Long-lasting subjective effects of LSD in normal subjects

This double-blind cross-over trial (n=16) found that LSD (200μg) led to positive well-being/life-satisfaction scores up to 12 months later. The subjects experienced it as one of the top 10 most meaningful experiences (70%) in their lives.

Abstract

Rationale: Lysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on subjective well-being and personality.

Methods: We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI).

Results: On the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found.

Conclusions: In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects.”

Authors: Yasmin Schmid & Matthias E. Liechti

Notes

Although the study did find many effects as noted above, there were no relevant changes in personality structure. Something that many studies (e.g. Griffiths et al. 2011) had previously found.

Summary

Abstract

We investigated the lasting effects of a single dose of LSD (200 g) on 16 healthy participants, including the Persisting Effects Questionnaire, Mysticism Scale, Death Transcendence Scale, NEO-Five Factor Inventory, and State-Trait Anxiety Inventory.

The administration of a single dose of LSD (200 g) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects. No relevant changes in personality measures were found.

Introduction

Classic hallucinogens act on serotonin 5-HT2A receptors to produce their psychotropic effects. They are used for recreational, personal/spiritual, and therapeutic purposes.

LSD has been associated with positive health outcomes in patients with anxiety, depression, and substance use disorder, as well as self-reported lasting effects on values, attitudes, personality, and well-being in normal subjects.

LSD clinical research has only recently been restarted, and the only recent study on lasting effects of LSD was conducted in 20 healthy subjects. Psilocybin clinical research has been conducted in 129 healthy subjects and 105 patients, and has shown to induce persisting positive changes in attitudes, social effects, mood, life satisfaction, behavior, and trait openness. Hallucinogens such as psilocybin have been shown to induce profound insights and mystical-type experiences in healthy participants, which have been correlated with lasting changes after psilocybin administration.

The present study aimed to investigate the persisting effects of LSD 1 and 12 months after administration of a single dose in 16 healthy participants. It found that LSD increased self-rated mystical experiences, total ratings on the Mysticism Scale, and total ratings on the Death Transcendence Scale.

Study design

The present study included short-term (1 month) and long-term (12 months) follow-ups after a single dose of LSD and placebo. It was conducted in accordance with the Declaration of Helsinki and ICH-GCP and was approved by the Ethics Committee of the Canton of Basel, Switzerland.

Participants

Sixteen healthy subjects were recruited by word of mouth or an advertisement on the web market platform of the University of Basel. They were well-educated, had no history of mental illness, and had never used a hallucinogen.

Study procedures

The study included a screening visit with the study physician, a psychiatric interview, two 25 h test sessions, a follow-up visit approximately 1 month after the LSD test session, and a follow-up mail contact at least 12 months after LSD administration. Participants were contacted 1 month after their LSD session to assess lasting effects, and were also asked about adverse events, psychological problems, and perceptual changes/disorders.

Drugs

LSD was administered in a single oral dose of 200 g (D-lysergic acid diethylamide base; Lipomed AG, Arlesheim, Switzerland) to induce robust effects in humans.

Outcome measures

The present LSD study used the same acute and long-term outcome measures as the previous psilocybin studies, but used forward-translated versions that were then backtranslated into German.

A 143-item questionnaire was used to assess long-term effects of psilocybin use. It includes items to assess positive and negative attitudes, positive and negative mood changes, altruistic/positive and antisocial/negative social effects, and positive and negative behavioral changes. The Griffiths et al. (2006) survey asks participants to indicate how personally meaningful an experience was, how spiritually significant it was, and whether the experience has led to a change in their current sense of personal well-being or life satisfaction. One subject was lost to follow-up at 12 months, one subject did not complete all of the questions at 1 month.

The Mysticism Scale is a validated 32-item questionnaire that was developed to assess primary mystical experiences. It consists of 16 positively worded statements and 16 negatively worded statements and is used to measure three empirically derived factors: interpretation, introvertive mysticism, and extrovertive mysticism. The MS was completed 24 h after the administration of LSD and placebo, and 14 subjects completed it at screening, 1 and 12 months after administration.

The validated 26-item Death Transcendence Scale (DTS) includes five factors/subscales reflecting different aspects of death transcendence. A non-validated German version was administered at screening and 1 and 12 months after LSD administration.

A 60-item NEO-Five-Factor Inventory was used to assess personality traits and a 12-item STAI was used to assess trait anxiety.

Two measures of acute mystical-type and mind-altering effects of LSD were used in the present data analysis, the MEQ and the 5D-ASC. The MEQ includes six subscales (internal unity, external unity, sacredness, noetic quality, deeply felt positive mood, transcendence of time/space, and ineffability). The 5D-ASC contains 94 items and measures five subscales/dimensions: BOceanic Boundlessness (27 items), BAnxious Ego Dissolution (21 items), BVisionary Restructuralization (18 items), AA (15 items), and BReduction of Vigilance (12 items).

MEQ43 and 5D-ASC ratings were administered 24 h after drug administration, and participants were asked to retrospectively rate drug effects during peak drug effects.

Statistical analysis

Data were analyzed using Statistica 12. Paired t tests, ANOVA, and Tukey post hoc tests were used to analyze differences between screening and the two follow-up assessments over time, and associations between the acute response to LSD and main 12-month outcome measures were assessed using Spearman rank order correlations.

