Where to begin? When it comes to psychedelic drugs, one thing is for sure; there is no shortage of fascinating talking points.
The storied history of psychedelics is richly decorated with everything from magico-religious indigenous traditions, scientific breakthroughs, and grossly illegal human experimentation, to devastating instances of unfounded drug classification, trailblazing underground therapists, charismatic drug advocates, and life-changing, mystical-type encounters with the divine.
Once Ernst Späth had skillfully synthesized mescaline in 1919, making available endless quantities of the psychedelic phenethylamine for scientific investigation and recreational use, psychedelics began to exert their significant influence not just on Western medicine, but Western culture, too. The psychedelic era of the 60s and 70s was a time of great social, musical, and artistic change interspersed with cultural and political tumult, speculative fiction, and wildly fascinating folklore.
Now, after a rather unnecessary decades-long pause in research, the modern-day psychedelic renaissance promises much in the way of advancing mental health care. Psychedelic compounds, some of which look soon to become legal medicines, are demonstrating clinical efficacy for a wide variety of psychological disorders.
One could very easily lament the years of research lost to prohibition, but the resurgence of psychedelic-augmented healing is finally upon us, and slowly but surely firmly establishing itself, at least, as a very effective treatment modality.
Classical psychedelics are a class of consciousness-altering drugs that include mescaline (the psychoactive component of peyote), psilocybin (the psychoactive component in magic mushrooms), dimethyltryptamine (DMT), and d-lysergic acid diethylamide (LSD). Classical psychedelics exert their powerful psychological effects primarily via activation of 5-HT2A serotonin receptors, however, although this pharmacological action is a common factor, it likely does not explain their broad-spectrum effects alone.
Structurally, serotonergic psychedelics can be divided into two broad categories: a) tryptamines such as LSD, psilocybin, DMT, and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT). 5-MeO-DMT was relatively recently discovered in nature when trace quantities were detected in the bark of Dictyoloma incanescens, but it is perhaps best known as the natural psychedelic drug found in the venom of the Colorado River toad, Bufo Alvarius. And, b) phenethylamines such as mescaline. In recent years, the category of psychedelics has been expanded to include several additional compounds that exert their psychoactive effects via different mechanisms, yet produce mind-altering experiences that bear resemblance to those induced by the classics.
These include the empathy-promoting entactogens 3,4-methylenedioxymethamphetamine (MDMA) aka ecstasy, and 4-Bromo-2,5-dimethoxyphenethylamine (2C-B), the dissociative anesthetics Phencyclidine (PCP), ketamine, dextromethorphan (DXM), and nitrous oxide aka laughing gas, the atypical dissociative salvinorin-A (the psychoactive component of the Oaxacan plant species Salvia divinorum), and the dissociative psychedelic ibogaine (the psychoactive component of the Central-West African shrub Tabernanthe iboga).
Hallmark subjective effects of psychedelics include:
- Physical euphoria
- Increased empathy
- Perceptual distortions
- Sensory enhancement
- Distortions of time and space perception
- Vivid closed-eye kaleidoscopic/geometric visuals
- Cognitive flexibility psychological insight
- Increase in nature connection
The term “psychedelic” was coined in a 1956 letter correspondence between famed English writer and philosopher Aldous Huxley and the English psychiatrist and psychedelic researcher Dr. Humphry Osmond, who, interestingly, was the first person to introduce Huxley to the first psychedelic to permeate the western world — mescaline.
In a letter to his psychiatric radical friend, Huxley suggested that this peculiarly psychoactive class of drugs be termed “phanerothyme” from the Greek phanein (to reveal) and thymos (soul).
In his letter, Huxley included the following rhyme: “To make this mundane world sublime, Take half a gram of phanerothyme.”
However, incompletely satisfied with Huxley’s suggestion, Osmond countered with his rhyme, “To fathom Hell or soar angelic, Just take a pinch of psychedelic.” The term “psychedelic,” derived from the Greek words psyche (mind) and delos (to manifest) ultimately prevailed, and Osmond formally announced it at the New York Academy of Sciences meeting in 1957.
In the golden age of psychedelic research, thousands of studies described the use and therapeutic potential of mescaline, psilocybin, and LSD, in a wide variety of clinical populations with mental health problems. It is estimated that between the years 1950 and 1965, some 40,000 patients received LSD therapy in one form or another.
