2C-iBu

2C-iBu is a highly potent and robustly efficacious serotonin 5-HT_2A receptor agonist. Its {{Abbrlink|EC₅₀|half-maximal effective concentration}} values are 1.3{{nbsp}}nM for calcium mobilization and 57.5{{nbsp}}nM for β-arrestin-2 recruitment, whereas its {{Abbrlink|E_max|maximal efficacy}} values are 103% for calcium mobilization and 77% for β-arrestin-2 recruitment relative to serotonin. The drug showed higher potency and efficacy as a serotonin 5-HT_2A receptor agonist than several other 2C drugs, including 2C-NP, 2C-B, 2C-I, 2C-H, and 2C-iP, whereas its activities were more comparable to or less than those of the DOx drugs DOIB, (R)-DOB, (R)-DOI, and DOiP. 2C-iBu has also been assessed and found to bind to other serotonin receptors, including the serotonin 5-HT_2C, 5-HT_2B, 5-HT_1B, 5-HT_1D, 5-HT_1A, 5-HT₇, and 5-HT₆ receptors, in that order of affinity and with varying avidities.

2C-iBu dose-dependently produces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents. In terms of {{Abbrlink|ED₅₀|median effective dose}}, 2C-iBu is about 3-fold less potent than (R)-DOI in producing the HTR. According to Eleusis, it is expected to have "greatly reduced" psychoactivity or hallucinogenic effects compared to related drugs like other members of the 2C family.{{cite web | vauthors = Newvine C | title=Eleusis Draws on Research Into Psychedelics To Develop New Medicines for Inflammation | website=Lucid News - Psychedelics, Consciousness Technology, and the Future of Wellness | date=8 July 2020 | url=https://www.lucid.news/eleusis-research-on-psychedelics-develop-inflammation-medicines/ | access-date=16 February 2025}}

The drug is effective in an allergic asthma model in rodents and showed similar potency as (R)-DOI. Due to its reduced potency in producing the HTR but retained anti-inflammatory potency, 2C-iBu is expected to show greater separation between the desired anti-inflammatory and the undesired psychedelic effects in humans compared to (R)-DOI. In contrast to certain other anti-inflammatory drugs like corticosteroids, serotonin 5-HT_2A receptor agonists like 2C-iBu are not immunosuppressants.{{cite web | vauthors = Lekhtman A | title=Researcher Charles Nichols Studies the Impact of Psychedelic Substances on Inflammation | website=Lucid News - Psychedelics, Consciousness Technology, and the Future of Wellness | date=8 July 2020 | url=https://www.lucid.news/researcher-charles-nichols-studies-the-impact-of-psychedelic-substances-on-inflammation/ | access-date=16 February 2025}}

2C-iBu, also known as 2,5-dimethoxy-4-isobutylphenethylamine, is a phenethylamine and 2C derivative.

Related drugs to 2C-iBu include 2C-Bu (the butyl analogue), 2C-tBu (the tert-butyl analogue), 2C-sBu (the sec-butyl analogue), and 2C-CPM (the cyclopropylmethyl analogue). In addition, 2C-iBu is related to DOx drugs such as DOIB (DOiBu).

