Serotonergic psychedelics and personality: A systematic review of contemporary research

This review article (2018) summarizes the effects of psychedelics on the serotonergic system and the subsequent (therapeutic) personality changes.

Abstract

“Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors and seem to induce personality changes. We conducted a systematic review of studies assessing the effects of these drugs on personality. Papers published from 1985–2016 were included from PubMed, LILACS, and SciELO databases. Three hundred and sixty-nine studies were identified, and 18 were included. Specific personality traits, such as Absorption and Self-Transcendence, seem to influence the effects of psychedelics, and psychedelic drug users and nonusers appear to differ in some personality traits. Psychedelics administered in controlled settings may induce personality changes, such as increased Openness and Self-Transcendence. Increases in global brain entropy induced by acute psychedelic administration predicted changes in Openness, and Self-Transcendence was negatively correlated with cortical thinning of the posterior cingulate cortex in long-term religious ayahuasca users. Acute and long-term use of psychedelics is associated with personality changes that appear to be modulated by 5-HT2A receptors. These changes seem to induce therapeutic effects that should be further explored in randomized controlled studies.”

Authors: José Carlos Bouso, Rafael G. dos Santos, Miguel Ángel Alcázar-Córcoles & Jaime E. C. Hallak.

Summary

José Carlos Bouso, Rafael G. dos Santos, Miguel ngel Alcázar-Córcoles, Jaime E. C. Hallak and colleagues investigated the effects of psychedelics on personality, and found that 5-HT2A receptors are expressed in fronto-temporo-parieto-occipital areas.

Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors and seem to induce personality changes. Psychedelic users and nonusers appear to differ in some personality traits, and these changes seem to induce therapeutic effects. Hallucinogens, psychedelics, personality, serotonin, 5-HT2A receptor are drugs that have always been surrounded by some kind of mythic attributions related with personal and psychological change.

Research reported that acute administration of these drugs induced changes on personality measures, although it was less clear if those changes were maintained on time. Psychedelic drugs have been classically attributed to their potential to induce personality change that could enhance therapeutic outcomes. The discrepancy between the eventual changes on personality that could be a consequence of repeated recreational use of psychedelics and the potential cause of drug use was also a theme of discussion since the 1960’s.

Most cross-sectional studies relating psychedelic drug use with personality change were done with poor and/or unethical methodologies, and most of the assertions regarding that phenomena usually came from a mixture of prejudges, biased clinical observations, and media articles reflecting the most sensationalist side of psychedelics use. Researchers find different evidences depending on the theoretical framework used in the design of their respective studies, suggesting that personality is not as stable over time or as predictable as previously thought.

The renewed interest in psychedelic research has focused on studying if these drugs can induce personality changes. The results show that both short and long-term personality changes have been studied after the administration of psychedelics/hallucinogens. This systematic review focused on serotonergic psychedelics/hallucinogens (5-HT2A receptor agonists) and personality. It was conducted using the PubMed, LILACS, and SciELO databases, and the reference lists of all included studies were manually screened for relevant studies.

A systematic review of studies on the effects of psychedelics/hallucinogens on personality was conducted. All studies were screened by two independent reviewers and included if they met the inclusion criteria.

The search of the literature yielded 369 separate references, of which 14 were considered relevant. Eight interventional studies were also included, of which four assessed the effects of psilocybin, three investigated the effects of LSD, and one assessed the effects of hallucinogens in general. Despite small sample sizes, observational design, and high degree of heterogeneity, the results suggest that acute administration of serotonergic hallucinogens to healthy volunteers in experimental settings is associated with significant increases in Openness.

The continued ritual use of these compounds is apparently associated with significant differences in personality measures, which are related to antidepressant, anxiolytic, and antiaddictive effects. An observational study performed in the United States among 309 industrial plant workers assessed possible correlations between hallucinogenic drug use, personality, and attitude. 24% of the sample tried LSD and 23% tried other psychedelics, and 36% reported less than monthly use for both LSD and other psychedelics.

The ZSS subscales Experience Seeking, Disinhibition, and Boredom-Susceptibility, as well as the SSPQ subscales Social Alienation and Traditionalism, significantly predicted one or more drug use scores. Schneider et al. 40 conducted a cross-sectional web survey with 8.646 participants to assess possible associations between personality traits and occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in adults.

Hallucinogen users showed higher scores on self-directedness and self-transcendence than people who never used hallucinogens, while novelty seeking was the trait most associated with increased use of alcohol, cannabis, and cocaine. Ayahuasca users scored significantly lower on the novelty seeking scale than matched controls on the Tridimensional Personality Questionnaire, including significantly greater stoic rigidity vs. exploratory excitability and regimentation vs. disorderliness.

