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

This single-blind placebo-controlled study (n=20) investigated the effects of LSD (75μg/70kg) in relation to participants’ ability to mentally project themselves backwards and forward in time, based on brain activity measures and subjective reports. There were significantly fewer cases of mental time travel to the past under LSD, meaning they were less likely to recollect aspects of the past autobiographical self. This phenomenon was correlated with the decreased integrity of the Default Mode Network (DMN).

Abstract

Introduction: This paper reports on the effects of LSD on mental time travel during spontaneous mentation.

Methods: 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.

Discussion: 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.”

Authors: Jana Speth, Clemens Speth, Mendel Kaelen, Astrid M. Schloerscheidt, Amanda Feilding, David J. Nutt & Robin L. Carhart-Harris

Summary

Introduction

Lysergic acid diethylamide (LSD) is a semi-synthetic tryptamine hallucinogen that is thought to be mediated by serotonin 2A receptor agonism. The current study used a linguistic tool to analyse mentation reports to quantify mental time travel under LSD and placebo.

Mental time travel is an ability of humans to mentally project themselves backwards and forwards in time. It has been linked to the default-mode network, and increased DMN RSFC has been found in depression, and decreased DMN RSFC has been found in the psychedelic state.

Twenty healthy volunteers participated in a placebo-controlled crossover study, in which intravenous administration of LSD (75 g) and placebo (saline) was incorporated prior to functional magnetic resonance imaging (fMRI). 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.

The results of the present study may help to define and quantify the phenomenon of ‘ego-dissolution’ or ‘ego-disintegration’, which is often reported to occur under psychedelics. This phenomenon is also known as a reduction in mental time travel to the past under LSD.

Method

A quantitative linguistic analysis was conducted on transcriptions of participants’ verbally delivered mentation reports collected after LSD or placebo administration. The analysis indicated that the mentation reports differed in the number of linguistic constructs that indicated references to mental time travel.

Participants

Twenty healthy volunteers were recruited via word-of-mouth and 19 were included in the analyses. All participants had at least one previous experience with a classic psychedelic drug, but not within 14 days of the first dosing session.

Experimental design

The current study was placebo-controlled, within-subjects/cross-over, balanced-order design, and received a favourable opinion from the National Research Ethics Service (NRES) ethics committee London-West London. All volunteers made three study visits that comprised screening, dosing session one, and dosing session two.

Screening

Prior to enrolment, volunteers attended a screening visit at the Wellcome Trust Clinical Research Facility at the Hammersmith Hospital in West London. They signed informed consent after being explained the study design, procedures, and psychological effects of LSD.

Experimental procedure

Participants were asked to arrive at the study centre at or before 09:00 and underwent a urine test for drugs abuse and pregnancy (where relevant). LSD was administered intravenously in 10 mL saline over 2 min.

After dosing, volunteers completed a functional neuroimaging protocol that included habituating to a scanner environment and a one-hour MRI scanning session.

The present analyses are concerned with the mentation reports obtained from participants at the beginning of structured interviews, performed soon (within 30 min) after the functional MRI scanning, 2.5 h post-dosing.

The subjective effects of LSD were assessed by a visual analogue scale with 20 increments, and subsided to a negligible level approximately 7 – 8 h post-infusion. Participants were discharged by the study physician when they were considered to be functioning normally.

Two blood-oxygenlevel dependent (BOLD)-weighted fMRI scans were performed on a 3T GE HDx system. The scans were eyes-closed and task-free, and the pre-processing involved will be reported in a separate publication.

A template DMN was acquired by using independent component analysis (ICA) performed on data derived separately as part of the Human Connectome Project (HCP). LSD caused a reduction in intra-DMN RSFC, which was measured using paired t-tests.

Mentation reports

The authors developed a linguistic tool to quantify mental time travel in mentation reports. This tool is partly grammatical and partly cognitive-semantic, and it has been used to link linguistic references to simulated motor activity with motor cortical activation in different states of consciousness.

Analysis of mental spaces hosting past, present or future scenarios

Theta system theory states that the initiator of an event takes on a specific thematic (theta) role within a sentence or phrase. The initiator is described by a noun phrase, but the agent does not necessarily correlate with the grammatical subject.

The current study focuses on cognitive agency, which is defined as agency that is related to the semantic field of cognition.

I was thinking about various things, including missing my Italian class yesterday, trying to figure out what went wrong during my date the other day, and wondering if I can ace the exam tomorrow.

Cognitive agents often build mental spaces that host past, present, and future scenarios. These mental spaces are not necessarily attributed a specific metaphysical value, and are not necessarily logically consistent.

Mental spaces are marked by grammatical clues, immediate semantic clues, and contextual clues. They are defined by the cognitive action carried out during the mentation period.

Report rating instructions

All raters were asked to judge all reports. They were given a hard copy of the transcribed reports and an instruction manual, and were asked to identify instances of cognitive agency and ensuing mental spaces in the reports.

Statistical analyses

A repeated-measures student’s t-test was used to compare word count between LSD and placebo condition, and a one-way repeated-measures multivariate analysis of variance (MANOVA) was conducted to test for an omnibus effect of LSD on the number of cognitive agencies referring to the present, past, and future.

