pharmaceuticals

Review
Lysergic Acid Diethylamide, Psilocybin and
Dimethyltryptamine in Depression Treatment:
A Systematic Review
Gniewko Wi˛eckiewicz * , Iga Stokłosa , Magdalena Piegza , Piotr Gorczyca and Robert Pudlo

Department and Clinic of Psychiatry, Medical University of Silesia, 42-612 Tarnowskie Góry, Poland;
[email protected] (I.S.); [email protected] (M.P.); [email protected] (P.G.);
[email protected] (R.P.)
* Correspondence: [email protected]; Tel.: +48-(32)-285-43-58

Abstract: Despite many different kinds of substances available for depression treatment, depression
itself still appears to be a clinical challenge. Recently, formerly illicit substances came to scientists’
attention, including lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT).
Some studies suggest that these substances might be effective in depression treatment. The aim of
this study was to evaluate the efficiency of LSD, psilocybin and DMT in depression treatment in the
light of current medical literature. The authors followed the Preferred Reporting Items for Systematic
Review and Meta-Analysis (PRISMA) guidelines for this systematic review. The authors searched
the PubMed and Cochrane Library databases to identify relevant publications. Finally, 10 papers
were included. Most of the selected studies showed significant correlation between psilocybin and





 DMT use and reduction in depression symptom intensity. By analyzing qualified studies, it can be
concluded that psilocybin and DMT could be useful in depression treatment, but further observations
Citation: Wi˛eckiewicz, G.; Stokłosa,
are still required.
I.; Piegza, M.; Gorczyca, P.; Pudlo, R.
Lysergic Acid Diethylamide,
Psilocybin and Dimethyltryptamine
Keywords: lysergic acid diethylamide (LSD); psilocybin; dimethyltryptamine (DMT); depression
in Depression Treatment: A
Systematic Review. Pharmaceuticals
2021, 14, 793. https://doi.org/
10.3390/ph14080793 1. Introduction
Psychedelic substances have accompanied humanity around the world for millen-
Academic Editor: Marek Krzystanek nia. Indigenous peoples of South America have used herbal dimethyltryptamine in folk
medicine and religious practice for at least a thousand years, and the 6000-year-old Spanish
Received: 28 July 2021
pictographs probably show the local species of the hallucinogenic mushroom Psilocybe
Accepted: 11 August 2021
hispanica [1,2]. While psychodysleptic substances can be dangerous to the user when used
Published: 12 August 2021
inappropriately, they can provide benefits under clinical conditions, as evidenced by the
increasing number of clinical trials on the use of psychedelics in treatment.
Publisher’s Note: MDPI stays neutral
Lysergic acid diethylamide (LSD) is a semisynthetic substance derived from the
with regard to jurisdictional claims in
lysergic acid of the fungus Caliceps pupurea. LSD is mainly taken orally, but it can also
published maps and institutional affil-
be smoked, snorted or injected [3]. This substance exists in the form of four isomers,
iations.
of which only the d-LSD form has psychoactive properties [4]. LSD has been shown to
be an agonist of 5HT2a, 5HT1a and 5HT2c receptors. By affecting the 5HT2a receptor
(and indirectly by enhancing glutamatergic transmission in the prefrontal cortex and
alterations in cortico-cortical and cortico-subcortical transmission), LSD use results in a
Copyright: © 2021 by the authors.
hallucinogenic effect [5]. The effects of LSD use are also associated with its pleiotropic
Licensee MDPI, Basel, Switzerland.
effects because, in addition to its affinity for serotonin receptors, LSD also affects dopamine
This article is an open access article
receptors (D1, D2, D4) and indirectly affects glutamatergic neurotransmission and TAAR
distributed under the terms and
receptors (in animal models). LSD also affects alpha-2 adrenergic receptors to a small extent,
conditions of the Creative Commons
stimulating the sympathetic nervous system, resulting in an increase in body temperature,
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
sweating, tachycardia, increased blood pressure and muscle tension, which are the first
4.0/).
to occur after LSD ingestion [6]. Doses greater than 100 ug cause heightened sensory

Pharmaceuticals 2021, 14, 793. https://doi.org/10.3390/ph14080793 https://www.mdpi.com/journal/pharmaceuticals

