HLP003

HLP003
Clinical data
Other namesHLP003; HLP-003; CYB003; CYB-003; Deuterated psilocybin analogue; Deuterated psilocin analogue
Routes of
administration		Oral[1]
Drug classSerotonergic psychedelic[1][2]
ATC code
  • None
Pharmacokinetic data
Onset of action30 minutes (Cmax) (rats)[3]
Elimination half-life45 minutes (rats)[3]

HLP003, or HLP-003, also known as deuterated psilocybin analogue and formerly as CYB003, is a serotonergic psychedelic related to psilocybin which is under development for the treatment of major depressive disorder, alcoholism, and other psychiatric disorders.[1][4][5][6][7][2][3] It is taken orally.[1] The drug is a tryptamine derivative and is a deuterated analogue of psilocybin and psilocin.[1][5][6][2]

Interactions

See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

Pharmacology

The pharmacodynamic profile of HLP003, including its interactions with serotonin receptors and its effects in animals, is similar to that of psilocin.[2] As with psilocin, HLP003 is a potent agonist of the serotonin 5-HT2A receptor and produces psychedelic-like effects in animals.[2] 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.[3]

Chemistry

The exact chemical structure of HLP003 (i.e., which specific hydrogen atoms have been deuterated) does not yet seem to have been disclosed.[6][5] However, an INNTooltip International Nonproprietary Name of deupsilocin for a deuterated form of psilocin called d10-psilocin (decadeuteropsilocin) with CAS number 1435934-64-7 was proposed in 2023 and recommended in 2024.[8][9][10][11] This deuterated analogue of psilocin has been patented by Helus Pharma (formerly Cybin) as well as by Lennham Pharmaceuticals.[12][13][10] Helus Pharma has also patented other deuterated psilocin analogues.[14] Other deuterated drugs related to HLP003 or deupsilocin/d10-psilocin include the deuterated DMT analogues HLP004 (CYB004) and SPL028 and the deuterated phenethylamine HLP005 (CYB005).[5][15]

Research

In 2024, HLP003 received a breakthrough therapy designation from the U.S. FDA[16] and was in phase 3 clinical trials for major depressive disorder and is in the preclinical stage of development for alcoholism and other psychiatric disorders.[1][4][17] Two phase 3 clinical trials for major depressive disorder are being initiated in November 2024 and February 2025.[1][4][17] The drug is under development by Helus Pharma (formerly Cybin).[1][4][17]

See also

References

  1. ^ a b c d e f g h "CYB 003". AdisInsight. 4 October 2024. Retrieved 23 October 2024.
  2. ^ a b c d e Palfreyman M, Krakowsky J, Morgan M, Canal C, Pathare P, Avery K, et al. (December 2022). "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" (PDF). Neuropsychopharmacology. 47 (Suppl 1): 220–370 (271). doi:10.1038/s41386-022-01485-0. PMC 9714399. PMID 36456694.
  3. ^ a b c d Inamdar A, Morgan M, Krakowsky J, Reichelt A, Canal C, Mueller T, et al. (December 2022). "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" (PDF). Neuropsychopharmacology. 47 (Suppl 1): 220–370 (271–272). doi:10.1038/s41386-022-01485-0. PMC 9714399. PMID 36456694.
  4. ^ a b c d "Delving into the Latest Updates on CYB-003 with Synapse". Synapse. 12 October 2024. Retrieved 23 October 2024.
  5. ^ a b c d Cano GH, Dean J, Abreu SP, Rodríguez AH, Abbasi C, Hinson M, et al. (December 2022). "Key Characteristics and Development of Psychoceuticals: A Review". Int J Mol Sci. 23 (24) 15777. doi:10.3390/ijms232415777. PMC 9779201. PMID 36555419.
  6. ^ a b c Di Martino RM, Maxwell BD, Pirali T (July 2023). "Deuterium in drug discovery: progress, opportunities and challenges". Nat Rev Drug Discov. 22 (7): 562–584. doi:10.1038/s41573-023-00703-8. PMC 10241557. PMID 37277503.
  7. ^ Rhee TG, Davoudian PA, Sanacora G, Wilkinson ST (December 2023). "Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders". Drug Discov Today. 28 (12) 103818. doi:10.1016/j.drudis.2023.103818. PMID 37925136.
  8. ^ 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=35
  9. ^ deupsilocinum 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
  10. ^ a b US 11000534, Bradford Sippy, "Deuterated Derivatives of Psilocybin and Uses Thereof", published 11 May 2021, issued 11 May 2021, assigned to Lennham Pharmaceuticals, Inc. 
  11. ^ "Deupsilocin". PubChem. Retrieved 19 February 2026.
  12. ^ Butler MS, Capon RJ, Blaskovich MA, Henderson IR (January 2026). "Natural product-derived compounds in clinical trials and drug approvals". Nat Prod Rep. 43 (1): 20–88. doi:10.1039/d5np00031a. PMID 40923383. In addition, Cybin is advancing CYB003, a deuterated psilocin that recently completed a phase I/II trial (NCT05385783) for MDD.242 While its structure has not been disclosed, Cybin's patents include psilocin-D10 4.21 and related analogues.243 [...] 242 Cybin, CYB003: Deuterated psilocin program with FDA breakthrough therapy designation, https://cybin.com/ cyb003/, accessed 7 April 2025. 243 A. Nivorozhkin, M. Palfreyman, P. Pathare, K. L. Avery, M. Shukoor, J. H. Huang, M. E. Morgan and J. M. Krakowsky, World Pat., WO2022195011A1, 2022. {{cite journal}}: External link in |quote= (help)
  13. ^ "Psilocybin analogs, salts, compositions, and methods of use". Google Patents. 17 March 2022. Retrieved 19 February 2026.
  14. ^ "Deuterated tryptamine derivatives and methods of use". Google Patents. 17 July 2023. Retrieved 23 October 2024. 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 [...]
  15. ^ Peplow M (June 2024). "Next-generation psychedelics: should new agents skip the trip?". Nat Biotechnol. 42 (6): 827–830. doi:10.1038/s41587-024-02285-1. PMID 38831049.
  16. ^ Jenkins C (19 March 2024). "FDA grants breakthrough designation to psilocybin analog for major depressive disorder". Healio. Retrieved 7 August 2025.
  17. ^ a b c Kuntz L (10 February 2025). "CYB003 for the Adjunctive Treatment of Major Depressive Disorder". Psychiatric Times. Retrieved 7 August 2025.
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