Chemistry:HLP004

From HandWiki

HLP004, or HLP-004, also known as deuterated dimethyltryptamine (dDMT) and formerly as CYB004, is a serotonergic psychedelic related to dimethyltryptamine (DMT) which is under development for the treatment of generalized anxiety disorder.[1][2][3][4][5] It is administered by inhalation or intravenous injection.[1][3] The drug is a tryptamine derivative and is a deuterated analogue and form of DMT.[1][2][4]

Interactions

Pharmacology

The pharmacodynamic profile of HLP004, including its interactions with serotonin receptors and its effects in animals, is similar to that of DMT.[4] As with DMT, HLP004 is a potent agonist of the serotonin 5-HT2A receptor and produces psychedelic-like effects in animals.[1][6][4] However, HLP004, due to its deuteration, is more resistant to metabolism than DMT and shows a longer elimination half-life (by 2.5- to 2.9-fold) and slower clearance (by 38 to 55%) in animals.[4] The brain to plasma ratio of HLP004 was also increased (by 30%) relative to DMT, indicating slightly greater central permeability as well.[4]

The pharmacokinetics and effects of HLP004 in humans have been studied and compared with those of DMT.[5][7] Its elimination half-life was 37 to 40 minutes and its duration was approximately 40 minutes.[5] For comparison, the half-life of DMT in humans has been reported to be 9 to 12 minutes (range 5–19 minutes).[8][9] HLP004 produced more robust psychedelic effects than DMT at lower concentrations.[5] Additional details on the pharmacokinetics of HLP004 in humans have also been reported.[7]

Chemistry

Error creating thumbnail:
Deudimethyltryptamine (INN; DMT-d10) structure.

The exact chemical structure of HLP004 (i.e., which specific hydrogen atoms have been deuterated) does not yet seem to have been disclosed.[1] However, Helus Pharma (formerly Cybin) patented deuterated tryptamines, including deuterated forms of DMT like DMT-d10 (decadeutero-DMT; CAS no. 2742678-60-8), in 2023.[10][11] In addition, DMT-d10 was given the INN deudimethyltryptamine in January 2026.[12] Other deuterated drugs related to HLP004 or DMT-d10 include the deuterated DMT analogue SPL028 (D2-DMT; α,α-dideutero-DMT), the deuterated psilocybin analogue HLP003 (CYB003) (possibly deupsilocin or d10-psilocin), and the deuterated phenethylamine HLP005 (CYB005).[6][3]

Research

As of August 2024, HLP004 is in phase 2 clinical trials for generalized anxiety disorder.[1][2] It was also under development for the treatment of substance-related disorders and of other psychiatric disorders, but development for these indications was discontinued.[1] The drug is under development by Helus Pharma (formerly Cybin).[1][2]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "CYB 004". 14 August 2024. https://adisinsight.springer.com/drugs/800062410. 
  2. ↑ 2.0 2.1 2.2 2.3 "Delving into the Latest Updates on Deuterated dtryptamine with Synapse". 27 October 2024. https://synapse.patsnap.com/drug/8577e733c46648599fdd96ed1661ea3b. 
  3. ↑ 3.0 3.1 3.2 "Next-generation psychedelics: should new agents skip the trip?". Nature Biotechnology 42 (6): 827–830. June 2024. doi:10.1038/s41587-024-02285-1. PMID 38831049. "Cybin’s pipeline also includes CYB004, a deuterated analog of DMT. When given intravenously, DMT itself is rapidly metabolized and causes an intense trip that lasts less than 20 minutes, which may be too brief to be an effective therapy. In contrast, a single intravenous injection of CYB004 produces a 90-minute trip, and Cybin is about to start recruiting patients to a phase 2 trial of the drug to treat generalized anxiety disorder.". 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "ACNP 62nd Annual Meeting: Poster Abstracts P1 - P250: P80. Preclinical Characterization of CYB004: A Novel, Deuterated N,N-Dimethyltryptamine (DMT) Analog for the Potential Treatment of Generalized Anxiety Disorder (GAD)". Neuropsychopharmacology (Springer Science and Business Media LLC) 48 (Suppl 1): 63–210 (109–110). December 2023. doi:10.1038/s41386-023-01755-5. PMID 38040809. 
  5. ↑ 5.0 5.1 5.2 5.3 "ACNP 62nd Annual Meeting: Poster Abstracts P251 – P500: P425. Early Clinical Development of a Deuterated N,N-Dimethyltryptamine (DMT) Analog for the Treatment of Mental Health Conditions". Neuropsychopharmacology 48 (Suppl 1): 211–354 (310–311). December 2023. doi:10.1038/s41386-023-01756-4. PMID 38040810. PMC 10729596. https://www.helus.com/wp-content/uploads/2025/04/ERLY_ACNP-2023-CYB004-Inamdar-Early-Clinical-Development-of-a-Deuterated-NN-Dimethyltryptamine-DMT-Analog.pdf. 
  6. ↑ 6.0 6.1 "Key Characteristics and Development of Psychoceuticals: A Review". International Journal of Molecular Sciences 23 (24). December 2022. doi:10.3390/ijms232415777. PMID 36555419. 
  7. ↑ 7.0 7.1 https://s28.q4cdn.com/259445127/files/doc_presentations/2026/Mar/18/Helus-Corporate-Deck-March-18-2026-Final.pdf
  8. ↑ "Pharmacokinetics of N,N-dimethyltryptamine in Humans". European Journal of Drug Metabolism and Pharmacokinetics 48 (3): 311–327. May 2023. doi:10.1007/s13318-023-00822-y. PMID 37086340. 
  9. ↑ "Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis". Clin Pharmacokinet 64 (2): 215–227. February 2025. doi:10.1007/s40262-024-01450-8. PMID 39838235. 
  10. ↑ Nivorozhkin A, Palfreyman M, "Deuterated tryptamine derivatives and methods of use", US patent 2023/0357147, published 8 October 2024
  11. ↑ "1,1,2,2-tetradeuterio-2-(1H-indol-3-yl)-N,N-bis(trideuteriomethyl)ethanamine". https://pubchem.ncbi.nlm.nih.gov/compound/167379785. 
  12. ↑ https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl134.pdf



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:HLP004&oldid=4309658"