Pharmaceuticals 2021, 14, 793 2 of 11

perceptions, synesthesias, pseudohallucinations, changes in time perception, feelings of

depersonalization and derealization [7]. Unlike other psychoactive substances, no physical
dependence has been observed, and low toxicity has been noted [8].
Psilocybin is one of the major psychedelic agents found in certain species of mush-
rooms around the world. Psilocybin is an agonist of 5HT2a serotonin receptors; however,
unlike LSD, it has no effect on dopamine receptors [9]. The undisputed advantage of this
tryptamine derivative is its low toxicity, minimal side effects and lack of substance depen-
dence [10]. The effects of psilocybin depend on the dose administered—at an amount of
about 20 mg taken at one time, users experience a state of altered consciousness, increased
introspection and hypnagogic experiences. Perceptual changes such as synesthesia, delu-
sions and alterations in the sense of time are also observed. The effects of the hallucinogen
are mainly associated with the activation of 5HT2a receptors in the thalamus, reducing
the activity of these areas [9,11]. In animal models, vegetative changes such as mydriasis,
tachycardia, a slight increase in blood pressure and hyperglycemia have also been observed
after ingestion of this substance. The main metabolite of psilocybin, produced by hepatic
metabolism, is psilocin, and the mean elimination time of it is about 50 min [11].
DMT, or dimethyltryptamine, is a psychedelic substance commonly found in plants
and in the organisms of some mammals, including humans. DMT is produced endoge-
nously in the pineal gland in small amounts, and its role is not yet known [12]. DMT is
an agonist of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B and 5-HT2C receptors
and a partial agonist of 5-HT5A, 5-HT6 and 5-HT7. The hallucinogenic effect is mainly
achieved by stimulating the 5-HT2A receptor and enhancing presynaptic glutamatergic
transmission in the prefrontal cortex [13]. DMT can be ingested, inhaled, injected intra-
venously or inflamed. In the first case, it must be taken together with monoamine oxidase
A inhibitors since DMT is metabolized in the first pass through the liver with the help of
this enzyme [14]. Depending on the route of ingestion, DMT causes psychedelic effects of
varying severity (from mild agitation to visual and auditory hallucinations) depending
on the metabolite content in plasma, but the subjective effects remain similar to those
associated with the use of LSD and psilocybin, which is associated with similar effects
of these substances via the 5-HT2A receptor to the central nervous system [15,16]. The
most common side effects of DMT use are vomiting and diarrhea [13]. It is estimated that
ingestion of DMT at doses used to achieve psychedelic effects (i.e., up to 100 mg) is not
toxic to mammals, and dependence is very rare [14]. Renal metabolism dominates, the
main metabolites detected in urine are 3-indoleacetic acid and 3-indoacetic acid, and the
half-life in the body ranges from a few minutes to several hours depending on the route of
administration [14].
Recently, ketamine has emerged as a new therapeutic option for drug-resistant de-
pression, which until recently was associated by psychiatrists primarily as an anesthetic
or as a component of the patient’s polytoxicomania. At the same time, research is be-
ing conducted into the use of another substance that is illegal in most countries, 3,4-
methylenedioxymethamphetamine (MDMA), popularly known as ecstasy, in the treatment
of drug-resistant post-traumatic stress disorder (PTSD). Research is well advanced, and
it is possible that MDMA will be approved as a drug by the FDA by 2022 [17]. For these
reasons, scientists worldwide are exploring other, previously known as illicit, drug sub-
stances. According to the Global Drug Survey 2020 report by an independent UK scientific
organization that studies the impact of psychoactive substance use on mental health, 8 of
the 20 most commonly used psychoactive substances in 2020 are in the psychedelics and
dissociatives group: in the past 12 months, 21.0% of respondents have used LSD, psilocybin
mushrooms were used by 16.1% of respondents and DMT by 4.8% of respondents. These
data come from over 110,000 individuals from over 25 countries, mostly in Europe [18].
By comparison, the 2019 Global Drug Survey reports that in the past 12 months, 17.5%
of respondents have used LSD, 14.8% of respondents have used psilocybin mushrooms,
and 4.2% of respondents have used DMT [19]. Equally popular is the interest in treat-
ing depression with psychedelics. On 23 June 2021, the Google search engine returned
Pharmaceuticals 2021, 14, 793 3 of 11

2,310,000 results for the query “psychedelic treatment for depression”, and the topic is
covered by well-known media outlets such as the BBC and Daily Mail [20,21]. Due to
the increasing popularity of psychedelics in society, it is important to conduct further
multidirectional research on them, including not only their use in therapy but also broadly
understood public health issues, which is why the authors decided to conduct a systematic
review of these substances in depression treatment.
The article presents a systematic review of LSD, psilocybin and DMT clinical use in
depression treatment. The authors also aimed to create a rationale for further studies on
use of psychedelics in psychiatry.

