List of investigational ME/CFS drugs
This is a list of investigational myalgic encephalomyelitis/chronic fatigue syndrome drugs, or drugs that are currently under development for clinical use for the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) but are not yet approved.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action [Reference]".
This list was last comprehensively updated in September 2025. It is likely to become outdated with time.
Under development
Phase 2/3
- Duloxetine (Ariclaim; Cymbalta; LY-227942; LY-248686; Xeristar; Yentreve) – serotonin–norepinephrine reuptake inhibitor (SNRI) [1]
Phase 2
- Alpha-1 antitrypsin modified process (Alpha-1 MP; Lynspad; Prolastin; Prolastina; Pulmolast; TAL-6004) – immunomodulator and serine endopeptidase inhibitor [2]
- Bocidelpar (ASP-0367; MA-0211; MTB-1) – peroxisome proliferator-activated receptor δ (PPARδ) modulator [3]
- OSU-6162 (PNU-9639; PNU-96391; PNU-96391A) – serotonin 5-HT2A receptor partial agonist (non-hallucinogenic), dopamine D2 receptor partial agonist, and sigma σ1 receptor ligand (so-called "monoaminergic stabilizer")[1][2][3][4][5][6][7]
Phase 1/2
- CT-38 (CT38) – CRF receptor type 2 modulator [4]
Preclinical
- Flmodafinil (CRL-40,940; NLS-14; NLS-4; JBG01-41; bisfluoromodafinil; lauflumide) – selective atypical dopamine reuptake inhibitor [5]
Not under development
No development reported
- Celecoxib/famciclovir (IMC-1) – combination of celecoxib (COX-2 inhibitor/NSAID) and famciclovir (antiviral) [6]
- Methylphenidate (KPAX-002) – norepinephrine–dopamine reuptake inhibitor (NDRI) [7]
- Midodrine (Amatine; Gudon; Gutron; Metligine; Midon; ProAmatine; ST-1085; TS-701) – α1-adrenergic receptor agonist [8]
- Rovunaptabin (BC-007) – oligonucleotide aptamer (binds to and neutralizes autoantibodies against GPCRs) [9]
- Valganciclovir (Cymeval; R127; RG-127; RO-1079070/194; RS-079070194; RS-79070; TA-9070; Valcyte; Valgancyclovir; Valixa) – antiviral [10]
Discontinued
- Droxidopa (L-DOPS; Threo-DOPS; Northera) – norepinephrine prodrug and non-selective adrenergic receptor agonist [11]
- Galantamine (GP-37267; Nivalin; R-113675; Razadyne; Reminyl) – acetylcholinesterase inhibitor [12]
- Research programme: androgen-based therapeutics - CPEX – androgen receptor agonists [13]
- SPV-30 – undefined mechanism of action [14]
Clinically used drugs
Approved drugs
- Rintatolimod (AMP-516; AMP-518; Ampligen; Atvogen; Rintamod; PolyI:PolyC12U) – mismatched double-stranded polymer of RNA (dsRNA) and toll-like receptor 3 (TLR3) agonist – only approved and available in Argentina [15][8][9][10]
Off-label drugs
- Analgesics (e.g., acetaminophen, NSAIDs)[11][12]
- Antidepressants (e.g., SSRIs, SNRIs, TCAs, MAOIs, mirtazapine, bupropion, trazodone)[13][14][12]
- Antivirals (e.g., inosine pranobex)[12]
- Atypical antipsychotics (e.g., aripiprazole)[14][15]
- Corticosteroids (e.g., hydrocortisone, fludrocortisone)[16]
- Gabapentinoids (α2δ voltage-dependent calcium channel ligands) (e.g., gabapentin, pregabalin)[11][14]
- Immunotherapy (e.g., rituximab, interferon, immunoglobulin)[16][12]
- Naltrexone (low-dose)[14]
- Sleep aids (e.g., antihistamines, orexin receptor antagonists, Z-drugs, benzodiazepines, trazodone, melatonin)[11][14][12]
- Stimulants (e.g., amphetamine, lisdexamfetamine, methylphenidate)[16][13][12][17]
- Vitamins, minerals, and dietary supplements (e.g., NADH, coenzyme Q10, carnitine, omega fatty acids, magnesium, vitamin B12)[11][12]
- Wakefulness-promoting agents (e.g., modafinil)[14][12]
See also
- List of investigational drugs
- List of investigational fatigue drugs
- List of investigational long COVID drugs
- List of investigational fibromyalgia drugs
- Management of ME/CFS
References
- ^ "OSU 6162 - AdisInsight". adisinsight.springer.com.
- ^ Canal CE, Morgan D (2012). "Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model". Drug Test Anal. 4 (7–8): 556–576. doi:10.1002/dta.1333. PMC 3722587. PMID 22517680.
