Microdosing psychedelics has no impact on cognitive function in naturalistic settings
In a within-subjects naturalistic study of 17 people repeatedly tested with the CNSVS battery, psychedelic microdosing produced no measurable improvement or impairment across processing speed, attention, executive function, working memory or memory. The authors suggest perceived benefits of microdosing are psychological rather than neurocognitive and note that remote cognitive batteries are feasible for longitudinal cross‑cultural research.
Authors
- Dinkelacker, J.
- Pop, I.
Published
Abstract
Background and aim: Subjective and anecdotal accounts link ingestion of psychedelic microdoses, quantities small enough to retain perceptual clarity, to enhanced cognitive function and performance. In this study we review current evidence, test the link between domains of cognitive function and microdosing psychedelics and evaluate a remote testing approach for cognitive function. Methods: In an observational within-subjects design, we repeatedly assessed 17 participants during their microdosing regimen using the CNSVS neurocognitive battery in a naturalistic setting. Results: We found that neither the day of microdosing, nor the day after microdosing are significantly linked to enhanced or diminished performance on processing speed, sustained attention, inhibitory control, set shifting, working memory, visual memory and verbal memory. Conclusion: Microdosing psychedelics may act on psychological rather than neurocognitive pathways to induce a subjective feeling of performance enhancement. The use of remote cognitive batteries might benefit longitudinal cross-cultural studies by reducing participant burden
Research Summary of 'Microdosing psychedelics has no impact on cognitive function in naturalistic settings'
Introduction
Earlier research and widespread anecdotal reports describe microdosing—regular ingestion of sub-perceptual amounts of classical psychedelics such as LSD or psilocybin—as an approach people use to boost cognition, mood and productivity. Experimental studies of medium and large doses have documented dose-dependent effects on attention, memory and executive functions, and some neurobiological mechanisms have been proposed (for example, effects on BDNF and functional connectivity). However, evidence for cognitive benefits from microdoses is sparse and mixed: some laboratory microdosing studies report small improvements in particular individuals, others find no change or slight impairments, and most prior work took place in tightly controlled experimental settings rather than in users' daily environments. This study, led by Dinkelacker and colleagues, set out to assess whether microdosing produces measurable changes in multiple neurocognitive domains when practised in naturalistic settings. The investigators aimed to provide a broad, within-subjects, longitudinal examination of processing speed, sustained attention, inhibitory control, cognitive flexibility, working memory, verbal memory and visual memory using remote testing and experience sampling over a 28-day period. By allowing participants to continue their habitual microdosing routines, the researchers sought to increase ecological validity relative to laboratory-based studies and to test whether acute (same-day or next-day) cognitive effects are detectable in everyday conditions.
Methods
The study used an observational within-subjects longitudinal design over 28 days. Recruitment occurred in two waves (February 20–March 5 and May 12–21, 2020) via a university and social media; 20 participants started and 18 completed the protocol. The final sample comprised 4 male and 14 female participants aged 19–57 (median 22) from Europe, North America and Africa. All participants had prior microdosing experience and provided written consent; ethical approval was obtained from the authors' university review board. Microdosing behaviour and psychological variables were recorded daily using the EthicaData smartphone app. Participants reported whether they had taken a microdose that day (MD 1), the day before (MD 2) or neither day (MD 0), and specified substance and quantity (LSD reported in micrograms; psilocybin mushrooms/truffles in grams). Sleep quality was rated each morning on a 0–3 scale. An index of positive and negative emotion was computed from repeated emotion items. Participants completed an instructional practice session before data collection to reduce practice effects. Cognitive function was assessed remotely using the CNS Vital Signs (CNSVS) battery administered on participants' personal computers. Tests included Symbol-Digit Coding (processing speed), a 4-Part Continuous Performance Test (sustained attention and 2n-back working memory), Stroop (inhibitory control), Shifting Attention Test (cognitive flexibility), and CNSVS verbal and visual memory tests (with delayed recall). Participants were instructed to distribute assessments across MD 1, MD 2 and MD 0 days and to keep testing conditions consistent; up to four assessments per week were allowed (maximum 16 total). Typical battery duration was ~25 minutes. Analyses were performed in RStudio using the lme4 package. Multilevel linear models with random intercepts for participants were used to examine whether Microdose Day (three levels: MD 1, MD 2, MD 0) predicted each cognitive outcome. Model building compared null, linear and unconditional intercept models using ANOVA; microdose day was only added if the unconditional model fit best. Sleep quality and positive/negative emotion were entered stepwise to control for motivational or sleep effects. Intraclass correlation coefficients (ICCs) were reported to indicate the proportion of variance between individuals.
