Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review

Low ZXB 1 , Yong SJ 2 , Alrasheed HA 3 , Al-Subaie MF 4 , Al Kaabi NA 5 , Alfaresi M 6 Show all authors , Albayat H 7 , Alotaibi J 8 , Al Bshabshe A 9 , Alwashmi ASS 10 , Sabour AA 11 , Alshiekheid MA 11 , Almansour ZH 12 , Alharthi H 13 , Al Ali HA 14 , Almoumen AA 14 , Alqasimi NA 14 , AlSaihati H 15 , Rodriguez-Morales AJ 16 , Rabaan AA 17

Affiliations 

  • 1 Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor, Malaysia
  • 2 School of Medical and Life Sciences, Sunway University, Selangor, Malaysia. Electronic address: shinjieyong@gmail.com
  • 3 Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
  • 4 Research Center, Dr. Sulaiman Alhabib Medical Group, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  • 5 College of Medicine and Health Science, Khalifa University, Abu Dhabi, United Arab Emirates; Sheikh Khalifa Medical City, Abu Dhabi Health Services Company, Abu Dhabi, United Arab Emirates
  • 6 Department of Microbiology, National Reference Laboratory, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; Department of Pathology, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
  • 7 Infectious Disease Department, King Saud Medical City, Riyadh, Saudi Arabia
  • 8 Infectious Diseases Unit, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • 9 Adult Critical Care Department of Medicine, Division of Adult Critical Care, College of Medicine, King Khalid University, Abha, Saudi Arabia
  • 10 Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
  • 11 Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
  • 12 Biological Science Department, College of Science, King Faisal University, Hofuf, Saudi Arabia
  • 13 Clinical Pharmacist, Pharmaceutical Care Department, King Faisal Medical Complex, Taif Health Cluster, Ministry of Health, Taif, Saudi Arabia
  • 14 Pediatrics Department, Maternity & Children Hospital, Dammam, Saudi Arabia
  • 15 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia
  • 16 Faculty of Health Sciences, Universidad Cientifica del Sur, Lima, Peru; Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
  • 17 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia; Department of Public Health and Nutrition, The University of Haripur, Haripur, Pakistan. Electronic address: arabaan@gmail.com
Prog Neuropsychopharmacol Biol Psychiatry, 2025 Feb 03.
PMID: 39909170 DOI: 10.1016/j.pnpbp.2025.111279

Abstract

RATIONALE: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.

OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.

RESULTS: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.

CONCLUSIONS: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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