Editing Mescaline

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

<!-- 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>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |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 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=[[Diário Oficial da União]] |language=pt-BR |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
| legal_UN = P I
| legal_status = 

<!-- Pharmacokinetic data -->
| bioavailability = Unknown<ref name="DrugBank">{{cite web | title=Mescaline: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=3 July 2024 | url=https://go.drugbank.com/drugs/DB19083 | access-date=19 May 2025}}</ref>
| protein_bound = Unknown<ref name="DrugBank" />
| metabolism = [[Oxidative deamination]], ''N''-[[acetylation]], ''O''-[[demethylation]], [[conjugation (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" />
| elimination_half-life = 3.6{{nbsp}}hours (range 2.6–5.3{{nbsp}}hours)<ref name="HolzeSinghLiechti2024" /><ref name="LeyHolzeArikci2023" /><ref name="KlaiberSchmidBecker2024" />
| 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, ≥27–30% 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="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 = Mescalin; Mezcalin; Mezcaline; 3,4,5-Trimethoxyphenethylamine; 3,4,5-TMPEA; TMPEA

<!-- 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 as '''mescalin''' or '''mezcalin''',<ref>{{Cite web | work = PubChem | publisher = U.S. National Library of Medicine |title=Mescaline |url=https://pubchem.ncbi.nlm.nih.gov/compound/Mescaline#section=Depositor-Supplied-Synonyms |access-date=2024-10-22  |language=en}}</ref> and in chemical terms '''3,4,5-trimethoxyphenethylamine''', is a [[natural product|naturally occurring]] [[psychedelic drug|psychedelic]] [[alkaloid|protoalkaloid]] of the [[substituted phenethylamine]] class, known for its [[hallucinogen]]ic effects comparable to those of [[lysergic acid diethylamide|LSD]] and [[psilocybin]].<ref name="CasselsSáez-Briones2018">{{cite journal | vauthors = Cassels BK, Sáez-Briones P | title = Dark Classics in Chemical Neuroscience: Mescaline | journal = ACS Chem Neurosci | volume = 9 | issue = 10 | pages = 2448–2458 | date = October 2018 | pmid = 29847089 | doi = 10.1021/acschemneuro.8b00215 | url = }}</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 | pages = 109294 | date = January 2023 | pmid = 36252614 | doi = 10.1016/j.neuropharm.2022.109294 | doi-access = free }}</ref><ref name="HolzeSinghLiechti2024">{{cite journal | vauthors = Holze F, Singh N, Liechti ME, D'Souza DC | title = Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile | journal = Biol Psychiatry Cogn Neurosci 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><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023">{{cite journal | vauthors = Doesburg-van Kleffens M, Zimmermann-Klemd AM, Gründemann C | title = An Overview on the Hallucinogenic Peyote and Its Alkaloid Mescaline: The Importance of Context, Ceremony and Culture | journal = Molecules | volume = 28 | issue = 24 | date = December 2023 | page = 7942 | pmid = 38138432 | pmc = 10746114 | doi = 10.3390/molecules28247942 | doi-access = free | url = }}</ref> It binds to and activates certain [[serotonin receptor]]s in the brain, producing hallucinogenic effects.<ref name="VamvakopoulouNarineCampbell2023" /><ref name="HolzeSinghLiechti2024" /> Mescaline occurs [[natural product|naturally]] in certain [[cactus|cacti]] such as [[peyote]] and [[San Pedro cactus (disambiguation)|San Pedro]].

==Uses==
Mescaline is used [[recreational drug|recreationally]], [[spirituality|spiritually]] (as an [[entheogen]]), and [[medicine|medically]].<ref name="VamvakopoulouNarineCampbell2023" /> It is typically taken [[oral administration|orally]].<ref name="Dinis-OliveiraPereiradaSilva2019" />

===Dosage===
{{See also|Psychedelic drug#Dosage}}

Mescaline is used as a psychedelic at doses of 100 to 1,000{{nbsp}}mg [[oral administration|orally]].<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022">{{cite book | vauthors = Liechti ME, Holze F | title = Disruptive Psychopharmacology | chapter = Dosing Psychedelics and MDMA | series = Curr Top Behav Neurosci | volume = 56 | pages = 3–21 | date = 2022 | pmid = 34734392 | doi = 10.1007/7854_2021_270 | isbn = 978-3-031-12183-8 | 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 = Int J Neuropsychopharmacol | volume = 21 | issue = 10 | pages = 926–931 | date = October 2018 | pmid = 29850881 | pmc = 6165951 | doi = 10.1093/ijnp/pyy047 }}</ref> Low doses are 100 to 200{{nbsp}}mg, an intermediate or "good effect" dose is 500{{nbsp}}mg, and a high or [[ego dissolution|ego-dissolution]] dose is 1,000{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022" /> [[Psychedelic microdosing|Microdosing]] involves the use of subthreshold mescaline doses of less than 75{{nbsp}}mg.<ref name="HolzeSinghLiechti2024" /><ref name="LiechtiHolze2022" />

In addition to pure form, mescaline is used in the form of mescaline-containing [[cactus|cacti]] such as [[peyote]] and [[San Pedro cactus (disambiguation)|San Pedro]].

