63,803
Views
83
CrossRef citations to date
0
Altmetric
Articles

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

, M.Sc., Ph.D. ORCID Icon, , Ph.D., , M.Sc., Ph.D. & , Ph.D. ORCID Icon
Pages 123-134 | Received 23 Oct 2018, Accepted 18 Jan 2019, Published online: 26 Feb 2019

ABSTRACT

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.

Introduction

Creativity and empathy are crucial for everyday interactions and cooperation, allowing us to adapt to an ever-changing environment, and motivating our prosocial behaviors (Decety et al. Citation2016). Interestingly, they have been found to be positively related (Carlozzi et al. Citation1995), and it has been suggested that creative, flexible thinking is a prerequisite for empathy (Eslinger Citation1998). Previous research demonstrates a reduction in these skills in populations where social interactions and subjective well-being are compromised (Beck Citation1967; Neumann et al. Citation2011).

Creativity is a multicomponent construct, consisting of convergent (CT) and divergent thinking (DT) (Guilford Citation1967). 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 Citation2012). Although both CT and DT are important in creative activities, DT may be a more useful estimate of the potential for creative thought in daily life (Runco and Acar Citation2012).

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 Citation1975). Previous research suggests a specificity of the two constructs (Davis Citation1980), in that emotional empathy may depend on state variables, whereas cognitive empathy requires a (trait) ability to identify another’s emotions (Hurlemann et al. Citation2010; Pokorny et al. Citation2017).

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. Citation2006; Cusi et al. Citation2011; Donges et al. Citation2005; Lee and Orsillo Citation2014; Morrison et al. Citation2016; Nietlisbach et al. Citation2010; Palm and Follette Citation2011; Parlar et al. Citation2014). Hallmarks of these disorders are repetitive and rigid patterns of negative and compulsive thoughts, together with social difficulties and impaired empathic abilities (Aldao, Nolen-Hoeksema, and Schweizer Citation2010; Beck Citation1967; Dos Santos et al. Citation2016; Morrison et al. Citation2016; Nietlisbach and Maercker Citation2009; Todd et al. Citation2015), the latter of which, most evident in depression, may contribute to more pronounced symptoms (Cusi et al. Citation2011; Donges et al. Citation2005).

Importantly, previous research has found that these processes demonstrate plasticity and can be enhanced by interventions such as therapy programs, hormone administration, and mindfulness induction, as well as (positive) changes in mood (Ashby, Isen, and Turken Citation1999; Baas, De Dreu, and Nijstad Citation2008; Davis Citation2009; Donges et al. Citation2005; Forgeard and Eichner Citation2014; Hurlemann et al. Citation2010; Lee and Orsillo Citation2014; Palgi, Klein, and Shamay-Tsoory Citation2016). 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. Citation2016; Harman et al. Citation1966; Krippner Citation1964; Kuypers Citation2018; Kuypers et al. Citation2016; Pokorny et al. Citation2017; Preller et al. Citation2015; Sessa Citation2008; Uthaug et al. Citation2018). Furthermore, clinical studies have found that administration of psilocybin can induce long-lasting positive psychological changes, such as symptom remission and enhancement of well-being, in clinical populations (Carhart-Harris et al. Citation2016; Griffiths et al. Citation2016; Johnson, Garcia-Romeu, and Griffiths Citation2017). However, the persistence of effects on creativity and empathy, and the relationship 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. Citation2017). 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.

Methods

Participants

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) participant age was 34.8 (8.9).

About half (52.7%) of the participants had used psilocybin before, and 49.1% had previously used a psychedelic other than psilocybin (LSD, ayahuasca, or DMT). Motivations for attending the retreat included “to understand myself” (83.6%), “curiosity” (80%), “to resolve problems” (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 amendments 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 provided. 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 disorders 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, participants 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 meeting.

Psilocybin

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 2–3 times. Afterwards participants could eat the remaining truffle contents in the cup.

Previous experimental studies have demonstrated that subjective alterations after psilocybin intake begin 20–40 minutes following administration, peak around 60–90 minutes, and subside by six hours post-intake (Hasler et al. Citation2004). However anecdotal reports suggest that when ingested in tea form, subjective alterations are felt more quickly, and for a shorter amount of time (Erowid Citation2015).

