Mescaline is a hallucinogenic compound with a long history of traditional use. It’s found in many different cacti, with the most well-known being peyote. Mescaline produces similar changes in perception as LSD, but not quite in the same way. Read more to learn how mescaline works and discover its effects on the body and mind.

What is Mescaline?

Definition

Mescaline is a hallucinogenic compound most notably found in the peyote cactus (Lophophora williamsii). It is also found in varying degrees in many other members of the cactus family [1].

It is an alkaloid in the phenethylamine class of compounds, which includes other hallucinogens as well as various stimulants, decongestants, and antidepressants. Mescaline alters consciousness similarly to the popular psychedelics psilocybin (“magic mushrooms”) and LSD [2, 3].

The “Mescaline Cactus”

Mescaline is found in high levels in the peyote cactus and acts as the major active compound. It is concentrated in the small, circular above ground stem tops called “buttons.” Mescaline content in the dried buttons ranges from 2.8% to 3.5% [1, 4, 5].

Peyote also contains other psychoactive alkaloids that may enhance the effects of mescaline [5].

History and Legal Status

Indigenous Use

Mescaline is one of the oldest known hallucinogens used by humans [6].

Native Americans in Mexico used peyote as far back as 5,700 years ago and considered it to be a divine substance with healing properties. Indigenous peoples of South America have used mescaline-containing cacti such as the San Pedro (Echinopsis pachanoi) and Peruvian torch (Echinopsis peruviana) for healing and religious ceremonies for thousands of years [7, 8, 1].

Scientific Boom

Scientific interest in peyote took off at the end of the 19th century after American newspaper reports of the ritualistic use of peyote by Native American tribes. The search was on to reveal the compound(s) responsible for peyote’s psychedelic effects [1].

This task was accomplished in 1896 by the German chemist Arthur Heffter. After identifying mescaline as one of the active alkaloids in peyote, he tested it on himself and was able to prove that it was responsible for the psychoactive effects of the cactus [1, 9].

Then in 1919, Austrian chemist Ernst Späth found a way to make mescaline in the lab. Shortly thereafter, researchers and scientists began dosing themselves and publishing their findings [10].

Psychiatrists in the 1930s and 1940s became particularly interested in mescaline’s ability to mimic certain features of psychosis, a mental condition in which a person loses contact with reality. It can be caused by mental illness such as schizophrenia as well as medications and life-threatening medical conditions [10, 11].

They thought that by artificially recreating the subjective experience of psychosis, they could better understand the condition [12].

In the 1950s, British psychiatrist Humphry Osmond began studying mescaline and LSD’s ability to address mental illnesses, including alcohol addiction. He was surprisingly successful, however, his work was cut short by the drug backlash in the1960s [13].

Osmond later became friends with Aldous Huxley. The famous writer was introduced to mescaline after reading one of Osmond’s papers and requested a sample. Huxley then went on to publish his seminal book “The Doors of Perception,” which gave a detailed account of his experiences with mescaline and spurred public interest in the drug [9].

Subsequent Ban

In 1970, mescaline became illegal with the passing of the Comprehensive Drug Abuse Prevention and Control Act. To this day, it’s classified as a Schedule 1 controlled substance, meaning lawmakers considered it to have [14, 15]:

  • A high potential for misuse and abuse
  • No accepted medical use
  • A lack of accepted safety

Mescaline is also illegal in most other countries. However, mescaline in the form of peyote is legal for religious use by members of the Native American Church (NAC). NAC is a religion that combines Native American beliefs and practices with Christianity and ritualistic peyote use [16, 17].

Clinical research on mescaline was limited after the 1970s ban. Although recent years have seen an increase in research on hallucinogens such as psilocybin, mescaline has not been included in this resurgence due to its relatively low potency and long duration of effects [1].

Effects of Mescaline

Alters Brain Chemistry

The primary mechanism by which mescaline causes hallucinogenic effects is activating 5HT-2A serotonin receptors. All psychedelic drugs, including psilocybin, LSD, and DMT, share this mechanism [3, 18, 19].

