Content uploaded by Nolan J Brown
Author content
All content in this area was uploaded by Nolan J Brown on Sep 14, 2022
Content may be subject to copyright.
Content uploaded by Nolan J Brown
Author content
All content in this area was uploaded by Nolan J Brown on May 17, 2022
Content may be subject to copyright.
Review began 08/12/2022
Review ended 09/13/2022
Published 09/14/2022
© Copyright 2022
Kurtz et al. This is an open access article
distributed under the terms of the Creative
Commons Attribution License CC-BY 4.0.,
which permits unrestricted use, distribution,
and reproduction in any medium, provided
the original author and source are credited.
The Use of Psychedelics in the Treatment of
Medical Conditions: An Analysis of Currently
Registered Psychedelics Studies in the American
Drug Trial Registry
Joshua S. Kurtz , Neal A. Patel , Julian L. Gendreau , Chenyi Yang , Nolan Brown , Nick Bui , Bryce
Picton , Mark Harris , Matthew Hatter , Ryan Beyer , Ronald Sahyouni , Luis Daniel Diaz-Aguilar ,
Joel Castellano , Nathaniel Schuster , Mickey E. Abraham
1. Neurological Surgery, University of California Irvine, Irvine, USA 2. Neurological Surgery, Mercer University School
of Medicine, Savannah, USA 3. Biomedical Engineering, Johns Hopkins University, Baltimore, USA 4. Neurological
Surgery, Loma Linda School of Medicine, Loma Linda, USA 5. Neurological Surgery, University of California Irvine (UCI)
School of Medicine, Irvine, USA 6. Neurological Surgery, UCI, School of Medicine,, Irvine, USA 7. Neurological Surgery,
University of California San Diego, San Diego, USA 8. Anesthesiology and Reanimation, University of California San
Diego, San Diego, USA 9. Center for Pain Medicine, University of California San Diego, San Diego, USA
Corresponding author: Julian L. Gendreau, jgendre1@jhu.edu
Abstract
Although early therapeutic research on psychedelics dates back to the 1940s, this field of investigation was
met with many cultural and legal challenges in the 1970s. Over the past two decades, clinical trials using
psychedelics have resumed. Therefore, the goal of this study was to (1) better characterize the recent
uptrend in psychedelics in clinical trials and (2) identify areas where potentially new clinical trials could be
initiated to help in the treatment of widely prevalent medical disorders. A systematic search was conducted
on the clinicaltrials.gov database for all registered clinical trials examining the use of psychedelic drugs and
was both qualitatively and quantitatively assessed. Analysis of recent studies registered in clinicaltrials.gov
was performed using Pearson’s correlation coefficient testing. Statistical analysis and visualization were
performed using R software. In totality, 105 clinical trials met this study’s inclusion criteria. The recent
uptrend in registered clinical trials studying psychedelics (p = 0.002) was similar to the uptrend in total
registered clinical trials in the registry (p < 0.001). All trials took place from 2007 to 2020, with 77.1% of
studies starting in 2017 or later. A majority of clinical trials were in phase 1 (53.3%) or phase 2 (25.7%).
Common disorders treated include substance addiction, post-traumatic stress disorder, and major
depressive disorder. Potential research gaps include studying psychedelics as a potential option for
symptomatic treatment during opioid tapering. There appears to be a recent uptrend in registered clinical
trials studying psychedelics, which is similar to the recent increase in overall trials registered. Potentially,
more studies could be performed to evaluate the potential of psychedelics for symptomatic treatment during
opioid tapering and depression refractory to selective serotonin reuptake inhibitors.
Categories: Psychiatry, Neurosurgery, Substance Use and Addiction
Keywords: psilocybin, post traumatic stress disorder, mdma, major depressive disorder, clinical trials
Introduction And Background
Although hallucinogens have been used as spiritual tools for millennia in non-Western cultures [1,2], they
were not introduced into the Western scientific community until 1896 when Arthur Heffter, a German
pharmacologist, isolated mescaline from peyote [3]. After this period in time, the study of psychedelics
became much more robust throughout the mid-1900s with the work of Albert Hofmann who studied the
psychoactive properties of LSD (lysergic acid diethylamide) and psilocybin [4,5]. Researchers began to study
the potential therapeutic uses of psychedelics for depression, alcoholism, and palliative care. LSD became a
model psychedelic for these therapeutic developments [6,7]. Ultimately, tens of thousands of patients were
treated in the 1950s and 1960s, predominantly in the psychotherapy setting [8,9]. Despite minimal adverse
events [10], most psychedelics were later criminalized and deemed schedule 1 drugs by the United Nations
Convention on Psychotropic Substances in 1971 due to their hypothesized close association with cultural
turmoil and anti-Vietnam war politics of this period. These stringent regulations stigmatized psychedelic
research, leaving investigators discouraged in the wake of these rapid changes [11]. Additionally, some
authors argue that the decline of research into psychedelics was more a result of the difficulty to establish
efficacy of the psychedelics given their mechanism of action and its clash with controlled trial
methodologies at the time [12].
In the last two decades, there has been a resurgence of psychedelics research that has broadly encompassed
the fields of neuroimaging [13-21], psychopharmacology [18,22-24], and psychology [25-31]. Focused mostly
on psilocybin and MDMA (methylenedioxymethamphetamine), researchers are now considering the
potential of these drugs being used to treat a variety of different psychiatric and neurological conditions
1 2 3 1 1 4
5 6 5 5 7 7
8 9 7
Open Access Review
Article DOI: 10.7759/cureus.29167
How to cite this article
Kurtz J S, Patel N A, Gendreau J L, et al. (September 14, 2022) The Use of Psychedelics in the Treatment of Medical Conditions: An Analysis of
Currently Registered Psychedelics Studies in the American Drug Trial Registry. C ureus 14(9): e29167. DOI 10.7759/cureus.29167
such as addiction, pain, depression, end-of-life anxiety, and post-traumatic stress disorder (PTSD). For
example, one study published in 2016 by Roland Griffiths and his team at Johns Hopkins was a randomized,
double-blind, crossover trial. This study gave cancer patients with poor prognoses and associated
anxiety/depression either a high dose of psilocybin or a low dose, functioning as a placebo [32]. Results
showed decreases in both clinician- and self-rated measures of depressed mood and anxiety among the
participants in the high-dose group, along with a general increase in quality of life.
Cannabis, and specifically tetrahydracannibidinol (THC), also plays a major role in this field of research. A
recent report published by the National Academies of Sciences, Engineering, and Medicine provided a
comprehensive review of over 20 years of cannabis research, considering more than 10,000 scientific
abstracts [33]. In this report, a committee discussed the health impacts of cannabis and cannabis-derived
products, ranging from therapeutic properties to increased risks for causing cancers, respiratory diseases,
and psychological disorders.
Despite the promising results that these investigations have yielded, there are still many barriers to
advancing psychedelics research. Stigma, legality, and cultural interest all influence the amount of research
that can be conducted in any field, but is especially prominent in the area of psychedelics. Ultimately, the
history of psychedelics all but requires promising results to be accepted with cautious optimism, leaving
researchers, clinicians, and the general public alike urging for a greater body of research into the therapy
and safety of these drugs. The purpose of this study is to review the current scope/character of current
psychedelic drug clinical trials, identify current cultural/legal challenges hindering progress in this field, and
discuss potential avenues for future investigation.
Review
Methods
This analysis of clinical trials studying psychedelic drugs was conducted using the ClinicalTrials.gov
database, a database that is supported by the National Library of Medicine through the National Institutes of
Health (Bethesda, Maryland, USA). This database contains more than 380,000 research studies conducted
throughout the United States and in 220 countries. This database can be accessed at
https://clinicaltrials.gov/. Information about trials is submitted by the sponsor or lead investigator for the
purposes of research integrity by establishing prespecified primary outcomes. In addition, this registration
of clinical trials also ensures publication of negative or null findings in addition to positive findings. This
database is continually updated as the study progresses while updating the number of participants and
preliminary results.
The authors queried the database using the input “psychedelic” in the “other terms” parameter. The search
was made on May 1, 2021. Of the studies identified, those that had been suspended, terminated, withdrawn,
or otherwise unknown statuses were excluded. For the studies that met the inclusion criteria, the following
data were extracted: identifier number, title, recruitment status, condition or disease, study type,
intervention, primary purpose, clinical phase, estimated number of participants, year of study initiation,
country of origin, and sponsoring institution. Studies including cannabidiol (CBD) and kratom were excluded
from the study.
