Mescaline, also known in chemical terms as 3,4,5-trimethoxyphenethylamine, is a naturally occurring psychedelic drug and alkaloid of the phenethylamine and scaline families found in certain cacti like peyote (Lophophora williamsii) and the San Pedro cactus (Echinopsis pachanoi, others).
The drug is used recreationally, spiritually, and medically, with psychedelic effects occurring at doses of 100 to 800mg (as its hydrochloride salt) orally and it can be used in pure form or in the form of mescaline-containing cacti. Mescaline induces a psychedelic experience characterized by visual changes, altered perception of time, space, and self, synesthesia, and spiritual experiences, with an onset of 30 to 60minutes, a time to peak of 2 to 4hours, and a duration that increases with dose and ranges from 6 to 14hours.
Mescaline primarily acts as a partial agonist at serotonin 5-HT2A receptors, with varying affinity and efficacy across multiple other receptors and targets. The serotonin 5-HT2A receptor antagonist ketanserin blocks mescaline's psychoactive effects. Mescaline is a relatively hydrophilic compound structurally related to dopamine, first synthesized in 1919, with numerous synthetic methods and potent analogues developed since. It occurs naturally in various cacti species, with concentrations varying widely, and is biosynthesized in plants from amino acids like phenylalanine and tyrosine.
The practice of humans consuming mescaline-containing cacti dates back over 6,000years. Peyote cacti were studied scientifically in the 1800s, culminating in the isolation of mescaline as the active psychedelic constituent in cacti, legal recognition of religious use, and ongoing exploration of the therapeutic potential of mescaline and other analogues. Mescaline was the first psychedelic compound to be characterized by the Western world and has been referred to as the "first psychedelic".
Mescaline and the cacti that produce it are largely illegal worldwide, though exceptions exist for religious, scientific, or ornamental use, and the compound has influenced many notable cultural figures, for instance Aldous Huxley and Alexander Shulgin among others. Very few studies of mescaline in people have been conducted since the early 1970s. However, the drug is now being studied in terms of its effects and for potential medical use once again as of the early 2020s.
Use and effects
Mescaline is used recreationally, spiritually, and medically. It is typically taken orally. The drug is used as a psychedelic at doses of 100 to 1,000mg orally. Low doses are 100 to 200mg, an intermediate or "good effect" dose is 500mg, and a high (ego-dissolution) dose is 1,000mg. However, doses of 800mg and above orally are not well-tolerated due to side effects like severe nausea and vomiting. In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin listed a dose range of 200 to 400mg as the sulfate salt and 178 to 356mg as the hydrochloride salt. Microdosing involves the use of daily mescaline doses of less than 75mg. Mescaline has also been studied via intravenous injection, with assessed doses in the range of 500 to 750mg as the sulfate salt. In addition to pure form, mescaline is used in the form of cacti such as peyote and the San Pedro cactus. Doses when mescaline is used in the form of fresh or dried cacti have also been described.
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 modern users will often grind it into a powder and pour it into capsules to avoid having to taste it. The average peyote button contains about 25mg mescaline. However, another source states that there is about 45mg mescaline per peyote button on average. Some analyses of traditional preparations of San Pedro cactus have found doses ranging from 34mg to 159mg of total alkaloids, a relatively low and barely psychoactive amount. It appears that patients who receive traditional treatments with San Pedro ingest sub-psychoactive doses and do not experience psychedelic effects.
The onset of the effects of mescaline given orally is 0.5 to 0.9hours on average with a range of 0.1 to 2.7hours. Its effects peak after 1.9 to 4.0hours with a range of 0.5 to 8.0hours. The duration of mescaline appears to be dose-dependent, varying from 6.4hours on average (range 3.0–10hours) at a dose of 100mg, 9.7 to 11hours on average (range 5.6–22hours) at moderate doses of 300 to 500mg, and 14hours on average (range 7.2–22hours) at a dose of 800mg. Cases of mescaline having unusually prolonged or delayed effects have also been described. Given intravenously, mescaline has been reported to have an onset of several minutes or within 10minutes, a time to peak of 1 to 2hours, and a duration of approximately 4 to 9hours in different studies.
Mescaline induces a psychedelic state comparable 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. In PiHKAL, Shulgin described the effects of mescaline based on a collection of experience reports. The effects included brightened colors, increased visual contrast, open-eye visuals like colors and patterns, pareidolia, increased significance of objects, enhanced music appreciation, feeling intoxicated, self-analysis, insights, increased body awareness, feelings of joy, happiness, and peacefulness, feeling hyper and energized, feelings of empathy, things feeling ridiculous, humor and laughter, religious feelings, restlessness, social discomfort and avoidance, and nausea, among others. https://erowid.org/library/books_online/pihkal/pihkal096.shtml Mescaline was one of Shulgin's "magical half-dozen" psychedelic drugs in PiHKAL.