==Effects==
{{See also|Psychedelic experience}}

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 sense of time and self-awareness, and closed- and open-eye visual phenomena.<ref name="Kovacic_2009">{{cite journal |vauthors=Kovacic P, Somanathan R |date=1 January 2009 |title=Novel, unifying mechanism for mescaline in the central nervous system: electrochemistry, catechol redox metabolite, receptor, cell signaling and structure activity relationships |journal=Oxidative Medicine and Cellular Longevity |volume=2 |issue=4 |pages=181–190 |doi=10.4161/oxim.2.4.9380 |pmc=2763256 |pmid=20716904}}</ref>

Prominence of color is distinctive, appearing brilliant and intense. Recurring visual patterns observed during the mescaline experience include stripes, checkerboards, angular spikes, multicolor dots, and very simple [[fractals]] that turn very complex. 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). Like LSD, mescaline induces distortions of form and [[Kaleidoscope|kaleidoscopic]] experiences but they manifest more clearly with [[Closed-eye hallucination|eyes closed]] and under low lighting conditions.<ref>{{Cite book |title=Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs: A Comprehensive Review on their Mode of Action, Treatment of Abuse and Intoxication |vauthors=Freye E |collaboration=Joseph V. Levy |publisher=Springer Science & Business Media |year=2009 |isbn=978-90-481-2447-3 |pages=227}}</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". The other three are the chessboard design, tunnel, and spiral. Klüver wrote that "many 'atypical' visions are upon close inspection nothing but variations of these form-constants."<ref>{{Cite book |title=A Dictionary of Hallucations |publisher=Springer |year=2010 |location=Oradell, NJ. |pages=102}}</ref>
 
As with LSD, [[synesthesia]] can occur especially with the help of music.<ref name="Diaz">{{Cite book |title=How Drugs Influence Behavior |vauthors=Diaz J |publisher=Prentice Hall |year=1996 |isbn=978-0-02-328764-0 |location=Englewood Cliffs}}</ref> An unusual but unique characteristic of mescaline use is the "geometrization" of three-dimensional objects. The object can appear flattened and distorted, similar to the presentation of a [[Cubism|Cubist]] painting.<ref>{{Cite book |title=Drugs of Abuse |vauthors=Giannini AJ, Slaby AE |publisher=Medical Economics Books |year=1989 |isbn=978-0-87489-499-8 |location=Oradell, NJ. |pages=207–239}}</ref>

Mescaline elicits a pattern of sympathetic arousal, with the [[peripheral nervous system]] being a major target for this substance.<ref name="Diaz" />

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

===Onset and duration===
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 | journal = Current Topics in Behavioral Neurosciences | series = Curr Top Behav Neurosci | volume = | issue = | pages = | date = July 2024 | pmid = 39080236 | doi = 10.1007/7854_2024_510 | 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" />

==Overdose==
The [[Median lethal dose|LD<sub>50</sub>]] of mescaline has been measured in various animals: 212–315{{nbsp}}mg/kg i.p. (mice), 132–410{{nbsp}}mg/kg i.p. (rats), 328{{nbsp}}mg/kg i.p. (guinea pigs), 54{{nbsp}}mg/kg in dogs, and 130{{nbsp}}mg/kg i.v. in [[rhesus macaque]]s.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Buckingham2014" /> For humans, the [[median lethal dose|LD<sub>50</sub>]] of mescaline has been reported to be approximately 880{{nbsp}}mg/kg.<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 very difficult to consume enough mescaline to cause death in humans.<ref name="Dinis-OliveiraPereiradaSilva2019" />

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

The [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[receptor antagonist|antagonist]] [[ketanserin]] has been found to block the psychoactive effects of mescaline.<ref name="KlaiberSchmidBecker2024" /><ref name="KlaiberBeckerStraumann2024">{{cite journal | vauthors=Klaiber A, Becker AM, Straumann I, Thomann J, Luethi D, Schmid Y, Liechti ME | 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 | date=21 May 2024 | issn=1424-3997 | doi=10.57187/s.3896 | doi-access=free | pages=126S | pmid=38771022 }}</ref>

It is unclear whether mescaline is [[drug metabolism|metabolized]] by [[monoamine oxidase]] (MAO) [[enzyme]]s<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="KapadiaFayez1970" /> or whether [[monoamine oxidase inhibitor]]s (MAOIs) might increase the effects of mescaline.<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> However, there are preliminary reports that [[harmala alkaloid]]s may potentiate mescaline, and the combination of mescaline or mescaline-containing cacti with harmala alkaloids has been referred to as "peyohuasca".<ref name="Ott1996" />

