LSD, madness and healing : Mystical experiences as possible link between psychosis model and therapy model, Isabel Wießner et al., 2021

LSD, madness and healing : Mystical experiences as possible link between psychosis model and therapy model

Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes, Amanda Feilding, Sidarta Ribeiro and Luís Fernando Tófoli

Psychological Medicine, 2021, 1-15.



Background : For a century, psychedelics have been investigated as models of psychosis for
demonstrating phenomenological similarities with psychotic experiences and as therapeutic
models for treating depression, anxiety, and substance use disorders. This study sought to
explore this paradoxical relationship connecting key parameters of the psychotic experience,
psychotherapy, and psychedelic experience.

Methods : In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy
volunteers received 50 μg D-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic
experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic
potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet
Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences
Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of
Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging
Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between
LSD-induced effects were examined.

Results : LSD induced psychedelic experiences, including alteration of consciousness, mystical
experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience
and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with
complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated
with no other effects. Individual mindfulness changes correlated with aspects of aberrant
salience and psychedelic experience.

Conclusions : The LSD state resembles a psychotic experience and offers a tool for healing.
The link between psychosis model and therapeutic model seems to lie in mystical experiences.
The results point to the importance of meaning attribution for the LSD psychosis model and
indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering
mystical experiences.



Since the discovery of its psychedelic properties, D-lysergic acid diethylamide (LSD) has carried a paradoxical history. On one hand, LSD was applied as a psychosis model, owing to its similarity to the schizophrenic phenomenology (Geyer & Vollenweider, 2008). On the other hand, it was applied as a therapeutic tool for conditions including alcoholism and mood disorders (Krebs & Johansen, 2012; Reiff et al., 2020). This study sought to bridge the gap between these parallel research lines by examining key parameters of both areas: aberrant salience reflecting psychosis model and suggestibility and mindfulness reflecting therapeutic models.

Regarding the psychosis model, there are remarkable similarities between psychedelic and psychotic experiences, namely altered perception of senses, self, body, time, altered emotions, impaired cognition, loss of intentionality, magical thinking, among other behavioral and neurophysiological phenomena (De Gregorio, Comai, Posa, & Gobbi, 2016; Geyer & Vollenweider, 2008; Vollenweider & Geyer, 2001). To explain the generation of psychotic experiences, schizophrenia research has emphasized salience processing. Salience is the quality of an element that makes it stand out from its environment and thereby catch attention, like a red dot on a wall (stimulus-driven) or a journal’s impact factor for scientists (goal-directed) (Paulus, Rademacher, Schäfer, Müller-Pinzler, & Krach, 2015). Salience prioritizes relevant binformation and influences perception and behavior, including knowledge activation (Higgins, 1996), attribution of causality (Taylor & Fiske, 1978), decision making (Tversky & Kahneman, 1974), and self- and other-perception (Callero, 1985).