Spectral signatures of psilocybin, lysergic acid diethylamide (LSD) and ketamine in healthy volunteers and persons with major depressive disorder and treatment-resistant depression: A systematic review
Abstract
Background Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents.Methods We conducted a systematic review investigating the spectral signatures of psilocybin, LSD, and ketamine in persons with major depressive disorder (MDD), treatment-resistant depression (TRD), and healthy controls.Results Ketamine and SPs are associated with increased theta power in persons with depression. Ketamine and SPs are also associated with decreased spectral power in the alpha, beta and delta bands in healthy controls and persons with depression. When administered with SPs, theta power was increased in persons with MDD when administered with SPs. Ketamine is associated with increased gamma band power in both healthy controls and persons with MDD.Limitations The studies included in our review were heterogeneous in their patient population, exposure, dosing of treatment and devices used to evaluate EEG and MEG signatures. Our results were extracted entirely from persons who were either healthy volunteers or persons with MDD or TRD.Conclusions Extant literature evaluating EEG and MEG spectral signatures indicate that ketamine and SPs have reproducible effects in keeping with disease models of network connectivity. Future research vistas should evaluate whether observed spectral signatures can guide further discovery of therapeutics within the psychedelic and dissociative classes of agents, and its prediction capability in persons treated for depression.
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- Authors
- Le, G. H., Wong, S., Badulescu, S., Au, H., Di Vincenzo, J. D., Gill, H., Phan, L., Rhee, T. G., Ho, R., Teopiz, K. M., Kwan, A. T. H., Rosenblat, J. D., Mansur, R. B., & McIntyre, R. S.
- Affiliations
- University Health Network (CA)
- Brain and Cognition Discovery Foundation (CA)
- Yale University (US)
- National University of Singapore (SG)
- University of Ottawa (CA)
- Corresponding author
- McIntyre, Roger S.
- ORCID
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 355
- Pages
- 342-354
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W4393364883
- Cited by
- 30
- References
- 34
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 9
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute on Aging (R21AG078972, R21AG070666)
- National Institute of Mental Health (R01MH131528)
- National Institute on Drug Abuse (R21DA057540)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- psilocybin, lysergic acid diethylamide, ketamine, serotonergic psychedelics, major depressive disorder, treatment-resistant depression, theta power, gamma power, brain network connectivity, treatment response biomarkers
- MeSH terms
- Depression, Depressive Disorder, Major, Major Depressive Disorder, Electroencephalography, Hallucinogens, Humans, Ketamine, Lysergic Acid Diethylamide, Psilocybin, Depressive Disorder, Treatment-Resistant, Healthy Volunteers
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