==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<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:#eaecf0; 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 | pages = e9019 | date = February 2010 | pmid = 20126400 | pmc = 2814854 | doi = 10.1371/journal.pone.0009019 | doi-access = free | bibcode = 2010PLoSO...5.9019R | url = }}</ref><ref name="RickliLuethiReinisch2015">{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = http://edoc.unibas.ch/56163/1/20170921163006_59c3cceeb8e5d.pdf}}</ref><ref name="RickliMoningHoener2016">{{cite journal |vauthors=Rickli A, Moning OD, Hoener MC, Liechti ME |date=August 2016 |title=Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens |url=http://edoc.unibas.ch/53326/1/20170117174852_587e4af45b658.pdf |journal=European Neuropsychopharmacology |volume=26 |issue=8 |pages=1327–1337 |doi=10.1016/j.euroneuro.2016.05.001 |pmid=27216487 |s2cid=6685927}}</ref><ref name="WallachCaoCalkins2023">{{cite journal | vauthors = Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD | title = Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential | journal = Nat Commun | volume = 14 | issue = 1 | pages = 8221 | date = December 2023 | pmid = 38102107 | pmc = 10724237 | doi = 10.1038/s41467-023-44016-1 }}</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 = J Pharmacol Exp Ther | 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 = Pharmacol Rev | 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 = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA| archive-url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | archive-date = 9 May 2025 }}</ref>
|}

In humans, mescaline acts similarly to other psychedelic agents.<ref name="pmid14761703">{{cite journal |vauthors=Nichols DE |date=February 2004 |title=Hallucinogens |journal=Pharmacology & Therapeutics |volume=101 |issue=2 |pages=131–181 |doi=10.1016/j.pharmthera.2003.11.002 |pmid=14761703}}</ref> It acts as an agonist,<ref name="pmid2707301">{{cite journal |vauthors=Appel JB, Callahan PM |date=January 1989 |title=Involvement of 5-HT receptor subtypes in the discriminative stimulus properties of mescaline |journal=European Journal of Pharmacology |volume=159 |issue=1 |pages=41–46 |doi=10.1016/0014-2999(89)90041-1 |pmid=2707301}}</ref> binding to and activating the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]].<ref name="pmid9301661">{{cite journal |vauthors=Monte AP, Waldman SR, Marona-Lewicka D, Wainscott DB, Nelson DL, Sanders-Bush E, Nichols DE |date=September 1997 |title=Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives |journal=Journal of Medicinal Chemistry |volume=40 |issue=19 |pages=2997–3008 |citeseerx=10.1.1.690.9370 |doi=10.1021/jm970219x |pmid=9301661}}</ref><ref name="KlaiberSchmidBecker2024">{{cite journal | vauthors = Klaiber A, Schmid Y, Becker AM, Straumann I, Erne L, Jelusic A, Thomann J, Luethi D, Liechti ME | title = Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects | journal = Translational Psychiatry | volume = 14 | issue = 1 | pages = 395 | date = September 2024 | pmid = 39349427 | doi = 10.1038/s41398-024-03116-2 | pmc = 11442856 }}</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-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="pmid17535909">{{cite journal |vauthors=Béïque JC, Imad M, Mladenovic L, Gingrich JA, Andrade R |date=June 2007 |title=Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=104 |issue=23 |pages=9870–9875 |bibcode=2007PNAS..104.9870B |doi=10.1073/pnas.0700436104 |pmc=1887564 |pmid=17535909 |doi-access=free}}</ref> In addition to the serotonin 5-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" /><ref>{{Cite web |date=27 March 2009 |title=Neuropharmacology of Hallucinogens |url=http://www.erowid.org/psychoactives/pharmacology/pharmacology_article1.shtml |access-date=7 September 2011 |publisher=Erowid.org}}</ref>

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">{{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 = Curr Mol Pharmacol | volume = 12 | issue = 3 | pages = 184–194 | date = 2019 | pmid = 30318013 | pmc = 6864602 | doi = 10.2174/1874467211666181010154139 | url = }}</ref><ref name="FreedmanGottliebLovell1970">{{cite journal | vauthors = Freedman DX, Gottlieb R, Lovell RA | title=Psychotomimetic drugs and brain 5-hydroxytryptamine metabolism | journal=Biochemical Pharmacology | publisher=Elsevier BV | volume=19 | year=1970 | issn=0006-2952 | doi=10.1016/0006-2952(70)90378-3 | pages=1181–1188}}</ref> This finding suggests that mescaline might [[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 = J Pharmacol Exp Ther | 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}}</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 = Eur J Pharmacol | 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 Schmiedebergs Arch Pharmacol | 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 [[trimethoxyamphetamines|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 (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 its [[structural analog|structural similarity]] to [[substituted amphetamine]]s and related compounds.<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 20-fold more potent (doses in the tens of milligrams) and [[lysergic acid diethylamide]] (LSD) is approximately 2,000-fold more potent (doses in the tens to hundreds of micrograms).<ref name="VamvakopoulouNarineCampbell2023" /> There have been efforts to develop more potent [[structural analogue|analogue]]s of mescaline.<ref name="CasselsSáez-Briones2018" /> Difluoro{{shy}}mescaline and [[Trifluoromescaline|trifluoro{{shy}}mescaline]] are more potent than mescaline, as is its amphetamine [[homologous series|homologue]] TMA.<ref>{{cite journal |vauthors=Trachsel D |year=2012 |title=Fluorine in psychedelic phenethylamines |url=http://bitnest.ca/external.php?id=%257DbxUgXXCNAUj%257E%257E%2507 |url-status=dead |journal=Drug Testing and Analysis |volume=4 |issue=7–8 |pages=577–590 |doi=10.1002/dta.413 |pmid=22374819 |archive-url=https://web.archive.org/web/20130603150127/http://bitnest.ca/external.php?id=%257DbxUgXXCNAUj%257E%257E%2507 |archive-date=2013-06-03}}</ref><ref>{{Cite web |title=#157 TMA - 3,4,5-TRIMETHOXYAMPHETAMINE |url=https://www.erowid.org/library/books_online/pihkal/pihkal157.shtml |access-date=9 January 2013 |work=PiHKAL: A Chemical Love Story |publisher=Erowid.org |vauthors=Shulgin A}}</ref> [[Escaline]] and [[proscaline]] are also both more potent than mescaline, showing the importance of the 4-position substituent with regard to receptor binding.<ref name="pmid3952123">{{cite journal |vauthors=Nichols DE |date=February 1986 |title=Studies of the relationship between molecular structure and hallucinogenic activity |journal=Pharmacology, Biochemistry, and Behavior |volume=24 |issue=2 |pages=335–340 |doi=10.1016/0091-3057(86)90362-x |pmid=3952123 |s2cid=30796368}}</ref>

