Most people have no idea that the Indigenous peoples of ancient Mexico and Central America curated what was likely the most powerful psychedelic medicine chest on Earth.

And there’s a reason you’ve never heard about it.

The Spanish Conquistadors tried to wipe this knowledge off the map, censoring, banning, and destroying anything tied to indigenous psychedelic practices.

They nearly succeeded…

But a few wisdom keepers—across both Mesoamerican and Spanish lineages—held the teachings close and passed them on.

Here are the sacred entheogenic medicines they fought to keep alive.

The Mesoamerican Psychedelic Apothecary

Many ancient cultures turned to psychoactive plants for healing and the ceremony:

• Amanita muscaria and Siberian shamans
• Blue Lotus and the ancient Egyptians
• The Hexing Herbs (Henbane, Belladonna, Mandrake) used by European witches and oracles
• Ergot—rich in LSD-like compounds—was the secret ingredient in the mysterious Ancient Greek drink known as the Kykeon
• Cannabis across the Middle East and Asia
• Haoma, the mind-altering sacrament of ancient Persia
• Iboga in Central West Africa

…and the list goes on.

But the Mesoamericans were operating on an entirely different level.

Archaeology, ethnography, and early Spanish chroniclers—especially Fray Bernardino de Sahagún—reveal the astonishing range of plants, fungi, and brews these cultures used and the profound states they induced.

What emerges is a psychedelic pharmacopeia loaded with some of the most potent psychoactive compounds known to humanity.

These weren’t recreational substances. They were tools used in ritual healing, religious ceremony, initiation, and divination.

Here’s what they relied on to crack open consciousness, and we might as well take a small dose of each.

Teonánactl (Psilocybin)

In the Aztec era, psilocybin mushrooms were called Teonanácatl, meaning “divine mushroom” or "flesh of the gods."

Mexico remains a global hotspot for Psilocybe, with roughly ~230 known species, at least 54 occur there, including:

• P. mexicana
• P. aztecorum
• P. caerulescens
• P. cubensis. [1]

Because of their abundance, many pre-Columbian cultures across Mesoamerica incorporated these mushrooms into healing rites, divination, and religious ceremonies. [2] Archaeological evidence suggests their use extends back roughly 3,500 years. [3]

The 16th-century chronicler Fray Bernardino de Sahagún recorded their effects:

Today, their ceremonial use survives most prominently among the Mazatec, where Indigenous tradition and Catholic symbolism have fused into a unique syncretic practice.

Peyote (Mescaline)

Peyote is a small, spineless, button-like cactus packed with mescaline—along with more than 60 other alkaloids—which together produce long-lasting, vividly colorful, geometry-warping visions, heightened sensory perception, and powerful spiritual or out-of-body experiences. [4]

It’s also one of the oldest ritual psychedelics in the Americas, with archaeological evidence stretching back over 5,000 years. Peyote remnants have been found in Cuatro Ciénagas, Coahuila, Mexico, and in Shumla Cave in Texas, confirming its prehistoric use. [5]

Multiple pre-Columbian cultures used it, including the Olmec, Zapotec, Maya, and Aztec. Fray Bernardino de Sahagún recorded its effects in the 16th century:

During the Inquisition, the Spanish fiercely suppressed peyote ceremonies, and by 1720, its use was officially banned.

But peyote survived.

It remains central to the spiritual traditions of the Tarahumara and Huichol of northern Mexico, as well as the Navajo, Comanche, and members of the Native American Church in the United States and Canada—used in vision quests, healing rites, and ceremonies meant to communicate with the spirit world.

Ololiuqui (LSA)

Ololiuqui refers to the seeds of the morning glory Turbina corymbosa, which contain LSD-like alkaloids—most notably d-lysergic acid amide (LSA), the primary psychoactive compound—along with several others that shape its visionary effects. [6]

The Aztec, Maya, Mixtec, and Zapotec peoples used these seeds to alter perception and enter trance-states for healing, diagnosis, and divination. Unlike communal peyote or mushroom ceremonies, ololiuqui was typically taken privately with a healer, making it an intimate, diagnostic form of medicine.