Regardless, a more parsimonious explanation is that certain 5-HT2 receptor-activating compounds, such as DOI and psilocin, cause specific conformations of 5-HT2 receptors that lead to LSD-like psychedelic effects.[94,232] Moreover, although the 5-HT2 agonists mCPP, lorcaserin, and quipazine, are often considered 'non-hallucinogenic', they actually do produce perceptual, cognitive, and emotional changes that may be considered 'hallucinogenic'.[15,233,234] These effects, however, are generally not considered LSD-like. Finally, it is noteworthy that novel, partial 5-HT2A/D2 receptor agonists also attenuate the DOI-elicited HTR.[235,236]
- ^ Mirchandani-Duque M, Choucri M, Hernández-Mondragón JC, Crespo-Ramírez M, Pérez-Olives C, Ferraro L, Franco R, Pérez de la Mora M, Fuxe K, Borroto-Escuela DO (April 2024). "Membrane Heteroreceptor Complexes as Second-Order Protein Modulators: A Novel Integrative Mechanism through Allosteric Receptor-Receptor Interactions". Membranes. 14 (5): 96. doi:10.3390/membranes14050096. PMC 11122807. PMID 38786931.
This concept is also supported by experiments on OSU-6162, a selective Sigma 1R ligand in low doses [176]. This Sigma1R ligand produced in the nucleus accumbens shell substantial increases in the density of the D2R–Sigma1R and A2AR–D2R heterocomplexes, supporting the existence of A2AR–D2R–Sigma1R trimeric complexes in which the Sigma1R agonist can strongly enhance the antagonistic allosteric A2AR–D2R interaction. This mechanism may mediate the enhanced antagonistic A2AR–D2R interaction, causing marked inhibition of cocaine reward, leading to cocaine addiction.
- ^ Carlsson ML, Burstein ES, Kloberg A, Hansson S, Schedwin A, Nilsson M, Rung JP, Carlsson A (November 2011). "I. In vivo evidence for partial agonist effects of (-)-OSU6162 and (+)-OSU6162 on 5-HT2A serotonin receptors". J Neural Transm (Vienna). 118 (11): 1511–1522. doi:10.1007/s00702-011-0704-8. PMID 21874578.
- ^ Burstein ES, Carlsson ML, Owens M, Ma JN, Schiffer HH, Carlsson A, Hacksell U (November 2011). "II. In vitro evidence that (-)-OSU6162 and (+)-OSU6162 produce their behavioral effects through 5-HT2A serotonin and D2 dopamine receptors". J Neural Transm (Vienna). 118 (11): 1523–1533. doi:10.1007/s00702-011-0701-y. PMID 21866391.
- ^ Sahlholm K, Århem P, Fuxe K, Marcellino D (January 2013). "The dopamine stabilizers ACR16 and (-)-OSU6162 display nanomolar affinities at the σ-1 receptor". Mol Psychiatry. 18 (1): 12–14. doi:10.1038/mp.2012.3. PMID 22349783.
- ^ Borroto-Escuela DO, Romero-Fernandez W, Wydra K, Zhou Z, Suder A, Filip M, Fuxe K (February 2020). "OSU-6162, a Sigma1R Ligand in Low Doses, Can Further Increase the Effects of Cocaine Self-Administration on Accumbal D2R Heteroreceptor Complexes". Neurotox Res. 37 (2): 433–444. doi:10.1007/s12640-019-00134-7. PMC 6989596. PMID 31782100.
- ^ Mitchell WM (June 2016). "Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)". Expert Rev Clin Pharmacol. 9 (6): 755–770. doi:10.1586/17512433.2016.1172960. PMC 4917909. PMID 27045557.
- ^ Seton KA, Espejo-Oltra JA, Giménez-Orenga K, Haagmans R, Ramadan DJ, Mehlsen J (January 2024). "Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives". J Clin Med. 13 (2): 325. doi:10.3390/jcm13020325. PMC 10816159. PMID 38256459.
- ^ Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J (March 2017). "Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome". Br J Pharmacol. 174 (5): 345–369. doi:10.1111/bph.13702. PMC 5301046. PMID 28052319.
- ^ a b c d Bested AC, Marshall LM (2015). "Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians". Rev Environ Health. 30 (4): 223–249. Bibcode:2015RvEH...30.0026B. doi:10.1515/reveh-2015-0026. PMID 26613325.
- ^ a b c d e f g h Van Houdenhove B, Pae CU, Luyten P (February 2010). "Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy?". Expert Opin Pharmacother. 11 (2): 215–23. doi:10.1517/14656560903487744. PMID 20088743. S2CID 34827174.
- ^ a b Pae CU, Marks DM, Patkar AA, Masand PS, Luyten P, Serretti A (July 2009). "Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants". Expert Opin Pharmacother. 10 (10): 1561–1570. doi:10.1517/14656560902988510. PMID 19514866.
- ^ a b c d e f Grach SL, Seltzer J, Chon TY, Ganesh R (October 2023). "Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Mayo Clin Proc. 98 (10): 1544–1551. doi:10.1016/j.mayocp.2023.07.032. PMID 37793728.
- ^ Crosby LD, Kalanidhi S, Bonilla A, Subramanian A, Ballon JS, Bonilla H (February 2021). "Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole". J Transl Med. 19 (1) 50. doi:10.1186/s12967-021-02721-9. PMC 7860172. PMID 33536023.
- ^ a b c Collatz A, Johnston SC, Staines DR, Marshall-Gradisnik SM (June 2016). "A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis". Clin Ther. 38 (6): 1263–1271.e9. doi:10.1016/j.clinthera.2016.04.038. PMID 27229907.
- ^ Valdizán Usón JR, Idiazábal Alecha MA (June 2008). "Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate". Expert Rev Neurother. 8 (6): 917–27. doi:10.1586/14737175.8.6.917. PMID 18505357. S2CID 37482754.