Background Microdosing psychedelics is a phenomenon with claimed cognitive benefts that are relatively untested
clinically. Pre-clinically, psychedelics have demonstrated enhancing efects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This ...
Background Microdosing psychedelics is a phenomenon with claimed cognitive benefts that are relatively untested
clinically. Pre-clinically, psychedelics have demonstrated enhancing efects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study
used a visual long-term potentiation (LTP) EEG paradigm to test the efects of microdosed lysergic acid diethylamide
(LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six
weeks. Healthy adult males (n=80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg
of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used
as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual
cortex to elucidate underlying synaptic circuitry.
Results Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes
in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete
timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This
primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also diferent between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3
into layer 5 and inhibitory input into layer 4 were diferent between groups.
Conclusions Without modulation of the ERPs it is difcult to relate the fndings to other studies visually inducing LTP.
It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP
plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity
as diferences in plasticity mediated laminar connectivity were found between the LSD and placebo groups.