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Being no one, being One: The role of ego-dissolution and connectedness in the therapeutic effects of psychedelic experience

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Background and aims Despite promising findings indicating the therapeutic potential of psychedelic experience across a variety of domains, the mechanisms and factors affecting its efficacy remain unclear. The present paper explores this by focusing on two psychedelic states which have been suggested as therapeutically significant in past literature: ego-dissolution and connectedness. The aim of the study is to investigate the impact of ego-dissolution and connectedness on the therapeutic effects of the psychedelic experience. Methods The investigation was carried out as a mixed methods systematic review, with the data from four databases analysed thematically and results presented through narrative synthesis. Results The analysis and synthesis of findings from 15 unique studies ( n = 2,182) indicated that both ego-dissolution and connectedness are associated with a higher chance of improvement following a psychedelic experience. However, there seem to be differences in the way the two experiences affect individuals psychologically. Ego-dissolution appears to trigger psychological change but does not typically exceed the psychedelic experience in its duration, while connectedness can be more sustained and is associated with several positive, potentially therapeutic feelings. Conclusions Moreover, the findings of this review have implications for further theory-building about the mechanisms which enable therapeutic effects in psychedelic experience. This in turn might lead to improved models for psychedelic therapy practice. Emphasis on ego-dissolution during the preparation phase and on connectedness during integration is one suggestion presented here, alongside overarching implications for the mental health debate and general practice.
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Being no one, being One: The role of ego-
dissolution and connectedness in the therapeutic
effects of psychedelic experience
ADA KAŁUŻNA
1
p, MARCO SCHLOSSER
1
,
EMILY GULLIKSEN CRASTE
2
, JACK STROUD
3
and
JAMES COOKE
4
1
Division of Psychiatry, UCL, United Kingdom
2
Department of Arts and Sciences, UCL, United Kingdom
3
Division of Psychology and Language Sciences, UCL, United Kingdom
4
Innerspace Institute, Portugal
Received: June 6, 2022 Revised manuscript received: August 19, 2022 Accepted: August 21, 2022
ABSTRACT
Background and aims: Despite promising findings indicating the therapeutic potential of psychedelic
experience across a variety of domains, the mechanisms and factors affecting its efficacy remain unclear.
The present paper explores this by focusing on two psychedelic states which have been suggested as
therapeutically significant in past literature: ego-dissolution and connectedness. The aim of the study is
to investigate the impact of ego-dissolution and connectedness on the therapeutic effects of the psy-
chedelic experience. Methods: The investigation was carried out as a mixed methods systematic review,
with the data from four databases analysed thematically and results presented through narrative syn-
thesis. Results: The analysis and synthesis of findings from 15 unique studies (n52,182) indicated that
both ego-dissolution and connectedness are associated with a higher chance of improvement following a
psychedelic experience. However, there seem to be differences in the way the two experiences affect
individuals psychologically. Ego-dissolution appears to trigger psychological change but does not
typically exceed the psychedelic experience in its duration, while connectedness can be more sustained
and is associated with several positive, potentially therapeutic feelings. Conclusions: Moreover, the
findings of this review have implications for further theory-building about the mechanisms which
enable therapeutic effects in psychedelic experience. This in turn might lead to improved models for
psychedelic therapy practice. Emphasis on ego-dissolution during the preparation phase and on
connectedness during integration is one suggestion presented here, alongside overarching implications
for the mental health debate and general practice.
KEYWORDS
self, oneness, psychedelic therapy, systematic review, mixed methods
INTRODUCTION
Serotonin 2A receptor (5-HT
2A
R) agonists, also known as classic psychedelics (Vollenweider
& Kometer, 2010), have been utilized by humans for millennia. Classic psychedelics can be
divided into the sub-classes of tryptamines and phenethylamines with substances like psy-
locibin, dimethyltryptamine, D-lysergic acid diethylamide (LSD) and ibogaine belonging to
the former category and mescaline to the latter (Forstmann & Sagioglou, 2017). Both kinds of
psychoactive substances were found to have been used by traditional cultures around the
world, as evidenced by the consumption of mescaline-containing San Pedro cacti in the
Andes (Sharon, 2000) and Psilocybe mushrooms use in Paleolithic Spain (Akers et al., 2011).
Journal of Psychedelic
Studies
DOI:
10.1556/2054.2022.00199
© 2022 The Author(s)
SYSTEMATIC REVIEW,
META-ANALYSIS
pCorresponding author.
E-mail: ada.kaluzna@outlook.com
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However, it was only upon the first LSD synthesis by
Albert Hofmann that widescale scientific investigation into
the therapeutic use of psychedelic substances began (Cos-
tandi, 2014;Garcia-Romeu & Richards, 2018). The progress
in the eld was slowed for several decades by legal re-
strictions due to the moral panicaround psychedelic
substances (Goode, 2008) and their associations with rec-
reational use within anti-war movements (Costandi, 2014).
After years of careful revival of the research area, psychedelic
therapy is now returning to mainstream science (Aday,
Davoli, & Bloesch, 2019).
Psychedelic therapy is usually a tripartite process of
preparation, psychedelic session(s), and integration (John-
son et al., 2008). During a psychedelic therapy session, the
appropriate dose of a psychedelic for the desired effect is
administered. In order to evoke intense and profound psy-
chological experiences researchers usually choose to
administer higher doses of the psychedelic substance (Grif-
ths et al., 2006;Pahnke, 1963), e.g. 25 mg of psilocybin
(Carhart-Harris et al., 2017). This takes place in a safe and
supervised environment (Garcia-Romeu & Richards, 2018).
The evidence for psychedelic therapysefcacy has been
growing rapidly over the last decade. It has been indicated as
an effective tool for reducing depression, anxiety, and
anhedonia (Carhart-Harris et al., 2016,2017) in addition to
nicotine (Johnson et al., 2014,2017), alcohol (Bogenschutz
et al., 2015,2018) and opioid dependence (Brown & Alper,
2018), as well as distress related to terminal illness diagnosis
(Grifths et al., 2016;Grob et al., 2011). It has also been
recognized for its potential to improve psychological well-
being in general (MacLean et al., 2011), a phenomenon
referred to as the betterment of well people(phrase coined
by Bob Jesse and quoted inter alia in Pollan, 2018).
While these initial findings suggest psychedelic experi-
ences could have therapeutic potential for many individuals,
understanding of how the therapeutic effects are achieved
remains limited. Dose and chemical composition being
controlled for, the therapeutic outcome still varies greatly
between individuals, depending on the contextual factors
before, during and after the psychedelic experience (Carhart-
Harris et al., 2018). The factors affecting the individual
before and during the session are referred to as the set and
setting(Leary et al., 1963) and include the psychological
state, attitude and expectations of the person ingesting a
psychedelic substance (set) as well as the physical and cul-
tural context (setting) in which the experience takes place.
Post-session factors include personal assessment of the
experience, willingness and ability to change, and support
received (Watts & Luoma, 2020). They inuence the nal
stage of psychedelic therapy called integration where a
person assimilates new insights and perspectives and pro-
cesses any challenging experiences which might have arisen
during the session.
Even when these factors are optimized according to the
current best research, however, the experiential content
itself plays a large role in determining the therapeutic
outcome by producing insights and perspectives for subsequent
integration (Klavetter & Mogar, 1967;Maji
cetal.,2015).
Among the types of subjective phenomena that a psyche-
delic might induce, one which has garnered attention since
early LSD research (Leary et al., 1964) and is still studied
presently (Millière, 2017) is ego-dissolution. It is a state
characterized by reduction of self-referential awareness
which can occur in various altered states of consciousness,
including those caused by ingestion of a psychedelic sub-
stance (Nour et al., 2016). Pioneering psychedelic
researcher Timothy Leary considered the ability to enter
ego-dissolution, without attachment to self, central to a
positive psychedelic experience (Leary et al., 1964). A
failuretodosocanresultindread of ego-dissolution,or
anxious ego-dissolution, i.e. negatively experienced deper-
sonalization (Studerus et al., 2010). During the more recent
wave of psychedelic research, ego-dissolution was found to
be occasioned by ingestion of psychedelics such as psilo-
cybin (Grifths et al., 2011), LSD (Goodman, 2002), or
ayahuasca, a brew containing N,N-Dimethyltryptamine
(DMT; Trichter et al., 2009).