2. Material and Methods

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines were followed while preparing this review. Two authors searched the PubMed
and Cochrane Library databases independently to select those articles that would best
reflect the assumptions of the article from the introduction. Chemical agents were combined
with the terms “pharmacology”, “tolerance”, “depression”, “anxiety”, “meta-analysis” and
“treatment” to find relevant articles (title/abstract). The authors included only original
articles in English language that were related directly to LSD, psilocybin and DMT in
depression treatment. The authors did not rule out articles due to the year of publication
of the article. No other specific inclusion or exclusion criteria were used. The databases
were searched in May–June 2021. The authors obtained 3023 records from the databases.
After initial review, 2929 articles were excluded as they were review articles, editorials,
commentaries, letters to editors, or they were not related to the topic of the review. In this
way, 94 articles were obtained, of which 84 were excluded because they were studies that
were not related directly to depression. The same two authors who searched the databases
used the Effective Public Health Practice Project’s (EPHPP) Quality Assessment Tool for
Quantitative Studies (QATQS) to assess risk of bias and study quality in quantitative studies.
QATQS is a tool that allows evaluation of many different types of studies, including RCTs
and non-RCTs. The tool contains different sections, each receiving a score of 1 (strong),
2 (moderate) or 3 (weak). QATQS contains questions such as selection bias, study design,
confounders, blinding, data collection methods, withdrawals and drop-outs, intervention
integrity and analyses. The final score is based on the number of weak ratings. One weak
component results in a moderate rating, and two or more weak components result in a
weak rating. Only studies without weak components have strong ratings [22,23]. The data
extraction process focused on information about sample size, protocols of the studies and
the outcomes. The authors conducted a narrative, qualitative summary. The flow diagram
of the analysis is presented in Figure 1.
Pharmaceuticals 2021, 14, 793 4 of 11

Figure 1. Flow diagram of systematic review of LSD, psilocybin and DMT in depression treatment.

3. Results
3.1. Primary Outcome
All of the studies found had statistically significant results in lowering the intensity
of depressive symptoms. A comprehensive report of the studies and their quality was
presented in Tables 1 and 2.

Table 1. Summary of clinical studies evaluating the antidepressant effect of psilocybin (n = 6). The abbreviations are
explained in the footer.

Characteristic QATQS
Type of Sample
Authors Year of Intervention Results Conclusions Global
Study Size
Participants Rating
Use of psilocybin
Psylocybin in two combined with
Subjects with sessions in several psychotherapy may
BDI score were reduced
depression weeks interval (0.2 provide an alternative
at 6 months after
Grob and anxiety mg/kg) with 250 mg of treatment especially in
treatment, STAI-T score
et al. 2011 RCT 12 and niacin as a placebo As the conditions with 1
reduction was
[24] advanced- an efficacy measure minimal response to
observed at 1 and 3
stage BDI, STAI-S, STAI-T, conventional therapies,
months after treatment
cancer Profile of Mood States which needs to be
(POMS) were used investigated further in
RCTs
Pharmaceuticals 2021, 14, 793 5 of 11

Table 1. Cont.