Study procedure

Creativity, empathy, and well-being assessments were taken on three separate occasions: at baseline (the evening 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 investigators 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 psilocybin and its metabolite, psilocin. The German Central Customs Authority determined the contents of psilocin and psilocybin after freeze-drying the truffles using a previously described HPLC method (Laussmann and Meier-Giebing Citation2010).

Picture concept task

In order to assess creativity, the picture concept task (PCT) was used (Kuypers et al. Citation2016). The PCT consists of 17 stimuli, each containing between 4 and 12 color pictures shown in a matrix of 2 × 2, 2 × 3, 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 dependent 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 parameters—i.e., fluency, originality, and the ratio of both—which reflect quantity and quality of divergent thinking. Fluency is defined as the number of alternative associations. The second parameter (i.e., originality) 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 participant 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 (creativity) 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 psychedelics (Kuypers et al. Citation2016; Prochazkova et al. Citation2018; Uthaug et al. Citation2018).

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. Citation2008). 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. Citation2008), and previous studies have found it to be sensitive to the effects of psychedelics (Hysek et al. Citation2014; Kuypers et al. Citation2014, Citation2017; Pokorny et al. Citation2017; Preller et al. Citation2015; Schmid et al. Citation2014).

Satisfaction with Life Scale

The Satisfaction with Life Scale (SWLS) is a five-item questionnaire designed to measure global cognitive judgments of satisfaction with one’s life (Diener et al. Citation1985), and has been used to measure the life satisfaction component of subjective well-being (Diener et al. Citation1985; Pavot et al. Citation1991). 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 ideal” and “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 5–19 defined as dissatisfied to below average life satisfaction, 20–24 defined as average life satisfaction, and 29–35 defined as high to very high life satisfaction (Pavot and Diener Citation2013). The scale has previously been shown to be a valid and reliable measure of life satisfaction (Pavot and Diener Citation2009).

Psilocybin experience

The morning after ingesting psilocybin, participants were asked to retrospectively rate the intensity of various 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 usually” and 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. Citation2012).

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 psilocybin) 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 compound 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 psilocybin experience differed from psilocybin-naïve participants on outcome measures, a further mixed-model analysis was conducted, with Session (three levels: baseline, morning after psilocybin, and seven days after psilocybin) 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 cognitive (creativity and empathy) and subjective (well-being) outcome parameters, Pearson’s correlations were carried out using baseline change scores (Morning after—baseline; seven days after—baseline).

Psilocybin experience ratings were analyzed separately using one-sample t tests 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. Citation2016).

Results

In total, 55 participants completed parts of the test battery at baseline, 50 completed parts of the test battery the morning after taking psilocybin, and 22 completed 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.

Psilocybin

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, psilocybin 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 (F2,37.48 = 5.94, p = .01) on the number of correct associations (see ). 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 morning after taking psilocybin.

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).

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).

Divergent thinking

Analysis revealed a significant main effect of Session on Fluency (F2,38.22 = 5.27, p = .01) and Originality (F2,45.09 = 7.23, p = .002) (see ). 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 significant effect of session on Ratio (F2,42.44 = 2.25, p = .12). Furthermore, there were no significant effects of psilocybin 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 (F2,23.26 = 3.18, p = .06); participants were able to recognize about 22 emotions on average in the three sessions (see ).

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 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).

Emotional empathy

Analysis revealed a significant main effect of Session (F2,48.31 = 4.29, p = .02) on average Explicit EE (see )). 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 (F2,38.04 = 5.87, p = .01) on concern ratings of negative 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 (F2,51.42 = 2.58, p= .09) on concern ratings of positive Explicit EE.

Analysis revealed a significant main effect of Session (F2,23.71 = 10.64, p = .001) on average Implicit EE ratings (see )). 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 (F2,25.72 = 7.89, p = .002) and negative (F2,19.18 = 4.93, p= .02) emotions. Separate contrasts indicated that, compared to baseline, individuals’ arousal to both positive (p = .001; d= .61) and negative (p = .01; d= .48) emotions was higher the morning after ingesting psilocybin. 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 (F2,48.31 = 17.83, p< .001) on individuals’ responses to the SWLS (see ). 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.

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).

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).

Previous experience with psilocybin

Twenty-nine participants reported previously using psilocybin, whereas 21 reported being psilocybin 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 (F2,52.44 = 16.768, p< .000) and Psilocybin experience (F1,46.93 = 5.39, p= .025) on individuals’ response to the SWLS ()). 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.

