In his book Pharmako Gnosis, Dale Pendell claims that mescaline use may date back over 10,000 years, with a discovery of lophophora williamsii (peyote) in a cave dating to around 8,500 BCE. If true, it would make peyote the oldest psychedelic medicine in the world.

Mike Jay expands on this idea in Mescaline: A Global History of the First Psychedelic, in which he uses ancient art from South America to show the prevalence of peyote and San Pedro (both of which contain mescaline) throughout the centuries.

The psychedelic that inspired Aldous Huxley to write The Doors of Perception and featured heavily in the work of Hunter S Thompson was likely used to facilitate spiritual experiences and may have been the catalyst for countless religious awakenings.

Despite its impactful history, it seems to have been largely overlooked in favor of LSD and psilocybin during the recent psychedelic resurgence. But as with those classic psychedelics, mescaline has shown promise in therapeutic studies, and plants like San Pedro and peyote could provide healing properties.

How Does Mescaline Work?

Mescaline (3,4,5-trimethoxyphenethylamine) is a serotonin 5HT2A/2C receptor agonist that also acts on adrenergic and dopaminergic receptors. (1)

It interacts with areas of the brain responsible for mood regulation and perception, leading to significant changes in both. It also disrupts normal brain activity, producing changes in perception and causing hallucinations associated with spiritual experiences. (2)

Mescaline also interacts with neurotransmitter systems that are responsible for everything from body temperature and hunger to motor control.

The Effects of Small and High Doses of Mescaline

Mescaline is thought to be several thousand times less potent than LSD and up to 30 times less potent than psilocybin on a dose-by-dose basis. It works in much the same way as these two psychedelics, though, and can cause hallucinations, mood changes, and feelings of euphoria, but the effects are typically much less intense. (3)

A mescaline experience can vary based on set, setting, dose, and individual experience. In a thread titled “What was your most impactful psychedelic experience?” on Third Wave’s Community, we had members such as Margaret, a counselor and coach, state that it made her “laugh [her] butt off”, while Alexis said it was their “most amazing experience so far”.

In another thread, Alexis spoke about a group experience in which everyone spent the day hiking on San Pedro, noting that “the whole group was clearly able to maintain balance and pace”.

Such experiences are common, especially with lower doses. At these levels, it’s easy to conduct typical daily activities while sitting with mescaline. It’s also commonly microdosed, as noted in our guide to microdosing mescaline.

However, with larger doses, more inexperienced sitters, and poor preparation, there is a risk of unsettling and uncomfortable experiences. The mescaline experience page on Erowid details various “bad trips”, including: (4)

• Extreme anxiety lasted for hours after the initial dose and took many weeks to fully fade away. (250 mg dose).
• Discomfort, paranoia, and a feeling of being overwhelmed accompanied by confusion and pain and the sensation that their body was “boiling”. (510 mg, later followed by diazepam and zolpidem).
• Crying, screaming, and weeping during a bad and uncomfortable inner journey. (400 mg dose, taken with antidepressants).

Side Effects, Addiction Potential, and Other Risks

Although mescaline is less potent than other classic psychedelics, there are still risks, and as the above reports highlight, it’s imperative that the journeyer has the right mindset going into the experience.

Caution is advised in those with preexisting illnesses, and it may not be suitable for those with extreme anxiety or depression, as well as schizophrenia. Other substances should be avoided, particularly in inexperienced individuals. Of the 11 “difficult” or “bad” reports on Erowid, six combined mescaline with other psychedelics, and several were also taking antidepressants, including one individual’s sister who thought she was melting and that those around her were burning, sending her into a panicked state in which she tried to tear off her clothes while scrambling for the window.

Mescaline fatalities are very rare, and when they do occur, they usually result from misadventure, including a case from 1985 where a man attempted a “swan dive” under the influence of mescaline and fell 600ft to his death. (5)

For this reason, and to ensure maximum results and benefits, practitioners must work closely with clients before, during, and after every experience, being sure to:

• Assess the client’s current state and readiness.
• Enquire about preexisting illnesses and medications that may cause complications.
• Consider their needs, expectations, and goals.
• Prepare a safe setting and encourage a calm, stress-free mindset.
• Keep the individual way out of harm’s way during their journey.
• Ask them to record their emotions and thoughts in a journal.
• Work through the journal to properly integrate the experience.

Are Bad Trips on Mescaline Common?

Bad trips are not common, and they become less so with proper preparation, but they can still happen.

Even experienced users can have bad tips. In Pharmako Gnosis, Pendell notes that such experiences also occurred among indigenous tribes during shamanic practices. In such cases, the negative experiences were often said to result from improper practices, suggesting that the individual didn’t complete the necessary rites or was clinging to negative thoughts or experiences. They were encouraged, therefore, to open up, talk through their experience, and ultimately turn it around.

In many ways, those early beliefs are in line with current psychedelic integration practices, as providing support, encouraging communication, and expelling “bad energies” by voicing uncomfortable thoughts and emotions can turn the experience around.

Mescaline and Healing: What the Science Says

Mescaline hasn’t been studied as much as psilocybin, MDMA, or LSD, but there has been some very promising research concerning its potential therapeutic benefits.

Many of these studies relate to its potential for helping those with alcoholism and substance abuse problems, something it has in common with other classic psychedelics. (6)

A study conducted in 2021 surveyed participants with mescaline experience. A third of them said that mescaline produced the most meaningful or spiritual experiences of their lives, while many reported improvements in their mood and anxiety levels. (7)

Conclusion: Integrating Mescaline Experiences as a Psychedelic Practitioner

Mescaline is one of the oldest—if not the oldest—psychedelics and has a long history of use in spiritual ceremonies. It’s not as popular as other classic psychedelics, and research is scant, but it seems to possess similar properties to much-studied medicines like psilocybin and could provide a variety of benefits in the right setting and with ongoing psychotherapy.

As with psilocybin, though, it’s imperative to get the set and setting right and to integrate the individual’s experiences. At the Psychedelic Coaching Institute, we train coaches in proper planning and support, guiding them through the scientific principles of psychedelic use while also considering the ethical, moral, and legal implications.

If you want to learn more about mescaline, advance your coaching career, and provide your clients with a background of trust, security, and insight, check out The Psychedelic Coaching Institute’s trainings.