Positive psychology in the investigation of psychedelics and entactogens: A critical review
This review looked at 77 studies with psychedelics and entactogens, to see how their effects relate to concepts of positive psychology. Psychedelics and entactogens showed positive effects e.g. on well-being, prosocial behaviours, empathy, creativity, personality, values and mindfulness. However, the authors stress that more longitudinal data on positive and adverse effects is needed.
Abstract
Rationale: We reviewed the concepts and empirical findings in studies with psychedelics and entactogens related to positive psychology - the study of healthy human functioning, well-being and eudaemonia. It is an unresolved question how beneficial effects of psychedelics and entactogens are related to the potential risks of these substances - particularly in non-clinical settings.Methods: We searched in PubMed, PsychINFO and the Cochrane Library for controlled clinical and epidemiological studies which applied concepts from positive psychology. We included N = 77 eligible studies with 9876 participants published before November 1st, 2017: (1) quantitative studies (N = 54), (2) preliminary or exploratory studies and reviews not including meta-analyses (N = 17), and (3) studies evidencing primarily negative results (N = 6).Results: Positive psychology concepts have been applied for measuring effects of clinical trials, recreational and ceremonial use of psychedelics and entactogens. Psychedelics and entactogens were shown to produce acute and long-term effects on mood, well-being, prosocial behaviours, empathy, cognitive flexibility, creativity, personality factors like openness, value orientations, nature-relatedness, spirituality, self-transcendence and mindfulness-related capabilities.Conclusions: There is preliminary evidence for beneficial effects of psychedelics and entactogens on measures of positive psychology in clinical and healthy populations, however their sustainability remains largely unresolved. The reported results must be considered preliminary due to methodological restrictions. Since longitudinal data on both positive and adverse effects of psychedelics are lacking, more rigorous and standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to carefully assess the benefit-risk-ratio.
Research Summary of 'Positive psychology in the investigation of psychedelics and entactogens: A critical review'
Introduction
Research on psychedelics and entactogens has historically concentrated on clinical pathology and mechanisms of disease, while their possible benefits for healthy human functioning have received much less systematic attention. Jungaberle and colleagues note that despite widespread recreational and ceremonial use and frequent anecdotal reports of enhanced well-being, self-transcendence and prosociality, empirical evidence linking these substances to positive psychological outcomes remains fragmentary and methodologically heterogeneous. This review set out to map how concepts from positive psychology have been applied in experimental, clinical and epidemiological studies of serotonergic psychedelics (e.g. LSD, psilocybin, DMT/ayahuasca) and entactogens (MDMA). The investigators aimed to identify what beneficial effects have been reported, how they were operationalised and measured, and what methodological limitations constrain interpretation. They organised the literature into acute versus persistent effects and social versus personal domains to evaluate claims about sustained improvements in well-being, creativity, prosocial attitudes and related constructs.
Methods
The authors performed an extensive literature search of MEDLINE (PubMed), PsycINFO and the Cochrane Library up to 1 November 2017. The protocol targeted controlled clinical and neuroscience studies as well as observational epidemiological investigations that employed constructs linked to positive psychology (for example well-being, prosocial behaviour, empathy, mindfulness, self-transcendence, creativity and openness). The search yielded 2,550 initial records and ultimately N = 77 eligible sources. Included sources comprised randomized controlled clinical and neuroscience studies with attention to bias and reporting transparency, together with cohort, case-control, cross-sectional and follow-up epidemiological studies. The reviewers excluded qualitative studies, case reports, opinion pieces, uncontrolled field studies, preclinical work and studies that focused exclusively on pathological symptom scales or screening for clinical worsening among recreational users. The selected studies were classified into four outcome-oriented categories — acute social change, persistent social change, acute personal change and persistent personal change — and results were presented by substance (for example psilocybin, LSD, MDMA, ayahuasca/DMT). The extracted text indicates that tables and a flow diagram were used to summarise included studies, but these figures are not present in the provided extraction. The authors conducted a critical, narrative synthesis rather than a quantitative meta-analysis.
