Depressive DisordersHealthy VolunteersNeuroimaging & Brain MeasuresAyahuascaLSDPsilocybin

Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide

In a placebo-controlled crossover fMRI study of 20 healthy volunteers, intravenous LSD (75 μg) reduced spontaneous mental time travel to the past (with no change for present or future) and the extent of this reduction correlated with decreased resting-state functional connectivity within the default‑mode network. This DMN disintegration may help explain how psychedelics could alleviate maladaptive rumination in disorders such as depression.

Authors

  • Robin Carhart-Harris
  • David Nutt
  • Amanda Feilding

Published

Journal of Psychopharmacology
individual Study

Abstract

This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured interviews performed shortly after the functional magnetic resonance imaging (fMRI) scans (approximately 2.5 h post-administration). Within each report, specific linguistic references to mental spaces for the past, present and future were identified. Results revealed significantly fewer mental spaces for the past under LSD and this effect correlated with the general intensity of the drug’s subjective effects. No differences in the number of mental spaces for the present or future were observed. Consistent with the previously proposed role of the default-mode network (DMN) in autobiographical memory recollection and ruminative thought, decreased resting-state functional connectivity (RSFC) within the DMN correlated with decreased mental time travel to the past. These results are discussed in relation to potential therapeutic applications of LSD and related psychedelics, e.g. in the treatment of depression, for which excessive reflection on one’s past, likely mediated by DMN functioning, is symptomatic.

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Research Summary of 'Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide'

Introduction

Lysergic acid diethylamide (LSD) is a classic psychedelic whose psychological effects are largely attributed to serotonin 2A receptor agonism, but the links between its neurobiology and subjective phenomenology remain incompletely understood. Previous work has associated spontaneous mental time travel—the tendency during mind-wandering to recollect past autobiographical episodes or imagine future experiences—with the brain's default-mode network (DMN), and has shown that DMN resting-state functional connectivity (RSFC) correlates with frequency of such self-referential cognition and is elevated in depression. Conversely, acute psychedelic states have been reported to reduce DMN RSFC and to occasion experiences described as ego-dissolution, suggesting a possible mechanistic connection between DMN disruption and altered temporal focus of spontaneous thought. Speth and colleagues therefore set out to combine linguistic analysis of spontaneous mentation reports with resting-state fMRI to test whether LSD reduces linguistic markers of mental time travel to the past, and whether any such change relates to LSD-induced decreases in intra-DMN connectivity. The study used a placebo-controlled, within-subject crossover design in healthy volunteers, analysing mentation reports obtained about 2.5 hours after intravenous administration of 75 µg LSD or saline placebo and relating these behavioural measures to contemporaneous DMN RSFC derived from task-free fMRI scans.

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