Characteristic QATQS
Type of Sample
Authors Year of Intervention Results Conclusions Global
Study Size
Participants Rating
Participants who get
Psilocybin 22 or 30
the high dose of Psilocybin decreases
mg/70 kg (high-dose)
psilocybin showed depressed mood as
Subjects with or placebo 1 or 3
more significantly well as anxiety and also
depression mg/70 kg (low-dose)
clinical response and increase the quality of
or/and administered in
Griffiths symptom remission in life in patients with a
anxiety controlled conditions in
et al. 2016 RCT 51 GRID-HAM-D-17 and life-threatening cancer, 1
associated two sessions in 5 weeks
[25] in HAM-A scale the more various
with life- interval. The effects
comparing to those population of patients
threatening were measured in
patients who got should be examined to
cancer GRID-HAM-D-17 scale
low-dose therapy, those evaluate the generality
and HAM-A assessed
effects were sustained 6 of psilocybin treatment
with the SIGH-A
months after treatment
Psylocybin 10 mg and
25 mg in two sessions
with 7 days interval.
BDI scores were
Effects were assessed
reduced at 1 week, 3
Subjects with with QIDS-SR, Beck
and 6 months after Psilocybin is in need for
Non- treatment- Depression Inventory
Carhart- treatment, STAI and further investigations
RCT resistant (BDI), STAI, Snaith
Harris SHAPS scores were in double-blind RCT as
2016 (open- 12 major Hamilton Pleasure 3
et al. reduced 1 week and 3 it seems to be effective
label depressive Scale (SHAPS),
[26] months after treatment, in fighting
trial) disorder HAM-D,
HAM-D and MADRS drug-resistant MDD
(MDD) Montgomery-Asberg
scores were reduced 1
Depression Rating
week after treatment
Scale and Global
Assessment of
Functioning (GAF)
In 19 patients who
completed all
assesment time points,
QIDS-SR16 scores were
Psylocybin 10 mg and significantly reduced,
25 mg in two sessions BDI and STAI scores
with 7 days interval. were reduced at 1 week,
Follow- Subjects with
Effects were assessed 3 and 6 months after Psilocybin is a
up, treatment-
Carhart- with QIDS-SR (mainly) treatment (p < 0.001), promising tool in
Non- resistant
Harris Beck Depression SHAPS scores were fighting unresponsive
2018 RCT 20 major 3
et al. Inventory (BDI), STAI, reduced at 1 week and MDD and needs
(open- depressive
[27] Snaith Hamilton 3 months after further investigations
label disorder
Pleasure Scale treatment (p < 0.001) in double-blind RCT
trial) (MDD)
(SHAPS), HAM-D and and HAM-D and GAF
Global Assessment of scores were reduced 1
Functioning (GAF) week after treatment
(p < 0.001). No serious
side-effects were
observed during the
treatment
Pharmaceuticals 2021, 14, 793 6 of 11

Table 1. Cont.

Characteristic QATQS
Type of Sample
Authors Year of Intervention Results Conclusions Global
Study Size
Participants Rating
Psylocybin in two Significant differences
sessions (0.3 mg/kg) between study and
In combination with
Subjects with with a 7 days interval control group,
psychotherapy in
depression combined with reductions on STAI-T,
Ross life-threatening illness
and anxiety psychotherapy and STAI-S, HADS-A( 58%
et al. 2016 RCT 29 psilocybin contributes 2
in life- niacin (250 mg) as vs. 14%), HADS-T,
[28] to quick and sustained
threatening placebo. Efficacy was HADS-D and BDI (83%
anti-depressant and
cancer measured via STAI-T vs. 14%) in 1 day, 2, 6,
anxiolytic effects
and STAI-S, HADS-A, and 7 weeks after first
HADS-D, HADS-T, BDI psylocybine session
After the session with
psilocybin 71% of
patients in 1 week and
Psilocybin 1 session in 4 weeks showed
20 mg/70 kg, 2 session more than 50%
30 mg/70 kg with reduction in Sessions with
supportive GRID-HAM score, 58% psilocybin-assisted
psychotherapy. Effects of participants in therapy demonstrated
Subjects with
were evaluated in 1 week and 54% of large and sustained
Davis major
Hamilton Rating Scale participants in 4 weeks antidepressant effects
et al. 2020 RCT 24 depressive 1
for Depression met the criteria of among patients with
[29] disorder
(HAM-D) and in the remission of MDD, however still
(MDD)
Quick Inventory of depression; in QIDS-SR further
Depressive scale after psilocybin placebo-controlled
Symptomatology-Self- session the rapid, large studies are needed
Report decrease in mean
(QIDS-SR) depression score were
observed which was
remained 4 weeks after
the treatment
QATQS—Quality Assessment Tool for Quantitative Studies, RCT—randomized controlled trial, Non-RCT—non- randomized controlled
trial, MDD—major depressive disorder, MADRS—Montgomery-Åsberg Depression Rating Scale, HAM-D—Hamilton Rating Scale for
Depression, HAM-D—Hamilton Rating Scale for Anxiety, QIDS-SR Quick Inventory of Depressive Symptomatology-Self-Report, BDI—
Beck’s Depression Inventory, STAI-S—State-Trait Anxiety Inventory State, STAI-T—State-Trait Anxiety Inventory Trait, SHAPS—Snaith
Hamilton Pleasure Scale, GAF—Global Assessment of Functioning, POMS—Profile of Mood States, HADS-A—Hospital Depression
and Anxiety Scale-Anxiety, HADS-D—Hospital Depression and Anxiety Scale-Depression, HADS-T—Hospital Anxiety and Depression
Scale-Total, SIGH-A—Structured Interview Guide for the Hamilton Anxiety Scale.
Pharmaceuticals 2021, 14, 793 7 of 11

Table 2. Summary of clinical studies evaluating the antidepressant effect of DMT (n = 4). The abbreviations are explained in
the footer.

