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Mescaline

Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin.

Not to be confused with mezcal, mesclun, or mexamine.

Clinical data

3,4,5-Trimethoxyphenethylamine, TMPEA, Peyote

  • None

C11H17NO3

211.261 g·mol−1

35 to 36 °C (95 to 97 °F)

180 °C (356 °F) at 12 mmHg

of 3,4,5-trimethoxy­phenyl­propionamide.[35]

Hofmann rearrangement

between potassium cyanide and 3,4,5-trimethoxy­benz­aldehyde followed by acetylation and reduction.[36][37]

Cyanohydrin reaction

of 3,4,5-trimethoxy­benz­aldehyde with nitromethane followed by nitro compound reduction of ω-nitro­trimethoxy­styrene.[38][39][40][41][42][43][44]

Henry reaction

of elemicin followed by reductive amination.[45]

Ozonolysis

of 3,4,5-trimethoxy­phenyl­acetamide.[49]

Amide reduction

Reduction of 3,4,5-trimethoxy­(2-nitrovinyl)benzene with lithium aluminum hydride.

[50]

Treatment of tricarbonyl-(η6-1,2,3-trimethoxy­benzene) chromium complex with acetonitrile carbanion in and iodine, followed by reduction of the nitrile with lithium aluminum hydride.[46]

THF

Pharmacokinetics[edit]

Tolerance builds with repeated usage, lasting for a few days. Mescaline causes cross-tolerance with other serotonergic psychedelics such as LSD and psilocybin.[51]


About half the initial dosage is excreted after six hours, but some studies suggest that it is not metabolized at all before excretion. Mescaline appears not to be subject to metabolism by CYP2D6[52] and between 20% and 50% of mescaline is excreted in the urine unchanged, with the rest being excreted as the deaminated-oxidised-carboxylic acid form of mescaline, a likely result of MAO degradation.[53] The LD50 of mescaline has been measured in various animals: 212 mg/kg i.p. (mice), 132 mg/kg i.p. (rats), and 328 mg/kg i.p. (guinea pigs). For humans, the LD50 of mescaline has been reported to be approximately 880 mg/kg.[54]

Behavioral and non-behavioral effects[edit]

Mescaline induces a psychedelic state comparable to those produced by LSD and psilocybin, but with unique characteristics.[30] Subjective effects may include altered thinking processes, an altered sense of time and self-awareness, and closed- and open-eye visual phenomena.[50]


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 kaleidoscopic experiences but they manifest more clearly with eyes closed and under low lighting conditions.[55]


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."[56]


As with LSD, synesthesia can occur especially with the help of music.[57] 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 Cubist painting.[58]


Mescaline elicits a pattern of sympathetic arousal, with the peripheral nervous system being a major target for this substance.[57]


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.[59]

Legality[edit]

United States[edit]

In the United States, mescaline was made illegal in 1970 by the Comprehensive Drug Abuse Prevention and Control Act, categorized as a Schedule I hallucinogen.[69] The drug is prohibited internationally by the 1971 Convention on Psychotropic Substances.[70] Mescaline is legal only for certain religious groups (such as the Native American Church by the American Indian Religious Freedom Act of 1978) and in scientific and medical research. In 1990, the Supreme Court ruled that the state of Oregon could ban the use of mescaline in Native American religious ceremonies. The Religious Freedom Restoration Act (RFRA) in 1993 allowed the use of peyote in religious ceremony, but in 1997, the Supreme Court ruled that the RFRA is unconstitutional when applied against states. Many states, including the state of Utah, have legalized peyote usage with "sincere religious intent", or within a religious organization, regardless of race.[71] Synthetic mescaline, but not mescaline derived from cacti, was officially decriminalized in the state of Colorado by ballot measure Proposition 122 in November 2022.[72]


While mescaline-containing cacti of the genus Echinopsis are technically controlled substances under the Controlled Substances Act, they are commonly sold publicly as ornamental plants.[73]

United Kingdom[edit]

In the United Kingdom, mescaline in purified powder form is a Class A drug. However, dried cactus can be bought and sold legally.[74]

Australia[edit]

Mescaline is considered a schedule 9 substance in Australia under the Poisons Standard (February 2020).[75] 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."[75]

Other countries[edit]

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.[9] In Canada, mescaline is classified as a schedule III drug under the Controlled Drugs and Substances Act, whereas peyote is exempt.[76]


In Russia mescaline, its derivatives and mescaline-containing plants are banned as narcotic drugs (Schedule I).[77]

wrote 1947's The Peyote Dance, where he describes his peyote experiences in Mexico a decade earlier.[78]

Antonin Artaud

took peyote prior to forming The Grateful Dead but later switched to LSD and DMT since they were easier on the stomach.

Jerry Garcia

took peyote. Part II of his poem "Howl" was inspired by a peyote vision that he had in San Francisco.[79]

Allen Ginsberg

took peyote prior to writing One Flew Over the Cuckoo's Nest.

Ken Kesey

took mescaline shortly before the publication of his first book, 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.

Jean-Paul Sartre

was the author of one of the first written reports to the public about an experience with mescaline (1898).[80][81][82]

Havelock Ellis

Polish writer, artist and philosopher, experimented with mescaline and described his experience in a 1932 book Nikotyna Alkohol Kokaina Peyotl Morfina Eter.[83]

Stanisław Ignacy Witkiewicz

described his experience with mescaline in the essay "The Doors of Perception" (1954).

Aldous Huxley

in The Basketball Diaries described using peyote that a friend smuggled from Mexico.

Jim Carroll

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.

Hunter S. Thompson

Psychedelic research pioneer said he was first inspired to explore psychedelic compounds by a mescaline experience.[84] In 1974, Shulgin synthesized 2C-B, a psychedelic phenylethylamine derivative, structurally similar to mescaline,[85] and one of Shulgin's self-rated most important phenethylamine compounds together with Mescaline, 2C-E, 2C-T-7, and 2C-T-2.[86]

Alexander Shulgin

produced Mars Ascends after trying the substance for the first time.[87]

Bryan Wynter

mentioned mescaline use during his youth while being interviewed in 2008.[88]

George Carlin

told about his mescaline use in a 1989 Rolling Stone interview.[89]

Carlos Santana

Disney animator described participating in a study of mescaline and peyote conducted by UCLA in the 1960s.[90]

Ward Kimball

used real mescaline for the movie Crystal Fairy & the Magical Cactus, as expressed in an interview.[91]

Michael Cera

was inspired to write Flow My Tears, the Policeman Said after taking mescaline.[92]

Philip K. Dick

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 mg. He experienced a psychedelic trip that caused profound changes in his life and outlook.

Arthur Kleps

List of psychedelic plants

Methallylescaline

Psychedelic experience

Psychoactive drug

Entheogen

The Doors of Perception

The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead

National Institutes of Health – National Institute on Drug Abuse Hallucinogen InfoFacts

at Erowid

Mescaline

at PsychonautWiki

Mescaline

PiHKAL entry

Mescaline entry in PiHKAL • info

on YouTube

Film of Christopher Mayhew's mescaline experiment

an essay by Alexander Shulgin

Mescaline: The Chemistry and Pharmacology of its Analogs

Mescaline on the Mexican Border