Mescaline also activates other serotonin receptors (5HT-1A, 5HT-2B, and 5HT-2C), which may contribute to its effects. These receptors play important roles in learning and memory, anxiety, mood, and sleep [18, 20, 21].

Besides serotonin receptors, mescaline also activates dopamine receptors in areas of the brain responsible for processing sounds and emotions. This may contribute to the drug’s effect of distorted hearing and enhanced emotions [22].

Mescaline increases blood flow and activity in the prefrontal cortex, an area of the brain that is responsible for planning and pursuing goals, solving problems, self-identity, and regulating emotions and behavior. This may lead to enhanced creativity and focus and may underlie the changes in self-identity that occur [23, 24, 25].

By activating neurons in a part of the brain called the locus coeruleus, mescaline increases the response to stimuli in the environment. This may explain why users become more sensitive to what’s happening in their environment and why “set and setting” is crucial during the psychedelic experience [26, 27].

Mescaline is also able to block the release of acetylcholine, a neurotransmitter that is used to contract muscles. This, in turn, blocks cholinergic activity and may lead to side effects such as muscle weakness and poor balance and coordination [28, 20].

Visuals, Sensory and Perceptual Changes

Mescaline causes a heightened perception of colors, making them more vibrant and intense. Like all psychedelics, it can cause intense visual hallucinations. They are most often vibrantly colored patterns including fractals that occur more readily in dim light. Hallucinations of sound, smell, and taste can also occur but are much less common [29, 30, 1, 31, 32].

It can also cause a distorted sense of time so that the user becomes unsure of how long they have been under the effects of the drug. Hearing and perception of space may also be distorted [33].

Mescaline can cause synesthesia, a phenomenon in which senses becomes mixed. For example, certain sounds can cause sensations in parts of the body or certain letters or numbers can be associated with different colors [34].

Users may also feel as if their body is weightless and that their limbs have changed size and shape [35].

Self-Identity

Common to all psychedelics, mescaline can alter the user’s concept of self. Higher doses can cause ego dissolution, a complete loss of the sense of self and the boundaries between self and the rest of the world [12, 32].

Thoughts and Emotions

Mescaline often produces a dreamlike state of profound wonder. This can be accompanied by a feeling of euphoria [32, 33].

Mescaline vs LSD

LSD is 1,000 to 3,000 times more powerful than mescaline [36, 37].

The effects of both compounds can last up to 12 hours with higher doses, however mescaline tends to last slightly longer [24, 37, 38].

Because they share the same mechanism of action, mescaline and LSD have very similar effects. They both cause hallucinations, increase suggestibility, enhance emotions and color perception, and create a sense of deep mysticism or profound wonder [39, 1, 40, 41].

However, users do report slightly different subjective experiences, suggesting they may work differently in certain aspects.

For example, mescaline is more likely to distort the user’s body image, while loss of control of thoughts is more commonly reported on LSD [40].

LSD may also cause sexual feelings, something rarely reported in mescaline users. The enhancement of colors appears to be more common with mescaline [40].

Another key difference between the two is that mescaline does not produce “flashbacks,” also known as hallucinogen persisting perception disorder (HPPD). Flashbacks occur when visual and auditory disturbances previously experienced during a trip reappear when not using the drug [42, 43, 44, 45].

Despite their differences in potency and effects, mescaline and LSD have enough in common that they are hard to tell apart. In fact, in blinded clinical trials, people are unable to distinguish which one they have taken [36, 38].

Potential Benefits of Mescaline

1) May Improve Creativity and Problem-Solving

Mescaline produces changes in thinking that may support creativity. For example, it can [46]:

  • Improve the ability to make associations between unrelated concepts or ideas
  • Reduce inhibitions and self-judgment
  • Enhance imagination

Researchers wondered if these effects could translate into solving problems that require creative thinking [46].

To do so, they recruited 27 people who worked in jobs that require creative problem-solving ability (e.g. engineers, physicists, and furniture designers). The researchers gave them 200 mg mescaline sulfate and then told them to work on problems related to their field that required a creative solution. The participants also took tests to measure their creativity both before and during the mescaline session [46].