Results
The search identified 77 eligible sources, which the authors divided into quantitative empirical studies (N = 54), preliminary or exploratory studies and reviews not including meta-analyses (N = 17), and studies reporting primarily negative results (N = 6). The corpus included 3 treatment/follow-up treatment studies (total n = 38), 54 neurophysiological/neuropsychological or psychological studies (n = 2,149), 7 epidemiological studies (n = 7,689), 11 reviews and 2 pooled/meta-analyses. The selected literature spanned several decades, but most studies (62) were published since 2010. Acute social change: Psilocybin was associated with acute improvements in mood and reductions in neural responses to negative stimuli; an fMRI study reported decreased right amygdala response to neutral (p < 0.001) and negative (p = 0.001) stimuli together with increased self-reported positive mood (p = 0.001). Other psilocybin studies observed reduced neural reactivity to social exclusion and increases in both implicit (p < 0.05) and explicit (p < 0.01) emotional empathy. LSD studies showed decreased right medial prefrontal cortex and left amygdala responses to anxiety-inducing stimuli (p < 0.05), reduced identification of fearful and sad faces (p < 0.001), and acute enhancements in perceived closeness, openness, trust, desire for social contact and prosocial behaviour (various p-values reported, many p < 0.001). MDMA produced robust prosocial effects: improved perception of emotional stimuli, increased ratings of trustworthiness and cooperative behaviour (p < 0.05), dose-dependent increases in self-reported loving and friendly feelings (1.5 mg/kg; p = 0.004 and p = 0.001), and altered amygdala/ventral striatum reactivity to emotional faces (attenuated left amygdala response to angry faces p = 0.052; enhanced ventral striatum response to happy faces at the lower dose p < 0.005). Some MDMA effects correlated with measures of sympathetic activity and with oxytocin levels. Acute personal change: LSD increased emotional response to music (p = 0.006) and produced acute rises in subjective well-being, happiness (p < 0.001) and openness (p < 0.001). fMRI under LSD revealed increased global brain connectivity, particularly in thalamic and high-level association cortices, which correlated with reports of ego-dissolution. Ayahuasca/DMT studies reported acute reductions in inner reactivity (p = 0.034) and judgmental processing (p = 0.01), increases in cognitive flexibility/divergent thinking (p = 0.023), and early increases on subscales of the Five Facet Mindfulness Questionnaire (FFMQ) 24 hours post-administration. Magnetic resonance spectroscopy showed decreases in glutamate+glutamine that correlated with increases in the FFMQ non-judging subscale (r = -0.589, p = 0.044); a two-month follow-up indicated a tendency for continued elevation in non-judging. MDMA was reported to increase self-compassion and to reduce self-criticism in at least one study of recreational users. Persistent social change: Studies defining persistence as at least two weeks (and up to years) reported associations between classical psychedelic use and prosocial or pro-environmental attitudes. An online general population study with 1,487 participants found self-reported pro-environmental behaviours predicted by past classical psychedelic experience (p < 0.001), with nature identification statistically accounting for the relationship (p < 0.001). LSD and psilocybin studies reported long-lasting subjective prosocial effects (LSD p < 0.001; psilocybin increases in long-term positive social effects observed at 14 months). A two-year follow-up after a Phase II MDMA-assisted psychotherapy trial for treatment-resistant PTSD found long-term increases in openness (p = 0.032) and decreases in neuroticism (p = 0.003) on the NEO-PI-R. Persistent personal change: Observational data indicated psychedelic users scored higher on spirituality and mystical beliefs (p < 0.001), greater concern for others (p = 0.001), and lower valuation of financial prosperity (p = 0.001) compared with non-psychedelic users, although pre-existing personality differences could account for some findings. Lifetime users showed greater creativity (p = 0.02, reported d = -0.87) and psychedelic experience positively predicted liberal political views (p = 0.001), openness (p < 0.001) and nature relatedness (p < 0.001) while negatively predicting authoritarianism (p = 0.002). Two double-blind controlled psilocybin studies found significant increases in openness after a high-dose session (p = 0.023, η2 = 0.10); one-year follow-up measures remained above baseline among participants reporting a significant mystical experience (p = 0.05, η2 = 0.13). Neuroimaging measures of increased brain entropy under LSD (p < 0.001) and self-reported ego-dissolution predicted subsequent openness (p = 0.035). Carhart-Harris and colleagues reported improved psychological well-being two weeks after LSD; other LSD studies found long-lasting improvements in mood (p < 0.01), life satisfaction (p < 0.001) and general positive outlook (p < 0.001). Neurobiological correlations reported in the extraction further linked neurochemical and connectivity changes to mindfulness and self-compassion metrics: reductions in glutamate+glutamine correlated with increases in FFMQ non-judging (r = -0.589, p = 0.044); superior rostral ACC–PCC connectivity correlated with Non-Judging (r = 0.604, p = 0.013) and Non-Reacting (r = 0.522, p = 0.038); medial temporal ACC connectivity correlated with Self-Compassion (r = 0.514, p = 0.042) and with Non-Judging/Non-Reacting (r values 0.637 and 0.656, p-values 0.008 and 0.006). At two months, decreased glutamate+glutamine in the PCC correlated with Non-Judging differences (r = -0.74, p = 0.009). A negative correlation was also reported between amygdala BOLD response to fearful stimuli and subjective drug effects (r = -0.46, p < 0.05).
Discussion
Jungaberle and colleagues conclude that concepts and measures from positive psychology have been usefully applied across a heterogeneous literature to capture acute and some persistent changes associated with serotonergic psychedelics and MDMA. The review highlights converging preliminary evidence for acute improvements in emotional processing, increased empathy and prosocial feelings, enhanced cognitive flexibility and creativity, shifts in life values (including greater nature relatedness and spirituality), and the induction of mystical-type experiences and mindfulness-related capacities. Neuroimaging and spectroscopic findings are presented as supportive evidence that changes in network dynamics, brain entropy and neurotransmitter markers relate to reported psychological changes, and that experiences such as ego-dissolution may predict later shifts in traits like openness. At the same time, the authors emphasise substantial methodological limitations that temper confidence in these findings. Many studies used small, convenience or experienced-user samples, within-subject designs, or correlational approaches that preclude causal inference. Selection biases — including the frequent inclusion of participants with prior psychedelic experience — and cultural homogeneity (largely Western samples) further limit generalisability. The reviewers note sparse longitudinal data on both positive and adverse outcomes, variable measurement strategies and the absence of standardised positive-psychology measures across studies. They therefore call for more rigorous prospective, randomised and controlled studies with standardised instruments, larger and less biased samples, and monitoring of potential harms and neuropsychological functioning. Finally, the discussion frames psychedelics and entactogens as valuable tools for probing bio-psycho-social mechanisms that underlie personal and social change, but stresses ethical and harm-reduction considerations. The authors argue that future research should measure both potential benefits and risks, track risk perception and behaviours, and engage in ethical debate about clinical use and access for healthy individuals. They caution against uncritical endorsement given the current evidence base and recommend that rigorous longitudinal and controlled research be used to inform policy and clinical practice.
