Psilocybin Therapy & Personality Structure

Major depression is an illness that frequently affects people and is linked to significant morbidity, socioeconomic hardship, and rates of successful suicide (1, 2). The World Health Organization (WHO) has rated it as the fourth largest contributor to the world burden of disease (5), with a prediction that it will overtake all other diseases by the year 2030. It affects between 7% and 40% of the general population.

• Treatment-resistant depression (TRD), which is commonly characterized as “a poor response after two adequate trials of various classes of anti-depressants,” has been linked to nearly half of the expense and disease burden caused by depression.

TRD is a serious issue for both individual and societal health since it is linked to a longer disease course, greater severity, and more persistent functional impairment. If TRD is defined as the absence of remission, it can afflict up to 60% of individuals with severe depression.

• Research concentrating on therapeutic methods with alternatives to traditional pharmaceutical and therapeutic techniques is warranted given the poor prognosis and socioeconomic burden associated with TRD.

The current study set out to determine whether psilocybin combined with psychological support modifies personality traits in people with treatment-resistant depression. It also sought to determine whether these modifications are related to the quality of the psychedelic experience and whether they may help explain the long-lasting effects of psilocybin-assisted therapy.

Introduction

After being suppressed for many years, interest in traditional serotonergic psychedelic substances like psilocybin, N, N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) gradually re-emerged starting in the 1990s. Recent pilot studies suggest that psychedelic-assisted therapy may be used to treat illnesses like alcohol and tobacco addiction, obsessive-compulsive disorder, despair and anxiety at the end of life, severe depression, and treatment-resistant depression.

• A moderate to high dose of a psychedelic substance is typically administered in supportive settings over the course of one or two sessions in order to induce “peak” or “mystical-type” experiences that are characterized by the dissolution of ego boundaries and an accompanying sense of connectedness, oneness, or unity. The technique of long-term daily pharmaceutical intervention associated with conventional therapy is different from this treatment paradigm.

The underlying processes of psychedelic therapy’s long-lasting therapeutic effects are yet unknown. The therapeutic results and the subjective sensations had during the psychedelic sessions seem to be related. Additionally, after a single dosage of psilocybin or LSD, healthy volunteers may exhibit an elevation in the NEO-PI-R personality characteristic Openness to Experience (or simply “Openness”). It’s interesting to note that in the subgroup of subjects who had mystical experiences while taking psilocybin, there may be a connection between the caliber of the event and its effect on personality.

• Even more than a year after the session, openness remained considerably higher than the baseline. Imagination, aesthetic appreciation, novelty seeking, non-conformity, and creativity are all associated with openness, which is one of the five major aspects of personality. Effective antidepressant therapy has been demonstrated to not only improve Openness scores in major depression, but also to dramatically alter three of the other four NEO-PI-R personality domains: decreasing Neuroticism, increasing Extraversion and Conscientiousness, while maintaining Agreeableness.

Findings

Clinical recovery among patients in this open-label research of psilocybin therapy for treatment-resistant severe depression was discovered to be accompanied by significant adjustments in personality tests. Thus, the NEO-PI-R “Big Five” score of Neuroticism considerably declined from baseline to the 3-month follow-up, whereas scores for Extraversion and Openness significantly increased, Conscientiousness exhibited a trend-level increase, and Agreeableness remained unchanged.

• Ten of the 30 NEO PI-R facets survived multiple comparisons correction, making a total of 11 of the 30 facets considerably altered. To our knowledge, this is the first time personality assessments of patients receiving psychedelic therapy for depression have been observed to change. These findings add to those of psilocybin-induced personality alterations in healthy participants.

Overall, findings from a study of patients who successfully received medication, mostly with selective serotonin reuptake inhibitors (SSRIs) for major depression, were consistent with improvements in trait and facet scores that were observed before and after treatment in our trial. The same four of “the Big Five” features, specifically, altered in both trials in the same way, that is, in the direction of the personality profile of healthy populations.

• Patients in both studies showed declines in their levels of despair, vulnerability, self-consciousness, and anxiety, which are all aspects of neuroticism. Warmth and joyful emotions were among the aspects of extraversion that increased. Competence and self-control were two aspects of conscientiousness that increased.

Previous research has shown that increases in Extraversion, a personality trait linked to general positive affect, and decreases in Neuroticism, a trait known to be a vulnerability marker for affective disorders, are significantly correlated with the SSRI/SNRI-induced reduction in depression severity. Accordingly, albeit only at a trend-level significance, QIDS declines in our sample were linked to declines in Neuroticism and increases in Extraversion. Increased Openness, on the other hand, did not differ between responders and non-responders and did not connect with treatment response.

This supports the idea that openness to experience is orthogonal to the symptoms of anxiety or depression, however other data also point to a tepid link between openness and psychological health. A recent naturalistic survey of more than 200 people who underwent a psychedelic experience and had their symptomatology and personality traits evaluated online by our team provides evidence that the change in Openness score may have been a side effect in addition to, rather than a direct result of, improved affective symptoms. Here, changes in Openness were seen in both depressed and non-depressed people, whereas changes in Neuroticism were only seen in depressed people.

Summation

In conclusion, the study found that major depressive patients who received psilocybin therapy experienced changes in personality traits from baseline to three months later. While pronounced increases in Extraversion and, in particular, Openness, might be an effect more specific to therapy with a psychedelic than with other antidepressant interventions, decreases in Neuroticism and (trend-level) increases in Conscientiousness were consistent with what has previously been found among patients responding to antidepressant treatment.

Future Implications

However, both this idea and the brain mechanisms underlying post-psychedelic personality change require more investigation in subsequent controlled investigations. The type of the acute experience under psilocybin was found to predict some changes in personality, with acute Insight being particularly implicated, according to some preliminary research. In addition, research into the neurological correlates of personality changes brought on by psychedelics is still lacking.