No evidence that LSD microdosing affects recall or the balance between distracter resistance and updating

This randomized double-blind, placebo-controlled preprint study (n=48) compared the effects of three different LSD microdoses (5 μg, 10μg and 20μg) with placebo to determine its effects on modulating working memory recall. Following a delay-match-to-sample task, no evidence was found that LSD microdoses affect memory recall.

Abstract

“The effect of low doses (<=20 μg) of LSD on working memory, in the absence of altered states of consciousness, remain largely unexplored. Given its possible effects on serotonin 5-HT2A receptors and dopaminergic signalling, it could be hypothesised that LSD microdoses modulate working memory recall. Moreover, in line with computational models, LSD microdoses could exert antagonistic effects on distracter resistance and updating. Here, we tested this hypothesis in a randomised double-blind, placebo-controlled study comparing three different LSD microdoses (5 μg, 10μg and 20μg) with placebo. After capsule administration, participants performed a modified delay-match-to-sample (DMTS) dopamine-sensitive task. The standard DMTS task was modified to include novel items in the delay period between encoding and probe. These novel items either had to be ignored or updated into working memory. There was no evidence that LSD microdoses affected the accuracy or efficiency of working memory recall and there was no evidence for differential effects on ignoring or updating. Due to the small sample of participants, these results are preliminary and larger studies are required to establish whether LSD microdoses affect short-term recall.”

Authors: Sean J. Fallon

Summary

Low doses of LSD (20 g) were tested on working memory recall in a modified delay-match-to-sample (DMTS) dopamine-sensitive task. There was no evidence that LSD microdoses affected recall or that LSD microdoses had a differential effect on ignoring or updating.

Despite the resurgence of interest in LSD, the cognitive effects of LSD remain largely unarticulated. Here, we investigate the effect of very low doses of LSD on working memory. In addition to retaining information, working memory systems need to efficiently maintain information in the presence of distracting input whilst enabling representations to be flexibly updated. The levels of dopaminergic signalling might determine the balance between these two processes.

Computational and empirical evidence suggests that too much or too little dopaminergic signalling can improve working memory recall, where cognitive flexibility is required. However, serotonin signalling also plays a role in working memory, and microdoses of LSD could affect both ignoring and updating. In a double-blind, placebo-controlled study, older adults were given three levels of LSD microdoses and compared with placebo on a modified delay-match-to-sample task. The results showed that LSD microdoses had no effect on performance on the n-back task.

Participants were 48 native English-speaking older adults (21 female, 27 male) between 55 and 75 years of age. They were not using LSD in the last five years, were post-menopausal, and had to agree to use double barrier method of contraception and not to donate sperm for 3 months after last dose.

A study was conducted in which healthy older adults received either placebo or one of three LSD doses. The ignore / update task was a modified delay match-to-sample task where novel stimuli were presented in the delay period between encoding items and probe. Participants were never explicitly instructed to ignore or update stimuli, but were told that only items presented with the letter ‘T’ had to be remembered. Participants were presented with a probe item and had to say whether the probe item matched or did not match the relevant target items. They completed 72 trials in total.

In Matlab, accuracy and response latencies were examined across conditions and drug conditions using a generalized linear mixed model with the binomial distribution with logit link.

Participants were less accurate for ignore trials compared to update trials and for ignore trials compared to maintain trials. There was no evidence for a difference between update and maintain trials.

Figure 2 shows that accuracy rates were affected by condition and drug dose, but no effect of drug dose was observed.

Microdoses of LSD are frequently taken by people who wish to improve their cognitive or emotional wellbeing. However, this study found no evidence that LSD affects working memory recall.

LSD microdoses have been found to affect emotion-related processing more than n-back working memory. This could be because of the small sample size or because the effect of LSD microdoses on working memory is smaller than the effect on time perception.

The de Wit study investigated the effects of LSD microdoses on working memory, but the n-back task was insufficiently sensitive to detect an effect. However, it has been well established that the effects of pharmacological compounds on working memory can be baseline dependent.

Acknowledgements

SJF received no financial remuneration for this study and is funded by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol.