The hallucinogenic cactus peyote is a psychedelic substance that has been consumed by Native Americans for spiritual purposes for thousands of years. While its legal status has hindered research, science shows that its active compound, mescaline, is non-addictive, non-toxic, and may have health benefits. Read on to learn more about the benefits, mechanisms, and risks of taking peyote and mescaline.

What Is Peyote?

Definition

Peyote (Lophophora williamsii), also known as divine cactus or mescal buttons, is a cactus that grows from southern Texas to central Mexico. It is estimated that approximately 30 million people in the United States have used mescaline (peyote), LSD, or psilocybin. Peyote is known for its psychoactive properties and religious, medicinal, and recreational uses [1, 2].

Peyote contains a compound called mescaline. Mescaline is a hallucinogenic molecule that alters human consciousness similarly to psilocybin (magic mushrooms) and LSD. Mescaline, psilocybin, and LSD affect serotonin activity in a way that is not fully understood [3, 4].

Many members of the cactus family also contain mescaline, including the San Pedro cactus (Echinopsis pachanoi) and the Peruvian torch cactus (Echinopsis peruviana) [5, 6].

Mescaline is found in the small, above-ground stem of the cactus. Experienced harvesters collect only the top few millimeters of the stem and leave the rest of the plant to regenerate [7].

Peyote can be consumed as fresh or dried buttons, powder, capsules, or tea [8].

Methods for making synthetic mescaline have also been developed [9].

History and Legality of Use

Native American cultures have used peyote for religious and medicinal purposes for over 5,000 years [10].

Traditional medicinal uses of peyote have included treatment for influenza, joint pain, toothache, intestinal disorders, diabetes, snake and scorpion bites, skin diseases, blindness, neurasthenia (a 19-20th-century diagnosis characterized by physical and mental fatigue), hysteria, and asthma [8, 11].

Although peyote is generally illegal in the United States, it can be used legally in Native American religious ceremonies. The Native American Church has a specific exemption from the law criminalizing peyote [12, 13].

Peyote is legal to sell in the United Kingdom and legal to grow in Canada (however, mescaline is a controlled substance under Canadian law) [8, 14].

Clinical Research

Peyote (mescaline) has been used in clinical research since the 1890s [15].

LSD has been similarly researched in clinical settings. Although LSD is much more potent than mescaline, patients are sometimes unable to tell the two apart [16].

Scientists and psychiatrists have been interested in studying the hallucinogenic effects of mescaline and LSD for insight into psychosis (a mental disorder characterized by a disconnect from reality). Sometimes their research has been controversial [17, 18].

Researchers have disagreed as to whether hallucinogenic drugs are an appropriate tool for studying schizophrenia [19].

In addition to public opposition in the 1960s, medical concerns about hallucinogenic drugs have also been documented [20].

Hallucinogenic drugs were largely prohibited in medical treatment and human research starting in the 1970s [21].

Peyote Effects on the Mind and Body

According to non-scientific sources, physical effects start within 30 minutes to an hour of consuming peyote. Psychoactive effects begin after 1 to 2 hours. These include a feeling of calm and acceptance [22].

Active Compounds & How They Work

Mescaline

Mescaline is a psychoactive phenylethylamine alkaloid, peyote’s main active compound.

It acts similarly to LSD (an indoleamine), psilocin (a tryptamine), and psilocybin to alter consciousness, but with a longer onset and greater duration of effects than LSD, psilocin, or psilocybin [8].

A dose of 250 to 500 mg of mescaline will produce effects lasting 8 to 10 hours [8].

Like LSD, psilocin, and psilocybin, mescaline is considered a serotonergic hallucinogen. Serotonergic hallucinogens act in a similar manner to serotonin, by activating serotonin receptors. Mescaline activates at least two serotonin receptors, the 5-HT2A receptors and 5-HT2C receptors [4, 23].

Imaging studies in humans suggest that mescaline excites some parts of the brain and reduces activity in the default mode network, a set of brain regions involved in thoughts about the self [4, 24].

Long-term use of mescaline produces changes in volume in certain brain regions (thinning the posterior cingulate cortex, thickening the anterior cingulate cortex) and receptor activity (decreasing 5-HT2A receptor binding in the cortex) [4].

Other Active Compounds

Peyote contains the compounds lophophine, homopiperonylamine, and lobivine [25].

Lophophine may be psychoactive.

Homopiperonylamine blocks serotonin receptors [26].

It is not clear if homopiperonylamine or lobivine are psychoactive.

Some authors have suggested that lobivine may be mildly psychoactive, but much less so than MDMA, which is a related compound [27, 26].

Physical Changes

Mescaline can have a wide variety of physical and neurological effects, including:

  • Increased heart rate (tachycardia) [28]
  • Decreased heart rate (bradycardia) [29]
  • Dilated pupils (mydriasis) [28]
  • Changes in eye movements [30]
  • Beta receptor (adrenaline receptor) blocking [31, 32]
  • Increased levels of cytokines (IL-1, IL-6, IL-8) [33]
  • Changes in circadian rhythms [34]
  • Reduced urination [35]
  • Increased free fatty acids in the blood [36]
  • Decreased urinary creatinine [36]
  • Decreased urinary inorganic phosphorus [36]
  • Numbness [37]
  • Central nervous system (brain) stimulation [33]
  • Brainwave changes [38]
  • Increased and decreased activity in the right brain hemisphere (hyperfrontality, hypofrontality) [39]

Hormonal Effects

Mescaline can:

Psychological and Sensory Alterations

Psychological and sensory effects of mescaline can include:

  • Hallucinations [28]
  • Changes in color perception [41]
  • Changes in mood [36]
  • Changes in perception of time [36]
  • Sensory changes [36]
  • Controlled schizophrenia [16]
  • Depersonalization [16]
  • Body image distortion [16]
  • Rapid personality change [16]
  • Apathy [42]
  • Changes in sense of body position [37]
  • Illusions of being touched [37]
  • The blending of senses (synesthesias) [37]
  • Feelings of omniscience [37]
  • Stupor [37]

The psychological effects of mescaline can be more apparent in patients with schizophrenia than in healthy users [43].

