Bretisilocin

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Bretisilocin

CAS2698331-35-8

MF C13H17FN2 MW220.29 g/mol

N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine
serotonin (5-HT2A) receptor agonist, GM-2505, GM 2505, 5-Fluoro-N-methyl-N-ethyltryptamine, 5F-MET, 5-F-MET, 5-Fluoro-MET, DS425RQ8SX

Bretisilocin, also known by its developmental code name GM-2505 and as 5-fluoro-N-methyl-N-ethyltryptamine (5F-MET or 5-fluoro-MET), is a serotonergic psychedelic of the tryptamine family which is under development for the treatment of major depressive disorder.[1][7][2][3] It is an analogue of dimethyltryptamine (DMT) and is the 5-fluorinated derivative of methylethyltryptamine (MET).[8] Bretisilocin’s route of administration is intravenous infusion.[1][2][3][4]

The drug acts as a potent and well-balanced serotonin 5-HT2A and 5-HT2C receptor agonist, serotonin 5-HT2B receptor partial agonist or antagonist, and serotonin releasing agent.[2][9][8][10] It produces psychedelic-like effects in animals and similarly produces robust hallucinogenic effects in humans.[9][3] The duration of bretisilocin is 60 to 90 minutes and is intermediate between the durations of DMT and psilocybin.[6][11][4][12][8][2] It has been regarded by its developer as an “improved version of DMT”.[12]

Bretisilocin was first described in the literature by 2022.[9][10] It is under development by Gilgamesh Pharmaceuticals.[1] As of June 2025, the drug is in phase 2 clinical trials for the treatment of major depressive disorder.[1] Bretisilocin was acquired from Gilgamesh Pharmaceuticals by AbbVie in a deal worth up to $1.2 billion in August 2025.[13][14] It was encountered as a novel recreational designer drug in 2026.[5]

Chemistry

Bretisilocin, also known as 5-fluoro-N-methyl-N-ethyltryptamine, is a substituted tryptamine derivative.[8] It is a derivative of dimethyltryptamine (DMT) and methylethyltryptamine (MET) as well as of 5-fluorotryptamine (5-FT).[6][8]

Synthesis

The chemical synthesis of bretisilocin has been described.[10]

Analogues

Some analogues of bretisilocin include 5-fluoro-DMT, 5-fluoro-DET, 5-fluoro-EPT, 5-chloro-DMT, 5-bromo-DMT, 5-fluoro-AMT, 5-fluoro-AET, 5-MeO-MET, and 7-F-5-MeO-MET, among others.

History

Bretisilocin was first described in the scientific literature by at least 2022.[9][10] It was patented by Jason Wallach and colleagues at the University of the Sciences in Philadelphia that year.[10] The drug was encountered as a novel recreational designer drug in March 2026.[5]

Society and culture

Names

Bretisilocin is the generic name of the drug and its INNTooltip International Nonproprietary Name.[16] It is also known by its developmental code name GM-2505.[1][9][3]

Legal status

Canada

Bretisilocin is not a controlled substance in Canada as of 2025.[17]

United States

Bretislocin is not an explicitly controlled substance in the United States.[18] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

Research

Bretisilocin is under development as a potential pharmaceutical drug by Gilgamesh Pharmaceuticals.[1] As of June 2025, it is in phase 2 clinical trials for the treatment of major depressive disorder.[1] A phase 2a trial of bretisilocin for major depressive disorder has been completed and the efficacy and safety data for the trial have been released.[1][19][20][21] The drug has since been acquired from Gilgamesh Pharmaceuticals by AbbVie in a deal worth up to $1.2 billion.[13][14] In 2026 bretisilocin entered European Medicines Agency’s priority medicines (PRIME) scheme for major depressive disorder.[22][23]

SYN

US20240286998,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US437765342&_cid=P12-MNXZVV-01144-1

Example 12: N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12)

Synthesis of N-[2-(5-fluoro-1H-indol-3-yl)ethyl]formamide

 To a solution of 5-fluorotryptamine hydrochloride (3 g, 14.0 mmol) in H 2O (200 mL) with stirring was added KOH until a precipitate was obtained. The aqueous mixture was extracted with EtOAc (3×70 mL), the organic phases were pooled, washed with brine, dried over anhydrous Na 2SO 4, and concentrated in vacuo. Residual EtOAc was removed by azeotropic distillation with ethyl formate (3×20 mL). The resulting 5-fluorotryptamine free base was transferred to a 30 mL oven-dried microwave vessel containing 3 Å molecular sieves (3.3 g). Ethyl formate (20 mL, 248 mmol) was added to the microwave vessel and the mixture was reacted for 2.5 h at 80° C. with 150 W in a microwave reactor. Upon completion, ethyl formate was removed under reduced pressure to provide N-[2-(5-fluoro-1H-indol-3-yl)ethyl]formamide (1.7 g, 8.24 mmol, 58.9% yield). The product was used in the subsequent reaction without further purification.

