Mescaline: Definition, Cacti, Effects & More
Many credit author Aldous Huxley for popularizing mescaline in his 1954 book The Doors of Perception, where he famously romanticized the folds of his gray flannel trousers in an experience that allowed him to see “things as they really are.” But in fact this compound has been used as a sacred medicine in many parts of the world for millennia and was the first psychedelic to enter mainstream Western culture.
And while the psychedelic renaissance continues to pick up more and more momentum driven by compounds like psilocybin, MDMA and LSD, mescaline has been getting a lot less buzz.
That’s poised to change, as academics and commercial interests are taking up the mantle on mescaline research. Additionally, conservation of the most rich source of naturally occurring mescaline, peyote, becomes a more pressing concern to the Indigenous communities who use it in their spiritual rituals and healing ceremonies.
Keep reading to uncover more about this ancient medicine, how it’s used, its effects and what the current medical research landscape looks like.
What Is Mescaline?
Mescaline (3,4,5-trimethoxyphenethylamine) is an alkaloid that naturally occurs in differing concentrations across a variety of cacti native to the Americas.
Mescaline-containing cacti have been used in this region as a sacramental medicine for thousands of years, and spread into more mainstream Western use in the late 19th century. Today, mescaline extracts from cacti and synthetic forms of the molecule are also used outside Indigenous and Native American communities.
Known for its brilliant visuals and its ability to induce novel interpretations of the world around you, mescaline is now starting to receive more attention from researchers and commercial entities alike for its potential as a therapeutic agent to treat a handful of conditions.
Brief Historical Context
Mescaline has a fascinating and largely unknown history that dates back thousands of years. It is often referred to as “the first psychedelic,” and there is direct archaeological evidence that cacti containing the compound are among the oldest psychedelics used in the New World.
Radiocarbon dating of peyote found in Texas suggests its use dates back at least 5,700 years, though some evidence suggests that these cacti have been more widely used by Indigenous cultures in the Americas for more than 7,000 years.
More recently, Europeans first came into contact with the compound when Spain conquered Mexico in the early 16th century. Spanish missionaries tried to eradicate its use by Indigenous populations, who would access the mescaline found in cacti called peyote (Lophophora williamsii) for ceremonial and spiritual uses — but its use by and importance to these communities endured.
As colonial displacement and persecution forced Indigenous populations out of their homelands, word of the mystical properties of peyote spread to Native American communities in the plains, where it too became an integral part of their spiritual practices and ceremonies.
By the late 19th century, knowledge of mescaline and its psychedelic experiences had spread beyond the Indigenous communities of Mexico and the U.S., though the term “psychedelic” hadn’t yet been assigned to these novel and fascinating substances.
Eventually, mescaline became the first psychedelic agent to gain medical attention and was being experimented with by a growing number of physicians, psychiatrists and psychologists.
In 1893, pharmaceutical company Parke-Davis introduced peyote tincture as a respiratory stimulant and heart tonic, and mescaline, the principal active ingredient in peyote, was identified and isolated in 1897 by German chemist Arthur Heffter.
By 1913 one of the first human trials took place in New York City to investigate whether the mescaline-induced experience shared any commonalities with schizophrenia.
In 1919, chemist Ernst Späth was the first to produce a synthetic form of mescaline, which was picked up and marketed by German pharmaceutical company Merck (who was also the first to synthesize MDMA) in 1920. Systematic clinical trials began in Germany in the 1920s, as Simon Brandt, a forensic chemist at Liverpool John Moores University, told Nature.
While research trying to uncover more about schizophrenia via the mescaline-induced trip eventually proved fruitless, the compound started getting still more attention from medical and non-medical communities alike. In Europe, artists, philosophers, psychiatrists and psychologists started using the compound to explore the human mind, with experiences ranging from positive to negative.
While the author, Aldous Huxley, found a new and blissful dimension to the human experience, others, like philosopher Jean-Paul Sartre, had challenging experiences with mescaline and these varying accounts of mescaline’s effects became more widely known.
