This review (2021) summarizes the study characteristics of all ongoing registered clinical trials investigating psychedelic drugs for psychiatric disorders and identifies that their majority focuses on investigating MDMA and psilocybin for treating depression or PTSD, while only 30% of their results are published.
Abstract
“Introduction: Psychedelics are a hallucinogenic class of psychoactive drugs with the primary effect of activating non-ordinary states of consciousness. Due to the positive preliminary findings of these drugs in the treatment of psychiatric disorders, the number of registered clinical studies has risen significantly.
Methods: In this paper, clinical studies registered on clinicaltrials.gov that evaluate the treatment of any psychiatric disorder with psychedelics (excluding ketamine) are summarized and analyzed. 70 registered studies were identified from a clinicaltrials.gov search on December 3, 2020.
Results: The majority of studies aim to investigate methylenedioxymethamphetamine (MDMA) (45.7%) and psilocybin (41.4%). Studies evaluating ayahuasca, lysergic acid diethylamide (LSD), ibogaine hydrochloride, salvia divinorum, 5-MeO-DMT and DMT fumarate were less common at 1.4%, 4.2%, 2.8%, 1.4%, 1.4% and 1.4% of total registered studies, respectively. Most of the studies on MDMA, psilocybin, ayahuasca and salvia divinorum investigated their therapeutic effect on post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). LSD was investigated for MDD, anxiety, and severe somatic disorders and ibogaine hydrochloride was investigated for substance and alcohol use disorders. 5-MeO-DMT and DMT fumarate were both investigated for MDD. Only 21/70 registered studies had published results with the majority not yet completed.
Discussion: In view of the large number of ongoing studies investigating psychedelics, it is imperative that these studies are considered by researchers and stakeholders in deciding the most relevant research priorities for future proposed studies.”
Authors: Ashley N. Siegel, Shakila Meshkat, Katie Benitah, Orly Lipsitz, Hartej Gill, Leanna M. W Lui, Kayla M. Teopiz, Roger S. McIntyre & Joshua D. Rosenblat
Notes
We are currently in the ‘third wave’ of psychedelics research. The first wave being the traditional use and/or the research that was done before the second half of the 20th century. The second wave was the research in the 1960s and ’70s. The current, third, wave is the research (and investments) that have started around the turn of the century.
This review article takes a bird-eye view of the current state of research and identifies which clinical trials are ongoing. The study looked at different psychedelics but has chosen to exclude ketamine from the results. Studies were included that were recruiting, active, or already completed. Most studies looked at treatment (of mental health disorders), whilst a smaller percentage conducted basic science.
What the review found
- Most studies are being done with MDMA and psilocybin (together 87%)
- Most studies are investigating psychedelics or psychedelic-assisted therapy for depression (MDD) and PTSD
- Of the 70 studies identified, only 21 had published their results as of March 2021
As expected, most trials were being done last year, and we can expect even more this year. As can be seen on this tracker, the amount of studies that is registered has been increased even further with 36 studies already registered (excluding ketamine studies).
The authors of the study recommend that future trials put more effort into discovering which protocols work best. This is both with regards to dosing and to the forms of therapy used. This way we can put more effort into finding what will be the most cost-effective or efficient way of providing psychedelic-assisted therapy for a whole range of mental health disorders.
Summary
Psychedelics are hallucinogenic drugs that activate non-ordinary states of consciousness. Many studies have been conducted to evaluate the therapeutic effect of psychedelics on psychiatric disorders, including post-traumatic stress disorder, major depressive disorder, anxiety, and severe somatic disorders.
- Introduction
Psychedelics are a broad category of drugs that affect the brain and behavior via serotonin receptor mechanisms. They can produce a wide range of experiential states, including feelings of boundlessness, unity and bliss, and anxiety-inducing experiences such as loss of ego-control and panic.
In the 1950’s, researchers explored the therapeutic effect of LSD for conditions such as anxiety, depression and addiction. In 1966, LSD was deemed a schedule one drug.
