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 altered states of consciousness induced by LSD. Data extracted from articles identified by a systematic literature review 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 performed meta-regression analyses using restricted cubic splines for data from studies with LSD doses of up to 200 μg base. Most scales revealed a sigmoid-like increase of effects, with a plateauing at around 100 μg. The most strongly modulated factors referred to changes in perception and illusory imagination, followed by positively experienced ego-dissolution, while only small effects were found for Anxiety and Dread of Ego Dissolution. The considerable variability observed in most factors and scales points to the role of non-pharmacological factors in shaping subjective experiences. The established dose-response relationships may be used as general references for future experimental and clinical research on LSD to compare observed with expected subjective effects and to elucidate phenomenological differences between psychedelics.

Decreased CO2 saturation during circular breathwork supports emergence of altered states of consciousness

“…Therefore, they might be expecting to see improved well-being post-session. Nevertheless, the subacute increases in well-being reported here were in line with previous reports (Bahi et al, 2023;Fincham, Strauss, et al, 2023;Uthaug et al, 2021), and improvements depended on ASC depth throughout the session -a relationship that has also been reported for psychedelic experiences (Hirschfeld et al, 2023). Together, these results suggests that improvements in well-being were substantial beyond the contribution e.g.…”

“…Scores for both questionnaires were similar to those expected in the context of psychedelic-augmented therapy, with 5 of 11 sub-scales of the 11-DASC and all 4 sub-scales of the MEQ indicating no significant difference from experiences typically evoked by e.g. a dose of 20-25 mg of psilocybin (Hirschfeld, Prugger et al, 2023;Liechti et al, 2017; see Fig. 2A-B and Database Analysis section of Methods).…”

Microbiome: The Next Frontier in Psychedelic Renaissance

“…Psychedelic substances, despite their demonstrated therapeutic potential, have long been recognized to exhibit a high degree of interpersonal variability in response [ 59 , 60 , 61 ]. Individuals who use the exact dosage of the same substance can experience vastly different subjective effects.…”

Flicker light stimulation induces thalamocortical hyperconnectivity with LGN and higher-order thalamic nuclei

“…With complex connectivity throughout the neocortex, the thalamus contributes to higher-order processing, cognition and is also thought to coordinate information availability across cortices (Halassa and Sherman, 2019;Sherman and Guillery, 2006). Correspondingly, thalamocortical hyperconnectivity has been related to various pathologies, such as psychosis (Avram et al, 2021;Ramsay, 2019), epilepsy (Chen et al, 2021;Kim et al, 2014) and migraine (Bolay, 2020;Martinelli et al, 2021;Tu et al, 2019), and during diverse altered states of consciousness (ASC; e.g., induced by psychoactive drugs (Carhart-Harris et al, 2016;Müller et al, 2017;Preller et al, 2019)), all of which involve hallucinatory experiences (consider also (Hirschfeld et al, 2023;Hirschfeld and Schmidt, 2021;Prugger et al, 2022;Schmidt and Majić, 2017)). However, the exact functional contributions of thalamocortical hyperconnectivity to the emergence of hallucinatory phenomena is unclear.…”