A phenomenon closely related to ego-dissolution is the
sense of boundless unity or connection with ones sur-
roundings. It has been referred to by different names from
oceanic boundlessness (OBN; Dittrich, 1998) to unitive
experience (Carhart-Harris et al., 2017) to oneness (Hayes
et al., 2020). Use of the term connectednessto refer to this
phenomenon, as proposed by Watts et al. (2017), seems
particularly useful for clinically-oriented psychedelic
research as it stands in opposition to disconnectedness, a
detrimental state commonly reported by depressed patients
before undergoing psychedelic therapy (Watts et al., 2017).
Secondly, the related Watts Connectedness Scale (Watts
et al., 2022) distinguishes between three distinct kinds of
connectedness: with self, with others, and with the world. All
three types are believed to be benecial to an individuals
mental wellbeing and health. This differentiation allows for
ner-grained analysis into the potential benets of each type,
which would not be possible using concepts such as OBN or
oneness.
The renewed interest in psychedelic research has led to a
sufficient number of papers on the effects of psychedelic
states being published in the past several years to warrant a
review of the field. This has not been done to date for either
ego-dissolution or connectedness. Thus, the present sys-
tematic review has been carried out to fill this research gap
and bring more understanding regarding the specific factors
which make the psychedelic experience therapeutic. This
could aid creation of improved psychedelic therapy models
as well as the introduction of connectedness and ego-
dissolution into the wider mental health debate. In terms of
the current psychedelic debate, the present piece of research
is relevant to the question of the therapeutic importance of
psychedelic-induced subjective effects (Olson, 2021;Yaden
& Grifths, 2021). The review will contribute to the dis-
cussion by examining the therapeutic consequence of psy-
chedelic phenomenology (through an investigation of two of
its elements), which could complement purely biochemical
considerations of the mechanisms of action at play in psy-
chedelic therapy.
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The primary research aim of the paper is to investigate
the extent to which ego-dissolution and connectedness are
predictive of the therapeutic effects of psychedelic experi-
ence. Additionally, the review analyses whether ego-disso-
lution and connectedness are associated with each other and
if their therapeutic efficacy varies between psychological
outcome domains. Only two aspects of connectednessas
proposed by Watts, i.e., with others and the world/universe,
are synonymous with oceanic boundlessnessand
oneness. The third category, connectedness with (own)
self, does not overlap with these terms sufciently as for
instance oceanic boundlessness can be described as posi-
tively experienced depersonalization(Studerus et al., 2010)
rather than reconnection with the deeper aspectsof the
individual self (Watts et al., 2022). Therefore connectedness
with selfis not investigated in this study. Moreover, the
review focuses on psychedelic experiences induced by
classic, serotonergic psychedelics (i.e., 5-HT2A-receptor
agonists (Pierce & Peroutka, 1989)), due to different
mechanisms of action and kinds of experience induced by
non-classic psychedelics such as MDMA or ketamine
(Carhart-Harris et al., 2014;Glennon et al., 1984).
It was hypothesized that ego-dissolution and connect-
edness would positively correlate with mental health and
wellbeing improvement across different outcome domains.
The secondary hypothesis was that ego-dissolution and
connectedness would be positively correlated with each
other as well.
METHODS
Study protocol
In line with PRISMA recommendations (Moher et al., 2009),
this review was pre-registered and its protocol was published
with PROSPERO in June 2021 [CRD42021256173].
Eligibility criteria
The reviews inclusion and exclusion criteria were as follows:
1. Population: Participants were eligible for inclusion if they
underwent a psychedelic experience induced by a classic
psychedelic substance. They would be excluded if they
underwent a psychedelic experience induced by either a
non-classic psychedelic or means other than adminis-
tration of a psychedelic substance (e.g., holotropic
breathing). The psychedelic substances which were
expressly searched for are listed in the search terms
(Appendix).
2. Exposure: A portion of participants needed to have
experienced ego-dissolution and/or connectedness while
under the inuence of a psychedelic substance for a study
to be included in the review. This would need to have
been reported either via a quantitative tool or qualitative
recollection. Studies which investigated connectedness as
an outcome, particularly social connectednessunder-
stood as the quality and number of interpersonal
relationships were excluded from the review as this was
incongruent with the denition employed here.
3. Comparator: Participantswellbeing or mental health at
baseline or retrospectively reported as prior to the psy-
chedelic experience was considered a comparator in this
review. Alternatively, or additionally, the mental health
or wellbeing change was compared between exposed and
non-exposed individuals.
4. Outcome: Mental health or psychological wellbeing after
a psychedelic experience had to be reported for a study to
be included in the review.
5. Study design: Included studies could be quantitative or
qualitative in nature. Both interventions and observa-
tional studies were considered, as well as dissertations if
they were based on original research which would satisfy
all the above inclusion criteria. Reviews and meta-ana-
lyses were not eligible for the review.
There were no date limits and so the publication dates
could range from the beginning of a database collection to
July 2021 when the search was re-run prior to final analysis.
The review was limited to human samples.
Databases
The databases searched included: MEDLINE, PsycINFO,
AMED, and Web of Science. Grey literature was not
searched. Journals were not searched manually due to time
and resource limitations.
Search terms
The search terms can be found in Appendix.
Study selection
The review management platform Covidence was used for
deduplication, title and abstract, and full-text screening.
Four reviewers screened titles and abstracts independently
and any emergent conflicts were resolved by a third party.
The subsequent full-text screening was carried out by one
reviewer only, with explicitly stated reasons for all exclu-
sions, as reported in Fig. 1. The same process was repeated
when the search was re-run prior to nal analysis.
Data collection
The following data was extracted from the included studies
(where available):
1. Study characteristics: authorship, year and country, study
design, psychedelic substance(s) used, the amount
administered, the context in which the psychedelic
experience took place, means of investigating ego-disso-
lution and/or connectedness in participants, mental
health and/or wellbeing outcome measures;
2. Participant characteristics: demographics (ethnicity
and/or nationality, gender, age), sample size, amount of
experience with psychedelic substances, any diagnosed
mental health conditions, self-reported mental health or
psychological wellbeing problems;
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3. Results: qualitative and quantitative data (psychometric
measures, ratings of the experience, interview transcripts,
written accounts).
Risk of bias appraisal
The studies were assessed for trustworthiness, relevance, and
usefulness using the Mixed Methods Appraisal Tool (Hong
et al., 2018). All studies were assessed against two opening
questions: (1) Are there clear research questions? (2) Do the
collected data allow to address the research questions? If the
study was assessed positively against these initial criteria, it
was then evaluated according to further ve questions
appropriate to its study design (qualitative, quantitative
randomized controlled trials, quantitative non-randomized,
quantitative descriptive, and mixed methods).
Data synthesis
At the stage of planning of the review, a preliminary search
was carried out to assess which methodology should be
decided upon. The relevant studies found at the time
differed greatly between each other in terms of methodology
employed. Focusing on only one study design could limit the
number of studies retrieved in the actual database search. It
was, therefore, decided that the review would include
methodologically heterogeneous studies. For this reason, the
data gathered in the review was planned to be synthesized
through narrative synthesis.
Extracted quantitative data was transformed into quali-
tative form, following which all data was analysed themati-
cally (following ESRCs Guidance on Conducting Narrative
Synthesis, Popay et al., 2006). The transformation involved
ridding the extracted data of scores, ratings and similar
numerical data and substituting those with relevant
descriptive terms. This could result in phrases such as
positive correlation between oceanic self-boundlessness and
mean positive attitude changesor lack of correlation be-
tween ego-dissolution and DASS ratings at follow-up.
During the transformation stage effect sizes were considered
to the extent that any signicant difference in effect size
would also be transformed into qualitative form. This could
take a form of contrasting results between outcome domains
with phrases like particularly signicant,very signicant
and signicant. Those differences were accordingly re-
ported in the results section. Effect sizes were not compared
across studies. Following the textual description of studies,
the vote-counting method (Popay et al., 2006) was imple-
mented as the next step of preliminary synthesis.
The analysis was inductive and had as its goal systematic
identification of the most important, recurrent themes in
data extracted from the reviewed studies (Popay et al., 2006).
Relationships between studies were explored using recip-
rocal translation, a method of synthesizing qualitative data
from multiple studies through examination of their simi-
larities to nd overarching categories of meaning (Noblit &
Hare, 1988). When translation is implemented, the
Papers retrieved
OVID (MEDLINE, PsycINFO, AMED): 106
Web of Science: 123
+ 1 paper added from manual search
Total number of papers after deduplication:
163
Papers excluded after title
and abstract screening: 132
Papers included for full-text review: 31
Papers eligible for the review: 15
Papers excluded: 16
Reasons:
Neither ego-dissolution nor
connectedness correlated
with mental health or
wellbeing outcomes: 12
Duplicate: 2
Same data explored in
another study already
included and more suitable
Fig. 1. PRISMA owchart
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interpretation of all studiesresults builds upon these
emergent themes (Popay et al., 2006). The studieshetero-
geneity was investigated through an analysis of the re-
lationships between the studiesoutcomes and psychedelic
substances studied, aspects of methodological diversity
(especially the physical context of the psychedelic experi-
ence) and study populations (Ryan & Cochrane, 2013).
