Psychedelic drug use and schizotypy in young adults

This observational survey (n=1032) and experimental (n=39) study investigated the relationship between psychedelic drug use and schizotypal behavior and personality trait. Results indicate that psychedelics do not pose serious risks for developing psychotic symptoms in healthy young adults, in fact, psychedelic drug exposure was associated with better evidence integration, less bias against disconfirmatory evidence, and more flexible aversive learning, compared to psychos-like behaviors that were more commonly associated with psychostimulant use.

Abstract

“Introduction: Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented.

Methods: Here, we studied an adult population (n = 1032) with a special focus on young (18–35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n = 39).

Results: We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen’s d = 0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen’s d = 0.13) and a higher sensitivity of fear responses (Cohen’s d = 1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance.

Discussion: Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.”

Authors: Alexander V. Lebedev, K. Acar, B. Garzón, R. Almeida, J. Råback, A. Åberg, S. Martinsson, A. Olsson, A. Louzolo, P. Pärnamets, M. Lövden, L. Atlas, Martin Ingvar & P. Petrovic

Summary

Psychedelic drug use and schizotypy in young adults Alexander V. Lebedev1,9*, K. Acar1,9, B. Garzón2,5, R. Almeida3, J. Råback1, A. Åberg1, S. Martinsson1, A. Olsson1, A. Louzolo1, P. Pärnamets1,4, M. Lövden2,5, L. Atlas6,7,8,

Classical serotonergic psychedelics are psychoactive substances that produce profound effects on mood and high-order cognition. They are being re-visited by scientists for their therapeutic value, as well as for overall wellbeing and life satisfaction in healthy people.

Although some studies have found a link between psychedelic use and psychosis-spectrum disorders, larger studies have failed to confirm this, nor could the use of these drugs be associated with other mental health problems.

In order to bridge the knowledge gap about past psychedelic use and higher-order cognition in a healthy non-clinical young population, a follow-up survey was conducted to collect information about total exposure to different drugs.

The study was approved by the Swedish Ethical Board and adhered to the principles of the Declaration of Helsinki. It studied Swedish adults with a special focus on healthy young adults.

Methods

We recruited 1032 participants through social media services, forums, and general platforms designed to recruit research subjects. We conducted a survey and conducted behavioural testing in a subset of subjects to assess the relation between psychedelics and psychosis-related symptoms in young adults that have no psychiatric or neurological comorbidities.

Table 1 shows the study samples, including demographics and descriptive statistics. The study also included the O-LIFE 43-item Oxford-Liverpool Inventory of Feelings and Experiences, PDI+ extended 21-item Peters Delusion Inventory, EPI, and BADE.

Schizotypy was assessed using 43-item Oxford-Liverpool Inventory of Feelings and Experiences, 21-item Peters Delusion Inventory and 21-item Adult ADHD Self-Report Scale.

In the BADE task, subjects are asked to rate the plausibility of four different interpretations of a scenario, three times. Evidence Integration Impairment (EII) was calculated from ratings of plausibility for different scenarios as recommended by Sanford et al.24.

In plain text, EII was computed as the sum of the plausibility ratings for absurd interpretations and the True interpretation.

Subjects underwent an instructed aversive fear reversal learning task in which mild electric shocks were used as unconditioned stimulus and two angry faces from the Karolinska Directed Emotional Faces database were used as conditioned stimuli. The task consisted of four blocks and rule reversals occurred three times during the task.

The primary outcome was checked for normality with the Shapiro-Wilk test, and outliers were screened with 1.5*interquartile range (IQR). General linear modelling was used to analyze the data.

The study GitHub repository provides R-scripts for all data analysis steps and models, including the modified Rescorla – Wagner model.

Data from 1032 subjects were analyzed, of which 701 were between 18 and 35 years old and had no neurological, psychiatric or serious medical illness.

In a multiple linear regression model, adjusting for concomitant drug use, there was no significant association between schizotypy and psychedelic use. However, stimulant use (cocaine, amphetamines, ephedrine) strongly predicted higher scores of schizotypy, whereas alcohol use was associated with lower scores.

Only diagnosis had a significant association with schizotypy, and the diagnosis-by-group (users vs non-users) interaction effect was non-significant.

We conducted multiple regression analyses on four major facets of schizotypy and found no significant associations between psychedelic use and subclinical manifestations of the investigated psychopathological features in otherwise healthy subjects.

Although multiple regression models did not show a significant association between psychedelic use and schizotypy, direct group comparisons revealed that psychedelic users scored significantly higher on schizotypy compared to non-users.

In a study of 39 subjects, 22 psychedelic drug users and 17 sex/age-matched non-users were included. Multiple regression analysis showed that psychedelic exposure significantly predicted lower scores of evidence integration impairment, while stimulant exposure significantly predicted higher scores.

Figure 2 shows the relationship between drug use and schizotypy, and figure 3 shows the relationship between drug use and evidence integration impairment.

One subject was excluded from the analyses after a request to discontinue the task, and one more subject did not exhibit skin conductance response. Overall, pupillometry-derived estimates of expected value dynamics fitted the data better than those derived with SCR.

Overall exposure to psychedelics was associated with higher sensitivity of fear responses to instructed knowledge, as measured by pupillometry and skin conductance response.

Discussion

Psychedelic users scored higher on schizotypy compared to controls, but the effect-size was notably low and when excluding all participants with history of psychiatric diagnoses, this difference was no longer significant. However, we cannot completely rule out a possibility of potentially detrimental effects of psychedelic use on other psychiatric and wellbeing dimensions.

Exposure to psychedelics was associated with better evidence integration in the BADE task, indicating a greater readiness to re-adjust initial plausibility ratings.

We found that stimulant exposure was associated with worse evidence integration in subjects with and without history of psychedelic drug use.

Psychedelic users showed higher sensitivity to instructed knowledge in the fear learning task, and this sensitivity was positively associated with overall level of exposure to psychedelics. This suggests that psychedelics may augment top-down fear learning in a lasting way.

We have for the first time demonstrated that higher-order evidence integration and fear learning flexibility are associated with history of psychedelic use.

Although efforts were made to address causal relationships, the results might be limited by the retrospective nature of the ratings and recall biases. We used a composite score to assess schizotypy, which was primarily done due to inconsistent literature on the association between specific domains of schizotypy and psychedelic drug use. However, follow-up analyses showed no relationships with psychedelic use and strongest associations observed between stimulant use and unusual experiences.

In conclusion, our analyses did not support the hypothesis that psychedelics pose serious risks for developing psychotic symptoms in healthy young adults. However, future experimental studies might provide further clarification of causal relationships.

Data availability

Data used in the main analyses are available as supplementary materials. Data can be requested from the authors and transferred for specific analysis projects with ethical approval.

Author contributions

A.L., P.P., K.A., J.R., S.M., A.L. conceived the study, P.P., A.L., K.A. designed the study, A.L., K.A., J.R., S.M. collected the data, A.L., K.A. analysed the data, and P.P. obtained funding.

Additional information

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