Mescaline, a natural hallucinogen found in cacti, is one of the OG psychedelics. Its use has been traced back 6,000 years, to prehistoric psychonauts tripping in caves near the Rio Grande in Texas.

Since then, its powerful effects have been sampled by everyone from Aztecs, Plains Indians and Mormons to WB Yeats, Aldous Huxley and a British MP, who took the drug on camera for a 1955 episode of the BBC's Panorama.

I recently spoke to cultural historian Mike Jay – who's just written a definitive history of the drug, Mescaline: A Global History of the First Psychedelic – about humanity's age-old fascination with this kaleidoscopic substance.

VICE: How long have people been tripping on mescaline?

Mike Jay: The earliest physical evidence of its use is effigies made of dried peyote cactus preserved in the Shumla caves, on the Texas side of the Rio Grande, that have been radiocarbon dated to 4000 BCE. There’s also evidence around this time for the use of other plant psychoactives: tobacco and coca leaf in the Andes, DMT-containing plants in the Amazon, opium and cannabis across Europe and Asia, and beer brewing in the Middle East.

There’s an amazing carving in a very early temple site in Peru, about 1000 BCE, of a fanged, clawed shaman figure holding a mescaline-containing San Pedro cactus. It looks as if this was a pilgrimage site where ceremonies were conducted that involved processions and subterranean passages, and probably DMT-containing snuffs and other mind-altering plants as well as San Pedro. The term "psychedelic" originated in an exchange between Aldous Huxley and the psychiatrist Humphry Osmond, after Huxley’s first mescaline trip in 1953.

What exactly is mescaline, and how is it different from other psychedelics?

Mescaline is an alkaloid that occurs in nature in two families of cacti: the San Pedro in the Andes and the peyote in Mexico, and a bit of what’s now Texas. It’s a phenethylamine, biosynthesised by the cacti from the amino acid phenylalanine, which is also present in foods such as eggs, milk and soybeans, in breast milk and in trace amounts in the human brain.

This makes it different from other psychedelics such as LSD, psilocybin and DMT, which are tryptamines, derived from a different amino acid, tryptophan. Other mind-altering phenethylamines include amphetamine and MDMA. Mescaline has some effects that are similar to these, though it’s also intensely visual and trippy. Compared to other psychedelics it's more physical, with an intense body load [a tactile sensation] that can be experienced as euphoria, or nausea, or both. It’s slower to cross the blood-brain barrier, so onset time is longer – up to two hours – and it also lasts longer, around 12 hours.

What part did the drug play in ancient Mexican culture?

When the Spanish arrived in Mexico they found peyote being traded and used as a sacrament. They noted that the people who used it saw visions, which their priests believed to be the work of the Devil. But they also recorded some Nahua [Aztec] prayers and songs which talk about it as a divine plant that takes people to the House of the Sun, a world of light and beauty.

The Spanish writings describe two different forms of peyote ritual. There’s a healing ceremony, where a curandero [doctor] uses it to divine the cause of an illness or a curse, or to see future events and distant places. Also, among the tribes – such as the Huichol – in the north of Mexico, where the peyote grows, they witnessed ceremonies where villagers would eat or drink peyote and dance around a fire all night in a communal trance or frenzy.

I was surprised to find out the Plains Indians took mescaline. Can you tell me more?

The Plains Indian peyote ceremony developed when the tribes were taken into forced captivity on the reservations. Before then, it was known only to those who visited the areas of Mexico and southern Texas where it grew – mostly Apache bands such as the Lipan and the Mescalero. But after the Texas-Mexico railroad opened in 1881, peyote from Texas began to reach the Comanche, Kiowa and Apache reservations in Oklahoma.

Following the Ghost Dance ceremonies in 1890, which were suppressed after the massacre at Wounded Knee, communal singing and dancing was banned on the reservations. Peyote ceremonies took place in tipis, away from the prying eyes of government agents. Participants ate peyote buttons, usually dried, while seated all night around a central fire, purified with prayers, tobacco and incense, and sang songs accompanied by a drum and rattle that passed around the group. Songs were channelled during the ceremonies and different traditions and forms of ritual evolved.

For men who had been brought up as warriors, the peyote meeting became a microcosm of their vanished world. Peyote worship preserved their culture and identity, and nurtured an ethos of self-respect, particularly abstinence from the alcohol that was destroying their societies.

How has mescaline mixed with religion such as the Native American Church and the Mormons?

The Native American ceremony brought peyote to the attention of western science, and in 1897 its active compound was isolated and named "mescaline". But it also attracted some who were looking for a spiritual experience. Aleister Crowley used it extensively in his magick practice, and obtained a special high-strength peyote extract from the pharmacists Parke-Davis in Detroit. The President of the Mormon Church, Frederick Smith, attended Native American peyote ceremonies in Oklahoma and believed "the peculiar and ecstatic state" it produced had "wonderful and beneficial effects". He considered introducing it to Mormon worship to generate an ecstatic religious experience.

On Indian reservations, peyote was often prohibited and its users harassed and imprisoned. In 1918, the federal government attempted to ban it as a narcotic. To protect themselves, peyote worshippers in Oklahoma incorporated the Native American Church, to give their sacrament legal status under the First Amendment’s freedom of worship. Of all the attempts to construct a religious practice around peyote, this was the one that survived. A century later, it’s still thriving.

What did scientists make of it in the West?