Descriptive statistics were used for the initial summary of the retrieved data. Statistical analysis was
performed with R software (R Core Team, Vienna, Austria) using the Pearson’s correlation test to discover if
there were any uptrends in clinical trials with each successive year included in the study. This was
performed for both the total number of clinical trials established on the clinicaltrials.gov website and to the
clinical trials of psychedelics retrieved from the search. A p-value of 0.05 was used for establishing
statistical significance, in addition to 95% confidence intervals. When analyzing for increasing trends in
clinical trials, the year 2020 was omitted due to the reduced amount of medical research as a result of the
COVID-19 pandemic. Visualization was performed using R software.
Results
The search results included 105 studies that met this study’s inclusion criteria (Appendix A). A flowsheet of
the inclusion/exclusion criteria is depicted in Figure 1. In total, 103 studies (98.1%) were interventional and
two (1.9%) were observational, including one (1%) cross-sectional study and one (1%) prospective study. All
trials took place from 2007 to 2020, with 81 (77.1%) studies starting in 2017 or later. Sixty-one trials had an
enrollment between 0 and 50 participants (57%), 24 had a sample size between 51 and 100 participants
(22.4%), 19 had a sample size between 101 and 500 participants (17.8%), and one had a sample size of >501
participants (0.9%). The mean number of study participants was 117 in all trials. No trials were completed.
However, 19 (18.1%) were active, 63 (60%) were recruiting, one (1%) was enrolling through invitation, and
22 (21%) were not yet recruiting.
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 2 of 20
FIGURE 1: Results of the clinical trials search strategy. Flowchart
depicts the search and screening process used to identify relevant
clinical trials.
PTSD, post-traumatic stress disorder
Country of Origin and Sponsoring Institutions
The United States of America has the most clinical trials, 74 (70.5%), with the rest originating in Switzerland
(9.5%), Canada (4.8%), and several other countries (Table 1; Figure 2A). These studies were largely
sponsored by Yale University (21.9%, n = 23), followed by Johns Hopkins University (10.5%, n = 11) and the
Multidisciplinary Association for Psychedelic Studies (MAPS) (8.6%, n = 9).
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 3 of 20
Characteristic Number of trials Percentage of all trials
Primary purpose
Treatment 53 50.50%
Basic science 40 38.10%
Other 5 4.80%
Supportive care 3 2.90%
Health services research 2 1.90%
Diagnostic 1 1.00%
Phase
1 56 53.30%
2 27 25.70%
3 7 6.70%
4 5 4.80%
Other 10 9.50%
N/A 9 8.60%
1 and 2 1 1.00%
Country of origin
United States 74 70.50%
Switzerland 10 9.50%
Canada 5 4.80%
Germany 3 2.90%
United Kingdom 3 2.90%
Austria 2 1.90%
Israel 2 1.90%
Brazil 1 1.00%
Denmark 1 1.00%
Finland 1 1.00%
The Netherlands 1 1.00%
Spain 1 1.00%
West Indies 1 1.00%
TABLE 1: Characteristics of clinical trials included in this analysis
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 4 of 20
FIGURE 2: Characteristics of included clinical trials. (A) Clinical trials by
nationality. Other includes clinical trials in the countries of Brazil,
Denmark, Finland, Netherlands, Spain, and the West Indies. (B)
Psychedelic drugs under analysis in each clinical trial. (C) Type of
clinical trial. (D) Stage of currently reported clinical trials underway.
1 and 2 refer to trials including patients in both phase 1 and phase 2, respectively. N/A refers to trials with no listed
phase. Other refers to exploratory trials before phase 1.
Types of Psychedelics
The most commonly studies psychedelics were cannabinoids (47.62%, n = 50), and psilocybin (24.76%, n =
26). MDMA was also used (13.33%, n = 14). Other less common psychedelics were also studied including LSD,
ibogaine hydrochloride, and salvinorin A (Figure 2B).
Purpose of Included Clinical Trials
The primary purposes of these trials were based on the following: treatment (50.5%, n = 53), basic science
(38.1%, n = 40), other/unspecified (4.8%, n = 5), supportive care (2.9%, n = 3), health services research (1.9%,
n = 2), and diagnostic (1.0%, n = 1) (Figure 2C).
Phases of Included Clinical Trials
The majority of the clinical trials are in phase 1 (53.3%, n = 56) or phase 2 (25.7%, n = 27). In addition, three
studies are in phase 3 (2.9%) and five (4.8%) studies are in phase 4. An overview of study characteristics is
depicted in Figure 2D.
Statistical Analysis
Both the number of clinical trials specifically measuring psychedelics and the number of trials in the overall
registry were found to be increasing over time (Figures 3A, 3B). Pearson’s correlation testing revealed an
uptrend with an increasing number of psychedelic clinical trials occurring each year from 2007 to 2019 (r =
0.784 [95% CI: 0.411-0.932], p = 0.002). The resulting t-test statistic value was 4.192. In addition, there was
also an increase in the total number of registered clinical trials each year as an entirety (r = 0.98 [95% CI:
0.919-0.993], p < 0.01). The resulting t-test statistic value was 14.832 (Figure 3C).
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 5 of 20
FIGURE 3: Amount of both psychedelic clinical trials and total clinical
trials in the clinicaltrials.gov registry have increased over time. (A) Bar
plot depicting the number of newly registered psychedelic-specific
studies each year. (B) Bar plot depicting the number of newly registered
studies in the clinicaltrials.gov database overall each year. (C) Pearson
correlation analysis finding statistically significant association of
increasing psychedelic studies per year in addition to overall registered
trials in the clinicaltrials.gov registry.
Condition or Disease
Healthy participants made up the largest group, who were studied in 35 (33.3%) trials, with 30 of them being
phase 1 trials (Table 2). The most commonly studied disorders were substance use disorders, with 14 studies
(13.3%). More specifically, there were five alcohol, four marijuana/cannabis, three opioids, one cocaine, and
one nicotine clinical trial regarding substance use. PTSD and depression were the next most frequently
studied disorders, having nine (8.6%) and eight (7.6%) clinical trials, respectively. Eight clinical trials were
conducted regarding pain, with chronic pain as the most studied (2.9%, n = 3). Studies regarding
cancer/cancer-related symptoms accounted for five of the results. Degenerative disorders, consisting of
multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and mild cognitive impairment had a total of
four (3.7%) clinical trials. Headache disorders had a total of four (3.7%) clinical trials included as well. Three
(2.8%) studies were included about psychosis/schizophrenia. There were also four trials where multiple
conditions or diseases were studied, most commonly with depression and related disorders (Figures 4A, 4B).
Condition or disease Number of trials Percentage of all trials
Healthy 35 33.3%
Substance use disorder 14 13.3%
Alcohol 5 4.8%
Marijuana/cannabis 4 3.8%
Opioids 3 2.9%
Cocaine 1 1.0%
Nicotine 1 1.0%
PTSD 9 8.6%
Depression 8 7.6%
Pain 8 7.6%
Chronic pain 3 2.9%
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 6 of 20
Post-operative pain 1 1.0%
Post-traumatic pain 1 1.0%
Neuropathic low back pain 1 1.0%
Inflammatory bowel disease 1 1.0%
Sickle cell disease 1 1.0%
Cancer 5 4.8%
Degenerative diseases 4 3.8%
Multiple sclerosis 2 1.9%
Alzheimer's disease 1 1.0%
Parkinson's disease 1 1.0%
Headache disorders 4 3.8%
Cluster headache 2 1.9%
Migraine 1 1.0%
Post-traumatic headache 1 1.0%
Multiple conditions or diseases 4 3.8%
Depression, Anxiety, PTSD 1 1.0%
Depression, depressive symptoms, Alzheimer's disease, mild cognitive impairment 1 1.0%
Distress/grief, depression 1 1.0%
Tourette syndrome, tic disorder 1 1.0%
Psychosis/schizophrenia 3 2.9%
OCD 2 1.9%
Anorexia nervosa 1 1.0%
Anxiety disorders 1 1.0%
Autism spectrum disorder 1 1.0%
Bipolar disorder 1 1.0%
Hepatic impairment 1 1.0%
HIV 1 1.0%
Obstructive sleep apnea 1 1.0%
Tourette syndrome 1 1.0%
Trichotillomania 1 1.0%
TABLE 2: Number of clinical trials by condition or disease.
PTSD, post-traumatic stress disorder; OC D, obsessive-compulsive disorder; HIV, human immunodeficiency virus
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 7 of 20
FIGURE 4: Number of psychedelic clinical trials per treating condition.
(A) Line plot depicting cumulative number of clinical trials over time
stratified by medical disorders. (B) Pie charts depicting percentage of
psychedelic studies in the treatment of substance abuse disorder,
headaches, pain, and neurodegenerative disorders.