QATQS
Type of Sample Characteristic of
Authors Year Intervention Results Conclusions Global
Study Size Participants
Rating
Significant
antidepressant effects
of ayahuasca when
Patients received a This study
compared with placebo
single dose of either brings new
at all-time points.
ayahuasca or placebo. evidence
MADRS scores were
Effects in depression supporting
significantly lower in
severity were assessed the safety
the ayahuasca group
Subjects with with the and
Palhano- compared with placebo
treatment- Montgomery-Åsberg therapeutic
Fontes at D1 and D2 and at D7.
2019 RCT 29 resistant major Depression Rating value of 1
et al. Response rates were
depressive Scale (MADRS) and ayahuasca,
[30] high for both groups at
disorder (MDD) the Hamilton dosed within
D1 and D2, and
Depression Rating an
significantly higher in
scale at baseline, and at appropriate
the ayahuasca group at
1 (D1), 2 (D2), and 7 setting, to
D7 (64% vs. 27%).
(D7) days help treat
Remission rate showed
after dosing depression
a trend toward
significance at D7
(36% vs. 7%)
Patients received
120–200 mL of
ayahuasca. Effects in
These results
depression severity
suggest that
were assessed with
ayahuasca
measured on the Statistically significant
has
Non- Hamilton Rating Scale reductions of up to 82%
Subjects with fast-acting
Osório RCT for Depression in depressive scores
current anxiolytic
et al. 2015 (open- 6 (HAM-D), the were observed between 3
depressive and antide-
[31] label Montgomery-Åsberg baseline and 1, 7, and
episode pressant
trial) Depression Rating 21 days after ayahuasca
effects in
Scale (MADRS), and administration
patients with
the
a depressive
Anxious-Depression
disorder
subscale of the Brief
Psychiatric Rating Scale
(BPRS)
Pharmaceuticals 2021, 14, 793 8 of 11

Table 2. Cont.

QATQS
Type of Sample Characteristic of
Authors Year Intervention Results Conclusions Global
Study Size Participants
Rating
Patients receive Results
ayahuasca (2.2 mL/kg) Increased suggest that
and were evaluated psychoactivity ayahuasca
with the Hamilton (Clinician may have
Rating Scale for Administered fast-acting
Depression, the Dissociative States and
Montgomery-Åsberg Scale) and significant sustained an-
Non-
Subjects with Depression Rating score decreases in tidepressive
Sanches RCT
recurrent Scale, the Brief depression-related properties.
et al. 2016 (open- 17 3
depression Psychiatric Rating scales (Hamilton These results
[32] label
episode Scale, the Young Mania Rating Scale for should be
trial)
Rating Scale, and the Depression, replicated in
Clinician Administered Montgomery-Åsberg randomized,
Dissociative States Depression Rating double-
Scale during acute Scale, Brief Psychiatric blind,
ayahuasca effects and 1, Rating Scale) from placebo-
7, 14, and 21 days after 80 min to day 21 controlled
drug intake trial.
Ayahuasca
could
possibly lead
Among individuals to rapid and
with suicidality at sustained
baseline (n = 15), there reductions in
were significant acute suicidality
Patient received single
(i.e., 40, 80, 140, and among
Non- dose of ayahuasca and
180 min after individuals
Zeifman RCT Subjects with were evaulated with
administration) and with MDD
et al. 2020 (open- 17 major depressive The 3
post-acute (1, 7, 14, and Random-
[33] label disorder (MDD) Montgomery-Åsberg
21 days after ized,
trial) Depression Rating
administration) double-blind
Scale
decreases in suicidality studies with
following larger
administration of sample sizes
ayahuasca are needed
to confirm
this early
finding
QATQS—Quality Assessment Tool for Quantitative Studies, RCT—randomized controlled trial, Non-RCT—non- randomized controlled
trial, MDD—major depressive disorder, BPRS—Brief Psychiatric Rating Scale, MADRS—Montgomery-Åsberg Depression Rating Scale,
HAM-D—Hamilton Rating Scale for Depression.