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METHODS
We searched in PubMed, PsychINFO and the Cochrane Library for controlled clinical and epidemiological studies which applied concepts from positive psychology. We included N = 77 eligible studies with 9876 participants published before November 1st2017:(1) quantitative studies (N = 54), (2) preliminary or exploratory studies and reviews not including meta-analyses (N = 17), and (3) studies evidencing primarily negative results (N = 6).
RESULTS
Positive psychology concepts have been applied for measuring effects of clinical trials, recreational and ceremonial use of psychedelics and entactogens. Psychedelics and entactogens were shown to produce acute and long-term effects on mood, well-being, prosocial behaviours, empathy, cognitive flexibility, creativity, personality factors like openness, value orientations, nature-relatedness, spirituality, self-transcendence and mindfulness-related capabilities.
CONCLUSIONS
There is preliminary evidence for beneficial effects of psychedelics and entactogens on measures of positive psychology in clinical and healthy populations, however their sustainability remains largely unresolved. The reported results must be considered preliminary due to methodological restrictions. Since longitudinal data on both positive and adverse effects of psychedelics are lacking, more rigorous and standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to carefully assess the benefit-risk-ratio.
INTRODUCTION
While previous psychedelic research mainly focused on pathophysiological disease models and clinical applications, potential beneficial effects of psychedelics and entactogens on healthy human functioning remain barely investigated. Psychedelics (serotonergic hallucinogens like LSD or psilocybin) and entactogens (like MDMA) are used for basic and clinical research, experimental therapy, but also in recreational and psychospiritual settings. Although the latter practices are illicit or strictly regulated for public health concerns, millions of users worldwide consume psychedelic substances without serious mental health problems. There are consistent claims by users and researchers that psychedelics might be useful in improving healthy human functioning, however more empirical research is needed to move beyond anecdotal evidence and carefully balance beneficial effects and harm potential.
TYPES OF STUDIES IN THE PSYCHEDELIC FIELD
Basic research with psychedelics is focused on understanding mental functions and their relationship with neuronal processes in the brain. Clinical research emphasizes the improvement of symptom measures in the treatment of diagnosed patients (e.g., Clinician-Administered PTSD Scale (CAPS) in trauma patients or depression scores) where psychedelics and entactogens are predominantly expected to provide valuable pharmacological tools for the augmentation of psychotherapy. Studies in non-clinical populations mostly focus on pathologies assumed to be induced by or associated with the misuse of these substances like impairment of memory, psychotic episodes or substance use disorders.
RISKS AND SAFETY ISSUES
Clinical settings supervised by medical doctors and psychotherapists were shown to provide safe environments for the administration of psychedelics and entactogens with marginal risks M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 2 for severe incidents). Yet a systematic evaluation of these risks in naturalistic medical settings still has to be conducted. In contrast, the recreational use of psychedelics and entactogens in the context of parties, festivals, ceremonies or private homes has generally been considered unsafe -not to speak of the fact that it is illicit to use, own or sell these substances in almost all countries. Globally there is a lack of structured and comparable reporting systems concerning drug-related incidents and deaths. Nevertheless, we see that MDMA related deaths are on the rise in several countries. Typical risks associated with the recreational use of MDMA include hyperthermia, dehydration, drug interactions, hyponatremia and overdose. A study conducted before the rise in media popularity of MDMA estimated the amount of ecstasy related deaths in the US to be about 50 a year. Death due to direct LSD toxicity is unknown. Major risks associated with the recreational use of classical psychedelics are anxiety and panic attacks, manifestation or exacerbation of psychotic disorder and hallucinogenic persisting perception disorders. It is agreed upon that toxicity of LSD, ayahuasca, psilocybin and DMT is generally low. Due to the development of new psychoactive substances like the NBOMe compounds several recent psychedelics have been linked to severe hospitalizations and fatalities.
BENEFITS AND POSITIVE PSYCHOLOGY IN THE INVESTIGATION OF PSYCHEDELICS AND ENTACTOGENS
Due to such risks LSD and other psychedelics have been listed in Schedule 1 of the US Controlled Substances Act and little attention has been given to the potential of psychedelics to improve healthy peoples' lives through the enhancement of characteristics that are not directly linked to risks and pathologies. Although it is recognized that adverse effects of these substances in uncontrolled settings may entail detrimental ramifications, the focus of the present paper revolves around beneficial effects across different intra-and interpersonal domains. In his reviewconcludes that for some people the psychedelic experience may not only produce improvements in mood but may also give access to states of consciousness and insights of great significance to the individual and his social group. With precursors since the 1960ties -like Maslow's theory of self-actualization-the domain of positive psychology started as a new field of research in the 1990ties.Hence, positive psychology provides a valuable conceptual framework to further elucidate the potential beneficial effects of psychedelics and entactogens on healthy human functioning. Here we investigate the claim that psychedelics and entactogens may produce acute and longterm beneficial outcomes in healthy mental functioning in both clinical and healthy populations by critically reviewing the current research literature. Specifically, we explored how beneficial effects were conceptually defined and empirically measured in these studies, including methodological limitations. Finally, we discuss the consequences of conducting research about psychedelics with concepts from positive psychology highlighting possible avenues for future studies.