Between the 1980s and 1990s, psilocybin and MDMA were investigated for psychiatric disorders such as anxiety and schizophrenia. Within the past two decades, there has been a substantial increase in research regarding the therapeutic effects of psychedelic substances.
Multiple studies have found that MDMA-assisted psychotherapy successfully reduced symptoms in patients with treatment-resistant PTSD, and that psilocybin-assisted therapy successfully reduced depression and anxiety symptoms and increased abstinence rates in addiction.
Psychedelics have promising therapeutic effects and a safety profile, and there are numerous ongoing studies investigating psychedelics for psychiatric disorders. The results of the current analysis are intended to provide investigators and other stakeholders with a comprehensive summary of psychedelic-related research questions likely to be answered in the near future.
2.1. Search strategy
A search of the National Institute of Health clinicaltrails.gov database was performed on December 3, 2020 and March 13, 2021 for clinical studies that investigated psychedelic drugs as treatment for psychiatric illness.
2.2. Study selection and eligibility criteria
A study selection schema was used to include all completed, active and upcoming clinical studies involving psychedelic drugs and psychiatric disorders.
2.3. Data extraction and analysis
Data were collected for each clinical study and analyzed using a descriptive statistical method. The study was similar to a study by Peyrovian et al. (2020), which investigated registered clinical trials of ketamine for psychiatric disorders.
The inclusion criteria were met by 70 registered clinical studies. 21 studies have published findings, and an additional four studies were either terminated, suspended or withdrawn.
3.1. Characteristics of all studies
At the time of data extraction, 32 studies used MDMA, 29 studies used psilocybin, one study used Ayahuasca, three studies used LSD, two studies used ibogaine hydrochloride, one study used salvia divinorum, one study used 5-MeO-DMT and one study used DMT fumarate. Clinical studies focused on a range of psychiatric disorders, including alcohol use disorder, anorexia nervosa, anxiety disorders, autism spectrum disorder, drug addiction, MDD, mood disorders, obsessive compulsive disorder, PTSD, severe somatic diseases, substance related disorders and treatment resistant depression.
3.2. Characteristics of MDMA studies
Of the 32 studies on MDMA, 23 are completed, two are active but not recruiting, four are recruiting, two are not yet recruiting and one status was not available. The majority of studies investigated MDMA and PTSD, 9.4% focused on substance related disorders, 3.1% on alcohol use disorder, 6.3% on anxiety disorders and 3.1% on autism spectrum disorder.
3.3. Characteristics of psilocybin studies
The majority of the studies investigated treatment using psilocybin, and the most common dosage was 25 mg and 0.1 – 0.3 mg/kg. Seven studies used microdoses, and six studies used doses of 0.1 – 0.3 mg/kg and one using 1 mg.
3.4. Characteristics of ayahuasca studies
One registered study investigated Ayahuasca for the treatment of MDD. It included 35 participants and took place in South America.
3.5. Characteristics of ibogaine hydrochloride studies
Two studies investigating ibogaine hydrochloride for treatment are currently registered, one recruiting participants with alcohol use disorder and the other recruiting participants with drug addiction. Both studies are randomized, but only one is placebo-controlled.
3.7. Characteristics of LSD studies
Three phase 3 studies are registered, one of which is completed and two are in the recruiting phase.
- Discussion
In this systematic review we investigated ongoing studies of psychedelics registered on clinicaltrials.gov. The majority of studies were in Phase 2, and the majority were randomized with parallel assignment and quadruple masking.
MDMA is a common psychedelic and may be used to treat PTSD. Its psychopharmacological characteristics make it potentially well suited as an adjunct to trauma-focused psychotherapy.
Psilocybin was the second most used psychedelic drug in registered studies, and most of the focus was on MDD. Two studies investigated the effects of ibogaine hydrochloride on drug addiction and alcohol use disorder, and one study investigated the efficacy of ayahuasca on depression.
The current study included clinical studies registered on clinicaltrials.gov, but some were missing information. Therefore, more details regarding the adjunct psychotherapy being used would be favourable.
Upon examining the current registered studies, gaps in the current research emerged. Future research should address the most effective type of psychotherapy intervention and the most effective range of doses for each drug.