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Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective Well-Being


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Creative thinking and empathy are crucial for everyday interactions and subjective well-being. This is emphasized by studies showing a reduction in these skills in populations where social interaction and subjective well-being are significantly compromised (e.g., depression). Anecdotal reports and recent studies suggest that a single administration of psilocybin can enhance such processes and could therefore be a potential treatment. However, it has yet to be assessed whether effects outlast acute intoxication. The present study aimed to assess the sub-acute effects of psilocybin on creative thinking, empathy, and well-being. Participants attending a psilocybin retreat completed tests of creative (convergent and divergent) thinking and empathy, and the satisfaction with life scale on three occasions: before ingesting psilocybin (N = 55), the morning after (N = 50), and seven days after (N = 22). Results indicated that psilocybin enhanced divergent thinking and emotional empathy the morning after use. Enhancements in convergent thinking, valence-specific emotional empathy, and well-being persisted seven days after use. Sub-acute changes in empathy correlated with changes in well-being. The study demonstrates that a single administration of psilocybin in a social setting may be associated with sub-acute enhancement of creative thinking, empathy, and subjective well-being. Future research should test whether these effects contribute to the therapeutic effects in clinical populations.
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Journal of Psychoactive Drugs
ISSN: 0279-1072 (Print) 2159-9777 (Online) Journal homepage:
Sub-Acute Effects of Psilocybin on Empathy,
Creative Thinking, and Subjective Well-Being
Natasha L. Mason, Elisabeth Mischler, Malin V. Uthaug & Kim P. C. Kuypers
To cite this article: Natasha L. Mason, Elisabeth Mischler, Malin V. Uthaug & Kim P. C. Kuypers
(2019): Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective Well-Being,
Journal of Psychoactive Drugs
To link to this article:
© 2019 The Author(s). Published with
license by Taylor & Francis Group, LLC
Published online: 26 Feb 2019.
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Sub-Acute Effects of Psilocybin on Empathy, Creative Thinking, and Subjective
Natasha L. Mason, M.Sc., Ph.D.
, Elisabeth Mischler, Ph.D.
, Malin V. Uthaug, M.Sc., Ph.D.
and Kim P. C. Kuypers, Ph.D.
Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The
Central Customs Authority, Centre of Education and Science, Cologne, Germany
Creative thinking and empathy are crucial for everyday interactions and subjective well-being.
This is emphasized by studies showing a reduction in these skills in populations where social
interaction and subjective well-being are significantly compromised (e.g., depression). Anecdotal
reports and recent studies suggest that a single administration of psilocybin can enhance such
processes and could therefore be a potential treatment. However, it has yet to be assessed
whether effects outlast acute intoxication. The present study aimed to assess the sub-acute
effects of psilocybin on creative thinking, empathy, and well-being. Participants attending
a psilocybin retreat completed tests of creative (convergent and divergent) thinking and empathy,
and the satisfaction with life scale on three occasions: before ingesting psilocybin (N= 55), the
morning after (N= 50), and seven days after (N= 22). Results indicated that psilocybin enhanced
divergent thinking and emotional empathy the morning after use. Enhancements in convergent
thinking, valence-specific emotional empathy, and well-being persisted seven days after use. Sub-
acute changes in empathy correlated with changes in well-being. The study demonstrates that
a single administration of psilocybin in a social setting may be associated with sub-acute
enhancement of creative thinking, empathy, and subjective well-being. Future research should
test whether these effects contribute to the therapeutic effects in clinical populations.
Received 23 October 2018
Accepted 18 January 2019
Convergent thinking;
creativity; divergent
thinking; empathy; life
satisfaction; psilocybin
Creativity and empathy are crucial for everyday inter-
actions and cooperation, allowing us to adapt to an
ever-changing environment, and motivating our proso-
cial behaviors (Decety et al. 2016). Interestingly, they
have been found to be positively related (Carlozzi et al.
1995), and it has been suggested that creative, flexible
thinking is a prerequisite for empathy (Eslinger 1998).
Previous research demonstrates a reduction in these
skills in populations where social interactions and sub-
jective well-being are compromised (Beck 1967;
Neumann et al. 2011).
Creativity is a multicomponent construct, consisting of
convergent (CT) and divergent thinking (DT) (Guilford
1967). CT is considered a process of generating a single
optimal solution to a particular problem, emphasizing
speed, accuracy, and logic. Conversely, DT is a process
used to generate many new ideas, in a context where more
than one solution is correct. An example of the latter is
a brainstorming session, where generating many
innovative ideas or solutions on a particular issue is the
ultimate goal (Colzato, Szapora, and Hommel 2012).
Although both CT and DT are important in creative
activities, DT may be a more useful estimate of the poten-
tial for creative thought in daily life (Runco and Acar
Emotional, or affective, empathy (EE) refers to the
sharing of emotions, or the ability to feel what another
person is feeling. In contrast, cognitive empathy (CE)
refers to mental perspective taking, or recognizing and
understanding what another person is feeling (Deutsch
and Madle 1975). Previous research suggests
a specificity of the two constructs (Davis 1980), in
that emotional empathy may depend on state variables,
whereas cognitive empathy requires a (trait) ability to
identify anothers emotions (Hurlemann et al. 2010;
Pokorny et al. 2017).
Both creative, flexible thinking and empathy deficits
have been found in stress-related psychopathologies
like depression, anxiety disorders, and post-traumatic
stress disorder (PTSD) (Chamberlain et al. 2006; Cusi
CONTACT Natasha L. Mason Department of Neuropsychology and Psychopharmacology, Faculty of
Psychology and Neuroscience, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands.
Color versions of one or more of the figures in the article can be found online at
© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (
nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built
upon in any way.
et al. 2011; Donges et al. 2005; Lee and Orsillo 2014;
Morrison et al. 2016; Nietlisbach et al. 2010; Palm and
Follette 2011; Parlar et al. 2014). Hallmarks of these
disorders are repetitive and rigid patterns of negative
and compulsive thoughts, together with social difficul-
ties and impaired empathic abilities (Aldao, Nolen-
Hoeksema, and Schweizer 2010; Beck 1967; Dos
Santos et al. 2016; Morrison et al. 2016; Nietlisbach
and Maercker 2009; Todd et al. 2015), the latter of
which, most evident in depression, may contribute to
more pronounced symptoms (Cusi et al. 2011; Donges
et al. 2005).
Importantly, previous research has found that these
processes demonstrate plasticity and can be enhanced by
interventions such as therapy programs, hormone admin-
istration, and mindfulness induction, as well as (positive)
changes inmood (Ashby, Isen, and Turken 1999;Baas,De
Dreu, and Nijstad 2008;Davis2009;Dongesetal.2005;
Forgeard and Eichner 2014; Hurlemann et al. 2010;Lee
and Orsillo 2014; Palgi, Klein, and Shamay-Tsoory 2016).