Study Interventions
Nearly half of all clinical trials were conducted with cannabis/cannabinoids as the study intervention (47.6%,
n = 50) (Table 3). Dronabinol, a synthetic substance containing compounds from the cannabis plant, was
used in 23 of those studies. The interventions consisted of psilocybin, MDMA, and LSD in 26 (24.8%), 14
(13.3%), and four (3.8%) studies, respectively. There were seven clinical trials that investigated all or a
combination of psychedelic substances, and in these psilocybin was most commonly administered alongside
other drugs (n = 3).
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 8 of 20
Study intervention Number of trials Percentage of trials
Cannabis/cannabinoids 50 47.6%
Dronabinol 23 21.9%
THC 12 11.4%
Dronabinol/CBD 3 2.9%
THC/CBD 3 2.9%
Nabilone 2 1.9%
Nabiximols 2 1.9%
THC/terpenes (alpha-pinene, limonene) 2 1.9%
THX-110 (dronabinol + PEA) 2 1.9%
Inje cocktail, THC cannabis extract, THC/CBD cannabis extract 1 1.0%
Psilocybin 26 24.8%
MDMA 14 13.3%
Multiple interventions 7 6.7%
All psychedelics 1 1.0%
MDMA, methamphetamine 1 1.0%
Psilocybin, ketamine 1 1.0%
Psilocybin, LSD 1 1.0%
Psilocybin, SSRI (escitalopram) 1 1.0%
THC, ketamine 1 1.0%
Dronabinol, ethanol 1 1.0%
LSD 4 3.8%
Ibogaine hydrochloride 2 1.9%
Salvinorin A 2 1.9%
TABLE 3: Number of clinical trials by intervention.
THC, tetrahydracannibidinol; CBD, cannabidiol; THC, tetrahydracannibidinol; PEA, palmitoylethanolamide; MDMA, methylenedioxymethamphetamine;
LSD, lysergic acid diethylamide; SSRI, selective serotonin reuptake inhibitors
Discussion
The sheer number of recently established current clinical trials reveals that research is increasing in this
area, especially since 2017 [34]. Statistical analysis of all trials registered into the database, however,
suggests an increasing amount of studies in all fields. Thus, the increasing trend in psychedelic intervention
studies could represent just improved registration of clinical trials overall by all medical researchers.
Furthermore, it is evident that many of these studies are still in their infancy. Many researchers are still
facing the challenge of first establishing the safety of hallucinogenic drugs. Thus, the fact that more than
50% of the current trials are phase 1 is not surprising. This is especially imperative as the schedule 1 status of
many psychedelic substances requires researchers to firmly establish the safety of the drugs on healthy
subjects before moving on to their potential therapeutic impacts.
Conditions or Diseases
With the exceptionally heavy burden of addiction and overdose rates in the United States [34], and in the
wake of the current opioid epidemic, it was fitting that substance use disorders overall were the most
commonly studied conditions in current psychedelic clinical trials. However, only three trials focused
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 9 of 20
specifically on opioid substance use disorder. Two of the studies are testing psychedelics as maintenance
therapy along with buprenorphine/naloxone, while one clinical trial is testing psychedelics as an adjunct
with methadone withdrawal. This is a large gap in this field of research as approximately 70,000 Americans
suffered from overdoses causing fatalities in 2018, and two-thirds of those were from opioids [35,36]. Thus,
successful treatments in this realm of psychedelic research could elicit a substantial impact on a psychiatric
disorder with rapidly increasing prevalence and rates of mortality. Ibogaine, a naturally occurring alkaloid
for which there are two clinical trials underway, has shown promise in reducing alcohol and opioid cravings
and withdrawals; however, its application is limited by its hallucinogenic and arrhythmogenic adverse
effects [37]. Cameron et al. recently formulated an analog, tabernanthalog (TBG), that addresses both issues,
which sets it apart as a candidate for substance use disorder clinical trials [3].
The next most studied disorders are PTSD and major depressive disorder, as both have nine and eight studies
currently underway, respectively. There is already early evidence that psychedelic treatment could be
successful in treating these disorders [36-39]. It is important to consider that the term “post-traumatic stress
disorder (PTSD)” was also not a term before its first appearance in 1980, when it was initially described in
the third edition of the Diagnostic and Statistical Manual of Mental Disorders. Therefore, this could
potentially have affected our search, thus not identifying a significant number of trials before the term
became incorporated into mainstream use and study. However, trauma-based research could potentially
have still been studied and registered using different terminologies and descriptions. The present study's
results on MDD trial prevalence align with Carhart-Harris and Goodwin, who, in a review outlining the
therapeutic potential of psychedelics, accept that treatment-resistant depression is the most logical place to
focus inquiry given the uncertainty in the treatment plan after SSRI failure [6]. The future should ideally
focus on creating innovative therapies for patients with SSRI refractory disease. There are also non-
psychiatric disorders that are currently being studied. Four studies used psychedelics to treat
neurodegenerative disorders and eight studies evaluated treatment options for different forms of pain
(chronic, post-operative, post-traumatic). Twelve studies were also found measuring psychedelic use for
treating pain and headache disorders, while eight studies specifically evaluated psychedelic use for pain
(chronic, postoperative, post-traumatic) and four studies evaluated treatment of headache disorders.
Interventions
The most common substances used in interventional studies were cannabis/cannabinoids. A large number of
drugs (dronabinol, nabilone, nabiximols, THX-110) fell under this category as there are multiple synthetic
cannabinoids currently under development or already brought to market. The fact that most studies use
dronabinol is understandable seeing as it is already FDA-approved for appetite stimulation and as an
antiemetic to combat chemo-induced nausea and vomiting, while nabilone is FDA-approved for nausea and
vomiting refractory to conventional medical management [40-41]. With that in mind, current trials are
studying broader uses of these drugs as treatments for chronic pain, Alzheimer’s, sleep apnea, and PTSD.
The next most researched drug is psilocybin, with 26 studies underway. This is the most popular drug of the
“classical psychedelics” in clinical trials. This is due to the promising research that has already been
performed with psilocybin and, historically, with a drug that has similar subjective effects, LSD (which is
itself currently being researched in four different studies). Furthermore, there is an expert consensus that
these two drugs cause less harm to society and individuals alike as compared to alcohol, tobacco, and other
recreational drugs [42-45]. The success of previous studies is clear from the exciting FDA breakthrough
therapy designation that it received in both 2018 and 2019, a promising pattern in the context of being a
schedule I drug with "no currently accepted medical use" [46]. Current studies are focused on psychiatric
issues such as depression, OCD, and alcohol-use disorder, but they are also studying potential uses in
treating headaches and anorexia. The sheer number of studies is a promising sign that the preliminary
success of prior studies is being taken seriously and being further advanced.
MDMA is the next most studied substance, with 14 studies ongoing. This reflects previous success in studies
researching MDMA-assisted psychotherapy as a treatment for PTSD. The first controlled clinical trial of
MDMA-assisted psychotherapy was published in 2011 [47] and produced promising results as 83% of the
experimental group no longer met criteria for PTSD at 2- and 12-month follow-ups. There have subsequently
been further promising studies in this area of research, and MDMA-assisted psychotherapy was even granted
a breakthrough therapy designation from the FDA in 2017. It is important to continue to push for more
robust clinical trials with high-quality randomized design and appropriate blinding. Additionally,
researchers should aim for large enough sample sizes to ensure adequate power of detecting treatment
effects that are not due to chance alone.
Primary Purpose and Phases
Although there has been a renewed and inspired interest in psychedelic therapies, the use of psychedelics
overall is ultimately still in a nascent stage. This is reflected in the fact that only 53 out of 105 studies are
studying the substances as treatments (rather than, for example, basic science research) and that 84/92
studies that are subject to classical study phases are in either phase 1 or phase 2 trials with only three trials
in phase 3 and five in phase 4. Of the classical psychedelics (MDMA, LSD, psilocybin, ibogaine) there are
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 10 of 20
only two current trials in phase 3 and they are both studying MDMA treatments for PTSD. This is also limited
by financial constraints as both phase 3 and phase 4 clinical trials require more financial backing and are
generally funded by industry. Potentially, when more studies progress, there will be an exponential increase
in both the volume and speed of the research.
Geography
The United States of America has the most clinical trials out of any country, with 74 studies currently
underway. This is despite strict government regulations regarding schedule 1 drugs and is a promising sign
that regulations may loosen in the coming years.
