelic | website = VICE | publisher = VICE | url = https://www.vice.com/en/article/history-of-mescaline-mike-jay/ | access-date = 26 June 2026 }}</ref><ref name="Jay2019" />

== Society and culture ==
=== Religious use ===
Mescaline-containing [[cactus|cacti]] are used as [[entheogen]]s for [[religion|religious]] purposes by certain [[Latin American]] and [[Native American]] and groups.<ref name="Falcon2025">{{cite journal | vauthors = Falcon J | title = Anthropology of Psychedelics | journal = Anthropology of Consciousness | volume = 36 | issue = 2 | date = 2025 | doi = 10.1111/anoc.70002 | issn = 1053-4202 }}</ref><ref name="Jay2019" /> The [[Huichol]] (Wixárika) people of [[Mexico]] and the [[Native American Church]] use [[peyote]], while the native people of [[Peru]] use the [[San Pedro cactus]] (huachuma).<ref name="Falcon2025" /><ref name="Jay2019" /> The use of mescaline-containing cacti for such purposes by [[Mexican people|Mexican]] and [[South American]] people dates back thousands of years.<ref name="Falcon2025" /><ref name="Jay2019" /> The use of peyote spread from the Huichol people into [[Native American]] tribes such as the [[Kiowa]] and [[Comanche]] in the late 1800s.<ref name="Falcon2025" /><ref name="Jay2019" />

