HLP003

{{Short description|Serotonergic psychedelic}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = | width = | caption =

<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = Oral<ref name="AdisInsight" /> | class = Serotonergic psychedelic<ref name="AdisInsight" /><ref name="PalfreymanKrakowskyMorgan2022" /> | ATC_prefix = None | ATC_suffix =

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<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = <15 minutes<ref name="HelusPharma2026" /> | elimination_half-life = | duration_of_action = 4–6 hours (humans)<ref name="HelusPharma2026" /> | excretion =

<!-- Identifiers --> | CAS_number = | CAS_supplemental = | PubChem = | PubChemSubstance = | IUPHAR_ligand = | DrugBank = | ChemSpiderID = | UNII = | KEGG = | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms = HLP003; HLP-003; CYB003; CYB-003; Deuterated psilocybin analogue; Deuterated psilocin analogue

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'''HLP003''', or '''HLP-003''', also known as '''deuterated psilocybin analogue''' and formerly as '''CYB003''', is a serotonergic psychedelic related to psilocybin which is under development for the treatment of major depressive disorder, alcoholism, and other psychiatric disorders.<ref name="AdisInsight">{{cite web |title=CYB 003 |website=AdisInsight |date=4 October 2024 |url=https://adisinsight.springer.com/drugs/800062409 |access-date=23 October 2024}}</ref><ref name="Synapse">{{cite web |title=Delving into the Latest Updates on CYB-003 with Synapse |website=Synapse |date=12 October 2024 |url=https://synapse.patsnap.com/drug/dcb535376933495783bad0ae5504a571 |access-date=23 October 2024}}</ref><ref name="CanoDeanAbreu2022">{{cite journal |vauthors=Cano GH, Dean J, Abreu SP, Rodríguez AH, Abbasi C, Hinson M, Lucke-Wold B |title=Key Characteristics and Development of Psychoceuticals: A Review |journal=Int J Mol Sci |volume=23 |issue=24 |date=December 2022 |article-number=15777 |pmid=36555419 |pmc=9779201 |doi=10.3390/ijms232415777 |doi-access=free |url=}}</ref><ref name="DiMartinoMaxwellPirali2023" /><ref name="RheeDavoudianSanacora2023">{{cite journal |vauthors=Rhee TG, Davoudian PA, Sanacora G, Wilkinson ST |title=Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders |journal=Drug Discov Today |volume=28 |issue=12 |article-number=103818 |date=December 2023 |pmid=37925136 |doi=10.1016/j.drudis.2023.103818 |url=}}</ref><ref name="PalfreymanKrakowskyMorgan2022">{{cite journal |vauthors=Palfreyman M, Krakowsky J, Morgan M, Canal C, Pathare P, Avery K, Reichelt A, Hartsel J, Nivorozhkin A, Inamder A, Varty G |title=ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P361. In Vitro and In Vivo Profile of CYB003: A Novel, Deuterated Psilocybin Analog for the Potential Treatment of Major Depressive Disorder |journal=Neuropsychopharmacology |volume=47 |issue=Suppl 1 |pages=220–370 (271) |date=December 2022 |pmid=36456694 |pmc=9714399 |doi=10.1038/s41386-022-01485-0 |url=https://cybin.com/wp-content/uploads/2023/09/ACNP_2022_CYB003_Poster-1.pdf}}</ref><ref name="InamdarMorganKrakowsky2022">{{cite journal |vauthors=Inamdar A, Morgan M, Krakowsky J, Reichelt A, Canal C, Mueller T, Avery K, Pathare P, Hartsel J, Nivorozhkin A, Varty G, Palfreyman M |title=ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P362. Pharmacokinetic Profile of CYB003: A Novel, Deuterated Psilocybin Analog for the Potential Treatment of Major Depressive Disorder |journal=Neuropsychopharmacology |volume=47 |issue=Suppl 1 |pages=220–370 (271–272) |date=December 2022 |pmid=36456694 |pmc=9714399 |doi=10.1038/s41386-022-01485-0 |url=https://cybin.com/wp-content/uploads/2023/09/ACNP-2022-CYB003-Poster-2.pdf}}</ref> It is taken orally.<ref name="AdisInsight" /> The drug is a tryptamine derivative and is a deuterated analogue of psilocybin and psilocin.<ref name="AdisInsight" /><ref name="CanoDeanAbreu2022" /><ref name="DiMartinoMaxwellPirali2023" /><ref name="PalfreymanKrakowskyMorgan2022" />

