Psychedelic Therapy Research Analysis

Q: What is the history of psychedelic research?

The origins of psychedelic research date back to 1913, when mescaline, a psychedelic compound derived from the peyote cactus, was found to induce a psychological state that researchers equated to psychosis. Over the next few decades, research focused on the psychological effects of mescaline, hoping it might bring a greater understanding of the biological basis of mental illness.[17] In 1943, Swiss chemist Albert Hofmann discovered the psychedelic effects of LSD (a drug he had previously synthesized from ergot fungus) through accidental exposure, thus leading to his infamous hallucinogenic bicycle ride home.[2] By 1947, the first human trial of LSD as a psychiatric therapy was published, and the drug began to be distributed by a pharmaceutical company and marketed as a psychiatric medication.[4] During the next two decades, a substantial amount of research was done on psychedelics (most of which does not meet today’s quality standards), the results of which showed promise for a variety of mental health conditions, most notably anxiety, depression, and alcohol use disorder.[2] However, while psychedelic research was booming, recreational use of psychedelics was also taking off and was generally associated with the anti-Vietnam-War counterculture in the United States. In response, in 1970 the United States government reclassified psychedelics as Schedule 1 controlled substances, making them strictly prohibited and effectively ending psychedelic research, a move that was mirrored internationally by the United Nations in 1971.[2] Psychedelic research was dormant for the next 25 years, but since the early 1990’s it has slowly been making its way back onto the scene.[4]

Q: What are some limitations of current psychedelic therapy research?

One of the major limitations of psychedelic therapy research is the lack of adequate blinding in randomized controlled trials. While many psychedelic therapy trials are placebo-controlled, the active medication (the psychedelic) produces such noticeable and distinct effects that both the participants and the researchers can reliably guess whether a placebo or psychedelic has been administered. This essentially unblinds the study and introduces bias, such as the placebo or expectancy effects, whereby simply believing you received an active medication and expecting a certain outcome influences the observed effects. This could increase the magnitude of the reported effects of the intervention.[3][5] It’s also important to note that most psychedelic therapy research has been done in populations that are primarily white; there is an overall lack of diversity in terms of ethnicity, culture, and socioeconomic status, which may limit the generalizability of the current research.[3]

Katie Jantz

Psychedelic Therapy

•Last Updated: September 20, 2023

Psychedelic therapy provides psychedelic drugs (e.g., psilocybin, ayahuasca, LSD) in a controlled setting where professional psychotherapy is used to both prepare for and integrate the psychedelic experience. Psychedelic therapy shows promise for the treatment of mental health conditions including depression, anxiety, and substance use disorders.

Dosage

Examine Database

Research feed

Psychedelic Therapy is most often used for

Katie Jantz, RPh, MSc

Nick Milazzo, MSc, MPH

Last Updated:September 20, 2023

Dosage Information
Examine Database
Research feed
Frequently asked questions
Update History
References

What is psychedelic therapy?

Psychedelic therapy is the use of psychedelic medications along with psychological support to improve quality of life and functioning. The word “psychedelic” is derived from the Greek words psychē (the mind/soul) and dēlos (to reveal), and psychedelics have a long history of traditional use for their “mind-revealing” effects.^[4] Psychedelic therapy uses “classic psychedelics” like psilocybin (most commonly found in certain species of mushroom), lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) (found in ayahuasca), with most current research using psilocybin.^[5] Psychedelic therapy research is rapidly expanding, but it is still considered to be in the early stages and public access to psychedelic therapy is limited. Additionally, psychedelics are still illegal in many regions of the world.

Psychedelic therapy generally consists of three phases: preparation, the psychedelic session, and integration. During the preparation phase, the person receiving treatment works with a health practitioner and/or mental health professional to learn about the psychedelic medication, discuss expectations, and set intentions for the experience. During the psychedelic session, the medication is administered in a safe and comfortable environment where the person can be monitored and supported if needed. Afterward, the integration phase provides an opportunity to debrief, reflect on, and integrate the experience. Therapy sessions using various models of support are often provided during the preparatory and integration phases, and in some studies, the psychedelic session is repeated after several weeks.^[3]^[6]

What is the history of psychedelic research?

What are psychedelic therapy’s main benefits?

