A relationship older than writing
Human interest in plants, fungi, and animals capable of altering consciousness predates any written record and, according to some authors, even predates our own species. Researchers like Ronald Siegel or Terence McKenna have suggested that early hominids learned from other animals to sample substances that induced strange behaviors, and that this is how they stumbled upon the first psychoactive compounds. These are suggestive hypotheses, but they should be read as such: speculative narratives about origins, not proven conclusions.
It is better documented that numerous ancient cultures employed these substances for their effects on the mind. African depictions of mushrooms associated with the human body have been described, and the influence of altered states on some European cave art is a subject of debate. From there, some authors have speculated that language, spiritual consciousness, or even religion may have their roots in these experiences. Again, these are theses that circulate with varying levels of support: interesting to think about, but fragile to assert.
What anthropology maintains more solidly is that many societies used visionary plants and fungi for specific functions: group cohesion, healing practices, artistic inspiration, and religious experience. Much of what we know chemically today—DMT, psilocybin, mescaline, and related compounds—comes from the analysis of materials from the Americas, where these uses never entirely disappeared.
The Old World and suspicion
The abundance of visionary plants in the Americas surprised and alarmed European colonizers. The relative scarcity of hallucinogens in Europe explains part of that bewilderment, but the decisive factor was another: the association of these practices with witchcraft. The Church effectively repressed their transmission and persecuted those who preserved them, to the point that it was only a few decades ago that it was confirmed that rituals with sacred mushrooms in Mexico had survived the 16th-century conquest.
In Europe itself, scholarly interest in these substances was marginal until the late 19th century, when authors like Baudelaire or Thomas de Quincey described the effects of opium and hashish. Even so, the doses required to reach intense states were considered excessive and unmanageable, and the subject remained in the realm of literature rather than science.
Mescaline opens the door
The turning point came with peyote (Lophophora williamsii), an American cactus from which, in the last decade of the 19th century, several German chemists isolated mescaline. Those who tried it spoke of “artificial paradises,” but the nausea that accompanied the experience cooled enthusiasm, and it generated little medical literature until the late 1930s.
There was also a deeper obstacle: Freudian psychoanalysis dominated psychiatry. Freud was interested in substances like cocaine, but he rejected the religious dimension of the mind, interpreting it as a defense against childhood fears. That intellectual climate was not the most conducive to a substance so linked to indigenous spirituality.
Hofmann and LSD: unprecedented potency
In 1938, Swiss chemist Albert Hofmann was working with ergot derivatives for Sandoz laboratories, searching for a compound useful for postpartum hemorrhaging. One of those derivatives was LSD-25 (lysergic acid diethylamide). The initial trials were unpromising, and he shelved it. Five years later, what he described as a “curious presentiment” led him to revisit it, and he accidentally discovered its intense effects on perception.
What is remarkable about LSD is that it acts in quantities on the order of millionths of a gram, a potency far superior to that of mescaline. Hofmann himself was overwhelmed by an amount he had judged too small to have an effect. Due to the magnitude of the alterations it produced, early scientists emphasized its “psychotic” properties: they understood it, above all, as a way to reproduce madness in the laboratory.
Serotonin and the birth of biological psychiatry
The years before and after World War II were decisive. Alongside LSD, the first antipsychotics appeared, such as chlorpromazine (Thorazine), which dramatically improved patients with severe conditions. From that intersection, “biological psychiatry” was born—the discipline that studies the relationship between mental states and brain chemistry. Its mediator was a molecule that was just beginning to be understood: serotonin, whose name combines the Latin serum (whey) and tonus (tension).
Around 1948, blood serotonin was linked to the regulation of artery and vein walls. In the 1950s, it was located in the brains of various animals, and it was found that the regions containing it influence sleep, wakefulness, sexual and aggressive behavior, and other basic functions. It was established as the first known neurotransmitter. When the similarity between LSD and serotonin molecules was also noted—the former sometimes blocking and other times mimicking the latter—LSD became the most useful tool for exploring the relationship between brain and mind.
