By Sami Ramsammy and Matthew X. Lowe
The Multiple Identities of Psychedelics
Classic psychedelics, often referred to as hallucinogens, consist of a group of substances such as lysergic acid diethylamide (LSD) and psilocybin. Prior to the synthesis of LSD by Swiss chemist Albert Hofmann in 19381, natural psychedelics such as psilocybin were used in indigenous medicinal practices for several thousand years2. Following the synthesis of LSD, psychedelics were used heavily as a tool for neuroscience research, fundamentally altering the course of our understanding of modern psychology and psychiatry. LSD became commonly known by various names, including Acid, Dots, Mellow Yellow, and Windowpane3. Public usage of psilocybin mushrooms, also known as Magic mushrooms, Shrooms, and Mushrooms, also gained popularity during this time4, and decades after the synthesis of LSD, Dr. Hofmann and his team isolated psilocybin from the Psilocybin genus of naturally-found psilocybin mushrooms5.Mechanisms of Psychedelic Treatment
Understanding the mechanisms of classic psychedelics is an important step in considering their potential as a viable treatment option. Psychedelics alter consciousness by acting on serotonin receptors in the brain6. This is done by agonism, which is where a drug will bind to a receptor inside a cell or the surface and produce the same action as the substance that would normally bind to the receptor. Physiological effects are dose-dependent. For example, in recent research, participants given 25mg of synthetic psilocybin (high dose group) showed rapid and significant improvements in symptoms of depression, while participants given 10 mg (low dose group) did not7. As psilocybin is broken down within the body, via the liver mostly, it will convert to psilocin which contains psychoactive properties8. Shortly after indigestion, psilocin will cross the blood brain barrier where it influences the serotonergic system. Agonism then occurs, particularly when psilocin binds to 5-HT1A, 5-HT2B, and 5-HT2C (HT represents hydroxytryptamine, AKA- serotonin). These effects can last anywhere from four to seven hours, depending on several factors. A few of the elements that vary are the individual themselves (drug tolerance if exposed to it before) along with their body’s metabolism, the potency of the drug, or how much was consumed. Similarly, LSD is metabolized in the liver once digested orally. It is rapidly metabolized and transformed into inactive compounds9. It is thought that LSD binds to serotonin receptors 5-HT2A, 5-HT2C and 5-HT1A, but also acts as a partial agonist of dopamine receptor subtypes10. The overall mechanism in regard to LSD is not entirely understood yet, which is why continuing further research is relatively important. The effects of this drug can last from eight to twelve hours but is still dependent on the previously listed factors.An Early History of Psychedelics for the Treatment of Addiction
Anecdotal evidence for the potential of psychedelics in the treatment of addiction dates back nearly a century. 20 years after setting up the Ohio-based sobriety movement in 1935, Bill Wilson, the cofounder of Alcoholics Anonymous (AA) believed LSD could be used to cure alcoholics and credited the drug with helping his own recovery from often debilitating depression11. Wilson came to believe that LSD could help “cynical alcoholics” achieve a “spiritual awakening” and start on the path to recovery. Evidential research into the use of psychedelics for the treatment of addiction dates to the mid-20th century when researchers began exploring their potential therapeutic benefits. In the 1950s and 1960s, early studies suggested that psychedelics such as LSD and psilocybin could be useful in the treatment of alcoholism, opioid addiction, and other substance use disorders. One of the pioneers of this research was Dr. Humphry Osmond, a British psychiatrist who began using LSD in his practice in the 1950s12. Osmond was particularly interested in the potential of LSD to help alcoholics overcome their addiction, and he conducted a number of studies that showed promising results. In later studies including 536 participants from 1960’s-1970’s, researchers Pål-Ørjan Johansen and Teri Krebs found that a single dose of LSD was associated with a decrease in alcohol misuse13. Following reports from participants, researchers noted that psychedelics weren’t being used to numb the pain of the participants, but rather helped by allowing them the opportunity to identify the root causes of their addiction. For example, an interview conducted with one participant regarding the successful treatment of AUD revealed that the patient described his experience meditating to let go of his past and focus on the present experience.The Fall of Psychedelics Research
As the use of psychedelics became more widespread in the 1960s and the drugs themselves became associated with counterculture movements and social unrest, research into their therapeutic benefits became more controversial. Although accumulating research from studies on psychedelics found promising evidence in the treatment of several psychiatric conditions14, under President Nixon, research on classic psychedelics slowed in the late 1960s and was eventually halted with the Controlled Substances Act of 197115. At the time, this was partly due to the increased usage of hallucinogens by students and fears of the addictive properties of psychedelics16. However, research at the time did not support these claims, as psychedelic research was producing promising results using psychedelic drug therapy to treat alcohol dependence and nicotine dependence17.