Results
Adherence and dosing: Eighteen completers produced a total of 100 microdosing occasions (each participant microdosed between 1 and 9 times, median 5). Across 40 mushroom occasions the dose range was 0.05–0.3 g (mean 0.163 g, median 0.15 g). For 39 LSD occasions the range was 5–30 µg (mean 13.6 µg, median 15 µg). Two truffle occasions involved 1 g each. The initial 20 participants completed 148 cognitive tests with at least one valid domain score; after matching test days to microdosing reports and excluding invalid scores, 100–104 usable test occasions remained. Per participant the number of usable batteries ranged from 2 to 15 (median 6, mean ~7.4). Timing of remote testing varied widely across and within participants. Processing speed: Analysis used 104 observations nested in 17 individuals. The unconditional multilevel model fit better than simpler models and the ICC indicated about 34% of variance was between individuals. Adding microdose day as a fixed effect did not improve model fit, indicating no detectable effect of microdosing day on processing speed. Sustained attention: The dataset comprised 100 observations nested in 17 individuals. The unconditional model again outperformed alternatives and ICC was about 30%. Microdose day did not improve fit, and this null finding remained when controlling for sleep quality (n=87) and for positive and negative emotion (n=63). Inhibitory control: With 103 observations nested in 17 individuals, the unconditional model was superior and ICC was approximately 50%. Inclusion of microdose day did not improve model fit; controlling for sleep and emotions (n up to 90 and 66 respectively) did not change this result. Cognitive flexibility: Analyses of accuracy and reaction time used 103 observations nested in 17 individuals. Unconditional models fitted better and ICCs were 52% (accuracy) and 54% (reaction time). Microdose day did not account for additional variance in either accuracy or speed, and this null result held when sleep and emotion covariates were added. Working memory: The 2n-back composite used 100 observations nested in 17 individuals. The unconditional model explained the data (ICC ~29%) and adding microdose day did not improve fit. Controlling for sleep quality and emotions (n=87 and n=63) did not alter the null finding. Visual memory: Analyses included 104 observations nested in 17 individuals. ICCs were about 32% for accuracy and 30% for reaction time. Microdose day did not improve model fit for either outcome, and the result persisted when controlling for sleep and affect (n up to 91 and 67). Verbal memory: Using 104 observations nested in 17 individuals, ICCs were roughly 50% for accuracy and 21% for reaction time. Adding microdose day did not improve explanatory power; controlling for sleep and emotions (n up to 91 and 67) again did not change the null result. Overall, across all seven neurocognitive domains tested, the researchers found no evidence that microdosing days (same day or day-after) produced measurable improvements or impairments in cognitive performance in this naturalistic sample.