By World War II, mescaline research had been taken up by the militaries in both Germany and the US, being used in human experimentation done by the Third Reich and by the US Office of Strategic Services (the precursor to the Central Intelligence Agency or CIA) to investigate its potential as a truth serum. Mescaline was also later part of the famous mind control project of the CIA, MK Ultra.
By the 1950s mescaline was being further investigated for its therapeutic use in psychiatry and psychology, as a way to help patients access repressed memories, gain insight into emotional issues or explore their ego defense mechanisms.
In the U.S., chemist and renowned psychedelic researcher Alexander Shulgin was captivated by the molecule only a few years after Huxley’s famous trip in May of 1953. Shulgin’s first experience with mescaline is what spurred him to leave his job at Dupont to pursue his now famous and extensive work in the chemistry of psychedelics.
Shulgin, often called the godfather of psychedelics, went on to experiment with and synthesize hundreds of different psychedelic compounds, but mescaline remained his favorite (Pollan, This Is Your Mind on Plants, Penguin Press, 2021).
Eventually, a new kid on the psychedelic block stole the spotlight from mescaline. Newly re-discovered LSD (lysergic acid diethylamide) had captured the minds of scientists, doctors and other mental healthcare practitioners as a compound that could induce similar, if not reliably more potent, hallucinogenic experiences to mescaline but without the same side effects, such as nausea, paranoia and increased heart rate.
In 1967 mescaline was added to Schedule I of the UN Convention on Drugs and then to the Controlled Substances Act in the U.S. in 1971, which made it illegal and recognized no medicinal value in the compound.
The American Indian Religious Freedom Act (AIRFA) of 1978 and its 1994 amendments protect the “non-drug” use of peyote in “bona fide religious ceremonies.” In 1981, the Native American Church received specific exemption for their use of peyote in religious ceremonies.
While mescaline use outside of Native communities has continued despite its legal status, today, in the midst of a renaissance of scientific research into the therapeutic use of psychedelics, mescaline had been largely absent until recently.
With a renewed interest in its potential therapeutic value, now both academic and corporate interests are beginning foundational research on mescaline.
Where Does Mescaline Come From?
Mescaline is a naturally occurring psychedelic compound found in a variety of cacti native to the Americas, such as peyote (Lophophora williamsii), San Pedro (Echinopsis pachanoi), Peruvian torch (Echinopsis peruviana), Bolivian torch (Echinopsis lageniformis) and the leaf or rose cactus (Pereskia aculeate). Mescaline can also be synthesized in a lab.
Which Cacti Contain The Most Mescaline?
Concentrations of mescaline in these cacti vary, though peyote is the most potent and has been reported to contain about 0.4 percent mescaline in fresh cacti and 3-6 percent in dried. Though data is limited, others seem to contain much less with both the Peruvian torch and San Pedro cacti containing about 0.3-2 percent each in dried material.
It’s imperative to point out that the natural peyote population is under pressure, and Native American access to wild peyote is becoming more and more limited.
Native to northern Mexico and the southwestern U.S., the wild populations of peyote have certainly been depleted but there is debate as to whether the populations are truly in danger of extinction or not. Regardless, poaching by non-Indigenous people remains a concern and federal protections for wild peyote populations are being sought out by the Native American Church (NAC).
Peyote is a slow growing cactus, and can only be harvested once every eight years. Peyote is now considered a vulnerable species and reduced sexual reproduction may pose a significant threat to the continuing survival of the wild species.
Synthetic Mescaline
The two most commonly produced synthetic forms of mescaline are mescaline hydrochloride and mescaline sulfate. The use of synthetic mescaline is gaining support as a way to help protect declining peyote populations in the face of growing demand from communities outside the NAC.
How Is Mescaline Used?
Epidemiological data around mescaline use is limited, but traditional use of San Pedro in Andean shamanistic culture for healing rituals continues to this day.
Among the communities belonging to the Native American Church, peyote use is not aimed at producing a hallucinogenic experience so much as a tool allowing ceremonial participants to access parts of the consciousness for healing.
The limited research and shared observations we do have on peyote’s sacred use shows that ceremonies are a way to foster health, balance, respect and a sense of community. Some research from the 1970s suggests that peyote has been used to treat alcohol use disorder within the NAC.
