Peyote Effects

Overview: Peyote is a mescaline-containing cactus used ceremonially by Indigenous cultures for thousands of years. It interacts with serotonin and adrenergic receptors in the brain, producing profound subjective effects. When used responsibly in a controlled, ceremonial context, peyote can lead to transformative, mystical experiences. However, irresponsible use can be psychologically destabilizing. Peyote may trigger psychotic reactions in susceptible individuals and can have mild-moderate cardiovascular effects. It is important to approach peyote with caution, considering set and setting, and consulting healthcare professionals. Nausea and vomiting are common side effects, but methods like mixing with fruit juices can alleviate them.

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What is Peyote? 

Peyote (Lophophora williamsii) is a unique cactus found in Northern Mexico and the Southwestern United States. With its small, spineless, globular shape, peyote contains the classic psychedelic compound mescaline and holds a significant place in the history of psychoactive substances, as evidenced by archaeological findings.

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Evidence suggests that peyote has been used ceremonially by Indigenous cultures in the USA and Mexico for approximately 6000 years. Despite historical challenges posed by early Spanish conquistadors in the 16th century, the ritual use of peyote has persevered to this day, thanks to the unwavering determination of indigenous-American communities.

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Ceremonial consumption of peyote reached the United States in the late 1800s, and in 1918, several indigenous groups amalgamated to form a pan-Indian religion called the Native American Church (NAC).

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Peyote is classified as a Schedule I substance, making its consumption illegal. However, there are exceptions under the American Indian Religious Freedom Act Amendments of 1994 (AIRFA). Members of the Native American Church (NAC) are allowed to use peyote for religious purposes, and non-Native Americans can also partake in bona fide traditional ceremonies associated with the NAC.

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As a foundational element of the NAC, peyote is revered by members for its medicinal qualities and the meaningful connection it has fostered between the people, their land, and the environment.

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Exploring the Effects of Peyote on the Brain 

The primary psychoactive compound in peyote, known as mescaline, was initially isolated in 1896 by the German chemist Arthur Heffter. In 1919, the Czechia-born Austrian chemist Ernst Späth synthesized mescaline by converting 3,4,5-trimethoxybenzoic acid into the respective aldehyde, which was then reduced to produce mescaline.

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Interactions with Serotonin Receptors and More

In a comprehensive 2019 manuscript, Ricardo Jorge Dinis-Oliveira and colleagues at the University of Porto, Portugal, provided an in-depth analysis of peyote composition and the way mescaline behaves in the brain and body. 

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Similar to other classic psychedelics such as LSD, psilocybin, and DMT, mescaline primarily produces its subjective effects by interacting with 5-HT2A serotonin receptors. Mescaline also has a low level of interaction with 5-HT1A and 5-HT2B receptors, but it has a strong interaction with 5-HT2C receptors, where it acts as a full agonist.

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In the 1970s, psychiatrist Dr. Daniel Freedman conducted research on mescaline, a compound found in peyote. His studies revealed that at low doses, mescaline reduced the levels of 5-hydroxyindoleacetic acid (5-HIAA), a major metabolite of serotonin — a neurotransmitter involved in regulating mood. On the other hand, high doses of mescaline increased the levels of 5-HIAA. Mescaline was found to increase the release and reuptake of serotonin. 

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Mescaline also interacts with alpha-2A adrenergic receptors (α2A adrenoceptors), a specific type of receptor found in the brain and body involved in regulating various bodily processes. In terms of its chemical structure, mescaline also has some similarities with amphetamine — a type of stimulant drug that can speed up the activity of the central nervous system.

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This means that mescaline exhibits some activity on the dopamine system, which is a network of brain pathways that uses the neurotransmitter dopamine to transmit signals between brain cells. However, the impact on dopamine receptors is relatively minor.

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Interestingly, there is no evidence to suggest that mescaline has a high potential for abuse or dependence, despite its classification as a Schedule I substance.

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Furthermore, after just a few days of use, users develop a tolerance to mescaline that produces cross-tolerance to other psychedelic drugs. One’s sensitivity to mescaline is typically restored to normal after 3-4 days of abstinence.

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From Brain to Body: Unraveling the Distribution of Mescaline

Mescaline is classified as a long-acting psychedelic substance with relatively low potency.

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To experience the psychoactive effects of mescaline, the recommended oral dosage of synthetic mescaline falls within the 200–400 mg range. This dosage is roughly equivalent to consuming 3 to 6 dried peyote buttons (around 10 to 20 grams) or 50-100 grams of fresh peyote buttons.

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In comparison to LSD and psilocybin, mescaline is less potent. However, when taken orally, mescaline has a longer half-life (around 6 hours), meaning that it takes approximately 6 hours for the concentration of mescaline in the body to decrease by half.

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Upon oral ingestion of peyote, the effects typically manifest within 30 minutes. The peak psychedelic effects occur approximately 2 hours after ingestion and can last for an additional 10 to 12 hours.

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It's interesting to note that the strongest effects of peyote don't occur when mescaline levels in the brain are highest. This suggests that there is a process called bioactivation, where the compound undergoes changes in the body to produce its maximum effect.

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In a research paper from 1966, psychiatrist K. D. Charalampous demonstrated that mescaline is metabolized by an enzyme called amine oxidase in the liver. Most orally consumed mescaline is eliminated unchanged in urine within the first hour, while the remaining portion is excreted as a metabolite called 3,4,5-trimethoxyphenylacetic acid (TMPA).

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Studies have found that mescaline is present in higher amounts in the liver and kidney compared to the brain and blood. This is because mescaline doesn't dissolve well in fats and has difficulty crossing the protective barrier of the brain. 

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When mescaline is broken down in the body, it forms different metabolites through a process called demethylation and acetylation. These metabolites can then undergo further changes to become urinary metabolites. The fact that the peak effects of mescaline don't happen when it's most concentrated in the brain suggests that the metabolites of mescaline play a role in its psychoactive effects. 

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The Subjective Effects of Peyote 

Despite sharing similar effects, classic psychedelics are thought to produce distinct experiences, particularly synthetic and peyote-derived mescaline.

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Limited research has been conducted on the subjective effects of mescaline and peyote. However, in 2021, a group of psychedelic researchers published an epidemiological study shedding light on the effects of  mescaline use.

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These effects generally involve alterations in cognition, perception, emotion, and one's sense of self or “ego.” According to the study, the most frequently reported subjective effects of both peyote and synthetic mescaline are:

• Intensification of visual stimuli (prominence of light and distinctive colors)
• Closed- and open-eyed visuals 
• Hypersensitivity/enhancement of touch, smells, and sounds
• Synesthesia (blending of the senses)
• Time and space distortion
• Sensation of floating
• Pleasant feelings
• Altered thinking processes
• Altered self-awareness
• Transcendence 

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Users of peyote often report a sense of direct communication with a higher power or deity. They describe entering an alternate reality where they encounter intelligent beings, leading to a feeling of transcending the ordinary laws of physics. This is partly why peyote has been revered as a sacred sacrament in indigenous American ritual ceremonies for countless generations.

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In the aforementioned study, 35% of participants rated their most memorable mescaline experience as one of the top five or single most personally meaningful, spiritually significant, or psychologically insightful experiences of their entire lives.

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Importantly, these participants consumed peyote in a controlled, ceremonial context facilitated by an experienced shamanic practitioner. This is significant as it emphasizes the importance of set and setting in psychedelic experiences.

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Peyote, when approached with respect and responsible usage, has the ability to facilitate transformative mystical experiences that bring about deep healing, personal significance, and valuable insights. However, it is crucial to recognize that irresponsible and unguided use of peyote can lead to unsettling experiences that may have a destabilizing impact on one's psychological well-being, especially when not adequately integrated.

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Adverse Side Effects of Peyote 

As with all psychedelics, challenging psychological effects can occur, particularly when used in an uncontrolled context. The main adverse effects of peyote are psychological and may include anxiety, paranoia, panic, and fear. 

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Peyote has the potential to trigger a psychotic reaction in individuals who have a predisposition to such conditions. It can also exacerbate existing psychotic disorders.

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Furthermore, peyote use may lead to mild to moderate cardiovascular effects, which could pose a risk to individuals with pre-existing cardiovascular diseases.

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It is important for individuals with these conditions to exercise caution and consult with healthcare professionals before using peyote or any substances that may affect their mental and cardiovascular health.

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Peyote users often report experiencing nausea and vomiting, which is likely attributed to the plant's bitter taste and the presence of over 50 compounds within it. In contrast, a study involving participants who received synthetic mescaline did not report any instances of vomiting.

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Mixing peyote with fruit juices or pulverizing peyote buttons into a powder to be placed into gelatin capsules is believed to reduce or even prevent nausea and vomiting.

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Key Takeaways: Peyote - Cultural Significance, Effects, and Safety Considerations

Peyote stands as a remarkable plant with a long history of ceremonial use among indigenous cultures. When approached with respect and consumed in controlled ceremonial contexts, peyote has the potential to facilitate transformative and meaningful experiences that can lead to healing and insight.

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However, it is crucial to recognize the importance of responsible usage and the potential risks associated with peyote. Individuals with predispositions to psychotic disorders or cardiovascular diseases should exercise caution and consult with healthcare professionals before engaging in its consumption. Additionally, peyote's bitter taste and the presence of multiple compounds can lead to nausea and vomiting, which can be mitigated by mixing it with fruit juices or encapsulating it.

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Overall, the exploration of peyote opens doors to intriguing realms of consciousness, offering unique experiences and insights for those who approach it with mindfulness and responsibility. By embracing the wisdom of indigenous traditions and combining it with scientific research, it is possible to continue to expand our understanding of these powerful substances like peyote and their potential for positive transformation.