According to Charles D. Nichols, 2,5-dimethoxyamphetamine (2,5-DMA) has potent anti-inflammatory activity with weak or no hallucinogenic effects.{{cite journal | vauthors = Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD | title = Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore | journal = ACS Pharmacol Transl Sci | volume = 4 | issue = 2 | pages = 488–502 | date = April 2021 | pmid = 33860179 | pmc = 8033619 | doi = 10.1021/acsptsci.0c00063 | url = https://www.researchgate.net/publication/360537036 | quote=The nature of the 4-position substituent of phenethylamine psychedelics has been previously linked to 5-HT2 receptor selectivity as well as agonist properties at 5-HT2 receptors.40 Analysis of the 4-position demonstrated that the identity of the moiety at this position was rather flexible. Fully efficacious substitutions at the 4-position included the halogens iodine and bromine (R)-DOI (Figure 3), 2C-B (Figure 7A), methoxy (TMA-2) (Figure 7G), short-chain hydrocarbons (R)-DOM (Figure 7H), (R)-DOET) (Figure 7I), and a branched hydrocarbon (DOiBu) (Figure 7J). [...] In a comparison of PenH-AUC values determined for each drug as a proxy measure of anti-inflammatory efficacy (Figure 8A) to either EC50 or EMax for calcium mobilization downstream of 5- HT2A receptor activation (Table 1), [...]}} Moreover, DOTFM has potent psychedelic effects with no anti-inflammatory activity.{{cite journal | vauthors = Flanagan TW, Billac G, Nichols CD | title=Differential Regulation of Inflammatory Responses Following 5-HT 2 Receptor Activation in Pulmonary Tissues | journal=The FASEB Journal | volume=36 | issue=S1 | date=2022 | issn=0892-6638 | doi=10.1096/fasebj.2022.36.S1.R2617 | page=| doi-access=free }}{{cite journal | vauthors = Flanagan TW, Foster TP, Galbato TE, Lum PY, Louie B, Song G, Halberstadt AL, Billac GB, Nichols CD | title = Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression | journal = ACS Pharmacology & Translational Science | volume = 7 | issue = 2 | pages = 478–492 | date = February 2024 | pmid = 38357283 | pmc = 10863441 | doi = 10.1021/acsptsci.3c00297 | quote = The effects of (R)-DOTFM were examined in the head-twitch response (HTR) assay. (R)-DOTFM produced a strong HTR with a potent ED 50 of 0.60 μmol/kg. These values are equivalent to (R)-DOI, as previously determined. }} Hence, it appears that the anti-inflammatory effects and psychedelic effects of serotonin 5-HT_2A receptor agonists can be fully dissociated.

The chemical synthesis of 2C-iBu has been described.

2C-iBu was developed as a novel anti-inflammatory drug by Charles D. Nichols and colleagues at Eleusis in the late 2010s. They are developing it for treatment of inflammatory conditions. Eleusis was acquired by and merged into Beckley Psytech in October 2022.{{cite web | vauthors = Gunther M | title=What's the Future of Eleusis Therapeutics After Acquisition by Beckley Psytech? | website=Lucid News - Psychedelics, Consciousness Technology, and the Future of Wellness | date=26 October 2022 | url=https://www.lucid.news/eleusis-therapeutics-acquisition-by-beckley-psytech/ | access-date=17 February 2025}}{{cite web | title=Beckley Psytech Strengthens Pipeline and Development Team With Acquisition of Eleusis Therapeutics Limited | website=Psychedelic Alpha | date=24 October 2022 | url=https://psychedelicalpha.com/news/beckley-psytech-strengthens-pipeline-and-development-team-with-acquisition-of-eleusis-therapeutics-limited | access-date=17 February 2025}} The drug has reached the preclinical research stage of development, but no recent development has been reported as of October 2023. Eleusis has licensed intellectual property surrounding 2C-iBu and has patent protection for 2C-iBu.

2C-iBu is not a controlled substance in the United States as of 2020.

• 5-HT_2A receptor § Anti-inflammatory effects

{{Reflist}}

• [https://isomerdesign.com/pihkal/explore/7302 2C-IB - isomer design]
• [https://www.patreon.com/posts/podcast-33-with-58708009 PODCAST 33: An interview with Dr. Charles D. Nichols (November 14, 2021) - The Hamilton Morris Podcast] (discusses 2C-iBu/ELE-02 from 48:22 to 53:56)

{{Psychedelics}}

{{Serotonin receptor modulators}}

{{Phenethylamines}}

Category:5-HT2A agonists

Category:2C (psychedelics)

Category:Anti-inflammatory agents

Category:Experimental drugs

Category:Isobutyl compounds

Category:Psychedelic phenethylamines

Category:Serotonin receptor agonists