OPEN Foundation

Personality

Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies

Abstract

Background: 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) is used both recreationally and therapeutically. Little is known about the factors influencing inter- and intra-individual differences in the acute response to MDMA. Effects of other psychoactive substances have been shown to be critically influenced by personality traits and mood state before intake.

Methods: We pooled data from 10 randomized, double-blind, placebo-controlled, cross-over studies performed in the same laboratory in 194 healthy subjects receiving doses of 75 or 125mg of MDMA. We investigated the influence of drug dose, body weight, sex, age, drug pre-experience, genetics, personality and mental state before drug intake on the acute physiological and psychological response to MDMA.

Results: In univariable analyses, the MDMA plasma concentration was the strongest predictor for most outcome variables. When adjusting for dose per body weight, we found that (a) a higher activity of the enzyme CYP2D6 predicted lower MDMA plasma concentration, (b) a higher score in the personality trait “openness to experience” predicted more perceived “closeness”, a stronger decrease in “general inactivation”, and higher scores in the 5D-ASC (5 Dimensions of Altered States of Consciousness Questionnaire) scales “oceanic boundlessness” and “visionary restructuralization”, and (c) subjects with high “neuroticism” or trait anxiety were more likely to have unpleasant and/or anxious reactions.

Conclusions: Although MDMA plasma concentration was the strongest predictor, several personality traits and mood state variables additionally explained variance in the response to MDMA. The results confirm that both pharmacological and non-pharmacological variables influence the response to MDMA. These findings may be relevant for the therapeutic use of MDMA.

Studerus, E., Vizeli, P., Harder, S., Ley, L., & Liechti, M. E. (2021). Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies. Journal of psychopharmacology (Oxford, England), 35(5), 556–565. https://doi.org/10.1177/0269881121998322

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Examining changes in personality following shamanic ceremonial use of ayahuasca

Abstract

The present study examines the association between the ceremonial use of ayahuasca-a decoction combining the Banistereopsis caapi vine and N,N-Dimethyltryptamine-containing plants-and changes in personality traits as conceived by the Five-Factor model (FFM). We also examine the degree to which demographic characteristics, baseline personality, and acute post-ayahuasca experiences affect personality change. Participants recruited from three ayahuasca healing and spiritual centers in South and Central America (N = 256) completed self-report measures of personality at three timepoints (Baseline, Post, 3-month Follow-up). Informant-report measures of the FFM were also obtained (N = 110). Linear mixed models were used to examine changes in personality and the moderation of those changes by covariates. The most pronounced change was a reduction in Neuroticism dzself-reportT1-T2 = – 1.00; dzself-reportT1-T3 = – .85; dzinformant-reportT1-T3 = – .62), reflected in self- and informant-report data. Moderation of personality change by baseline personality, acute experiences, and purgative experiences was also observed.

Weiss, B., Miller, J. D., Carter, N. T., & Keith Campbell, W. (2021). Examining changes in personality following shamanic ceremonial use of ayahuasca. Scientific reports, 11(1), 6653. https://doi.org/10.1038/s41598-021-84746-0

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Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects

Abstract

Psychedelic drugs are increasingly being incorporated into therapeutic contexts for the purposes of promoting mental health. However, they can also induce adverse reactions in some individuals, and it is difficult to predict before treatment who is likely to experience positive or adverse acute effects. Although consideration of setting and dosage as well as excluding individuals with psychotic predispositions has thus far led to a high degree of safety, it is imperative that researchers develop a more nuanced understanding of how to predict individual reactions. To this end, the current systematic review coalesced the results of 14 studies that included baseline states or traits predictive of the acute effects of psychedelics. Individuals high in the traits of absorption, openness, and acceptance as well as a state of surrender were more likely to have positive and mystical-type experiences, whereas those low in openness and surrender or in preoccupied, apprehensive, or confused psychological states were more likely to experience acute adverse reactions. Participant sex was not a robust predictor of drug effects, but 5-HT2AR binding potential, executive network node diversity, and rACC volume may be potential baseline biomarkers related to acute reactions. Finally, increased age and experience with psychedelics were individual differences related to generally less intense effects, indicating that users may become slightly less sensitive to the effects of the drugs after repeated usage. Although future well-powered, placebo-controlled trials directly comparing the relative importance of these predictors is needed, this review synthesizes the field’s current understanding of how to predict acute reactions to psychedelic drugs.