=== Notable individuals ===
* [[Arthur Heffter]] isolated mescaline from peyote and discovered its psychedelic effects via [[self-experimentation]].<ref name="Jay2019" /><ref name="Perrine2001">{{cite journal | author = Daniel M. Perrine | title = Visions of the Night Western Medicine Meets Peyote 1887-1899 | journal = The Heffter Review of Psychedelic Research | volume = 2 | pages = 6–52 | date = 2001 | url = https://www.heffter.org/wp-content/uploads/2020/04/chap2.pdf }}</ref><ref name="Heffter1898" /> He published these findings in 1898.<ref name="Jay2019" /><ref name="Perrine2001" /><ref name="Heffter1898">{{cite journal | vauthors = Heffter A | date = 1898 | title = Ueber Pellote: Beiträge zur chemischen und pharmakologischen Kenntniss der Cacteen Zweite Mittheilung | language = de | journal = Archiv für Experimentelle Pathologie und Pharmakologie | volume = 40 | issue = 5–6 | pages = 385–429 | doi = 10.1007/BF01825267 | doi-access = free | trans-title = About Pellote: Contributions to the chemical and pharmacological knowledge of cacti, second communication | issn = 0028-1298 }}</ref> Heffter was the first person to experience psychedelic effects with a pure psychedelic compound.<ref name="Jay2019" /><ref name="Trout2013" />
* [[Silas Weir Mitchell (physician)|Silas Weir Mitchell]] was one of the first to experiment with mescaline, as peyote, and published his experience in 1896.<ref name="Metzer1989">{{cite journal | vauthors = Metzer WS | title = The experimentation of S. Weir Mitchell with mescal | journal = Neurology | volume = 39 | issue = 2 Pt 1 | pages = 303–304 | date = February 1989 | pmid = 2644583 | doi = 10.1212/wnl.39.2.303 | url = }}</ref><ref name="Mitchell1896">{{cite journal | vauthors = Mitchell SW | title = Remarks on the Effects of Anhelonium Lewinii (the Mescal Button) | journal = British Medical Journal | volume = 2 | issue = 1875 | pages = 1625–1629 | date = December 1896 | pmid = 20756623 | doi = 10.1136/bmj.2.1875.1625 | url = | pmc = 2511273 }}</ref>
* [[Havelock Ellis]] was the author of one of the first written reports to the public about an experience with mescaline (1898).<ref name="Ellis1898">{{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 name="Giannini1997">{{cite book | vauthors = Giannini AJ | year = 1997 | title = Drugs of Abuse | location = Los Angeles | publisher = Practice Management Information Corp | edition = Second | isbn = 978-1-57066-053-5 }}</ref>
* [[William James]] was one of the first to experiment with mescaline, as peyote.<ref name="Cairns1929">{{cite web | vauthors = Cairns H | date = 1 November 1929 | title = A Divine Intoxicant | website = The Atlantic | url = https://www.theatlantic.com/magazine/archive/1929/11/a-divine-intoxicant/650792/ | access-date = 8 June 2026 }}</ref><ref name="Wertz2023">{{cite journal | vauthors = Wertz SK | year = 2023 | title = James's Encounter with Mescal, Mescaline, and Peyote | journal = William James Studies | publisher = William James Society | volume = 18 | issue = 2 | pages = 85–90 | issn = 19338295 | jstor = 48749700 }}</ref> However, he took a low dose (1 peyote button), became violently ill for 2{{nbsp}}days, and experienced no  other effects.<ref name="Cairns1929" /><ref name="Wertz2023" /> He opted not to retry the drug.<ref name="Cairns1929" /><ref name="Wertz2023" /> James tried peyote in 1896 but his experience was not published until decades later.<ref name="Cairns1929" /><ref name="Wertz2023" />
* [[Jean-Paul Sartre]] took mescaline shortly before the publication of his book, ''[[The Imaginary (Sartre)|L'Imaginaire]]'' (1940); he had a [[bad trip]] during which he imagined that he was menaced by sea creatures.<ref name="Jay2019b">{{cite web | vauthors = Jay M | date = 2019-08-21 | title = Sartre's Bad Trip by Mike Jay | website = The Paris Review | url = https://www.theparisreview.org/blog/2019/08/21/sartres-bad-trip/ | access-date = 2026-05-25 }}</ref><ref name="Allens-Mills2009">{{cite web | vauthors = Allen-Mills T | date = 22 November 2009 | title = Mescaline left Jean Paul Sartre in the grip of lobster madness | website = The Times | publisher = The Sunday Times | 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="Jay2019b" /><ref name="Allens-Mills2009" /> Lobsters and crabs figure in his novel ''[[Nausea (novel)|Nausea]]'' (1938).<ref name="Allens-Mills2009" /><ref name="Jay2019b" />
* [[Salvador Dalí]] has been persistently rumored to have taken psychedelics such as mescaline.<ref name="Jay2019" /> However, in response to these rumors, Dalí famously exclaimed "I don't do drugs. I ''am'' drugs!" in 1982.<ref name="Jay2019" />
* [[Antonin Artaud]] wrote 1947's ''The Peyote Dance'', where he describes his peyote experiences in Mexico a decade earlier.<ref name="Doyle2019">{{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><ref name="Pollan2021" />
* [[Allen Ginsberg]] took peyote. Part II of his poem "Howl" was inspired by a peyote vision that he had in San Francisco.<ref name="Kramer1968">{{cite magazine | author = [[Jane Kramer]] | 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>
* [[Aldous Huxley]] described his experience with mescaline in the essay "[[The Doors of Perception]]" (1954).
* [[Ken Kesey]] took peyote prior to writing ''[[One Flew Over the Cuckoo's Nest (novel)|One Flew Over the Cuckoo's Nest]]''.
* [[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. | location = Warsaw | publisher = Drukarnia Towarzystwa Polskiej Macierzy Szkolnej | url = https://pl.wikisource.org/wiki/Nikotyna_Alkohol_Kokaina_Peyotl_Morfina_Eter_%2B_Appendix }}</ref>
* [[Jim Carroll]] in ''[[The Basketball Diaries (book)|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]]''.
* [[Alexander Shulgin]], the prolific [[psychedelic chemist]], said that he was first inspired to explore psychedelic compounds by a mescaline experience in 1960.<ref name="Jay2019" /><ref name="PiHKAL" /><ref name="Shulgin1996">{{cite web | year = 1996 | title = Alexander Shulgin: why I discover psychedelic substances | location = Mexico | website = YouTube | url = https://www.youtube.com/watch?v=QD260LPqHKA&t=3m18s | archive-date = 2021-12-11 | archive-url = https://ghostarchive.org/varchive/youtube/20211211/QD260LPqHKA | url-status = live }}{{cbignore}}</ref> In 1974, Shulgin synthesized [[2C-B]], a psychedelic phenylethylamine derivative, structurally similar to mescaline,<ref name="PapaseitFarréPérez-Mañá2018">{{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 name="Bauer2019">{{cite web | vauthors = Bauer BE | date = 2019-12-02 | title = Mescaline | language = en-US | website = Psychedelic Science Review | publisher = Psychedelic Science Review | url = https://psychedelicreview.com/compound/mescaline/ | access-date = 2023-10-30 }}</ref>
* [[Bryan Wynter]] produced ''Mars Ascends'' after trying the substance for the first time.<ref name="Bird2012">{{cite book | vauthors = Bird M | date = 2012 | title = 100 Ideas that Changed Art. | location = London | publisher = Laurence King Publishing }}</ref>
* [[George Carlin]] mentioned mescaline use during his youth while being interviewed in 2008.<ref name="Dixit2008">{{cite web | vauthors = Dixit J | date = 23 June 2008 | title = George Carlin's Last Interview | website = Psychology Today | publisher = 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 name="Santana1989">{{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 [[University of California, Los Angeles|UCLA]] in the 1960s.<ref name="Cartoonician2016">{{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}}</ref>
* [[Michael Cera]] used real mescaline for the movie ''[[Crystal Fairy & the Magical Cactus]]'', as expressed in an interview.<ref name="Boardman2013">{{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 name="PKDFans">{{cite web | title = FLOW MY Tears | publisher = www.philipkdickfans.com | url = http://www.philipkdickfans.com/mirror/websites/pkdweb/FLOW%20MY%20TEARS.HTM | 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}}
* [[Michael Pollan]] has described his experiences with mescaline and San Pedro cactus.<ref name="Pollan2021">{{cite book | vauthors = Pollan M | date = 2021 | title = This Is Your Mind on Plants | location = New York | publisher = Penguin Press | pages = 161–248 | isbn = 978-0-593-29690-5 | url = https://books.google.com/books?id=Fxs3EAAAQBAJ | author-link = Michael Pollan | section = Mescaline | section-url = https://books.google.com/books?id=Fxs3EAAAQBAJ&pg=PA161 }}</ref>

