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.

Lee Phan, Sebastian Badulescu, Hartej Gill, Sabrina Wong, Angela T H Kwan, Kayla M Teopiz, Rodrigo B Mansur, Roger Ho, Taeho Greg Rhee, Joshua D Di Vincenzo, Roger S McIntyre, Joshua D Rosenblat, Gia Han Le, Hezekiah Au

Journal: Journal of affective disorders 2024;355():342-354

PMID: 38570038

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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.

Address: Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Brain and Cognition Discovery Foundation, Toronto, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Brain and Cognition Discovery Foundation, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Brain and Cognition Discovery Foundation, Toronto, Canada. Electronic address: [email protected].; Brain and Cognition Discovery Foundation, Toronto, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Brain and Cognition Discovery Foundation, Toronto, Canada. Electronic address: [email protected].; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Department of Public Health Sciences, Farmington, CT, USA. Electronic address: [email protected].; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore. Electronic address: [email protected].; Brain and Cognition Discovery Foundation, Toronto, Canada. Electronic address: [email protected].; Brain and Cognition Discovery Foundation, Toronto, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada. Electronic address: [email protected].; Mood Disorder and Psychopharmacology Unit, University Health Network, Toronto, Canada; Brain and Cognition Discovery Foundation, Toronto, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada. Electronic address: [email protected].

DOI: 10.1016/j.jad.2024.03.165

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MeSH Terms: Humans, Psilocybin, Lysergic Acid Diethylamide, Ketamine, Depressive Disorder, Major, Hallucinogens, Depressive Disorder, Treatment-Resistant, Healthy Volunteers, Electroencephalography