And the pharmacology aligns with the tradition: LSA, though structurally similar to LSD, produces a more sedating, inward-turning experience. It's often described as lucid, dreamlike, and introspective, with visual trails, color shifts, brightened lights, and soft, hazy imagery. [7]

The conquistador Juan de Cárdenas described ololiuqui intoxication as follows:

Today, these seeds—along with other LSA-containing species like Ipomoea violacea and Hawaiian Baby Woodrose (Argyreia nervosa)—are often used recreationally as a so-called “legal high.” [0]

Pipiltzintli (Salvia divinorum)

Known as Pipiltzintli by the Mazatec people of Oaxaca, Salvia divinorum is a visionary plant from the mint family (Lamiaceae). Its active molecules—especially Salvinorin A—make it the most potent naturally occurring hallucinogen known, with powerful effects at doses as low as 200 micrograms [8,9], roughly 100× stronger by weight than psilocybin mushrooms.

But salvia is fundamentally different from classic psychedelics like psilocybin, LSD, LSA, DMT, or mescaline.

Instead of acting on serotonin (5-HT2A) receptors, Salvia divinorum activates the kappa-opioid receptors (KOR), producing its distinct, dreamlike, and often disorienting effects. [10]

Importantly, those intense breakthrough states only occur when salvia is smoked, a modern practice.

Traditionally, Mazatec shamans chewed the fresh leaves [11], which creates a far gentler, more meditative, and deeply introspective state rather than full dissociation. This softer, inward-turning effect is what made it a revered tool in divination (hence the name, "divinorum").

Bufo (5-MeO-DMT)

Bufo refers to the venomous secretion of the Sonoran Desert toad (Bufo alvarius), a milky defensive toxin loaded with 5-MeO-DMT—one of the most powerful psychedelics on Earth—along with bufotenin. [12]

Chemically, it’s a close relative of DMT, the active molecule in Ayahuasca. But the experience is nothing like DMT’s hyper-visual, kaleidoscopic journeys.

5-MeO-DMT is far less visual and far more deconstructive, driving the user into total ego dissolution, pure presence, and what many describe as “merging with infinity.” [13]

Archaeological evidence suggests that the Olmec used the secretions (and even the dried skins) of Bufo species in ceremony—smoked, eaten, or mixed into alcoholic drinks—to enter trance states. Countless toad remains discovered in ritual contexts alongside Olmec priests point to its role as a sacrament.

Toloache (Datura)

Toloache was the name given to Datura stramonium, a plant in the nightshade family commonly called the “devil’s herb” throughout Mesoamerica.

Despite its ominous reputation, it occupied a powerful place in ritual and healing traditions. Indigenous peoples across northern Mexico and the southern United States used it as medicine, a diagnostic oracle to reveal the roots of illness, an initiatory gateway in puberty rites, and even as an aid in hunting.

But unlike other hallucinogenic plants that expanded awareness or clarified perception, toloache carried a far darker signature.

Rich in tropane alkaloids—scopolamine, hyoscyamine, and atropine—it produces intense anticholinergic delirium: agitation, disorientation, violent confusion, and vivid, often nightmarish hallucinations. [14,7]

Because of its ability to dissolve reality so profoundly, toloache is believed to have been used in rituals linked to human sacrifice, where crossing the threshold between worlds was central to the ceremony.

Despite the Spanish conquest and its crusade to erase these sacramental traditions, the knowledge survived. It went underground, hid in stories, rituals, and the hands of a few determined keepers.

But it never died.

Mesoamerican healers, shamans, and curanderos continued practicing in secret, blending the old ways with imposed Christianity and creating a powerful syncretic system where entheogenic plants remained central to communion with the divine.

A practice that is still alive, well, and thriving to this day.

Their apothecary overflowed with numerous psychedelics—peyote, ololiuqui (LSA), toloache, psilocybin mushrooms, Bufo, Salvia divinorum, and countless others—plants, animals, and fungi that opened the gates of healing, divination, and higher consciousness.

Without the resilience of these knowledge keepers, much of this ancient pharmacopeia may have been lost forever.

I owe them deep reverence. Without their traditions, I wouldn’t be here sharing this wisdom with you today.

—Onjae

P.S. Whenever you're ready, here are ways I can help you:

• My calendar is officially open! I’m now taking on new microdosing and macrodosing clients. If you want guidance on your psychedelic journey, you can schedule time with me here.
• And if you want to explore the Mesoamerican psychedelic apothecary for yourself but don’t know where to start, my Sourcing Master List has the goods. Go wild.