Scientists across the USA and Europe were fascinated by peyote, and especially by mescaline once it was synthesised in the laboratory in 1919. It didn’t behave predictably like other drugs: some people had ecstatic experiences, others nightmarish. It was the first example of what we now call a psychedelic, and researchers zeroed in on the visual hallucinations it produced. Dozens of experimental subjects described and recorded their hallucinations, and artists were given mescaline and asked to draw or paint what they were seeing.

Psychiatrists noticed that its effects had similarities with the symptoms of psychosis – hallucinations, delusions, paranoia, loss of identity – and speculated that disorders such as schizophrenia might be caused by a mescaline-like toxic chemical in the brain. During the 1950s it was used widely in clinical research. By the 1960s, this "psychotomimetic" theory had been largely abandoned, and mescaline itself was mostly replaced by LSD, which produced similar effects at a tiny fraction of the dose.

Mescaline was used by many culturally important people in the 20th century. Why was this?

For the first half of the 20th century, mescaline was the only psychedelic, and people experimented with it from many different perspectives: scientific, artistic, philosophical, spiritual. The spiritual tradition that began with figures like Aleister Crowley and Frederick Smith went mainstream in the 1950s with Aldous Huxley’s book on his first mescaline experience, The Doors of Perception, in which he wrote that it revealed "the miracle, moment by moment, of naked existence". In the 1970s peyote was popularised by [author] Carlos Castaneda, who claimed that his mysterious teacher Don Juan had led him through a series of trips to the hidden world of the nagual, or shaman.

Others, though, used mescaline not for spiritual enlightenment but for artistic and philosophical experiments. In the 1890s, aesthetes and poets such as Havelock Ellis and WB Yeats experimented with it, looking at art objects and listening to music under the influence. In the 1930s, avant-garde artists painted on it, and psychiatrists gave it to intellectuals like Walter Benjamin and Jean-Paul Sartre. Sartre had a very unpleasant experience, after which he believed he was being followed around by crabs that nobody else could see.

Beat writers including Allen Ginsberg and William Burroughs were early adopters of peyote: Ginsberg wrote that it was "like telepathy, like electricity", and Burroughs fantasised that after eating it he was turning into a plant: "we turn green and no one can kick a chlorophyll habit". The most enduring trip in this vein was Hunter S. Thompson's in Fear and Loathing in Las Vegas, in which his white-knuckle escapades are further amplified by "the fearful intensity that comes at the peak of a mescaline seizure".

What impact did the Doors of Perception have on our perception of psychedelics?

Before The Doors of Perception, most people – Aldous Huxley included – thought of drugs as "dope", of interest only to psychiatrists, bohemians and criminals. Huxley presented mescaline as something different, connected both to ancient wisdom and to cutting-edge science. The term "psychedelic" freed it from its associations with psychiatry and mental illness, and made it part of a new generation’s quest for personal growth and spiritual illumination.

You found that mescaline has a growing following for use in ceremonies. Why is this?

The Native American Church has undergone an expansion over recent years. It’s now estimated to have at least 250,000 members across the USA and Canada. It’s spread rapidly through tribes where it used to be uncommon, such as the Navajo, where new religious movements such as evangelical and pentecostal Christianity are also on the rise.

The NAC offers a form of worship that keeps Native American cultural identity alive in the modern world. Its members are often very active in their communities, in initiatives such as alcohol recovery programmes. Among the Navajo, the mescaline ceremony has developed a powerful healing element, and is often seen as being more effective than western psychiatry in addressing problems of trauma and social dislocation.

In the book, you describe the effects of the drug on yourself in an amazing setting – can you explain what this felt like?

Prior to writing the book, most of my experience with mescaline was in the form of the San Pedro cactus, which is the easiest to access and much more sustainable ecologically than peyote. I write a bit about a trip in Peru a few years ago. It’s hard to describe what mescaline "does", because it’s a lot of contradictory sensations: on one hand it’s euphoric, visually rich and enchanted; on the other, it’s quite physically uncomfortable and draining. People have very different experiences with it as a result.

Although there are some pharmacological differences between San Pedro, peyote and pure mescaline, I found they are all pretty similar in their effects. The physical weirdness isn’t just side effects from the cactus, it’s the same with the pure alkaloid too. The big difference is in the context. When taking it on my own, or in an experimental session, I found myself absorbed in the sensations and the visuals. When I took it in a Native American Church ceremony in Oklahoma, it was all about the communal experience.

What impact did mescaline have on the drug world and drug culture?

By the time psychedelic drug culture kicked off in the 1960s, mescaline had been almost entirely replaced by LSD, which was massively more potent: a gram of mescaline is about three doses, a gram of acid is tens of thousands.

But mescaline has had a massive – if indirect – impact on modern drug culture. After the chemist Alexander Shulgin’s first mescaline trip in 1960, he resolved to discover other phenethylamines that might have similar effects. His search led him to synthesise MDMA, which by the 1970s had made its way from psychotherapy to the dance clubs of Texas, Chicago and New York. Shulgin synthesised dozens of variants, such as DOM, 2C-B and 2C-T-7, many of which share mescaline’s more psychedelic properties. In a sense, all these new drugs can be seen as mescaline "tamed" for the chemical generation: less trippy, but also more physically manageable, and lasting three hours instead of a gruelling 12.

Today, pure mescaline has pretty much disappeared from everywhere but the recesses of the dark web. Mescaline-containing cacti, by contrast, are more widely used than ever before. Along with the growth of the NAC, peyote is increasingly popular in Mexico for ceremonies and herbal remedies, to the point where the ecology of the cactus is becoming threatened. The San Pedro cactus, though, grows abundantly across Peru, Eduador and Bolivia, and San Pedro shamans and healing ceremonies are spreading round the globe.