Low-dose LSD and the stream of thought: Increased Discontinuity of Mind, Deep Thoughts and abstract flow

In this double-blind randomized controlled trial (n=24) healthy participants were given 50μg of LSD to determine the effects of LSD on the stream of thought. It was found that LSD similarly affected the passive and active stream of thought towards deviant but meaningful thought patterns with increased chaos and meaning during mind-wandering and abstract flow during free association.

Abstract

“Rationale: Stream of thought describes the nature of the mind when it is freely roaming, a mental state that is continuous and highly dynamic as in mind-wandering or free association. Classic serotonergic psychedelics are known to profoundly impact perception, cognition and language, yet their influence on the stream of thought remains largely unexplored.

Objective: To elucidate the effects of LSD on the stream of thought.

Methods: In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy participants received 50 μg lysergic acid diethylamide (LSD) or inactive placebo. Mind-wandering was measured by the Amsterdam Resting State Questionnaire (ARSQ), free association by the Forward Flow Task (FFT) for three seed word types (animals, objects, abstract words). ARSQ and FFT were assessed at +0 h, +2 h, +4 h, +6 h, +8 h and +24 h after drug administration, respectively.

Results: LSD, compared to placebo, induced different facets of mind-wandering we conceptualized as “chaos” (Discontinuity of Mind, decreased Sleepiness, Planning, Thoughts under Control, Thoughts about Work and Thoughts about Past), “meaning” (Deep Thoughts, Not Sharing Thoughts) and “sensation” (Thoughts about Odours, Thoughts about Sounds). LSD increased the FFT for abstract words reflecting an “abstract flow” under free association. Overall, chaos was strongest pronounced (+2 h to +6 h), followed by meaning (+2 h to +4 h), sensation (+2 h) and abstract flow (+4 h).

Conclusions: LSD affects the stream of thought within several levels (active, passive), facets (chaos, meaning, sensation, abstractness) and time points (from +2 h to +6 h). Increased chaos, meaning and abstract flow at +4 h indicate the utility of a late therapeutic window in psycholytic therapy.

Authors: Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes, Lucas Oliveira Maia, Amanda Feilding, Sidarta Ribeiro, Natália Bezerra, Draulio B. Araujo, Luís F. Tófoli

Summary

Abstract

Psychedelics have been investigated as models of psychosis and as therapeutic models for depression, anxiety, and substance use disorders.

In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 g D-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience, therapeutic potential, and psychedelic experience were assessed.

LSD increased aberrant salience and suggestibility, but not mindfulness, and these effects correlated with aspects of psychedelic experience.

The LSD state resembles a psychotic experience, and therapeutic suggestions fostering mystical experiences might be helpful.

Introduction

Since the discovery of its psychedelic properties, LSD has carried a paradoxical history. This study sought to bridge the gap between these parallel research lines by examining key parameters of both areas.

Regarding the psychosis model, salience processing is a key factor in the generation of psychotic experiences, including altered perception of senses, self, body, time, altered emotions, impaired cognition, loss of intentionality, magical thinking, among other behavioral and neurophysiological phenomena.

Aberrant salience is related to hallucinations, delusions, and negative symptoms in schizophrenia, first-episode psychosis, and healthy controls, and increases with cannabis use. It also mediates the cannabis-induced development of schizotypal symptoms.

Regarding the therapeutic model, psychedelic-induced suggestibility and mindfulness seem to be promising approaches to date. These approaches might potentially boost treatment efficiency in cases of pain, anxiety, somatization, asthma, and nicotine addiction.

This study explored the effects of LSD on mindfulness and suggested that LSD increases aberrant salience, suggestibility, and mindfulness, and that there are positive correlations between LSD-induced aberrant salience, suggestibility, mindfulness, and psychedelic experience.

Study design

This study used a randomized, double-blind, placebo-controlled, crossover design and was approved by the University Research Ethics Committee and the National Health Surveillance Agency.

Participants

Twenty-five healthy participants were recruited in a convenience sample. They provided written informed consent before participation, and were subject to screening for psychiatric symptoms, heart disease, and non-native speaking of Brazilian Portuguese.

Drug

Participants received 50 g LSD or inactive placebo (alcohol solution) orally diluted in 30 ml water. The dose was chosen to minimize the risk of adverse reactions and exert noticeable effects without impairing the subjects’ ability to complete the measurements.

Psychedelic experience

Subjective intensity and valence of drug effects were assessed by visual analog scales. Maximum intensity, maximum and minimum valence, area under the curve for intensity, and positive and negative valence were calculated.

The LSD-induced experience was self-rated using the Brazilian Portuguese versions of the Altered State of Consciousness Questionnaire (ASC), Mystical Experiences Questionnaire (MEQ), Challenging Experiences Questionnaire (CEQ), and Ego-Dissolution Inventory (EDI).

Aberrant salience

The Aberrant Salience Inventory measures the trait aberrant salience using 29 items in yes – no format. The scale was adapted to a state scale by converting items from present tense to past tense.

Suggestibility

The Creative Imagination Scale (CIS) measures suggestibility and contains 10 items of different modalities. The scale was translated by our team and split into two parallel versions, which were balanced across participants and counterbalanced across treatments.

Mindfulness

Mindfulness was measured by the Five Facet Mindfulness Questionnaire, Mindful Attention Awareness Scale, and Experiences Questionnaire. All scales were applied before drug administration, 24 h afterward, and 2 weeks afterward.