Lastly, the overall weight of evidence was assessed
through critical evaluation of the methodological quality
and trustworthiness of the included studies (Popay et al.,
2006). This assessment was informed by all the previous
steps of data synthesis, particularly the quality assessment.
Additionally, the applicability of the results to different
populations and cultural contexts was evaluated by
comparing the effects of ego-dissolution and connectedness
reported in different study populations. Risk of bias within
the selected papers was considered at this stage, too. A
subgroup analysis of the therapeutic effects of ego-disso-
lution vs connectedness was carried out as planned prior to
the commencement of the review. Moreover, it became
apparent at the data extraction stage that a subgroup
analysis of mental health outcomes could alike be of value,
and thus its results form part of the narrative synthesis
as well.
RESULTS
Study selection
The systematic literature search of four databases to July
2021 resulted in a total of 229 title-abstracts which were
then deduplicated resulting in 162 unique papers (as pre-
sented in Fig. 1). Additionally, one paper on ayahuasca-
assisted therapy for addiction (Thomas et al., 2013)was
added manually bringing the total of papers to 163.
Following title and abstract screening, 132 papers were
excluded and 31 were considered in full-text screening.
After the full-text examination, 15 papers were included as
eligible for the review. Among the excluded papers was
Thomas et al. (2013), as one of the studies retrieved
through the systematic search Argento et al. (2019) was
found to be exploring the same data but in a manner more
suitable for the review, i.e., with more information on the
relationship between participantspsychedelic experiences
and their wellbeing post-session, revealed in interviews that
this study analysed.
Study characteristics
Extracted characteristics of the 15 eligible studies are
presented in Table 1 (study design). The 15 included
studies were all published within the last 5 years (20172021),
with majority of them being carried out in the United
States, the United Kingdom, or the Netherlands (six, four
and four, respectively), although many studies were con-
ducted across several countries. There were ve qualitative
studies, eight quantitative, and two with mixed study
design.
Participant characteristics
Detailed participant characteristics are presented in Table 2
(study population). Overall, the sample sizes ranged from
9 to 654, bringing the total to 2,182 participants. Their na-
tionality information was available in seven studies (n52,048),
wherein 25% were European (including at least 10% from
the United Kingdom), 52% from North America (including
at least 36% from the United States), 1% from South
America, 1% from Australia, 0.7% from Africa (including
at least 0.6% from South Africa), and 0.5% from Asia. The
remaining 18% of participants were categorized as coming
from othercountries.
Ethnicity was provided by six papers (n5525), in which
81% were White. The study with the largest sample
among them categorized all non-White ethnicities together
(n577). The other ve studies (n573) classied non-
White ethnicities separately, among which 10% were Black,
4% were Asian or Pacic Islander, 3% were Hispanic, and
3% were multiracial. Additionally, one study recruited
members of an indigenous community from Coast Salish in
Canada (n511).
While all studies provided sex or gender data, within one
study (Amada et al., 2020) only 276 out of 418 survey re-
spondents provided researchers with their demographic
data. Among the participants from all studies who disclosed
their gender, around 28% were female and 70% were male.
The remaining 2% identied as otheror transgender/
gender-uid. All the samples besides Uthaug et al. (2018)
had more males than females.
Risk of bias and results of individual studies
The MMAT user guide discourages presenting the risk of
bias numerically as a total score (Hong et al., 2018), there-
fore a short descriptive evaluation of the studiesquality is
presented alongside the summaries of their results in
Table 3. One common nding was moderately high attrition
rate in surveys and observational studies which might have
exaggerated some effects or obscured other relationships.
Moreover, some samples were very specic due to inclusion
criteria based on clinical diagnoses, or antidepressant use
history. The effects of SSRI use on responsiveness to sero-
tonergic psychedelic substances were generally not consid-
ered. Lastly, the majority of the studiesndings would be
considered not applicable to other cultural contexts due to
their homogeneity.
Narrative synthesis
Among the included 15 studies, more of them investigated
connectedness (11) than ego-dissolution (10). However,
many of them (6) researched both experiences. Despite the
significant methodological diversity of the studies, it was
possible to group them in several ways during the analysis
process.
Study design. Psilocybin was the most frequently researched
psychedelic substance across the studies, with seven focusing
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Table 1. Study characteristics: design
Author, year Country Study type Design Substance Amount Context
Means of ED/C
investigation
Means of MH/
wellbeing
investigation
Uthaug et al.
(2020)
Czechia Quantitative Observational with
psychometric tools.
Synthetic 5-MeO-
DMT
Various (14
inhalations)
[Appendix:]
Days-long
preparation.
Indoors,
individual
experience with a
facilitator.
EDI & 5D-ASC MH: DASS-21,
SWL scale;
Mindfulness:
FFMQ-39.
Nielson
et al.
(2018)
US Mixed Interview and
psychometric tools.
Psilocybin 2 sessions:
0.3 mg kg
1
rst,
0.4 or 0.3 mg kg
1
second.
Preparation and
integration with a
psychotherapist.
MEQ & ASC Reduction in
heavy drinking
days and
interviews.
Amada et al.
(2020)
US Mixed (mostly
qualitative)
Survey All psychedelics N/A Various Open-ended
questions on
psychedelic
experience.
Open-ended
questions, scores
on the impact and
quality of the
psychedelic
experience.
Watts et al.
(2017)
UK Qualitative Semi-structured
interview with thematic
analysis, guided by 3
main questions.
Psilocybin 2 sessions: 10 mg
& 25 mg.
Sessions in a
relaxed
environment with
music and 2
guides. Integration
sessions post-
treatment.
Open-ended
questions on
psychedelic
experience.
Open-ended
questions
Roseman
et al.
(2018)
UK Quantitative Experimental within-
subject design
Psilocybin 2 sessions: 10 mg
& 25 mg.
Pre-session
preparation.
Music and support
of a guide during
the sessions.
Integration with a
psychotherapist.
ASC, PQ QIDS-SR16, BDI,
HAM-D, DAS,
STAI, LOT-R,
SHAPS. 50%
from baseline
considered a
meaningful
reduction in
depression.
Uthaug et al.
(2019)
The Netherlands,
Czechia, Spain
Quantitative Observational with
psychometric tools
5-MeO-DMT
from the Bufo
alvarius toad
Various Czechia & the
Netherlands:
outside in nature;
Spain: inside (tipi/
rented house).
EDI & 5D-ASC SWL, DASS-21,
FFMQ-15, BSI-18
(continued)
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Table 1. Continued
Author, year Country Study type Design Substance Amount Context
Means of ED/C
investigation
Means of MH/
wellbeing
investigation
Kettner et al.
(2019)
UK Quantitative Observational with
psychometric tools
Psilocybin, LSD/
1P-LSD,
ayahuasca, DMT/
5-MeO-DMT,
Salvia divinorum,
mescaline,
ibogaine)
Various Various, assessed
for nature
involvement.
MEQ, EDI, CEQ. the WEMWBS,
the short form of
NR-6
Argento
et al.
(2019)
Canada Qualitative Semi-structured
interview with thematic
analysis, guided by 3
main questions
Ayahuasca 2 ceremonies,
small glasses
(50100 mL).
(1 participant took
part only once.)
A ceremonial
ayahuasca retreat,
intended to aid
working with
addiction and
stress.
Open-ended
questions
Open-ended
questions
van
Mulukom
et al.
(2020)
UK & the
Netherlands
Quantitative Survey (descriptive
account and several
scales)
Classic
psychedelics
(psilocybin, LSD,
DMT, ayahuasca,
mescaline, peyote
or 5-MeO-DMT)
Various Various AWE-S, EDI IOSS, ECQ,
NPI13, Brief
Sensation Seeking
Scale
Uthaug et al.
(2018)
The Netherlands
& Colombia
Quantitative Observational with
psychometric tools
Ayahuasca 200 ml of
ayahuasca of
variable DMT,
harmine &
harmaline content
Ceremonial EDI DASS-21, SWLS,
Five Facets of
Mindfulness
Belser et al.