 To a solution of 5-fluorotryptamine hydrochloride (3 g, 14.0 mmol) in H 2O (200 mL) with stirring was added KOH until a precipitate was obtained. The aqueous mixture was extracted with EtOAc (3×70 mL), the organic phases were pooled, washed with brine, dried over anhydrous Na 2SO 4, and concentrated in vacuo. Residual EtOAc was removed by azeotropic distillation with ethyl formate (3×20 mL). The resulting 5-fluorotryptamine free base was transferred to a 30 mL oven-dried microwave vessel containing 3 Å molecular sieves (3.3 g). Ethyl formate (20 mL, 248 mmol) was added to the microwave vessel and the mixture was reacted for 2.5 h at 80° C. with 150 W in a microwave reactor. Upon completion, ethyl formate was removed under reduced pressure to provide N-[2-(5-fluoro-1H-indol-3-yl)ethyl]formamide (1.7 g, 8.24 mmol, 58.9% yield). The product was used in the subsequent reaction without further purification.

Synthesis of 2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine

  A three neck 500 mL round bottom flask, 300 mL addition funnel, stir bar, and condenser were dried overnight in an oven at 70° C., then further dried with external heat while flushing argon through the sealed system. Once drying was deemed completion the round bottom flask was placed into an ice bath (0° C.), and the apparatus was allowed to cool to room temperature. THF (100 mL) was added via the addition funnel and was allowed to reach 0° C., then sodium bis(2-methoxyethoxy)aluminium hydride (Red-Al) (18.41 mL, 59.6 mmol) was added to the reaction vessel. Next, N-[2-(5-fluoro-1H-indol-3-yl)ethyl]formamide (4.1 g, 19.8 mmol) in THE (20 mL) was added dropwise to the reaction vessel, with stirring, under argon over 30 mins at 0° C. Following the addition, the reaction was heated at reflux for 4 h. Upon completion, the reaction was cooled to 0° C. and cautiously quenched by the dropwise addition of THF/H 2O (1:1, v/v) with ice. Once quenched a small amount of KOH (aq.), then 100 mL of EtOAc were added.
      The inorganic solids were then gravity filtered and washed with EtOAc. The filtrate was extracted with 0.2 M HCl (aq.) (3×166 mL). The pooled aqueous phases were then basified with KOH pellets and extracted with EtOAc (3×100 mL). The pooled organic extractions were washed with brine (20 mL), dried over anhydrous Na 2SO 4, and concentrated in vacuo to provide 2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine as a yellow oil (3.14 g, 0.0163 mol, 82.32% yield). The product was used in the subsequent reaction without further purification. ASAP-MS: m/z 193.2 (theoretical [M+H] +, C 11H 13FN 2 +), m/z 193.2 (observed).

Synthesis of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12)

N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12) was synthesized in a similar manner as described above for N-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N-propylpropan-1-amine (5), starting from 2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (0.7 g, 3.64 mmol), and acetaldehyde (0.96 g, 21.8 mmol), to provide the title compound as a colorless oil after purification by column chromatography using silica gel as a stationary phase and 20% EtOH/EtOAc (1% Et 3N v/v) as the mobile phase (0.62 g, 2.81 mmol, 77.2% yield), and subsequently the corresponding HCl salt as a white crystalline solid. HR-ASAP-MS: m/z 221.1442 (theoretical [M+H] +, C 13H 18FN 2 +), m/z 221.1449 (observed, Δ=−3.2 ppm). 1H-NMR (400 MHz, d 6-DMSO) δ 11.15 (s, 1H), 10.74 (s, 1H), 7.44 (dd, J=10.1, 2.5 Hz, 1H), 7.36 (dd, J=8.8, 4.6 Hz, 1H), 7.33 (d, J=2.3 Hz, 1H), 6.93 (dt, J=9.2, 2.5 Hz, 1H), 3.31-3.13 (m, 4H), 3.13-3.05 (m, 2H), 2.78 (d, J=3.1 Hz, 3H), 1.26 (t, J=7.3 Hz, 3H). 13C-NMR (101 MHz, d 6-DMSO) δ 156.74 (d, J=231.1 Hz, 1C), 132.88 (s, 1C), 126.96 (d, J=10.0 Hz, 1C), 125.42 (s, 1C), 112.48 (d, J=9.9 Hz, 1C), 109.51 (s, 1C), 109.32 (d, J=26.0 Hz, 1C), 103.13 (d, J=23.1 Hz, 1C), 54.37 (s, 1C), 49.82 (s, 1C), 38.13 (s, 1C), 19.68 (s, 1C), 8.79 (s, 1C). 19F-NMR (377 MHz, d 6-DMSO) δ−124.79 (s, 1F).

