Mescaline

Mescaline

Systematic (IUPAC) name
2-(3,4,5-trimethoxyphenyl)ethanamine
Clinical data
AHFS/Drugs.com	entry
Pregnancy cat.	C (US)
Legal status	Prohibited (S9) (AU) Schedule III (CA) ? (UK) Schedule I (US)
Routes	Oral, Intravenous
Pharmacokinetic data
Half-life	6 hours
Identifiers
CAS number	54-04-6 Y
ATC code	None
PubChem	CID 4076
ChemSpider	3934 Y
UNII	RHO99102VC Y
KEGG	C06546 Y
ChEBI	CHEBI:28346 Y
ChEMBL	CHEMBL26687 Y
Synonyms	3,4,5-trimethoxyphenethylamine
Chemical data
Formula	C11H17NO3
Mol. mass	211.257 g/mol
SMILES	eMolecules & PubChem
InChI InChI=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 Y Key:RHCSKNNOAZULRK-UHFFFAOYSA-N Y
Physical data
Melt. point	183 °C (361 °F)
Y (what is this?)  (verify)

Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class, known for its mind-altering effects similar to those of LSD and psilocybin.

It occurs naturally in the Peyote cactus (Lophophora williamsii), the San Pedro Cactus (Echinopsis Pachanoi) and in the Peruvian Torch (Echinopsis Peruviana), and as well in a number of other members of the Cactaceae plant family. It is also found in small amounts in certain members of the Fabaceae (bean) family, including Acacia berlandieri. Mescaline was first isolated and identified in 1897 by the German Arthur Heffter and first synthesized in 1919 by Ernst Späth.

Naturally derived mescaline powder extract.

History and usage

Peyote has been used for over 3000 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 at ground level, leaving the large tap roots to grow new 'Heads'. These 'Heads' are then dried to make disk-shaped buttons. Buttons are chewed to produce the effects or soaked in water for an intoxicating 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."

Aldous Huxley described his experience with mescaline in The Doors of Perception. Aleister Crowley reported using mescaline in his diary. The sex psychologist Havelock Ellis also tried mescaline. Hunter S. Thompson recounted an extremely detailed account of his first use of mescaline in First Visit with Mescalito, appearing in his book Songs of the Doomed. Psychedelic research chemical pioneer Alexander Shulgin said he was first inspired to explore psychedelic compounds by an experience on mescaline.^{[citation needed]}

Biosynthesis of mescaline

Mescaline can be synthesized from tyrosine or a hydroxylated phenylalanine. In Lophophora williamsii, dopamine converts into mescaline in a biosynthetic pathway involving m-O-methylation and aromatic hydroxylation.

Pharmacokinetics

Tolerance builds with repeated usage, lasting for a few days. Mescaline causes cross-tolerance with other serotonergic psychedelics such as LSD, psilocybin/psilocin, and DMT. THC and muscimol do not produce cross tolerance with each other or with serotonergic psychedelics as they operate on different receptors.

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 to not 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 its own unique characteristics. Subjective effects may include altered thinking processes, an altered sense of time and self-awareness, and closed and open-eye visual phenomena.

Like LSD and psilocybin, the subjective "open-eye visuals" are not true hallucinations as they are consistent with actual experience and manifest as intensifications and alterations of existing stimuli (objects and sounds), not the appearance of non-existent fanciful objects or actions that the user believes are real; the appearance of non-existent persons or objects is a feature of true hallucinations, and believing that the hallucinations are "real" is a defining feature of delusions, which is not a common effect of psychedelics.

Prominence of color is distinctive, appearing brilliant and intense. Recurring visual patterns observed during the mescaline experience include stripes, checkerboards, angular spikes, multicolored dots, and very simple fractals which 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 which manifest more clearly with eyes closed and under low lighting conditions; however, all of these visual descriptions are purely subjective.

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 elicits a pattern of sympathetic arousal, with the peripheral nervous system being a major target for this substance. Effects typically begin 1-2 hours after ingestion, and may last 12-18 hours depending on dosage.

Mode of action

Mescaline acts similarly to other psychedelic agents. It binds to and activates the serotonin 5-HT_2A receptor with a high affinity as a partial agonist. How activating the 5-HT_2A receptor leads to psychedelia is still unknown, but it likely somehow involves excitation of neurons in the prefrontal cortex. Mescaline is also known to bind to and activate the serotonin 5-HT_2C receptor.

In addition to serotonin receptor activity, mescaline also stimulates the dopamine receptors. Whether mescaline possesses dopamine receptor agonist properties or initiates the release of dopamine remains unclear.

Difluoro and trifluoromescaline have shown to be more potent than their unfluorinated analogue.

Legality

In the United States, mescaline was made illegal in 1970 by the Comprehensive Drug Abuse Prevention and Control Act. The drug was prohibited internationally by the 1971 Convention on Psychotropic Substances and is categorized as a Schedule I hallucinogen by the CSA. Mescaline is legal only for certain religious groups (such as the Native American Church) and in scientific and medical research. In 1990, the Supreme Court ruled that the state of Oregon could bar 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 was unconstitutional when applied against states. However, in a subsequent case, the Court held that the Government had not carried the burden under the Religious Freedom Restoration Act of showing a compelling interest that allowed no exception to the ban on the use of the drug to accommodate a sincere religious practice. Thus, the current state of the law is that, while the federal government may not restrict use of peyote in ceremony, individual states do have a right to restrict its use.

In the UK, mescaline in purified powder form is a Class A drug. However, dried cactus can be bought and sold legally, unlike raw "magic" (psilocybin containing) mushrooms, which are now illegal. In Australia the peyote cacti and mescaline are strictly illegal, however San Pedro and other mescaline-containing plants are legal for ornamental/gardening purposes.^{[citation needed]} In Canada 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 San Pedro and San Peruvianus without restriction, as it is specifically exempt from legislation.

See also

• PiHKAL
• List of psychedelic plants
• Psychedelic experience
• Psychoactive drug
• The Doors of Perception
  • Mind at Large (concept in The Doors of Perception)
• The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead
  • Entheogen

External links

• National Institutes of Health - National Institute on Drug Abuse Hallucinogen InfoFacts
• Mescaline at Erowid
• PiHKAL entry
• Mescaline entry in PiHKAL • info
• Film of Christopher Mayhew's mescaline experiment on YouTube
• Mescaline: The Chemistry and Pharmacology of its Analogs, an essay by Alexander Shulgin
• Mescaline on the Mexican Border