However, these interventions typically target only one of
the two mentioned processes. Thus, by finding treatments
that promote both processes, individual deficits could be
further decreased, potentially enhancing well-being and
quality of life.
Anecdotal evidence and (quasi-)experimental studies
suggest that a single administration of a psychedelic
drug like ayahuasca, LSD, or psilocybin can enhance
creative, flexible thinking and emotional empathy in
the neuro-typical population (Dolder et al. 2016;
Harman et al. 1966; Krippner 1964; Kuypers 2018;
Kuypers et al. 2016; Pokorny et al. 2017; Preller et al.
2015; Sessa 2008; Uthaug et al. 2018). Furthermore,
clinical studies have found that administration of psi-
locybin can induce long-lasting positive psychological
changes, such as symptom remission and enhancement
of well-being, in clinical populations (Carhart-Harris
et al. 2016; Griffiths et al. 2016; Johnson, Garcia-
Romeu, and Griffiths 2017). However, the persistence
of effects on creativity and empathy, and the relation-
ship with subjective well-being, has yet to be assessed.
The present study was designed to assess the sub-acute
effects of psilocybin on creative thinking, empathy, and
subjective well-being. We hypothesized that divergent and
convergent thinking, emotional empathy, and satisfaction
with life would be enhanced sub-acutely with no effect on
cognitive empathy (Pokorny et al. 2017). Furthermore,
based on clinical research demonstrating reductions in
creativity and empathy in individuals with compromised
well-being, we hypothesized that enhancements in such
processes would correlate with increased satisfaction with
life. Finally, as psilocybin has been shown to induce long-
lasting positive increases in well-being, we hypothesized
that participants with previous psilocybin experience
would have a higher baseline satisfaction with life score,
compared to those who are psilocybin-naïve.
Participants were volunteers attending psilocybin retreats
in the Netherlands, organized by the Psychedelic Society
UK. In total, 55 participants (26 female) consented after
goals and methods of the study were explained. Most
participants were from Europe (80%), while the rest
were from North America (7.3%), Africa (3.6%), Central
America (1.8%), and Asia (1.8%), or undisclosed (5.4%).
The highest completed levels of education were graduate
school (41.8%), undergraduate school (41.8%), secondary
school (7.3%), or undisclosed (9.1%). Mean (SD) partici-
pant age was 34.8 (8.9).
About half (52.7%) of the participants had used psilocy-
bin before, and 49.1% had previously used a psychedelic
other than psilocybin (LSD, ayahuasca, or DMT).
Motivations for attending the retreat included to under-
stand myself(83.6%), curiosity(80%), to resolve pro-
blems(49.1%), and other(18.2%). For 69.1% of the
participants, this was the first time taking a psychedelic in
a retreat setting.
The study was conducted in accordance with the
Declaration of Helsinki and subsequent amend-
ments concerning research in humans and was
approved by the Ethics Review Committee of
Psychology and Neuroscience. Participation was
voluntary and no incentive to participate was pro-
vided. All volunteers gave their written informed
consent to participate.
Study procedure
Psilocybin retreats
Prior to participation in the retreat, personal intakes
were done by the facilitators, which included screening
for (and excluding) individuals with psychiatric disor-
ders or taking psychiatric medications, and medical
factors like high blood pressure.
The setting in which psilocybin was taken was the
same throughout all of the retreats. Participants stayed
in a large house set in nature, hosted by at least two or
more experienced psilocybin facilitators. They arrived
the evening before psilocybin administration, and were
able to get acquainted with each other, the facilitators,
and the schedule of the retreat. The next day, partici-
pants received the psilocybin-containing truffles
around noon, in a tea form. After ingestion,
participants were instructed to stay on the premises,
and were able to do what they wanted, as long as they
did not disturb other participants. Facilitators provided
music, tools to draw and/or write, and food. In the
evening, all participants and facilitators came back
together as a group. The next morning, all participants
had breakfast together and had a closing group
Participants ingested the truffles in a tea form, guided
by the facilitators. To do this, the truffles were crushed,
and boiling hot ginger tea was added. After infusing for
a few minutes, the participants drank the tea, and were
subsequently free to add more water and repeat the
process 23 times. Afterwards participants could eat
the remaining truffle contents in the cup.
Previous experimental studies have demonstrated
that subjective alterations after psilocybin intake begin
2040 minutes following administration, peak around
6090 minutes, and subside by six hours post-intake
(Hasler et al. 2004). However anecdotal reports suggest
that when ingested in tea form, subjective alterations
are felt more quickly, and for a shorter amount of time
(Erowid 2015).
Study procedure
Creativity, empathy, and well-being assessments were
taken on three separate occasions: at baseline (the eve-
ning before ingesting psilocybin), the morning after
ingesting psilocybin, and seven days after ingesting
psilocybin. Participants completed pre- and post-
psilocybin assessments at the retreat, with the investi-
gators present. The third assessment was completed
online. The total amount of psilocybin truffles taken
by each participant was recorded, and a sample of the
truffles was taken to determine concentrations of psi-
locybin and its metabolite, psilocin. The German
Central Customs Authority determined the contents
of psilocin and psilocybin after freeze-drying the truf-
fles using a previously described HPLC method
(Laussmann and Meier-Giebing 2010).
Picture concept task
In order to assess creativity, the picture concept task
(PCT) was used (Kuypers et al. 2016). The PCT con-
3 × 3, or 3 × 4. Participants were instructed to find
an association between one of the pictures in each
row. Specifically, they were asked first to provide the
correct solution, as there is only one correct answer.
The number of correct answers served as the depen-
dent measure of convergent thinking. In order to
assess divergent thinking, participants were asked to
provide as many alternative answers as possible. This
is the regular instruction included in measures of
divergent thinking, and it is used to calculate several
parametersi.e., fluency, originality, and the ratio of
bothwhich reflect quantity and quality of divergent
thinking. Fluency is defined as the number of alter-
native associations. The second parameter (i.e., ori-
ginality) is calculated by evaluating the originality of
the alternative association relative to those provided
by all other participants in a session. Alternative
answers that were uniquely reported by a single par-
ticipant received an originality score of 2. Answers
that were shared with a single participant were valued
as 1, and answers that were shared by three or more
participants were rated zero. Mean originality (crea-
tivity) scores and ratio originality scores weighed for
fluency (originality/fluency) were used as measures of
divergent thinking. Three parallel versions of the PCT
were used at baseline and the two follow-up measures
after the retreat to avoid learning effects; participants
had 30 seconds per stimulus. Previous studies have
found the PCT to be sensitive to the effects of psy-
chedelics (Kuypers et al. 2016; Prochazkova et al.