Prominence of color with mescaline 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 can turn very complex. The English writer Aldous Huxley described these self-transforming amorphous shapes as like animated stained glass illuminated from light coming through the eyelids in his autobiographical book The Doors of Perception (1954). Like LSD, mescaline induces distortions of form and kaleidoscopic experiences but they manifest more clearly with eyes closed and under low lighting conditions. 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." An unusual but unique characteristic of mescaline use is the "geometrization" of three-dimensional objects. The object can appear flattened and distorted, similar to the presentation of a Cubist painting. Detailed descriptions of the psychedelic experience induced by mescaline have been given by many authors.
The subjective effects of mescaline are qualitatively similar to those of LSD and psilocybin. Based on anecdotal evidence however, mescaline is said to be less threatening and to produce less ego dissolution than other psychedelics like LSD. This may in part be due its slow onset allowing for a more comfortable ease-in of effects. In addition, mescaline is typically dosed at lower doses than LSD or psilocybin in terms of doses with equivalent or comparable strength. According to a study in the Netherlands, ceremonial San Pedro use seems to be characterized by relatively strong spiritual experiences, and low incidence of challenging experiences. Mescaline, LSD, and psilocybin appear to produce similar color enhancement in clinical studies, though more research is needed.
Contraindications
Contraindications of psychedelic drugs like mescaline include severe cardiovascular disease, epilepsy or seizures, schizophrenia and other psychotic disorders, bipolar disorder, and pregnancy, among others. Serotonin 5-HT2A receptor antagonists such as atypical antipsychotics and certain antidepressants may block mescaline's hallucinogenic effects and hence may be considered contraindicated in this sense.
Adverse effects Side effects of mescaline include fatigue, weakness, impaired concentration, restlessness, tension, anxiety, panic, and social discomfort and avoidance, headache, pupil dilation, nausea, vomiting, sweating, trembling, discomfort, feeling hot or cold, palpitations, chest and neck pains, shortness of breath, increased heart rate and blood pressure, and increased body temperature, among others. Nausea and vomiting are important dose-limiting side effects of mescaline and occur at greater rates than with other psychedelics like LSD and psilocybin. High doses of mescaline, such as 800mg and above, are not well-tolerated due to substantial nausea and vomiting. On the other hand, mescaline appears to induce less fear and anxiety than LSD and psilocybin even at equivalent doses.
Psychiatric adverse effects Hallucinogen-induced psychotic disorder
Mescaline use may rarely lead to hallucinogen-induced psychotic disorder (HIPD). HIPD is a type of substance-induced psychosis. Hallucinogen-induced psychotic disorder symptoms are psychosis with paranoia, delusions, hallucinations, or disorganized thinking that persist beyond the effects of the drug. HIPD due to psychedelics is most commonly seen with LSD use, but may also be caused by mescaline. Hallucinogen-induced psychotic disorder is a medical emergency. Without treatment, the psychotic state can continue for weeks or months. HIPD is treated with an atypical antipsychotic medication such as aripiprazole, quetiapine, olanzapine, or risperidone. Individuals with a personal or family history of mental health issues are at the highest risk for hallucinogen-induced psychotic disorder. The condition occurs in fewer than 1% of people with psychedelics.
Tolerance Mescaline is associated with rapid tolerance development, including cross-tolerance with other psychedelics like LSD and psilocybin. This tolerance is apparent within a few days and resets after 3 or 4days of abstinence.
Overdose Only a single case of death due to mescaline, as peyote, has been described, and was likely due to asphyxiation by vomit rather than overdose or toxicity. However, there is also a case report of death due to jumping off a cliff while on a high dose of mescaline. In terms of extrapolated human lethal dose based on animal studies, the lethal dose of mescaline relative to a typical recreational dose has been estimated to be 24-fold or around 8,400mg. However, mescaline has reportedly been taken by humans at doses of up to 8,000mg without apparent toxic reactions. On the other hand, there is one unverified reported case of death due to a dose of 15,000mg intravenously, which would equate to about 150 to 200mg/kg. The median lethal dose (LD50) of mescaline has been determined in various animal species, with the values including 212 to 315mg/kg i.p. in mice, 132 to 410mg/kg i.p. in rats, 328mg/kg i.p. in guinea pigs, 54mg/kg in dogs, and 130mg/kg i.v. in rhesus macaques, among others. It has been said that it would be difficult to take enough mescaline to cause death in humans. No deaths due to peyote use have been reported aside from the asphyxiation case. The highest dose of peyote known to have been taken is 90dried buttons.
Interactions
Trip killers