==Interactions== {{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology== The pharmacodynamic profile of HLP003, including its interactions with serotonin receptors and its effects in animals, is similar to that of psilocin.<ref name="PalfreymanKrakowskyMorgan2022" /> As with psilocin, HLP003 is a potent agonist of the serotonin 5-HT_2A receptor and produces psychedelic-like effects in animals.<ref name="PalfreymanKrakowskyMorgan2022" /> However, it was developed to have improved pharmacokinetic properties compared to psilocybin, including reduced variability in circulating levels, a faster onset of action, and a shorter duration.<ref name="InamdarMorganKrakowsky2022" />

In humans, HLP003 has been reported to have 2.2-fold higher peak levels and 3.5-fold higher area-under-the-curve (AUC) levels than psilocybin at equivalent doses.<ref name="HelusPharma2026">https://s28.q4cdn.com/259445127/files/doc_presentations/2026/Mar/18/Helus-Corporate-Deck-March-18-2026-Final.pdf</ref> It is said to have a rapid onset of less than 15{{nbsp}}minutes and a duration of 4 to 6{{nbsp}}hours.<ref name="HelusPharma2026" />

==Chemistry== thumb|right|200px|class=skin-invert-image|Deupsilocin ({{Abbrlink|INN|International Nonproprietary Name}}; d₁₀-psilocin) structure.

The exact chemical structure of HLP003 (i.e., which specific hydrogen atoms have been deuterated) does not yet seem to have been disclosed.<ref name="DiMartinoMaxwellPirali2023">{{cite journal |vauthors=Di Martino RM, Maxwell BD, Pirali T |title=Deuterium in drug discovery: progress, opportunities and challenges |journal=Nat Rev Drug Discov |volume=22 |issue=7 |pages=562–584 |date=July 2023 |pmid=37277503 |pmc=10241557 |doi=10.1038/s41573-023-00703-8 |url=}}</ref><ref name="CanoDeanAbreu2022" /> However, an {{Abbrlink|INN|International Nonproprietary Name}} of '''''deupsilocin''''' for a deuterated form of psilocin called '''d₁₀-psilocin''' (decadeuteropsilocin) with CAS number 1435934-64-7 was proposed in 2023 and recommended in 2024.<ref name="WHO2023">deupsilocinum deupsilocin 3-[2-{di[(²H₃)methyl]amino}(²H₄)ethyl]-1''H''-indol-4-ol psychodysleptic [...] C₁₂H₆²H₁₀N₂O 1435934-64-7 https://www.who.int/docs/default-source/international-nonproprietary-names-(inn)/pl129.pdf#page=35</ref><ref name="WHO2024">deupsilocinum deupsilocin 3-[2-{di[(²H₃)methyl]amino}(²H₄)ethyl]-1''H''-indol-4-ol [...] C₁₂H₆²H₁₀N₂O https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-%28inn%29/rl91.pdf</ref><ref name="US11000534">{{cite patent | country = US | number = 11000534 | inventor = Bradford Sippy | status = | title = Deuterated Derivatives of Psilocybin and Uses Thereof | pubdate = 11 May 2021 | gdate = 11 May 2021 | fdate = 10 December 2020 | pridate = 10 December 2020 | assign1 = Lennham Pharmaceuticals, Inc. | url = }}</ref><ref name="PubChem">{{cite web | title=Deupsilocin | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/117065176 | access-date=19 February 2026}}</ref> This deuterated analogue of psilocin has been patented by Helus Pharma (formerly Cybin) as well as by Lennham Pharmaceuticals.<ref name="ButlerCaponBlaskovich2026">{{cite journal | vauthors = Butler MS, Capon RJ, Blaskovich MA, Henderson IR | title = Natural product-derived compounds in clinical trials and drug approvals | journal = Nat Prod Rep | volume = 43 | issue = 1 | pages = 20–88 | date = January 2026 | pmid = 40923383 | doi = 10.1039/d5np00031a | url = | quote = In addition, Cybin is advancing CYB003, a deuterated psilocin that recently completed a phase I/II trial (NCT05385783) for MDD.242 While its structure has not been disclosed, Cybin's patents include psilocin-D10 4.21 and related analogues.243 [...] 242 Cybin, CYB003: Deuterated psilocin program with FDA breakthrough therapy designation, https://cybin.com/ cyb003/, accessed 7 April 2025. 243 A. Nivorozhkin, M. Palfreyman, P. Pathare, K. L. Avery, M. Shukoor, J. H. Huang, M. E. Morgan and J. M. Krakowsky, World Pat., WO2022195011A1, 2022.}}</ref><ref name="WO2022195011">{{cite web | title=Psilocybin analogs, salts, compositions, and methods of use | website=Google Patents | date=17 March 2022 | url=https://patents.google.com/patent/WO2022195011A1/en | access-date=19 February 2026}}</ref><ref name="US11000534" /> Helus Pharma has also patented other deuterated psilocin analogues.<ref name="US20230357147A1">{{cite web |title=Deuterated tryptamine derivatives and methods of use |website=Google Patents |date=17 July 2023 |url=https://patents.google.com/patent/US20230357147A1/en |access-date=23 October 2024 |quote=Binding affinity (Ki) and functional potency (EC50) values of PI and PI-α-d2 are summarized in Table 1. Deuteration was found to have little effect on the affinity and function at key receptor targets. [...] TABLE 1: PI and PI-α,α-d2 Affinities and Functions at Target Serotonin Receptors [...]}}</ref> Other deuterated drugs related to HLP003 or deupsilocin/d₁₀-psilocin include the deuterated DMT analogues HLP004 (CYB004) and SPL028 and the deuterated phenethylamine HLP005 (CYB005).<ref name="CanoDeanAbreu2022" /><ref name="Peplow2024">{{cite journal | vauthors = Peplow M | title = Next-generation psychedelics: should new agents skip the trip? | journal = Nat Biotechnol | volume = 42 | issue = 6 | pages = 827–830 | date = June 2024 | pmid = 38831049 | doi = 10.1038/s41587-024-02285-1 | url = }}</ref>