Correlations

Analysis showed medium to strong positive correlations 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 (rs) = .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 psilocybin are shown in . The one-sample t tests showed psilocybin-induced significant increases in all VAS items (t49 = 14.56–23.73; p≤ .000; d= 2.05–3.35).

Figure 4. Mean (±SE) of visual analogue scale item scores on a 10 cm scale. Scores are retrospective of the psilocybin experience.

Figure 4. Mean (±SE) of visual analogue scale item scores on a 10 cm scale. Scores are retrospective of the psilocybin experience.

Discussion

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 at a psychedelic retreat, were demonstrated relative to baseline. Correlational analyses suggest a positive relationship between sub-acute enhancements in EE and LS.

The findings demonstrate a time- and construct-related differentiation of effects of psilocybin on creativity; 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-HT2A agonist N,N-Dimethyltryptamine (DMT), acutely enhanced DT and impaired CT in individuals participating in an ayahuasca ceremony (Kuypers et al. Citation2016). Furthermore, a similar study demonstrated persisting sub-acute enhancements of CT one month after participation in an ayahuasca ceremony (Uthaug et al. Citation2018). Taken together, our findings suggest that whereas psychedelic-induced enhancements of DT outlast 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 implications, 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 Citation2014). 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. Citation2008; Frecska, Bokor, and Winkelman Citation2016; Frecska et al. Citation2012). 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. Citation2016).

Findings demonstrate a time-, component-, and valence-differentiation of effects of psilocybin on empathy; whereas explicit and implicit EE were shown to increase the morning after psilocybin use, CE was unaffected. Furthermore, enhancement in implicit EE to pictures 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. Citation2014; Kuypers et al. Citation2014, Citation2017; Pokorny et al. Citation2017; Preller et al. Citation2015; Schmid et al. Citation2014) without impairing CE. Taken together, these findings suggest that psilocybin (sub)-acutely increases individuals’ ability to feel what other people are feeling, without affecting individuals’ ability 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, participants 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 20–24 reflect an “average” LS, defined by general satisfaction, but with a desire for improvement in major domains (e.g., work/school, family) (Pavot and Diener Citation2013). A score of 25–29 is considered a “high” score, suggestive of an enjoyable life and satisfaction in the major domains. Based on interpretation scores, results suggest that psilocybin ingestion increased individuals’ LS from “average” to “high” until at least seven days after use. This finding is consistent with previous studies showing acute (Schmid et al. Citation2014), sub-acute (Barbosa, Giglio, and Dalgalarrondo Citation2005; Uthaug et al. Citation2018), and long-term (Barbosa et al. Citation2009; Bouso et al. Citation2012; Garcia-Romeu, Griffiths, and Johnson Citation2015; Griffiths et al. Citation2011; Grob et al. Citation2011; Lawn et al. Citation2017; Osorio et al. Citation2015; Thomas et al. Citation2013) 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 creativity would correlate with changes in satisfaction with life. Correlational analysis suggested a positive relationship 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 other’s positive emotions (Morelli, Lieberman, and Zaki Citation2015). Specifically, it has been demonstrated that the ability to share, celebrate, and enjoy others’ positive emotions correlates with increased prosocial behavior and well-being (Morelli, Lieberman, and Zaki Citation2015). Furthermore, it has been hypothesized that enhanced positive empathy may increase subjective well-being (Morelli, Lieberman, and Zaki Citation2015), 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 formally assess a causal relationship between (positive) empathy and well-being. Alternatively, because psilocybin acutely enhances response bias towards positive emotions (Kometer et al. Citation2012), individuals may feel more “aroused” when 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. Citation2012), increasing individuals’ psychological well-being. Importantly, previous studies have implicated empathic deficits in symptom severity of depression (Cusi et al. Citation2011; Derntl et al. Citation2012). Therefore, enhancing implicit emotional empathy could decrease depressive symptom severity by shifting emotional biases towards positive emotions.

Correlational analysis also suggested a relationship between changes in LS and changes in explicit EE. Morning-after change score increases in concern for emotional 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 consistent with previous findings of a relationship between empathic concern and well-being (Gleichgerrcht and Decety Citation2013; Thomas et al. Citation2007).