Multifaceted empathy test
The multifaceted empathy test (MET) consists of 40
pictures of people in various emotional states, with
50% being positive and 50% negative (Dziobek et al.
2008). To assess cognitive empathy (CE), participants
were asked to select the emotion word, out of four
words, which matched the depicted emotion. To
assess emotional empathy (EE), participants were
asked to rate on a scale from 1 to 9 how aroused
does this picture make you feel(implicit EE) and
how concerned do you feel for this person(explicit
EE). The number of correctly classified pictures (CE)
and the implicit EE and explicit EE ratings per
valence and averaged across valences were used as
dependent variables. Previous validity and reliability
analysis of the MET have shown to be in the good to
highly satisfactory range (Dziobek et al. 2008), and
previous studies have found it to be sensitive to the
effects of psychedelics (Hysek et al. 2014;Kuypers
et al. 2014,2017; Pokorny et al. 2017;Prelleretal.
Satisfaction with Life Scale
The Satisfaction with Life Scale (SWLS) is a five-item
questionnaire designed to measure global cognitive judg-
ments of satisfaction with ones life (Diener et al. 1985),
and has been used to measure the life satisfaction compo-
nent of subjective well-being (Diener et al. 1985;Pavot
et al. 1991). Individuals answer each item on a Likert scale
ranging from 1 (strongly disagree) to 7 (strongly agree).
The total score is then obtained by summing the ratings
form each item. Sample items include In most ways my
life is close to my idealand If I could live my life over,
I would change almost nothing.The minimum possible
score is 5, and the maximum possible score 35, with
a score of 519 defined as dissatisfied to below average
life satisfaction, 2024 defined as average life satisfaction,
and 2935 defined as high to very high life satisfaction
(Pavot and Diener 2013). The scale has previously been
shown to be a valid and reliable measure of life satisfac-
tion (Pavot and Diener 2009).
Psilocybin experience
The morning after ingesting psilocybin, participants
were asked to retrospectively rate the intensity of var-
ious aspects of the acute psilocybin experience using 10
visual analog scales (VASs). The VASs were 10 cm
horizontal lines, with a bottom anchor of not more
than usuallyand a top anchor of much more than
usually.These items have previously been shown to be
sensitive to the acute effects of psilocybin (Carhart-
Harris et al. 2012).
Statistical analyses
Statistical analysis was conducted in IBM SPSS
Statistics 24 using a linear repeated measures model
analysis that included Session (three levels: baseline,
morning after psilocybin, and seven days after psilocy-
bin) as a within-subject factor. Due to small sample size
at the seven-day follow-up, a separate linear repeated
measures model analysis was done for each outcome
variable. Similarly, as for the MET, if a main effect of
Session was found on emotional or cognitive empathy,
two further analyses were done, separating valence-
specific (positive or negative emotion) responses.
The covariance structure was chosen according to
best fit and could vary across outcome variables.
Different covariance structures used included com-
pound symmetry heterogenous (CSH) and first lag
autoregressive (AR1) structures. If a main effect of
Session was found, separate contrasts were performed
between baseline and the follow-up sessions with
Bonferroni adjustment for multiple comparisons.
In order to test whether people with previous psilocy-
bin experience differed from psilocybin-naïve partici-
pants on outcome measures, a further mixed-model
analysis was conducted, with Session (three levels: base-
line, morning after psilocybin, and seven days after psilo-
cybin) as a within-subject factor and previous experience
with psilocybin (two levels: yes, no) as a between-subjects
factor, though only for outcome parameters which
showed a significant main effect of Session in the first
analysis. The analysis was performed to determine
whether sub-acute effects of psilocybin differed between
experienced versus naïve psilocybin users.
In order to investigate the association between cog-
nitive (creativity and empathy) and subjective (well-
being) outcome parameters, Pearsons correlations
were carried out using baseline change scores
(Morning afterbaseline; seven days afterbaseline).
Psilocybin experience ratings were analyzed sepa-
rately using one-sample ttests comparing the scores
on each VAS after psilocybin versus a zero distribution,
since previous studies have shown that placebo scores
are low, not rising above a 0 in a scale from 0 to 100
(Valle et al. 2016).
In total, 55 participants completed parts of the test
battery at baseline, 50 completed parts of the test bat-
tery the morning after taking psilocybin, and 22 com-
pleted parts of the test battery seven days after taking
psilocybin. Incomplete or missing test batteries were
due to time constraints and/or participant drop-out.
The truffle sample (15 grams; Psilocybe Hollandia)
contained 1.9 mg of psilocybin and 10.5 mg of psilocin.
Participants ingested an average (SD) 34.2 (8.9) grams
of truffles throughout the day. Once ingested, psilocy-
bin is quickly metabolized to psilocin at a calculation
factor of 0.719, resulting in a final (average) psilocin
consumption of 27.1 mg.
Picture concept test
Convergent thinking
Analysis revealed a significant main effect of Session
= 5.94, p= .01) on the number of correct
associations (see Figure 1(d)). Compared to baseline,
participants were able to identify a higher number of
correct associations seven days after ingesting
psilocybin (p= .01; d= .46). There were no significant
effects of psilocybin on convergent thinking the morn-
ing after taking psilocybin.
Divergent thinking
Analysis revealed a significant main effect of Session on
Fluency (F
= 5.27, p= .01) and Originality
= 7.23, p= .002) (see Figure 1(a, b)).
Compared to baseline, participants were able to come
up with more associations (p= .01; d= .47), and had
a higher originality score (p = .001; d= .55), the
morning after taking psilocybin. There was no signifi-
cant effect of session on Ratio (F
= 2.25, p= .12).
Furthermore, there were no significant effects of psilo-
cybin on Fluency, Originality, or Ratio seven days after
taking psilocybin.
Multifaceted empathy test
Cognitive empathy
There was no significant effect of Session on cognitive
empathy (F
= 3.18, p= .06); participants were able
to recognize about 22 emotions on average in the three
sessions (see Figure 2(c, d)).
Emotional empathy
Analysis revealed a significant main effect of Session
=4.29,p= .02) on average Explicit EE (see
Figure 2(b)). Compared to baseline, participants felt
more concern for people depicting emotions the
morning after ingesting psilocybin (p= .02;
d= .45). When assessing valence-specific responses,
analysis revealed a significant main effect of Session
=5.87,p= .01) on concern ratings of nega-
tive emotions; compared to baseline, individuals
concern for negative emotions was increased the
morning after taking psilocybin (p= .01; d= .49)
without effects on day 7. There was no significant
effect of Session (F
=2.58,p= .09) on concern
ratings of positive Explicit EE.
