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SPT-348
Clinical data
Other namesSPT348
Drug classNon-hallucinogenic psychoplastogen; Non-selective serotonin receptor modulator; Non-hallucinogenic serotonin 5-HT2A receptor partial agonist
ATC code
  • None

SPT-348 is a serotonin receptor modulator and non-hallucinogenic psychoplastogen of the lysergamide family which is under development for the treatment of depression, anxiety, and other neuropsychiatric disorders.[1][2][3][4] It is a prodrug of 2-bromo-LSD (bromolysergide; BOL-148), a non-selective serotonin receptor modulator and partial agonist of the serotonin 5-HT2A receptor,[5][6] and is an analogue of the serotonergic psychedelic LSD.[3][4] The drug is said to employ a novel formulation involving a triglyceride linker that helps it to bypass first-pass metabolism in the liver that is said to be prominent with LSD.[2] As of 2025, SPT-348 is in the discovery or preclinical research stage of development.[2][1]

See also

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References

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  1. ^ a b "Delving into the Latest Updates on SPT-348 with Synapse". Synapse. 8 May 2025. Retrieved 12 May 2025.
  2. ^ a b c Peplow M (June 2024). "Next-generation psychedelics: should new agents skip the trip?". Nature Biotechnology. 42 (6): 827–830. doi:10.1038/s41587-024-02285-1. PMID 38831049. Table 1 | Selected companies working on next-generation psychedelic therapeutics [...] Delix's Boston neighbor Seaport is also developing neuroplastogens, along with other compounds, to treat depression and anxiety disorders. "Our particular play is based on the notion that you don't need a psychedelic trip experience to gather the beneficial effects of these psychedelic agents," says founder and board chair Steve Paul. One of the company's preclinical antidepressants is a non-hallucinogenic LSD analog called SPT-348. LSD itself is a 5-HT2A agonist, but there is a lot of variation between patients in how quickly it is metabolized in the liver, making it challenging to determine the optimal dose. So Seaport has tethered its LSD analog to a novel drug delivery system called Glyph that helps the drug to circumvent the liver. The drug is attached via a linker to a triglyceride, which is absorbed through the gastrointestinal lymphatic system just like dietary fats and passes directly into the bloodstream before breaking down to release the drug. Classical psychedelic drugs are challenging to blind with a placebo in a clinical trial, but SPT348 should be able avoid that difficulty. "Since we don't have a psychedelic experience, the idea is you could do a real placebo-controlled trial, which I think is helpful," says Paul.
  3. ^ a b "March & April 2025 Psychedelic Patent Update: Lykos' Patent Woes Continue; Filings Provide First Look at Seaport's 2-Bromo-LSD Program; Delix's Ergoline Analogues; CaaMTech's Spinout". Psychedelic Alpha. 1 May 2025. Retrieved 12 May 2025. Patent Filings Provide First Look At Seaport Therapeutics' SPT-348 (2-Bromo-LSD) Program [...]
  4. ^ a b "New lipid prodrugs of bromolysergide disclosed in Seaport Therapeutics patent". BioWorld. 11 May 2025. Retrieved 12 May 2025. Seaport Therapeutics Inc. has divulged lipid prodrugs of bromolysergide reported to be useful for the treatment of cluster headache and mood disorder. [...] It hydrolyzed to active compound (release of 2-bromo-LSD>25%) in human plasma. [...]
  5. ^ Gumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". British Journal of Pharmacology. doi:10.1111/bph.17361. PMID 39354889.
  6. ^ Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, et al. (March 2023). "A non-hallucinogenic LSD analog with therapeutic potential for mood disorders". Cell Reports. 42 (3): 112203. doi:10.1016/j.celrep.2023.112203. PMC 10112881. PMID 36884348.
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