The country with the most studies on a per-capital basis, however, is Switzerland, with 10. This may be
reflective of the power of stigma and culture in facilitating research. Switzerland has a long history of being
more accepting of psychedelic use, even legalizing LSD and MDMA therapies from 1988 to 1993 [48] and
granting individual allowances for the therapeutic use of LSD and MDMA since 2014 [49]. It is no surprise
that the country that celebrates “bicycle day” is also the country with the highest rate of research on the
topic [50]. This holiday became commemorated after Albert Hofmann first synthesized and intentionally
self-ingested LSD. Thus, he experienced the effects of the substance while also riding on a bicycle. This was
one of the first well-known events where the hallucinogenic properties of LSD were identified, and thus
Switzerland is now regarded largely as the birthplace of LSD.
It is also important to consider that several other clinical trial databases exist such as the European clinical
trials registry at https://www.clinical trialsregister.eu. In addition, an Australian registry can be found at
https://www.australianclinicaltrials.gov.au. This study only analyzed registered characteristics of each trial
found on the clinicaltrials.gov website, which most likely created a bias toward being predominantly U.S.
clinical trials compared to the other data from the other databases.
Types of Clinical Trials
When reviewing the clinical trial questions and their hypotheses over time, it appears that the questions
asked by researchers have become more robust after each consecutive year. The few initial trials before 2010
mainly consisted of using psychedelics for the treatment of mood symptoms such as after cancer treatment
(NCT00957359), during smoking cessation (NCT01943994), and for psychological therapy (NCT01404754).
These studies had the primary goal of improving the mood of patients that underwent separate treatments
for their medical diseases. Now recently, psychedelics are being used to actually treat many diseases as the
sole drug of choice including many psychiatric diseases. Additionally, many studies have now also been
added to achieve even basic scientific pursuits. Randomization with quadruple masking of the participant,
care provider, investigator, and outcomes assessor appeared largely throughout all the years of clinical trials
for psychedelics.
Current Challenges
While adverse psychotic reactions could theoretically be adverse events of psychedelic treatments, there has
so far been an absence of any such reaction in recent studies [8,50,51]. Indeed, researchers now consider
hallucinogens as one of the classes of drugs with the least amount of adverse side-effects [43,52-55]. Most
countries have scheduled psychedelic drugs, increasing the standards of research design needed to approve
and conduct research with them [40].However, there remain many factors that limit the potential
application of psychedelics in a clinical setting. These barriers, compounded with a lack of acceptance from
mainstream medicine and weariness from the general public, urge psychedelic researchers to adopt a
measured approach if progress is to be achieved [56,57]. As a result, many current trials are small-scale, early
phase studies to observe the safety and tolerability of this class of drugs [58]. Ultimately, if there is to be
progress, it will likely be slow, which is not unwelcome by the psychedelic community. However, overcoming
this image will not just depend upon sound research, as there are early data that suggest the therapeutic
effects of psychedelics are correlated with the degree of the subjective opinion on the efficacy of the drugs.
Thus, the progression of the field with research studies may potentially be hindered once again due to
stigma. Ultimately, a proactive approach to performing rigorous research is needed for future innovation in
the field. This could be potentially performed by obtaining a better basic science understanding of the drugs
on a molecular level and educating the public. In addition, educating the public on the safety profile of these
drugs is paramount.
Limitations
This study has several limitations. Only one United States sponsored database was searched. The opinions of
the patients in these trials could also not be evaluated, and future studies should examine patient attitudes
toward these particular drugs as treatment options for their medical disorders.
Conclusions
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 11 of 20
In the past two decades, there has been a recent uptrend in clinical trials of psychedelic drugs. Psychedelic
therapies potentially hold much promise for the treatment of psychiatric disorders, but their current legal
status and social stigmatization will likely continue to be a barrier to their progression to becoming a widely
used treatment option for patients. However, the progress that has occurred over the years is encouraging
and shows that the field is trending positively. More studies could be performed to evaluate the potential of
psychedelics for symptomatic treatment during opioid tapering and depression refractory to selective
serotonin reuptake inhibitors. Ultimately, a proactive approach to educating the scientific and general
community alike is warranted.
Appendices
Clinical trials
number
Title
Recruitment
status
Condition or disease Study type Intervention
Primary
purpose
Phase
Estimated
enrollment
Study
start
date
Country Sponsor
NCT03984214
Efficacy and Safety of Dronabinol in
the Improvement of Chemotherapy-
induced and Tumor-related
Symptoms in Advanced Pancreatic
Cancer
Recruiting Cancer Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 3 140 2019 Austria
Austrian Group
Medical Tumor
Therapy
NCT04003948
Preliminary Efficacy and Safety of
Ibogaine in the Treatment of
Methadone Detoxification
Not yet
recruiting
Substance use disorder –
opioids
Interventional Ibogaine hydrochloride Treatment 2 20 2019 Spain Barcelona
NCT03756974
BX-1 in Spasticity Due to Multiple
Sclerosis
Recruiting
Degenerative diseases –
multiple sclerosis
Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 3 384 2019 Germany Bionorica SE
NCT03948074
Cannabis For Cancer-Related
Symptoms (CAFCARS)
Not yet
recruiting
Cancer Interventional
Cannabis/cannabinoids
– THC, CBD
Treatment 2 150 2019 Canada
British Columbia
Cancer Agency
NCT02983773
Marijuana's Impact on Alcohol
Motivation and Consumption
Recruiting
substance use disorder –
alcohol
Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
2 173 2017 USA Brown
NCT02492074
Gene-Environment-Interaction:
Influence of the COMT Genotype on
the Effects of Different Cannabinoids
- a PET Study
Not yet
recruiting
Healthy Interventional
Cannabis/cannabinoids
– dronabinol, CBD
Basic
science
1 60 2020 Germany
Central Institute
of Mental Health,
Mannheim
NCT03106363
Combined Alcohol and Cannabis
Effects on Skills of Young Drivers
Recruiting Healthy Interventional
Cannabis/cannabinoids
– THC
Other 1 70 2017 Canada
Centre for
Addiction and
Mental Health
NCT03928015
Evaluation of Dronabinol For Acute
Pain Following Traumatic Injury
Not yet
recruiting
Pain – post-traumatic pain Interventional
Cannabis/cannabinoids
– dronabinol
Supportive
care
2 216 2019 USA Centura Health
NCT04099355
Investigating the Effect of Dronabinol
on Post-surgical Pain
Recruiting Pain – post-operative pain Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 1 80 2019 USA
Columbia - New
York Psychiatric
Institute
NCT03775200
The Safety and Efficacy of Psilocybin
in Participants With Treatment
Resistant Depression (P-TRD)
Recruiting Depression Interventional Psilocybin Treatment 2 216 2019 UK
COMPASS
Pathways
NCT03766269
Dronabinol Opioid Sparing Evaluation
(DOSE) Trial
Recruiting Pain – chronic pain Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 2 280 2018 USA
Daisy Pharma
Opioid Venture
NCT01964404
Cannabis, Schizophrenia and
Reward: Self-Medication and Agonist
Treatment?
Recruiting Psychosis/schizophrenia Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 240 2014 USA
Dartmouth
College
NCT04203498
Safety and Effectiveness of
Nabiximols Oromucosal Spray as
Add-on Therapy in Participants With
Spasticity Due to Multiple Sclerosis
Not yet
recruiting
degenerative diseases –
multiple sclerosis
Interventional
Cannabis/cannabinoids
– nabiximols
Treatment 3 446 2020 USA
GW
Pharmaceuticals,
Inc.