Analysis revealed a significant main effect of Session
=10.64,p= .001) on average Implicit EE ratings
(see Figure 2(a)). Compared to baseline, participants felt
more aroused by the emotional content of the stimuli the
morning after ingesting psilocybin (p< .001; d= .71).
When assessing valence-specific responses, analysis
revealed a significant main effect of Session on both
positive (F
=4.93,p= .02) emotions. Separate contrasts indicated
that, compared to baseline, individualsarousal to both
positive (p= .001; d= .61) and negative (p= .01; d=.48)
Figure 1. Mean (±SE) outcome variables of divergent and convergent thinking, measured before, the morning after, and seven days
after psilocybin ingestion. Panels A to C depict outcome variables of divergent thinking; (a) fluency; (b) originality; (c) ratio; panel (d)
depicts the outcome variable of convergent thinking (*p < .05).
emotions was higher the morning after ingesting psilocy-
bin. Furthermore, implicit arousal to negative stimuli, but
not positive stimuli, remained increased seven days after
ingesting psilocybin (p=.05;d= .41).
Satisfaction with Life Scale
Analysis revealed a significant main effect of Session
= 17.83, p< .001) on individualsresponses to
the SWLS (see Figure 3(a)). Contrasts indicated that,
compared to baseline, satisfaction with life significantly
increased both the morning after (p< .001; d= .77) and
seven days after (p= .001; d= .50) ingesting psilocybin.
Previous experience with psilocybin
Twenty-nine participants reported previously using
psilocybin, whereas 21 reported being psilocybin
Figure 2. Mean (±SE) outcome variables of implicit emotional empathy (a), explicit emotional empathy (b), and cognitive empathy (c;
total (d)), measured before, the morning after, and seven days after psilocybin ingestion (*p< .05).
Figure 3. Panel A depicts the total group mean (±SE) ratings of satisfaction with life measured before, the morning after, and
seven days after psilocybin ingestion. In panel B, a second analysis was performed to assess differences in satisfaction with life
between those who had previous experience with psilocybin (experienced) and those who had not (naïve). Mean (±SE) ratings per
group are shown (*p< .05).
naïve, and five chose not to disclose their previous
drug use history. The latter were thus not included in
this analysis. The analysis revealed a significant main
effect of Session (F
= 16.768, p< .000) and
Psilocybin experience (F
=5.39,p= .025) on
individualsresponse to the SWLS (Figure 3(b)).
Contrasts indicated that those who had previous
experience with psilocybin reported a significantly
higher quality of life at baseline compared to those
who were psilocybin naïve (p= .012; d=.39).The
sub-acute effects of psilocybin did not differ between
participants who had used psilocybin vs. those who
had not for any other outcome measures.
Analysis showed medium to strong positive correla-
tions between changes in implicit and explicit EE
towards a positive stimulus and changes in satisfaction
with life. Specifically, as changes in arousal to pictures
of people in positive mood states increased, changes in
satisfaction with life also increased, when comparing
baseline to both the morning after psilocybin intake
(Spearman correlation (r
) = .43, p= .05) and seven days
after intake (r
= .61, p= .02). Furthermore, as changes
in ratings of concern for people in various emotional
states increased between baseline and the morning after
intake, ratings of satisfaction with life increased
between baseline and seven days after intake (r
= .57,
p= .03). Finally, as changes in ratings of concern for
people in positive mood states increased, changes in
quality of life increased between baseline and seven days
after psilocybin intake (r
= .58, p= .03). No significant
correlations were found between outcome variables of
the PCT and ratings of quality of life, or between
variables of the PCT and the MET.
Psilocybin experience
Mean (SE) ratings on the different VAS items after psilo-
cybin are shown in Figure 4. The one-sample ttests
showed psilocybin-induced significant increases in all
VAS items (t
=14.5623.73; p.000; d=2.053.35).
We believe that this study demonstrates the first attempt
to assess the sub-acute influence of psilocybin on creative
thinking, empathy, and their relationship with well-being.
Using a naturalistic approach, significant sub-acute
enhancements of outcome measures of divergent thinking
(DT), convergent thinking (CT), emotional empathy (EE),
and satisfaction with life (LS), after ingestion of psilocybin
Figure 4. Mean (±SE) of visual analogue scale item scores on a 10 cm scale. Scores are retrospective of the psilocybin experience.
at a psychedelic retreat, were demonstrated relative to
baseline. Correlational analyses suggest a positive relation-
ship between sub-acute enhancements in EE and LS.
The findings demonstrate a time- and construct-
related differentiation of effects of psilocybin on crea-
tivity; whereas DT was shown to increase the morning
after ingesting psilocybin relative to baseline, CT was
unaffected. Seven days after ingestion, DT performance
returned to baseline, whereas CT was enhanced.
Previous research has shown that ayahuasca, a South
American plant tea consisting of the similar-acting 5-
agonist N,N-Dimethyltryptamine (DMT), acutely
enhanced DT and impaired CT in individuals partici-
pating in an ayahuasca ceremony (Kuypers et al. 2016).
Furthermore, a similar study demonstrated persisting
sub-acute enhancements of CT one month after parti-
cipation in an ayahuasca ceremony (Uthaug et al.
2018). Taken together, our findings suggest that
whereas psychedelic-induced enhancements of DT out-
last the acute phase, decrements in CT do not. This
discrepancy in acute versus sub-acute effects after
a psychedelic is interesting in light of therapeutic impli-
cations, as both DT and CT are important components
in the therapeutic process. Specifically, it has been
suggested that DT can enhance psychological flexibility
by allowing individuals to generate new, more effective
strategies that facilitate adaptive interpretations and
coping abilities (Forgeard and Elstein 2014).
Consequently, the ability of psilocybin to enhance DT
sub-acutely could help patients to relive events, recall
various associations, and consider their situation from
another perspective (Bouso et al. 2008; Frecska, Bokor,
and Winkelman 2016; Frecska et al. 2012). Longer-term
effects on CT could then be studied in a subsequent
integration session where patients discuss their acute
experiences and decide on a strategy to help them cope
with intensive emotions (Kuypers et al. 2016).
Findings demonstrate a time-, component-, and
valence-differentiation of effects of psilocybin on empa-
thy; whereas explicit and implicit EE were shown to
increase the morning after psilocybin use, CE was unaf-
fected. Furthermore, enhancement in implicit EE to pic-
tures depicting negative emotions persisted until
seven days after use. The sub-acute enhancements in EE
are in line with previous studies assessing acute effects of
psilocybin, as well as other serotonergic psychedelics like
LSD and MDMA, on empathy. Specifically, psilocybin,
LSD, and MDMA have been found to enhance EE on the
MET (Hysek et al. 2014; Kuypers et al. 2014,2017;
Pokorny et al. 2017; Preller et al. 2015;Schmidetal.