A relationship was not found between changes in DT or CT and LS. However, the therapeutic implications of enhanced creativity are still relevant. It may be that, while not directly increasing subjective well-being, enhancements in constructs of creativity open up a “window of opportunity” where therapeutic interventions 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 control, it could be argued that sub-acute enhancements are due to uncontrolled factors such as psychological expectations, 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. Citation2017; Shewan, Dalgarno, and Reith Citation2000). However, previous studies demonstrating significant enhancement of psychedelics on creativity, empathy, and positive psychological outcomes have been found in a wide range of settings, including clinical (Garcia-Romeu, Griffiths, and Johnson Citation2015; Griffiths et al. Citation2016, Citation2011, Citation2006; Osorio et al. Citation2015), experimental (Hysek et al. Citation2014; Kuypers et al. Citation2014, Citation2017; Pokorny et al. Citation2017; Preller et al. Citation2015; Schmid et al. Citation2014), and naturalistic environments (Barbosa et al. Citation2009; Barbosa, Giglio, and Dalgalarrondo Citation2005; Bouso et al. Citation2012; Kuypers et al. Citation2016; Uthaug et al. Citation2018). 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 ideally control for the potential influence of non-pharmacological factors. Finally, future longitudinal clinical research into the therapeutic mechanisms of psilocybin 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 possible underlying role of enhanced creativity and empathy in the therapeutic potential of psychedelics. Importantly, the effects outlast the acute state, potentially opening up a “window of opportunity” where 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.

Acknowledgments

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.

