Peyote has been used for at least 5,700 years by Native Americans in Mexico. Europeans noted use of peyote in Native American religious ceremonies upon early contact, notably by the Huichols in Mexico. Other mescaline-containing cacti such as the San Pedro have a long history of use in South America, from Peru to Ecuador.
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 contemporary users will often grind it into a powder and pour it in capsules to avoid having to taste it. The usual human dosage is 200–400 milligrams of mescaline sulfate or 178–356 milligrams of mescaline hydrochloride. The average 76 mm (3.0 in) button contains about 25 mg mescaline.
In 1955, English politician Christopher Mayhew took part in an experiment for BBC's Panorama, in which he ingested 400 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".
Potential medical usage
Mescaline has a wide array of suggested medical usage, including treatment of alcoholism and depression, due to these disorders having links to serotonin deficiencies. 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 humans have been conducted since the early 1970s.
Mescaline is biosynthesized from tyrosine which, in turn, is derived from phenylalanine by the enzyme phenylalanine hydroxylase. In Lophophora williamsii (Peyote), dopamine converts into mescaline in a biosynthetic pathway involving m-O-methylation and aromatic hydroxylation.
Tyrosine and phenylalanine serve as the metabolic precursors to synthesis of mescaline. Tyrosine can either undergo a decarboxylation via tyrosine decarboxylase to generate tyramine and subsequently undergo an oxidation at carbon 3 by a monophenol hydroxylase or first be hydroxylated by tyrosine hydroxylase to form L-DOPA and decarboxylated by DOPA decarboxylase. These create dopamine, which then experiences methylation by a catechol-O-methyltransferase (COMT) by an S-adenosyl methionine (SAM)-dependent mechanism. The resulting intermediate is then oxidized again by a hydroxylase enzyme, likely monophenol hydroxylase again, at carbon 5, and methylated by COMT. The product, methylated at the two meta positions with respect to the alkyl substituent, experiences a final methylation at the 4 carbon by a guaiacol-O-methyltransferase, which also operates by a SAM-dependent mechanism. This final methylation step results in the production of mescaline.
Phenylalanine serves as a precursor by first being converted to L-tyrosine by L-amino acid hydroxylase. Once converted, it follows the same pathway as described above.
Biosynthesis of mescaline
Laboratory synthetic mescaline. Biosynthesized by peyote, this was the first psychedelic compound to be extracted and isolated.
Mescaline was first synthesized in 1919 by Ernst Späth from 3,4,5-trimethoxybenzoyl chloride. Subsequent to this, numerous approaches utilizing different starting materials have been developed. Notable examples include the following:
About half the initial dosage is excreted after 6 hours, but some studies suggest that it is not metabolized at all before excretion. Mescaline appears not to be subject to metabolism by CYP2D6 and between 20% and 50% of mescaline is excreted in the urine unchanged, and the rest being excreted as the carboxylic acid form of mescaline, a likely result of MAO degradation. 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).
Behavioral and non-behavioral effects
Mescaline induces a psychedelic state similar to those produced by LSD and psilocybin, but with unique characteristics. Subjective effects may include altered thinking processes, an altered sense of time and self-awareness, and closed- and open-eye visual phenomena.
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. Aldous Huxley described these self-transforming amorphous shapes as like animated stained glass illuminated from light coming through the eyelids. Like LSD, mescaline induces distortions of form and kaleidoscopic experiences but they manifest more clearly with eyes closed and under low lighting conditions. Mescaline may cause Hallucinogen persisting perception disorder.
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."
As with LSD, synesthesia can occur especially with the help of music. An unusual but unique characteristic of mescaline use is the "geometricization" of three-dimensional objects. The object can appear flattened and distorted, similar to the presentation of a Cubist painting.
Mescaline is produced when products of natural mammalian catecholamine-based neuronal signaling such as dopamine and noradrenaline are subjected to additional metabolism via methylation, and mescaline's hallucinogenic properties stem from its structural similarities with these two neurotransmitters. In plants, this compound may be the end-product of a pathway utilizing catecholamines as a method of stress response, similar to how animals may release compounds such as cortisol when stressed. The in vivo function of catecholamines has not been investigated, but they may function as antioxidants, as developmental signals, and as integral cell wall components that resist degradation from pathogens. The deactivation of catecholamines via methylation produces alkaloids such as mescaline.
Difluoromescaline and trifluoromescaline are more potent than mescaline, as is its amphetamine homologue trimethoxyamphetamine. Escaline and proscaline are also both more potent than mescaline, showing the importance of the 4-position substituent with regard to receptor binding.
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. The drug was prohibited internationally by the 1971 Convention on Psychotropic Substances. 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.
In the United Kingdom, mescaline in purified powder form is a Class A drug. However, dried cactus can be bought and sold legally.
Mescaline is considered a schedule 9 substance in Australia under the Poisons Standard (October 2015). 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." 
The peyote cacti and other mescaline-containing plants such as San Pedro are illegal in Western Australia, Queensland, and the Northern Territory, whilst in other states such as Tasmania, Victoria and New South Wales, they are legal for ornamental and gardening purposes.
In Canada, France, The Netherlands and Germany, mescaline in raw form and dried mescaline-containing cacti are considered an illegal drug. 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. In Canada, mescaline is classified as a schedule III drug under the Controlled Drugs and Substances Act, whereas peyote is exempt.
In Russia mescaline, its derivatives and mescaline-containing plants are banned as narcotic drugs (Schedule I).
Havelock Ellis was the author of one of the first written reports to the public about an experience with mescaline (1898).
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.
Martin Kemp, English actor and former Spandau Ballet bassist, described in an interview experiencing mescaline at a late-night party during the height of his musical career in the 1980s: "Mescaline is the drug The Beatles wrote Rubber Soul about. It turns everything to rubber. Every step you take feels like rubber. It is a lot of fun, I have to say. But it goes on for hours – like eight hours".
Psychedelic research pioneer Alexander Shulgin said he was first inspired to explore psychedelic compounds by a mescaline experience.
Bryan Wynter produced Mars Ascends after trying the substance his first time.
According to Paul Strathern's book Sartre in 90 Minutes, Jean-Paul Sartre experimented with mescaline, and his description of ultimate reality (in Nausea) as "viscous and obscene" was written under mescaline's influence.
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