(2017)
US Qualitative Semi-structured
interview with IPA
Psilocybin Within-subject
placebo-controlled
(2 sessions):
psilocybin
(0.3 mg kg
1
)or
placebo of niacin
(250 mg).
Laboratory
(clinical trial at
NYU)
Open-ended
questions
Open-ended
questions
Smigielski
et al.
(2019)
Switzerland Quantitative Experimental, double-
blind, placebo-controlled
Psilocybin 315 μgkg
1
5-day mindfulness
retreat
5D-ASC & M-
scale 6h after
FMI, TMS,
MEDEQ. Long-
term outcomes:
LCI-R at 4-month
follow-up.
(continued)
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Table 1. Continued
Author, year Country Study type Design Substance Amount Context
Means of ED/C
investigation
Means of MH/
wellbeing
investigation
Noorani
et al.
(2018)
US Qualitative Semi-structured
interview with thematic
analysis
Psilocybin 1st session:
0.29 mg kg
1
2nd & 3rd
sessions: 0.43 mg
kg
1
.
Smoking cessation
pilot study
between 2009 and
2015 at Johns
Hopkins.
Open-ended
questions
Open-ended
questions
Agin-Liebes
et al.
(2021a)
US Qualitative
(enhanced with
quantitative data
from the original
study by
Anderson et al.
2020)
Microphenomenological
interviews (IPA)
Psilocybin [Anderson et al.
2020 (parent
study):]
0.30.36 mg kg
1
Psilocybin-assisted
group therapy for
older long-term
AIDS survivor
men.
Open-ended
questions
Open-ended
questions (and
PCL-5 & ICG-R
from previous
study)
Agin-Liebes
et al.
(2021b)
US (based on a
larger
epidemiological
study carried out
in the
Netherlands)
Quantitative Survey (retrospective) Mescaline Various Various
(naturalistic use)
MEQ, EDI, CEQ PEQ þopen-
ended questions
on mental health
Abbreviations: 5D-ASC 5-Dimensional Altered States of Consciousness Rating Scale; 5-MeO-DMT 5-methoxy-N,N-dimethyltryptamine; AIDS acquired immunodeciency syndrome;
ASC Altered States of Consciousness (questionnaire); AWE-S Awe Experience Scale; BDI Beck Depression Inventory; BSI-18 Brief Symptom Inventory-18; CEQ Challenging
Experiences Questionnaire; DAS Dysfunctional Attitudes Scale; DASS-21 Depression Anxiety Stress Scale-21; DMT N,N-dimethyltryptamine; ECQ Existential Concerns Questionnaire;
ED/C ego-dissolution or connectedness; EDI Ego Dissolution Inventory; FFMQ-39 Five Facet Mindfulness Questionnaire; FMI Freiburg Mindfulness Inventory; HAM-D Hamilton
Depression Scale; ICG-R Inventory of Complicated Grief; IOSS Inclusion of Other in the Self Scale; LCI-R Life Changes Inventory-Revised; LOT-R Life Orientation Test Revisited; LSD
lysergic acid diethylamide; MEDEQ Meditation Depth Questionnaire; MEQ Mystical Experience Questionnaire; MH mental health; NPI13 Narcissistic Personality Inventory; NR-6
Nature-Relatedness Scale; PCL-5 Posttraumatic Stress Disorder Checklist; PEQ Persisting Effects Questionnaire; PI Psychological Insight Questionnaire; PQ Psychedelic Questionnaire;
QIDS-SR16 Quick Inventory of Depressive Symptomatology; SHAPS Snaith-Hamilton Pleasure Scale; STAI Spielbergers Trait Anxiety; SWL Satisfaction with Life Scale; TMS Toronto
Mindfulness Scale; WEMWBS Warwick-Edinburgh Mental Well-being Scale.
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Table 2. Study characteristics: population information
Author, date
Demographics (nationality/
ethnicity; female to male ratio;
age mean (range)) Psychedelic experience Sample size Diagnoses
Self-reported psychological
issues
Uthaug et al. (2020) Europe (8), North America (3);
3:8; 33.
All had previous experience
(9 no experience with 5-MeO-
DMT, 1 used 33, 1 used 53)
11 [Appendix:] None. Many
conditions screened out based
on self-report.
Depression: 4; depression &
anxiety: 1, depression &
anxiety & PTSD: 1; other:1.
Nielson et al. (2018) N/A, 4:6, 40.1 (2556). Exclusion if: used psychedelics
>103or at all in the past 30
days.
10 All met DSM-IV-TR criteria
for alcohol dependence.
Excluded if: family history of
schizophrenia, bipolar
disorder, suicide; cocaine,
psychostimulant, or opioid
dependence.
Amada et al. (2020) US (67%), Canada (6%), UK
(4%), other parts of Europe
(13%), South Africa (3%),
Australia (2%), Asia (2%),
Central or South America (2%).
Only 276 provided
demographic information:
113:163, 38.6 (1780).
At least 1 past experience
required to participate in the
survey.
418 N/A N/A
Watts et al. (2017) 15 White, 3 Black, 1 Asian, and
1 Hispanic; 6:13; (3064).
5 had experience, 4 in a
recreational context in early
adulthood.
20 Inclusion for: score of 17þon
the HAM-D and no response
to at least 2 different ADs.
Exclusion if: personal or
family history of psychosis.
N/A
Roseman et al.
(2018)
[Carhart-Harris et al. 2017:]
15 White, 3 Black, 1 Asian,
1 Hispanic; 6:14; 44.1 (2764).
Only psilocybin experience
reported: 13 had never taken,
3 once, 1 twice, 3 thrice.
20 (19 completed all the
measures)
Inclusion for: major
depression of a moderate to
severe degree (16þon the
HAM-D), and no response to
2 adequate courses of AD
treatment.
N/A
Uthaug et al. (2019) Europe (34; 81%), Asia
(2; 4.8%), Australia (2; 4.8%),
South America (3; 7.1%),
North America (1; 2.4%);
17:25; 38.
15 had no experience with
5-MeO-DMT. 92.9% had
experience with other
psychedelics.
42 Exclusion if: current use of
ADs; experiencing
schizophrenia or other
psychoses; a cardiovascular
illness.
No MH condition: 32.
Depression: 1; personality
disorder: 1; a MH disorder not
on the list: 1. Anxiety: 4.
Addiction:3.
Kettner et al. (2019) US (199; 30.4%), UK (128;
19.6%), Denmark (60; 9.2%),
Germany (32; 4.9%), Canada
(32; 4.9%), other 50 countries
in total (203; 31.0%); 165:485
(4 other); 28.9.
Never: 62 (9.5%)
Once: 40 (6.1%)
25 times: 148 (22.6%)
610 times: 106 (16.2%)
1120 times: 109 (16.7%)
2150 times: 110 (16.8%)
51100 times: 39 (6.0%)
More than 100 times: 40 (6.1%)
Baseline: 654.
Follow-ups: N15379; N25
315; N35212; N4564.
N/A Specic WEMWBS data not
provided.
(continued)
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Table 2. Continued
Author, date
Demographics (nationality/
ethnicity; female to male ratio;
age mean (range)) Psychedelic experience Sample size Diagnoses
Self-reported psychological
issues
Argento et al. (2019) Indigenous (all from Coast
Salish band); 5:6; 38 (1956).
Inclusion for: no experience
with ayahuasca.
11 Exclusion if: current use of
SSRIs; current or recent
experience of psychosis.
Substance abuse
van Mulukom et al.
(2020)
US (251; 60.6%), UK (50;
12.1%), Canada (23; 5.6%),
Germany (13; 3.1%), Australia
(11; 2.7%), remaining
participants from 31 other
countries (<10 in each
country); 91:310 (13 other);
30 (1878).
Psilocybin: 179 (45.0%)
LSD: 129 (32.4%)
DMT: 32 (8.0%)
Ayahuasca: 21 (5.3%)
Mescaline/peyote: 5 (1.3%)
5-MeO-DMT: 2 (0.5%)
Other (including 2CP and
4-HO-MET): 16 (4.0%)
A combination of CSPs:
12 (3.0%)
A combination of CSP and
non-CSP: 13 (3.3%).
414 had experience with classic
serotonergic psychedelics
N/A Some assessed as maladaptive
narcissists through the study
procedure.
Uthaug et al. (2018) Netherlands sample: Europe
(93.3%), Asia (3.3%), North
America (3.3%); 18:12.
Colombia sample: South
America (70.4%), Africa
(11.1%), North America
(18.5%); 18:9. Age not
provided.