Discussion
Dinkelacker and colleagues interpret their findings as evidence that, in a naturalistic setting among people with prior microdosing experience, microdosing does not produce acute improvements or impairments in a broad range of cognitive domains. This outcome contrasts with some prior work that reported dose-dependent improvements in a subset of individuals or small effects on processing speed and sustained attention, but it aligns with other studies that observed no change at low doses. The authors note that medium and higher doses show dose-dependent cognitive impairment in laboratory studies, and their results suggest that typical microdoses in daily practice do not reach thresholds that alter tested cognitive functions. The researchers discuss several possible explanations for the discrepancy between widespread subjective reports of cognitive benefit and the null objective results. One possibility is that beneficial effects accrue cumulatively after prolonged use, which would require longer follow-up than the 28-day window used here; they cite evidence from long-term ayahuasca users showing better executive function over years. Another explanation is that standard neurocognitive tests may not capture the kinds of psychological changes users subjectively experience; subjective improvements might instead be driven by expectation, set and setting, or other non-neurocognitive mechanisms. The authors highlight prior work showing expectancy effects predict well-being changes with microdosing. Strengths emphasised by the authors include the ecological validity afforded by remote, self-organised testing, the within-subjects longitudinal design and the multilevel analytic approach which captures intra- and inter-individual variability. Limitations they acknowledge are important: lack of experimental control over testing conditions (for example, hardware and distance to monitor), wide variability in testing times, modest sample size and variable adherence, absence of placebo control and no direct measurement or control of expectation effects. The investigators also note that remote testing requires incentives and larger samples to achieve adequate power for longitudinal analyses. In closing, the authors suggest that naturalistic remote testing combined with experience sampling offers a promising route to study pharmacological and psychological effects in ecologically valid contexts, but they caution that larger, controlled studies that address expectation and dosing variability are needed to resolve remaining uncertainties about microdosing's effects.
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METHODS
Data was obtained in an observational within-subjects longitudinal design over 28 days.
RESULTS
Our 18 final participants each microdosed at least one, at most nine and a median of five times throughout the study period resulting in a total of 100 microdosing occasions. The minimum, mean, median, and maximum quantity across 40 occasions with mushrooms were 0.05g, 0.163g, 0.15g, and 0.3g respectively. In 39 occasions of LSD microdosing the minimum was 5µg, mean 13.6µg, median 15µg, and maximum 30µg. In two occasions in which participants microdosed with Truffles, they administered 1g each. The initial 20 participants conducted a total of 148 cognitive tests that had at least one valid score in any cognitive domain. The minimum per participant was one test, the median seven tests, mean 7.4 and the maximum 16 tests. The average length of a test battery was 25.12 minutes. Only four tests were shorter than 10 minutes and six longer than 32 minutes, which might have occured due to technical difficulties or short breaks participants took and have resulted in partially valid test scores. There was considerable variation in the time at which participants conducted their tests. After accounting for timezone differences, we calculated an average time and the standard deviation from this average time for each participant. The earliest average time of testing was 07:55 in the morning and the latest 21:43 in the night. The median average time of testing across participants was 16:18 in the afternoon. Standard deviations for each participant ranged from circa 10 minutes to about 10 hours with most individuals regularly conducting their tests within about 2 to 4 hours. For an overview of the timing of each remote testing session see Figurein the appendix. For the following analysis we only used test scores that were valid and conducted on days on which participants also reported their microdosing behavior. This resulted in a minimum amount of two, median of six and maximum of 15 cognitive test batteries per participant and a sum of 100 to 104 usable test occasions over the period of the study.
