Serotonergic psychedelics and personality: a systematic review of contemporary research, José Carlos Bouso et al., 2018

Serotonergic psychedelics and personality: a systematic review of contemporary research

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

Neuroscience and Biobehavioral Reviews, 2018

PII: S0149-7634(17)30301-9


 Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors
 5-HT2A receptors are expressed in fronto-temporo-parieto-occipital areas
 Some personality traits seem to be related to 5-HT2A receptor expression
 Acute and long-term use of psychedelics is associated with personality changes
 Personality changes induced by psychedelics may have therapeutic effects


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 to 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.

Keywords : hallucinogens; psychedelics; personality; serotonin; 5-HT2A receptor.


1. Introduction

Psychedelics are drugs that have always been surrounded by some kind of special mythic attributions related with personal and psychological change (for the better or for the worse, depending from the source of the message). If narcotics like heroin and/or psychostimulants like cocaine are associated with personal degradation, addiction and crime,1-3 psychedelics are conceptualized for some as a potential inductor of madness,4 and for others as tools for beneficial personal change.5 Several studies performed in the early times of psychedelic research reported that acute administration of these drugs induced changes on personality measures,6-9 although it was less clear if those changes were maintained on time. For some, the eventual long-term personal changes induced by psychedelics were classically considered as a direct consequence of their dramatic effects on the mind, which induced deep changes in the person world view that could produce long-term changes on personality.10,11 In fact, the meme-acting quote from the infamous guru of the 1960’s psychedelic era Timothy Leary “Turn on, tune in, drop out” was referring precisely to that eventual potential power of psychedelic drugs to induce personality change, allowing youth to get liberated from the symbolic chains that attached them to a world culture based on materialism and interpersonal possessiveness. At the same time, the potential psychotherapy properties of psychedelic drugs have been classically attributed precisely to that potential for personality change that inside the context of a psychotherapeutic setting could enhance therapeutic outcomes. Psychiatrists that worked with alcoholics, neurotics, terminal patients and other clinical populations attributed the good results of their treatment to the personality changes induced by the psychedelic experiences of their patients in controlled settings.12 The discrepancy regarding the eventual changes on personality that could be a consequence of repeated recreational use of psychedelics was also a theme of discussion since the 1960’s, when the term acid heads was popularized to refer precisely to some kind of special, while not aberrant, kind of personality expressed by a set of magical-mystical beliefs and profound nonaggressive attitudes that some researchers related with an intensive use of high and repeated doses of psychedelics.13 Other researchers asserted that such abnormal personality profile was the cause, not the consequence, of the involvement in that intensive and repeated use of psychedelics.14 These controversies persisted at least until the mid-1990’s.15 A similar dilemma between the possible consequences of drug exposure and the potential cause of drug use was also present in the debate of other drugs, such as 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”, “molly”): the retrospective nature of most cross-sectional studies does not allow a conclusion of whether the identified deficits (involving psychological/personality, functional and structural findings) were due to the MDMA exposure or predisposed the subjects to the MDMA abuse.16-18 The fact is that most of the former studies relating psychedelic drug use both in controlled and/or in uncontrolled settings with personality change were done with poor and/or unethical methodologies,19 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. But in recent years, with the renewed interest of researchers in the study of the neurobiological basis of the effects of psychedelic drugs, as well as their psychotherapeutic potential (a new scenario coined by some researchers as ‘Psychedelic Renaissance’,20,21 following the expression that firstly appeared in 2010 in the Playboy magazine22), interest has also reemerged regarding the potential effects of these drugs on eventual personality change.23 The malleability of personality is a classical controversial theme in psychology and psychiatry sciences, where researchers find different kind of evidences depending on their particular theoretical framework used in the design of their respective studies.24,25 For instance, there are several models of personality and personality disorders, and the terms used to characterize personality domains are not always equivalent among models and are in fact in permanent transformation.24-26 Furthermore, recent advances in molecular biology and epigenetics suggest that personality could be modulated by gene X environment interactions, where changes in gene expression could be caused by psychological (e.g., distress) or toxicological (e.g., drugs) factors, suggesting that personality is not as stable over time or as predictable as previously thought.25 One of the scientific expressions of the renewed interest in psychedelic research has focused in studding if these drugs can induce personality changes, thus offering other type of evidences to the debate. Moreover, these new investigations also began to explore the possible mechanisms of action involved in these personality changes, as well as their neural basis and neurochemistry, since it is well known that these compounds act as agonists at cortical serotonergic 5-HT2A receptors expressed in fronto-temporo-parieto-occipital areas.27

In the present work, we performed a systematic review of all of these contemporary clinical trials where personality has been studied related with administration of psychedelics/hallucinogens and/or with long-term use of these compounds. Our results show that these evidences come both from clinical studies where short and long-term personality changes have been studied after the administration of a psychedelic drug, and from studies comparing long-term psychedelic drug users with controls (nonusers).