Two decades of field research
For about twenty years, dozens of teams administered psychedelics to thousands of healthy volunteers and patients, with public and private funding and an abundant output of papers and conferences. Sandoz distributed LSD to induce controlled “psychotic” states to better understand disorders like schizophrenia, and it was even proposed that psychiatric staff try it to get closer to their patients’ experiences.
From there, it moved into psychotherapy: many studies described promising results in obsessive conditions, post-traumatic stress, depression, alcoholism, and other dependencies, as well as in end-of-life care, where less demand for painkillers and greater acceptance of the prognosis were observed. It is worth qualifying the optimism of those reports: many lacked the controls we would demand today, and the enthusiasm of the therapists may have inflated the conclusions. Even so, they marked a line of research that current psychiatry has returned to with more rigorous methods.
Mysticism, Huxley, and crossed wires
It was soon observed that some psychedelic experiences resembled those described by practitioners of Eastern meditation. That parallel attracted writers like Aldous Huxley, who experimented with mescaline and LSD under the guidance of psychiatrist Humphry Osmond and left influential accounts of the value of the visionary experience. It is significant that Huxley, despite boosting cultural interest in these substances, advocated for restricting their access to a minority of artists and intellectuals: he did not believe the general population was prepared to use them without risk.
The problem is that mixing healing, mysticism, and science tangled the field. Research drifted away from the initial medical framework just as the debate was beginning to leave the laboratory.
1970: the door slams shut
In the 1960s, LSD escaped the laboratories. The press was filled with stories about suicides, emergency room visits, alleged birth defects, and chromosomal damage, and the behavior of figures like Timothy Leary at Harvard reinforced the idea that not even scientists were in control of these substances. Much of that alarm was exaggerated or outright false, and later studies debunked the supposed extreme toxicity; but they arrived late and with little impact.
The available data suggested that, in controlled sessions with stable individuals, psychiatric complications were very infrequent. Serious problems usually appeared in a different setting: vulnerable people consuming impure or unknown products, mixed with alcohol or other drugs, and without support. That distinction—between the context and the substance—was lost in the climate of panic. In 1970, the United States Congress made LSD and other psychedelics illegal, overriding scientific objections. Permits, supplies, and funding were withdrawn, and research was shut down almost overnight.
What remained: amnesia and reopening
It is hard to understand how a field that had supported much of the development of psychiatry for two decades disappeared from the medical horizon until it became unknown to new generations of professionals. The trajectory was as abrupt as it was unnatural: from “miracle cures” to “abominable drugs” in a few years.
The reason was not so much the research results as their termination. For many eminent psychiatrists, the closure was a humiliating experience: they saw that evidence and method were not enough in the face of laws driven by public emotion and the media. Added to this was an internal fracture—between those who defended a strictly cerebral approach and those who valued the spiritual dimension of these experiences—from which the transpersonal movement would eventually emerge. We would have to wait until the mid-1990s, when Dr. Rick Strassman organized a seminar on psychedelics for psychiatry residents at the University of New Mexico—likely the first in decades—and reopened, with DMT as the protagonist, research that seemed closed. We will address that work in the second part.
Critical reading
This historical overview mixes well-established facts with speculative hypotheses, and it is best not to confuse them. The chronology of mescaline, LSD, serotonin, and the 1970 prohibition is documented; the grand theories about the psychedelic origin of language or religion are authorial suggestions, not scientific consensus.
Regarding the substances: N,N-dimethyltryptamine and other psychedelics are not harmless nor are they “safe gateways” to anything. You will not find instructions for procurement, dosage, or consumption here. If you are interested in the subject, prioritize verified sources—scientific reviews and harm reduction archives like Erowid—distrust accounts that promise guaranteed healing or enlightenment, and remember that the context, the prior psychological state, and interactions with other drugs or medications weigh as much as the molecule itself. Anyone going through a moment of mental vulnerability should treat these substances with special caution.
As a central reference for this series, we use DMT: The Spirit Molecule (Rick Strassman, 2001), an influential text but one written in part from the author’s own hypothesis, which deserves to be read with a critical spirit.