Mescaline can reactivate psychosis in schizophrenic patients and may worsen schizophrenia symptoms [44, 43].

Mescaline can cause sleepiness, delusion, and paranoia in patients with epilepsy [38].

The user’s level of anxiety when taking mescaline may influence which psychological effects they experience [42].

Tolerance

Tolerance to mescaline and cross-tolerance to psilocybin and LSD from taking peyote are possible [45].

Benefits of Peyote

1) May Improve Problem-Solving

In a pilot study of 27 adult males, a single dose of 200 mg mescaline sulfate improved creative problem-solving. Increased creativity was seen weeks after the study ended [46].

2) May Improve Mental Health

In a survey of 21,967 individuals reporting lifetime use of psychedelics, mescaline use was not associated with an increased rate of mental health problems. Additionally, in several cases, psychedelic use was associated with a lower rate of mental health problems [47].

Mescaline has caused remission of psychiatric symptoms [48].

Because studies have connected depression to low serotonin, hallucinogenic drugs such as mescaline have been considered for the treatment of depression [49].

3) May Affect Learning

Mescaline improved the rate at which goldfish learned to avoid a shock in a shock-avoidance shock test [50].

Peyote Side Effects

Adverse effects of mescaline include [42, 28, 37]:

  • Anxiety
  • Agitation
  • Psychologically-based movement abnormalities (catatonia)
  • Nausea

Side effects of mescaline include [40, 40]:

In rats, mescaline:

  • Increased the amount of time that is taken to crawl through a maze [51]
  • Caused motor impairment [52]
  • Increased memory decay without daily training [53]
  • Increased food consumption [53]
  • Caused aggression [54, 55]
  • Caused tremor [56]
  • Increased startle reflex [57]

In mice, long-term consumption of mescaline disrupted social hierarchies [58].

Risks

Psychosis and Psychotic Reactions

Some responses to mescaline are negative [59].

Negative responses to mescaline have included reactions resembling schizophrenia [59].

Psychosis is a mental state characterized by loss of contact with reality.

According to one case report, an individual with a habit of withdrawal into fantasies during stress, who also took mescaline under stress, temporarily experienced worsening of his psychotic symptoms [59].

Mescaline is considered a major cause of drug-induced psychosis [60].

Psychotic reactions to mescaline may be more common in individuals with anxious and introverted personalities [61].

One study found a low rate of emotional disturbance associated with peyote use in Native American populations using it for religious purposes [62].

Other Negative Reactions

Mescaline may harm the fetus when taken during pregnancy [63].

Death under the influence of mescaline has been reported [64].

Addictive Potential?

Hallucinogenic substances including mescaline are not known to cause addiction [65].

A study of individuals who regularly consumed peyote found no cognitive or psychological deficits [66].

Illicit (non-religious) use of mescaline is not common among Native American adolescents with substance abuse problems [67].

Drug Interactions

Chlorpromazine quickly blocks the behavioral and brain effects of mescaline [68, 42, 69].

Sodium amytal (a “truth serum”) and sodium succinate block effects of mescaline [70, 48].

Sodium succinate is an antidote against mescaline psychosis [71].

In animal studies, effects or levels of mescaline were:

  • Increased by clozapine [72]
  • Increased by molindone [72]
  • Increased by benzodiazepines (effect blocked by cyproheptadine, a serotonin blocker) [73]
  • Increased by naloxone [74]
  • Increased by parachlorophenylalanine [75]
  • Increased or decreased by desipramine [76]
  • Decreased by idebenone [77]
  • Decreased by minaprine [77]
  • Decreased by nebracetam [77]
  • Decreased by tetrahydroaminoacridine (cholinesterase inhibitor) [77]
  • Decreased by physostigmine (cholinesterase inhibitor) [77]
  • Decreased or blocked by chlorpromazine [78]
  • Decreased or blocked by thioridazine [78]
  • Decreased by zotepine [79]
  • Decreased by asarone [80]
  • Decreased by Frenquel [81]
  • Blocked by cinaserin [82]
  • Blocked by perphenazine [83]
  • Blocked by chlorprothixene [83]
  • Blocked by l-methadone [83]
  • Blocked by ritanserin (5-HT2 receptor blocker) [57]
  • Blocked by ketanserin (5-HT2 receptor blocker) [57]
  • Blocked by methysergide (serotonin blocker) [84]
  • Blocked or decreased by haloperidol (dopamine blocker) [84, 79]

In rats, mescaline:

  • Increased effect of apomorphine
  • Increased the effect of d,1-amphetamine [85, 86]

Genetics

HTR2A is the gene coding for the 5-HT2A receptor, which interacts with various hallucinogenic drugs including mescaline [87].

Evidence from family, adoption, and twin studies suggests that addiction to hallucinogens, in general, is less likely to be something that runs in the family than addiction to other drugs such as cocaine [88].

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