No past experience with
ayahuasca:
13 (43.3%) Netherlands;
11 (40.7%) Colombia.
Experience with other
psychedelic substances:
20 (66.7%) Netherlands;
19 (70.4%) Colombia.
No experience with other
psychedelic substances:
10 (33.3%) Netherlands;
(no information for
Colombia).
Netherlands: 30
Colombia: 27
None of the participants were
currently on any medication
that could have affected their
ayahuasca intake.
No MH diagnosis:
23 Netherlands;
15 Colombia.
Depression: 3 Netherlands,
4Colombia.
Anxiety: 1 Netherlands,
2Colombia.
Personality disorder:
2Netherlands.
Addiction: 1 Netherlands.
In Colombia some participants
did not answer the related
question.
Belser et al. (2017) 12 White, 1 Multiracial; 6:7; 50
(1876). .
No past experience: 7
Some experience: 6
13 selected from the
quantitative trial
Inclusion for: life expectancy
of at least 1 year and a primary
diagnosis of acute stress
disorder, generalized anxiety
disorder, anxiety disorder due
to cancer, or adjustment
disorder with anxiety.
N/A
Smigielski et al.
(2019)
[SM:] Psilocybin group: 8:12;
52.
Placebo group: 8:11; 50. (All
expert Buddhist meditation
[SM:] No experience:
11 psilocybin; 10 placebo.
Less than 33, over 20 years
ago: 6 psilocybin;
39 Exclusion if: major somatic or
neurological disorder; current
or past psychiatric disorder or
history of a psychiatric
N/A
(continued)
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Table 2. Continued
Author, date
Demographics (nationality/
ethnicity; female to male ratio;
age mean (range)) Psychedelic experience Sample size Diagnoses
Self-reported psychological
issues
practitioners with minimum
500 h of lifetime formal
meditation practice.) Ethnicity/
nationality information not
provided.
4placebo.
More than 33in the last 20
years: 3 psilocybin;
5placebo.
Inclusion for: "no or very
limited exposure to
hallucinogenic drugs".
disorder in a rst-degree
relative; alcohol or drug
dependence or abuse; current
or recent use of substances
affecting the nervous system.
Noorani et al. (2018) Not provided; 5:7; 54 (3167). No experience with CSPs:
5 Some experience
with CSPs: 7
Average experience: 103,
30 years before intake to the
treatment study.
12 Inclusion for: nicotine
dependence (FTCD mean
score of 5.1 and range 36.)
N/A
Agin-Liebes et al.
(2021a)
67% non-Hispanic White, 11%
Black, 11% Asian/Native
Hawaiian or Other Pacic
Islander, 11% Multiracial
(White/American & Indian/
Alaskan Native); all male; 57.9
(5064).
N/A 9 Severe PTSD (score above
median of the original studys
sample); complicated grief in
relation to long-term AIDS.
Inclusion for: clinically
signicant level of
demoralization (DS-II score of
8.)
N/A
Agin-Liebes et al.
(2021b)
83% White, 17% non-White;
North America (60%), Europe
(20%), other (20%); 90:344
(trans/uid: 18); 38 (SD 5
14.4).
Lifetime use of mescaline
13: 46%
Mescaline used once per year
or less frequently: 70%
452 N/A Depression, anxiety, PTSD,
alcohol misuse or drug misuse
disorder.
Abbreviations: 2-CP - 2-(2,5-dimethoxy-4-propylphenyl)ethanamine; 4-HO-MET 4-hydroxy-N-methyl-N-ethyltryptamine; AD antidepressant; CSP classic serotonergic psychedelic; DS-II
Demoralization Scale-II; DSM-IV-TR the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision; FTCD - Fagerström Test for Cigarette Dependence; HAM-D
Hamilton Depression Rating Scale; MH mental health; N/A not applicable; PTSD post-traumatic stress disorder; SM supplementary material; UK the United Kingdom; US the United
States; WEMWBS Warwick-Edinburgh Mental Well-Being Scale.
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Table 3. Results, including risk of bias appraisal
Author, date Risk of bias appraisal
Primary MH/wellbeing outcome
area Resultsp
Uthaug et al., (2020) Quantitative descriptive. Relevant
sampling strategy and
representative sample of 5-MeO-
DMT users. Appropriate
measurements and the risk of
nonresponse bias low 1 out of 11
participants did not return for
follow-up. Appropriate statistical
analysis.
MH: depression, anxiety.
Wellbeing: stress, satisfaction with
life and mindfulness.
Positive correlation between post-
session ratings of the psychedelic
experience (assessed via EDI & 5D-
ASC) and post and follow-up
session ratings of non-judgement
(facet of mindfulness) and
satisfaction with life.
Negative correlation between
ratings of the psychedelic
experience (EDI & 5D-ASC) and
post and follow-up session ratings
depression, anxiety, and stress.
Oceanic boundlessness correlated
positively with non-judgement and
SWL and negatively with
depression. Anxious ego
dissolution correlated negatively
with non-judgement.
Nielson et al., (2018) Mixed methods. Clear research
goal, but no guiding questions for
the interviews reported.
Quantitative outcome
measurement and qualitative data
generated through interviews are
well integrated and their outputs
are adequately interpreted. E.g.,
participantsaccounts of the
experience and their MEQ scores
were analysed conjunctly. An
outlierresult (Heather) is
adequately addressed in the
discussion.
MH: reduction in heavy drinking
days.
Wellbeing: general information
gathered through interviews.
One participant (Adam) reported
experiencing ego-dissolution
during his 2nd session (0.3 mg kg
1
),
even though he was glad to have
resisted it during the rst one. The
excerpt suggests a sense of rebirth
following the ego-dissolution:
TherestheoldAdam,thenthe
new Adam without alcohol.He
was1of4participantswhohada
100% reduction in heavy drinking
days.
Another participant (Michelle)
reported experiencing a sense of
connectedness with that bigger,
ultimate place to bewhich led to
an epistemic breakthrough and
sense of peacefulness (which
correlated with her high blissful
state score of 92). She also achieved
a 100% reduction in heavy drinking
days, and her experience alike took
place during the 2nd session (0.4
mg kg
1
). Both Michelle and Adam
had high intensity scores for the
2nd session.
Another participant reporting
100% reduction in heavy drinking
days (Heather) had very low MEQ,
HRS intensity and ASC blissful
state scores.
Amada et al., (2020) Mixed methods. The quantitative
data gathered through two survey
questions informs the qualitative
accounts on psychedelic
experiences which constitute most
of the studys data. The integration
and interpretation are adequate,
however the results of quantitative
questions reveal a potential
Wellbeing: assessed based on
psychedelic experiences valence
and impact rating as well as the
descriptive account.
The surveys results include many
accounts of ego-dissolution and
connectedness experiences. Ego-
dissolution was reported to have
allowed for a reassessment of lifes
issues and own self without
attachment or judgement and with
a clearer, more objective view.
Based on the participantsaccounts
(continued)
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Table 3. Continued
Author, date Risk of bias appraisal
Primary MH/wellbeing outcome
area Resultsp
sampling bias of the study, i.e.
majority of participants reported
their psychedelic experiences to
have had a major, positive impact
on their lives, with only 2%
reporting negative changes.
the positive changes to their self-
perception were permanent.
Connectedness was also commonly
reported, in the sense of
interconnectedness of self with a
larger context, even if those contexts
varied between individuals
(spiritual, human, natural).
Participants reported many lasting
effects of the experience, e.g., love
for nature, sense of responsibility for
otherswellbeing or for the Earth.
Watts et al., (2017) Qualitative. Clear guiding
questions for the interviews stated
in the paper. The overarching
themes stem clearly from the
subthemes which in turn are
supported with adequate transcript
excerpts.
MH: depression.
Both MH and wellbeing assessed
through interviews. Participants
would have participated in
quantitative studies beforehand
which included psychometric
measurements.
One of the two main themes that
emerged from the series of
interviews was disconnection to
connection. The realms in which
connectedness was experienced
included: senses, self, others, the
world/Nature, spiritual principle/
God. Some of the lasting effects of
the experience were increased
connection with friends, family, and
strangers as well as more
engagement in world affairs. One
participant experienced connection
to a past abuser where a newfound
sense of compassion enabled healing
of trauma. Feeling of love was also
important in one participants
experience: [During the dose] I was
everybody, unity, one life with 6
billion faces, I was the one asking
for love and giving love, I was
swimming in the sea, and the sea
was me. The effects of the
experience were felt by participants
for weeks or months afterwards.
Roseman et al., (2018) Quantitative non-randomized.
