Chemistry:SPL028

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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.[1][2][3][4] It is the analogue of dimethyltryptamine (DMT) in which the α carbon has been dideuterated.[1][5] SPL028's route of administration is intravenous injection or intramuscular injection.[6]

The drug shows similar pharmacodynamics as DMT in vitro.[1][5] Relatedly, SPL028 generalized with DMT in rodent drug discrimination tests.[5][7] On the other hand, SPL028 differs from DMT in terms of pharmacokinetics; it is more resistant to metabolism and shows a prolonged duration.[1][5][7] In a phase 1 clinical trial, SPL-028 by intramuscular injection produced robust psychedelic effects of short duration in humans.[8]

SPL028 was originated by Small Pharma and is under development by Cybin.[3] Small Pharma was acquired by Cybin in 2023.[9] As of February 2024, SPL028 is in phase 1 clinical trials.[3]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 "Discovery and In Vitro Characterization of SPL028: Deuterated N , N -Dimethyltryptamine". ACS Medicinal Chemistry Letters 14 (9): 1216–1223. 14 September 2023. doi:10.1021/acsmedchemlett.3c00143. ISSN 1948-5875. PMID 37736183. 
  2. ↑ "Application of Deuterated N , N -Dimethyltryptamine in the Potential Treatment of Psychiatric and Neurological Disorders". ACS Medicinal Chemistry Letters 13 (9): 1402–1404. 8 September 2022. doi:10.1021/acsmedchemlett.2c00354. ISSN 1948-5875. PMID 36105328. 
  3. ↑ 3.0 3.1 3.2 "SPL 028". 16 February 2024. https://adisinsight.springer.com/drugs/800063710. 
  4. ↑ "Delving into the Latest Updates on SPL-028 with Synapse". 14 June 2025. https://synapse.patsnap.com/drug/84f9d558e2f5408c8522c5172a80d73e. 
  5. ↑ 5.0 5.1 5.2 5.3 "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. 2023. doi:10.1177/23982128231180246. ISSN 2398-2128. "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.". 
  6. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Marino_2023
  7. ↑ 7.0 7.1 "In vivo characterisation of SPL028: a deuterated derivative of N,N-dimethyltryptamine, developing a treatment for mental health disorders". British Neuroscience Association 2023 (BAN2023). April 2023. https://cybin.com/wp-content/uploads/2025/04/BAP-2023-poster-In-vivo-characterisation-of-SPL028.pdf. 
  8. ↑ "Cybin Announces Positive Topline Data from Phase 1 Studies of Proprietary Deuterated DMT Molecules CYB004 and SPL028". 5 April 2024. https://www.nasdaq.com/press-release/cybin-announces-positive-topline-data-from-phase-1-studies-of-proprietary-deuterated. 
  9. ↑ "Cybin Set to Acquire British DMT Drug Developer Small Pharma". 28 August 2023. https://psychedelicalpha.com/news/cybin-set-to-acquire-british-dmt-drug-developer-small-pharma. 


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