METHODS
An extensive literature search and critical reviewwas conducted including papers until November 1 st , 2017. We searched the electronic databases MEDLINE (PubMed), Cochrane Library and PsycINFO with the aim to identify studies that applied concepts related to positive psychology in clinical and epidemiological research on psychedelics and entactogens. Our protocol included (1) randomized controlled clinical and neuroscience studieswith transparency in addressing possible biases and rigor in reporting characteristics. (2) From the observational field we included cohort studies, case-control studies, cross-sectional studies and follow-up studies)(Table1). Our protocol excluded qualitative studies, case reports, opinion papers, field studies as well as treatment or pre-clinical studies that either were not controlled and randomized, that exclusively used pathological measurements (like symptom scales) or had only screened for the worsening of clinical parameters in recreational user. The following search strings were used: "(psychedelics OR LSD OR psilocybin OR In the results the four categories acute/persistent/personal/social are presented under the heading of the substances ("Psilocybin", "MDMA" etc.). In the conclusion the studies are discussed under the headings of positive psychology constructs ("mindfulness", "creativity" etc.).
RESULTS
The electronic searches resulted in 2550 hits (2095 in PubMed, 323 in the Cochrane Library, and 132 results in PsychINFO)(Diagram 1). We found N = 77 eligible sources that were subsequently divided into the categories: (1) quantitative empirical studies (N = 54; see Table), (2) preliminary or exploratory studies and reviews not including meta-analyses (N = 17; see Table), and (3) studies evidencing primarily negative results (N = 6; see Table). The count is as follows: 3 treatment/follow-up of treatment studies (n = 38), 54 neurophysiological/neuropsychological or psychological studies (n = 2149), 7 epidemiological studies (n = 7689), 11 reviews and 2 pooled-/meta-analyses. Two of the selected studies were conducted in the 1960ties, 2 studies in the 1970ties, 1 study in the 1980ties, 2 studies in the 1990ties, 8 studies in the 2000s and 62 studies since 2010. We organized the results in the four categories "acute social change", "persistent social change", "acute personal change" and "persistent personal change". If overlap between the categories occurred, we decided based on main reported findings. Tableprovides an overview of the selected and reported studies and table 2 separately lists older, methodologically less elaborate studies and reviews that are mentioned selectively.
INSERT HERE DIAGRAM 1 FLOW DIAGRAM OF ELIGIBLE LITERATURE INSERT HERE TABLE 1 OVERVIEW OF SELECTED STUDIES WITH POSITIVE PSYCHOLOGY MEASURES INSERT HERE TABLE 2 TABLE 2: PRELIMINARY, EXPLORATORY STUDIES AND REVIEWS
Tablesummarizes studies we excluded because of methodological weakness that are of historical importance. Tableprovides a list of negative results within the eligible studies. These are explicitly not the result of an extensive search of negative adverse effects (which would provide much more extensive results). They are rather a byproduct of the search string that was performed to discover concepts and research about positive psychology related to psychedelics.
ACUTE SOCIAL CHANGE
This category includes phenomena that are precursors to or directly related to social behaviors.
PSILOCYBIN
Study participants under the influence of psilocybin report positive changes in mood. This positive effect on mood was found to be associated with reduced responses to negative stimuli subsequent to acute psilocybin administration. A functional magnetic resonance imaging (fMRI) study by, showed decreased right amygdala response to neutral (p < 0.001) and negative (p = 0.001) stimuli and increases in self-reports of positive mood (p = 0.001) in people under the influence of psilocybin.found decreased neural reactivity to self-reported social exclusion in the dorsal anterior cingulated cortex (dACC; p < 0.05) and the middle frontal gyrus (p < 0.05) in healthy subjects after the administration of psilocybin. Therefore, it was hypothesized that psilocybin reduces the processing of social pain.assessed how multiple facets of empathy and hypothetical decision making are acutely influenced by psilocybin in healthy volunteers. Both implicit (p < 0.05) and explicit (p < 0.01) emotional empathy were significantly affected by psilocybin compared to placebo. While moral-decision making was not influenced by psilocybin, heightened implicit emotional empathy was found to be related to the altered meaning of percepts induced by psilocybin (p < 0.01).
