CYB003

{{Short description|Serotonergic psychedelic}}

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| routes_of_administration = By mouth

| class = Serotonergic psychedelic

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| onset = 30 minutes (C_max) (rats)

| elimination_half-life = 45 minutes (rats)

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| synonyms = CYB-003; deuterated psilocybin analogue; deuterated psilocin analogue

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CYB003, or CYB-003, also known as deuterated psilocybin analogue, is a serotonergic psychedelic related to psilocybin which is under development for the treatment of major depressive disorder, alcoholism, and other psychiatric disorders.{{cite web |title=CYB 003 |website=AdisInsight |date=4 October 2024 |url=https://adisinsight.springer.com/drugs/800062409 |access-date=23 October 2024}}{{cite web |title=Delving into the Latest Updates on CYB-003 with Synapse |website=Synapse |date=12 October 2024 |url=https://synapse.patsnap.com/drug/dcb535376933495783bad0ae5504a571 |access-date=23 October 2024}}{{cite journal |vauthors=Cano GH, Dean J, Abreu SP, Rodríguez AH, Abbasi C, Hinson M, Lucke-Wold B |title=Key Characteristics and Development of Psychoceuticals: A Review |journal=Int J Mol Sci |volume=23 |issue=24 |date=December 2022 |page=15777 |pmid=36555419 |pmc=9779201 |doi=10.3390/ijms232415777 |doi-access=free |url=}}{{cite journal |vauthors=Rhee TG, Davoudian PA, Sanacora G, Wilkinson ST |title=Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders |journal=Drug Discov Today |volume=28 |issue=12 |pages=103818 |date=December 2023 |pmid=37925136 |doi=10.1016/j.drudis.2023.103818 |url=}}{{cite journal |vauthors=Palfreyman M, Krakowsky J, Morgan M, Canal C, Pathare P, Avery K, Reichelt A, Hartsel J, Nivorozhkin A, Inamder A, Varty G |title=ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P361. In Vitro and In Vivo Profile of CYB003: A Novel, Deuterated Psilocybin Analog for the Potential Treatment of Major Depressive Disorder |journal=Neuropsychopharmacology |volume=47 |issue=Suppl 1 |pages=220–370 (271) |date=December 2022 |pmid=36456694 |pmc=9714399 |doi=10.1038/s41386-022-01485-0 |url=https://cybin.com/wp-content/uploads/2023/09/ACNP_2022_CYB003_Poster-1.pdf}}{{cite journal |vauthors=Inamdar A, Morgan M, Krakowsky J, Reichelt A, Canal C, Mueller T, Avery K, Pathare P, Hartsel J, Nivorozhkin A, Varty G, Palfreyman M |title=ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P362. Pharmacokinetic Profile of CYB003: A Novel, Deuterated Psilocybin Analog for the Potential Treatment of Major Depressive Disorder |journal=Neuropsychopharmacology |volume=47 |issue=Suppl 1 |pages=220–370 (271–272) |date=December 2022 |pmid=36456694 |pmc=9714399 |doi=10.1038/s41386-022-01485-0 |url=https://cybin.com/wp-content/uploads/2023/09/ACNP-2022-CYB003-Poster-2.pdf}} It is taken by mouth.

It is a tryptamine derivative and is a deuterated analogue of psilocybin and psilocin. The pharmacodynamic profile of CYB003, including its interactions with serotonin receptors and its effects in animals, is similar to that of psilocin. As with psilocin, CYB003 is a potent agonist of the serotonin 5-HT_2A receptor and produces psychedelic-like effects in animals. However, it was developed to have improved pharmacokinetic properties compared to psilocybin, including reduced variability in circulating levels, a faster onset of action, and a shorter duration.

As of October 2024, CYB003 is in phase 3 clinical trials for major depressive disorder and is in the preclinical stage of development for alcoholism and other psychiatric disorders. Two phase 3 clinical trials for major depressive disorder are being initiated in November 2024 and February 2025. The drug is under development by Cybin. The chemical structure of CYB003 has not yet been disclosed.{{cite journal |vauthors=Di Martino RM, Maxwell BD, Pirali T |title=Deuterium in drug discovery: progress, opportunities and challenges |journal=Nat Rev Drug Discov |volume=22 |issue=7 |pages=562–584 |date=July 2023 |pmid=37277503 |pmc=10241557 |doi=10.1038/s41573-023-00703-8 |url=}} However, Cybin patented deuterated tryptamines including the dideuterated psilocin analogue PI-α,α-d₂ (psilocin dideuterated at the α carbon) in 2023.{{cite web |title=Deuterated tryptamine derivatives and methods of use |website=Google Patents |date=17 July 2023 |url=https://patents.google.com/patent/US20230357147A1/en |access-date=23 October 2024 |quote=Binding affinity (Ki) and functional potency (EC50) values of PI and PI-α-d2 are summarized in Table 1. Deuteration was found to have little effect on the affinity and function at key receptor targets. [...] TABLE 1: PI and PI-α,α-d2 Affinities and Functions at Target Serotonin Receptors [...]}} Other related drugs include the deuterated tryptamine CYB004, the deuterated phenethylamine CYB005, and the phenethylamine CYB210010.{{cite journal | vauthors = Peplow M | title = Next-generation psychedelics: should new agents skip the trip? | journal = Nat Biotechnol | volume = 42 | issue = 6 | pages = 827–830 | date = June 2024 | pmid = 38831049 | doi = 10.1038/s41587-024-02285-1 | url = }}

An {{Abbrlink|INN|International Nonproprietary Name}} of deupsilocin for a deuterated form of psilocin called d₁₀-psilocin with CAS number 1435934-64-7 was proposed in 2023 and recommended in 2024.deupsilocinum deupsilocin 3-[2-{di[(²H₃)methyl]amino}(²H₄)ethyl]-1H-indol-4-ol psychodysleptic [...] C₁₂H₆²H₁₀N₂O 1435934-64-7 https://www.who.int/docs/default-source/international-nonproprietary-names-(inn)/pl129.pdf#page=35deupsilocinum deupsilocin 3-[2-{di[(²H₃)methyl]amino}(²H₄)ethyl]-1H-indol-4-ol [...] C₁₂H₆²H₁₀N₂O https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-%28inn%29/rl91.pdf{{cite patent | country = US | number = 11000534 | inventor = Bradford Sippy | status = | title = Deuterated Derivatives of Psilocybin and Uses Thereof | pubdate = 11 May 2021 | gdate = 11 May 2021 | fdate = 10 December 2020 | pridate = 10 December 2020 | assign1 = Lennham Pharmaceuticals, Inc. | url = }} This deuterated analogue of psilocin was patented in 2021 by Lennham Pharmaceuticals. It is said to be in phase 3 trials.{{cite journal | vauthors = Chen J, Zhu YY, Huang L, Zhang SS, Gu SX | title = Application of deuterium in research and development of drugs | journal = Eur J Med Chem | volume = 287 | issue = | pages = 117371 | date = April 2025 | pmid = 39952095 | doi = 10.1016/j.ejmech.2025.117371 | url = | quote = Moreover, several deuterated compounds have entered Phase III clinical trials, including deupirfenidone, deupsilocin, deutenzalutamide, AVP-786, ALK-001, RT001 and Jaktinib, and numerous deuterated drugs are in phase I and II clinical studies.}}