Measurements are appropriate,
outcome data complete and some
confounders accounted for (e.g.,
overlapping treatments at follow-
up). The samples
representativeness is limited, due to
the very specic inclusion criteria:
treatment-resistant depression
despite at least two courses of
antidepressants, last one stopped at
least two weeks ago. The possible
antidepressant withdrawal
symptoms are a confounder not
accounted for.
MH: reduction in depressive
symptoms.
Oceanic boundlessness (OBN) and
dread of ego-dissolution (DED)
predicted changes in depressive
symptoms up to 5 weeks. OBN was
positively correlated and predicted
the participantsimprovement
signicantly better than the 2 other
elements of ASC it was compared
to (i.e., visionary restructuralization
and auditory alterations). DED was
negatively correlated. Those who
experienced completeOBN
(>0.6) scored better for secondary
clinical outcomes (such as trait
anxiety, anhedonia, optimism,
pessimism) than those who had a
non-completeOBN. The effect
persisted at different time points
(1-day, 1-week, 5-weeks, 3-months,
and 6-months).
(continued)
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Table 3. Continued
Author, date Risk of bias appraisal
Primary MH/wellbeing outcome
area Resultsp
Uthaug et al., (2019) Quantitative descriptive.
Appropriate sampling strategy.
Sample representative sample of
the European population which
constituted 81% of the sample.
Measurements and statistical
analysis were also adequate.
However, there is a moderate risk
of nonresponse bias as 33 (40%)
out of the 75 recruited participants
did not ll in the post-session test
battery. And of those who
completed post-session
measurements, 50% did not return
for follow-up. This could bias the
sample to participants who had a
more positive and/or impactful
experience.
MH: depression, anxiety.
Wellbeing: stress, satisfaction with
life, mindfulness.
Ego-dissolution (ED) and
connectedness were found not to
correlate with each other. ED
positively correlated with changes
in satisfaction with life and
negatively correlated with
depression, anxiety and stress
(DASS-21, BSI-18) and convergent
thinking (PCT) on the day
following the 5-MeO-DMT session.
However, none of the correlations
persisted at the 4-weeks follow-up.
Oceanic boundlessness positively
correlated with satisfaction with life
and negatively correlated with
convergent thinking on the day
following the 5-MeO-DMT session.
OBN had no correlation with any
ratings at the 4-weeks follow-up.
Kettner et al., (2019) Quantitative descriptive.
Appropriate sampling strategy.
Somewhat representative sample:
anglophone-centric (50% from US
and UK) and with much higher
male participation (485 vs 169
women & other). There is a
moderate risk of nonresponse bias
as only 379 out of baseline 654
participants lled the rst follow-
up survey. Measurements and
statistical analysis were
appropriate.
Wellbeing and nature-relatedness. Only ego-dissolution signicantly
predicted changes in nature
relatedness (NR), with signicant
interaction between time and EDI
scores. NR, in turn, was positively
correlated with psychological well-
being. Where individuals had low
NR scores before the psychedelic
experience (below the mean 4.01),
the relationship between ego-
dissolution an NR was mediated by
context, i.e. whether the experience
took place in nature or not. Mean
NR scores were found to be the
highest two years after the
experience which suggests a
possible positive feedback loop.
Argento et al., (2019) Qualitative. Both the qualitative
approach and the data collection
method were appropriate to the
investigation. The research was
further focused with three
questions which guided the
interviews. Findings are adequately
derived and interpreted. There is
coherence between all the elements
of the study.
MH: addiction.
Wellbeing: stress.
An experience of connectedness
was common during the ayahuasca
ceremony and led to an enhanced
sense of connection with spirit and
nature following the session, which
in turn increased participants
wellbeing. With 1 exception, all
participants expressed having pre-
existent sense of connection with
spirit/nature. Still, in the interview
process they indicated that this
connection was deepened or
reawakened through the ayahuasca
ceremony.
van Mulukom, et al.
(2020)
Quantitative descriptive. Relevant
sampling strategy. The sample is
representative of Western
anglophone countries and has 33
more male than female participants
which might be reective of a bias
in the user base of the websites
MH: maladaptive narcissism. Ego-dissolution during a recent
psychedelic experience was not
associated with increased feelings
of connectedness and empathy,
unlike the experience of awe. The
lasting feelings of connectedness
and empathy were in turn
(continued)
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Table 3. Continued
Author, date Risk of bias appraisal
Primary MH/wellbeing outcome
area Resultsp
used for recruitment.
Measurements were appropriate,
the risk of nonresponse bias was
low and the statistical analysis
appropriate. Referring to
connectedness as an element of the
psychedelic experience (part of the
Awe Experience Scale) as well as
the long-term outcome (considered
equivalent to inclusion of self in
others) makes the paper less
straightforward than it could be.
associated with reduced levels of
maladaptive narcissism.
Connectedness considered an
element of awe in this study
predicted lower levels of
exploitative-entitled narcissism
specically if it was experienced
towards nature or humanity, but
not in the case of connectedness
with the universe. AWE-S
connectedness rating was
signicantly correlated with the
extent to which the experience was
considered of spiritual or religious
nature.
Uthaug et al., (2018) Quantitative descriptive. Relevant
sampling strategy which yielded a
sample representative of ayahuasca
retreat goers in both Europe and
South America, with majority of
female participants on both
continents. Measurements and
statistical analysis were
appropriate, the risk of
nonresponse bias low for
immediate post-measurement,
moderate at 4-weeks follow-up
(completed by 54%).
MH: depression, anxiety.
Wellbeing: stress, satisfaction with
life, mindfulness.
On the day following the ayahuasca
ceremony, ego-dissolution
negatively correlated with stress
and depression and positively
correlated with different facets of
mindfulness (awareness, non-
judgement, and nonreactivity) and
with satisfaction with life. Only
non-reactivity remained
signicantly correlated with ego-
dissolution scores at the 4-weeks
follow-up. Anxiety levels were
already low at baseline, and so the
observed reduction post-session
and at follow-up was insignicant.
Belser et al., (2017) Qualitative. The right approach
and data collection method were
chosen for the studys research
goals. Not only are the ndings
supported by relevant quotes, but
the excerpts are also placed in the
context of individualslife pre-
psilocybin to highlight the
signicance of the reported shifts.
MH: acute stress disorder,
generalized anxiety disorder,
anxiety disorder due to cancer, or
adjustment disorder with anxiety.
7 out of 13 participants expressed
the theme labelled From
Separateness to
Interconnectedness. The
dissolution of self often resulted in
a sense of interconnectedness with
people, the planet, or the whole
universe. These blissful and
comforting experiences left
participants with new, lasting
feelings of empowerment, self-
determination, belonging, and
acceptance in relation to their
own communities and the universe.
While the insights on
interconnectedness of all things
were often reported to have been
achieved through direct knowing
and as difcult to put into words, 8
participants felt that they could still
access the knowledge in ordinary
states of consciousness.
Smigielski et al., (2019) Quantitative RCT. The participants
were comparable at baseline
matched for sex, age, meditation
experience, and dispositional
mindfulness. Information on
Wellbeing: trait and state
mindfulness, changes in behaviour
and attitudes.
Optimistic attitude toward life and
openness signicantly predicted the
variance in oceanic boundlessness
measure as well as mysticism.
Psilocybin intake and ego-
(continued)
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Table 3. Continued
Author, date Risk of bias appraisal
Primary MH/wellbeing outcome
area Resultsp
ethnicity/nationality not provided.
Randomization was carried out
correctly and outcome assessors
were blinded to the intervention
provided insofar that the blinded
participants lled the forms
themselves. Outcome data was
complete and participants adhered
to the assigned intervention.
dissolution signicantly correlated
with the positive changes in
behaviour and attitudes.
Additionally, reappraisal of
emotions was found to decrease the
intensity of anxious ego-
dissolution.
Noorani et al., (2018) Qualitative. Adequate data
collection methods and study
design for the chosen research
question. Findings are adequately
and coherently derived, with
interpretation substantiated by
quotations.
MH: nicotine dependence. Among the psilocybin-related
factors which contributed to
smoking cessation the researchers
included insights into self-identity
(a different, deeper, better, more
essential self)and experiences of
interconnectedness. The latter was
experienced by 8 out of 12
participants and 6 of them were
biologically conrmed as smoking-
abstinent 12 months post-
treatment. Of the 2 participants
who were still smoking one never
quit and reported a non-reduction
in withdrawal symptoms. Another
relapsed between 12-month and
the long-term follow-up.