In an observational study conducted in Brazil, 21 volunteers showed higher TAS scores compared to normative data, and absorption scores were significantly (P 0.05, uncorrected) related to synesthesia during the acute effects of ayahuasca. In another study conducted in Brazil, subjects who ingested ayahuasca in the UDV context had lower scores in reward dependence compared to baseline scores, while subjects in the Santo Daime context only had ACCEPTED MANUSCRIPT.

Ayahuasca use was associated with less dependence of social approval and more confidence, optimism and independence. The lower scores on reward dependence were positively correlated with the intensity of ayahuasca use and negatively correlated with the length of wash-out period. In an observational study conducted in Brazil, Bouso et al.36 assessed the personality of long-term members of the Brazilian ayahuasca religions Santo Daime and Barquinha, and compared them with rural and urban controls.

The TCI-R assesses three dimensions of character: self-directedness, cooperativeness, and self-transcendence. Self-directedness is measured by anticipatatory worry, uninhibited optimism, fear of uncertainty, confidence, shyness with strangers, gregariousness, fatigability and asthenia, and vigor. Ayahuasca users showed significantly higher scores on reward dependence, self-transcendence, self-directedness, responsibility, purposefulness, resourcefulness, and self-acceptance compared to controls, and significantly lower scores on harm avoidance, anticipatory worry, shyness, and fatigability and asthenia compared to the urban ACCEPTED MANUSCRIPT.

Ayahuasca users showed higher scores on the reward dependence subscales attachment and dependence, on the harm avoidance subscale fatigability and asthenia, and on the self-directedness subscale resourcefulness compared to controls. They also showed lower scores on the scales measuring spiritual orientation, purpose in life, and psychosocial well-being. In an observational study performed in Spain, Bouso et al.38 found that Spanish members of the Santo Daime had significantly lower scores on harm avoidance and its subscale ACCEPTED MANIPULATION than non-ayahuasca users.

The ayahuasca group had higher scores on self-transcendence, self-forgetfulness, transpersonal identification, and spiritual acceptance, and a thinning of the posterior cingulate cortex. However, there were no significant differences between the groups regarding psychopathology measures. A study was performed to evaluate the personality of foreigners that had travelled to South America with the aim of using ayahuasca and had participated in at least one ayahuasca session. The results showed that ayahuasca users had higher scores on the intuitive, optimistic, ambitious, charming, and helpful scales.

A study of 30 experienced UDV members found that they had a pleasant, trustful, optimistic, and emphatic personality style, characterized by inhibition of analytic thinking and valorization of intuitive behavior. They also showed better scores on mood and quality of life compared to controls. Anglin et al. 30 compared the personalities of 53 college undergraduates users of psilocybin-containing hallucinogenic mushrooms with 53 matched controls with no history of mushroom use.

There was no evidence of increased psychopathology in mushroom users, but male users showed significantly higher scores on the Experience Seeking subscale of the Zuckerman Sensation-Seeking Scale and significantly lower scores on the Lie subscale of the Eysenck Personality Questionnaire and on the Socialization subscale of the California Psychological Inventory. Griffiths et al.47 conducted a double-blind, between-group, crossover study in the United States with 36 hallucinogen-naive adults reporting regular participation in religious/spiritual activities.

18 sessions were randomly assigned to ingest oral psilocybin or methylphenidate, and personality was evaluated before and 2 months after each drug session. Psilocybin administration was not associated with significant effects on personality. A 14-month follow-up study of the original double-blind study from 2006 showed that participants who received psilocybin had significantly lower scores on the neuroticism subscale of the NEO PI-R and significantly higher scores on the extroversion, openness, and agreeableness subscales of the NEO PI-R and on the Measure of Actualization Potential.

Participants who had a “complete mystical experience” (measured with the States of Consciousness Questionnaire, SOCQ) had higher Openness scores than those who did not. This increase was positively correlated with scores on the SOCQ, the Mysticism Scale, and the Altered States of Consciousness questionnaire. The group that had a “complete mystical experience” had higher Openness scores at the 1-2-month and 16-month follow-ups than the group that did not, although the last follow-up was only marginally higher than baseline values.

In an experimental study performed in Zurich, Studerus et al.36 analyzed 24 predictor variables in relation to 15 response variables in 23 placebo-controlled experimental studies involving 261 healthy volunteers. The TAS and ZKPQ were used to assess the personality dimensions Impulsive Sensation Seeking, Neuroticism-Anxiety, Aggression-Hostility, Activity, and Sociability. Psilocybin dose and other variables significantly predicted drug response. High TAS scores and low Sociability scores predicted pleasant and ACCEPTED MANUSCRIPT mystical-type experiences.

A study of 29 polydrug users found that their personality traits correlated with the frequency of unpleasant LSD experiences, unpleasant visual hallucinations, and the recurrence of drug effects after acute effects have subsided. In an experimental study conducted in Germany, 11 of 16 “hysterics/extraverted neurotics” reported all three acute effects, eight of 16 “stable extraverts” reported only “affective reactions”, six of 11 “dysthymics/introverted neurotics” reported only “thinking disturbances”, and seven of 17 “stable introverts” reported only “blackouts”.