NCT03087201
CANNAbinoids in the Treatment of
TICS (CANNA-TICS) (CANNA-TICS)
Recruiting
Multiple – Tourette
syndrome, tic disorder
Interventional
Cannabis/cannabinoids
– nabiximols
Treatment 3 96 2018 Germany
Hannover
Medical School
NCT03380442 Psilocybin and Depression (Psilo101)
Not yet
recruiting
Depression Interventional
Multiple – psilocybin,
ketamine
Basic
science
2 60 2018 Finland
Helsinki
University
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 12 of 20
NCT03429075
Psilocybin vs Escitalopram for Major
Depressive Disorder: Comparative
Mechanisms (Psilodep-RCT)
Recruiting Depression Interventional Psilocybin Treatment 2 50 2019 UK
Imperial College
London
NCT04158778
Bristol Imperial MDMA in Alcoholism
Study (BIMA)
Active, not
recruiting
Substance use disorder –
alcohol
Interventional MDMA Treatment 1 20 2018 UK
Imperial College
London
NCT02792257
Trial of Dronabinol Adjunctive
Treatment of Agitation in Alzheimer's
Disease (AD) (THC-AD)
Recruiting
Degenerative diseases –
Alzheimer's disease
Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 2 160 2017 USA
Johns Hopkins
University
NCT02145091
Effects of Psilocybin on Behavior,
Psychology and Brain Function in
Long-term Meditators
Active, not
recruiting
Healthy Interventional Psilocybin
Basic
science
1 100 2014 USA
Johns Hopkins
University
NCT02243813
Effects of Psilocybin-facilitated
Experience on the Psychology and
Effectiveness of Professional Leaders
in Religion
Recruiting Healthy Interventional Psilocybin
Basic
science
1 12 2015 USA
Johns Hopkins
University
NCT03609853
Behavioral Pharmacology of THC
and D-limonene
Recruiting Healthy Interventional
Cannabis/cannabinoids
– THC, limonene
(terpene)
Basic
science
1 20 2019 USA
Johns Hopkins
University
NCT03181529
Effects of Psilocybin in Major
Depressive Disorder
Active, not
recruiting
Depression Interv entional Psilocybin Treatment 2 24 2017 USA
Johns Hopkins
University
NCT04052568
Effects of Psilocybin in Anorexia
Nervosa
Recruiting Anorexia nervosa Interventional Psilocybin Treatment 1 18 2019 USA
Johns Hopkins
University
NCT04123314
Psilocybin for Depression in People
With Mild Cognitive Impairment or
Early Alzheimer's Disease
Recruiting
Multiple – depression,
depressive symptoms,
Alzheimers disease, mild
cognitive impairment
Interventional Psilocybin Treatment 1 20 2019 USA
Johns Hopkins
University
NCT04201197
Interactions Between Cannabinoids
and Cytochrome P450-Metabolized
Drugs
Not yet
recruiting
Healthy Interventional
Cannabis/cannabinoids
– inje cocktail, THC
Cannabis extract,
THC/CBD cannabis
extract
Basic
science
1 25 2020 USA
Johns Hopkins
University
NCT04130633
Behavioral Pharmacology of THC
and Alpha-pinene
Not yet
recruiting
Healthy Interventional
Cannabis/cannabinoids
– THC, alpha-pinene
(terpene)
Basic
science
1 32 2020 USA
Johns Hopkins
University
NCT01943994
Psilocybin-facilitated Smoking
Cessation Treatment: A Pilot Study
Recruiting
Substance use disorder –
nicotine
Interventional Psilocybin Treatment NA 95 2008 USA
Johns Hopkins
University
NCT03418714
Effects of Salvinorin A on Brain
Function
Active, not
recruiting
Healthy Interventional Salvinorin A Other
1 and
2
20 2017 USA
Johns Hopkins
University
NCT03555968
Effects of THC and Alcohol on
Driving Performance
Not yet
recruiting
Healthy Interventional
Cannabis/cannabinoids
– THC
Basic
science
4 135 2020 Canada
Lakehead
University
NCT03655717
Using Imaging to Assess Effects of
THC on Brain Activity (fNIRS)
Recruiting
Substance use disorder –
marijuana/cannabis
Interventional
Multiple – dronabinol,
ethanol
Diagnostic 4 50 2018 USA
Massachusetts
General Hospital
NCT03550352
Cannabinoids in PLWHIV on
Effective ART
Not yet
recruiting
HIV Interventional
Cannabis/cannabinoids
– THC, CBD
Treatment 2 26 2018 Canada McGill University
NCT03773796
Nabilone for Non-motor Symptoms in
Parkinson's Disease (NMS-Nab2)
Recruiting
Degenerative diseases –
Parkinson's disease
Interventional
Cannabis/cannabinoids
– nabilone
Treatment 3 48 2018 Austria
Medical
University of
Innsbruck
NCT04155008
Nutrition and Pharmacological
Algorithm for Oncology Patients
Study
Not yet
recruiting
Cancer Interventional
Cannabis/cannabinoids
– dronabinol
Supportive
care
4 30 2019 USA
Montefiore
Medical Center
NCT03422861
Nabilone Use For Acute Pain in
Inflammatory Bowel Disease Patients
Not yet
recruiting
Pain – inflammatory
bowel disease
Interventional
Cannabis/cannabinoids
– nabilone
Supportive
care
NA 80 2019 USA
Mount Sinai
Health System
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 13 of 20
NCT01404754
Psychological Effects of
Methylenedioxymethamphetamine
(MDMA) When Administered to
Healthy Volunteers (MT-1)
Enrolling by
invitation
Healthy Interventional MDMA
Basic
science
1 100 2011 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT03181763
Evaluation of MDMA on Startle
Response
Recruiting Healthy Interventional MDMA
Basic
science
1 30 2017 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT04077437
A Multi-Site Phase 3 Study of
MDMA-Assisted Psychotherapy for
PTSD II
Not yet
recruiting
PTSD Interventional MDMA Treatment 3 100 2020 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT03537014
A Multi-Site Phase 3 Study of
MDMA-Assisted Psychotherapy for
PTSD (MAPP1)
Recruiting PTSD Interventional MDMA Treatment 3 100 2018 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT03485287
Study of Safety and Effects of
MDMA-assisted Psychotherapy for
Treatment of PTSD
Active, not
recruiting
PTSD Interventional MDMA Treatment 2 5 2018 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT03282123
Open Label Multi-Site Study of Safety
and Effects of MDMA-assisted
Psychotherapy for Treatment of
PTSD
Active, not
recruiting
PTSD Interventional MDMA Treatment 2 38 2017 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT04073433
Psychological Effects of
Methylenedioxymethamphetamine
(MDMA) When Administered to
Healthy Volunteers (MT-2)
Not yet
recruiting
Healthy Interventional MDMA
Basic
science
1 150 2020 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT03606538
MDMA in Subjects With Moderate
Hepatic Impairment and Subjects
With Normal Hepatic Function
Not yet
recruiting
Hepatic impairment Interventional MDMA
Basic
science
1 16 2020 USA
Multidisciplinary
Association for
Psychedelic
Studies (MAPS)
NCT04030169
Open Label Multi-Site Study of Safety
and Effects of MDMA-assisted
Psychotherapy for Treatment of
PTSD With Optional fMRI Sub-Study
Not yet
recruiting
PTSD Interventional MDMA Treatment 2 40 2019 Netherlands
Multidisciplinary
Association for
Psychedelic
Studies (MAPS) -
Europe
NCT00957359 Psilocybin Cancer Anxiety Study
Active, not
recruiting
Cancer Interv entional Psilocybin Treatment 1 29 2009 USA
New York
University
NCT02421263
The Effects of Psilocybin-Facilitated
Experience on the Psychology and
Effectiveness of Religious
Professionals
Recruiting Healthy Interventional Psilocybin
Health
services
research
1 12 2015 USA
New York
University
NCT02061293
A Double-Blind Trial of Psilocybin-
Assisted Treatment of Alcohol
Dependence
Recruiting
Substance use disorder –
alcohol
Interventional Psilocybin Treatment 2 180 2014 USA
New York
University
NCT03560934
Tetrahydrocannabinol (THC) and
Sleep
Recruiting Healthy Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 14 2018 USA
Oregon Health
and Science
University
NCT03289949
The Neurobiological Effect of 5-
HT2AR Modulation
Recruiting Healthy Interventional Psilocybin
Basic
science
1 45 2019 Denmark Rigshospitalet
NCT03337503
Safety and Efficacy of Medical
Cannabis Oil in the Treatment of
Patients With Chronic Pain
Recruiting Pain – chronic pain Interventional
Cannabis/cannabinoids
– THC, CBD
Treatment 4 160 2018 Canada Sante Cannabis
NCT04060108
Stanford Reward Circuits of the Brain
Study - MDMA (RBRAIN-MDMA)
Not yet
recruiting
Healthy Observational MDMA NA NA 40 2020 USA
Stanford
University
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 14 of 20
NCT03646552
A Study to Examine the Efficacy of a
Therapeutic THX-110 for Obstructive
Sleep Apnea
Recruiting Obstructive sleep apnea Interventional
Cannabis/cannabinoids
– THX-110 (dronabinol
+ PEA)
Treatment 2 30 2018 Israel
Therapix
Biosciences Ltd.
NCT03651726
A Study to Examine the Efficacy of a
Therapeutic THX-110 for Tourette
Syndrome
Not yet
recruiting
Tourette syndrome Interventional
Cannabis/Cannabinoids
– THX-110 (Dronabinol
+ PEA)
Treatment 2 60 2018 Israel
Therapix
Biosciences Ltd.