2014) without impairing CE. Taken together, these find-
ings suggest that psilocybin (sub)-acutely increases indi-
vidualsability to feel what other people are feeling,
without affecting individualsability to understand what
other people are feeling. Furthermore, psilocybin-induced
increments in arousal to the (negative) emotion of others
outlast induced increments in the ability to feel for others.
Self-rated LS increased after psilocybin ingestion
compared to baseline, both the morning after and
seven days after use. Specifically, at baseline, partici-
pants reported a mean (±SE) score of 22.3 (.96),
a morning-after score of 26.5 (1.03), and seven-day-
after score of 25.6 (1.11). Scores between 2024 reflect
an averageLS, defined by general satisfaction, but
with a desire for improvement in major domains (e.g.,
work/school, family) (Pavot and Diener 2013). A score
of 2529 is considered a highscore, suggestive of an
enjoyable life and satisfaction in the major domains.
Based on interpretation scores, results suggest that psi-
locybin ingestion increased individualsLS from aver-
ageto highuntil at least seven days after use. This
finding is consistent with previous studies showing
acute (Schmid et al. 2014), sub-acute (Barbosa, Giglio,
and Dalgalarrondo 2005;Uthaug et al. 2018), and long-
term (Barbosa et al. 2009; Bouso et al. 2012; Garcia-
Romeu, Griffiths, and Johnson 2015; Griffiths et al.
2011; Grob et al. 2011; Lawn et al. 2017; Osorio et al.
2015; Thomas et al. 2013) positive psychological
changes after psychedelic use. We also assessed whether
there was a relationship between previous experience
with psilocybin and baseline LS scores. In line with the
aforementioned research, it was found that those who
had previously used psilocybin reported higher LS at
baseline compared to those who were psilocybin naïve;
however, this was not related to differences between
groups on performance measures. Altogether, these
results add to the growing body of literature suggesting
beneficial subjective psychological effects of psychedelic
use outlasting acute intoxication.
We hypothesized that changes in empathy and crea-
tivity would correlate with changes in satisfaction with
life. Correlational analysis suggested a positive relation-
ship between changes in LS and changes in implicit EE
(arousal). Morning-after change score increases in
arousal in response to positive emotions correlated with
morning-after and seven-day-after change score increases
in subjective ratings of LS. This relationship could be due
to an increase in positive empathy, the phenomenon of
sharing and understanding others positive emotions
(Morelli, Lieberman, and Zaki 2015). Specifically, it has
been demonstrated that the ability to share, celebrate, and
enjoy otherspositive emotions correlates with increased
prosocial behavior and well-being (Morelli, Lieberman,
and Zaki 2015). Furthermore, it has been hypothesized
that enhanced positive empathy may increase subjective
well-being (Morelli, Lieberman, and Zaki 2015), although
directionality has not been established. Our results could
provide limited evidence for directionality, as they
demonstrate that an earlier (morning after) increase in
positive arousal strongly correlates with a later (seven days
after) increase in well-being. However, future research
should more formallyassess a causal relationship between
(positive) empathy and well-being. Alternatively, because
psilocybin acutely enhances response bias towards posi-
tive emotions (Kometer et al. 2012), individuals may feel
more arousedwhen viewing positive emotions because
they are paying more attention to them. The shift of
emotional bias to positive emotions is a proposed
mechanism of antidepressant effects (Kometer et al.
2012), increasing individualspsychological well-being.
Importantly, previous studies have implicated empathic
deficits in symptom severity of depression (Cusi et al.
2011; Derntl et al. 2012). Therefore, enhancing implicit
emotional empathy could decrease depressive symptom
severity by shifting emotional biases towards positive
Correlational analysis also suggested a relationship
between changes in LS and changes in explicit EE.
Morning-after change score increases in concern for emo-
tional pictures and seven-day-after change score increases
in concern for negative pictures correlated with seven-day-
after change score increases in subjective LS. This is con-
sistent with previous findings of a relationship between
empathic concern and well-being (Gleichgerrcht and
Decety 2013;Thomasetal.2007).
A relationship was not found between changes in
DT or CT and LS. However, the therapeutic implica-
tions of enhanced creativity are still relevant. It may be
that, while not directly increasing subjective well-being,
enhancements in constructs of creativity open up
awindow of opportunitywhere therapeutic interven-
tions could prove more effective.
The current study is not without its limitations. The
small sample size restricts the generalizability of the data,
and high drop-out rates result in loss of statistical power
at the seven-day follow-up. Additional factors that restrict
generalizability include the selection bias, as individuals
chose to attend the retreat for various reasons. Due to the
non-random sample, as well as the lack of placebo con-
trol, it could be argued that sub-acute enhancements are
due to uncontrolled factors such as psychological expec-
tations, or the environment in which the drug is taken.
Previous research has shown that both factors, termed set
and setting, play an important role in the outcome of
a psychedelic experience (Lawn et al. 2017;Shewan,
Dalgarno, and Reith 2000). However, previous studies
demonstrating significant enhancement of psychedelics
on creativity, empathy, and positive psychological out-
comes have been found in a wide range of settings,
including clinical (Garcia-Romeu, Griffiths, and Johnson
2015; Griffiths et al. 2016,2011,2006;Osorioetal.2015),
experimental (Hysek et al. 2014; Kuypers et al. 2014,2017;
Pokorny et al. 2017; Preller et al. 2015;Schmidetal.2014),
and naturalistic environments (Barbosa et al. 2009;
Barbosa, Giglio, and Dalgalarrondo 2005; Bouso et al.
2012; Kuypers et al. 2016;Uthaugetal.2018). Taken
together, this is a strong indicator that the present study
effects are directly related to drug intake. That being said,
future placebo-controlled experimental studies could ide-
ally control for the potential influence of non-
pharmacological factors. Finally, future longitudinal clin-
ical research into the therapeutic mechanisms of psilocy-
bin could further assess the role of creativity and empathy
in symptom alleviation in the pathological population.
In conclusion, the present study demonstrates that
psilocybin, taken in a naturalistic setting, promotes
constructs of creativity and empathy, and enhances
subjective well-being. These findings highlight the pos-
sible underlying role of enhanced creativity and empa-
thy in the therapeutic potential of psychedelics.
Importantly, the effects outlast the acute state, poten-
tially opening up a window of opportunitywhere
therapeutic interventions could prove more effective.
These findings add further support to growing evidence
suggesting that psychedelics may hold therapeutic value
for treating stress-related mood disorders.
