Physics:Deudimethyltryptamine

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Deudimethyltryptamine (INN; developmental code names HLP004 and CYB004), also known as deuterated dimethyltryptamine (dDMT) or as DMT-d10, is a psychedelic drug of the tryptamine family related to dimethyltryptamine (DMT) which is under development for the treatment of generalized anxiety disorder, anxiety disorders, and depressive disorders.[1][2][3][4][5][6][7] It is administered by inhalation or intravenous injection.[1][3] The drug is a deuterated isotopologue of DMT with altered pharmacokinetics.[1][2][4][5][8]

Interactions

Pharmacology

The pharmacodynamic profile of deudimethyltryptamine, including its interactions with serotonin receptors and its effects in animals, is similar to that of DMT.[4] As with DMT, deudimethyltryptamine is a potent agonist of the serotonin 5-HT2A receptor and produces psychedelic-like effects in animals.[1][9][4] However, deudimethyltryptamine, 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 deudimethyltryptamine was also increased (by 30%) relative to DMT, indicating slightly greater central permeability as well.[4]

The pharmacokinetics and effects of deudimethyltryptamine in humans have been studied and compared with those of DMT.[5][8] 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).[10][11] Deudimethyltryptamine produced more robust psychedelic effects than DMT at lower concentrations.[5] Additional details on the pharmacokinetics of deudimethyltryptamine in humans have also been reported.[8]

Pharmacokinetics of deudimethyltryptamine in humans[8][12]
  • Levels of deudimethyltryptamine i.m. versus DMT i.v.[8][12]
    Levels of deudimethyltryptamine i.m. versus DMT i.v.[8][12]
  • Levels of deudimethyltryptamine at doses of 2 to 30 mg i.m.[8][12]
    Levels of deudimethyltryptamine at doses of 2 to 30 mg i.m.[8][12]

Chemistry

Analogues

Other deuterated drugs related to deudimethyltryptamine or DMT-d10 include the deuterated DMT analogue SPL028 (D2-DMT; α,α-dideutero-DMT), the deuterated psilocin analogue deupsilocin (HLP003; CYB003; d10-psilocin), and the deuterated phenethylamine HLP005 (CYB005).[9][3]

Research

Deudimethyltryptamine is under development by Helus Pharma (formerly Cybin).[1][2] It is under development for the treatment of generalized anxiety disorder, anxiety disorders, and depressive disorders.[1][2] As of July 2026, deudimethyltryptamine is in phase 2 clinical trials for generalized anxiety disorder and phase 1 trials for anxiety disorders and depressive disorders.[1][2] It was also under development for the treatment of substance-related disorders and other psychiatric disorders, but development for these indications was discontinued.[1]

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 2.4 "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 5.4 "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. ↑ Nivorozhkin A, Palfreyman M, "Deuterated tryptamine derivatives and methods of use", US patent 2023/0357147, published 8 October 2024
  7. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN)". p. 36. https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl134.pdf#page=36. "deudimethyltryptamine 2-(1H-indol-3-yl)-N,N-di[(2H3)methyl](1,1,2,2-2H4)ethan-1-amine serotonin 5-HT2A receptor agonist [...] C12H62H10N2 2742678-60-8 [...]" 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 "Helus Pharma Corporate Presentation March 2026". Helus Pharma. March 2026. https://s28.q4cdn.com/259445127/files/doc_presentations/2026/Mar/18/Helus-Corporate-Deck-March-18-2026-Final.pdf. 
  9. ↑ 9.0 9.1 "Key Characteristics and Development of Psychoceuticals: A Review". International Journal of Molecular Sciences 23 (24). December 2022. doi:10.3390/ijms232415777. PMID 36555419. 
  10. ↑ "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. 
  11. ↑ "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. 
  12. ↑ 12.0 12.1 12.2 "HLP004 Helus Pharma Announces Positive Phase 2 Data For Its Novel Serotonergic Agonist in Generalized Anxiety Disorder (GAD)". Helus Pharma. March 2026. https://s28.q4cdn.com/259445127/files/HLP004-Phase-2-Data-Presentation-Mar-5-2026-Website.pdf. 



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