[[Drug tolerance|Tolerance]] to mescaline builds with repeated usage, lasting for a few days. The drug causes [[cross-tolerance]] with other [[serotonergic psychedelics]] such as [[lysergic acid diethylamide|LSD]] and [[psilocybin]].<ref>{{Cite web |url=http://www.erowid.org/archive/rhodium/chemistry/psychedelicchemistry/chapter1.html |title=Psychedelics and Society | vauthors = Smith MV |publisher=Erowid.org |access-date=6 April 2012 }}</ref>

The [[cryo-EM]] [[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 | pages = 2734 | date = March 2025 | pmid = 40108183 | doi = 10.1038/s41467-025-57956-7 | pmc = 11923220 | 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" /> [[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" /> 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" />

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" /> However, it is still able to cross into the [[central nervous system]] and produce [[psychoactive]] effects at sufficienty high doses.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" />

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

The primary [[metabolic pathway]] of mescaline is [[oxidative deamination]].<ref name="Dinis-OliveiraPereiradaSilva2019" /><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 = J Pharm Sci | volume = 59 | issue = 12 | pages = 1699–1727 | date = December 1970 | pmid = 5499699 | doi = 10.1002/jps.2600591202 | url = }}</ref> The specific [[enzyme]]s mediating the deamination of mescaline are controversial however.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="KapadiaFayez1970" /><ref name="SmythiesJohnstonBradley1967" /> [[Monoamine oxidase]] (MAO), [[diamine oxidase]] (DAO; histamine oxidase), and/or other enzymes may be responsible.<ref name="Dinis-OliveiraPereiradaSilva2019" /><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="KapadiaFayez1970" /><ref name="Patel1968" /><ref name="MusacchioGoldstein1967">{{cite journal | vauthors = Musacchio JM, Goldstein M | title = The metabolism of mescaline-14-C in rats | journal = Biochem Pharmacol | 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 = J Biol Chem | 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 appears not to be subject to metabolism by [[CYP2D6]] based on ''in-vitro'' studies with human liver microsomes.<ref name="pmid9264312">{{cite journal | vauthors = Wu D, Otton SV, Inaba T, Kalow W, Sellers EM | title = Interactions of amphetamine analogs with human liver CYP2D6 | journal = Biochemical Pharmacology | volume = 53 | issue = 11 | pages = 1605–1612 | date = June 1997 | pmid = 9264312 | doi = 10.1016/S0006-2952(97)00014-2 }}</ref> Similarly, the ''in-vitro'' [[cytotoxicity]] of mescaline does not appear to be affected by [[cytochrome P450]] (CYP450) [[enzyme 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 (Basel) | 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 3,4,5-trimethoxyphenylacetic acid (TMPAA) are similar with oral administration of mescaline.<ref name="KlaiberSchmidBecker2024" /> Conversely, levels of [[N-acetylmescaline|''N''-acetylmescaline]] (NAM) are far lower than those of mescaline or TMPAA.<ref name="KlaiberSchmidBecker2024" /> [[Intravenous injection]] of mescaline may result in less hepatic deamination than with oral administration.<ref name="VamvakopoulouNarineCampbell2023" />

[[Active metabolite]]s of mescaline might contribute to its psychoactive effects.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="CasselsSáez-Briones2018" /> However, both TMPAA and NAM have been said to be inactive based on human tests.<ref name="CharalampousWalkerKinross-Wright1966" /> Similarly, 3,4,5-trimethoxyphenylethanol (TMPE), 3,4,5-trimethoxyphenylacetaldehyde (TMPA), and NAM all failed to produce mescaline-like effects in rodent [[drug discrimination]] tests.<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 = Pharmacol Biochem Behav | volume = 3 | issue = 1 | pages = 109–114 | date = 1975 | pmid = 1129346 | doi = 10.1016/0091-3057(75)90088-x | url = }}</ref>

