Alterations of consciousness and mystical-type experiences after acute LSD in humans

This double-blind, placebo-controlled study (n=40) suggests that mystical-type experiences may be more frequently induced by psilocybin than LSD, and that the subjective effects of LSD are dose-dependent.

Abstract

“Rationale: Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration response functions with regard to alterations of consciousness are lacking.

Methods: We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg.

Results: On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg.

Conclusions: Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.”

Authors: Matthias E. Liechti, Patrick C. Dolder & Yasmin Schmid

Summary

Abstract

LSD is used recreationally and in clinical research. No data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness.

We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 g LSD in 24 and 16 subjects, respectively.

LSD produced similar effects to those of psilocybin in healthy subjects and patients, but higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 g comparedwith100g.

In this study, LSD produced infrequent mystical-type experiences, possibly because of the set and setting used in the study.

Introduction

Lysergic acid diethylamide (LSD) is the prototypical hallucinogen, and is used for recreational and personal purposes. There is much interest in its therapeutic potential, but only one modern study has tested the effects of LSD in patients.

We examined whether and the extent to which LSD produces mystical-type effects in the Mystical Experience Questionnaire (MEQ) and evaluated the way in which mystical experiences are related to LSD-induced increases in 5D-ASC scale scores and plasma levels of LSD.

Clinical experimental research with LSD has recently seen a resurgence, with numerous studies examining the effects of LSD on the brain. Researchers have correlated subjective drug effects with brain functional magnetic resonance imaging data, but the way in which LSD exposure in the body is linked to subjective effects in these studies is unclear.

The present study assessed the dose- and plasma concentration-response functions of LSD using the 5D-ASC scale in 40 subjects and found associations across subjects between the peak and total plasma exposure to LSD and its effects on 5D-ASC scale scores.

Study design

We performed two studies using double-blind, placebo-controlled, cross-over designs with two experimental test sessions (LSD and placebo) in a balanced order. The washout periods between sessions were at least 7 days.

Participants

Forty healthy participants were recruited from the University of Basel campus via online advertisement. They were divided into two groups, with 16 participants in study 1 and 24 participants in study 2. The subjects were asked to abstain from excessive alcohol consumption and to not drink xanthine-containing liquids after midnight before the study day. No substances were detected during the study.

Study procedures

Each study included a screening visit, psychiatric interview, two25-hexperimentalsessions, and an end-of-study visit. The subjects were resting in hospital beds except when going to the restroom, and LSD or placebo was administered at 9:00 AM.

Study drug

LSD hydrate was administered in single oral doses of 100 or 200 g as gelatin capsules. The doses used in the study were within the range of doses that are taken for recreational purposes.

Measures

In study 2, mystical experiences were assessed using a 43-item MEQ embedded in a 100-item SOCQ. The German version was independently forward-translated into German by two translators with German as their mother tongue.

The MEQ has been used in numerous experimental and therapeutic trials with psilocybin. It provides scale scores for seven domains of mystical experiences, and a total of all scale scores was used as an overall measure of the mystical-type experience. MEQ ratings were obtained 24 h after drug administration, and participants were asked to retrospectively rate drug effects during peak drug effects.

The 5D-ASC scale was used in both studies to assess alterations of consciousness. It contains 94 items and has five subscales/dimensions.

The 5D-ASC is a well-validated and widely used scale that measures derealization and depersonalization associated with positive emotional states, including heightened mood to euphoric exaltation. It also measures ego dissolution and loss of self-control phenomena associated with anxiety.

Analysis of plasma LSD concentrations

Blood samples were collected before and 0.5, 1, 1.5, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 h after LSD administration. Plasma was immediately centrifuged and analyzed using liquid-chromatography-tandem mass-spectrometry.

Statistical analyses

The data analysis was performed using Statistica 12 software and Pearson correlations were used to assess associations between outcome measures.

Mystical-type experiences

LSD significantly increased all MEQ scores compared with placebo in healthy subjects and in patients during LSD-assisted psychotherapy. Only two subjects in each study had a complete mystical experience.

Alterations of consciousness

LSD increased the overall ASC score, the dimension of visionary restructuralization, and the blissful state, insightfulness, and changed meaning of percepts subscales significantly compared with the 100 g dose.

Associations between alterations of consciousness and mystical-type experiences

LSD-induced alterations of consciousness were significantly correlated with ratings of mystical experience on the MEQ30, and positive mood on the ASC.

Correlations between plasma LSD concentrations and LSD-induced alterations of consciousness and mystical-type experiences

LSD Cmax and AUC values were not positively correlated with ratings of peak subjective effects on the 5D-ASC scale or MEQ across subjects or within dose groups.

Discussion

The present study evaluated associations between plasma LSD concentrations and subjective effects of LSD, including mystical experiences, in participants after a dose of 200 g. The MEQ30 has been used with psilocybin and has produced high mean MEQ30 ratings of 77 % and complete mystical experiences in as many as 67 % of healthy subjects. However, placebo increased MEQ30 scores only to 1 %. Psilocybin-assisted psychotherapy in tobacco smokers produced complete mystical experiences in only 10 of 26 sessions (38 %) and LSD produced greater ineffability and positive mood but lower effects on the mystical subscale than psilocybin.

In a therapeutic setting, LSD produced similar mystical experiences as in the present study, but complete mystical experiences were only in two of 11 patients. Additionally, the participants may have been more spiritually inclined.

LSD produced greater placebo-adjusted positive mood ratings than psilocybin on the MEQ30 and very pronounced increases in 5D-ASC blissful state ratings than the highest doses of psilocybin or dimethyltryptamine (DMT) that were tested so far.

One could argue that mystical and spiritual experiences are not the most prominent feature of the LSD response, but they are highly associated with other alterations of consciousness on the 5D-ASC scale and LSD produced additional effects on emotion processing that could facilitate psychotherapeutic interventions.

Recent experimental studies have associated the subjective effects of LSD with fMRI data, but without data on plasma LSD levels. The present study used an oral dose of 100 g LSD, but produced significantly greater mean ratings on the 5D-ASC scale.

LSD produces greater effects than lower doses, including feelings of closeness to others, happiness, openness, and trust. The 200 g dose is currently being used in LSD-assisted psychotherapy, and the lower dose is being tested in experimental fMRI studies.

The present analyses showed no positive correlations between LSD levels and effects across subjects, possibly because of the high levels of LSD used and the high subjective response ratings in most subjects.

Responses to MDMA or LSD may vary in a standardized experimental setting due to individual differences in drug absorption/distribution or when a lower dose is used. The correlations between plasma levels of MDMA and subjective and cardiovascular effects of MDMA across subjects are only weak during the peak response but stronger at onset. This is an important consideration when interpreting associations between ego dissolution and fMRI parameters. In the present study, 200 g doses of LSD produced particularly marked increases in visionary restructuralization including changed meaning of percepts. These alterations were significantly greater in participants with relatively lower Cmax levels of LSD.

LSD (200 g) rarely produced full mystical experiences in the present study and in patients during LSD-assisted psychotherapy compared with psilocybin. It produced significantly greater bliss, insightfulness, and changes in meaning of percepts at 200 gcomparedwith100g.