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.
Gia Han Le, Sabrina Wong, Sebastian Badulescu, Hezekiah C.t. Au, Joshua D. Di Vincenzo, Hartej Gill, Lee Phan, Taeho Greg Rhee, Roger Ho, Kayla M Teopiz, Angela T H Kwan, Joshua D. Rosenblat, Rodrigo B. Mansur, Roger S McIntyre
Journal of Affective Disorders June 15, 2024 DOI: 10.1016/j.jad.2024.03.165 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Persons with major depressive disorder, treatment-resistant depression, and healthy controls |
| Interventions | Psilocybin Lysergic acid diethylamide (LSD) Ketamine |
| Topics | Depression Esketamine Ketamine LSD Psilocybin |
| Keywords | Electroencephalography Glutamatergic dissociatives Magnetoencephalography Serotinergic psychedelics Spectral signatures Psychedelics hallucinogens Entheogens Psychoactive drugs Brain activity EEG Patterns Clinical depression Research methods |
| Citations | 25 |
| Key findings | Ketamine and serotonergic psychedelics are associated with increased theta power in depressed individuals and decreased alpha, beta, and delta power in both healthy controls and depressed individuals, with ketamine also increasing gamma power. |
Abstract
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. 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. 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. 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. 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.
Comparable studies
Other systematic reviews and meta-analyses on LSD for depression, most cited first.
Citations in the library
Cited by 16
- Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis. Journal of Affective Disorders April 1, 2025
- The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges. CNS Spectrums December 1, 2024
- Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder Psychedelic Medicine November 18, 2024
- Psilocybin alters brain activity related to sensory and cognitive processing in a time-dependent manner medRxiv September 11, 2024
- A systematic review of ketamine and esketamine-induced long-term potentiation and synaptic scaling: Do the molecular and synaptic plasticity effects inform dosing intervals? Journal of Affective Disorders April 15, 2026
and 11 more in the library
Cites 15
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Broadband Cortical Desynchronization Underlies the Human Psychedelic State Journal of Neuroscience September 18, 2013
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
and 10 more in the library