Researchers found that mescaline increased creativity as measured by the tests. It also improved their ability to solve creative problems by

  • Boosting concentration
  • Increasing the capacity for visual imagery
  • Improving the ability to see problems from different angles
  • Improving the sense of “knowing” when the right solution appears

These improvements were still seen when the participants were assessed two weeks later [46].

Mescaline appears to be a powerful tool that can put people in the right mindset for creative problem-solving.

2) May Improve Mental Health

One study looked at the mental health of 61 long-term peyote users in the Native American Church compared to 79 members of the Navajo tribe with no or little history of drug use. The study found that peyote users reported better psychological well-being and more positive emotions [45].

It’s important to note that mental health was not measured before peyote use started so we don’t know how (or if) it changed over time.

Another study of over 130K people found that mescaline use was linked to lower rates of both serious psychological distress and needing psychiatric medication compared to never using the drug [47].

Mescaline use was also associated with a lower rate of agoraphobia, an anxiety disorder in which people fear environments that might cause them to feel trapped or helpless [47].

We can’t say for certain that mescaline improves mental health due to the nature of the research. However, these studies suggest it may provide a boost to well-being and positivity without any obvious negative effects.

3) May Help With Alcohol Addiction

Serotonin receptor-activators may have the potential to treat alcohol and cocaine dependence [48].

In fact, clinical trials have revealed that LSD is effective in reducing alcoholism [49].

Due to their comparable mechanisms and effects, mescaline may be similarly effective.

Unsurprisingly, there are many reports of members of the Native American Church using peyote to prevent alcohol abuse [50].

While there are no clinical trials examining mescaline’s effects on alcohol addiction, research on LSD and peyote provide in indirect evidence of its therapeutic potential.

4) Mixed Effects on Learning

In higher doses, mescaline improved learning in goldfish. However, lower doses actually decreased their ability to learn to avoid a negative stimulus [51].

Mescaline Side Effects, Risks & Drug Interactions

Case Reports

There is one case report of an individual under the influence of mescaline who died of an accidental fall while experiencing hallucinations. It is unknown how much mescaline the person took. However, high blood levels indicated they took a much larger dose than is normally recommended [52].

Taking mescaline in a safe and familiar environment can help reduce the risk of harm [52].

Pregnant women should avoid mescaline as it can cause brain, spinal cord, and liver issues in newborns [53, 54].

Psychiatrist Humphry Osmond, who used mescaline in his practice, noted that people who had hepatitis experienced prolonged responses to mescaline [55].

Long-Term Risks

A study of 61 Native American Church members found that peyote use had no negative effects on mental function or psychology. Another study of 130k people found that mescaline and peyote use was not linked to a higher rate of mental health issues [47, 56].

Mescaline is not addictive and does not cause dependence [56, 47, 6].

Body Side Effects

Mescaline can produce a wide array of effects on the body, including [29, 57, 33, 32]:

  • Dilated pupils
  • Blurred vision
  • Sweating
  • Dry mouth
  • Elevated heart rate
  • High blood pressure
  • Fidgeting and restlessness
  • Muscle weakness
  • Poor coordination and balance
  • Headaches
  • Nausea and vomiting

During the first four hours, body temperature will slightly decline. Thereafter, body temperature increases and may become moderately high. Blood sugar may also rise rapidly for the first hour and then return to normal over the course of the following couple hours [17, 57].

Side effects are usually mild to moderate, non life-threatening, and resolve within 24 hours [29].

Cognitive Side Effects

Mescaline has the potential to cause negative thoughts and emotions as well, including [57, 1, 32]:

  • Sadness and irritability
  • Fear
  • Anxiety and nervous excitement
  • Depersonalization
  • Difficulty expressing thoughts and focusing
  • Delusions
  • Paranoia

Psychosis and Schizophrenia

The 5-HT2A receptor is thought to play a key role in the development of schizophrenia and psychosis. By activating this receptor, mescaline can produce temporary changes in the brain that mimics those seen in psychotic episodes caused by schizophrenia [58, 59, 60, 23, 24].

