Reduced EEG complexity after eight weeks of microdosed LSD in patients with depression
Poster No:
444
Submission Type:
Abstract Submission
Authors:
Dimitri Daldegan-Bueno1, Carina Donegan1, Rachael Sumner1, Malak Alshakhouri1, Suresh Muthukumaraswamy1, Anna Forsyth1
Institutions:
1The University of Auckland, Auckland, New Zealand
First Author:
Co-Author(s):
Introduction:
Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and side effects that often lead to discontinuation (GBD, 2022). In the context of the current limitations of antidepressant pharmacotherapy, microdosing psychedelics has emerged as a self-treatment approach for depression within lay communities (Polito & Liknaitzky, 2022); however, clinical trials evaluating these effects are still lacking. Advancements in electroencephalography (EEG) data quality and analysis have allowed new and promising investigations into the identification of biomarkers to predict treatment response and track outcomes in mental health-related clinical trials (de Aguiar Neto & Rosa, 2019). Leveraging this, we evaluated resting state EEG data from a 16-dose, open-label trial of microdosed lysergic acid diethylamide (LSD) in people with MDD.
Methods:
Nineteen participants (15 male) took 16 doses of LSD. The first dose (8 µg) was taken in the clinic, then 15 doses were taken at home, twice weekly, titrated from 6–20 µg based on self-perception of the effects (Donegan et al., 2023). At the end of the intervention, participants experienced a 60% reduction in their depression severity. Continuous, eyes-closed, resting-state EEG data were collected using 64-channel Brain Products active shielded electrodes before the intervention (Baseline), two hours after the first dose (Dosing), and 2-7 days after the last dose (Measure). Pre-processed data were filtered into six frequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), low beta (13-28 Hz), high beta (28-40 Hz), and low gamma (42-53 Hz). Spectral analysis was performed using Slepian multitapers with spectral smoothing of +/- 0.5 Hz. Power was averaged across the five minutes. To determine changes in EEG complexity, broadband data were bandpassed at 1-45 Hz and segmented into trials lasting five seconds, and the Lempel-Ziv 1976 compression (LZc) algorithm was applied. Two-tailed, permuted paired-t tests with FDR for multiple comparison (electrode) correction were used to compare whole-head baseline spectral power and LZc complexity to that collected at dosing and measure.
Results:
We found increased centro-frontal high beta and low gamma power at dosing. Lower frequency modulation at dosing trended in similar directions to previous literature in healthy controls (Hutten et al., 2024) (Fig. 1), but were not significant. Significant reductions from baseline in LZc complexity were found at measure in centro-temporo-parietal areas, with wider spread changes observed in the right hemisphere (Fig. 2).
·Figure 1. EEG spectral power of resting state with eyes closed on dosing and measure session compared with baseline.
·Figure 2. LZc of resting state with eyes closed on dosing and measure session compared with baseline.
Conclusions:
We identified reduced brain complexity at the end of an eight-week microdosing LSD regimen in people with MDD, measured using LZc. This data is in accordance with previous studies indicating increased LZc in people experiencing depression (Li et al., 2008) and reduced LZc after undergoing an effective pharmacological antidepressant treatment (Méndez et al., 2012). Thus, the EEG results also corroborate the reduced depression severity identified in our clinical trial. While limited significant power spectra modulations were seen during the acute drug effect, it is important to consider that the dose investigated was the initial, low 0.8 µg dose, as opposed to the titrated, therapeutic dose. The next steps include analysing other EEG measures shown to modulate depression and its treatment and replicating these analyses in the ongoing larger placebo-controlled cohort, where the dosing day measurement will be once they have reached their titrated, therapeutic dose (Daldegan-Bueno et al., 2024).
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Novel Imaging Acquisition Methods:
EEG 2
Keywords:
Electroencephaolography (EEG)
Psychiatric Disorders
Seretonin
Other - Psychedelic; Microdosing; LSD
1|2Indicates the priority used for review
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Provide references using APA citation style.
de Aguiar Neto, F. S., & Rosa, J. L. G. (2019). Depression biomarkers using non-invasive EEG: A review. Neurosci Biobehav Rev, 105, 83-93.
Donegan, C. J., Daldegan-Bueno, D., Sumner, R., Menkes, D., Evans, W., Hoeh, N., Sundram, F., Reynolds, L., Ponton, R., Cavadino, A., Smith, T., Roop, P., Allen, N., Abeysinghe, B., Svirskis, D., Forsyth, A., Bansal, M., & Muthukumaraswamy, S. (2023). An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1). Pilot Feasibility Stud, 9(1), 169.
GBD. (2022). Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry, 9(2), 137-150.
Hutten, N. R. P. W., Quaedflieg, C. W. E. M., Mason, N. L., Theunissen, E. L., Liechti, M. E., Duthaler, U., Kuypers, K. P. C., Bonnelle, V., Feilding, A., & Ramaekers, J. G. (2024). Inter-individual variability in neural response to low doses of LSD. Translational Psychiatry, 14(1), 288.
Li, Y., Tong, S., Liu, D., Gai, Y., Wang, X., Wang, J., Qiu, Y., & Zhu, Y. (2008). Abnormal EEG complexity in patients with schizophrenia and depression. Clinical Neurophysiology, 119(6), 1232-1241.
Méndez, M. A., Zuluaga, P., Hornero, R., Gómez, C., Escudero, J., Rodríguez-Palancas, A., Ortiz, T., & Fernández, A. (2012). Complexity analysis of spontaneous brain activity: effects of depression and antidepressant treatment. Journal of psychopharmacology (Oxford, England), 26(5), 636-643.
Polito, V., & Liknaitzky, P. (2022). The emerging science of microdosing: A systematic review of research on low dose psychedelics (1955–2021) and recommendations for the field. Neuroscience & Biobehavioral Reviews, 139, 104706.