Microdosing psychedelics and its effect on creativity: Lessons learned from three double-blind placebo controlled longitudinal trials

This preprint of three double-blind placebo-controlled longitudinal experiments (n=175) investigated the effects of microdosing psilocybin (0.74 – 1.71mg) on creativity and found that it increased the originality of their ideas while generating novel applications for ordinary things (divergent thinking). However, it did not increase the number of novel ideas, or their ability to detect features that are common across multiple things (convergent thinking).

Abstract

Introduction: Microdosing refers to the repetitive administration of tiny doses of psychedelics (LSD, Psilocybin) over an extended period of time. This practice has been linked to alleged cognitive benefits, such as improved mood and creativity, potentiated by targeting serotonergic 5-HT2A receptors and facilitating cognitive flexibility. Nonetheless, in the absence of robust, quantitative and double-blind research on the effect of microdosing, such claims remain anecdotal.

Methods: Here, our main aim was to quantitatively explore the effect of microdosing psychedelic truffles on two creativity tasks assumed to rely on separable processes: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. We present results from 3 double-blind placebo-controlled longitudinal trials (of which one was pre-registered) conducted in a semi-naturalistic setting. Furthermore, we controlled for expectation and learning biases, and the data were mega-analyzed across trials with a pooled sample of 175 participants in order to maximize statistical power.

Results: In the final analyses we found that active microdosing increased the ratio of original responses (originality/fluency), indicating higher quality of divergent answers in the active microdosing condition. The unadjusted originality score was significantly more pronounced in the active microdosing condition, but only when relative dosage (dose/weight of participants) was considered. These effects were present after controlling for expectation and demographic biases. No effects of active microdosing were found for convergent thinking or any other divergent-thinking score.

Discussion: The results suggest that the effects of truffle mirodosing are limited to divergent quality and are more subtle than initially anticipated. Our findings furthermore highlighted the importance of controlling for expectation biases, placebo effects, and prior psychedelic experience in microdosing practice and research.

Authors: Luisa Prochazkova, Michiel van Elk, Josephine Marschall, Ben David Rifkin, George Fejer, Neil Schoen, Donatella Fiacchino, Martin Kuchar & Bernhard Hommel

Notes

Microdosing remains a controversial topic within psychedelic science. The practice has been shown to be beneficial to many and is practiced by a large number of people. It has positive effects on mood, creativity, productivity, amongst other positive changes (e.g. Kuypers, 2021). But, much of that can be attributed to placebo or expectancy effects. Researchers have been struggling to find a common ground between the lived experience of thousands of microdosers and double-blind placebo-controlled studies.

This meta-analysis grouped the data of three of those studies and analyzed the creativity scores of 171 participants. Two commonly used creativity tasks (Picture Concept Task, Alternative Uses Task) were used to measure the convergent (honing in on a solution) and divergent (finding multiple possibilities/solutions/uses) creativity.

This is what we know about creativity and microdosing in the lab

• The microdosing group scores higher on the ratio of original responses, which indicates an improvement in the quality of divergent answers
• But no effect was found on the other sub-scales of divergent creativity, nor on the convergent creativity scale
• The study did control for expectation effects, making the findings more robust

The current study finds that the effects of microdosing are still very subtle. One explanation could be that the participants were already using psychedelics for a longer time, which may have reduced the effects found in the current study. A way around this is to research those who haven’t used psychedelics before. Another reason could be the mismatch between the measure (the two tasks) and ‘real life’ creativity. Whereas the tasks are well-defined, creativity in the broadest sense may still be helped by someone engaging in microdosing (or going on a full trip to work on a problem).

The jury is still out, but this is one more point for team placebo.

Summary

A study was conducted with 30 military veterans with combat-related PTSD to assess the effects of ketamine on depression, PTSD, and substance use.

Symptoms of depression and PTSD decreased significantly during the study period, while self-reported levels of substance use trended down.

INTRODUCTION

Combat veterans are at high risk for the development of posttraumatic stress disorder (PTSD), as well as comorbid mental health and substance use disorders. Few veterans receive mental health treatment.

Study participants

The study population consisted of 30 US military veterans who had been diagnosed with combat-related PTSD by clinicians at the Department of Veterans Affairs. The participants passed medical screening, were not receiving lamotrigine or any monoamine oxidase inhibitors, and did not have psychosis.

Participants underwent a standard induction series of six 1-hour ketamine infusions. The dose was adjusted up or down until the participant experienced the psychotropic therapeutic response (PTR), which was an individualized dose specific to each patient.

Infusions of ketamine were performed in a private room over a 2-to 3-week period. Patients were monitored using continuous pulse oximetry and 3-lead cardiac monitoring, and blood pressure was recorded prior to and at regular intervals during and after each infusion.

Study design and outcome measures

This was an observational case series of US veterans who received ketamine infusion therapy for the treatment of PTSD. They completed a series of self-report questionnaires to monitor change in PTSD symptoms, and to assess alcohol, drug, and marijuana use.

RESULTS

Although the ketamine doses administered in this study were generally higher than those in previously reported research, no significant adverse events or significant vital sign abnormalities were experienced by any participants.

On the PCL-5, 3 participants endorsed increased symptoms of depression and PTSD, and on the DAST-10 and AUDIT, 6 and 7 participants had missing data, respectively. However, the level of substance abuse trended down during the study period.

DISCUSSION

This observational study suggests that ketamine infusion therapy may be an effective treatment for veterans with combat-related PTSD. Further research is needed to understand ketamine’s safety and efficacy in this population.

Ketamine has been shown to be an effective treatment for PTSD in combat veterans. Ketamine works at the N-methyl-d-aspartate receptor and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, and can help patients to reset their thought patterns. Some authors have suggested that ketamine therapy may increase symptoms of PTSD, but in our study, 3 of 30 participants endorsed increased symptoms, and 2 of the 3 had a decline in their depressive symptoms. Additionally, none of the participants reported subjectively that the experience worsened their symptoms.

Limitations

This study was an observational study and did not have a placebo arm. The data demonstrate the effect of ketamine after 5 infusions, but we suspect that the effect size would have been greater after 6 infusions.

There was an incomplete data set with regards to the effect of ketamine on veterans’ use of alcohol and illicit drugs, but there was a trend towards a decrease in alcohol use.

CONCLUSIONS

This study provides valuable evidence of the role that ketamine can play in the treatment of combat-related PTSD. The success we had with significantly higher doses than those used in other studies suggests that the psychedelic effect of ketamine may be a critical element of how it works therapeutically.