=== Media representations ===
==== Movies ====
* ''[[Fantasia (1940 film)|Fantasia]]'' (1940), with lead visualist [[Oskar Fischinger]], may have been inspired by mescaline-induced visuals.<ref name="Doblin2001">{{cite thesis | vauthors = Doblin R | date = June 2001 | title = Regulation of the Medical Use of Psychedelics and Marijuana | publisher = Harvard University | url = https://maps.org/2014/11/18/dissertation-rick-doblin-ph-d/ | degree = Ph.D. | quote = In 1927, German physician Kurt Beringer published a description of his mescaline studies in research subjects.70 One subject of his, who reportedly felt that the remarkable visual images he experienced should be captured in film, was subsequently hired by Walt Disney as the chief visualist for the Disney film, Fantasia.71 }}</ref>
* ''[[Fear and Loathing in Las Vegas]]'' (1998) starring [[Johnny Depp]] and [[Benicio del Toro]] featured mescaline use.
* ''[[The Matrix]]'' (1999) by the [[The Wachowskis|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 [[Echinopsis pachanoi|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 [[Echinopsis pachanoi|San Pedro cactus]].
* ''[[How to Change Your Mind (miniseries)|How to Change Your Mind]]'' (2022) features an episode on mescaline.

=== Legal status ===
{{See also|Legal status of psychedelic drugs|Legal status of psychoactive cacti by country}}

==== United States ====
In the [[United States]], mescaline was made illegal in 1970 by the [[Controlled Substances Act|Comprehensive Drug Abuse Prevention and Control Act]], categorized as a Schedule I hallucinogen.<ref name="USDOJ">{{cite web | author = United States Department of Justice | date = 2026-07-01 | 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 }}</ref> The drug is prohibited internationally by the 1971 [[Convention on Psychotropic Substances]].<ref name="INCB">{{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 |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 of the United States|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 name="FJC-Boerne-v-Flores">{{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 name="UTCCourts-State-v-Mooney">{{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 name="Ballotpedia2022">{{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 plant]]s.<ref name="Gupta2018">{{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 name="Erowid2007">{{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 [[Standard for the Uniform Scheduling of Medicines and Poisons|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 (''Lophophora williamsii'') as well as ''Echinopsis pachanoi'' and ''Echinopsis peruviana'' (San Pedro cactus) without restriction, as they are 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 | 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 = Garant.Ru | url = http://base.garant.ru/12112176/ }}</ref>