At this time, the foremost formal models of psychedelic-assisted psychotherapy employed were the psycholytic and psychedelic approaches.
According to Johns Hopkins researcher Albert Garcia-Romeu and legendary psychedelic therapist Bill Richards, the psycholytic model was informed by psychoanalysis and took the form of in-depth talk therapy over multiple sessions, with numerous administrations of low-to-moderate doses of psychedelics.
Therapists following the psychedelic therapy model administered high doses of psychedelics to produce a powerful, transcendent experience that was believed to kickstart the psychotherapeutic process and serve as a basis for engendering psychological improvement and behavior change. As is the case in today’s clinical trials, therapists largely took a non-directive approach during drug sessions to allow the psychedelic experience to unfold in an unrestricted manner.
Unfortunately, diffusion into wider society and increased recreational use spurred on by the impassioned proselytizing of countercultural figureheads, compounded by hardened sociopolitical attitudes towards drug use and sensationalized, fear-mongering media reporting, ultimately provoked the banning of psychedelics in the late 60s, and put a stop to almost all scientific research and medical use of psychedelics.
Of course, long before their recreational and medicinal use in the West, many psychedelic substances had been ritually ingested in religious ceremonies for millennia by indigenous communities all over the world. The ancient, sacred use of mind-manifesting substances continues to this day, particularly in South and Central America, where indigenous peoples peacefully and responsibly undertake shamanic journeys to reconnect to Spirit, heal themselves of black-magic occasioned illnesses, and commune with forest-dwelling plants and animals.
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Recent discoveries suggest that psilocybin-containing so-called “magic mushrooms” have been used as part of religious and/or social rituals for 6000 years. The Selva Pascuala mural, a cave painting near the town of Villar del Humo in Cuenca, Spain, represents the earliest reliable evidence of the use of psilocybin in Europe. This post-Paleolithic piece of rock art depicting the use of Psilocybe hispanica dates back to 4000 BCE, and is part of a set of more than 12 cave art sites declared World Heritage Sites by UNESCO.
In addition, nine miniature mushroom stones and nine stone tools from the Verbena cemetery at Kaminaljuyu, Guatemala dating back to 1000-500 BCE are indicative of sophisticated religious use of Psilocybe mexicana. Archaeologists Botany professor Bernard Lowy has suggested that these sculptures may have been associated with Mayan religious ceremonies wherein psychedelic fungi played a major role, and may have been linked to a fertility cult.
In 1955, amateur mycologist R. Gordon Wasson traveled to Oaxaca, Mexico to take part in a traditional Mazatec mushroom ceremony. Having received permission to do so from the most highly regarded Mexican healer, María Sabina, aka the “priestess of mushrooms,” and, having enjoyed a powerful experience, Wasson persuaded world-famous French mycologist Roger Heim to join him on a trip to Oaxaca.
In 1958, having received some Psilocybe mexicana from Heim, Swiss chemist Albert Hofmann isolated psilocybin as the mushroom’s psychoactive ingredient, before becoming the first person to artificially synthesize it soon thereafter. Psilocybin has since been detected in almost 200 species of psychoactive mushrooms worldwide.
Archaeological evidence from the Guitarrero Cave located in the Callejón de Huaylas valley in Yungay Province in the Ancash region of Peru suggests that the psychedelic cacti San Pedro (Echinopsis pachanoi), also called huachuma, of which mescaline is the psychoactive principal, has been used in shamanic rituals since 8200-6800 BCE. Here, remnants of San Pedro were discovered with ceremonial artifacts dating back to 8200–6800 BCE to the Lithic period.
Perhaps the most well-known representation of the ancient origins of San Pedro use is the Raimondi stele, a Chavín stone carving from 1300 BCE located in the temple site of Chavín de Huántar, in the Andean highlands of Peru that depicts a fearsome anthropomorphic creature, the “Staff God,” holding a staff in each hand that double as San Pedro cactus.
Much like San Pedro, peyote (Lophophora williamsii) has been used by indigenous tribes for thousands of years. Radiocarbon analysis of peyote effigies made from ground peyote and other plant material demonstrates the use of peyote in the Shumla Caves in the Lower Pecos region of southwest Texas approximately 6000 years ago.
Mescaline was identified as the sought-after psychoactive component of peyote in 1897 by the esteemed German chemist, Arthur Heffter. Despite its schedule 1 status under the Controlled Substances Act, members of the Native American Church have religious exemption to consume peyote as part of their religion — the largest pan-Indian religion in North America.
