This cross-sectional study (n=45) evaluates associations between recreational use of psychedelics and MDMA and (a) personality measures and (b) key markers of cerebral serotonergic signaling (serotonin transporter and serotonin-2A-receptor binding).
Abstract
“Background: Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes.
Aim: To test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (MDMA) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2A-receptor binding).
Methods: In 10 psychedelic-preferring recreational users, 14 MDMA-preferring users and 21 non-using controls, personality was assessed using the ‘big five‘ instrument Revised NEO Personality Inventory (NEO-PI-R). Frontal serotonin transporter and serotonin-2A-receptor binding potentials were quantified using [11C]DASB and [18F]altanserin positron emission tomography, respectively.
Results: Of the five NEO-PI-R traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both MDMA-preferring users and controls. Openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all MDMA-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding – but not frontal serotonin-2A-receptor binding – was positively associated with openness to experience.
Conclusion Our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of ‘recreational’ psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. A modulation of personality induced by psychedelic experiences may have important therapeutic implications via its impact on peoples’ value systems, cognitive flexibility, and individual and social behaviour.”
Authors: David Erritzoe, James Smith, Patrick M. Fisher, Robin Carhart-Harris, Vibe G. Frokjaer & Gitte M. Knudsen
Summary
Introduction
Psychedelic substances have been used in various cultures for more than 5000 years, and may belong to the first class of psychopharmacological agents known to man. Recently, clinical pilot studies have been carried out to test the use of psychedelics in conjunction with psychotherapies to treat a variety of mental health conditions.
Recent studies suggest that psychedelics have therapeutic benefits.
MDMA and psychedelic compounds have a similar primary serotonergic action as pharmaceuticals used to treat affective disorders, but the treatment effect after such sessions appears to last for several months. In follow-up studies, exposure to psychedelics or MDMA leads to long-lasting changes in personality. In particular, an increase in openness to experience (Openness) has been observed after a single administration of psilocybin to psychedelic-nave healthy individuals and a single dose of LSD to healthy subjects with previous experience with psychedelics. Cognitive flexibility is positively modulated by 5-HT2A-R functioning and 5-HT2A-R agonists such as LSD, DMT and psilocybin facilitate enhanced cognitive flexibility and creative thinking. The mechanisms underlying the long-lasting therapeutic effects of 5-HT2A-R are not yet explored.
This study evaluated potential links between molecular brain imaging markers of key features of 5-HT signalling and personality domain scores among individuals who recreationally use psychedelics/MDMA and non-using matched controls.
Methods
Study design
This study assessed personality structure and serotonergic brain imaging markers in 24 young adult users of recreational serotonergic drugs and 21 age-gender-matched non-using controls.
Participants
24 adult users of psychedelics and/or MDMA were recruited via flyers, advertisements, word of mouth and websites. They were divided into two groups according to their lifetime exposures to psychedelics and MDMA, and brain imaging was performed on 10 psychedelic preferring users and 14 MDMA preferring users. Abstinence from illegal drug intake was confirmed by urine drug screenings, and self-reported recent use of MDMA was confirmed by gas chromatography mass spectroscopy analysis of hair segments.
Personality assessment
The Revised NEO Personality Inventory (NEO-PI-R) was used to assess the Big Five personality traits, and each trait can be further divided into six correlated facets.
Brain imaging
PET imaging was conducted with [11C]-labelled 3-amino-4-[2-[(di(methyl)amino)methyl] phenyl] sulfanylbenzonitritile (DASB) and [18F]-labelled altanserin, respectively. A frontal cortical region of interest (ROI) was automatically delineated on each participant’s transaxial magnetic resonance image sections.
Statistical analysis
All analyses were conducted in SPSS version 21.0 and R version 3.3.1. We used one-way analysis of variance (ANOVA) to compare personality scores between MPUs, PPUs and controls, and linear regression analysis to test whether lifetime use of psychedelics was associated with Openness scores.
We estimated a structural equation model for the association between lifetime number of exposures to psychedelics and Openness using n=21 individuals with lifetime psychedelic use.
Results
NEO-PI-R scores and psychedelic use
Group comparison of PPUs, MPUs and controls showed a statistically significant difference in Openness scores, with PPUs having statistically significantly higher levels of Openness than MPUs and non-using controls. There were no statistically significant differences in any of the other four personality domains.
Time number of psychedelic exposures was positively associated with Openness, with the highest increase in score per doubling in lifetime psychedelic exposure being for openness to values, openness to actions, and openness to ideas.
mediators of the effect on Openness?
Frontal SERT binding was positively associated with Openness among all MPU/PPU individuals, but not among controls. This association was not moderated by MPU/PPU group, and SERT binding did not mediate the association between lifetime psychedelic use and Openness.
Discussion
In this study, recreational drug users scored higher on the NEO-PI-R trait, Openness, than both MPUs and non-using matched controls. Furthermore, Openness was positively associated with lifetime psychedelic use.
People with regular ceremonial use of ayahuasca had higher Openness scores than matched ayahuasca-naive controls, and were more creative than other substance users. An on-line survey with 893 participants found that Openness was positively associated with self-reported lifetime psychedelic use. The cross-sectional nature of this study does not allow for conclusions about the direction of causality between psychedelic use and Openness. However, individuals with high Openness might be more prone to use psychedelics, but not in general. Further support for the interpretation that psychedelic experiences can increase Openness comes from longitudinal studies that have assessed personality before and after exposure to a psychedelic. These studies have shown that Openness changes equally for depressed and non-depressed individuals.
The two facets openness to actions and openness to values are particularly strongly correlated with lifetime psychedelic use, and are likely to be modified by psychedelics rather than the more broad concept of trait of Openness itself. LSD use in ‘non-medical’ settings is associated with attitudes of ‘personal liberty’ and ‘foreign policy liberalism’. Psychedelic use is also associated with greater nature-relatedness and anti-authoritarianism, pro-environmental behaviour, concerns for others and lower value on financial prosperity.
MDMA-assisted therapy for post-traumatic stress disorder has been reported to lead to long-lasting increases in Openness, and it is therefore worth considering why it was the psychedelic preferring users exclusively – and not also MPUs – who had high Openness scores in our study.
The use of recreational MDMA is frequently combined with other drugs, whereas the use of recreational psychedelics is less common. This may explain why psychedelics are more potent at boosting Openness than recreational MDMA use.
In this study, we explored whether cortical SERT or 5-HT2A-R binding mediated the observed drug-group-related differences in personality scores. We could not demonstrate a significant difference in association between PPUs/MPUs and controls, which we interpret with caution due to power limitations. We found no difference in SERT or 5-HT2A-R binding between PPUs, MPUs and matched non-using controls, with only MPUs versus controls showing low SERT binding. This suggests that high SERT binding among psychedelic/MDMA users is associated with high Openness scores. Cognitive flexibility is positively modulated by 5-HT2A-R functioning, and 5-HT2A-R agonists facilitate enhanced cognitive flexibility and creative thinking. Therefore, we hypothesized that 5-HT2A-R binding would be negatively correlated with Openness.
The combined high SERT (low synaptic 5-HT) and high Openness may be explained by a general effect of psychedelic use on the 5-HT system, rather than its main target receptor.
In conclusion, this study supports the idea that psychedelics affect openness and may have important implications for people’s value systems, cognitive flexibility, and individual and social behaviour.
Study details
Participants
45