== 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="Agin-LiebesHaasLancelotta2021">{{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 name="ABCNews2012">{{cite web | vauthors = News AB | date = 9 March 2012 | title = Could LSD treat alcoholism? | website = ABC News | publisher = ABC News | url = https://abcnews.go.com/blogs/health/2012/03/09/could-lsd-treat-alcoholism/ | access-date = 5 October 2012 }}</ref><ref name="ShawYongLee2026">{{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 [[Controlled Substances Act#Schedule I|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 name="Carpenter2021">{{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="Agin-LiebesHaasLancelotta2021" /><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> However, the drug is under development by Journey Colab under the code name ''JOUR-5700'' and by Biomind Labs under the code names ''BMND04'', ''BMND06'', and ''BMND09'' for various medical applications, such as treatment of [[alcoholism]].<ref name="Bender_2022" /><ref name="PsychedelicAlpha-Tracker">{{cite web | title = Psychedelic Drug Development Tracker | website = Psychedelic Alpha | publisher = Psychedelic Alpha | url = https://psychedelicalpha.com/resources/psychedelic-drug-development-tracker/ | access-date = 26 June 2026 }}</ref><ref name="CopesHochstetlerRagland2026">{{cite journal | vauthors = Copes H, Hochstetler A, Ragland J, Hendricks PS | title = Hitting the Reset Button: Ceremonial Use of Peyote and Experiences of Personal Change | journal = Journal of Drug Issues | volume = 56 | issue = 1 | pages = 150–170 | date = 2026 | doi = 10.1177/00220426241274737 | issn = 0022-0426 }}</ref><ref name="AdisInsight-JOUR-5700">{{cite web | title=Mescaline HCl | website=AdisInsight | date=2 August 2022 | url=https://adisinsight.springer.com/drugs/800069596 | access-date=26 June 2026}}</ref><ref name="AdisInsight-BMND-06/09">{{cite web | title=BMND 06 | website=AdisInsight | date=28 April 2025 | url=https://adisinsight.springer.com/drugs/800067963 | access-date=26 June 2026}}</ref><ref name="AdisInsight-BMND-04">{{cite web | title=Biomind Labs | website=AdisInsight | date=28 September 2025 | url=https://adisinsight.springer.com/drugs/800064976 | access-date=26 June 2026}}</ref><ref name="Metzger2022">{{cite web | vauthors = Metzger L | date = 26 April 2022 | title = Mental Health Startup Journey Colab Aims To Develop Mescaline As An FDA-Approved Treatment For Alcohol Use Disorder | website = Forbes | publisher = Forbes | url = https://www.forbes.com/sites/louismetzgeriv/2022/04/26/mental-health-startup-journey-colab-aims-to-develop-mescaline-as-an-fda-approved-treatment-for-alcohol-use-disorder/ | access-date = 26 June 2026 }}</ref><ref name="Gunther2022">{{cite web | vauthors = Gunther M | date = 17 May 2022 | title = Journey Colab Looks to Mescaline for Treating Alcohol Use Disorder | website = Lucid News - Psychedelics | url = https://www.lucid.news/journey-colab-looks-to-mescaline-for-treating-alcohol-use-disorder/ | access-date = 26 June 2026}}</ref>

== See also ==
* [[Scaline]]

== References ==
{{Reflist}}

== 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]

{{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:Biased ligands]]
[[Category:Cacti]]
[[Category:Entheogens]]
[[Category:Experimental hallucinogens]]
[[Category:Lophophora alkaloids]]
[[Category:Native American Church]]
[[Category:Phenethylamine alkaloids]]
[[Category:PiHKAL]]
[[Category:Psychedelic-assisted therapy]]
[[Category:Psychoplastogens]]
[[Category:Scalines]]
[[Category:Serotonin receptor agonists]]
[[Category:TAAR1 modulators]]