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021168082&_cid=P12-MNXZSN-99000-1

PAT

Methods of treating mood disorders

Publication Number: US-2022041551-A1

Priority Date: 2020-02-18

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References

References

  1.  “GM 2505”. AdisInsight. 5 June 2025. Retrieved 29 July 2025.
  2.  Marek GJ, Makai-Bölöni S, Umbricht D, Christian EP, Winters J, Dvorak D, et al. (2025). “A novel psychedelic 5-HT 2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer”. Journal of Psychopharmacology 02698811251378512. doi:10.1177/02698811251378512. hdl:1887/4298848. PMID 41099491.
  3.  Hughes Z, Christian E, Dvorak D, Umbricht D, Winters J, Raines S, et al. (December 2023). “ACNP 62nd Annual Meeting: Poster Abstracts P1 – P250: P238. Subjective and Pharmacodynamic Effects of the Novel 5-HT2A Receptor Agonist GM-2505 in Healthy Volunteers Show High Translatability From Rodent Data and Hold Promise for Future Development in Patients With Depression”. Neuropsychopharmacology. 48 (Suppl 1). Springer Science and Business Media LLC: 63–210 (202–203). doi:10.1038/s41386-023-01755-5. PMC 10729595. PMID 38040809.
  4.  Umbricht D, Christian E, Winters J, Raines S, Hughes ZA, Leong W, et al. (2024). “Pharmacokinetic, pharmacodynamic and subjective and effects of the novel 5-HT2A receptor agonist GM-2505 in healthy volunteers”. Neuroscience Applied. 3 104845. doi:10.1016/j.nsa.2024.104845.
  5.  “Бретисилоцин (5F-MET)”. АИПСИН (in Russian). Retrieved 18 March 2026.
  6.  Peplow M (22 June 2024). “Should Next-Generation Psychedelics Skip the Trip?”. Scientific American. Retrieved 20 February 2025. Gilgamesh is also working on GM-2505, a 5-HT2A agonist that is structurally related to psilocybin and DMT. GM-2505 completed a phase 1 trial late last year and should enter phase 2 for major depressive disorder this year. Its psychedelic effect lasts 60 to 90 minutes — long enough for patients to “explore the altered state of consciousness that might be needed for long-term durable efficacy,” Krugel says, yet within a timeframe that is manageable for healthcare systems. “Personally, I believe that the hallucinogenic effects are an important component, as multiple hallucinogenic compounds have demonstrated durable, transformational changes from a single dose in human studies,” he adds.
  7.  Witkin JM, Golani LK, Smith JL (April 2023). “Clinical pharmacological innovation in the treatment of depression”. Expert Review of Clinical Pharmacology. 16 (4): 349–362. doi:10.1080/17512433.2023.2198703. PMID 37000975. GM-2505 is a dual-acting compound with both agonist activity at 5-HT 2A receptors and a releaser of 5-HT. […]
  8.  “Methods of treating mood disorders”. Google Patents. 2022. Retrieved 14 November 2024.
  9.  Hughes Z, Klein A, Austin E, Dvorak D, Gatti S, Kiss L, et al. (December 2022). “ACNP 61st Annual Meeting: Poster Abstracts P1 – P270: P254. Gm-2505 is a Novel 5-Ht2a Receptor Agonist and 5-Ht Releaser That Induces Rapid, Robust, and Durable Antidepressant Effects at Doses Associated With Decreased Power in Low Frequency EEG Bands in Rats”. Neuropsychopharmacology. 47 (Suppl 1): 63–219 (209–209). doi:10.1038/s41386-022-01484-1. PMC 9714397. PMID 36456693.
  10.  WO 2022/256554, Wallach J, Dybek M, “Fluorinated Tryptamine Compounds, Analogues Thereof, and Methods Using Same”, published 8 December 2022, assigned to University of the Sciences in Philadelphia[…] Synthesis of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12) [structure] N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine (12) was synthesized […] […] Table 1. Selected compounds of the present invention. […] [Compound 12:] […] Table 3. Functional Activity of Compounds at 5-HT2A (Ca2+), 5-HT2B (Ca2+), 5-HT2c (Ca2+), and 5-HT1A (cAMP inhibition) […]
  11.  Hughes Z, Klein A, Dvorak D, Austin E, Kiss L, Marek G, et al. (2023). “22. GM-2505 has Rapid Onset Antidepressant Activity and Causes Dose-Dependent Changes in qEEG With Increasing 5-HT2A Receptor Occupancy”. Biological Psychiatry. 93 (9): S102–S103. doi:10.1016/j.biopsych.2023.02.262.
  12.  Gunther M (31 January 2023). “Gilgamesh Tweaks Known Psychedelics To Improve Therapies”. Lucid News – Psychedelics, Consciousness Technology, and the Future of Wellness. Retrieved 20 February 2025.
  13.  Taylor NP (25 August 2025). “AbbVie tunes in to Gilgamesh’s story, inking $1.2B deal for psychedelic program”. Fierce Biotech. Retrieved 15 October 2025.
  14.  Psychedelic Alpha (25 August 2025). “AbbVie to Acquire Gilgamesh’s Bretisilocin for Up to $1.2B”. Psychedelic Alpha. Retrieved 15 October 2025.
  15.  Halberstadt AL, Geyer MA (2018). “Effect of Hallucinogens on Unconditioned Behavior”. Behavioral Neurobiology of Psychedelic Drugs. Curr Top Behav Neurosci. Vol. 36. pp. 159–199. doi:10.1007/7854_2016_466. ISBN 978-3-662-55878-2. PMC 5787039. PMID 28224459.
  16.  https://iris.who.int/bitstream/handle/10665/380497/9789240107038-eng.pdf “bretisilocinum bretisilocin N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine serotonin (5-HT2A) receptor agonist”
  17.  “Controlled Drugs and Substances Act”. Department of Justice Canada. Retrieved 19 January 2026.
  18.  Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) (PDF), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026
  19.  Psychedelic Alpha (27 May 2025). “Gilgamesh’s Next-Gen Psychedelic GM-2505 Prints Impressive Results in Phase 2a Major Depressive Disorder Study”. Psychedelic Alpha. Retrieved 29 July 2025.
  20.  Taylor NP (27 May 2025). “Gilgamesh links psychedelic to 94% remission rate in midphase depression trial”. Fierce Biotech. Retrieved 29 July 2025.
  21.  Dunne R (31 May 2025). “Gilgamesh’s psychedelic drug demonstrates exceptional efficacy for treating depression”. Mugglehead Investment Magazine. Retrieved 29 July 2025.
  22.  Psychedelic Access and Research European Alliance (2026-03-19). “Bretisilocin Becomes First Psychedelic in EMA PRIME Scheme for Depression”. Drug Policy Tracker. Retrieved 2026-03-29.
  23.  European Medicines Agency (EMA) (2026-03-18). “New PRIME tools to accelerate development of medicines in the EU”. www.ema.europa.eu. Retrieved 2026-03-19.