The authors would like to acknowledge and thank Stefana
Bosse and the Psychedelic Society UK for their collaboration
and permission to collect data at their experience weekends.
They would also like to thank all participants for their time
and effort.
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... American biochemist Kary Mullis considers his use of LSD to have played an important role in his discovery of a means to automate the polymerase chain reaction (PCR) (Doyle, 2002), a breakthrough for which he was awarded the Nobel Prize in Chemistry in 1993 (Shampo & Kyle, 2002). Notably, Mullis's breakthrough came not while under the influence of LSD, but subsequent to its usage, suggesting a more enduring change in cognition or creativity, as suggested by some studies (Frecska et al., 2012;Harman et al., 1966;Mason et al., 2019Mason et al., , 2021Uthaug et al., 2018). ...
... Further research with LSD has suggested it can enhance primary process thinking . Consumption of psilocybin truffles has been found to yield distinct effects on measures of creativity as part of the acute and persisting effects of the substance, increasing ratings of divergent thinking the morning following usage, and enhancing convergent thinking a week following usage (Mason et al., 2019). A moderate dose of psilocybin has been associated with spontaneous creative insights, while decreasing deliberate task-based creativity during the acute experience, with an increase in the number of novel ideas at seven days post experience reported (Mason et al., 2021), while a moderate (50 µg) dose of LSD has also been found to increase originality and novelty in thinking (Wießner et al., 2021b). ...
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Creativity, that is the creation of ideas or objects considered both novel and valuable, is among the most important and highly valued of human traits, and a fundamental aspect of the sciences. Dreams and hypnagogic states have been highly influential in promoting scientific creativity and insight, contributing to some important scientific breakthroughs. Phenomenologically, the latter states of consciousness share a great deal of overlap with the psychedelic state, which has also been associated with facilitating scientific creativity on occasion. The current article proposes that the dream, hypnagogic and psychedelic states share common features that make them conducive to supporting some aspects of scientific creativity and examines the putative underlying neurophenomenological and cognitive processes involved. In addition , some notable occurrences of scientific insights that have emerged from these types of altered states are reviewed and shared common features are presented, providing a ground for future research. The psychedelic state may have its own characteristic features making it amenable to creativity enhancement, such as brain hyperconnectivity, meta-cognitive awareness, access to a more dependable and sustained altered state experience, and potential for eliciting sustained shifts in trait openness. The contextual factors which may contribute to enhancement of scientific creativity and insight will be evaluated. While research in this area is limited, further work to elucidate how psychedelics may best contribute to scientific creativity enhancement is warranted.
... Takáto príprava môže pomôcť pri redukcii nepríjemných a náročných psychických skúsenosti, panických reakcií či paranoidných epizód. Aj ďalšie výskumy podporujú dôležitosť bezpečného a upraveného settingu (prostredia) a význam profesionálneho sittera (Bouso et al., 2012;Gasser et al., 2014;Mason et al., 2019;Palhano-Fontes et al., 2018). Pod vplyvom psychedelík je telesná schránka odkázaná na okolie. ...
... Dnešná tzv. "psychedelická renesancia" akcentuje bezpečné užívanie v kontrolovanom prostredí (Bouso et al., 2012;Gasser et al., 2014;Johnson et al., 2008;Mason et al., 2019;Palhano-Fontes et al., 2018). ...
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Introduction. With growing interest in hallucinogens, majority of psychedelic research focus mostly on the therapeutic potential and benefits. The objective of this paper is to explore how users of psychedelics verbalize their experience and perceived risks of using such substances. Methods. The authors used a questionnaire with open-ended and multiple-choice items. The sample included persons with at least one phenomenological experience with psychedelics (N = 422, age M=27.78; SD=7.84; SE=0.38; 35.1% women). Qualitative data were analyzed using concepts of The Grounded Theory using the Atlas.ti suite. Results. The target group uses terms taken from the English language (“bad trip”, “set and setting”, “sitter”, or the grammatically localized version of the word „psychedelic“), with shared and well-understood semantic meaning within the community. The central domain “inappropriate set and setting” and its inadequate preparation is linked to the negative experience of “bad trip” which can lead to difficult “integration of experience” or even “psychotic disorders”. Users of psychedelics report various harm reduction strategies which are consistent with relevant literature. Conclusion. This study illustrates that Slovak users of psychedelics seem to understand and use the established terminology of international discourse related to these substances. At the same time, the authors suggest that users seem to use various relevant strategies to lower risks associated with the use of psychedelics.
... On the other hand, the latter study did reveal higher positive attitudes about life and/or self, positive mood changes, social effects, and behavioral changes, and well-being/life satisfaction both at 1 and 12 months [2]. Ayahuasca (consisting of N,N-Dimethyltryptamine (DMT) and a monoamine oxidase inhibitor) also seems to produce less consistent effects on personality; Openness 3 weeks post-drug intake increased in only one of two trials [10], but relative to baseline, it enhanced emotional and cognitive processes, lasting up to 4 weeks after the experience [11,12]. It should be mentioned that some of these studies were observational and far from all placebo controlled. ...
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The serotonergic classical psychedelics include compounds that primarily activate the brain’s serotonin 2 A receptor (5-HT2AR), such as LSD, psilocybin, and DMT (ayahuasca). The acute effects of these compounds are well-known as are their ability to increase the emotional state both in healthy people and in those with neuropsychiatric disorders. In particular psilocybin, the psychoactive constituent in “magic mushrooms”, has shown great potential for treatment of anxiety and depression. A unique and compelling feature of psychedelics is that intake of just a single psychedelic dose is associated with long-lasting effects. This includes effects on personality, e.g., higher openness, and amelioration of depressive symptoms. This review focuses on these stunning effects and summarizes our current knowledge on which behavioral, biochemical, neuroimaging, and electrophysiological data support that the intriguing effects of psychedelics on the human brain and mind are based on neural plasticity. The review also points to so far understudied areas and suggests research questions to be addressed in future studies which potentially can help to understand the intriguing long-term effects after intake of a single (or a few) psychedelic doses.
... Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD) or MDMA, cause a profound e ect on perception (Kometer et al. 2015;Kraehenmann et al. 2017), consciousness (Lebedev et al. 2015;Liechti et al. 2017;Smigielski et al. 2019), mood (Schmid and Liechti 2018;Forstmann et al. 2020), personality (Lebedev et al. 2016), and behavior (Kometer et al. 2012;Gri ths et al. 2018;Schmid and Liechti 2018). There is growing evidence that psychedelic substances can increase openness (MacLean et al. 2011), enhance creative thinking, along with empathy and subjective well-being Mason et al. 2019). In addition, altered states of consciousness, which contribute to the "mystical-type experiences" phenomena, seem to be one of the most important factors that can cause positive outcomes of the psychedelic experience (Gri ths et al. 2006MacLean et al. 2011;Barrett and Gri ths 2017; can deeply a ect human cognition, therefore, its potential to contribute to the positive outcomes of the psychedelic-assisted therapy should not be underestimated (Barrett et al. , 2018b. ...
