Chemistry:HLP003

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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][2][3][4][5][6][7] It is taken orally.[1] The drug is a tryptamine derivative and is a deuterated analogue of psilocybin and psilocin.[1][3][4][6]

Interactions

Pharmacology

The pharmacodynamic profile of HLP003, including its interactions with serotonin receptors and its effects in animals, is similar to that of psilocin.[6] As with psilocin, HLP003 is a potent agonist of the serotonin 5-HT2A receptor and produces psychedelic-like effects in animals.[6] 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.[7]

In humans, HLP003 has been reported to have 2.2-fold higher peak levels and 3.5-fold higher area-under-the-curve (AUC) levels than psilocybin at equivalent doses.[8] It is said to have a rapid onset of less than 15 minutes and a duration of 4 to 6 hours.[8]

Chemistry

Deupsilocin (INN; d10-psilocin) structure.

The exact chemical structure of HLP003 (i.e., which specific hydrogen atoms have been deuterated) does not yet seem to have been disclosed.[4][3] However, an INN 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.[9][10][11][12] This deuterated analogue of psilocin has been patented by Helus Pharma (formerly Cybin) as well as by Lennham Pharmaceuticals.[13][14][11] Helus Pharma has also patented other deuterated psilocin analogues.[15] 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).[3][16]

Research

In 2024, HLP003 received a breakthrough therapy designation from the U.S. FDA[17] 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][2][18] Two phase 3 clinical trials for major depressive disorder are being initiated in November 2024 and February 2025.[1][2][18] The drug is under development by Helus Pharma (formerly Cybin).[1][2][18]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "CYB 003". 4 October 2024. https://adisinsight.springer.com/drugs/800062409. 
  2. ↑ 2.0 2.1 2.2 2.3 "Delving into the Latest Updates on CYB-003 with Synapse". 12 October 2024. https://synapse.patsnap.com/drug/dcb535376933495783bad0ae5504a571. 
  3. ↑ 3.0 3.1 3.2 3.3 "Key Characteristics and Development of Psychoceuticals: A Review". Int J Mol Sci 23 (24). December 2022. doi:10.3390/ijms232415777. PMID 36555419. 
  4. ↑ 4.0 4.1 4.2 "Deuterium in drug discovery: progress, opportunities and challenges". Nat Rev Drug Discov 22 (7): 562–584. July 2023. doi:10.1038/s41573-023-00703-8. PMID 37277503. 
  5. ↑ "Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders". Drug Discov Today 28 (12). December 2023. doi:10.1016/j.drudis.2023.103818. PMID 37925136. 
  6. ↑ 6.0 6.1 6.2 6.3 "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". Neuropsychopharmacology 47 (Suppl 1): 220–370 (271). December 2022. doi:10.1038/s41386-022-01485-0. PMID 36456694. PMC 9714399. https://cybin.com/wp-content/uploads/2023/09/ACNP_2022_CYB003_Poster-1.pdf. 
  7. ↑ 7.0 7.1 "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". Neuropsychopharmacology 47 (Suppl 1): 220–370 (271–272). December 2022. doi:10.1038/s41386-022-01485-0. PMID 36456694. PMC 9714399. https://cybin.com/wp-content/uploads/2023/09/ACNP-2022-CYB003-Poster-2.pdf. 
  8. ↑ 8.0 8.1 https://s28.q4cdn.com/259445127/files/doc_presentations/2026/Mar/18/Helus-Corporate-Deck-March-18-2026-Final.pdf
  9. ↑ 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
  10. ↑ 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
  11. ↑ 11.0 11.1 Bradford Sippy, "Deuterated Derivatives of Psilocybin and Uses Thereof", US patent 11000534, published 11 May 2021, issued 11 May 2021, assigned to Lennham Pharmaceuticals, Inc.
  12. ↑ "Deupsilocin". https://pubchem.ncbi.nlm.nih.gov/compound/117065176. 
  13. ↑ "Natural product-derived compounds in clinical trials and drug approvals". Nat Prod Rep 43 (1): 20–88. January 2026. 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.". 
  14. ↑ "Psilocybin analogs, salts, compositions, and methods of use". 17 March 2022. https://patents.google.com/patent/WO2022195011A1/en. 
  15. ↑ "Deuterated tryptamine derivatives and methods of use". 17 July 2023. https://patents.google.com/patent/US20230357147A1/en. "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 [...]" 
  16. ↑ "Next-generation psychedelics: should new agents skip the trip?". Nat Biotechnol 42 (6): 827–830. June 2024. doi:10.1038/s41587-024-02285-1. PMID 38831049. 
  17. ↑ Jenkins, Cassandra (19 March 2024). "FDA grants breakthrough designation to psilocybin analog for major depressive disorder". https://www.healio.com/news/psychiatry/20240319/fda-grants-breakthrough-designation-to-psilocybin-analog-for-major-depressive-disorder. 
  18. ↑ 18.0 18.1 18.2 Kuntz, Leah (10 February 2025). "CYB003 for the Adjunctive Treatment of Major Depressive Disorder". https://www.psychiatrictimes.com/view/cyb003-for-the-adjunctive-treatment-of-major-depressive-disorder. 




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