LYSERGIC ACID DIETHYLAMIDE (LSD)
Similar effects were reported using Lysergic acid diethylamide (LSD) in a laboratory study by. Using fMRI, LSD was shown to decrease right medial prefrontal cortex and left amygdala responses during the presentation of anxiety inducing stimuli (p < 0.05). This suggests that altered emotional processing under the influence of LSD relies on modulatory effects on cortico-limbic neurocircuitries. In line with this result,found that LSD reduced the identification of fearful and sad faces on the Face Emotion Recognition Task (FERT; p < 0.001). Additionally, acute social changes after administration of LSD included enhancements in perceived closeness to others (p < 0.001), openness (p < 0.001), trust (p < 0.001), desire to be with other people (p < 0.001), prosocial behavior (p < 0.05), as well as explicit (p < 0.001) and implicit (p = 0.01) emotional empathy. There is evidence that Methylenedioxymethamphetamine (MDMA) improves users' selfreported perception of and responses to emotional stimuli with social content, influences how people talk about significant others, increases empathy for positive emotional situations and enhances interpersonal empathy in social interactions.found MDMA to improve users' perception of trustworthiness (p < 0.05) and co-operative behaviors (p < 0.05), possibly contributing to the enhancement of empathy. Empathy on the Multifaceted Empathy Test (MET) was shown to be most distinct upon presentation of positive emotions compared to negative emotions (p = 0.001, partial η2 = 0.09).measured correlates of prosocial reactions under the influence of MDMA. Subjective changes were assessed through self-report ratings of affective states and tasks in which participants identified emotions from images of faces, pictures of eyes, and vocal cues. The higher dose of MDMA (1,5mg/kg) increased ratings of "loving" (p = 0.004, η 2 = 0.21) and "friendly" (p = 0.001, η 2 = 0.26), whereas the lower dose of MDMA (.75mg/kg) increased "loneliness" (p = 0.008). In another study, a higher dose of MDMA (1.5 mg/kg) increased self-reported sociability (η 2 = 0.28) compared to lower dose MDMA (0.75 mg/kg) and placebo. Higher dose MDMA (1.5 mg/kg) attenuated left amygdala response to angry facial expressions (p = 0.052), but MDMA did not affect amygdala reactivity to fearful expressions. Lower dose MDMA (0.75 mg/kg) enhanced ventral striatum response to happy expressions relative to placebo (p < 0.005).linked MDMA's prosocial effects to measures of sympathetic activity whilefound that prosocial feelings, i.e. subjective amicability (p = 0.001) and subjective gregariousness (p = 0.049), were correlated with variation in oxytocin levels. Participants in a study byshowed enhanced accuracy in decoding positive stimuli (p < 0.05) but decreased ability to decode negative stimuli (p < 0.01) on the Reading the Mind in the Eye Test. Similar effects were reported by.hypothesized MDMA to induce 'socially selective' effects which then influence prosocial behavior through increases in the ability to judge and compare closeness with others and social contact. In addition, under the acute influence of MDMA self-reported mood and self-esteem may be influenced to a lesser degree by social rejection.found evidence that positive effects of MDMA on self-evaluation might be due to the perception of increased authenticity which in turn potentially facilitates emotional and autobiographic In summary, a number of pro-social feelings and behaviors might be fostered under the acute influence of MDMA.
ACUTE PERSONAL CHANGE
Lysergic acid diethylamide (LSD)found LSD to significantly enhance participants' emotional response to music compared to placebo (p = 0.006).showed LSD to produce acute increases in subjective well-being (p < 0.05), happiness (p < 0.001), openness (p < 0.001), and trust (p < 0.001).used fMRI to depict heightened global connectivity within the brain, particularly in the thalamus and high-level association cortices of participants under the influence of LSD. These increases in global connectivity were found to correlate with subjective reports of 'ego dissolution' which is conceptually related to positive psychology constructs like "flow" and "spirituality".
AYAHUASCA AND DMT
The Amazonian plant tea ayahuascawas described to acutely decrease inner reactivity (p = 0.034) and judgmental processing (p = 0.01) in a non-controlled study, which are considered classical goals and beneficial effects associated with mindfulness practice. Conversely, ayahuasca increased cognitive flexibility, i.e. creative divergent thinking, in a quasi-experimental design (p = 0.023;.reported increases on certain subscales (nonjudging and nonreacting) of the Five Facets Mindfulness Questionnaire (FFMQ) 24h after ayahuasca administration. Magnetic resonance spectroscopy (MRS) illustrated decreases in glutamate and glutamine which correlated with increases in the nonjudging subscale of the FFMQ (r = -0.589, p = 0.044). Two month later, results still pointed to a tendency towards elevations in nonjudging.
METHYLENEDIOXYMETHAMPHETAMINE (MDMA)
MDMA was found to increase self-reported ratings of self-compassion and to decrease selfcriticism.
PERSISTENT SOCIAL CHANGE
We included results that were sustainable for at least two weeks with a range up to several years. We pooled psychometric variables of prosocial personal attitudes into this category, too, since they are highly predictive of prosocial behaviors (e.g. openness) Classical Psychedelicsconducted a general population online study with 1487 participants that demonstrated self-reported engagement in pro-environmental behaviors that were predicted by respondents' past experiences with classical psychedelics (p < 0.001). Their degree of self-identification with nature statistically accounted for the relationship (p < 0.001). The authors hypothesized that incorporation of nature into one's self-construal (possibly facilitated by psychedelics) may account for the effects on pro-environmental behavior. Yet the causality of this relationship must be further investigated. Furthermore,outline that LSD experience produced long lasting subjective effects of prosocial and altruistic behaviors in participants (p < 0.001). In a 14-month followup to their 2006 study,reported significant increases in self-ratings of long-lasting positive social effects and behaviors following psilocybin administration in hallucinogen-naïve adults.
METHYLENEDIOXYMETHAMPHETAMINE (MDMA)
Wagner et al. () conducted a two-year follow-up study to a phase two trial on MDMAassisted psychotherapy for treatment resistant PTSD. Results indicated long-term increases in openness (p = 0.032) and persistent decreases in neuroticism (p = 0.003) on the NEO-PI-R Personality Inventory on the personal effect side.
