Mescaline: A Global History of the First Psychedelic UC Berkeley Center for the Science of Psychedelics

Others, though, used mescaline not for spiritual enlightenment but for artistic and philosophical experiments. In the 1890s, aesthetes and poets such as Havelock Ellis and WB Yeats experimented with it, looking at art objects and listening to music under the influence. In the 1930s, avant-garde artists painted on it, and psychiatrists gave it to intellectuals like Walter Benjamin and Jean-Paul Sartre. Sartre had a very unpleasant experience, after which he believed he was being followed around by crabs that nobody else could see. For men who had been brought up as warriors, the peyote meeting became a microcosm of their vanished world.

Today, the church is active and legally able to harvest peyote to use as a sacrament in their religious practices. Peyote (Lophophora williamsii) has been traditionally consumed by Indigenous North American tribes for at least 5,500 years. The crowns of the cacti growing above ground are called the peyote buttons, which are carefully harvested to allow the plant to continue to grow.

The pharmacology of mescaline has been assessed in animal models (Bevan et al., 1974; Darvesh and Gudelsky,2003; Kyzar et al.,2012; Nichols,2004), and the subjective effects have been reported in numerous casestudies (Frederking,1955; Halpern,1961; Klüver,1926; Osmond andSmythies, 1952). The hallucinogenic effects of mescaline will last longer for some people than others. Depending on a person’s height, weight, mental state, previous drug use, mescaline can last between 10 and 20 hours.

Furthermore, similar to MDMA (and unlike any of the other classical psychedelics that bind to and activate serotonin receptors), it is thought that mescaline may increase the release and/or re-uptake of serotonin4. For this reason, ‘microdosing’ phenethylamines like MDMA (and possibly mescaline) on a regular basis may cause depletion of neurotransmitters and unwanted side effects. Tracing back its history19, mescaline has been used as a religious sacrament for at least one hundred years in the USA. The religious use of peyote was formed by the Native American Church in the late nineteenth century in Oklahoma, USA. However, the Native American Church fought for their right to use peyote and succeeded in keeping the sacred cacti as part of their religious ceremonies through the American Indian Religious Freedom Act of 1978 (and the Amendment in 1994).

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Although chemically related to dopamine and norepinephrine, psychedelic phenethylamines also interact with the serotonin pathway by stimulating serotonin receptors and increasing the release of serotonin. Mescaline has unique effects compared to serotonin 2A receptor agonists like psilocybin and, in many ways, can induce effects similar to adrenaline, such as nausea and increased heart rate. The experience and side effects of mescaline are a cross between the classical psychedelics and amphetamines1,2. As shown in Table 3,there were several differences across the four mescaline subgroups, whereinthose in the Peyote subgroup reported consuming more doses (2.9) in their mostmemorable experience compared to all other subgroups. Likewise, largerproportions of respondents in the San Pedro (27%) and Peyote (31%) subgroupsreported that their mescaline was administered by a shamanic practitionercompared to those in the synthetic or extracted subgroups.

Cognitive effects

Though it’s not as prevalent today, mescaline was the first psychedelic to enter mainstream Western culture—before the widespread use of LSD and psilocybin. More recently, the extracted compound has shown promise in the medical and psychotherapeutic treatment of substance abuse and depression, among other conditions. Mescaline is a naturally occurring psychoactive alkaloid that is the main psychedelic compound in a range of psychedelic cacti native to the Americas, including peyote, San Pedro, and Peruvian Torch. In its natural state, mescaline has been used in Native American religious and shamanic ceremonies for thousands of years. Mescaline is known to provide spiritual insights, psychological healing, and deep contemplative states22. However, the current research on psychotherapeutic applications is quite limited compared to other psychedelic substances.

Substance

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.

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Phenylethylamines are compounds that work on the sympathetic (also known as the ‘fight or flight’) nervous system. There are many types of phenethylamines, including the endogenous (produced by the human body) neurotransmitters norepinephrine and dopamine, as well as non-psychoactive pharmaceuticals like salbutamol (commonly used in inhalers for asthma) and phenylephrine (a nasal decongestant). Examples of psychoactive phenethylamines include amphetamines (used for the treatment of ADD/ADHD), MDMA, and mescaline. Like most psychedelic hallucinogens, mescaline is not physically addictive; however, it can cause tolerance meaning higher doses are need to achieve the same hallucinogenic effect.

Visual effects

Through community outreach at the grassroots level, people who use drugs and public health officials leaders work together to improve health. Mescaline was isolated in 1897 from the peyote cactus, first encountered by Europeans during the Spanish conquest of Mexico. During the twentieth century it was used by psychologists investigating the secrets of consciousness, spiritual seekers from Aleister Crowley to the president of the Church of Jesus Christ of Latter-day Saints, artists exploring the creative process, and psychiatrists looking to cure schizophrenia. Meanwhile peyote played a vital role in preserving and shaping Native American identity. Drawing on botany, pharmacology, ethnography, and the mind sciences and examining the mescaline experiences of figures from William James to Walter Benjamin to Hunter S. Thompson, this is an enthralling narrative of mescaline’s many lives.