CONCLUSION
In the current observational study we investigated the effect of microdosing on cognitive function in a naturalistic setting. Microdosing has not affected any of the domains of cognitive function tested in this study. According to our results microdosing neither diminishes nor improves the cognitive functions processing speed, sustained attention, inhibitory control, cognitive flexibility, working memory, visual memory, and verbal memory. This is in contrast to some of the previous research that indicated that microdoses of LSD could improve processing speed and sustained attention in some people Hutten et al.,as well as the mixed findings regarding effects of medium and minidoses on inhibitory controland cognitive flexibility.The lack of change in cognitive flexibility during microdosing might suggest that the previously reported afterglow effect that persists for several days or weeks after administration of medium doses has an effect that is different from the acute effect of microdosing.The findings regarding explicit (visual and verbal) memory as well as working memory were in line with previous research. It is curious that both subjective reports and molecular mechanisms support enhanced cognitive function, yet these seem not to translate into measurable performance increases in the daily lives of our participants. One possibility is that the cognitive effects are cumulative over a sustained period of time and therefore require longer tracking of participants. Support for this cumulative effect comes from evidence in regular Ayahuasca users, who have been drinking the psychedelic brew at least twice a month for 15 years. When compared to controls, these regular users showed better inhibitory control measured by the stroop test and cognitive flexibility measured by the Wisconsin-Card-Sorting-Test at two measurement occasions one year apart.Another possibility is that our current distinction between neurocognitive domains and the established measures thereof are not sensitive to the changes induced by psychedelics in naturalistic settings. While this conclusion can not be ultimately ruled out, to draw a broad picture of microdosing effects, we employed composite tests such as processing speed which require multiple different cognitive functions on the one hand and tests for the lower cognitive functions of inhibitory control, cognitive flexibility, and specific types of memory on the other hand. All in all, this suggests that the effect of subjectively enhanced cognitive performance might arise from a psychological rather than a neurocognitive mechanism. The idea that non-biological factors contribute to the effects of psychedelics is not new. Hartogsohnhas discussed how set (mindset including thoughts, mood and emotions) and setting (surrounding physical, legal, and social environment), similar to the placebo response in other therapeutic interventions, shape expectations that can alter psychedelic experiences. A prospective study has already shown that positive expectancy scores at baseline predicted improvements in well-being through microdosing.It remains unclear what individual differences might contribute to the susceptibility to such expectation effects and whether those vary depending on the dose. This study fortifies the previous literature showing that acute cognitive impairment due to psychedelics might appear in a dose-dependent manner. Here we show that microdoses administered in a naturalistic setting do not reach a threshold that impairs or improves functioning. It is important to note that all of the participants in our study have already had experience with microdosing and therefore had not have to go through excessive testing of which doses might be too much for daily life. Using our remote testing approach we have successfully addressed challenges that arise in strict experimental studies that do not allow individual variation in susceptibility to psychedelic substances to be accounted for. In naturalistic settings, microdosing practitioners commonly go through a trial and error process of finding the dose in the first few dosing days. The use of remote testing along with an experience sampling method has shown to be a powerful tool to address such challenges of generizability of experimental studies. Since our participants were instructed to complete the cognitive tests at a time that was suitable and sustainably repeatable for them instead of limiting them to academic working hours, we have seen that some participants conducted those tests even late at night or early in the morning before starting their regular days. This added flexibility might allow early risers or night owls to participate in studies that are otherwise challenging to integrate in their daily routines. Additionally, remote testing allowed us to enrol participants from Europe, North America, and Africa simultaneously. As shown in Figure, there was considerable variability in the time our participants have conducted their cognitive tests. While most participants conducted tests in the afternoon, some people conducted them early in the morning and others late in the evening. Assuming people were motivated to perform well during these cognitive tests, there might be considerable benefit in remote testing to allow inter-individual differences in timing of cognitively demanding tasks to be captured in scientific studies. Further, the regularity of each participant in conducting their tests differed strongly across individuals. One reason for this might be that participants needed to use a laptop or computer for their tests, which might not always be around. Without further speculating about why there was so much variation, our data shows how restricting fixed appointments for experimental testing can be when conducting longitudinal research. Through the use of this self-organized remote testing approach we have strongly minimized the burden on participants, allowing them to live their lives as close as possible to usual conditions, while gathering valuable data in the process. The main strength of the current study is the strong ecological validity of our findings as well as the multilevel design that allows for tracking changes between as well as within participants over time. One large limitation is the lack of control of experimental conditions, as variables such as distance from monitor, and hardware differences between participants could not be controlled. Our longitudinal design with repeated measures may have accounted for some of the downside of this limitation. Additionally, we have not used any placebo controls and have not accounted for expectation effects, which has become common practice in recent studies of psychedelics. A further limitation is the necessity for a large sample size and incentives to increase compliance to attain a sufficient amount of completed tests. Finally, the use of remote cognitive tests in naturalistic settings in combination with experience sampling methods bears a promising opportunity to conduct large cross-cultural longitudinal studies that track intraindividual changes in response to pharmacological treatment, especially with large sample sizes.
Study Details
- Study Typeindividual
- Populationhumans
- Characteristicsobservational
- Journal
- Topic