[[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="Nichols1981">{{cite journal | vauthors = Nichols DE | title = Structure-activity relationships of phenethylamine hallucinogens | journal = J Pharm Sci | volume = 70 | issue = 8 | pages = 839–849 | date = August 1981 | pmid = 7031221 | doi = 10.1002/jps.2600700802 | url = https://bitnest.netfirms.com/external/10.1002/jps.2600700802}}</ref> This suggests that the deamination of mescaline have a relatively limited impact on its potency, compared to for example the [[2C (psychedelics)|2C]] series of psychedelics.<ref name="Nichols1981" />

====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 = Neurochem Res | 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" />

Mescaline was originally reported to have an [[elimination half-life]] of 6{{nbsp}}hours based on a study conducted in the 1960s.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="VamvakopoulouNarineCampbell2023" /><ref name="LeyHolzeArikci2023" /><ref name="CharalampousWalkerKinross-Wright1966" /> However, subsequent research published in the 2020s found that its half-life is actually about 3.6{{nbsp}}hours (range 2.6–5.3{{nbsp}}hours).<ref name="HolzeSinghLiechti2024" /><ref name="LeyHolzeArikci2023">{{cite journal | vauthors = Ley L, Holze F, Arikci D, Becker AM, Straumann I, Klaiber A, Coviello F, Dierbach S, Thomann J, Duthaler U, Luethi D, Varghese N, Eckert A, Liechti ME | title = Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants | journal = Neuropsychopharmacology | volume = 48 | issue = 11 | pages = 1659–1667 | date = October 2023 | pmid = 37231080 | doi = 10.1038/s41386-023-01607-2 | pmc = 10517157 }}</ref><ref name="KlaiberSchmidBecker2024" /> 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" />

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 | 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 on the [[serotonin|serotonergic]] system rather than on the [[dopaminergic]] or [[adrenergic]] systems.

The drug 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" />

The physical properties and general chemistry of mescaline have been reviewed.<ref name="Patel1968">{{cite journal | vauthors = Patel AR | title = Mescaline and related compounds | journal = Fortschr Arzneimittelforsch | volume = 11 | issue = | pages = 11–47 | date = 1968 | pmid = 4873202 | doi = 10.1007/978-3-0348-7062-7_1 | isbn = 978-3-0348-7064-1 | url = }}</ref>

===Synthesis===
[[File:Synthetic mescaline powder i2001e0151 ccby3.jpg|right|thumb|Laboratory synthetic mescaline biosynthesized{{clarify|reason=Is it lab synthesized or biosynthesized then lab extracted??|date=March 2025}} from {{nowrap|peyote{{hsp}}{{mdash}}{{hsp}}}}this was the first psychedelic compound to be extracted and isolated<ref>{{cite web|url=https://www.mescaline.com/exp/|title=Mescaline : D M Turner|website=www.mescaline.com}}</ref>]]
[[File:Dried Peyote.jpg|thumb|250px|Dried Peyote (''Lophophora williamsii''), containing around 5-6% mescaline by weight]]

Mescaline was first synthesized in 1919 by [[Ernst Späth]] from 3,4,5-trimethoxy{{shy}}benzoyl chloride.<ref name="Späth_1919" /> Several approaches using different starting materials have been developed since, including the following:

* [[Hofmann rearrangement]] of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}propionamide.<ref>{{cite journal | vauthors = Slotta KH, Heller H |title=Über β-Phenyl-äthylamine, I. Mitteil.: Mezcalin und mezcalin-ähnliche Substanzen |journal= Berichte der Deutschen Chemischen Gesellschaft (A and B Series) |year=1930 |volume=63 |issue=11 |pages=3029–3044 |doi=10.1002/cber.19300631117 }}</ref>
* [[Cyanohydrin reaction]] between [[potassium cyanide]] and [[3,4,5-trimethoxybenzaldehyde|3,4,5-trimethoxy{{shy}}benz{{shy}}aldehyde]] followed by [[acetylation]] and [[Organic redox reaction|reduction]].<ref>{{cite journal| vauthors = Amos D |title= Preparation of Mescaline from Eucalypt Lignin|journal=Australian Journal of Pharmacy |date=1964 |volume=49 |page=529 |url=https://www.erowid.org/archive/rhodium/chemistry/mescalyptus.html}}</ref><ref>{{cite journal| vauthors = Kindler K, Peschke W |title=Über neue und über verbesserte Wege zum Aufbau von pharmakologisch wichtigen Aminen VI. Über Synthesen des Meskalins|journal=Archiv der Pharmazie|year=1932|volume=270|issue=7|pages=410–413|doi=10.1002/ardp.19322700709|s2cid=93188741 }}</ref>
* [[Henry reaction]] of 3,4,5-trimethoxy{{shy}}benz{{shy}}aldehyde with [[nitromethane]] followed by [[Reduction of nitro compounds|nitro compound reduction]] of ω-nitro{{shy}}trimethoxy{{shy}}styrene.<ref>{{cite journal| vauthors = Benington F, Morin R |title=An Improved Synthesis of Mescaline|journal=Journal of the American Chemical Society|year=1951|volume=73|issue=3|pages=1353|doi=10.1021/ja01147a505|bibcode=1951JAChS..73Q1353B }}</ref><ref>{{cite book| vauthors = Shulgin A, Shulgin A |title=PiHKAL: A Chemical Love Story|year=1991|publisher=Transform Press|location=Lafayette, CA|isbn=9780963009609|page=703|url=https://books.google.com/books?id=O8AdHBGybpcC&q=9780963009609}}</ref><ref>{{cite journal| vauthors = Hahn G, Rumpf F |title=Über β-[Oxy-phenyl]-äthylamine und ihre Umwandlungen, V. Mitteil.: Kondensation von Oxyphenyl-äthylaminen mit α-Ketonsäuren|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|year=1938|volume=71|issue=10|pages=2141–2153|doi=10.1002/cber.19380711022}}</ref><ref>{{cite journal| vauthors = Toshitaka O, Hiroaka A |title=Synthesis of Phenethylamine Derivatives as Hallucinogen|journal=Japanese Journal of Toxicology and Environmental Health|date=1992|volume=38|issue=6|pages=571–580|doi=10.1248/jhs1956.38.571 |url=https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_ohshita1992.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_ohshita1992.pdf |archive-date=2022-10-09 |url-status=live|access-date=20 June 2014|doi-access=free}}</ref><ref>{{cite journal| vauthors = Ramirez F, Erne M |title=Über die Reduktion von β-Nitrostyrolen mit Lithiumaluminiumhydrid|journal=Helvetica Chimica Acta|date=1950|volume=33|issue=4|pages=912–916|doi=10.1002/hlca.19500330420}}</ref><ref>{{cite journal| vauthors = Szyszka G, Slotta KH |title=Über β-Phenyl-äthylamine.III. Mitteilung: Neue Darstellung von Mescalin|journal=Journal für Praktische Chemie|date=1933|volume=137|issue=9–12|pages=339–350|doi=10.1002/prac.19331370907}}</ref><ref>{{cite journal| vauthors = Burger A, Ramirez FA |title=The Reduction of Phenolic β-Nitrostyrenes by Lithium Aluminum Hydride|journal=Journal of the American Chemical Society|date=1950|volume=72|issue=6|pages=2781–2782|doi=10.1021/ja01162a521|bibcode=1950JAChS..72.2781R }}</ref>
* [[Ozonolysis]] of [[elemicin]] followed by [[reductive amination]].<ref>{{cite journal| vauthors = Hahn G, Wassmuth H |title=Über β-[Oxyphenyl]-äthylamine und ihre Umwandlungen, I. Mitteil.: Synthese des Mezcalins|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|year=1934|volume=67|issue=4|pages=696–708|doi=10.1002/cber.19340670430}}</ref>
* [[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>{{cite journal| vauthors = Dornow A, Petsch G |title=Über die Darstellung des Oxymezcalins und Mezcalins 2. Mitteilung|journal=[[Archiv der Pharmazie]]|year=1952|volume=285|issue=7|pages=323–326|doi=10.1002/ardp.19522850704|s2cid=97553172 }}</ref><ref>{{cite book| vauthors = Ikan R |title=Natural Products: A Laboratory Guide 2nd Ed|year=1991|publisher=Academic Press, Inc.|location=San Diego|isbn=978-0123705518|pages=232–235|url=https://books.google.com/books?id=B7P8HQimBAIC&pg=PA243}}</ref>
* [[Amide reduction]] of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}acetamide.<ref>{{cite journal| vauthors = Banholzer K, Campbell TW, Schmid H |title=Notiz über eine neue Synthese von Mezcalin, N-Methyl- und N-Dimethylmezcalin|journal=Helvetica Chimica Acta|date=1952|volume=35|issue=5|pages=1577–1581|doi=10.1002/hlca.19520350519}}</ref>
*Reduction of 3,4,5-trimethoxy{{shy}}(2-nitrovinyl)benzene with lithium aluminum hydride.<ref name="Kovacic_2009" />
* Treatment of tricarbonyl-(η6-1,2,3-trimethoxy{{shy}}benzene) chromium complex with acetonitrile carbanion in [[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|Substituted mescaline analogue}}

A large number of [[structural analogue]]s of mescaline that act as psychedelics have been developed. These drugs often have far greater [[potency (pharmacology)|potency]] than mescaline itself. Examples include [[substituted mescaline analogue|scaline]]s like [[escaline]], [[3C (psychedelics)|3C]]s like [[3,4,5-trimethoxyamphetamine]] (TMA or TMA-1), [[2C (psychedelics)|2Cs]] like [[2C-B]], and [[DOx]] drugs like [[DOM (drug)|DOM]], among others. Other notable analogues of mescaline include [[N-methylmescaline|''N''-methylmescaline]] (found in ''[[Pachycereus pringlei]]'') and [[trichocereine]] (''N'',''N''-dimethylmescaline), among others.