Agin-Liebes et al.,
(2021a)
Qualitative. Appropriate design,
data collection method and
interpretation.
MH: PTSD & complicated grief in
relation to long-term AIDS.
5 participants reported positive
changes (less fear, anxiety, shame,
guilt) due to acute
phenomenological reductions in
self-focus. These changes in turn
enabled them to deepen their
connection with others,
communities, and the world and to
experience more compassion,
forgiveness, and gratitude also
towards themselves. For instance,
one participant said his ego-
dissolution experience made him
refrain from self-judgement and
that this made his anxiety fully
disappear. Many participants
experienced connectedness with
other group members during the
session and reported deriving a
sense of emotional security from
their connection which helped
them process painful memories.
Agin-Liebes et al.,
(2021b)
Quantitative descriptive. Relevant
sampling strategy. Sample
representative of White (83%) male
(76%) psychedelic users from
North America and Europe (60%
and 20%, respectively).
Appropriate measurements for the
research goals. Only 477 out of 788
people who consented to
MH: depression, anxiety, AUD,
DUD, PTSD.
Wellbeing: changes in mood,
attitudes, and behaviour.
Ego-dissolution correlated with
improvement across all measured
conditions. It was the most
signicant for depression and
anxiety (P< 0.001), very signicant
for drug use disorder (P< 0.01)
and signicant for alcohol use
disorder (P< 0.05). The correlation
with PTSD was found statistically
(continued)
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on it exclusively, followed by two studies looking at the ef-
fects of ayahuasca, two investigating DMT and one
researching mescaline. The remaining three studies were all
surveys and looked at psychedelics in general. While Kettner
et al. (2019) and van Mulukom et al. (2020) specied that
they only included experiences induced by classic psyche-
delics, Amada et al. (2020) makes no mention of such a
criterion. The paper was nevertheless included as the brief
descriptive analyses section of the study indicates that LSD
and psilocybin alone constituted 90% of the samples early
psychedelic experiences. Additionally, the qualitative part of
the studys results only mentions different classic psyche-
delics and no non-classic ones.
There was no apparent difference in the effectiveness of
ego-dissolution and connectedness in improving wellbeing
and mental health outcomes between the eight studies which
investigated psychedelic use in naturalistic settings and the
six studies where psychedelics were taken in a lab setting.
However, Kettner et al. (2019) found that having the psy-
chedelic experience in the natural environment had a sig-
nicant inuence on the outcome. It was the only study to
compare outcomes after outdoors and indoors experiences.
Moreover, it would likely be informative to replicate the
unique setting of ve-day mindfulness retreats in Smigielski
et al. (2019) as the paper report particularly persistent long-
term effects of ego-dissolution.
Population. Most of the participants were White and from
Western anglophone countries United Kingdom, United
States and Canada and some European countries.
Two studies represent exceptions from this demographic
norm: Uthaug et al. (2018) where half of the sample was
recruited in Colombia and Argento et al. (2019) where the
psychedelic treatment was offered to members of a specic
indigenous community only. Coincidentally, these more
ethnically diverse studies are at the same time the only two
ayahuasca studies in the review, with the psychedelic session
being ceremonial in both cases. This might confound any
possible effects of either ethnicity or ceremonial ayahuasca
experience on the outcome.
While the studies included participants from age groups
above the age of 18 and from various educational and
employment backgrounds, the majority of the samples were
predominantly male. This might be partially due to the
recruitment means in the case of online surveys which
sought participants through websites such as Reddit with a
largely male user base (Duggan & Smith, 2013). Still, given
the persistence of the gender bias across surveys, it is also
possible that the samplescomposition is reective of an
actual gender ratio among the psychedelic users. Regardless,
none of the included studies reported a difference in the
effects of ego-dissolution or connectedness on mental health
or wellbeing based on gender, and no such difference was
detectable in the analysis of individual participantsdata.
Finally, the studiesresults were analysed to see whether
previous experience with psychedelic substances correlated
with higher or lower effect of ego-dissolution or connect-
edness on psychological outcomes. One study, Uthaug et al.
(2018), carried out an analysis to investigate this issue and
reported directly that the subacute effects of ayahuasca did
Table 3. Continued
Author, date Risk of bias appraisal
Primary MH/wellbeing outcome
area Resultsp
participate completed the whole
survey. Still, it was likely due to the
large number of questionnaires
rather than the dropouts being
distinct. Hence, the nonresponse
bias can still be considered low.
non-signicant. In the nal models
(odds ratio), a greater intensity of
insight was associated with
increased odds of reporting
improvement in all conditions but
PTSD where mystical experience
intensity was associated with
symptom improvement.
Almost all individuals whose
psychological condition reportedly
improved rated their mescaline
experience as more personally
meaningful, spiritually signicant,
and psychologically insightful than
individuals who reported no
improvement.
pReferences to ego-dissolution or connectedness are underlined.
Abbreviations: 5D-ASC 5-Dimensional Altered States of Consciousness Rating Scale; ASC Altered States of Consciousness
(questionnaire); AUD Alcohol Use Disorder; AWE-S Awe Experience Scale; BSI-18 Brief Symptom Inventory-18; DASS-21
Depression Anxiety Stress Scale-21; DED Dread of Ego Dissolution; DUD Drug Use Disorder, EDI Ego Dissolution Inventory; HRS
Hallucinogen Rating Scale; MEQ Mystical Experience Questionnaire; MH mental health; PCT Picture Concept Test; PTSD post-
traumatic stress disorder; RCT randomized controlled trial; SWL Satisfaction With Life Scale.
Journal of Psychedelic Studies 17
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not differ depending on participantsprevious experience
with the brew (acute effects were not investigated in the
study). No study reported a correlation between past psy-
chedelic experience and psychological outcomes following
the most recent psychedelic session.
Ego-dissolution, connectedness, and psychological outco-
mes. Immediate therapeutic effect of ego-dissolution on
the studys outcome area was reported by seven studies
(Agin-Liebes, Ekman, et al., 2021;Amada et al., 2020;
Nielson et al., 2018;Smigielski et al., 2019;Uthaug et al.,
2018,2019,2020), four out of which reported the correla-
tions between ego-dissolution and their outcomes sustained
in the long-term (subjectively perceived positive psycho-
logical changes in Amada et al., 2020; alcohol use in Nielson
et al., 2018; changes in behaviour and attitudes in Smigielski
et al., 2019; the non-reactivity facet of mindfulness in
Uthaug et al., 2018). Nevertheless, despite the lasting asso-
ciation between ego-dissolution and non-reactivity at 4-
weeks follow-up reported in Uthaug et al. (2018),ve other
associations present immediately after the psychedelic
experience were no longer statistically signicant at this later
timepoint. Uthaug et al. (2020) employed a shorter, 7-day
follow-up and found all the psychological outcomes to still
be affected at this time point, with the correlation between
ego-dissolution and anxiety becoming even more signicant.
Two studies, Kettner et al. (2019) and Agin-Liebes et al.
(2021b), found an indirect effect of ego-dissolution on
psychological improvement, mediated by nature-relatedness
and psychological insight, respectively.
Ego-dissolution did not correlate with the measured
psychological outcome to some extent in five studies, most
profoundly in van Mulukom et al. (2020), where there was
no association between the levels of maladaptive narcissism
and ego-dissolution at all. Whilst Agin-Liebes et al. (2021b)
found a correlation between ego-dissolution and decreased
symptoms of other mental health conditions, there was no
correlation with post-traumatic stress disorder (PTSD). In
the other three studies, it was only at follow-up that the
effect was found to have waned (Uthaug et al., 2018,2019)
or was reported only by one out of nine participants (Agin-
Liebes et al., 2021a). Anxious ego-dissolution (or dread of
ego-dissolution) was investigated in two papers and in both
it was found to correlate with negative psychological out-
comes (Roseman et al., 2018;Uthaug et al., 2020).
Different types of connectedness were reported across
the included papers, usually several kinds within a study.
Thus, a sense of unity with others during the experience was
mentioned in four papers (Agin-Liebes, Ekman, et al., 2021;
Amada et al., 2020;Belser et al., 2017;Watts et al., 2017).
