SPL028

SPL028
Clinical data
Other namesSPL-028; α,α-Dideutero-N,N-dimethyltryptamine; N,N-D2-dimethyltryptamine; D2-DMT; DMT-d2
Routes of
administration		Intravenous injection, intramuscular injection[1]
Drug classSerotonin receptor modulator; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Identifiers
PubChem CID
ChemSpider
Chemical and physical data
3D model (JSmol)
  • [2H]C([2H])(CC1=CNC2=CC=CC=C21)N(C)C
  • InChI=1S/C12H16N2/c1-14(2)8-7-10-9-13-12-6-4-3-5-11(10)12/h3-6,9,13H,7-8H2,1-2H3/i8D2
  • Key:DMULVCHRPCFFGV-MGVXTIMCSA-N

SPL028, or SPL-028, also known as α,α-dideutero-N,N-dimethyltryptamine (D2-DMT), is a psychedelic drug of the tryptamine family which is under development for the treatment of depressive disorders.[2][3][4][5] It is the analogue of dimethyltryptamine (DMT) in which the α carbon has been dideuterated.[2][6] SPL028's route of administration is intravenous injection or intramuscular injection.[1]

Pharmacology

SPL028 shows similar pharmacodynamics as DMT in vitro.[2][6] Relatedly, SPL028 generalized with DMT in rodent drug discrimination tests.[6][7] On the other hand, SPL028 differs from DMT in terms of pharmacokinetics; it is more resistant to metabolism and shows a prolonged duration.[2][6][7] In a phase 1 clinical trial, SPL-028 by intramuscular injection produced robust psychedelic effects of short duration in humans.[8]

Research

SPL028 was originated by Small Pharma and is under development by Cybin.[4] Small Pharma was acquired by Cybin in 2023.[9] As of February 2024, SPL028 is in phase 1 clinical trials.[4]

See also

References

  1. ^ a b Marino D (15 February 2023). "First Subject Dosed in Small Pharma's First-in-Human Phase 1 Clinical Trial". Drug Development and Delivery. Retrieved 27 July 2025.
  2. ^ a b c d Layzell M, Rands P, Good M, Joel Z, Cousins R, Benway T, et al. (14 September 2023). "Discovery and In Vitro Characterization of SPL028: Deuterated N , N -Dimethyltryptamine". ACS Medicinal Chemistry Letters. 14 (9): 1216–1223. doi:10.1021/acsmedchemlett.3c00143. ISSN 1948-5875. PMC 10510671. PMID 37736183.
  3. ^ Kargbo RB (8 September 2022). "Application of Deuterated N , N -Dimethyltryptamine in the Potential Treatment of Psychiatric and Neurological Disorders". ACS Medicinal Chemistry Letters. 13 (9): 1402–1404. doi:10.1021/acsmedchemlett.2c00354. ISSN 1948-5875. PMC 9465894. PMID 36105328.
  4. ^ a b c "SPL 028". AdisInsight. 16 February 2024. Retrieved 27 July 2025.
  5. ^ "Delving into the Latest Updates on SPL-028 with Synapse". Synapse. 14 June 2025. Retrieved 27 July 2025.
  6. ^ a b c d Good M, Cheetham S, Davis I (2023). "The International BNA 2023 Festival of Neuroscience: Preclinical characterisation of SPL028: a deuterated derivative of N,N-dimethyltryptamine, developing a treatment for mental health disorders". Brain and Neuroscience Advances. 7: 77. doi:10.1177/23982128231180246. ISSN 2398-2128. PMC 10236260. The PK and pharmacology of SPL028 (α,α-bisdeutero-N,N-dimethyltryptamine (D2DMT) fumarate) [di-deuterated analogue of SPL026] was investigated through a series of preclinical studies. [...] SPL028 exhibited prolonged PK and pharmacodynamic effects compared to SPL026. In vitro & in vivo studies found the metabolic stability of SPL028 increased relative to SPL026. The in vitro & ex vivo receptor profiles of SPL028 and SPL026 were equivalent. These findings were consistent with drug discrimination study: rats were not able to distinguish SPL028 from SPL026.
  7. ^ a b Good M, Joel Z, Cheetham S, Davis I, Rowley H, James E, et al. (April 2023). In vivo characterisation of SPL028: a deuterated derivative of N,N-dimethyltryptamine, developing a treatment for mental health disorders (PDF). British Neuroscience Association 2023 (BAN2023).
  8. ^ "Cybin Announces Positive Topline Data from Phase 1 Studies of Proprietary Deuterated DMT Molecules CYB004 and SPL028". Nasdaq. 5 April 2024. Retrieved 27 July 2025.
  9. ^ Alpha P (28 August 2023). "Cybin Set to Acquire British DMT Drug Developer Small Pharma". Psychedelic Alpha. Retrieved 27 July 2025.

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