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

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

[[File:Troncos de cactus Echinopsis pachanoi.jpg|thumb|''Trichocereus pachanoi'' in Peru]]

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

In plants, mescaline may be the end-product of a pathway utilizing catecholamines as a method of stress response, similar to how animals may release such compounds and others such as [[cortisol]] when stressed. The ''in vivo'' function of catecholamines in plants has not been investigated, but they may function as [[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. In ''Lophophora williamsii'' ([[Peyote]]), [[dopamine]] converts into mescaline in a biosynthetic pathway involving ''m''-''O''-methylation and aromatic hydroxylation.<ref>{{Cite book |title=Medicinal Natural Products: A Biosynthetic Approach | vauthors = Dewick PM |location=United Kingdom |publisher=John Wiley & Sons |pages=335–336 |year=2009 |isbn=978-0-471-49641-0 }}</ref>

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

Phenylalanine serves as a precursor by first being converted to <small>L</small>-tyrosine by [[L-amino acid hydroxylase]]. Once converted, it follows the same pathway as described above.<ref name="10.1016/j.plantsci.2006.10.013">{{cite journal |vauthors=Kulma A, Szopa J |date=March 2007 |title=Catecholamies are active compounds in plants |journal=Plant Science |volume=172 |issue=3 |pages=433–440 |doi=10.1016/j.plantsci.2006.10.013|bibcode=2007PlnSc.172..433K }}</ref><ref>{{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}}

[[Peyote]] has been used for at least 5,700 years by [[Indigenous peoples of the Americas]] in Mexico.<ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name=prehistoric>{{cite journal | vauthors = El-Seedi HR, De Smet PA, Beck O, Possnert G, Bruhn JG | 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 | date = October 2005 | pmid = 15990261 | doi = 10.1016/j.jep.2005.04.022 }}</ref> Europeans recorded use of peyote in Native American religious ceremonies upon early contact with the [[Huichol people]] in Mexico.<ref>{{cite book | vauthors = Ruiz de Alarcón H |title= Treatise on the Heathen Superstitions that Today Live Among the Indians Native to this New Spain, 1629 |date=1984 |publisher=University of Oklahoma Press |isbn=978-0806120317}}</ref> Other mescaline-containing cacti such as the San Pedro have a long history of use in South America, from Peru to Ecuador.<ref>{{Cite journal | vauthors = Socha DM, Sykutera M, Orefici G |date=2022-12-01 |title=Use of psychoactive and stimulant plants on the south coast of Peru from the Early Intermediate to Late Intermediate Period |journal=Journal of Archaeological Science |language=en |volume=148 |pages=105688 |doi=10.1016/j.jas.2022.105688 |bibcode=2022JArSc.148j5688S |s2cid=252954052 |issn=0305-4403|doi-access=free }}</ref><ref>{{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 | pages = 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 | pages = 26 | date = February 2014 | pmid = 24565054 | pmc = 3975971 | doi = 10.1186/1746-4269-10-26 | doi-access = free }}</ref><ref>{{Cite journal | vauthors = Samorini G |date=2019-06-01 |title=The oldest archeological data evidencing the relationship of Homo sapiens with psychoactive plants: A worldwide overview |journal=Journal of Psychedelic Studies |language=en |volume=3 |issue=2 |pages=63–80 |doi=10.1556/2054.2019.008|s2cid=135116632 |doi-access=free }}</ref> While religious and ceremonial peyote use was widespread in the [[Aztec Empire]] and northern Mexico at the time of the Spanish conquest, religious persecution confined it to areas near the Pacific coast and up to southwest Texas. However, by 1880, peyote use began to spread north of South-Central America with "a new kind of peyote ceremony" inaugurated by the Kiowa and Comanche people. These religious practices, incorporated legally in the United States in 1920 as the Native American Church, have since spread as far as Saskatchewan, Canada.<ref name=prehistoric/>

In traditional peyote preparations, the top of the cactus is cut off, leaving the large tap root along with a ring of green photosynthesizing area to grow new heads. These heads are then dried to make disc-shaped buttons. Buttons are chewed to produce the effects or soaked in water to drink. However, the taste of the cactus is bitter, so modern users will often grind it into a powder and pour it into capsules to avoid having to taste it. The typical dosage is 200–400 milligrams of mescaline sulfate or 178–356 milligrams of mescaline hydrochloride.<ref>{{Cite web |url=http://www.erowid.org/library/books_online/pihkal/pihkal096.shtml |title=#96 M – Mescaline (3,4,5-Trimethoxyphenethylamine) |work=PIHKAL |publisher=Erowid.org |access-date=7 September 2011 }}</ref><ref>{{cite journal | vauthors = Uthaug MV, Davis AK, Haas TF, Davis D, Dolan SB, Lancelotta R, Timmermann C, Ramaekers JG | title = The epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects | journal = Journal of Psychopharmacology | volume = 36 | issue = 3 | pages = 309–320 | date = March 2022 | pmid = 33949246 | pmc = 8902264 | doi = 10.1177/02698811211013583 }}</ref> The average {{convert|76|mm|in|abbr=on}} peyote button contains about 25{{nbsp}}mg mescaline.<ref>{{Cite book|title=Handbook of Overdose and Detoxification Emergencies |location=New Hyde Park, NY. |publisher=Medical Examination Publishing Company |year=1982 |isbn=978-0-87488-182-0 | vauthors = Giannini AJ, Slaby AE, Giannini MC }}</ref> Some analyses of traditional preparations of San Pedro cactus have found doses ranging from 34{{nbsp}}mg to 159{{nbsp}}mg of total alkaloids, a relatively low and barely psychoactive amount. It appears that patients who receive traditional treatments with San Pedro ingest sub-psychoactive doses and do not experience psychedelic effects.<ref>{{Cite web |date=2019-09-20 |title=San Pedro: Basic Info |url=https://www.iceers.org/san-pedro-basic-info/ |access-date=2024-06-06 |website=ICEERS |language=en-US}}</ref>