References

  • Aldao, A., S. Nolen-Hoeksema, and S. Schweizer. 2010. Emotion-regulation strategies across psychopathology: A meta-analytic review. Clinical Psychology Review 30 (2):217–37. doi:10.1016/j.cpr.2009.11.004.
  • Ashby, F. G., A. M. Isen, and A. U. Turken. 1999. A neuropsychological theory of positive affect and its influence on cognition. Psychological Review 106 (3):529–50.
  • Baas, M., C. K. De Dreu, and B. A. Nijstad. 2008. A meta-analysis of 25 years of mood-creativity research: Hedonic tone, activation, or regulatory focus? Psychological Bulletin 134 (6):779–806. doi:10.1037/a0012815.
  • Barbosa, P. C., I. M. Cazorla, J. S. Giglio, and R. Strassman. 2009. A six-month prospective evaluation of personality traits, psychiatric symptoms and quality of life in ayahuasca-naive subjects. Journal of Psychoactive Drugs 41 (3):205–12. doi:10.1080/02791072.2009.10400530.
  • Barbosa, P. C., J. S. Giglio, and P. Dalgalarrondo. 2005. Altered states of consciousness and short-term psychological after-effects induced by the first time ritual use of ayahuasca in an urban context in Brazil. Journal of Psychoactive Drugs 37 (2):193–201. doi:10.1080/02791072.2005.10399801.
  • Beck, A. T. 1967. Depression: Clinical, experimental, and theoretical aspects. Philadelphia: University of Pennsylvania Press.
  • Bouso, J. C., R. Doblin, M. Farre, M. A. Alcazar, and G. Gomez-Jarabo. 2008. MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. Journal of Psychoactive Drugs 40 (3):225–36. doi:10.1080/02791072.2008.10400637.
  • Bouso, J. C., D. González, S. Fondevila, M. Cutchet, X. Fernández, P. C. R. Barbosa, M. A. Alcázar-Córcoles, W. S. Araújo, M. J. Barbanoj, and J. M. Fábregas. 2012. Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of ayahuasca: A longitudinal study. PloS One 7 (8):e42421. doi:10.1371/journal.pone.0042421.
  • Carhart-Harris, R. L., M. Bolstridge, J. Rucker, C. M. J. Day, D. Erritzoe, M. Kaelen, M. Bloomfield, J. Rickard, B. Forbes, A. Feilding, et al. 2016. Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. The Lancet Psychiatry 3 (7):619–27. doi:10.1016/S2215-0366(16)30065-7.
  • Carhart-Harris, R. L., D. Erritzoe, T. Williams, J. M. Stone, L. J. Reed, A. Colasanti, R. J. Tyacke, R. Leech, A. L. Malizia, K. Murphy, et al. 2012. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences 109 (6):2138–43. doi:10.1073/pnas.1119598109.
  • Carlozzi, A. F., K. S. Bull, G. T. Eells, and J. D. Hurlburt. 1995. Empathy as related to creativity, dogmatism, and expressiveness. The Journal of Psychology 129 (4):365–73. doi:10.1080/00223980.1995.9914974.
  • Chamberlain, S. R., N. A. Fineberg, A. D. Blackwell, T. W. Robbins, and B. J. Sahakian. 2006. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. The American Journal of Psychiatry 163 (7):1282–84. doi:10.1176/appi.ajp.163.7.1282.
  • Colzato, L., A. Szapora, and B. Hommel. 2012. Meditate to create: The impact of focused-attention and open-monitoring training on convergent and divergent thinking. Frontiers in Psychology 3 (116). doi: 10.3389/fpsyg.2012.00116.
  • Cusi, A. M., G. M. Macqueen, R. R. Spreng, and M. C. McKinnon. 2011. Altered empathic responding in major depressive disorder: Relation to symptom severity, illness burden, and psychosocial outcome. Psychiatry Research 188 (2):231–36. doi:10.1016/j.psychres.2011.04.013.
  • Davis, M. A. 2009. Understanding the relationship between mood and creativity: A meta-analysis. Organizational Behavior and Human Decision Processes 108 (1):25–38. doi:10.1016/j.obhdp.2008.04.001.
  • Davis, M. H. 1980. A multidimensional approach to individual differences in empathy.JSAS Catalog of Selected Documents in Psychology 10, 85
  • Decety, J., I. B. A. Bartal, F. Uzefovsky, and A. Knafo-Noam. 2016. Empathy as a driver of prosocial behaviour: Highly conserved neurobehavioural mechanisms across species. Philosophical Transactions of the Royal Society B: Biological Sciences 371 (1686):20150077. doi:10.1098/rstb.2015.0077.
  • Derntl, B., E. M. Seidel, F. Schneider, and U. Habel. 2012. How specific are emotional deficits? A comparison of empathic abilities in schizophrenia, bipolar and depressed patients. Schizophrenia Research 142 (1):58–64. doi:10.1016/j.schres.2012.09.020.