PERSISTENT PERSONAL CHANGE
Classical psychedelicsassessed the values, beliefs, and emotional empathy of users of psychedelics. Compared to users of non-psychedelic drugs and non-illicit drug-using social drinkers, psychedelic users exhibited increased values of spirituality (p < 0.001) and "mystical beliefs" (p < 0.001) as well as concern for others (p = 0.001), while displaying less appreciation of financial prosperity (p = 0.001). However, due to study limitations these findings may be due to personality characteristics preceding the use of psychedelics. In addition,found lifetime users of classical psychedelics to exhibit greater creativity than non-users (p = 0.02, d = -.87).found lifetime use of psychedelics to positively predict liberal political views (p = 0.001), openness (p < 0.001), and nature relatedness (p < 0.001) and to negatively predict authoritarian political views (p = 0.002). Changes in life values subsequent to psychedelic experiences, may account for continuous smoking cessation and reduction and were clinically associated with less severe affective withdrawal symptoms. This is further In two double-blind controlled studies of psilocybinfound a significant enhancement of the big-five trait openness (measured with the NEO inventory) in participants subsequent to a high-dose session with psilocybin (p = 0.023, η 2 = 0.10). In a one-year followup, measures of openness continued to be above baseline in those who had reported a significant mystical experience during the psilocybin session (p = 0.05, η 2 = 0.13). This may imply that mystical experience mediated by psilocybin potentially facilitate sustainable adult personality change. In a methodologically improved version ofwith a nontheologian clienteledemonstrated, that psilocybin lead to increases in self-rated measures of mystical experiences (p < 0.001). Additionally, a 14-month-follow-up study was conducted evaluating participants' psilocybin experiences to be important in terms of personal meaning and to constitute one of the five most spiritually significant events of their lives. Similar findings are reported in a study by. Expanded states of consciousness are known to sometimes entail acute distress such as anxiety during the acute drug effects. Nevertheless, in an online surveyfound 84% of the participants to endorse having benefited from their most challenging experience with psilocybin mushrooms.used fMRI to evidence global increases in brain entropy (p < 0.001), regarding sensory (p < 0.001) and hierarchically higher networks (p < 0.001), subsequent to LSD administration. Such modulations -as well as experienced ego-dissolution during the LSD-state -predicted an enhancement in the personality trait openness measured two weeks after LSD administration (p = 0.035).
CARHART-HARRIS ET AL. (2016) EXAMINED THE PSYCHOLOGICAL EFFECTS OF LSD ADMINISTRATION.
Improved psychological well-being was measured two weeks after the LSD experience. The authors hypothesized that heightened mood may be a secondary effect to an essential alteration in the quality of cognition.found that LSD may result in long lasting subjective effects of improved mood (p < 0.01), life satisfaction (p < 0.001) and an overall positive view on life (p < 0.001). In a preliminary dose-response relationship studyconcluded that LSD experiences significantly predicted scores on the Mysticism Scale (p < 0.001).
AYAHUASCA AND DMT
Two other psychedelics demonstrated the potential to induce psychospiritual experiences are
DISCUSSION
Positive psychology is a domain of scientific inquiry that emerged in the late 1990ties but has numerous antecessors in the history of science and philosophy. It highlights the importance of well-being, happiness and eudaemonia that support healthy human functioning. It is related to resilience research and salutogenesis (Kröninger-Jungaberle & Grevenstein, 2013). Interestingly, there are numerous anecdotal claims and preliminary scientific data about sustainable positive effects of psychedelics on aspects of healthy human functioning. Such claims motivate recreational and ceremonial uses of these substances, however, more empirical research is needed to further investigate possible beneficial effects and individual risk factors associated with the widespread use of these substances. To guide future research hypotheses, we critically reviewed studies using constructs from positive psychology related to psychedelics and entactogens.
STUDY SELECTION
Our analysis included 77 studies with a search string focused on concepts related to positive psychology (e.g. well-being, introspection, prosocial behaviour, empathy, mindfulness, selftranscendence, creativity and personality factors like openness). We found 3 treatment/followup of treatment studies (n = 38), 54 neurophysiological/neuropsychological or psychological studies (n = 2149), 7 epidemiological studies (n = 7689), 11 reviews and 2 pooled-/metaanalyses (Tables). Two of the selected studies were conducted in the 1960ties, 2 studies in the 1970ties, 1 study in the 1980ties, 2 studies in the 1990ties, 8 studies in the 2000s and 62 studies since 2010.
BENEFICIAL EFFECTS ON EMOTIONAL PROCESSING AND PROSOCIAL ATTITUDES
Acute changes in mood and psychological well-being have been reported as an effect of the administration of classical psychedelics like psilocybinincluding altered neural responses to negative or fearful stimuli. Reduction of fronto-limbic neural reactivity and altered emotional processing of aversive or negative valenced stimuli was also found after LSD administration. Conversely, MDMA increased ventral striatal reactivity to positive valenced stimuli (Bedi et. This is in line with the notion, that under the acute influence of MDMA self-reported mood and self-esteem may be influenced to a lesser degree by social rejection. Neural markers of increased brain entropy as well as the experience of ego-dissolution under the influence of LSD were specifically predictive of enhancements in the personality trait openness two weeks after LSD administration. Similarly, long-term increases in openness were reported in a 2-year-follow up after a clinical MDMA trialas well as following a high-dose psilocybin session that was persistent for participants who had reported a significant mystical experience during the session. For LSD, improved psychological well-being and long lasting subjective effects of improved mood, life satisfaction and an overall positive view on life have been described, similar findings including lower psychopathology scores were reported for regular ayahuasca use in ritual contexts. The later study, though, is typical of using rather selective convenient samples that were not sufficiently tested for pre-existing conditions. If the reported acute effects of LSD and MDMA may play a beneficial role in the augmentation of psychotherapeutic processes or psychospiritual practices remains to be further investigated. Concerning long-term effects on personality factors like openness future studies should investigate the role of social amplification that may play a role in sustaining these effects. Particularly MDMA was found to increase self-reported ratings of selfcompassion and to decrease self-criticism in a study with recreational users (e.g.. However, it remains unclear which social and psychological factors mediate and sustain or discontinue these effects under real life conditions.
