Traditional serotonergic psychedelic substances, such as psilocybin, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD), have regained interest after being suppressed for several years. Pilot studies have shown that psychedelic-assisted therapy may be used to treat various illnesses, including alcohol and tobacco addiction, obsessive-compulsive disorder, despair and anxiety at the end of life, severe depression, and treatment-resistant depression.

Psychedelic Therapy

Psychedelic therapy typically involves administering a moderate to high dose of a psychedelic substance in supportive settings over one or two sessions to induce “peak” or “mystical-type” experiences characterized by a dissolution of ego boundaries and a sense of connectedness, oneness, or unity. This approach is different from the long-term daily pharmaceutical intervention typically associated with conventional therapy. The underlying processes of psychedelic therapy’s long-lasting therapeutic effects remain unknown, but the therapeutic outcomes and subjective experiences during the psychedelic sessions appear to be linked.

Effects on Personality

Furthermore, after taking a single dose of psilocybin or LSD, healthy volunteers may show an increase in the NEO-PI-R personality trait Openness to Experience, particularly in the subgroup of individuals who had mystical experiences during the session. Openness is associated with imagination, aesthetic appreciation, novelty seeking, non-conformity, and creativity, and is one of the five major aspects of personality. Effective antidepressant therapy has also been shown to improve Openness scores in major depression, as well as dramatically alter three of the other four NEO-PI-R personality domains: decreasing Neuroticism, increasing Extraversion and Conscientiousness, while maintaining Agreeableness.

Findings on Psilocybin Therapy for Depression

Significant changes in personality tests were observed among patients with treatment-resistant severe depression who underwent open-label psilocybin therapy in a clinical study. The NEO-PI-R “Big Five” score of Neuroticism considerably decreased from baseline to the 3-month follow-up, whereas Extraversion and Openness scores significantly increased, Conscientiousness exhibited a trend-level increase, and Agreeableness remained unchanged. Out of the 30 NEO PI-R facets, 10 survived multiple comparisons correction, resulting in a total of 11 facets that were considerably altered, which is the first time personality assessments of patients receiving psychedelic therapy for depression have been observed to change. These results are consistent with those from a previous study of patients with major depression who received selective serotonin reuptake inhibitors (SSRIs) and demonstrated improvements in trait and facet scores, including alterations in the same four “Big Five” features towards the personality profile of healthy populations.


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