Aday, J. S., Davis, A. K., Mitzkovitz, C. M., Bloesch, E. K., & Davoli, C. C. (2021). Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects. ACS pharmacology & translational science, 4(2), 424–435. https://doi.org/10.1021/acsptsci.1c00014

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The Psychedelic Personality: Personality Structure and Associations in a Sample of Psychedelics Users

Abstract

Research on the relationship between personality and psychedelics use has found evidence of a two-way influence where the personality structure predicts individual responses to psychedelics, and psychedelics use results in lasting changes to the individual’s personality structure. This study used brief personality measures in the form of the Ten-Item Personality Inventory (TIPI) and a simplified version of the Risk Taking Index (RTI) in order to measure personality traits in a sample of psychedelics users (N = 319). The participants in the study scored consistently higher than norms on each of the Big Five traits except Extraversion, and on every dimension of risk taking in the RTI. In multivariate logistic regression analyses, personality structure was associated with characteristics of the psychedelic experience that included the feelings of fear, love, and peace as well as states of perceived contact with non-ordinary beings and transcendent forces.

Johnstad P. G. (2021). The Psychedelic Personality: Personality Structure and Associations in a Sample of Psychedelics Users. Journal of psychoactive drugs, 53(2), 97–103. https://doi.org/10.1080/02791072.2020.1842569

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Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis

Abstract

Background: Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias.

Methods: We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain.

Results: A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges’ gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects.

Conclusions: High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

Goldberg, S. B., Shechet, B., Nicholas, C. R., Ng, C. W., Deole, G., Chen, Z., & Raison, C. L. (2020). Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis. Psychological medicine, 50(16), 2655–2666. https://doi.org/10.1017/S003329172000389X

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Who takes the trip? Personality and hallucinogen use among college students and adolescents

Abstract

Research examining hallucinogen use has identified potential benefits, as well as potential harms, associated with use. The acute effects of hallucinogen use can be intense, disorienting, cognitively impairing, and may result in perceptual changes mimicking aspects of temporary psychosis. Hallucinogen use may also lead to the onset of more chronic issues, such as Hallucinogen Persisting Perception Disorder, which impairs daily functioning even when sober. However, research on factors that predict who will misuse hallucinogens is an understudied area. In particular, while sensation seeking, impulsivity, and emotion dysregulation have all been shown to be predictive of problematic substance misuse, there is almost no research on how these personality variables predict hallucinogen use. The present study assessed how these personality traits predicted hallucinogen use in a sample of college undergraduates (N = 10,251) and a sample of adolescents in an inpatient residential psychiatric hospital (N = 200). Results indicated that facets of sensation seeking, impulsivity, and emotion dysregulation positively predicted ever having used hallucinogens, earlier initiation of use, and lifetime use among college students. Findings also indicated that facets of sensation seeking, impulsivity, and emotion dysregulation positively predicted having ever used hallucinogens in the adolescent inpatient sample. Results highlight the need for more research on who is likely to misuse hallucinogens. If confirmed in future research, the findings presented herein indicate viable personality variables as predictors. This is especially important as there has been a recent explosion of research on the positive benefits of therapeutic hallucinogen use.

Parnes, J. E., Kentopp, S. D., Conner, B. T., & Rebecca, R. A. (2020). Who takes the trip? Personality and hallucinogen use among college students and adolescents. Drug and alcohol dependence, 217, 108263. https://doi.org/10.1016/j.drugalcdep.2020.108263

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Modulatory effects of ayahuasca on personality structure in a traditional framework

Abstract

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth.

Rationale: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration.

Objectives: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists.

Method: Within a mixed design, we examined the effect of ayahuasca on participants’ personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca).

Results: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism.

Conclusions: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.

Netzband, N., Ruffell, S., Linton, S., Tsang, W. F., & Wolff, T. (2020). Modulatory effects of ayahuasca on personality structure in a traditional framework. Psychopharmacology, 237(10), 3161–3171. https://doi.org/10.1007/s00213-020-05601-0

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LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

