TL;DR: Psychedelics are a class of consciousness-altering drugs that produce changes in thought, perception, emotion, and sense of self. They can be divided into three categories: tryptamines, lysergamides, and phenethylamines. Psychedelics were extensively researched in the 1950s and 60s for their therapeutic potential but were banned due to a number of factors including increased recreational use and concerns about public health and safety. Indigenous cultures have been using psychedelics in ceremonial contexts for thousands of years, and recent discoveries suggest that they may be effective in treating certain mental health conditions.
Psychedelics are a group of drugs that profoundly alter consciousness, causing significant shifts in perception, cognition, emotion, and sense of self. “Classic psychedelics'' include mescaline (derived from the peyote cactus), psilocybin (the active compound in magic mushrooms), N, N-dimethyltryptamine (DMT), and d-lysergic acid diethylamide (LSD).
Classic psychedelics primarily exert their effects by binding to 5-HT2A receptors, a specific type of serotonin receptor located on the surface of nerve cells (neurons) which are responsible for generating information in the brain. When classic psychedelics bind to 5-HT2A receptors, it triggers changes in brain activity and leads to the characteristic effects of psychedelic drugs.
While binding to 5-HT2A receptors is a shared mechanism among classic psychedelics, it is likely not the sole explanation for their diverse effects.
Understanding the Different Categories of Psychedelics
Psychedelics can be divided into three main categories based on their chemical structure: tryptamines, lysergamides, and phenethylamines.
Tryptamines are a diverse group of compounds derived from the amino acid tryptophan. While tryptamine itself is not psychoactive, it serves as the foundation for various natural and synthetic psychedelics.Examples of tryptamines include DMT and psilocin, which is derived from psilocybin found in magic mushrooms. Another notable tryptamine is the powerful psychedelic 5-MeO-DMT which is found in certain plant species and the venom of the Colorado River toad.
Lysergamides, another category of classic psychedelics, share a common foundation with tryptamines but have a more complex molecular structure. One well-known lysergamide is LSD, first synthesized by Albert Hofmann in 1938. LSD has gained widespread recognition as one of the most renowned psychedelics in history. Lysergic acid amide (LSA) is a simpler lysergamide that occurs naturally in the seeds of certain morning glory plants and Hawaiian Baby Woodrose.
Phenethylamines form the third category of classic psychedelics, characterized by a molecular structure built around a phenethylamine backbone. Mescaline is a prominent representative of phenethylamines and is derived from various cacti, most notably the Peyote and San Pedro cacti.
Mescaline has a structure that can be easily modified through simple chemical changes, leading to the creation of new compounds. Alexander “Sasha” Shulgin, a renowned psychedelic chemist, pioneered the synthesis and personal experimentation of over 150 novel phenethylamines. His work contributed to the development of 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as “ecstasy” or “molly.”
Understanding these three categories provides insight into the diverse range of classic psychedelics and their origins. Each category encompasses distinct compounds that offer unique psychoactive effects, contributing to the rich tapestry of psychedelic experiences.
In addition to classic psychedelics, there are other compounds that produce comparable effects but act through different brain mechanisms. These include entactogens like MDMA and 2C-B, dissociative anesthetics like PCP, ketamine, DXM, and nitrous oxide (also known as “laughing gas”), Salvinorin-A from Salvia divinorum, and Ibogaine from Tabernanthe iboga.
In 1956, the English psychiatrist and psychedelic researcher Dr. Humphry Osmond wrote to the famed English writer and philosopher Aldous Huxley, seeking his help in coming up with a name for this class of drugs. Interestingly, Huxley had become interested in psychedelic drugs after being introduced to mescaline by Osmond in 1953.
In response to Osmond's request, Huxley suggested the term “phanerothyme,” derived from the Greek phanein (to reveal) and thymos (soul), and included a rhyme in his letter: “To make this mundane world sublime, Take half a gram of phanerothyme.”
However, Osmond was not satisfied with Huxley's suggestion and countered with his own rhyme: “To fathom Hell or soar angelic, Just take a pinch of psychedelic.”
In the end, the term “psychedelic,” which Osmond derived from the Greek words psyche (mind) and delos (to manifest), prevailed. Osmond announced the term “psychedelic” formally at the New York Academy of Sciences meeting in 1957.
In the golden age of psychedelic research between the 1950s and 1970s, 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.
During that time, the most popular models of psychedelic-assisted psychotherapy were the “psycholytic” and “psychedelic” approaches.
The psycholytic model was informed by psychoanalysis, a form of therapy that aims to explore and resolve unconscious conflicts and patterns in a person's thoughts, feelings, and behaviors. The psycholytic model of psychedelic-assisted therapy took the form of in-depth talk therapy over multiple sessions, with numerous administrations of low-to-moderate doses of psychedelics.
On the other hand, therapists following the psychedelic therapy model administered high doses of psychedelics to produce a powerful, transcendent experience that was believed to kickstart the therapeutic process and serve as a basis for producing psychological improvement and behavior change. As is the case in contemporary psychedelic research, therapists took a non-directive approach during drug sessions, meaning they acted as a facilitator and allowed the patient to take the lead in the therapy session, without imposing their own opinions or judgments. This allowed the psychedelic experience to unfold in an unrestricted manner.
However, diffusion of psychedelic substances into wider society, increased recreational use, hardened social and political beliefs and opinions about drug use, and sensationalist media reporting ultimately led to the banning of psychedelics in the late 1960s. This put a stop to almost all scientific research and medical use of psychedelics.
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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.
Ibogaine is a naturally occurring indole alkaloid derived from the roots of an threatened species of perennial rainforest shrub called Tabernanthe iboga. Ibogaine, which is believed to have potent anti-addictive properties, has been used by the indigenous peoples of central west Africa for centuries.
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 evidence suggests that psilocybin mushrooms have been historically used in ritual settings for spiritual and medicinal purposes, they have gained popularity for recreational use, and clinical research on the therapeutic effects of psilocybin is promising.
Salvia is a psychotropic flowering herb from the Lamiaceae, or mint, family. Salvia’s large green leaves contain the powerful psychoactive compound, salvinorin A. Salvia leaves are used for medicinal and religious purposes by Mazatec shamans in the Mexican state of Oaxaca, and they are often used recreationally in the west.
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.