NCT02037126
Psilocybin-facilitated Treatment for
Cocaine Use
Recruiting
Substance use disorder –
cocaine
Interventional Psilocybin Treatment 2 40 2015 USA
University of
Alabama
NCT03153579
LSD Treatment in Persons Suffering
From Anxiety Symptoms in Severe
Somatic Diseases or in Psychiatric
Anxiety Disorders (LSD-assist)
Recruiting Anxiety disorders Interventional LSD Treatment 2 40 2017 Switzerland
University
Hospital, Basel
NCT03866252
LSD Therapy for Persons Suffering
From Major Depression (LAD)
Recruiting Depression Interventional LSD Treatment 2 60 2019 Switzerland
University
Hospital, Basel
NCT03781128
Lysergic Acid Diethylamide (LSD) as
Treatment for Cluster Headache
(LCH)
Recruiting
Headache disorders –
cluster headache
Interventional LSD Treatment 2 30 2019 Switzerland
University
Hospital, Basel
NCT03527316
Effect of
Methylenedioxymethamphetamine
(MDMA) (Serotonin Release) on Fear
Extinction (MFE)
Recruiting Healthy Interventional MDMA
Basic
science
1 30 2019 Switzerland
University
Hospital, Basel
NCT03604744
Direct Comparison of Altered States
of Consciousness Induced by LSD
and Psilocybin (LSD-psilo)
Recruiting Healthy Interventional
Multiple – psilocybin,
LSD
Basic
science
1 30 2019 Switzerland
University
Hospital, Basel
NCT03912974
Effects of SERT Inhibition on the
Subjective Response to Psilocybin in
Healthy Subjects
Recruiting Healthy Interventional
Multiple – SSRI
(escitalopram),
Psilocybin
Basic
science
1 24 2019 Switzerland
University
Hospital, Basel
NCT03661892
Pilot, Syndros, Decreasing Use of
Opioids in Breast Cancer Subjects
With Bone Mets
Recruiting Cancer Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 1 20 2018 USA
University of
Arizona
NCT03300947
Psilocybin for Treatment of
Obsessive Compulsive Disorder
(PSILOCD)
Recruiting OCD Interventional Psilocybin Treatment 1 15 2019 USA
University of
Arizona
NCT02460692
Trial of Dronabinol and Vaporized
Cannabis in Neuropathic Low Back
Pain
Recruiting
Pain – neuropathic low-
back pain
Interventional
Cannabis/cannabinoids
– dronabinol, cannabis
Treatment 2 120 2016 USA
University of
California, San
Diego
NCT02950467
Psilocybin-assisted Group Therapy
for Demoralization in Long-term AIDS
Survivors
Active, not
recruiting
Multiple – distress/grief,
depression
Interventional Psilocybin Treatment 1 36 2018 USA
University of
California, San
Francisco
NCT03790618
Effect of Stimulant Drugs on Social
Perception (ESP)
Recruiting Healthy Interventional
Multiple – MDMA,
methamphetamine
Basic
science
1 40 2016 USA
University of
Chicago
NCT03530800
Dronabinol in Trichotillomania and
Other Body Focused Repetitive
Behaviors
Recruiting Trichotillomania Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 2 50 2018 USA
University of
Chicago
NCT03809546
Individual Differences in Drug
Response (IDT)
Recruiting Healthy Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 60 2018 USA
University of
Chicago
NCT03790358 Mood Effects of Serotonin Agonists Recruiting H ealthy Interventional LSD
Basic
science
1 40 2018 USA
University of
Chicago
NCT04053036
Effects of Drugs on Responses to
Brain and Emotional Processes
(MAT)
Recruiting Autism spectrum disorder Interventional MDMA
Basic
science
1 45 2019 USA
University of
Chicago
NCT03944954
Neural Mechanisms of Cannabinoid-
impaired Decision-Making in
Emerging Adults
Recruiting
Substance use disorder –
marijuana/cannabis
Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 40 2017 USA
University of
Kentucky
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 15 of 20
NCT03380728
Ibogaine in the Treatment of
Alcoholism: a Randomized, Double-
blind, Placebo-controlled, Escalating-
dose, Phase 2 Trial
Not yet
recruiting
Substance use disorder –
alcohol
Interventional Ibogaine hydrochloride Treatment 2 12 2020 Brazil
University of Sao
Paulo
NCT03744091
Evaluation of the Pharmacokinetics
of Prana P1 Capsules
Active, not
recruiting
Healthy Interventional
Cannabis/cannabinoids
– THC
Treatment 1 13 2018 West Indies
University of the
West Indies
NCT03215940
Treatment of Chronic Pain With
Cannabidiol (CBD) and Delta-9-
tetrahydrocannabinol (THC)
Recruiting Pain – chronic pain Interventional
Cannabis/cannabinoids
– dronabinol, CBD
Treatment 1 75 2018 USA
University of
Utah
NCT04161066
Adjunctive Effects of Psilocybin and
Buprenorphine
Not yet
recruiting
Substance use disorder –
opioids
Interventional Psilocybin
Health
services
research
1 10 2020 USA
University of
Wisconsin
NCT03715127
Clinical, Neurocognitive, and
Emotional Effects of Psilocybin in
Depressed Patients - Proof of
Concept
Recruiting Depression Interventional Psilocybin Treatment 2 60 2019 Switzerland
University of
Zurich
NCT03736980
Beyond the Self and Back:
Neuropharmacological Mechanisms
Underlying the Dissolution of the Self
Active, not
recruiting
Healthy Interventional Psilocybin
Basic
science
NA 140 2018 Switz erland
University of
Zurich
NCT03853577
Characterization of Altered Waking
States of Consciousness in Healthy
Humans
Recruiting Healthy Interventional Psilocybin
Basic
science
NA 25 2019 Switzerland
University of
Zurich
NCT04141501
Clinical and Mechanistic Effects of
Psilocybin in Alcohol Addicted
Patients
Not yet
recruiting
Substance use disorder –
alcohol
Interventional Psilocybin Treatment 2 60 2020 Switzerland
University of
Zurich
NCT03866174
A Study of Psilocybin for Major
Depressive Disorder (MDD)
Recruiting Depression Interventional Psilocybin Treatment 2 80 2019 USA Usona Institute
NCT03008005
Effects of Delta-9
Tetrahydrocannabinol (THC) on
Retention of Memory for Fear
Extinction Learning in PTSD: R61
Study
Recruiting PTSD Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
4 104 2017 USA
Wayne State
University
NCT02069366
Cannabinoid Control of Fear
Extinction Neural Circuits in Post-
traumatic Stress Disorder
Active, not
recruiting
PTSD Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
NA 130 2014 USA
Wayne State
University
NCT04080427
Effects of Delta9-
tetrahydrocannabinol (THC) on
Retention of Memory for Fear
Extinction Learning in PTSD: R33
Study
Not yet
recruiting
PTSD Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 100 2020 USA
Wayne State
University
NCT04040582
Psychedelics and Wellness Study
(PAWS)
Recruiting
Multiple – depression,
anxiety, PTSD
Observational
Multiple – All
psychedelics
Treatment NA 5000 2019 USA Wild 5 Wellness
NCT00678730
Pharmacogenetics of Cannabinoid
Response
Active, not
recruiting
Healthy Interventional
Cannabis/cannabinoids
– THC
Basic
science
1 162 2007 USA Yale U niversity
NCT00982982
Effects of Delta-9-THC and Iomazenil
in Healthy Humans
Active, not
recruiting
Psychosis/schizophrenia Interventional
Cannabis/cannabinoids
– THC
Basic
science
1 60 2009 USA Yale University
NCT00700596
Effects of Salvinorin A in Healthy
Controls
Active, not
recruiting
Healthy Interventional Salvinorin A
Basic
science
1 41 2009 USA Yale University
NCT01180374
The Effects of Cannabidiol and ∆-9-
THC in Humans
Active, not
recruiting
Healthy Interventional
Cannabis/cannabinoids
– dronabinol, CBD
Basic
science
1 75 2010 USA Yale University
NCT01591629
The Effects of ∆-9-THC and Naloxone
in Humans
Active, not
recruiting
Healthy Interventional
Cannabis/cannabinoids
– THC
Basic
science
1 56 2011 USA Yale University
NCT02335060
N-acetylcysteine Effects on Active, not
Healthy Interventional
Cannabis/cannabinoids Basic
1 36 2014 USA Yale University
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 16 of 20
Tetrahydrocannabinol recruiting – THC science
NCT02781519
Gender Related Differences in the
Acute Effects of Delta-9-
Tetrahydrocannabinol in Healthy
Humans (THC-Gender)
Recruiting Healthy Interventional
Cannabis/cannabinoids
– THC
Basic
science
1 100 2015 USA Yale U niversity
NCT02811939
Testing the Interactive Effects of
Delta-9-Tetrahydrocannabinol and