Abstract

Adapting one’s attitudes and behaviors to group norms is essential for successful social interaction and, thus, participation in society. Yet, despite its importance for societal and individual functioning, the underlying neuropharmacology is poorly understood. We therefore investigated its neurochemical and neural correlates in a pharmacological functional magnetic resonance imaging study. Lysergic acid diethylamide (LSD) has been shown to alter social processing and therefore provides the unique opportunity to investigate the role of the 5-HT2A receptor in social influence processing. Twenty-four healthy human volunteers received either (1) placebo + placebo, (2) placebo + LSD (100 µg), or (3) the 5-HT2A receptor antagonist ketanserin (40 mg) + LSD (100 µg) at three different occasions in a double-blind, randomized, counterbalanced, cross-over design. LSD increases social adaptation but only if the opinions of others are similar to the individual’s own. These increases were associated with increased activity in the medial prefrontal cortex while participants received social feedback. Furthermore, pretreatment with the 5-HT2A antagonist ketanserin fully blocked LSD-induced changes during feedback processing, indicating a key role of the 5-HT2A system in social feedback processing. Our results highlight the crucial role of the 5-HT-system in social influence and, thus, provide important insight into the neuropharmacological basis of social cognition and behavior.
Duerler, P., Schilbach, L., Stämpfli, P., Vollenweider, F. X., & Preller, K. H. (2020). LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors. Scientific reports10(1), 1-11., https://doi.org/10.1038/s41598-020-68899-y
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Broadening Your Mind to Include Others: The relationship between serotonergic psychedelic experiences and maladaptive narcissism

Abstract

Rationale: Recent research has shown that classical serotonergic psychedelic (CSP) drugs may be used to ameliorate certain health issues and disorders. Here we hypothesised that CSP experiences, through their ability to induce awe and ego-dissolution, may result in a reduction of maladaptive narcissistic personality traits, such as a strong sense of entitlement and lack of empathy.

Objectives: Our objective was to investigate whether high levels of awe and ego dissolution during recent CSP experiences are associated with currently lower levels of maladaptive narcissism.

Methods: In this pre-registered high-powered (N = 414) study, we used an online retrospective survey asking participants to describe their ‘most awe-inspiring, impressive, significant, or emotionally intense experience’, as well as several validated scales to test our hypothesis.

Results: A statistically significant mediation model indicated that recent CSP-induced experiences were associated with currently increased feelings of connectedness and affective empathetic drive, which in turn were associated with decreased exploitative-entitled narcissism. This relationship held even when taking into account sensation-seeking personality features. We found no evidence for feelings of ego dissolution to have the same effect.

Conclusions: Feelings of awe, but not ego dissolution, during recent CSP experiences were associated with increased feelings of connectedness and empathy, which in turn were associated with decreased levels of maladaptive narcissism personality features. This suggests that CSPs hold therapeutic potential for disorders involving connectedness and empathy, such as the treatment of pathological narcissism, and that the induction of connectedness through awe appears to be the driving force behind this potential.

van Mulukom, V., Patterson, R. E., & van Elk, M. (2020). Broadening Your Mind to Include Others: The relationship between serotonergic psychedelic experiences and maladaptive narcissism. Psychopharmacology, 237(9), 2725–2737. https://doi.org/10.1007/s00213-020-05568-y

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Broadening Your Mind to Include Others: The relationship between serotonergic psychedelic experiences and maladaptive narcissism

Abstract

Rationale: Recent research has shown that classical serotonergic psychedelic (CSP) drugs may be used to ameliorate certain health issues and disorders. Here we hypothesised that CSP experiences, through their ability to induce awe and ego-dissolution, may result in a reduction of maladaptive narcissistic personality traits, such as a strong sense of entitlement and lack of empathy.
Objectives: Our objective was to investigate whether high levels of awe and ego dissolution during recent CSP experiences are associated with currently lower levels of maladaptive narcissism.
Methods: In this pre-registered high-powered (N = 414) study, we used an online retrospective survey asking participants to describe their ‘most awe-inspiring, impressive, significant, or emotionally intense experience’, as well as several validated scales to test our hypothesis.
Results: A statistically significant mediation model indicated that recent CSP-induced experiences were associated with currently increased feelings of connectedness and affective empathetic drive, which in turn were associated with decreased exploitative-entitled narcissism. This relationship held even when taking into account sensation-seeking personality features. We found no evidence for feelings of ego dissolution to have the same effect.
Conclusions: Feelings of awe, but not ego dissolution, during recent CSP experiences were associated with increased feelings of connectedness and empathy, which in turn were associated with decreased levels of maladaptive narcissism personality features. This suggests that CSPs hold therapeutic potential for disorders involving connectedness and empathy, such as the treatment of pathological narcissism, and that the induction of connectedness through awe appears to be the driving force behind this potential.
van Mulukom, V., Patterson, R., & van Elk, M. (2020). Broadening Your Mind to Include Others-The relationship between serotonergic psychedelic experiences and maladaptive narcissism_PREPRINT. PsyArXiv. March10., https://doi.org/10.1007/s00213-020-05568-y
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