Ayahuasca, a psychoactive botanical brew made by prolonged boiling of the leaves of the Psychotria viridis shrub and the Banisteriopsis caapi vine, has been used by indigenous Amazonian communities for millennia.
Various anthropological investigations and ethnographic sources have enlightened as to the traditional purposes of ayahuasca use, indicating that indigenous shamanic healers facilitate magical-religious ceremonies, in which they consume and utilize the visionary properties of ayahuasca, to diagnose, heal, communicate with spirits, engage in spiritual warfare, and acquire magic Amazonian songs called “icaros.”
Archaeological evidence during the Tiwanaku empire expansion demonstrates the presence of 1000-1500-year-old snuffing tablets and grave goods buried along with preserved mummies. Gas chromatography-mass spectrometry analysis of the mummies' hair samples identified constituents of the ayahuasca vine, Banisteriopsis caapi, providing the earliest evidence of its use among ancient Andean communities. That said, many anthropologists claim that indigenous communities of the Amazon have likely been using ayahuasca for at least 5000 years.
In recent years, ayahuasca ceremonies have become increasingly popular Western world, with many indigenous shamans traveling Westwards yearly to offer the medicine and many thousands of Westerners traveling to the Amazon to take ayahuasca at multi-day retreats.
One of the main psychoactive constituents of ayahuasca, DMT, is also present in the beans of Anadenanthera peregrina, a perennial tree native to the Caribbean and South America. The beans, traditionally ground into a snuff called yopo, have been used in ceremonial contexts for thousands of years by indigenous populations.
DMT was first synthesized in 1931 by German-Canadian chemist Richard Manske before Hungarian chemist Stephen Szara discovered the tryptamine’s unique psychedelic properties in 1965. Interestingly, DMT has since been identified in human blood, urine, and cerebrospinal fluid, which has led to much speculation regarding the whereabouts of its production and its biological function.
LSD was first synthesized in 1938 by the Swiss chemist Albert Hofmann, who at the time was plying his trade at leading pharmaceutical company Sandoz Pharmaceuticals based in Basel, Switzerland. Hofmann was trying to produce an effective circulatory and respiratory stimulant, when, instead, he synthesized the 25th lysergamide from lysergic acid — LSD-25, as it was originally known.
Unimpressed by the modest, “restless” effects that the drug was observed to produce in animal studies, LSD was temporarily discarded. That was until Hofmann was overcome with a “peculiar presentment” five years later, on April 16, 1943, that encouraged him, rather mysteriously, to resynthesize LSD.As he was nearing the end of his day's work, Hofmann was interrupted by unusual sensations that forced him to prematurely finish up and head home, where his consciousness would become more strangely and intensely altered to the point where he was captivated by “an uninterrupted stream of fantastic pictures, extraordinary shapes with an intense, kaleidoscopic play of colors.”
Unsure of exactly what had happened, but with a hunch that perhaps he had accidentally ingested a microscopic yet powerfully compelling dose of LSD, Hofmann decided to self-experiment with 250 micrograms (a quarter-milligram). Unaware of the strength of his dose, the skilled chemist was planning on documenting his experience, but, of course, this was made impossible by LSD’s profound psychoactive effects.
The resulting trip report consisted merely of 13 barely decipherable, scribbled words. But it wasn't to matter. With the help of his lab assistant, Susi Ramstein, Hofmann made it home on his bicycle where he continued to be nursed by a bewildered neighbor who appeared witchlike, and, having come out the other side, was surprised to find that could remember the entirety of his frightening experience.
Not only did Hofmann remember his experience in fine detail, but he felt refreshed and overcome with “a feeling of good fortune and gratitude." The following morning, when Hofmann walked out into his garden after a rainfall, "everything glistened and sparkled in a fresh new light. The world was as if newly created."
Albert Hofmann’s discovery of the psychedelic experience produced by LSD is commemorated every year on April 19 ("Bicycle Day”).
In addition to its central influences on culture, art, and music in the mid-20th century, the discovery of LSD was crucial to the advance of neuroscience and psychiatry, inspiring American biochemist Betty Twarog to become the first person to isolate serotonin in the mammalian brain, and facilitating effective psychotherapeutic treatment of many thousands of patients suffering from a variety of mental health conditions through its remarkable tendency to loosen tightly-held ego identifications, amplify one’s internal landscape, and impose mind at large.