Pregnenolone: Sub-Study I (THC-
PREG-I)
Recruiting Healthy Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 19 2016 USA Yale University
NCT02811510
Gender Related Differences in the
Acute Effects of Delta-9-
Tetrahydrocannabinol in Healthy
Humans: Sub-Study I (THC-Gender-
I)
Recruiting Healthy Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 40 2016 USA Yale University
NCT02981173
Psilocybin for the Treatment of
Cluster Headache
Recruiting
Headache disorders –
cluster headache
Interventional Psilocybin Treatment 1 24 2016 USA Yale University
NCT03206463
Cognitive and Psychophysiological
Effects of Delta-9-
Tetrahydrocannabinol in Bipolar
Disorder (THC-BD)
Active, not
recruiting
Bipolar disorder Interventional
Cannabis/cannabinoids
– THC
Treatment 1 40 2017 USA Yale University
NCT03191084
Examine the Feasibility of a
Standardized Field Test for Marijuana
Impairment: Laboratory Evaluations
Recruiting
Substance use disorder –
marijuana/cannabis
Interventional
Cannabis/cannabinoids
– THC
Other 1 28 2017 USA Yale University
NCT03341689
Psilocybin for the Treatment of
Migraine Headache
Recruiting
Headache disorders –
migraine
Interventional Psilocybin Treatment 1 24 2017 USA Yale University
NCT02102113
Probing the Cannabinoid System in
Individuals With a Family History of
Psychosis
Active, not
recruiting
Psychosis/schizophrenia Interventional
Cannabis/cannabinoids
– THC
Other NA 21 2014 USA Yale University
NCT02757313
Neuroscience of Marijuana Impaired
Driving (MJDriving)
Recruiting
Substance use disorder –
marijuana/cannabis
Interventional
Cannabis/cannabinoids
– THC
Other NA 96 2016 USA Yale University
NCT03554174
Psilocybin - Induced Neuroplasticity in
the Treatment of Major Depressive
Disorder
Recruiting Depression Interventional Psilocybin Treatment 1 18 2018 USA Yale University
NCT03356483
Efficacy of Psilocybin in OCD: a
Double-Blind, Placebo-Controlled
Study
Recruiting OCD Interventional Psilocybin Treatment 1 30 2018 USA Yale University
NCT03978156
Dronabinol for Pain and Inflammation
in Adults Living With Sickle Cell
Disease
Recruiting Pain – sickle cell disease Interventiona l
Cannabis/cannabinoids
– dronabinol
Treatment 1 30 2019 USA Yale University
NCT04025359
Effects of Dronabinol in Opioid
Maintained Patients (THC)
Recruiting
Substance use disorder –
opioids
Interventional
Cannabis/cannabinoids
– dronabinol
Treatment 1 20 2019 USA Yale University
NCT03752918
The Effects of MDMA on Prefrontal
and Amygdala Activation in PTSD
Recruiting PTSD Interventional MDMA Treatment 1 20 2019 USA Yale University
NCT04199468
THC and Ketamine Effects in
Humans: Relation to Neural
Oscillations and Psychosis
Recruiting Healthy Interventional
Multiple – THC,
ketamine
Basic
science
1 21 2019 USA Yale University
NCT03806985
Effects of Psilocybin in Post-
Traumatic Headache
Recruiting
Headache disorders –
post-traumatic headache
Interventional Psilocybin Treatment 1 24 2019 USA Yale University
NCT02710331
Ethanol and Cannabinoid Effects on
Simulated Driving and Related
Cognition: Substudy III (THC-ETOH-
III)
Recruiting Healthy Interventional
Cannabis/cannabinoids
– dronabinol
Basic
science
1 40 2020 USA Yale University
TABLE 4: Supplemental A. Total data of clinical trials in response to the query of clinicaltrials.gov.
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 17 of 20
CBD, cannabidiol; HIV, human immunodeficiency virus; LSD, lysergic acid diethylamide; MDMA, methylenedioxymethamphetamine; OCD, obsessive
compulsive disorder; PEA, palmitoylethanolamide; SSRI, selective serotonin reuptake inhibitors; THC, tetrahydracannibidinol
Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.
References
1. U.S. FDA. Cesamet™. (2016). Accessed: July 8, 2022:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018677s011lbl.pdf.
2. Switzerland Briefly Legalized LSD Therapy and Then Couldn't Let It Go . (2015). Accessed: July 8, 2022:
https://www.vice.com/en/article/aekz8g/switzerland-briefly-legalized-lsd-therapy-and-then-couldnt-let-it-
go.
3. Cameron LP, Tombari RJ, Lu J, et al.: A non-hallucinogenic psychedelic analogue with therapeutic potential .
Nature. 2021, 589:474-9. 10.1038/s41586-020-3008-z
4. Carhart-Harris RL, Bolstridge M, Rucker J, et al.: Psilocybin with psychological support for treatment-
resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016, 3:619-27. 10.1016/S2215-
0366(16)30065-7
5. Carhart-Harris RL, Erritzoe D, Williams T, et al.: Neural correlates of the psychedelic state as determined by
fMRI studies with psilocybin. Proc Natl Acad Sci U S A. 2012, 109:2138-43. 10.1073/pnas.1119598109
6. Carhart-Harris RL, Goodwin GM: The therapeutic potential of psychedelic drugs: past, present, and future .
Neuropsychopharmacology. 2017, 42:2105-13. 10.1038/npp.2017.84
7. Carhart-Harris RL, Kaelen M, Bolstridge M, et al.: The paradoxical psychological effects of lysergic acid
diethylamide (LSD). Psychol Med. 2016, 46:1379-90. 10.1017/S0033291715002901
8. Carhart-Harris RL, Kaelen M, Whalley MG, Bolstridge M, Feilding A, Nutt DJ: LSD enhances suggestibility in
healthy volunteers. Psychopharmacology (Berl). 2015, 232:785-94. 10.1007/s00213-014-3714-z
9. Carhart-Harris RL, Muthukumaraswamy S, Roseman L, et al.: Neural correlates of the LSD experience
revealed by multimodal neuroimaging. Proc Natl Acad Sci U S A. 2016, 113:4853-8.
10.1073/pnas.1518377113
10. Carter OL, Hasler F, Pettigrew JD, Wallis GM, Liu GB, Vollenweider FX: Psilocybin links binocular rivalry
switch rate to attention and subjective arousal levels in humans. Psychopharmacology (Berl). 2007, 195:415-
24. 10.1007/s00213-007-0930-9
11. Chi T, Gold JA: A review of emerging therapeutic potential of psychedelic drugs in the treatment of
psychiatric illnesses. J Neurol Sci. 2020, 411:116715. 10.1016/j.jns.2020.116715
12. Daumann J, Wagner D, Heekeren K, Neukirch A, Thiel CM, Gouzoulis-Mayfrank E: Neuronal correlates of
visual and auditory alertness in the DMT and ketamine model of psychosis. J Psychopharmacol. 2010,
24:1515-24. 10.1177/0269881109103227
13. Dos Santos RG, Bouso JC, Hallak JE: Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of
human studies. Ther Adv Psychopharmacol. 2017, 7:141-57. 10.1177/2045125316689030
14. El-Seedi HR, De Smet PA, Beck O, Possnert G, Bruhn JG: Prehistoric peyote use: alkaloid analysis and
radiocarbon dating of archaeological specimens of Lophophora from Texas. J Ethnopharmacol. 2005,
101:238-42. 10.1016/j.jep.2005.04.022
15. Garcia-Romeu A, Kersgaard B, Addy PH: Clinical applications of hallucinogens: a review . Exp Clin
Psychopharmacol. 2016, 24:229-68. 10.1037/pha0000084
16. Research Update: Psychedelic Group Therapy in Switzerland. (2017). Accessed: July 8, 2022:
https://maps.org/news/bulletin/research-update-psychedelic-group-therapy-in-switzerland/.
17. Gouzoulis-Mayfrank E, Heekeren K, Neukirch A, Stoll M, Stock C, Obradovic M, Kovar KA: Psychological
effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy
volunteers. Pharmacopsychiatry. 2005, 38:301-11. 10.1055/s-2005-916185
18. Griffiths RR, Johnson MW, Carducci MA, et al.: Psilocybin produces substantial and sustained decreases in
depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J
Psychopharmacol. 2016, 30:1181-97. 10.1177/0269881116675513
19. Griffiths RR, Richards WA, McCann U, Jesse R: Psilocybin can occasion mystical-type experiences having
substantial and sustained personal meaning and spiritual significance . Psychopharmacology (Berl). 2006,
187:268-83; discussion 284-92. 10.1007/s00213-006-0457-5
20. Grinspoon L, Bakalar JB: Psychedelic Drugs Reconsidered. Basic Books, New York; 1979.
21. Grob C: Psychiatric research with hallucinogens: What have we learned? . Yearbook for Ethnomedicine and
the Study of Consciousness. Verlag fur Wissenschaft und Bildung, Berlin; 1994.