SOCIAL COGNITION, EMPATHY AND PROSOCIAL BEHAVIORS
Acute social changes after LSD administration included enhancements in perceived closeness to others, openness, trust, desire to be with other people, prosocial behavior, as well as explicit and implicit emotional empathy. Notably,outline that LSD experience produced lasting subjective effects of prosocial and altruistic behaviors that were sustained after 12 months.reported heightened implicit emotional empathy that was related to the altered meaning of percepts induced by psilocybin. MDMA was also found to enhance prosocial feelings and behaviors as well as interpersonal empathy in social interactions. Acute prosocial changes were further demonstrated in brain imaging studies 13 depicting heightened ventral striatum reactivity to happy facial expressions and reduced amygdala reactivity to angry faces.found evidence that positive effects of MDMA on self-evaluation could be due to the perception of increased authenticity. Finally,andconcluded that MDMA partially improves the judgement of social situations and induces socially selective effects which then improve prosocial behavior. In conclusion, converging evidence suggests that serotonergic psychedelics and entactogens increase prosocial behaviors and attitudes, which makes them suitable tools to support psychotherapeutic processes. However, it remains to be shown how sustainable these effects are in the medium or longterm interval and whether overuse may be also associated with negative effects on social functioning.
COGNITIVE FLEXIBILITY, CREATIVITY, AND PROBLEM SOLVING
Enhanced cognitive flexibility, creativity, and imagination are generally found in psychedelic states, with long-term increases in creative problem-solving abilities and personality trait of openness. Specifically, ayahuasca may have the potential to increase cognitive flexibility through divergent thinkingand enhanced visual creativity. Two double blind controlled studies found a significant enhancement of imagination, creativity and aesthetic appreciation in participants after a high-dose session with psilocybin. These preliminary findings motivate further systematic research into the potential of psychedelics to enhance cognitive flexibility and problem-solving capacity. Specifically, acute vs. long-term effects need to be clearly distinguished, since performance on neurocognitive tasks might be affected under the acute influence of psychedelics, while divergent and more associative styles of thinking might be facilitated through repeated exposures.
CHANGES IN LIFE-VALUES AND ORIENTATIONS
Changes in core life-values and behavioral attitudes were found in several observational studies with psychedelic users. Psychedelic users scored higher on values of spirituality as well as concern for others, while displaying less appreciation of financial prosperity, compared to users of non-psychedelic drugs and non-illicit drug-using social drinkers. Conversely, classical psychedelic induced changes in life values may account for reductions in addictive behaviors. Experience with classical psychedelics was further related to increased self-identification with nature and actual proenvironmental behaviors. Finally, higher scores in spirituality
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and better psychosocial adaptation as reflected by some attitudinal traits such as Purpose in Life and Subjective Well-Being were found in ritual users of ayahuasca. In conclusion, there is preliminary evidence that psychedelic use is associated with changes in core life values that might be associated with prosocial and pro-environmental behaviors, however more longitudinal studies are needed to further corroborate those changes over time.
PSYCHOSPIRITUAL EXPERIENCES AND MINDFULNESS-RELATED CAPABILITIES
Increased levels of self-transcendenceand reduced cortical thickness in the posterior cingulate cortex (PCC) were found in regular ayahuasca users. This suggests that PCC cortical thickness, a key node of self-referential information processing in the brain, is inversely correlated to measures of spirituality and selftranscendence. This longitudinal finding is in line with the observation that reduced activity of the PCC is linked to acute experiences of ego dissolution under the influence of psychedelics. At the whole brain level, heightened global connectivity particularly in thalamo-cortical networks was found to be correlated to subjective reports of "ego dissolution" under LSD, which is in line with the entropic brain hypothesis. States of ego-dissolution or self-transcendence are a central characteristic of mystical-type experiences that are frequently reported in psilocybin subjects. Notably, psilocybin users mostly rate these among the five most significant spiritual experiences of their lives. Converging evidence highlights the relevance of mystical-type experience and participants' ratings of spiritual significance and personal meaning of the psilocybin sessions to mediate therapeutic outcomes in clinical studies with psychedelics (e.g. smoking cessation:. In a one-year follow-up of MacLean et al.'s (2011) two double blind controlled studies, measures of openness continued to be above baseline in those who had reported a significant mystical experience during the psilocybin session.found psychedelic users exhibited increased values of spirituality and "mystical beliefs". In a doseresponse studyconcluded that LSD experiences correlates positively with the Mysticism Scale. Notably, Mystical Experience scores correlated with changes in well-being and life satisfaction 12 months after LSD administration in another study. Apart from inducing acute and intense mystical-type experiences that may be perceived deeply meaningful or transformative by the participants, psychedelics were also found to increase mindfulness-related capabilities. For instance,
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15 elevated levels of mindfulness, self-compassion, and "decentering" that refers to the capacity to observe thoughts and emotions as transitory mental events without being trapped by them, was found after ayahuasca intake. In conclusion, the induction of transformative mystical-type experiences and mindfulness-related capabilities may both contribute to the noted increases in wellbeing and mood following exposure to psychedelics.