No studies have clearly demonstrated that mescaline causes psychosis or schizophrenia.

There is a case report of one otherwise healthy person undergoing a 2-week long psychotic episode after taking peyote in which they experienced visual and auditory hallucinations and could barely sleep. Their symptoms resolved when they finally got proper sleep suggesting that the psychosis was likely due to being sleep-deprived and not the drug itself [61].

Clinical Trials

There have been a few clinical trials examining the effects of mescaline in chronic schizophrenics. The drug produces similar effects in this population as it does in normal volunteers, including [62, 31, 63]:

  • Visual hallucinations
  • Distorted body image
  • Distorted sense of time
  • Euphoria
  • Paranoia

However, mescaline also caused schizophrenic patients to become highly sexual, verbalizing sexual desires and past experiences. This is rare in normal volunteers [62, 31, 63].

In general, the hallucinogenic experience is much more intense for schizophrenic patients and causes a notable increase in anxiety and disorganized thoughts. Mescaline appears to enhance symptoms specific to the type of schizophrenia the patient has, such as paranoia, fear, and disorganized thinking [62, 31, 63].

Despite the increase in symptoms, the experience has been beneficial for some patients.

In a study of 24 hospitalized schizophrenics, one patient was able to permanently return to her home after significant improvement in her condition. Seven other patients experienced partial improvement, but their symptoms returned within the following weeks [62].

While mescaline has the potential to improve symptoms of schizophrenia, large trials are still needed to confirm its therapeutic benefits and safety.

Drug Interactions

Drugs that block the 5-HT2A receptor may reduce the effects of mescaline. These include [64, 65, 66, 67]:

  • Antidepressants including mirtazapine and trazodone
  • Antipsychotics including haloperidol, clozapine, and risperidone
  • Pizotifen (Sandomigran), used to treat migraines

Members of the Native American Church warn against combining alcohol with peyote [68].

Mescaline Dosage

Mescaline does not pass through the blood-brain barrier very well. This means that in comparison to other hallucinogens, higher doses are needed to see a psychoactive effect. Because of this, mescaline is used less frequently than popular psychedelic hallucinogens psilocybin and LSD [1, 69, 29].

In clinical trials, doses between 200-500 mg mescaline sulfate were used. The suggested hallucinogenic dose was 5 mg/kg body weight, or 350 mg for a 70 kg (154 lbs) person [59, 23, 70, 71].

Each peyote button contains around 45 mg of mescaline. The buttons are usually dried and eaten or soaked in water to drink [50, 10].

Tolerance to mescaline builds after repeated use over the course of days. Taking mescaline will also cause tolerance to LSD, and vice-versa. Cross-tolerance with psilocybin is also likely due to their similar effects on serotonin receptors [72, 70, 73].

Cross-tolerance may also occur with morphine [74].

Dosage and purity of mescaline sold on the streets illegally are often unknown and may contain LSD or other related (or unrelated) drugs [47].

Limitations and Caveats

Compared to the other psychedelics, there are few clinical trials exploring the therapeutic benefits of mescaline. This is likely due to its greater onset of action and duration.

Although mescaline is not addictive and may have therapeutic potential, it remains classified as a Schedule I drug. Until more research emerges or regulations change, mescaline use outside of a research or medical environment is not considered safe.

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Takeaway

Mescaline the active hallucinogenic compound found in peyote and other cacti. It is one of the oldest psychedelics known to humans, the history of its use dating back thousands of years.

While clinical trials are sparse, mescaline has been shown to improve creative problem-solving and may improve mental health and help with alcohol addiction.

Mescaline is not addictive and does not cause dependence. Side effects are not dangerous and resolve after use. It can increase schizophrenia symptoms and cause much more intense effects in people with the disorder.

Lastly, mescaline can cause tolerance to LSD and vice-versa.

About the Author

Will Hunter

BA (Psychology)
Will received his BA in Psychology from the University of California, Los Angeles. 
Will's main passion is learning how to optimize physical and mental performance through diet, supplement, and lifestyle interventions. He focuses on systems thinking to leverage technology and information and help you get the most out of your body and brain.

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