Mescaline: The forgotten psychedelicIoanna A Vamvakopoulou 1, Kelly A D Narine 2, Ian Campbell 2, Jason R B Dyck 3, David J Nutt 4
Mescaline is a naturally occuring alkaloid found in cacti, including the peyote and San Pedro cacti.
Mescaline is a serotonin 5HT2A/2C receptor agonist, also acting on dopaminergic D1/2/3 and adrenergic α1A/2A receptors.
Mescaline may be useful in treating alcoholism and improving mental well-being in a naturalistic or religious setting.
IntroductionMescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited.
ObjectivesThis article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research.
FindingsMescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting.
ConclusionThe pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings.
This article is part of the Special Issue on ‘Psilocybin Research’.
- PMID: 36252614
- DOI: 10.1016/j.neuropharm.2022.109294
PERSONAL GROWTHMost users find mescaline personally or spiritually transformative, and many emerge with a lasting appreciation for the interconnectedness of all life in the universe, and of their role within it. Sometimes the mere thought of a separate identity can even seem “obscene.” Others feel a deep sense of gratitude and unconditional compassion for everyone and everything around them. Early studies of mescaline also found that the experience left people with a greater sense of wellbeing, inner strength, and vitality.
In line with Native American ritual use of peyote, mescaline can also help people solve sticky problems. In one study, a group of 27 men were given mescaline and asked to think about a problem they were facing at work, some of which had persisted for months. After just one dose, almost every participant either solved the problem for themselves or came up with new ways to approach it.
Peyote may also boost learning capabilities. In another study, researchers found that mescaline helped goldfish learn to avoid a shock more quickly. These findings support the prevailing view that mescaline and other psychedelics can enhance creativity. As the psychologist Stanley Krippner put it, “to invent something new, one cannot be completely conditioned or imprinted.” Psychedelics like mescaline tend to dissolve preconceptions and elicit fresh perspectives on reality.
3,4,5-Trimethoxyphenethylamine (also known as mescaline) is a naturally-occurring classical psychedelic substance of the phenethylamine class. It occurs naturally in the peyote cactus (Lophophora williamsii), San Pedro cactus (Echinopsis pachanoi), Peruvian Torch cactus (Echinopsis peruviana) as well as the Cactaceae plant and the Fabaceae bean families. It is one of the oldest known hallucinogens and the parent compound of the psychedelic phenethylamines, one of the two major subclasses of psychedelic compounds (along with tryptamines).
Mescaline was first isolated from peyote in 1897 by the German chemist Arthur Heffter. The ritual use of the peyote cactus has occurred for at least 5700 years by Native Americans in Mexico and other mescaline-containing cacti such as the San Pedro have a long history of use in the South American continent, from Peru to Ecuador. Mescaline is an important part of the life's work of the American chemist Alexander Shulgin, who used it as a starting point for synthesizing dozens of novel psychedelic compounds that are documented in his 1991 book PiHKAL ("Phenethylamines I Have Known and Loved").
Subjective effects include open and closed-eye visuals, time distortion, enhanced introspection, conceptual thinking, euphoria, and ego loss. Mescaline is generally considered to be one of the most gentle, insightful, and euphoric psychedelics. It is known for placing greater emphasis on bodily and tactile sensations (sometimes compared to MDMA) than psychedelic tryptamines like psilocybin or DMT, which tend to have a more frenetic headspace and dynamic visual geometry. It is considered to be one of the best agents for psychedelic therapy due to its mellow, organic, yet complex character. Synthetic mescaline is highly sought after by connoisseurs and is typically produced in limited batches, owing to its low potency and relatively high production cost.
Unlike other highly prohibited substances, mescaline has not been proven to be physiologically toxic or addictive. Nevertheless, adverse psychological reactions such as anxiety, paranoia, delusions, and psychosis can still always occur, particularly among those predisposed to mental disorders. Additionally, it should be noted that in street markets terms like "mescaline" or "synthetic mescaline" are commonly used as deceptive labels for other psychedelics (e.g. 2C-x, DOx, or 25x-NBOMe) that are typically more dangerous. It is highly advised to use harm reduction practices if using this substance.
History and cultureThe ritual use of the Peyote cactus has occurred for at least 5700 years by Native Americans in Mexico. Upon early contact, Europeans noted the use of Peyote in Native American religious ceremonies. Additionally, alternative mescaline-containing cacti such as the San Pedro have a long history of use in the South American continent, spanning from Peru to Ecuador. The principal psychoactive component in both Peyote and San Pedro, mescaline, was first isolated and identified in 1897 by the German chemist Arthur Heffter and first synthesized in 1919 by Ernst Späth. It was one of the first psychedelics to be experimented with by Western intellectuals like Aldous Huxley, who famously described its effects in the 1954 essay "The Doors of Perception".
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 disc-shaped buttons and the buttons are chewed to produce the effects or soaked in water to drink. In modern times, users will often grind it into a powder and pour it into gel capsules to avoid having to come into contact with the bitter taste of the cactus. The usual human dose 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.
Mescaline is an important part of the life's work of Alexander Shulgin, a psychedelic chemist and researcher. Shulgin used mescaline as a starting point for synthesizing dozens of novel psychedelic phenethylamine compounds such as the 2C-x and DOx families. It is a member of the so-called "magical half-dozen" which refers to Shulgin's self-rated most important phenethylamine compounds with psychedelic activity, all of which except mescaline he developed and synthesized himself. They are found within the first book of PiHKAL, and are as follows: Mescaline, DOM, 2C-B, 2C-E, 2C-T-2 and 2C-T-7.
ChemistryMescaline, or 3,4,5-trimethoxyphenethylamine, is a substituted phenethylamine featuring a phenyl ring bound to an amino -NH2 group through an ethyl chain. Mescaline contains three methoxy functional groups CH3O- which are attached to carbons R3, R4, and R5 of the phenyl ring.
Mescaline has a number of structural analogs, which include but are not limited to: proscaline, escaline, and methallylescaline. It is also the synthetic starting point of the 2C-x and DOx family of psychedelic phenethylamines. 2C-x compounds like 2C-B (also known as bromomescaline) produce mescaline-like psychedelic effects but with greater potency and a reduced duration. DOx compounds (e.g. DOM, DOB) have a significantly extended duration and more stimulant effects.
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|Common names||Mescaline, Peyote, San Pedro, Cactus, Buttons|
Currently only Native American Tribes can get a special exception to use it religiously, but "Freedom of Religion" doesn't hold up for everyone else in the United States currently.