Unfortunately, the gradual leakage of LSD from the laboratory, its subsequent widespread popularity as a recreational panacea, its association with the counterculture movement of the 1960s, and hysterical newspaper reporting provoked the US government to outlaw the substance in 1968.
As schedule 1 substances, psychedelics remain the most stigmatized and legally restricted of psychoactive agents, despite their impressively favorable safety profile. Scientific use of psychedelics has been severely restricted since their placement into schedule 1 of the 1970 Controlled Substances Act, making it unnecessarily difficult to conduct research investigating their therapeutic and spiritual potential.
Thankfully, however, institutional review boards have loosened restrictions in recent years, opening the doors to regulated clinical investigations and facilitating the emergence of an exciting psychedelic renaissance.Clinical trials sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) have demonstrated MDMA’s clinical efficacy for post-traumatic stress disorder (PTSD), prompting the US Food and Drug Administration(FDA) to grant breakthrough status to MDMA-assisted psychotherapy. The (FDA) has also granted psilocybin “breakthrough” therapy designation after it, in conjunction with supportive psychotherapy, demonstrated substantial improvement over existing treatments for treatment-resistant depression and major depressive disorder (MDD).
With psychedelics having already proven themselves as effective treatments for substance use disorders and end-of-life anxiety, and with ongoing clinical trials further investigating their ability to treat a range of mental health and chronic pain conditions, there is much to be excited about in this endlessly fascinating field of study.
5-MeO-DMT (5-methoxy-N, N-dimethyltryptamine) is a short acting, serotonergic psychedelic, found naturally in the venom of the Sonoran Desert Toad (Bufo Alvarius). 5-MeO-DMT is gaining popularity as an effective tool for spiritual exploration and healing due to its extremely powerful psychoactive effects.
What is unique about ayahuasca is that it is a concoction of two plants, the combination of which is essential for the ayahuasca experience. Combining two plants to use as medicine may not seem groundbreaking in and of itself, but the fact that if one is taken without the other, the experience is entirely different, and arguably non-existent, is what makes the discovery of ayahuasca so surprising.
For millennia indigenous-American tribes have consumed N,N-dimethyltryptamine (DMT) as a key ingredient in sacred botanical brews, such as ayahuasca, and snuffs, such as yopo, as part of religious ceremonies in Central and South America.
Though ketamine gained a reputation for being dangerous and easily misused and abused, it wasn’t until 1999 that the US classified it as a Schedule III controlled substance. While it is often associated with the party scene, ketamine therapy is helping change the lives of many with severe depression, PTSD, OCD and even chronic migraines.
In 1938, a Swiss chemist by the name of Albert Hofmann, working out of Sandoz Pharmaceuticals, became the first man to synthesize Lysergic Acid Diethylamide (LSD). Active at the microgram level (one-thousandth of a gram), LSD is the most potent psychoactive drug known to humankind.
The MDMA molecule bears structural resemblance to stimulants and some psychedelics, invoking feelings of euphoria, empathy, and boundless energy. MDMA also intensifies sensory perception, enhancing one’s appreciation of music and color which makes it one of the most popular drugs among festival-goers and electronic dance music fans alike.
In the 16th century, Spanish chroniclers attempted to eradicate ritual use of peyote cactus among indigenous American cultures, which led to the plant’s eventual prohibition in 1720. In the face of adversity, several indigenous communities righteously persevered, continuing and preserving their sacred practice in clandestine secrecy, and even managing to spread it widely over the last 150 years.
Peyote is a green spineless cactus that contains the classic psychedelic compound mescaline. Numerous Mesoamerican cultures, including the Huichol (Wixárika), the Cora (náayeri), the Tepehuanes, the Tonkawa, the Mescalero, and the Tarahumara (Rarámuri) have long regarded the plant as sacred, using it in spiritual and healing ceremonies for millennia.
While shrooms were initially used for ceremonial purposes and spiritual awakenings, they have gained popularity for recreational use and current research on shrooms effects in a therapeutic setting is promising.
Since prehistory, San Pedro has been instrumental to Peruvian cultural traditions. in northern Peru in particular, it has been a tool to facilitate the shaman’s ‘‘journey’’ for healing purposes. Throughout this period, the visionary cactus has been known by many names, including huachuma or achuma.