Acute effects of LSD on the Mysticism Scale

LSD significantly increased the total score, all three factors, and ratings on all subscales of the MS compared with placebo. The acute effects of LSD and placebo on the 5D-ASC and MEQ30 have previously been reported.

Lasting effects of LSD

At the 1- and 12-month follow-ups, ratings of positive attitudes, positive mood changes, altruistic/positive social effects, and positive behavioral changes significantly increased compared with the assumption of no change. Ratings of meaningfulness of the LSD experience were not different at the 1- and 12-month follow-ups. At both 1 and 12 months, ratings of spiritual significance increased, and five participants considered the LSD experience to be among the five most spiritually meaningful experiences in their lives. No subject rated the LSD experience as decreasing well-being or life satisfaction.

Conscientiousness increased significantly on the NEO-FFI at 12 months compared with pre-LSD screening, but no other changes were observed.

Correlations between acute and long-term effects of LSD

The acute effects of LSD on the MS, MEQ, and 5D-ASC were positively associated with several long-term changes in mood, behavior, well-being/life satisfaction, and total score on the PEQ, MS, and DTS 12 months after LSD administration.

Acute mystical-type effects were positively correlated with PEQ well-being/life satisfaction ratings at 12 months, and negatively correlated with DTS total scores at 12 months.

At the 1-month follow-up, one subject reported problems falling asleep and having more vivid dreams, but no psychological problems were reported.

Discussion

LSD induced subjectively meaningful experiences in healthy volunteers and was associated with lasting positive effects on well-being and lifetime mystical experiences. LSD did not increase trait openness or produce relevant changes in personality measures.

In our study, most of our hypotheses were confirmed, and the lasting effects of psilocybin were confirmed in healthy subjects using the same outcome measures. The lasting effects of LSD were also confirmed in healthy subjects in older studies.

Most participants rated their acute LSD experience as a very dramatic and interesting experience, but the comparison of pre-LSD and post-LSD personality and creativity test ratings did not document relevant changes.

A cross-over study was conducted in 30 hallucinogen-naive and spiritually active healthy subjects to evaluate the long-term effects of psilocybin. The MS and MEQ were used to assess acute mystical-type experiences, and the PEQ and MS were used to assess lasting effects at 2 and 14 months. In a dose-effect study, 18 participants received four different single doses of psilocybin and placebo and experienced acute mystical-type experiences on the MS and MEQ, but also reported strong or extreme fear sometimes during the session after administration of psilocybin at this dose.

The MS lifetime version score increased 2 months after a single dose of psilocybin and at the 14-month follow-up, similar to the present findings, and the DTS Mysticism subscale score increased 1 and 12 months after LSD administration.

The present study found no lasting effects of LSD on various personality trait measures 1 or 12 months after LSD administration. Psilocybin did not alter personality trait ratings 2 or 14 months after psilocybin administration, although increases in openness were noted 14 months after psilocybin administration.

The findings of controlled clinical studies are consistent with the view that serotonergic hallucinogens mainly produce lasting increases in lifetime mystical experiences and enduring positive effects on attitudes, mood, and behavior.

The use of LSD and psilocybin has been associated with mystical experiences, which have been shown to have long-term positive effects in healthy subjects and patients. The overall alterations in consciousness that are acutely induced by LSD may contribute to these long-term positive effects.

The extent of acute hallucinogen-induced mystical-type experiences was dose-dependent, and higher rates of meditation/spiritual practice or greater support for spiritual practice contributed to the positive long-term effects compared with a group that received psilocybin but less spiritual support. In the studies by Griffiths and colleagues, the acute hallucinogen-induced increases in MS and MEQ scores were greater after LSD administration than psilocybin, but placebo or active placebo (i.e., methylphenidate) also produced MEQ30 mean ratings of 23 and 33%, respectively. In contrast to Griffiths and colleagues, the participants in the present study were mostly university students who received monetary compensation. Participants in the present study were not explicitly told that the hallucinogen would have mystical or lasting effects, and thus reported lower ratings of mystical-type effects than in previous studies. The settings of the studies by Griffiths and colleagues appeared to be highly optimized to foster the emergence of mystical experiences, whereas fewer mystical-type experiences were reported in studies that were conducted by other groups. The acute effects of psilocybin on the 5D-ASC and MEQ were intercorrelated, and the MEQ scores predicted long-term changes in subjective well-being and life satisfaction on the PEQ at 12 months. The present study has several limitations, including that it did not include a true control condition for the long-term effects of LSD, that its sample was small, and that its questionnaires were not sufficiently powered to detect small effects on personality.

Study details

Compounds studied
LSD

Topics studied
Healthy Subjects

Study characteristics
Original Placebo-Controlled Double-Blind Within-Subject Randomized

Participants
16 Humans

Authors

Authors associated with this publication with profiles on Blossom

Matthias Liechti
Matthias Emanuel Liechti is the research group leader at the Liechti Lab at the University of Basel.

Institutes

Institutes associated with this publication

University of Basel
The University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.

Compound Details

The psychedelics given at which dose and how many times

LSD 200 μg | 1x

Linked Clinical Trial

Psychological, Physiological, Endocrine, and Pharmacokinetic Effects of LSD in a Controlled Study
The purpose of this study is to characterize the acute psychological, physiological, endocrine, and pharmacokinetic, as well as long-term psychological effects of LSD in humans.

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