Like with many other psychedelic drugs, mescaline’s potential as a therapeutic substance was studied in the 1950s and 1960s—particularly in combination with LSD. Studies suggest, for example, that mescaline may increase blood flow and activity in the prefrontal cortex, the area of the brain in charge of planning, problem-solving, emotional regulation, and behavior. Low activity in this area is linked to depression and anxiety, leading scientists to hypothesize that mescaline could help alleviate symptoms of these disorders. People have used hallucinogens for hundreds of year, mostly for religious rituals or ceremonies. From the earliest recorded time, peyote has been used by natives in northern Mexico and the southwestern United States, where it grows, as a part of traditional religious rites. It has an effect that is similar to LSD or psilocybin (magic mushrooms) and other hallucinogenic drugs.

This Heidelberg school of thought would eventually influence the mesclun psychedelic understanding that mescaline could be used for therapeutic purposes, such as psychotherapy. Jaspers would eventually be removed from his teaching post as Heidelberg came under Nazi control. It’s spread rapidly through tribes where it used to be uncommon, such as the Navajo, where new religious movements such as evangelical and pentecostal Christianity are also on the rise.

• This diverse group of substances all share the same chemical backbone and have a similar overall molecular structure.
• For many, a mescaline journey offers deep insight into the self and the universe, giving one a greater sense of connection and spirituality.
• Mescaline is a naturally-occurring psychoactive alkaloid found in several cacti, including the Peyote cactus (Lophophora williamsii), San Pedro cactus (Echinopsis pachanoi), and Peruvian Torch cactus (Echinopsis peruviana).
• Plants of Gods is written by ethnopharmacologist Christian Ratsch, who provides knowledge on various psychoactive plants, including mescaline.

Analyses were conductedusing the IBM SPSS Statistics v.25 and v.26 (IBM Corp., Armonk, NY, USA). Most respondents with prior psychiatric conditions (i.e. depression, anxiety,post-traumatic stress disorder, and drug and alcohol misuse) reported improvementsin these conditions following their most memorable experience with mescaline. Onecan speculate whether the experience was memorable due to the improvement in suchhealth functioning. These numbers are similar to reports from 5-MeO-DMT users (Davis et al., 2018) andrelatively low in comparison to reported craving for more widely used substances(e.g. alcohol) (McCabe et al.,2017). Consistent with prior research (Johansen and Krebs, 2015; Krebs and Johansen, 2013),these findings may indicate that mescaline has a relatively favorable psychologicalsafety profile for the use in naturalistic settings as evidenced by reports of lowabuse liability.

Beyond kaleidoscopic visuals, mescaline can alter tactile sensations and the perception of space and time4. And yet, one self-blinding study suggests that the placebo effect is more likely to be the source of reported benefits of microdosing, but microdosing is definitely difficult to study in controlled settings given all of the possible factors involved. But controlling for things as variable as weather, hormonal shifts, not to mention the news cycle, means that marginal changes in well-being might be less beneficial to study than things like long-term relief from chronic symptoms. Perhaps if combined with additional efforts toward self-care rituals like proper rest, consistent meal times, adequate hydration and good exercise, microdosing with mescaline can lead to long-term wellness. As inquiries began coming in and people began sharing their progress, Fadiman began conducting studies of the subjective effects of microdosing alongside his assistant Sophia Korb. These studies revealed that those who microdose report increased levels of focus, creativity, and energy.

If someone is taking synthetic mescaline produced in a lab then it will most commonly come in the form of a pill that is swallowed. There are also reports of people injecting liquid mescaline directly into their bloodstream, though these cases are rare. Mescaline is taken in a variety of ways spending on what form of the drug is being used. Traditional peyote is taken by chewing, smoking, or eating specific parts of the plant. These parts of the plant, commonly referred to as buttons, are extracted from the roots. Anecdotal reports suggest that there are no negative health effects attributed to simply trying mescaline by itself at low to moderate doses and using it very sparingly (but nothing can be completely guaranteed).

LSD took mescaline’s research crown from the 1950s onwards (see M. Jay Nature 497, 435–436; 2013). But its reign, too, petered out, under pressure from the drug-control lobby during the 1970s. In the past decade or so, as Michael Pollan’s 2018 How to Change Your Mind chronicled, a smattering of research using hallucinogens has resumed. With the Fadiman protocol, a microdose is taken every third day, beginning on Day 1, Day 4, Day 7, Day 10, etc. If the dose is not small enough — the goal is for a microdose to be sub-perceptible. It would seem that this group of scholars and philosophers recognized that mescaline could be an intense experience for heightening self-awareness and phenomenological thought and analysis.

Atai Life Sciences is working to combine psychedelics with brain-computer interfaces for mental health treatment. Due to its status as an internationally controlled substance, research into the harm potential of mescaline—especially long-term—has been limited. A lethal dose has never been identified, probably because it’s too high to be taken accidentally.9 In other words, to the best of our knowledge, nobody has ever died from a mescaline overdose.

The San Pedro cactus, though, grows abundantly across Peru, Eduador and Bolivia, and San Pedro shamans and healing ceremonies are spreading round the globe. Variables may not equal 100% due to rounding error.N is varied due to participants choosing“prefer not to answer” on specific items. Scores of themystical-type, challenging, insight, and ego-dissolution effects canrange from 0 to 5. Ratings of personal meaning, spiritualsignificance, psychological challenge, and psychological insight canrange from 0 to 7. Characteristics of the “most memorable” mescaline experience in the fullsample and comparisons of characteristics across mescalinesubgroups.