POTENTIAL ROLES OF PSYCHEDELICS IN REVEALING BRAIN MECHANISMS ASSOCIATED WITH POSITIVE PERSONAL AND SOCIETAL CHANGE PROCESSES
As reviewed above, psychedelics and entactogens appear to show potential for the study of bio-psycho-social mechanisms of acute and persistent personal and social change. In supportive environments, these substances promote feelings of trust, empathy, bonding, closeness, tenderness, forgiveness, acceptance, and connectedness. There is an increasing number of studies exploring the neurobiological basis of prosocial feelings and their impact on psychological health and wellbeing. Hence, the use of entactogens and psychedelics may be informative to further explore quantitative changes in brain network dynamics by means of specific pharmacological interventions to identify neurocircuitries of prosocial feelings that serve personal growth and well-being. Specifically, drug-induced experiences of "ego-dissolution" and changes in self-referential processing systems show considerable promise as predictors of long-term behavioural change in terms of more adaptive emotion regulation and increased pro-social attitudes and behaviours. Recently, the concept of brain entropy was introduced to characterize the phenomenology of psychedelic states and their underlying neurodynamics
HARM REDUCTION AND ETHICAL CHALLENGES
Many users from the therapeutic, recreational or ceremonial field claim. While a risk-oriented discourse may prevail in public media, in clandestine discourses (e.g. on drug online forums) there seems to be a dominance of users that are biased towards positive experience or self-treatment. These users often set the social norms in those drug savvy subcultures (ibid.). A critical and harm-reduction focussed voice that acknowledges potential gains, but is supporting to distinguish real benefits from illusionary gains is an asset for the prevention of problematic drug use. Regarding future research on positive psychology we conclude that studies should not only measure and report positive psychology constructs. Both ethically and in terms of unknown side-effects it seems necessary to monitor risk perception and behaviours as well as neuropsychological abilities of users. There is also serious criticism about distortions of reality from "positive illusions": a form of high positivity is correlated with the incapability to critically self-reflect and prejudice. Following the range of potentially positive effects associated with psychedelics or entactogens as reviewed here, an ethical debate seems appropriate that discusses the clinical admission of patients to safe and supervised psychedelic-assisted treatments. Moreover, the access of healthy people to such potential benefits of psychedelics needs to be debated.
LIMITATIONS
The studies reviewed above vary considerably in methodology and study designs. To further corroborate this preliminary evidence about beneficial effects of serotonergic psychedelics and empathogens on healthy human functioning, more randomized controlled studies with specific hypotheses are needed. Most reported studies used within-subject designs (Table), probably because it is more convenient in terms of resources. Small sample sizes and the use of convenient samples make generalization of the results difficult for many studies (e.g.. Most of the designs are correlational and thus inadequate to allow for causal inferences. For ethical reasons, the majority of study participants had prior experience with psychedelic substances which further limits the generalization of the results. A larger number of the studies reported very specific convenient samples including rather experienced, poly-drug users from white European and American cultural backgrounds. Most imaging studies reported here allowed for statistically sufficient control of the experimental variables. On the other hand, controlled laboratory studies render inferences about naturalistic settings difficult. We thus provided a combination of naturalistic,
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epidemiological, and laboratory studies, in order to collect a wide range of preliminary evidence to guide future study designs.
FUTURE RESEARCH ON FACTORS RELATED TO POSITIVE PSYCHOLOGY
Based on this review we conclude that psychedelics and entactogens are 1) valuable pharmacological tools to measure psychological states or behaviors that advance the understanding of brain function and mental phenomena. 2) First clinical studies show that efficacy of psychedelics and entactogens in reducing pathological symptoms is related to measures of positive psychology, and 3) there is preliminary evidence that for a part of the population psychedelics and entactogens sustain and enhance healthy human functioning including emotional responsiveness, cognitive and social abilities and psychospiritual practices such as mindfulness. However, since observational studies suffer from selection biases, these findings cannot be applied to the general population and further longitudinal or controlled study designs need to carefully assess the benefit-risk-ratio to inform drug policy and regulations. Particularly prospective, randomized and controlled studies clarifying causal relationships between the use of those substances, genetical predispositions, personality traits and environmental factors are needed.. 'Ecstasy'as a social drug: MDMA preferentially affects responses to emotional stimuli with social content. Social cognitive and affective neuroscience, 9, 1076-1081. doi:10.1093/scan/nsu035 Watts, R.,. Patients' accounts of increased "connectedness" and "acceptance" after psilocybin for treatment-resistant depression. Journal of Humanistic Psychology, 57, 520-564. Correlations between glutamate + glutamine reductions and increases in the "Non-Judging" subscale of the Five Facets Mindfulness Questionnaire (FFMQ) (r = -0.589, p = 0.044) Increases in superior rostral ACC-PCC connectivity correlated with increases in Non-Judging (r = 0.604, p = 0.013) and Non-Reacting (r = 0.522, p = 0.038) on the FFMQ • Increased anterior cingulated cortex connectivity in the medial temporal lobe correlated with increased scores on the Self-Compassion questionnaire (r = 0.514, p = 0.042) and increases in Non-Judging (r = 0.637, p = 0.008) and Non-Reacting (r = 0.656, p = 0.006) on the FFMQ • In the two month follow-up: Decreased glutamate + glutamine in the posterior cingulated cortex correlated with differences in Non-Judging (r = -0.74, p = 0.009); Increased anterior cingulated cortex connectivity in the medial temporal lobe (r = 0.566, p = 0.035) and the superior rostral ACC-PCC (r = 0.637, p = 0.008) correlated with Non-Judging Negative correlation between addition, there was a significant negative correlation between amygdala blood oxygen-level dependent response to fearful stimuli and subjective drug effects (r = -0.46; p < 0.05)
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