Psychedelic therapy seems to be a promising tool for the management of mental health conditions including depression,^[3]^[1]^[7]^[2] anxiety,^[7]^[2] and substance use disorders^[8]^[9]^[10] (primarily alcohol and tobacco use disorders). Currently, the strongest evidence exists for depression and anxiety, including difficult-to-treat conditions like treatment-resistant depression (when two different antidepressants have failed to work) and depression/anxiety related to major illnesses (e.g., terminal cancer).^[3] Even in people with no apparent mental or physical diseases, psychedelic therapy has demonstrated long-term (>1 year) improvements in well-being.^[11]^[12] The vast majority of research has been done using psilocybin, although ayahuasca and LSD have also been studied with seemingly comparable efficacy.^[2]

A major benefit of psychedelic therapy is the minimal dosing required to achieve a therapeutic effect. Unlike antidepressants, which need to be dosed daily and can take upwards of 4 weeks to begin to work, a single psychedelic session has been found to improve depression and anxiety symptoms rapidly (in some studies within 1 day), with effects potentially lasting 6 months or longer.^[13] While positive effects have been consistently shown after a single session, there is some evidence to suggest that two psychedelic sessions produces better results.^[2]

In what other contexts are psychedelics used, and how are these contexts different from psychedelic therapy?

What are some limitations of current psychedelic therapy research?

What are psychedelic therapy’s main drawbacks?

Current research suggests that, with proper screening protocols (e.g., the exclusion of people with a personal or family history of psychosis), psychedelic therapy is quite safe. Although side effects can occur during the psychedelic session, they are generally short-term and resolve soon after the medication’s effects have worn off; these include anxiety, nausea, vomiting (particularly in the case of ayahuasca), headache, and mild increases in blood pressure and heart rate.^[3]^[5]

Psychedelics produce profound short-term psychological effects when consumed in full doses, including changes in thinking, perception, sense of self, and emotions (positive and negative) that may lead to mystical/spiritual experiences and an increased sense of social connectedness. While these “side effects” might be uncomfortable for some people, they are suggested to be an important component of the therapeutic effect of psychedelic therapy.^[5]

A rare possible side effect that has been identified in case reports is hallucinogen persisting perception disorder (HPPD), which is when perceptual disturbances experienced while under the influence of psychoactive drugs (e.g., classic psychedelics, cannabis, MDMA) re-emerge after the drug's effects have worn off. This might include visual “flashbacks” or other disturbances like visual snow (grainy, pixelated vision) or floaters. HPPD has not been reported in any psychedelic therapy studies and the true risk is not clear.^[14]^[11]

How does psychedelic therapy work?

The mechanisms underpinning psychedelic therapy’s effects are being actively researched, but they likely involve a combination of psychological and biological changes. Psychologically, psychedelic therapy seems to increase insight, enhance emotional processing, and promote psychological flexibility (the ability to adapt our thoughts, emotions, and behaviors when faced with challenging or new situations).^[3] This could create an opportunity to shift negative core beliefs and maladaptive thought patterns.^[5] Interestingly, having a spiritual or mystical experience during the psychedelic session has repeatedly been found to predict a sustained psychological benefit.^[5]^[11] This can be assessed by researchers using a questionnaire and generally involves positive feelings of oneness/interconnectedness with the world and an intuitive understanding of some aspect of life.^[11]

At a biological level, psychedelic therapy may induce structural and functional changes in the brain. Classic psychedelics primarily activate serotonin 2A (5-HT2A) receptors in the brain, which produces an altered state of consciousness and also seems to activate neurobiological pathways that lead to changes in neuroplasticity—the ability of the brain to change in both structure and function. Preclinical trials in mice have found that a single dose of psychedelics increases the expression of genes and proteins related to plasticity, including brain-derived neurotrophic factor (BDNF); induces cellular changes (the density/number of neurons and dendrites); and increases learning behaviors. Only a few studies have been performed in humans and the results are less clear, but preliminary neuroimaging studies report shifts in functional connectivity that are sustained after the drug has worn off.^[15]^[16] For a deeper dive into these mechanisms, check out our study summary.

What are other names for Psychedelic Therapy?

Note that Psychedelic Therapy is also known as:

Psychedelic-Assisted Therapy
Psychedelic-Assisted Psychotherapy

Dosage information

There is a high level of variability between studies when it comes to the type and frequency of therapy sessions provided; the psychedelic medication type, dosage, and frequency; and the environment provided for the psychedelic sessions. Currently, the optimal psychedelic therapy protocol is not clear.

Most research has used psilocybin in dosages ranging from 20–45 mg per dose, either taken only once or taken twice with a separation of at least seven days between doses. Preliminary research suggests that protocols using higher doses (≥30 mg)^[1] and two psychedelic sessions^[2] may have better effects, although further research is needed to validate these findings. LSD is most commonly given as an oral dose of 200 μg, and ayahuasca dosing, while not well-defined, is generally based on weight and DMT content.^[3]