Limited data is available on when and how often peyote is used, but a 2022 epidemiological survey reported that members of the NAC may use peyote anywhere from once per year to two to three times per week.
While mescaline can be consumed in naturally-derived tinctures, refined powders and synthetic forms, they are not necessarily interchangeable from a cultural standpoint. Mescaline is most often consumed by these communities in the fresh or dried peyote button.
Outside traditional use, a recent global epidemiological survey of 452 adults who have used mescaline shows that a large majority of respondents (74 percent) seek out mescaline as a way to explore spirituality or connect with nature.
Most respondents believe that mescaline could be used as a tool for personal growth (90 percent), spiritual growth (87 percent), psychotherapeutic work (81 percent) or for boosting creativity (76 percent) and cognitive abilities (61 percent).
Respondents to this survey were asked to reference their “most memorable” mescaline experience and reported that symptoms around anxiety, depression, post-traumatic stress disorder and alcohol use disorder were improved after this trip.
The researchers who conducted the survey pointed out that very few of the respondents took mescaline with that explicit intention.
How Is Mescaline Taken?
Mescaline can be consumed in different formats, which does have some impact on dosing. Like many psychedelics, mescaline also induces a rapid-onset tolerance.
Forms Of Mescaline
According to Dr. James Giordano, Pellegrino Center Professor of Neurology and Biochemistry at Georgetown University Medical Center, “mescaline is usually taken by cutting off the top portion of the cactus plants that produce it, and drying these cuttings to make ‘buttons’ or small coin shaped dried slices of the plant.” Both fresh cactus and dried buttons can be chewed or soaked in water to make drinkable liquids.
Mescaline can be extracted from cacti into a liquid solution like a tincture or turned into a powder. It can also be chemically synthesized in a lab into a pure mescaline powder.
Mescaline powders can range in color depending on how they were made and the degree or purification. Mescaline powder made from cacti may have a greenish color to them, while synthetic mescaline is usually available as a white to brownish powder. Powders are often packed into capsules as a pill.
Based on anecdotal reports from an international survey, the data suggests that most people access mescaline through the San Pedro cactus (66 percent), with a smaller number of people consuming mescaline via peyote (36 percent) and about 31 percent having taken synthetic mescaline.
Most people in this survey consumed mescaline orally (97 percent) though extracts could be taken sublingually or by snorting powder.
While more medical research is needed comparing the subjective effects people feel (“the trip”) between these different methods of consumption, it seems that consuming fresh or dried cacti or an extraction made from them produces a different experience than a synthesized or pure mescaline product. At least part of this is likely due to the variety of other compounds that are found in the fresh cactus versus extractions or refined powders.
Notably, it seems nausea and vomiting are more often connected to the consumption of cactus flesh (fresh or dried) as compared to other more purified forms of mescaline.
Dosing
A typical dose is 200–400 milligrams of mescaline sulfate or 178–356 milligrams of mescaline hydrochloride, with a common dose being about 300 milligrams.
There are slight differences between mescaline sulfate and mescaline hydrochloride in terms of dosing because of their molecular weight: 200 mg of mescaline sulfide is a comparable dose to 178 mg of mescaline hydrochloride, for example.
As with any drug, each person’s physiology and optimal dosage will be different. Starting with a low dose (considered to be anywhere from 50 milligrams to 200 milligrams) is a good way to understand your own body’s response to mescaline and as a baseline to increase or decrease the dose as needed.
Typically, effects are felt within an hour or so of ingestion. Peak effects come about 2-4 hours afterwards, with the entire trip lasting anywhere from 8-12 hours.
Tolerance
A common trait among other psychedelics, such as MDMA for example, is a period of “rapid-onset tolerance” after a trip where repeated use would offer fewer (if any) effects. For mescaline, it seems this period lasts about three to four days, assuming no further mescaline is consumed.
Dr. Giordano points out that “repeated low dosing of mescaline can lead to progressive tolerance, wherein iteratively higher doses of mescaline may be required to produce the desired (psychedelic) effects.”