Study procedures

Two investigators were present at each study session, a psychologist and a psychiatrist. They were continuously available for questions and doubts via e-mail and phone.

The session started at 7:30 a.m. with baseline measurements, followed by diverse tests and questionnaires throughout the day. After the session, the subject returned to complete measurements of mindfulness and aberrant salience, and was released around 10:00 a.m.

Participants completed online follow-up measurements including mindfulness scales two weeks and four months after the second session. No persisting side effects were reported.

Data analysis

Statistical analysis was performed with IBM SPSS Statistics (version 22). Results were Bonferroni-corrected post hoc for multiple comparisons unless stated otherwise, and Spearman’s rank correlation coefficients were calculated between LSD-induced changes on psychedelic experience, aberrant salience, suggestibility, and mindfulness.

Psychedelic experience

LSD increased intensity and positive valence compared to placebo, and there was a significant period effect for IntAUC. There were no other effects of period and carryover.

The ASC and MEQ were significantly higher under LSD than placebo in Total and all factors except Anxiety, and the CEQ was significantly higher under LSD than placebo in Total, Grief, Physical Distress, Insanity, and Isolation.

Aberrant salience

Under LSD, ASI scores were significantly higher compared to placebo, with no effects of period or carryover.

Suggestibility

Under LSD, CIS ratings were significantly increased compared to placebo, and increases were observed in Extern Ambience, Weight, Sensation, and Taste, but not Intern Ambience.

Correlations

Regarding aberrant salience, psychedelic experiences were positively correlated with mindfulness at T1 but negatively with mindfulness at T2. Furthermore, suggestibility was not correlated with other LSD-induced effects.

Discussion

This study explored the relationship between psychedelic experiences and aberrant salience, suggestibility, mindfulness and the psychosis model. It found that psychedelic experiences were positively correlated with aberrant salience and suggestibility at T1 but negatively correlated with mindfulness at T2.

Psychedelic experience

A low dose of LSD (50 g) induces predominantly positive emotions, including increased positive valence, Positive Mood, only slightly increased Grief, Physical Distress, Insanity, and Isolation, and unaltered negative valence, Anxiety, Fear, Death, and Paranoia. This dose also induces mystical experiences and ego-dissolution, which might support an altered perspective on the self.

Psychosis model

LSD increases all aberrant salience factors, including Senses Sharpening, Impending Understanding, Increased Significance, Heightened Emotionality, and Heightened Cognition. However, emotional aspects of aberrant salience and psychedelic experience showed few correlations, pointing to the limits of the psychosis model.

Altogether, our findings highlight the potential of low psychedelic doses to induce psychotic-like, meaning-laden experiences, including hallucinations and delusions. Furthermore, aberrant salience might provide an intriguing perspective to explain psychedelic phenomena including altered cognition, logical thinking, self- and other-perception, empathy, and prosocial attitudes.

Therapy model

LSD increased suggestibility in a manner similar to previous results, and the modulated Extern Ambience indicates application potential for mood disorders, somatization, pain, and eating disorders. However, psychedelic-induced suggestibility needs to be prudently applied, since suggestions can engender potentially harmful results.

In contrast to previous findings, LSD did not increase mindfulness. This might be explained by setting or placebo effects, or by substance differences, such as the different psychoactive components of ayahuasca, toad secretion, and mushrooms.

Connecting psychedelic experience, psychosis model, and therapy model

Suggestibility was not correlated with other effects, and mindfulness changes were correlated with mystical experiences and ego-dissolution, positively in the short term and negatively in the mid-term.

Aberrant salience showed no correlations with suggestibility or mindfulness, but robustly correlated with mystical and ego-dissolution experiences, which are fundamental within psychedelic-assisted treatments and psychotic experiences.

In some non-Western cultures, mystical and psychotic experiences are reframed as spiritual trance and shamanism, and psychedelic use in shamanic rituals and psychedelic-assisted psychotherapy underlies different conceptions of illness and healing. Therefore, mystical experiences might constitute the link between the psychosis model and therapy model.

Limitations

Several limitations should be considered when interpreting the results, such as the difficulty of blinding, imbalanced education levels across groups, and lack of drug screening. Moreover, future research should specify how mystical experiences are comparable in quality and quantity within the psychosis model and therapy model.

Conclusions

This study explored the use of low dose LSD as a psychosis model and therapeutic tool. It found that LSD increased suggestibility but not mindfulness, and increased aberrant salience, suggesting a greater weight of psychosis- than therapy-related aspects in the psychedelic phenomenology.

Author contributions: IW designed and coordinated the study, MF conducted clinical interviews, FPF contributed to data analysis, and LFT reviewed the manuscript.

Conflict of interest. None.

1 Other similarities between schizophrenia and bipolar disorder include distorted perception of senses, time, space, self, and body, thought disturbances, perceived loss of control, reduced organization and adjustment of behavior, impaired cognition, disorganized language, and several neurophysiological parameters. Most studies compared psychedelic effects in healthy subjects to experiences of patients with psychotic disorders. Interestingly, a number of studies administered psychedelics to patients with schizophrenia or people with predisposition to schizophrenia.

Many patients with schizophrenia experience spirituality as important, and it influences their attitudes toward medical treatment and helps them cope with challenging symptoms. However, the conception of psychosis as disorder is culture-specific, and influences public and personal attitudes and the unfavorable progression of symptoms.