  • Deutsch, F., and R. A. Madle. 1975. Empathy: Historic and current conceptualizations, measurement, and a cognitive theoretical perspective. Human Development 18 (4):267–87.
  • Diener, E., R. A. Emmons, R. J. Larsen, and S. Griffin. 1985. The satisfaction with life scale. Journal of Personality Assessment 49 (1):71–75. doi:10.1207/s15327752jpa4901_13.
  • Dolder, P. C., Y. Schmid, F. Müller, S. Borgwardt, and M. E. Liechti. 2016. LSD acutely impairs fear recognition and enhances emotional empathy and sociality. Neuropsychopharmacology 41 (11):2638. doi:10.1038/npp.2016.82.
  • Donges, U. S., A. Kersting, U. Dannlowski, J. Lalee-Mentzel, V. Arolt, and T. Suslow. 2005. Reduced awareness of others’ emotions in unipolar depressed patients. The Journal of Nervous and Mental Disease 193 (5):331–37.
  • Dos Santos, R. G., F. L. Osório, J. A. S. Crippa, J. Riba, A. W. Zuardi, and J. E. C. Hallak. 2016. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): A systematic review of clinical trials published in the last 25 years. Ther Adv Psychopharmacol 6 (3):193–213. doi:10.1177/2045125316638008.
  • Dziobek, I., K. Rogers, S. Fleck, M. Bahnemann, H. R. Heekeren, O. T. Wolf, and A. Convit. 2008. Dissociation of cognitive and emotional empathy in adults with Asperger syndrome using the Multifaceted Empathy Test (MET). Journal of Autism and Developmental Disorders 38 (3):464–73. doi:10.1007/s10803-007-0486-x.
  • Erowid. 2015. Mushroom tea preparation. Erowid.org. Accessed October 15, 2018. https://erowid.org/plants/mushrooms/mushrooms_prep2.shtml.
  • Eslinger, P. J. 1998. Neurological and neuropsychological bases of empathy. European Neurology 39 (4):193–99. doi:10.1159/000007933.
  • Forgeard, M. J. C., and K. V. Eichner. 2014. “Creativity as a target and tool for positive interventions”. In The Wiley Blackwell handbook of positive psychological interventions, edited by A. C. Parks & S. M. Schueller, 137–54. Wiley-Blackwell.
  • Forgeard, M. J. C., and J. G. Elstein. 2014. Advancing the clinical science of creativity. Frontiers in Psychology 5:613. doi:10.3389/fpsyg.2014.00613.
  • Frecska, E., P. Bokor, and M. Winkelman. 2016. The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization. Frontiers in Pharmacology 7:35. doi:10.3389/fphar.2016.00035.
  • Frecska, E., C. E. Móré, A. Vargha, and L. E. Luna. 2012. Enhancement of creative expression and entoptic phenomena as after-effects of repeated ayahuasca ceremonies. Journal of Psychoactive Drugs 44 (3):191–99. doi:10.1080/02791072.2012.703099.
  • Garcia-Romeu, A., R. R. Griffiths, and M. W. Johnson. 2015. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Current Drug Abuse Reviews 7 (3):157–64. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342293/.
  • Gleichgerrcht, E., and J. Decety. 2013. Empathy in clinical practice: How individual dispositions, gender, and experience moderate empathic concern, burnout, and emotional distress in physicians. PloS One 8 (4):e61526. doi:10.1371/journal.pone.0061526.
  • Griffiths, R. R., M. W. Johnson, M. A. Carducci, A. Umbricht, W. A. Richards, B. D. Richards, M. P. Cosimano, and M. A. Klinedinst. 2016. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology 30 (12):1181–97. doi:10.1177/0269881116675513.
  • Griffiths, R. R., M. W. Johnson, W. A. Richards, B. D. Richards, U. McCann, and R. Jesse. 2011. Psilocybin occasioned mystical-type experiences: Immediate and persisting dose-related effects. Psychopharmacology 218 (4):649–65. doi:10.1007/s00213-011-2358-5.
  • Griffiths, R. R., W. A. Richards, U. McCann, and R. Jesse. 2006. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology. 187 (3):268–83. discussion 284-92. doi:10.1007/s00213-006-0457-5.
  • Grob, C. S., A. L. Danforth, G. S. Chopra, M. Hagerty, C. R. McKay, A. L. Halberstadt, and G. R. Greer. 2011. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry 68 (1):71–78. doi:10.1001/archgenpsychiatry.2010.116.
  • Guilford, J. P. 1967. The nature of human intelligence. New York, NY, US: McGraw-Hill.
  • Harman, W. W., R. H. McKim, R. E. Mogar, J. Fadiman, and M. J. Stolaroff. 1966. Psychedelic agents in creative problem-solving: A pilot study. Psychological Reports 19 (1):211–27. doi:10.2466/pr0.1966.19.1.211.
  • Hasler, F., U. Grimberg, M. A. Benz, T. Huber, and F. X. Vollenweider. 2004. Acute psychological and physiological effects of psilocybin in healthy humans: A double-blind, placebo-controlled dose–Effect study. Psychopharmacology 172 (2):145–56. doi:10.1007/s00213-003-1640-6.