In other words, regular use can result in more lasting and increasing levels of tolerance. As people take increasing doses to overcome tolerance, it could lead to greater impacts to the central nervous system such as arousal, increased heart rate and blood pressure.
“Also, mescaline can cause cross tolerance to other psychedelic drugs such as LSD and psilocybin, and their combined use is not recommended,” he added.
Mescaline’s Effects: What Does Mescaline Feel Like?
The effects you experience from mescaline will vary depending on a variety of factors, such as the methods of consumption, the dose, your physiology, mindset, cultural context and the setting in which you take it. Each person’s journey is different.
Although mescaline is often compared to other psychedelic substances like psilocybin or LSD, mescaline is more closely related (from a chemistry perspective) to MDMA (Molly).
With that being said, there are a few commonly reported effects and experiences that can help you prepare for a trip:
- Closed-eye hallucinations of patterns and colors
- Visual effects such as spatial and visual distortions
- Altered sense of time
- Synesthesia
- Changed perspectives and ways of thinking
- Altered interpretations of the world around you
- Heightened empathy and feelings of connection
- Potential nausea and vomiting
- Possible anxiety and paranoia
It’s been reported that mescaline brings on altered states in a relatively easy and unthreatening way, especially compared to more potent psychedelics like LSD, for example.
In a recent global survey of mescaline users, respondents characterized various subjective effects of the mescaline trip, including ego-dissolution, psychological insight, mystical-type effects and challenge, as “very light to moderate,” which the authors suggest is related to mescaline’s relative low potency and the “low to moderate” dose reported by 40 percent of the 452 respondent.
Feelings of connection and empathy seem to vary from person to person.
For instance, Alexander and his wife, Ann, reported “a remarkable effect” of mescaline to induce “extreme empathy felt for small all small things; a stone, a flower, an insect” in their book PiHKAL: A Chemical Love Story.
In Doors of Perception, Huxley states that mescaline produced a feeling of being part of the “manifest glory of things” that “left no room, so to speak, for the ordinary, the necessary concerns of human existence, above all for concerns involving persons.”
These differing experiences simply go to underscore the individuality of psychedelic experiences.
One other consideration that may impact mescaline’s effect is the type of mescaline taken: cactus flesh versus an extraction versus a synthesized product.
Some suggest that there is a subjective difference in the experience based on what form mescaline is taken in, with pure mescaline producing a more lucid and clear-headed effect while cactus flesh offers a more euphoric and body-centric experience, but more research is needed to understand these potential differences. The nonprofit Chacruna details the varying effects among different cacti species.
To learn more, you can find a variety of online communities where people share their experiences, or “trip reports,” and these offer a good way to put together a general sense as to what the mescaline experience might feel like.
How Does Mescaline Work In The Brain?
Psychedelics produce their effects by impacting neurotransmitters in the brain, including serotonin, dopamine and norepinephrine.
“Most notably, mescaline‘s hallucinogenic effects are produced by its action at serotonin type two receptors of the brain,” said Dr. Giordano.
He explained that other effects, including other aspects of the psychedelic experience and impacts on physiology such as heart rate, overall arousal, altered sensation, perception, and cognition, are mediated through the brain’s dopamine and norepinephrine systems.
Is Mescaline Safe?
Due to the illegal status of mescaline, research is lacking on the general safety and toxicity profile of the compound, though new efforts are focused on carrying out this basic research (covered in the Current Research Landscape section).
Anecdotal evidence supports that mescaline is relatively safe.
“Through the Native American Church and other groups, there are hundreds of thousands of people who regularly, consistently and safely use botanical forms of mescaline-containing plants, primarily peyote,” says Jeeshan Chowdhury, founder and chief executive of Journey Colab, told Nature.
Dr. Giordano echoed that mescaline is relatively safe, and typical recreational doses are well below the lethal dose.
Animal testing looking at lethal doses has produced a variety of estimates ranging from 54 mg/kg to 880 mg/kg across different species and routes of administration, and it has been speculated that a lethal dose in humans would be very difficult to consume and unlikely to happen accidentally.
