A Comparative Literature Survey of Psilocybin and LSD-25 Metabolism, Ian Joyce, 2017

A Comparative Literature Survey of Psilocybin and LSD-25 Metabolism

Ian Joyce

Capstone Project CHM 400 H Cal Poly Pomona, Winter 2017 | 1 – &ç


Psilocybin and lysergic acid diethylamide (LSD-25) are two of the most popular and well known psychedelic drugs. Although both of the compounds are currently illegal in the United States, a renewed interest has begun in recent years to examine and analyze these drugs for therapeutic use. This review analyzes the current research pertaining to the metabolism, biochemical pathways, receptor activity, biological signaling, physiological effects and the behavioral effects associated with both of these compounds. For psychedelic compounds to be used in future therapeutic settings, it is important to understand how each compound affects the body and which psychedelic could provide more effective treatment for a particular ailment. Accordingly, this review addresses the chemical biology of psilocybin and LSD-25 and provides an initial comparative framework for assessing the effectiveness of each drug under certain circumstances.



Psychedelic and hallucinogenic drugs have an extensive history and have been used by humans for century in a variety of rituals and religious ceremonies. These substances exert powerful effects on an individual’s attitude, thoughts, cognition, and behaviour without leading to the addiction or the habit formation often caused by the use of other use of other legal and illicit drugs (see Figure 1.1–4).

The term “psychedelic” (i.e. mind-manifesting) is used to classify a group of substances that possess the ability to alter human perception and transcend established personnal and cultural conditionning Depending on the user’s state of mind and location, known as the set and setting, these  substances can evoke profound “mystical” of “religious-like” experiences.6,7 Although the terms are similar, it is important to note the distinction between a ‘psychedelic’ and ‘hallucinogen’. A hallucinogen is defined as “a substance that causes a person to see or sense things that are not real”.8 Psychedelics rarely cause hallucinations; instead, they cause the user to experience altered perceptions or illusory distortions based on real and existing stimuli.5,9

One of the most appealing aspects of psychedelic compounds is their ability to be applied therapeutically or in a medical setting. Psychedelic compounds tend to stimulate neural receptors in an abnormal fashion, which can result in novel synergistic or discordant effects.5,10 This altered neural state changes the flow of sensory information and cognition and allows the user to develop unique and novel perceptions toward pre-existing ideas or beliefs. 10,11 For these reasons, there has been a renewed effort in recent years to utilize these psychedelic compounds in tandem with psychotherapy to treat a myriad of mental ailments including depression, anxiety, post-traumatic stress disorder and others.10–12 Additionally, neurochemical studies on these compounds are likely to provide new insights into neural function and may contribute to the development new medicines and strategies for the treatment of psychiatric disorders.

Psychedelic compounds can occur naturally inboth plants and fungus, while others may be derived synthetically. One example is N,N-dimethyltryptamine (DMT), which is present in the hallucinogenic beverage Ayahuasca. This sacred tea is traditionally brewed using the bark of Banisteriopsis caapi along with various other plants and tends to produce an intense dream-like state in the user.13 The Peyote cactus is another example of a naturally occurring psychedelic compound. Native Americans have utilized the Peyote cactus, which contains the mind-altering compound known as mescaline, in religious rituals and ceremonies for thousands of years.9 Other popular psychedelics compounds and their forms of delivery are illustrated in Figure 2.

Although there are many psychedelic substances that produce profound altered states of consciousness, the primary focus of this study will be on two of the most common and well known psychedelic compounds : psilocybin and LSD-25, see Figure 3.

Psilocybin occurs naturally and is one the main psychedelic ingredients found in “magic” mushrooms.14 The first recorded use of these mushrooms dates back to about 3000 years ago to the northern region of Mexico.15

The compound was originally introduced to the scientific community in 1957 by Robert G. Wasson and then successfully isolated by Dr. Albert Hofmann in 1958.16 There are over 100 species of psychedelic mushrooms in the world with varying degrees of psilocybin content ranging from about 0.2%-1.0% by dry weight.17,18 Today, psilocybin mushrooms are used both recreationally and in a psychiatric setting for the treatment of various mental ailments and neurosis.11

The compound LSD-25 is a semi-synthetic variation of an ergot alkaloid produced by the fungus Claviceps purpurea, which naturally grows on rye wheat.16 Ergot alkaloids are generally utilized for the treatment of childbirth bleeding as well as migraines.19 Although these ergot alkaloids are used as medicines today, during the Middle Ages, this fungus is suspected to have been accidently baked into breads and caused it’s consumers to experience vivid and often hellish hallucinations, known at the time as “St Anthony’s fire”.19