==Research== In 2024, HLP003 received a breakthrough therapy designation from the U.S. FDA<ref name="Jenkins 2024">{{cite web |last=Jenkins |first=Cassandra |title=FDA grants breakthrough designation to psilocybin analog for major depressive disorder |website=Healio |date=19 March 2024 |url=https://www.healio.com/news/psychiatry/20240319/fda-grants-breakthrough-designation-to-psilocybin-analog-for-major-depressive-disorder |access-date=7 August 2025}}</ref> and was in phase 3 clinical trials for major depressive disorder and is in the preclinical stage of development for alcoholism and other psychiatric disorders.<ref name="AdisInsight" /><ref name="Synapse" /><ref name="Kuntz 2025">{{cite web |last=Kuntz |first=Leah |title=CYB003 for the Adjunctive Treatment of Major Depressive Disorder |website=Psychiatric Times |date=10 February 2025 |url=https://www.psychiatrictimes.com/view/cyb003-for-the-adjunctive-treatment-of-major-depressive-disorder |access-date=7 August 2025}}</ref> Two phase 3 clinical trials for major depressive disorder are being initiated in November 2024 and February 2025.<ref name="AdisInsight" /><ref name="Synapse" /><ref name="Kuntz 2025"/> The drug is under development by Helus Pharma (formerly Cybin).<ref name="AdisInsight" /><ref name="Synapse" /><ref name="Kuntz 2025"/>

== See also == * Substituted tryptamine * List of investigational hallucinogens and entactogens * List of investigational antidepressants * Deudimethyltryptamine * Deuterated 5-MeO-DMT

== References == {{Reflist}}

== External links == * [https://cybin.com/cyb003/ CYB003 – Cybin]

{{Psychedelics}} {{Serotonin receptor modulators}} {{Tryptamines}}

Category:5-HT2A agonists Category:Deuterated psychedelics Category:N,N-Dialkyltryptamines Category:Drugs with undisclosed chemical structures Category:Experimental antidepressants Category:Experimental hallucinogens Category:Experimental psychiatric drugs Category:4-Hydroxytryptamines Category:Psychedelic tryptamines Category:Serotonin receptor agonists