Some fatalities linked to (though not caused by) mescaline have been reported. However, the details are limited, and there are no recorded overdose deaths caused by mescaline.
A retrospective review of the California Poison Control System database covering the years 1997–2008 found 31 reported cases, where commonly reported effects included hallucinations, increased heart rate, agitation, and pupil dilation. Vomiting was reported in one case. The authors categorized these effects as mild or moderate, and life-threatening toxicity was not reported in any of the cases in their review.
More research is necessary to examine the effects of using mescaline long term.
One study from 2005 found no evidence that long-term use among Native Americans led to psychological or cognitive deficits. The authors point out that traditional use in the NAC does not reflect how mescaline might be used recreationally, and so the findings should not be generalized to all long-term mescaline consumption.
Although more research is necessary, limited animal evidence suggests that it should be avoided by pregnant or breastfeeding women. And, as a general rule with psychedelics, individuals with mental illness or a history of mental illness such as schizophrenia should avoid taking them. There may also be risks associated with prescription drug interactions.
Is Mescaline Legal?
In the United States, mescaline and peyote are Schedule I illegal substances as defined by the Controlled Substances Act. Exemptions for peyote have been made for its specific religious use by members of the Native American Church.
In Canada, the legal status is slightly different: mescaline is illegal and included in Schedule III of the Controlled Drugs and Substances Act, but peyote has been exempted from the Act in recognition of its use by members of the NAC. Peyote is legal to grow and sell, but it is illegal to isolate mescaline from peyote.
Additionally, there is a wave of effort to decriminalize psychedelics from natural sources in cities across the U.S., and Canada has expanded medicinal access to psychedelics through its Section 56 exemption for medical research and its Special Access Program. The program grants access to healthcare professionals treating patients with serious or life-threatening conditions.
Snapshot Of The Current Research Landscape
While mescaline had been largely absent from the medical research renaissance, a growing number of academic researchers and startups in the space are starting to dig into mescaline’s potential as a therapeutic agent.
The University Hospital in Basel, Switzerland, is conducting two trials.
One compares the acute effects of LSD, psilocybin and mescaline. The second examines the serotonin 2A receptor’s role in how mescaline induces altered states of consciousness.
Still, other startups are getting clinical trials underway.
Journey Colab will be launching a trial looking at mescaline for alcohol use disorder. Likewise, Biomind Labs will be studying a drug based on mescaline to target inflammation, which the company believes is “responsible for several types of depression.”
Similarly, XPhyto Therapeutics is planning a Phase I clinical trial to investigate a mescaline-based treatment for a variety of mental health concerns.
As more commercial interest and money pours into psychedelic research, there is come concern among the scientific community as to how mescaline and novel mescaline-like compounds may be used.
For instance, mescaline’s relative low potency, slower onset and longer duration of effects may be viewed as less than desirable to drug companies and those who pay for medical care. But shorter isn’t necessarily better.
Gül Dölen, a neuroscientist at Johns Hopkins University in Baltimore, who told Nature, “we don’t want to go shorter.”
She explained that clinical research often shows a correlation between the duration of the trip and the duration of its therapeutic effects: ketamine effects typically last for less than 2 hours with benefits lasting for about a week, whereas ibogaine’s effects can last for days and its benefits can last for more than a year.
Others are concerned about how psychedelic compounds like mescaline might be used in a therapeutic context and whether they will be integrated into a treatment plan that utilizes these medicines as tools in an ongoing healing process rather than just a quick fix.
In the meantime, much foundational clinical research needs to be done before we might see a mescaline-based treatment come to market.
The Takeaway
Mescaline is a psychedelic alkaloid found naturally in a variety of cacti such as peyote, Peruvian torch and San Pedro. It has a long history of religious and sacred use in the Americas dating back at least 5,700 years.
While mescaline enjoyed a brief period of scientific interest in the late 18th and early 19th centuries, eventually, it was outlawed in the U.S., Canada and internationally with exceptions made for religious use by the Native American Church. Today, research interest in mescaline has resumed as a broader psychedelic renaissance fuels both academic and corporate interest in the therapeutic use of these compounds.
