Define Psychedelic

Overview: Psychedelics are consciousness-altering drugs that profoundly impact perception, cognition, and emotion. Classic psychedelics like mescaline, psilocybin, DMT, and LSD have shaped our understanding of altered states of consciousness. While psychedelics have been used in rituals, spiritual practices, and artistic expressions across cultures, their classification is not always straightforward. Classic psychedelics activate the 5-HT2A receptor, but some argue that defining psychedelics solely based on pharmacological action overlooks their complex and experiential nature. The personal and cultural factors influencing psychedelic experiences present challenges in establishing a precise definition. Further research is needed to explore the effects and classifications of these remarkable substances.

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The Expansive Realm of Psychedelics: Navigating Definitions and Classifications

Psychedelics are a class of consciousness-altering drugs that produce pronounced changes in perception, cognition, emotion, and sense of self. Throughout history, different cultures and civilizations have incorporated psychedelics into their rituals, spiritual practices, healing ceremonies, and artistic expressions.

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Classic psychedelics, which have greatly influenced culture and science, encompass four primary substances. These include mescaline, found naturally in visionary cacti species such as peyote (Lophophora williamsii); psilocybin, the active component of magic mushrooms; N, N-Dimethyltryptamine (DMT), the psychedelic element of the plant-based Amazonian beverage called ayahuasca; and the quintessential psychedelic, lysergic acid diethylamide (LSD).

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These substances have played a pivotal role in shaping our understanding of altered states of consciousness and have contributed to the exploration of human perception and the mind.

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While certain substances are commonly referred to as classic psychedelics, it is worth noting that the classification of psychedelics is not always clear-cut. Some compounds that may not fit the traditional definition of psychedelics still produce similar effects and are considered psychedelic by some individuals and researchers.

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Categories of Classic Psychedelics: Tryptamines, Lysergamides, and Phenethylamines

Classic psychedelics can be divided into three broad categories based on their molecular structure: tryptamines, lysergamides, and phenethylamines. 

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Tryptamines

Tryptamines, derived from the amino acid tryptophan, encompass a diverse group of psychedelic compounds. The conversion of tryptophan to tryptamine occurs through a simple chemical transformation involving a single step.

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While tryptamine itself does not possess psychoactive properties, it serves as the foundational structure for a wide range of natural and synthetic psychedelics. Notable examples include DMT and psilocin (derived from psilocybin).

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While not classified as a classic psychedelic, another noteworthy tryptamine is 5-MeO-DMT, a potent and intense psychedelic. It can be found in various plant species as well as the venom of the Colorado River toad, Bufo alvarius.

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In addition to naturally occurring tryptamines, synthetic derivatives within this class have been developed, with psychedelic chemist Alexander "Sasha" Shulgin pioneering their creation. Examples of such synthetic tryptamines include N, N-diisopropyltryptamine (DiPT) and 5-methoxy-N, N-diisopropyltryptamine (5-MeO-DiPT). 

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Lysergamides 

Lysergamides represent a distinct class of molecules that share a common foundation with tryptamine but possess a more intricate molecular structure. Among the lysergamides, the simplest psychoactive compound is lysergic acid amide (LSA), which occurs naturally in the seeds of various morning glory plants and Hawaiian Baby Woodrose.

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Another significant lysergamide is ergotamine, an alkaloid derived from the fungus Claviceps purpurea. It serves as a natural precursor to the iconic lysergic acid diethylamide (LSD), which was first synthesized by Albert Hofmann in 1938 and has since gained widespread recognition as one of the most renowned psychedelics in history.

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Phenethylamines

Phenethylamines comprise the third class of classic psychedelic molecules, characterized by a molecular structure built around a phenethylamine backbone. Among these compounds, mescaline stands as the quintessential representative of phenethylamines.

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The straightforward molecular composition of mescaline offers ample room for chemical alterations—an opportunity that was embraced by Sasha Shulgin. Shulgin, a renowned psychedelic chemist, pioneered the creation and personal experimentation of over 150 entirely novel phenethylamines. Notably, his work gave rise to 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as “ecstasy” and “molly.”

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The Activation of 5-HT2A Receptors: Key to Classic Psychedelic Effects

All classic psychedelics, despite belonging to distinct chemical classes, induce their psychedelic effects by activating 5-HT2A serotonin receptors. However, each psychedelic binds and activates the 5-HT2A receptor in its unique way, resulting in a distinct profile of subjective effects for each substance.

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It's important to consider that the dosage consumed, as well as the individual's mindset, intention, and expectations (set) along with the physical and social environment (setting), can also influence the subjective effects of psychedelic drugs.

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Understanding the molecular and pharmacological differences between these two classes of psychedelics can provide valuable insights for those interested in exploring their effects and potential benefits.

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The Origin of the Term “Psychedelic”

The origin of the term “psychedelic” can be traced back to a fascinating correspondence in 1956 between Aldous Huxley, the renowned English writer and philosopher, and Dr. Humphry Osmond, an English psychiatrist and researcher. It was through Osmond that Huxley first encountered the psychedelic substance mescaline.

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In a letter to Osmond, Huxley proposed a term called “phanerothyme,” derived from the Greek words “phanein” meaning “to reveal” and "thymos" meaning “soul.” To emphasize its potential, Huxley even included a catchy rhyme: “To make this mundane world sublime, Take half a gram of phanerothyme.”

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However, Osmond felt that "phanerothyme" wasn't quite the right fit and offered an alternative suggestion: "psychedelic." This term derived from the Greek words “psyche” meaning “mind” or “soul,” and “delos” meaning "to manifest." Osmond responded with his own memorable rhyme: “To fathom Hell or soar angelic, Just take a pinch of psychedelic.”

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The term “psychedelic” gained favor and was officially introduced by Osmond during a meeting of the New York Academy of Sciences in 1957, solidifying its place in the lexicon of mind-altering substances.

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Beyond the Classic Psychedelics: The Ambiguity of Definition

The definition of psychedelics can be somewhat ambiguous, as there are substances that elicit similar effects to traditional psychedelics despite not doing so by binding to the 5-HT2A receptor. These substances are still thought of as psychedelics by some due to their ability to induce psychedelic-like experiences.

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Among these compounds are “entactogens” like MDMA and 2C-B, which promote feelings of empathy and foster prosocial behavior. There are also dissociative anesthetics such as ketamine, PCP, DXM, and nitrous oxide, which produce altered states of consciousness and a sense of detachment from the environment.

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Additionally, Salvinorin-A, a compound found in the leaves of Salvia divinorum, and ibogaine, a complex alkaloid derived from the root bark of the African shrub Tabernanthe iboga, are also widely recognized as psychedelics.

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While these substances differ in their mode of action, they share the ability to induce profound psychological effects, leading many to consider them within the realm of psychedelics.

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Definitional Challenges and Perspectives

In an attempt to establish clear boundaries for what qualifies as a psychedelic, a recent paper titled “Proposed Consensus Statement on Defining Psychedelic Drugs,” suggests that only drugs interacting with the 5-HT2A receptor should be classified as psychedelics. This definition encompasses the well-known classic psychedelics, as well as MDMA and ketamine, which also exhibit some affinity for the 5-HT2A receptor.

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While defining a drug class based solely on its brain effects may facilitate research categorization, some commentators and psychedelic researchers argue that the term “psychedelic” is too intricate to be captured by simple definitions. The mechanistic definition proposed by the authors may overlook the complex and experiential nature inherent in psychedelics.

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For instance, this proposed definition may not fully encompass substances that many consider psychedelic in their effects, such as salvinorin A, a substance that produced psychedelic effects by activating the kappa opioid receptor. In a thought-provoking article for Psychedelic Press, writer Robert Dickens reminds us that Dr. Osmond never intended the psychedelic class of compounds to be defined solely based on pharmacological action. Instead, he emphasized that the term should describe the unique quality of psychedelic experiences.

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The nature of a psychedelic experience is highly personal, influenced by cultural factors, and heavily reliant on contextual circumstances. The nuanced complexity associated with the term “psychedelic” presents challenges in its precise definition.

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Some argue that the term “psychedelic” encompasses the multifaceted and diverse range of experiences associated with certain substances, even those that are not 5-HT2A agonists. According to Dickens, while pharmacological action may indicate psychedelic effects, a true understanding of these effects might only be attained through direct, personal experience.

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Exploring the Definition of Psychedelics: A Complex and Evolving Debate

In conclusion, the definition of psychedelics remains a subject of ongoing debate. While some scientists propose a mechanistic definition based on the interaction with the 5-HT2A receptor, others argue that the term “psychedelic” encompasses a broader range of experiential and cultural factors.

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The complex and personal nature of psychedelic experiences makes it challenging to establish a universally accepted definition solely based on pharmacological action. Further research and exploration are needed to gain a deeper understanding of these substances and their effects.