  • Hurlemann, R., A. Patin, O. A. Onur, M. X. Cohen, T. Baumgartner, S. Metzler, I. Dziobek, J. Gallinat, M. Wagner, W. Maier, et al. 2010. Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. The Journal of Neuroscience 30 (14):4999–5007. doi:10.1523/jneurosci.5538-09.2010.
  • Hysek, C. M., Y. Schmid, L. D. Simmler, G. Domes, M. Heinrichs, C. Eisenegger, K. H. Preller, B. B. Quednow, and M. E. Liechti. 2014. MDMA enhances emotional empathy and prosocial behavior. Social Cognitive and Affective Neuroscience 9 (11):1645–52. doi:10.1093/scan/nst161.
  • Johnson, M. W., A. Garcia-Romeu, and R. R. Griffiths. 2017. Long-term follow-up of psilocybin-facilitated smoking cessation. The American Journal of Drug and Alcohol Abuse 43 (1):55–60. doi:10.3109/00952990.2016.1170135.
  • Kometer, M., A. Schmidt, R. Bachmann, E. Studerus, E. Seifritz, and F. X. Vollenweider. 2012. Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biological Psychiatry 72 (11):898–906. doi:10.1016/j.biopsych.2012.04.005.
  • Krippner, S. 1964. The hypnotic trance, the psychedelic experience, and the creative act. American Journal of Clinical Hypnosis 7 (2):140–47. doi:10.1080/00029157.1964.10402408.
  • Kuypers, K. P. C. 2018. Out of the box: A psychedelic model to study the creative mind. Medical Hypotheses 115:13–16. doi:10.1016/j.mehy.2018.03.010.
  • Kuypers, K. P. C., R. de la Torre, M. Farre, S. Yubero-Lahoz, I. Dziobek, W. van Den Bos, and J. G. Ramaekers. 2014. No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation. PloS One 9 (6):e100719. doi:10.1371/journal.pone.0100719.
  • Kuypers, K. P. C., P. C. Dolder, J. G. Ramaekers, and M. E. Liechti. 2017. Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies. Journal of Psychopharmacology 31 (5):589–98. doi:10.1177/0269881117699617.
  • Kuypers, K. P. C., J. Riba, M. de la Fuente Revenga, S. Barker, E. L. Theunissen, and J. G. Ramaekers. 2016. Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking. Psychopharmacology 233 (18):3395–403. doi:10.1007/s00213-016-4377-8.
  • Laussmann, T., and S. Meier-Giebing. 2010. Forensic analysis of hallucinogenic mushrooms and khat (Catha edulisForsk) using cation-exchange liquid chromatography. Forensic Science International 195 (1):160–64. doi:10.1016/j.forsciint.2009.12.013.
  • Lawn, W., J. E. Hallak, J. A. Crippa, R. Dos Santos, L. Porffy, M. J. Barratt, J. A. Ferris, A. R. Winstock, and C. J. A. Morgan. 2017. Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: A large, international, self-selecting online survey. Scientific Reports 7 (1):15201. doi:10.1038/s41598-017-14700-6.
  • Lee, J. K., and S. M. Orsillo. 2014. Investigating cognitive flexibility as a potential mechanism of mindfulness in Generalized Anxiety Disorder. Journal of Behavior Therapy and Experimental Psychiatry 45 (1):208–16. doi:10.1016/j.jbtep.2013.10.008.
  • Morelli, S. A., M. D. Lieberman, and J. Zaki. 2015. The emerging study of positive empathy. Social and Personality Psychology Compass 9 (2):57–68. doi:10.1111/spc3.v9.2.
  • Morrison, A. S., M. A. Mateen, F. A. Brozovich, J. Zaki, P. R. Goldin, R. G. Heimberg, and J. J. Gross. 2016. Empathy for positive and negative emotions in social anxiety disorder. Behaviour Research and Therapy 87:232–42. doi:10.1016/j.brat.2016.10.005.
  • Neumann, M., F. Edelhäuser, D. Tauschel, M. R. Fischer, M. Wirtz, C. Woopen, A. Haramati, and C. Scheffer. 2011. Empathy decline and its reasons: A systematic review of studies with medical students and residents. Academic Medicine 86 (8):996–1009. doi:10.1097/ACM.0b013e318221e615.
  • Nietlisbach, G., and A. Maercker. 2009. Social cognition and interpersonal impairments in trauma survivors with PTSD. Journal of Aggression, Maltreatment & Trauma 18 (4):382–402. doi:10.1080/10926770902881489.
  • Nietlisbach, G., A. Maercker, W. Rossler, and H. Haker. 2010. Are empathic abilities impaired in posttraumatic stress disorder? Psychological Reports 106 (3):832–44. doi:10.2466/pr0.106.3.832-844.
  • Osorio, F. L., R. F. Sanches, L. R. Macedo, R. G. Santos, J. P. Maia-de-Oliveira, L. Wichert-Ana, D. B. Araujo, J. Riba, J. A. Crippa, and J. E. Hallak. 2015. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A preliminary report. Revista brasileira de psiquiatria 37 (1):13–20. doi:10.1590/1516-4446-2014-1496.
