Varied responses to LSD may muddy microdosing results

Some people who regularly take tiny doses of psychedelic drugs report improvements in memory, alertness and mood. For others, though, microdosing doesn't seem to have much of an effect. The results from research are mixed too, with some studies, but not all, finding small benefits.

In a new study in Translational Psychiatry, Nadia Hutten at Maastricht University and colleagues provide a possible explanation for these discrepancies: they found that not everyone's brain responds in the same way to microdoses of LSD.

The team studied 47 healthy volunteers, who received either 4 doses of 15mcg of LSD on four occasions over two weeks, or a placebo. Before, during, and one week after this two-week period, the participants were given a series of EEG-based assessments. These tests measured three different things: their level of brain arousal — or alertness — while at rest; brain processes that underpin their ability to form visual memories; and, finally, how well they were able to detect occasional mismatching tones in a stream of other tones. This last test was a measure of 'pre-attentive processing' — their ability to unconsciously gather information from their environment.  

When the team analysed the data overall, they found that LSD did have some effects. It boosted resting brain arousal both while the participants were microdosing, and one week on. It was also associated with improvements in the auditory test. But there was a negative impact, too: after the fourth dose, the microdosing group demonstrated slight impairments in the processes that underpin visual learning. This last finding wasn't a big surprise, the team notes, as earlier studies have found that moderate to high doses of LSD can impair memory temporarily.

When the team analysed the data further, though, they found that the brains of the participants who'd been microdosing didn't respond to the drug in exactly the same way. In fact, the stimulant effects of the LSD were strongest for those who'd had the lowest arousal levels at the start of the study. Also, the level of impairment in visual learning processes was bigger for those who'd demonstrated better learning and memory responses at the start of the study.

In other words, the team writes, the changes that they observed were biggest in those people whose initial neural state offered the most room for either improvement or impairment.

These findings may have implications for healthy people, but potentially even bigger ones for those with certain conditions. The team notes that in this study, the small doses of LSD had a similar boosting effect on some types of arousal-related brain activity as standard ADHD medication, such as Ritalin — and the participants whose brain arousal patterns were, at the start of the study, closest to those of people with ADHD got the biggest stimulant boost from the drug. It's possible, the researchers write, that microdosing LSD could work as well as standard drugs to reduce ADHD symptoms, but clearly further research will be needed to verify this.

The duration of this study was quite short, with the microdosing period lasting only two weeks; most people who microdose take the drug in the longer term. One further limitation is that the team didn't ask the participants whether they'd noticed any changes in how they felt, but instead focused on EEG data. Even so, the work does add weight to some previous findings suggesting that microdosing LSD can have some positive effects on brain functioning — while also providing a potential explanation for why such findings have been inconsistent.

Read the paper in full:

Nadia, Conny W. E. M. Quaedflieg, Mason, N. L., Theunissen, E. L., Liechti, M. E., Urs Duthaler, Kim, Bonnelle, V., Feilding, A., & Ramaekers, J. G. (2024). Inter-individual variability in neural response to low doses of LSD. Translational Psychiatry, 14(1). https://doi.org/10.1038/s41398-024-03013-8

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