Peyote: The Chemistry, Effects, and Brain Science

By Tessa Eskin

For over 6000 years, shamans, healers, and ‘roadmen’ have used Peyote as a conduit for communion with the spirit world. Lophophora williamsii is a cactus stemming from the Cactaceae family, native to the dry regions of northern Mexico and the southern US. The fleshy cacti store alkaloid mescaline in their crowns as a defense against predators. This compound is deadly to small animals. But when ingested by humans, peyote produces hallucinatory and mystical effects. Many consider the cactus sacred to this day.

Across North America and Mexico, practitioners have held peyote ceremonies for expansion of consciousness and psychological healing. These ceremonies center on a deep respect for the cacti, believed to connect humans to the ‘Great Spirit’ or ‘Creator’. Peyote entered the western annals in 1560, when the Spanish priest Bernadino de Sahagún recorded its use by the Aztecs. In 1638, Hernandez, the naturalist of Philip II of Spain, recorded the first botanical description.  By the early 1900s, Peyote was an established treatment for snakebites, burns, rheumatism, toothaches, fever, and scorpion stings.

The US federal government outlawed its use in 1967, with special exemption granted to the Native American Church for ceremonial purposes. The American Indian Religious Freedom Act Amendments of 1994 allowed selective use in religious services, but peyote is still categorized a Schedule 1 substance. This may soon change, as current studies investigate mescaline as a treatment for mental health disorders, including schizophrenia, addiction, OCD, and dementia.

Preparation & Effects

Peyote buttons grow on the crown of the cacti. The small discs are cut and dried, then often chewed or boiled into a psychoactive tea. Some cook the buttons in a pressure cooker, producing a tarry material then formed into pills. Others sprinkle the dried buttons onto tobacco or cannabis for inhalation.

Peyote takes effect within 30 minutes of ingestion. For most, the trip starts with an increase in heart rate, blood pressure, and temperature. Following this, the first two hours often include nausea, sweating, and chills, which dissolve into a calm, accepting state. Then, the psychedelic effects kick in, reaching a peak at 2-4 hours that gradually declines over the next 8-12 hours. Many liken it to the effects of LSD and psilocybin, with similar optical and audio distortion, altered perceptions, and intensified emotions. Like all psychedelics, the experience depends on potency, dosage, mood, setting, and the user’s mental health history.

The Peyote Experience

Peyote ceremonies often last throughout a sleepless night, and generally include blessings, chanting, and drumming. Many set a personal intention, such as health, spiritual guidance, or accepting the loss of a loved one. The trip often features a “mystical transcendental state” and a dreamlike high. Many report a feeling of oneness and unity, euphoria, self-realization, enhanced empathy, and ego-death. Visuals become heightened, with vivid colors and optical distortion as the environment appears to melt and breath. Some report visions of geometric patterns and entities, such as a little green man, or plant spirit often called “Mescalito”.

Those who embark on the peyote journey do so for spiritual cleansing, insight into the self, and connection to the cosmos. The purging aspect can unroot deep fears and negative emotions, resulting in a peaceful afterglow. Additionally, the effects encourage creativity, compassion, and gratitude, and even alleviate anxiety, depression, PTSD, and addiction. Many emerge with a deeper understanding and acceptance of their place in the grander scheme of things.


The main psychedelic agent in peyote is mescaline, a morphine-like alkaloid causing sedative-soporific symptoms. It is a derivative of phenethylamines, referring to substances with psychoactive and stimulant effects. According to a report published in the Oxidative Medicine and Cellular Longevity journal, mescaline directly impacts the central nervous system. It is absorbed through the intestinal tract and processed through the pancreas, liver, kidneys, and spleen. It then binds to serotonin receptors in the brain, stimulating the cortical area.

Mescaline is responsible for the vivid visual hallucinations and distorted perception of time and the self during a peyote experience. The psychedelic crosses the brain barrier and binds to virtually all dopamine, serotonin and adrenaline receptors, similar in structure to LSD and psilocybin.

Studies indicate that mescaline may improve blood flow and prefrontal cortex activity, enhancing problem-solving, emotional regulation, and behavior. This may be why peyote is considered to boost creativity. With prefrontal cortex activity linked to psychological disorders, clinical trials are currently exploring mescaline as the next big treatment for depression and anxiety. 

Cover image credit: painting by Jose Benitez Sanchez

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