External links

Clinical data
Other namesGM-2505; GM2505; 5-Fluoro-N-methyl-N-ethyltryptamine; 5F-MET; 5-F-MET; 5-Fluoro-MET
Routes of
administration		Intravenous,[1][2][3][4] intranasal[5]
Drug classSerotonergic psychedelic; Hallucinogen; Serotonin 5-HT2A and 5-HT2C receptor agonist; Serotonin 5-HT2B receptor partial agonist or antagonist; Serotonin releasing agent
Legal status
Legal statusInvestigational
Pharmacokinetic data
Onset of actionIVTooltip Intravenous injection: 10–20 minutes (peak)[2]
Elimination half-life45 (40–50) minutes[2][3]
Duration of actionIVTooltip Intravenous injection: 60–90 minutes[2][6]
Identifiers
IUPAC name
CAS Number2698331-35-8 
PubChem CID156836209
ChemSpider129221851
ChEMBLChEMBL5028766
Chemical and physical data
FormulaC13H17FN2
Molar mass220.291 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

//////////bretisilocin, serotonin (5-HT2A) receptor agonist, GM-2505, GM 2505, 5-Fluoro-N-methyl-N-ethyltryptamine, 5F-MET, 5-F-MET, 5-Fluoro-MET, DS425RQ8SX

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