Among them, Agin-Liebes, Ekman, et al. (2021) was the only
study where the psychedelic sessions were carried out in
group setting which enabled the experience of connected-
ness with other cohort members. Additionally, connected-
ness with nature was reported in four papers (Argento et al.,
2019;Amada et al., 2020;Belser et al., 2017;Watts et al.,
2017). The most commonly reported kind of connectedness
was connection with Spirit/All, alternatively referred to as:
that bigger ultimate place to be(Nielson et al., 2018), the
universe (Agin-Liebes, Ekman, et al., 2021;Amada et al.,
2020;Noorani et al., 2018;Watts et al., 2017), God (Watts
et al., 2017), a great plane of consciousness(Belser et al.,
2017), etc., or described as a sense of connection to every-
thing in the world. This kind of connectedness featured in
seven studies (Agin-Liebes, Ekman, et al., 2021;Amada et al.,
2020;Argento et al., 2019;Belser et al., 2017;Nielson et al.,
2018;Noorani et al., 2018;Watts et al., 2017), which also
happened to be all the studies in the review that incorpo-
rated a qualitative element. Additionally, connectedness was
experienced as love by certain participants in two studies
(Amada et al., 2020;Noorani et al., 2018) and was described
as a tool for resolving trauma in two others (Agin-Liebes,
Ekman, et al., 2021;Watts et al., 2017).
An immediate therapeutic effect of connectedness was
found in ten studies (Agin-Liebes, Ekman, et al., 2021;
Amada et al., 2020;Argento et al., 2019;Belser et al., 2017;
Nielson et al., 2018;Noorani et al., 2018;Uthaug et al., 2019,
2020;Watts et al., 2017) and a long-term therapeutic effect,
from ve weeks to 30 months to an unspecied timeframe in
retrospective surveys, was established in eight studies
(Amada et al., 2020;Argento et al., 2019;Belser et al., 2017;
Nielson et al., 2018;Noorani et al., 2018;van Mulukom,
et al., 2020;Roseman et al., 2018;Watts et al., 2017).
Connectedness did not correlate with a psychological
outcome in three studies Uthaug et al., 2019 (at 4-weeks
follow-up), Noorani et al., 2018 (for two participants), and
for the same single participant in Agin-Liebes, Ekman, et al.
(2021) mentioned above as not improving despite ego-
dissolution. In Uthaug et al. (2020) the positive correlation
between the measure of oceanic boundlessness and non-
judgement became more signicant at the 7-day follow-up,
while the positive correlation with satisfaction with life and
the negative correlation with depression lost their signi-
cance at this timepoint. Connectedness correlated with
improvement on at least one measure of mental health or
wellbeing in all the studies included in this review.
Subgroup analysis: outcome domains. The last analysis
carried out focused on the therapeutic effectiveness of ego-
dissolution and connectedness within different outcome
domains. Firstly, many studies did not investigate
improvement within clinical categories, but rather through
ratings and descriptions of participantswellbeing, stress
reduction, quality of and satisfaction with life, psychosocial
functioning or trait and state mindfulness. There were nine
studies that reported on one or more of these outcomes, out
of which six found a positive correlation between ego-
dissolution and wellbeing (Amada et al., 2020;Kettner et al.,
2019;Smigielski et al., 2019;Uthaug et al., 2018;Uthaug
et al., 2018,2018,2019,2019,2020,2020;Watts et al., 2017)
and six found a positive correlation between connectedness
and wellbeing (Amada et al., 2020;Argento et al., 2019;
Belser et al., 2017;Uthaug et al., 2019,2020;Watts et al.,
2017). No study found a negative correlation either with ego-
dissolution or connectedness. The effect of ego-dissolution on
wellbeing was found to be limited in Uthaug et al. (2019),
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where the correlation diminished to non-signicant levels in
majority of categories after 4 weeks.
Depression was the second most frequently researched
domain with six studies reporting on the outcome, followed
by anxiety with five studies. Ego-dissolution was found to
negatively correlate with depression in four studies (Agin-
Liebes et al., 2021b;Uthaug et al., 2018,2019,2020) and with
anxiety in four studies, too (Agin-Liebes et al., 2021b;Belser
et al., 2017;Uthaug et al., 2019,2020). Out of the latter
subgroup, Belser et al. (2017) focused on anxiety related to
cancer diagnosis and found that dissolution of self as well as
experiences of interconnectedness had a lasting positive
impact on the participantsmental health. While Uthaug
et al. (2018) measured anxiety as well, due to very low
baseline levels of anxiety in the sample, the observed
reduction in the scores post-session was statistically non-
signicant.
Three studies looked at the relationship between
connectedness and depression. Uthaug et al. (2020) found
oceanic boundlessness to negatively correlate with depres-
sion immediately after the 5-methoxy-N,N-dimethyltrypta-
mine (5-MeO-DMT) session, with the correlation rendered
insignicant by the 7-day follow-up. Watts et al. (2017)
found lasting improvement in previously depressed partici-
pants, while Roseman et al. (2018) found the measure of
OBN to predict improvement in depressive symptoms for at
least 5 weeks post-session. A completeOBN (>0.6) was
associated with better scores for secondary clinical outcomes
like trait anxiety, anhedonia, optimism, or pessimism.
Four studies investigated the effectiveness of psychedelic
therapy in treating addiction. Noorani et al. (2018) found
that out of eight individuals who reported experiencing
interconnectednessseven stopped smoking, with one
person relapsing after the 12-month follow-up. Two studies
focused on alcohol dependence, Agin-Liebes et al. (2021b)
and Nielson et al. (2018). The former study showed that out
of four participants who experienced a 100% reduction in
heavy drinking days, two described experiencing radical
changes to the sense of self during the sessions, which
included the sense of loss of self as well as oneness, and
which correlated with high Mystical Experience Question-
naire (MEQ) scores. Meanwhile, the latter study showed that
ego-dissolution signicantly correlated with reduction in
alcohol misuse, but the association with drug misuse score
was even more signicant. Lastly, the interviews carried out
by Argento et al. (2019) suggest that connectedness was
common and had a positive impact on the wellbeing of
substance-dependent participants.
Individuals with PTSD participated in two studies by
Agin-Liebes et al. (2021a,2021b).Therst paper focused
solely on males with long-term AIDS (AIDS), PTSD, and
complicated grief. The interviews with this sample revealed
ego-dissolution in particular to have had profoundly pos-
itive effects on the participantsmental state, while the
experience of connectedness with other group therapy
members during the psilocybin session was a source of
signicant emotional support. Yet, the second study, a
mescaline-focused survey, found PTSD to be the only
conditionmeasuredthatdidnotshowasignicant nega-
tive correlation with ego-dissolution.
The last clinical category considered in the included
studies was maladaptive narcissism (van Mulukom et al.,
2020). The retrospective survey did not nd an association
between present levels of maladaptive narcissism and past
experience of ego-dissolution, but did nd a negative cor-
relation between connectedness and exploitative-entitled
narcissism. However, this correlation was only true in the
case of connectedness towards nature or humanity, but not
connectedness to the universe at large.
Subgroup analysis: ego-dissolution vs connectedness. Quan-
titative studies found both ego-dissolution and connectedness
to significantly correlate with improvements in mental health
and psychological wellbeing outcomes. However, it seems that
effects of connectedness tend to be more long-lasting, while
ego-dissolution correlates with short-term rather than long-
term changes. Only three studies found sustained effects of
ego-dissolution: on alcohol consumption reduction at least
until 4 weeks after the second psilocybin session in Nielson
et al. (2018); on enabling a positive, permanent trans-
formation of self in Amada et al. (2020) and on positive
behavioural and attitudinal changes in Smigielski et al. (2019)
at 4-month follow-up. In Uthaug et al. (2018) only one cor-
relation out of the six detected immediately after the
ayahuasca ceremony was still present at the 4-week follow-up,
while Uthaug et al. (2019) found no correlations between ego-
dissolution and any of the measured outcomes 4 weeks after a
5-MeO-DMT session.
A notion repeated throughout a number of studies is that
ego-dissolution might act more as an intermediary enabling
therapeutic action, rather than as a remedy in itself. The
experience was described as a tool for gaining an objective,
outside perspective on ones own self and life in four
different studies: Agin-Liebes et al. (2021a,2021b),Amada
et al. (2020),Nielson et al. (2018). In the last study,
mescaline-induced ego-dissolution was originally found to
correlate with improved outcomes for depression, anxiety,
alcohol, and drug use disorders. When an odds ratio analysis
was run, however, it was found that after controlling for ego-
dissolution and mystical experiences, only psychological
insight was signicantly predictive of improvements in these
groups. These ndings suggest that while experiencing ego-
dissolution is associated with more positive mental health
changes, it might be due to the larger number or greater
profundity of psychological insights it enables.
Connectedness might differ from ego-dissolution in two
ways immediate psychological impact and duration of the
state. Firstly, the reviewed studies indi