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Psychedelics are getting closer to being widely used in clinical treatment. Music is known as a key element of psychedelic-assisted therapy due to its psychological effects, specifically on the emotion, meaning-making and sensory processing. However, there is still a lack of understanding in how psychedelics influence brain activity in experimental settings involving music listening. The main goal of our research is to investigate the effect of music, as a part of "setting", on the brain states dynamics after lysergic acid diethylamide (LSD) intake. We used an open dataset, where a group of 15 participants underwent two scanning sessions under LSD influence and under placebo. Every scanning session contained three runs: two resting-state runs separated by one run with music listening. We applied the K-Means clustering to identify the repetitive patterns of brain activity, so-called brain states. For further analysis, we calculated states' dwell time, fractional occupancy and transition probability. We found that the brain states dynamics during the resting-state and listening to music on both LSD and placebo does not differ significantly. Furthermore, we found that the music itself could potentially have a long-term influence on the resting-state, in particular on the states involving task-positive networks. Collectively, these findings suggest that the whole-brain states' dynamics during psychedelic experience and placebo is relatively stable, however, music, as a crucial element of setting, can potentially have an influence on the subject's resting-state. Further studies should replicate these results on a larger sample size.
... For example, standard ayahuasca doses increased scores in the WCST the day after its administration in healthy volunteers compared to the day prior (Murphy-Beiner and Soar 2020), and similar improvements were observed in regular ayahuasca users one year after baseline assessment . Moreover, high doses of ayahuasca and psilocybin influence cognitive thinking style days to weeks after administration (Mason et al. , 2019Uthaug et al. 2018), and psilocybin (11.9 mg/70 kg) also increased scores of novelty in the Alternative Users Test as a measure of creative thinking at 1-week follow-up compared to placebo . Importantly, similar effects on cognitive flexibility may occur in depressed populations as well. ...
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Recent trials with psychedelics in major depressive disorder and treatment-resistant depression showed remarkable improvements in depressive symptoms that can last for up to several months after even a single administration. The lack of an appropriate placebo control group—as patients are often able to discriminate the subjective effects of the drug—and an incomplete understanding of the role of the hallucinogenic and mystical experience, hampers the interpretation of these therapeutic effects. To control for these factors, we developed a translational framework based on establishing pharmacokinetic/pharmacodynamic (PK/PD) relationships in rodents and humans for hallucinogenic (i.e., discriminative stimulus effects in rodents and humans; head twitch responses in rodents; questionnaires in humans) and therapeutic effects. For the latter, we selected the pattern separation and attentional set-shifting tasks as measures for cognitive flexibility because of their high translational value. We predict that these PK/PD analyses will lead to a more objective evaluation of improvements in patients compared to relying only on the currently used self-reported questionnaires. We hypothesize that—if the role of the hallucinogenic experience is not central in the antidepressant effects of psychedelics—the ED50’s for the therapeutic effects will be significantly lower than for the hallucinogenic and mystical effects. Our framework will help to inform future studies that aim at the elucidation of the mechanism(s) of action of psychedelics in depression, and the role of the acute subjective and/or hallucinogenic experience in their effects.
... While some studies reported psychedelics to increase fluency and originality, others reported decreased fluency, originality and convergent thinking (Frecska et al., 2012;Harman et al., 1966;Kuypers et al., 2016;Mason et al., 2021). This could be attributed to relatively high doses impairing cognitive processing, in line with findings of increased fluency, originality and convergent thinking after psychedelic ceremonies and under microdoses (Mason et al., 2019;Prochazkova et al., 2018;Uthaug et al., 2018Uthaug et al., , 2019. ...
Background: Controversy surrounds psychedelics and their potential to boost creativity. To date, psychedelic studies lack a uniform conceptualization of creativity and methodologically rigorous designs. Aims: This study aimed at addressing previous issues by examining the effects of lysergic acid diethylamide (LSD) on creativity using multimodal tasks and multidimensional approaches. Methods: In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy volunteers received 50 μg of LSD or inactive placebo. Near drug peak, a creativity task battery was applied, including pattern meaning task (PMT), alternate uses task (AUT), picture concept task (PCT), creative metaphors task (MET) and figural creativity task (FIG). Creativity was assessed by scoring creativity criteria (novelty, utility, surprise), calculating divergent thinking (fluency, originality, flexibility, elaboration) and convergent thinking, computing semantic distances (semantic spread, semantic steps) and searching for data-driven special features. Results: LSD, compared to placebo, changed several creativity measurements pointing to three overall LSD-induced phenomena: (1) 'pattern break', reflected by increased novelty, surprise, originality and semantic distances; (2) decreased 'organization', reflected by decreased utility, convergent thinking and, marginally, elaboration; and (3) 'meaning', reflected by increased symbolic thinking and ambiguity in the data-driven results. Conclusion: LSD changed creativity across modalities and measurement approaches. Three phenomena of pattern break, disorganization and meaning seemed to fundamentally influence creative cognition and behaviour pointing to a shift of cognitive resources 'away from normal' and 'towards the new'. LSD-induced symbolic thinking might provide a tool to support treatment efficiency in psychedelic-assisted therapy.
... Since psilocybin is a preferential partial agonist of the 5-HT 2A and 5-HT 1A receptors, it is well-suited for investigation of the relative contributions of these subtypes to aspects of emotional processing. In healthy participants, 5-HT 2A / 1A -receptor stimulation following psilocybin administration acutely enhanced mood and empathy (Mason et al., 2019;Pokorny et al., 2017), prosocial behaviour (Gabay et al., 2018) and attenuated processing of negative facial expressions and social pain (Bernasconi et al., 2014;Kometer et al., 2012;Preller et al., 2016). While these acute effects of psilocybin indicate that serotonin receptor stimulation is a promising target for improvement of emotional processing, investigation of the longer-term effects is of clinical relevance, as it is unclear whether psilocybin's prosocial effects persist post-acutely. ...
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Background Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin’s effects on cognitive function have not been widely or systematically studied. Aim The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. Methods In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants ( n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session. Results In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. Conclusions These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. Clinical Trial Registration EudraCT ( ) number: 2018-000978-30.
