Dose-response relationships of LSD-induced subjective experiences in humans

Abstract

Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first meta-analysis establishing dose-response relationship estimates of the phenomenological states induced by LSD. Data extracted from articles identified by a systematic literature search following PRISMA guidelines were obtained from the Altered States Database. The psychometric data comprised ratings of subjective effects from standardized and validated questionnaires: the Altered States of Consciousness Rating Scale (5D-ASC, 11-ASC) and the Mystical Experience Questionnaire (MEQ30). We used a meta-regression approach to obtain estimates for linear dose-response relationships of questionnaire ratings after LSD administration to healthy, highly selected study participants in controlled settings for a dosage range between 25 μg and 200 μg. LSD doses positively correlated with ratings on most factors and scales of the questionnaires, with strongest responses for visionary phenomena such as audio-visual synesthesia and altered imagery, followed by positively perceived ego dissolution comprising depersonalization and derealization phenomena. Measures referring to mystical experiences exhibited weak modulations by dose. The established dose-response relationships in the given range may be used as general references for future experimental and clinical research on LSD with low to moderate dosages to relate observed with expected subjective effects and to elucidate phenomenological differences between psychedelics.

Thalamocortical interactions reflecting the intensity of flicker light-induced visual hallucinatory phenomena

“…To investigate which thalamic nuclei display thalamocortical hyperconnectivity, it is crucial to identify an experimental tool that can selectively elicit hallucinatory experiences without additional confounding effects. For example, while thalamocortical connectivity during psychotic states and psychedelic experiences has been extensively investigated (Anticevic et al, 2014a(Anticevic et al, , 2014bMüller et al, 2017;Ferri et al, 2018;Preller et al, 2019;Avram et al, 2020Avram et al, , 2022Bedford et al, 2023;Pizzi et al, 2023), hallucinatory experiences within these populations co-occur with other physiological effects, such as long-term compensatory changes for psychotic patients (Lieslehto et al, 2021) and widespread systemic effects arising from pharmacological intervention (Schmid et al, 2015;Luppi et al, 2021;Hirschfeld et al, 2023). This means that the described neural correlates are not necessarily specific to the visual experience.…”

Update of the Altered States Database (ASDB): 2022-12-31

“…The ASDB provides psychometric data extracted from original research publications in an easily accessible data format. It is designed to catalyse meta-analyses, as e.g., for the identification of dose-response relationships as well as of cross-study variability (for examples, see: Hirschfeld and Schmidt, 2021 and Prugger et al, 2022b). Beyond this, the data might become relevant for the development of new treatment options for psychiatric disorders, where currently diverse CMTs are explored (Schmidt and Majić, 2016).…”