Botanical studies of peyote began in the 1840s and the drug was listed in the Mexican [[pharmacopeia]].<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> The first use of mescal buttons was published by John Raleigh Briggs in 1887.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> In 1887, the German pharmacologist [[Louis Lewin]] received his first sample of the peyote cactus, found numerous new alkaloids and later published the first methodical analysis of it.<ref>{{Cite web |title=Botany of Peyote |url=https://www.druglibrary.org/schaffer/lsd/pbotany.htm |access-date=2025-03-03 |website=www.druglibrary.org}}</ref> Mescaline was first isolated and identified in 1897 by the German chemist [[Arthur Heffter]].<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /><ref name="Dinis-OliveiraPereiradaSilva2019" /><ref name="Erowid-Heffter">{{Cite web |url=http://www.erowid.org/culture/characters/heffter_arthur/heffter_arthur.shtml |title=Arthur Heffter |work=Character Vaults |publisher=Erowid.org |access-date=9 January 2013 }}</ref> He showed that mescaline was exclusively responsible for the psychoactive or hallucinogenic effects of peyote.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> However, other components of peyote, such as [[hordenine]], [[pellotine]], and [[anhalinine]], are also [[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>

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]]. Though the recording was deemed too controversial and ultimately omitted from the show, Mayhew praised the experience, calling it "the most interesting thing I ever did".<ref>{{Cite web |url=http://sotcaa.net/hiddenarchive/mayhew01.html |title=Panorama: The Mescaline Experiment |date=February 2005 |archive-url=https://web.archive.org/web/20120726183523/http://sotcaa.net/hiddenarchive/mayhew01.html |archive-date=26 July 2012 }}</ref>

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

The mechanism of action of mescaline, activation of the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]]s, became known in the 1990s.<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" />

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

While mescaline-containing cacti of the genus ''[[Echinopsis]]'' are technically controlled substances under the [[Controlled Substances Act]], they are commonly sold publicly as [[ornamental plant]]s.<ref>{{cite book | vauthors = Gupta RC |title=Veterinary Toxicology: Basic and Clinical Principles |date=2018 |publisher=Academic Press |isbn=9780123704672 |pages=363–390 |edition=Third }}</ref>

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

====Australia====
Mescaline is considered a schedule 9 substance in Australia under the [[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, or ''Lophophora williamsii'', as well as ''Echinopsis pachanoi'' and ''Echinopsis peruviana'' without restriction, as it is specifically exempt from legislation.<ref name=Bib/> In Canada, mescaline is classified as a schedule III drug under the [[Controlled Drugs and Substances Act]], whereas peyote is exempt.<ref>{{cite web |url=http://laws-lois.justice.gc.ca/Search/Search.aspx?txtS3archA11=mescaline&txtT1tl3=%22Controlled+Drugs+and+Substances+Act%22&h1ts0n1y=0&ddC0nt3ntTyp3=Acts. |title=Justice Laws Search |publisher=laws-lois.justice.gc.ca |access-date=5 October 2012}}</ref>

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

{{See also|Legal status of psychoactive cactus by country}}

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

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

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

==References==
{{Reflist}}

==Further reading==
{{refbegin}}
* {{cite book | vauthors = Jay M | date = 2019 | title = Mescaline: A Global History of the First Psychedelic | publisher = Yale University Press }}
* {{cite book | vauthors = Klüver H | author-link = Heinrich Klüver | date = 1942 | chapter = Mechanisms of hallucinations. | veditors = [[Quinn McNemar|McNemar Q]], Merrill MA | title = Studies in personality | pages = 175–207 | publisher = McGraw-Hill | chapter-url = https://maps.org/research-archive/psychedelicreview/n07/n07041klu.pdf }}
* {{cite book | vauthors = Pollan M | author-link = Michael Pollan | date = 2021 | title = This Is Your Mind on Plants | publisher = Penguin Press | isbn = 9780593296905 }}
{{refend}}

==External links==
{{Commons}}
* {{YouTube|Hd4rgyZzseY|Film of Christopher Mayhew's mescaline experiment}}
* [https://web.archive.org/web/20060215094333/http://diseyes.lycaeum.org/cact/final.htm Mescaline: The Chemistry and Pharmacology of its Analogs], an essay by [[Alexander Shulgin]]
* [http://www.houstonpress.com/2008-02-14/news/mescaline-on-the-mexican-border/ Mescaline on the Mexican Border]

{{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:Alkaloids found in Fabaceae]]
[[Category:Cacti]]
[[Category:Entheogens]]
[[Category:Experimental hallucinogens]]
[[Category:Native American Church]]
[[Category:Phenethylamine alkaloids]]
[[Category:Scalines]]
[[Category:Serotonin receptor agonists]]
[[Category:TAAR1 modulators]]