3.2. LSD
No clinical studies of LSD use in depression were found.

3.3. Psylocybin
Six studies were included in the analysis. The total number of participants included
in the psilocybin studies ranged from 12 to 51, both male and female. Subjects were
adults. In three studies the sample was composed of subjects with major depressive
disorder [26,27,29], and in the other three studies the sample was composed of subjects with
depression and anxiety in the course of life-threatening cancer [24,25,28]. A comprehensive
report of findings is presented in Table 1.

3.4. DMT
Four studies were included in the analysis. The total number of participants included
in the psilocybin studies ranged from 6 to 29, both male and female. Subjects were adults.
In two studies the sample was composed of subjects with major depressive disorder [30,33],
and in the other two studies the sample was composed of subjects with recurrent depression
episodes [31,32]. A comprehensive report of findings is presented in Table 1.
Pharmaceuticals 2021, 14, 793 9 of 11

4. Discussion
The use of psychedelics in depression treatment could be a safe treatment option, but
further studies are necessary as there are some issues that researchers face.
The authors did not find any studies on LSD use in depression treatment even though
the three substances that are the subject of this review share very similar mechanisms of
action, which justifies conducting such studies.
Three out of six of the psilocybin studies included in this review were rated strong
according to the Quality Assessment Tool for Quantitative Studies. Considering this and
the fact that one other RCT study was rated moderate, psilocybin is the best documented
substance in depression treatment from the three substances that are the subjects of this
review, which makes psilocybin in a medical setting a very promising treatment option for
patients with depression.
Only one out of four DMT studies included in this review was rated high according
to the Quality Assessment Tool for Quantitative Studies. Three out of four of the DMT
studies included were non-RCT studies, which do not allow to draw final conclusions on
efficiency in depression treatment. No clinical studies of DMT use alone in depression
treatment were found, as all of the included studies dosed ayahuasca, and it should be
remembered that ayahuasca is administered with monoamine oxidase inhibitors, which
may have an effect on mood themselves. It should also be remembered that ayahuasca
contains other alkaloids, such as harmine or harmaline, and since it is a decoction of the
plants themselves, it is difficult to estimate the dose of alkaloids consumed [34,35].
The use of psychedelic substances is not without risks. The pharmacology and mech-
anism of action of each substance is fairly well understood, and while LSD, psilocybin
and DMT have relatively low health and life risks somatically, the risk of psychiatric
complications must be considered. In addition to psychosis, another clinically significant
complication that can occur after even a single ingestion of a psychedelic substance is
Hallucinogen Persisting Perception Disorder or HPPD for short, classified as F16 in ICD-10
and 292.89 in DSM-V. This disorder manifests as chronic perceptual changes that can
interfere with daily functioning and reduce quality of life and satisfaction. Duration is
an individual matter, usually transient symptoms lasting from a few minutes to several
months, although in extreme cases symptoms can last throughout life [36]. There are two
types of HPPD: type 1, in which there is a brief recurrence of psychedelic effects in the form
of a “flashback”, occurs in 1:20 people, and type 2, which occurs less frequently, in 1:50,000
and in which symptoms are chronic. Since the etiology and scientifically proven treatments
remain unknown, HPPD should be considered a significant risk for patients undergoing
treatment with psychedelics, according to the authors [37]. None of the studies included in
the systematic review assessed occurrence of HPPD after clinical trials; therefore, further
studies require assessing the psychological risks of psychedelics consumption.

5. Conclusions
By analyzing qualified studies, it can be concluded that psilocybin and DMT could
be efficient and useful in depression treatment, but further studies and observations on
bigger groups of patients are still required to assess safety. Considering social interest in
psychedelics, studies for LSD use in depression treatment are urgent.

Author Contributions: G.W. conceptualized and designed the review; G.W. and I.S. conducted the
literature search and wrote the draft. R.P. revised the draft. All authors (G.W., I.S., M.P., P.G., R.P.)
participated in the screening and review of studies. All authors have read and agreed to the published
version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data sharing not applicable.
Pharmaceuticals 2021, 14, 793 10 of 11

Acknowledgments: The authors would like to thank Mieszko Wi˛eckiewicz from Wrocław Medical
University for his support in conducting this systematic review.
Conflicts of Interest: The authors declare no conflict of interest.

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