In a single-blind, placebo-controlled, within-subjects study performed in the United Kingdom, 20 healthy volunteers were administered LSD or placebo and their mood and personality measures were assessed. LSD administration significantly increased optimism and openness scores two weeks after the experimental sessions. LSD increased brain entropy both globally and specifically in clusters located in the frontoparietal, medial occipital, posterior and dorsal cingulate regions. This increase in brain entropy predicted changes in Openness scores, and this relationship was enhanced by music-listening.

We found several studies that assessed the effects of psychedelics on personality measures, both after acute administration and in long-term regular users compared with controls (nonusers). The most used questionnaires were the NEO-PI-R and the TCI, and there were different kinds of studies conducted. Studies with recreational users found that neuroticism and extroversion were related to negative experiences with psychedelic drugs.

In clinical studies, neurotic subjects had negative reactions to psilocybin, and extraverted subjects enjoyed the psychedelic experience more, but these subjects did not achieve mystical-type experiences. Furthermore, high scores in Experience Seeking, General Sensation Seeking, and Disinhibition were associated with recreational psychedelic drug use. In a study with Brazilian drug users, Schneider et al.40 found some differences in personality traits between occasional recreational psychedelic drug users and abusers. The abusers scored higher in Persistence than the occasional users, but both groups scored high in Self-Transcendence.

Psychedelic abuse with Traditionalism and Persistence does not necessarily reflect psychological problems, except for the recreational use of a drug. The people who attend nonreligious ayahuasca retreats have a profile characterized by increased scores on intuitivism, optimistic, ambitious, charming, and helpful. In noncontrolled studies, ayahuasca retreatment attenders scored higher compared to normative data on the TAS, and in PET studies, subjects that scored high on Self-Transcendence had lower 5-HT1A receptor levels.

These results add new evidence to the biological theories of personality by showing that modulation of specific serotonergic receptors expressed in specific brain areas modulates specific personality traits. Since 1996, several studies have compared regular religious ayahuasca users with matched nonusers in several neuropsychological, neuroimaging, and psychological measures, including personality. The studies found lower scores in Harm Avoidance compared to controls in all three studies, and higher scores in Reward Dependence in the rural sample.

The TPQ does not measure character variables, so only the studies by Bouso and collaborators can be directly compared. Ayahuasca users scored higher than controls in Self-Transcendence, but the two Brazilian samples scored lower in Self-Directedness than controls. The authors suggested that the lower scores in Self-Directedness in the Brazilian samples could probably reflect cultural differences, and that the higher scores in Self-Transcendence in the Spanish sample could be related to genetic differences related to personality traits.

Although it is not possible to attribute causality to ayahuasca intake in the differences observed between ayahuasca users and nonusers, participation in religious ayahuasca ceremonies may be associated with changes in personality traits. There are several studies involving psychedelic drugs and personality changes. In one open-label study performed with LSD in Germany,45 and in a series of placebo-controlled clinical trials performed with psilocybin33,35,47 and LSD,42,43, no changes in personality were found using the NEO PI-R questionnaire. Regarding the studies with LSD, Lienert and Netter45 found that personality type affected response to the drug.

The controlled administration of LSD induces significant increases in Optimism and Openness, and this increase is predicted by cortical 5-HT1A/2A receptors. However, there are no consistent long-term changes in personality after the controlled administration of psilocybin, so replication of these results is necessary before stating that the controlled administration of a psychedelic drug can induce permanent changes on personality traits. The findings of the present review suggest that personality traits may change as a result of specific life events or therapeutic interventions.

Research shows that personality traits can change more quickly than commonly thought, and that therapeutic interventions can also lead to changes in personality traits. The results discussed in the present review suggest that acute administration of serotonergic psychedelics associated (or not) with psychotherapies can lead to fast and enduring changes in personality. Further research is needed to assess if administration of psychedelics can indeed induce fast and enduring therapeutic changes in personality.

The studies comparing personality traits between psychedelic users and nonusers used the TCI and the BFI, which are classical instruments to assess personality. A recent cross-validation study of the TAS found that its subscales have acceptable internal consistency and construct reliabi lity ( 0.70), and excellent fit indices. The NEO PI-R is another standard measure within personality psychology.

We found three types of evidences: personality traits may influence psychedelic experience, differences between psychedelic users and nonusers, and controlled settings.

There are a series of limitations for each of those evidences, including a lack of well controlled studies researching the responses of different people with different personality profiles to the psychedelic experience, and a lack of prospective studies to better understand the causal relations between users and nonusers.

To keep implementing personality measures in psychedelic research is a promising field in psychology. The authors have no conflict of interests to disclose.