The field of psychedelic research is undergoing a revival, yet research focused on non-clinical psychedelic use remains relatively limited. The current qualitative study sheds light on how people use magic mushrooms, what they perceive the effects of such use to be, and the meanings that users attach to their magic mushroom experiences. To be eligible to participate in the study, participants were required to be young adults who had used magic mushrooms within the past three months and residents of Victoria, Canada. Semi-structured, one-on-one in-person interviews regarding magic mushroom use habits, culture, knowledge and other factors were conducted with each participant and subsequently analyzed thematically. Participants associated magic mushroom use with lasting impacts on their lives including transformation and learning experiences. Additionally, participants described strategies to optimize their magic mushroom experiences, including engaging in research regarding magic mushrooms as well as making use of peer supports. Furthermore, aspects of magic mushroom experiences conceptualized as harmful in previous studies were described by participants as associated with learning experiences and few harms. Participants' perceived positive outcomes and relatively low risk profile warrants further research to inform how magic mushroom users can maximize potential positive outcomes and also minimize harms.
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Recent clinical and preclinical evidence points towards empathogenic and prosocial effects elicited by psychedelic compounds, notably the serotonin 5-HT 2A agonists lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), and their derivatives. These findings suggest a therapeutic potential of psychedelic compounds for some of the behavioural traits associated with autism spectrum disorder (ASD), a neurodevelopmental condition characterized by atypical social behaviour. In this review, we highlight evidence suggesting that psychedelics may potentially ameliorate some of the behavioural atypicalities of ASD, including reduced social behaviour and highly co-occurring anxiety and depression. Next, we discuss dysregulated neurobiological systems in ASD and how they may underlie or potentially limit the therapeutic effects of psychedelics. These phenomena include: 1) synaptic function, 2) serotonergic signaling, 3) prefrontal cortex activity, and 4) thalamocortical signaling. Lastly, we discuss clinical studies from the 1960s and 70s that assessed the use of psychedelics in the treatment of children with ASD. We highlight the positive behavioural outcomes of these studies, including enhanced mood and social behaviour, as well as the adverse effects of these trials, including increases in aggressive behaviour and dissociative and psychotic states. Despite preliminary evidence, further studies are needed to determine whether the benefits of psychedelic treatment in ASD outweigh the risks associated with the use of these compounds in this population, and if the 5-HT 2A receptor may represent a target for social-behavioural disorders.
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Introduction Taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults. Methods During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested. Results We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected. Conclusion While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.
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Rationale: Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT2A agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness. Objective: Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters. Methods: Eight subjects received placebo (PL), and 45 ("very low dose, VLD”), 115 ("low dose, LD”), 215 ("medium dose, MD”), and 315 ("high dose, HD”) μg/kg body weight PY. The "Altered States of Consciousness Rating Scale” (5D-ASC), the "Frankfurt Attention Inventory” (FAIR), and the "Adjective Mood Rating Scale” (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined. Results: PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. "General inactivation”, "emotional excitability”, and "dreaminess” were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY. Conclusion: PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health
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Rationale Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects. Objectives The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style. The second objective was to assess whether sub-acute and long-term effects of ayahuasca depend on the degree of ego dissolution that was experienced after consumption of ayahuasca. Results Ayahuasca ceremony attendants (N = 57) in the Netherlands and Colombia were assessed before, the day after, and 4 weeks following the ritual. Relative to baseline, ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks. Likewise, convergent thinking improved post-ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and several aspects of mindfulness increased the day after the ceremony, but these changes failed to reach significance 4 weeks after. Changes in affect, satisfaction with life, and mindfulness were significantly correlated to the level of ego dissolution experienced during the ayahuasca ceremony and were unrelated to previous experience with ayahuasca. Conclusion It is concluded that ayahuasca produces sub-acute and long-term improvements in affect and cognitive thinking style in non-pathological users. These data highlight the therapeutic potential of ayahuasca in the treatment of mental health disorders, such as depression.
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Our creativity is challenged daily when facing new situations asking for novel solutions. Creativity, a multicomponent construct includes flexible divergent and rigid convergent thinking. Psychedelic drugs like psilocybin can enhance creativity and affect state of mind (mood, empathy, openness). Of note, flexible thinking is disturbed in psychopathological conditions like anxiety disorders and depression and preliminary findings have shown psychedelics to be efficacious in the treatment of those conditions. The question how psychedelics induce this state of enhanced flexible thinking remains to be answered and investigating the neurobiology underlying this phenomenon will not only help in understanding why psychedelics are of use in the therapeutic setting but also in other settings where flexible thinking is challenged. A model including neuronal networks, neurotransmitters and personal factors playing a role in this process will be proposed which can be put to the test by means of placebo-controlled pharmaco-imaging studies in healthy volunteers.
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Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.
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Introduction: This paper reports results from a preliminary observational study of ayahuasca-assisted treatment for problematic substance use and stress delivered in a rural First Nations community in British Columbia, Canada. Methods: The "Working with Addiction and Stress" retreats combined four days of group counselling with two expert-led ayahuasca ceremonies. This study collected pre-treatment and six months follow-up data from 12 participants on several psychological and behavioral factors related to problematic substance use, and qualitative data assessing the personal experiences of the participants six months after the retreat. Findings: Statistically significant (p < 0.05) improvements were demonstrated for scales assessing hopefulness, empowerment, mindfulness, and quality of life meaning and outlook subscales. Self-reported alcohol, tobacco and cocaine use declined, although cannabis and opiate use did not; reported reductions in problematic cocaine use were statistically significant. All study participants reported positive and lasting changes from participating in the retreats. Conclusions: This form of ayahuasca-assisted therapy appears to be associated with statistically significant improvements in several factors related to problematic substance use among a rural aboriginal population. These findings suggest participants may have experienced positive psychological and behavioral changes in response to this therapeutic approach, and that more rigorous research of ayahuasca-assisted therapy for problematic substance use is warranted.
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Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants (n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.
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Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration identifier: NCT00465595
Background: Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behaviour. Although the serotonin (5-HT) system has been implicated in modulating empathy and moral behaviour, the relative contribution of the various 5-HT receptor subtypes is still unknown. Methods: We investigated the acute effect of psilocybin (0.215mg/kg p.o.) in healthy human subjects on different facets of empathy and hypothetical moral decision-making using the Multifaceted Empathy Test (MET) (n=32) and the Moral Dilemma Task (MDT) (n=24). Results: Psilocybin significantly increased emotional, but not cognitive empathy compared to placebo, and the increase in implicit emotional empathy was significantly associated with psilocybin-induced changed meaning of percepts. In contrast, moral decision-making remained unaffected by psilocybin. Conclusions: These findings provide first evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behaviour. Furthermore, together with previous findings psilocybin appears to promote emotional empathy presumably via activation of 5-HT2A/1A receptors suggesting that targeting 5-HT2A/1A receptors has implications for potential treatment of dysfunctional social cognition.