Results

A total of 38 mentation reports were collected approximately 2.5 h post dosing. The linguistic samples from reports collected after LSD and placebo can be seen in Table 1.

Participants took more LSD than placebo and delivered longer reports. There were fewer references to the past after LSD than after placebo, but no significant differences in the number of references to the present or future.

A correlation analysis was run to look at the relationship between the intensity of the subjective effects of LSD and reduced cognitive agencies connected to mental spaces for the past.

A correlational analysis was run to look at the relationship between within-DMN RSFC or ‘integrity’ and the number of cognitive agencies connected to mental spaces for the past.

Discussion

LSD reduced mental time travel to the past, and the intensity of LSD’s subjective effects was correlated with the reduction in mental time travel to the past.

The DMN is linked to autobiographical memory, self-reflection, and spontaneous cognition. It is decreased in integrity in people who have trouble time traveling to the past.

The DMN does not possess an obvious anchor point, but it is known to possess strong anatomical and functional connections with the hippocampus, via the parahippocampal cortex. The hippocampus-DMN circuit may be important for the maintenance of one’s sense of self.

The present results may help to extend our knowledge of the psychological effects of LSD and inspire a new perspective on the construct of ‘ego-dissolution’. If similarities are observed between the concepts of ego-disturbances in psychosis and ego-dissolution, this may substantiate the LSD state as a model of psychosis.

The notion of the narrative self may be relevant to the findings of the present study and how they relate to psychedelic-induced ego-dissolution. The hippocampal-DMN circuit may be an important part of this feed.

LSD is used in psychotherapy to facilitate emotional insight and release, and patients often report re-experiencing past memories with unusual vividness. The present study shows that LSD decreases mental time travel to the past.

LSD improved access to autobiographical memory, but less spontaneous reflections on the past under LSD. This paradox may be explained by the nature of the phenomena themselves, as well as how they are tested and measured.

Standing 4 yards away was my father with his fishing rod. The picture has remained with me ever since, because my father died just before my illness.

In normal waking consciousness, mental time travel to the past may occur with greater regularly than in the psychedelic state, however, the content of these reflections may be more anodyne and (ego) syntonic or unthreatening.

In controlled research with psychedelics, participants were explicitly cued to recollect positive episodic memories. However, measures of spontaneous cognition may be more informative, since the experimental aims and hypotheses motivating these measures are effectively hidden.

The raters found the tool of quantitative linguistic analysis easy to apply, and the inter-rater reliability was high. It has been used successfully to differentiate between different states of consciousness.

LSD-induced mentation reports were longer and more elaborate than placebo-induced mentation reports. This is in line with findings from other studies of altered states of consciousness and especially dream research.

This study highlights some limitations, such as the fact that participants were intoxicated on LSD when asked to deliver their retrospective accounts of their experience in the MRI scanner.

The sample size of 15 in the present study is too small to demonstrate a reliable relationship between individual differences in DMN connectivity and mental time travel.

The present study’s findings suggest that LSD reduces reflection on the past, but this effect might be due to a more general effect of LSD on cognition. However, this possibility must be explored by examining the effects of other intoxicants on the same measures.

The therapeutic potential of psychedelics is currently being revisited, with promising preliminary results. Psilocybin-assisted psychotherapy for treatment-resistant depression has been found to decrease DMN RSFC, which correlates positively with ruminative thinking.

The present analyses found that mental time travel to the past decreased under LSD. This finding is intriguing to consider whether psychedelics work in a similar way to mindfulness-based therapies, and whether this effect is mediated by decreases in intra-DMN functional connectivity.

Ever since the psilocybin session on Thursday, I have found it easier to engage in the moment, whether this be watching water in a fountain or sitting in science talks and meetings this morning.

Conclusion

The present study sought to investigate the effect of LSD on mental time travel, and found that there was a selective effect of LSD on mental spaces linked to the past. This effect correlated with the general intensity of LSD’s subjective effects.

Study details

Compounds studied
LSD

Topics studied
Neuroscience

Study characteristics
Original Placebo-Controlled Single-Blind Within-Subject

Participants
20 Humans

Authors

Authors associated with this publication with profiles on Blossom

Mendel Kaelen
Mendel Kaelen is a neuroscientist and entrepreneur, researching and developing a new category of psychotherapeutic tools for care-seekers and care-providers. Mendel has researched the incomparable effects of music on the brain during LSD-assisted psychotherapy. His work has determined how LSD increases enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. This gives light to how music can be used as another dimension in helping psychotherapists create the ideal setting for their patients.

Amanda Feilding
Amanda is the Founder and Director of the Beckley Foundation. She's called the 'hidden hand' behind the renaissance of psychedelic science, and her contribution to global drug policy reform has also been pivotal and widely acknowledged.

David Nutt
David John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

Institutes

Institutes associated with this publication

Beckley Foundation
The Beckley Foundation is one of the leading voices that has spurred the scientific renaissance of psychedelics research. Led by Amanda Fielding, the NGO funds research and engages with politicians.

Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.

Compound Details

The psychedelics given at which dose and how many times

LSD 75 μg | 1x

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