22. Grof S: LSD Psychotherapy. San Jose, CA (ed): Multidisciplinary Association for Psychedelic Studies, 2001.
23. Basel in the spolight: the city that learned to love LSD . (2018). Accessed: July 12, 2022:
https://www.theguardian.com/cities/2018/apr/19/basel-in-the-spotlight-the-city-that-learned-to-love-lsd-
albert-hofmann.
24. Heffter A: Berichte der deutschen chemischen Gesellschaft . Ueber Cateenalkaloïde. 1896, 29:216-27.
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 18 of 20
10.1002/cber.18960290145
25. Hofmann A, Heim R, Brack A, Kobel H: [Psilocybin, a psychotropic substance from the Mexican mushroom
Psilicybe mexicana Heim] [Article in German]. Experientia. 1958, 14:107-9. 10.1007/BF02159243
26. Koenig X, Hilber K: The anti-addiction drug ibogaine and the heart: a delicate relation . Molecules. 2015,
20:2208-28. 10.3390/molecules20022208
27. Kometer M, Schmidt A, Bachmann R, Studerus E, Seifritz E, Vollenweider FX: Psilocybin biases facial
recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through
different serotonergic subreceptors. Biol Psychiatry. 2012, 72:898-906. 10.1016/j.biopsych.2012.04.005
28. Lieberman JA, Shalev D: Back to the future: research renewed on the clinical utility of psychedelic drugs . J
Psychopharmacol. 2016, 30:1198-200. 10.1177/0269881116675755
29. Ludwig AM: LSD treatment in alcoholism . Hallucinogenic Drug Research: Impact on Science and Society.
Gamage JR, Zerkin EL (ed): Stash Press, Beloit, WI; 1970.
30. MacLean KA, Johnson MW, Griffiths RR: Mystical experiences occasioned by the hallucinogen psilocybin
lead to increases in the personality domain of openness. J Psychopharmacol. 2011, 25:1453-61.
10.1177/0269881111420188
31. Malleson N: Acute adverse reactions to LSD in clinical and experimental use in the United Kingdom . Br J
Psychiatry. 1971, 118:229-30. 10.1192/bjp.118.543.229
32. Mithoefer MC, Mithoefer AT, Feduccia AA, et al.: 3,4-methylenedioxymethamphetamine (MDMA)-assisted
psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a
randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018, 5:486-97.
10.1016/S2215-0366(18)30135-4
33. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R: The safety and efficacy of {+/-}3,4-
methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant
posttraumatic stress disorder: the first randomized controlled pilot study . J Psychopharmacol. 2011, 25:439-
52. 10.1177/0269881110378371
34. Muthukumaraswamy SD, Carhart-Harris RL, Moran RJ, et al.: Broadband cortical desynchronization
underlies the human psychedelic state. J Neurosci. 2013, 33:15171-83. 10.1523/JNEUROSCI.2063-13.2013
35. National Academies of Sciences, Engineering, and Medicine:
The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research.
National Academies Press, Washington, DC; 2017. 10.17226/24625
36. Nutt D, King LA, Saulsbury W, Blakemore C: Development of a rational scale to assess the harm of drugs of
potential misuse. Lancet. 2007, 369:1047-53. 10.1016/S0140-6736(07)60464-4
37. Nutt DJ, King LA, Nichols DE: Effects of Schedule I drug laws on neuroscience research and treatment
innovation. Nat Rev Neurosci. 2013, 14:577-85. 10.1038/nrn3530
38. Nutt DJ, King LA, Phillips LD: Drug harms in the UK: a multicriteria decision analysis . Lancet. 2010,
376:1558-65. 10.1016/S0140-6736(10)61462-6
39. Oram M: Efficacy and enlightenment: LSD psychotherapy and the Drug Amendments of 1962 . J Hist Med
Allied Sci. 2014, 69:221-50. 10.1093/jhmas/jrs050
40. Overdose Death Rates. (2021). Accessed: July 8, 2022: https://www.drugabuse.gov/drug-topics/trends-
statistics/overdose-death-rates .
41. Palhano-Fontes F, Andrade KC, Tofoli LF, et al.: The psychedelic state induced by ayahuasca modulates the
activity and connectivity of the default mode network. PLoS One. 2015, 10:e0118143.
10.1371/journal.pone.0118143
42. Preller KH, Herdener M, Pokorny T, et al.: The fabric of meaning and subjective effects in LSD-induced
states depend on serotonin 2A receptor activation. Curr Biol. 2017, 27:451-7. 10.1016/j.cub.2016.12.030
43. Riba J, Anderer P, Jané F, Saletu B, Barbanoj MJ: Effects of the South American psychoactive beverage
ayahuasca on regional brain electrical activity in humans: a functional neuroimaging study using low-
resolution electromagnetic tomography. Neuropsychobiology. 2004, 50:89-101. 10.1159/000077946
44. Riba J, Romero S, Grasa E, Mena E, Carrió I, Barbanoj MJ: Increased frontal and paralimbic activation
following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology (Berl). 2006, 186:93-8.
10.1007/s00213-006-0358-7
45. Schmid Y, Enzler F, Gasser P, et al.: Acute effects of lysergic acid diethylamide in healthy subjects . Biol
Psychiatry. 2015, 78:544-53. 10.1016/j.biopsych.2014.11.015
46. Schultes E, Hofmann A, Ratsch C: Plants of the Gods: Their Sacred, Healing, and Hallucinogenic Powers .
Healing Arts Press, Rochester, VT; 1998.
47. Schünemann HJ, Fretheim A, Oxman AD: Improving the use of research evidence in guideline development:
1. Guidelines for guidelines. Health Res Policy Syst. 2006, 4:13. 10.1186/1478-4505-4-13
48. Sessa B: Can psychedelics have a role in psychiatry once again? . Br J Psychiatry. 2005, 186:457-8.
10.1192/bjp.186.6.457
49. St John Sessa B: Are psychedelic drug treatments seeing a comeback in psychiatry? . Prog Neurol Psychiatry.
2008, 12:5-10. 10.1002/pnp.94
50. Taylor M, Mackay K, Murphy J, McIntosh A, McIntosh C, Anderson S, Welch K: Quantifying the RR of harm
to self and others from substance misuse: results from a survey of clinical experts across Scotland. BMJ
Open. 2012, 2:e000774. 10.1136/bmjopen-2011-000774
51. Valle M, Maqueda AE, Rabella M, et al.: Inhibition of alpha oscillations through serotonin-2A receptor
activation underlies the visual effects of ayahuasca in humans. Eur Neuropsychopharmacol. 2016, 26:1161-
75. 10.1016/j.euroneuro.2016.03.012
52. van Amsterdam J, Nutt D, Phillips L, van den Brink W: European rating of drug harms. J Psychopharmacol.
2015, 29:655-60. 10.1177/0269881115581980
53. van Amsterdam J, Opperhuizen A, Koeter M, van den Brink W: Ranking the harm of alcohol, tobacco and
illicit drugs for the individual and the population. Eur Addict Res. 2010, 16:202-7. 10.1159/000317249
54. van Amsterdam J, Opperhuizen A, van den Brink W: Harm potential of magic mushroom use: a review .
Regul Toxicol Pharmacol. 2011, 59:423-9. 10.1016/j.yrtph.2011.01.006
55. van Amsterdam J, Pennings E, Brunt T, van den Brink W: Physical harm due to chronic substance use . Regul
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 19 of 20
Toxicol Pharmacol. 2013, 66:83-7. 10.1016/j.yrtph.2013.03.007
56. Vollenweider FX, Leenders KL, Scharfetter C, Maguire P, Stadelmann O, Angst J: Positron emission
tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the
psilocybin model of psychosis. Neuropsychopharmacology. 1997, 16:357-72. 10.1016/S0893-133X(96)00246-
1
57. Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D: Psilocybin induces
schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport. 1998, 9:3897-902.
10.1097/00001756-199812010-00024
58. Wilson N, Kariisa M, Seth P, Smith H 4th, Davis NL: Drug and opioid-involved overdose deaths - United
States, 2017-2018. MMWR Morb Mortal Wkly Rep. 2020, 69:290-7. 10.15585/mmwr.mm6911a4
2022 Kurtz et al. Cureus 14(9): e29167. DOI 10.7759/cureus.29167 20 of 20
