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Mescaline is Resurgent (Yet Again) As a Potential Medicine

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Mescaline is Resurgent (Yet Again) As a Potential Medicine

Mescaline is regarded as the one of the first classical psychedelic drugs alongside LSD and psilocybin, but it is only beginning to attract the interest of researchers conducting clinical trials. Recent efforts by MindMed, however, suggest that mescaline is poised to make a significant contribution to the emerging psychedelics industry. 

The use of mescaline for inner exploration is actually how the word “psychedelic” was first coined. The term arose from an exchange between psychiatrist Humphry Osmond and author Aldous Huxley, after the latter’s infamous, inaugural mescaline trip in 1953 ― at 59 years old ― spawned his influential work The Doors of Perception the following year. Osmond famously wrote in a letter to Huxley around the time of publishing: “To fathom Hell or soar angelic/Just take a pinch of psychedelic,” melding the Greek words psyche (mind) and delos (manifesting). 

In the book, Huxley describes his expansive mescaline trip in grand detail moving about Los Angeles ― from West Hollywood to the hills above the town to the Owl Drug Store on La Cienega Blvd ― including a period where he became lost in the texture of his slacks. “I looked down by chance, and went on passionately staring by choice, at my own crossed legs,” wrote Huxley. “Those folds in the trousers ― what a labyrinth of endlessly significant complexity!”

It’s interesting to note that while Huxley had especially troubled eyesight, a fair amount of his experience was punctuated by vivid visual distortions. Typical effects of mescaline tend to include bright visual hallucinations, whether eyes closed or open, revival of long-forgotten memories, sensitivity to light and color, synesthesia (particularly with music) and altered perception of time. Another distinctive characteristic of mescaline use is the geometrization of 3D objects, which can appear to be flattened and warped, like the appearance of a Cubist painting.

Naturally occurring mescaline is an alkaloid that’s found in two families of cacti ― San Pedro in South America and peyote in North America ― and has a long history of usage dating back nearly 6,000 years. The first known use of peyote was uncovered in the painted Shumla Caves in the Lower Pecos region of the Chihuahuan Desert (today’s southwest Texas) with radiocarbon dating confirming use of ground peyote by inhabitants there in Late Prehistoric times. 

Author Mike Jay, who wrote Mescaline: A Global History of the First Psychedelic, shared in an interview with Vice that when the Spanish arrived in Mexico in the 1500s, they encountered locals chanting Aztec prayers and songs to the divine plant that takes people to the “House of the Sun, a world of light and beauty.” 

The Spanish also recorded two different types of peyote ritual: a healing ceremony, where a curandero divines the cause of an illness or a curse; and ceremonies where inhabitants consume peyote and dance around a fire all night in a communal celebration. Later in the 1800s in the U.S., in roughly the same geographic region, the Native American Church was also established, a key part of which is the consumption of peyote as a religious sacrament during overnight ceremonies. It is a sacramental activity Native Americans have enjoyed for generations ― and still legally enjoy in the U.S. for traditional ceremonial purposes.

Nearing the 1900s, the drugmaker Parke-Davis in Detroit, Michigan, got wind of such indigenous treatments and began examining some of the novel botanicals long in use in places like Central and South America. In search of healing plants to add to their catalogue, they were looking for an alternative to the popular drug cocaine, which was showing addictive properties in users. Parke-Davis soon began offering peyote tincture as a respiratory stimulant and heart tonic. 

In 1919, synthetic mescaline came on the scene and became commonly available after chemist Ernst Späth first synthesized it at the University of Vienna. The following year, the pharmaceutical company Merck began marketing it. (Merck was also the first to synthesize MDMA a few years prior to that in 1912.) Over the next couple of decades, medical practitioners employed mescaline for mental maladies, hoping it might help reveal the underlying causes of schizophrenia or potentially point to cures for other psychological disorders. 

Up until the mid-1960s, just prior to Richard Nixon fully launching his war on drugs and the Controlled Substances Act into law, mescaline was one of the many valuable drugs being studied and plumbed for its potential as a medicine. In 1967, the dominoes began to fall, and that year peyote was made a Schedule 1 drug by the federal government. 

Now nearly a half a century later, scientists are again looking into the mescaline molecule in an attempt to create next-generation novel medicines. In fact, the clinical stage psychedelic medicine company MindMed recently announced approval in Switzerland of the first clinical trial evaluating the acute effects of different doses of mescaline and the role of the serotonin 5-HT2A receptor in mescaline-induced altered states of consciousness. 

Dr. Dan Karlin, Chief Medical Officer at MindMed, believes that the thousands of years of use by indigenous cultures in the Americas suggests the potential efficacy of mescaline for a number of conditions. He also thinks that data on the drug may well inform creation of other new chemical entities or analogues. 

“Mescaline is a tricky compound because of a high rate of nausea and vomiting, and experiences that are reportedly quite variable from person to person,” says Karlin. “We don’t necessarily see ourselves developing mescaline toward regulatory approval, but we do think it’s absolutely critical to the science of psychedelic and psychedelic adjacent compounds to better understand, through careful study, the range of currently known and available molecules, and their effects on people both in the short term and in the period after use.”

Exploring psychedelic adjacent compounds is a big part of their mission, which is to discover, develop and deploy psychedelic-inspired medicines and therapies to address addiction and mental illness. MindMed has already created a structural analog of another useful drug, ibogaine, and is advancing the substance specifically for opioid use disorder patients. Modeled after tabernanthe iboga, a perennial rainforest shrub native to West Africa, the medicine has long been employed to help individuals stuck in cycles of substance abuse to break free of their addictions. 

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While certain anecdotal evidence from mescaline’s storied history suggests particular efficacy in substance use disorders, the lack of current hard data on the substance makes it too early to tell if it could be a useful therapy to break addiction patterns. But more data is coming, says Karlin. An ongoing double-blind, placebo-controlled study in 32 healthy subjects comparing mescaline/LSD/psilocybin is about 60% completed. 

The data from that analysis, conducted at the University Hospital Basel Liechti Lab in Basel, Switzerland, will inform their decision going forward. Karlin notes that while MindMed is not funding the study, they will retain an exclusive license to all IP and any patents generated from data or findings in the study and related work.

“This data-driven understanding will inform all of our strategic choices for the development of classical psychedelics and next generation novel chemical entities,” says Karlin. 

A new relationship that the company entered into this year with Swiss startup MindShift Compounds AG ― to develop and patent next-gen psychedelic compounds with psychedelic or empathogenic properties ― should provide a roadmap forward for MindMed’s mescaline endeavors.

“Through our partnership with MindShift,” says Karlin, “we anticipate being able to evaluate through various assessments a number of mescaline analogues, which they are currently working on.”

Image: Nicki Adams using modified graphics by Jorge Pacheco and Cacycle

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