  • Palgi, S., E. Klein, and S. G. Shamay-Tsoory. 2016. Oxytocin improves compassion toward women among patients with PTSD. Psychoneuroendocrinology 64:143–49. doi:10.1016/j.psyneuen.2015.11.008.
  • Palm, K. M., and V. M. Follette. 2011. The roles of cognitive flexibility and experiential avoidance in explaining psychological distress in survivors of interpersonal victimization. Journal of Psychopathology and Behavioral Assessment 33 (1):79–86. doi:10.1007/s10862-010-9201-x.
  • Parlar, M., P. Frewen, A. Nazarov, C. Oremus, G. MacQueen, R. Lanius, and M. C. McKinnon. 2014. Alterations in empathic responding among women with posttraumatic stress disorder associated with childhood trauma. Brain and Behavior 4 (3):381–89. doi:10.1002/brb3.215.
  • Pavot, W., and E. Diener. 2013. The Satisfaction with Life Scale (SWL). Measurement instrument database for the social science. www.midss.ie.
  • Pavot, W., E. Diener, C. R. Colvin, and E. Sandvik. 1991. Further validation of the Satisfaction with Life Scale: Evidence for the cross-method convergence of well-being measures. Journal of Personality Assessment 57 (1):149–61. doi:10.1207/s15327752jpa5701_17.
  • Pavot, W., and E. Diener. 2009. “Review of the satisfaction with life scale”. In Social Indicators Research Series: Vol. 39. Assessing Well-Being: The Collected Works of Ed Diener (pp. 101–117). New York, NY: Springer Science + Business Media.
  • Pokorny, T., K. H. Preller, M. Kometer, I. Dziobek, and F. X. Vollenweider. 2017. Effect of psilocybin on empathy and moral decision-making. International Journal of Neuropsychopharmacology 20 (9):747–57. doi:10.1093/ijnp/pyx047.
  • Preller, K. H., T. Pokorny, R. Krähenmann, I. Dziobek, P. Stämpfli, and F. X. Vollenweider. 2015. The effect of 5-HT2A/1a agonist treatment on social cognition, empathy, and social decision-making. European Psychiatry 30:22. doi:10.1016/j.eurpsy.2014.02.004.
  • Prochazkova, L., D. P. Lippelt, L. S. Colzato, M. Kuchar, Z. Sjoerds, and B. Hommel. 2018. Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting. Psychopharmacology 235 (12):3401–13. doi:10.1007/s00213-018-5049-7.
  • Runco, M. A., and S. Acar. 2012. Divergent thinking as an indicator of creative potential. Creativity Research Journal 24 (1):66–75. doi:10.1080/10400419.2012.652929.
  • Schmid, Y., C. M. Hysek, L. D. Simmler, M. J. Crockett, B. B. Quednow, and M. E. Liechti. 2014. Differential effects of MDMA and methylphenidate on social cognition. Journal of Psychopharmacology 28 (9):847–56. doi:10.1177/0269881114542454.
  • Sessa, B. 2008. Is it time to revisit the role of psychedelic drugs in enhancing human creativity? Journal of Psychopharmacology 22 (8):821–27. doi:10.1177/0269881108091597.
  • Shewan, D., P. Dalgarno, and G. Reith. 2000. Perceived risk and risk reduction among ecstasy users: The role of drug, set, and setting. International Journal of Drug Policy 10 (6):431–53. doi:10.1016/S0955-3959(99)00038-9.
  • Thomas, G., P. Lucas, N. R. Capler, K. W. Tupper, and G. Martin. 2013. Ayahuasca-assisted therapy for addiction: Results from a preliminary observational study in Canada. Current Drug Abuse Reviews 6 (1):30–42.
  • Thomas, M. R., L. N. Dyrbye, J. L. Huntington, K. L. Lawson, P. J. Novotny, J. A. Sloan, and T. D. Shanafelt. 2007. How do distress and well-being relate to medical student empathy? A multicenter study. Journal of General Internal Medicine 22 (2):177–83. doi:10.1007/s11606-006-0039-6.
  • Todd, A. R., M. Forstmann, P. Burgmer, A. W. Brooks, and A. D. Galinsky. 2015. Anxious and egocentric: How specific emotions influence perspective taking. Journal of Experimental Psychology General 144 (2):374–91. doi:10.1037/xge0000048.
  • Uthaug, M. V., K. van Oorsouw, K. P. C. Kuypers, M. van Boxtel, N. J. Broers, N. L. Mason, S. W. Toennes, J. Riba, and J. G. Ramaekers. 2018. Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution. Psychopharmacology 235(10): 2979-2989.
  • Valle, M., A. E. Maqueda, M. Rabella, A. Rodriguez-Pujadas, R. M. Antonijoan, S. Romero, J. F. Alonso, M. A. Mananas, S. S. Barker, P. P. Friedlander, et al. 2016. Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. European Neuropsychopharmacology 26 (7):1161–75. doi:10.1016/j.euroneuro.2016.03.012.