2,5-Dimethoxy-4-isobutylphenethylamine (2C-iBu or 2C-IB), also known by its developmental code name ELE-02, is a

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

, and anti-inflammatory drug which is under development for the treatment of

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

. It is a member of the phenethylamine and 2C families of compounds. The drug is being developed as a topical eye drop for treatment of inflammatory eye conditions. There is also interest in 2C-iBu and related drugs for treatment of systemic

and neuroinflammation. 2C-iBu was not assessed or discovered by Alexander Shulgin and was not described in ''

PiHKAL ''PiHKAL: A Chemical Love Story'' is a book by Alexander Shulgin and Ann Shulgin published in 1991. The subject of the work is Psychoactive drug, psychoactive phenethylamine Derivative (chemistry), chemical derivatives, notably those that act ...

'' (''Phenethylamines I Have Known and Loved'') (1991). However, he did include 2C-iBu (as "2C-IB") as a DOM analogue in a table in '' The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds'' (2011). In addition, he stated in a footnote that a 5mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

dose of 2C-iBu produces threshold activity and has a long duration of about 20hours. The cited source for these observations, however, was only a 2006 personal communication with "M. Mueller." 2C-iBu was subsequently more thoroughly characterized by Charles D. Nichols and colleagues at Louisiana State University School of Medicine as a novel anti-inflammatory drug in the late 2010s.

Eleusis Elefsina () or Eleusis ( ; ) is a suburban city and Communities and Municipalities of Greece, municipality in Athens metropolitan area. It belongs to West Attica regional unit of Greece. It is located in the Thriasio Plain, at the northernmost ...

has licensed 2C-iBu

intellectual property Intellectual property (IP) is a category of property that includes intangible creations of the human intellect. There are many types of intellectual property, and some countries recognize more than others. The best-known types are patents, co ...

from LSU and the drug has reached the preclinical research stage of development, but no recent development has been reported as of October 2023.

Pharmacology

2C-iBu is a highly potent and robustly efficacious

5-HT_2A receptor

. Its values are 1.3nM for

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

mobilization and 57.5nM for β-arrestin-2 recruitment, whereas its 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 Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

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 , 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

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic effects compared to related drugs like other members of the 2C family. The drug is effective in an

allergic Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

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

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

s, serotonin 5-HT_2A receptor agonists like 2C-iBu are not immunosuppressants.

Chemistry

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

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. Related drugs to 2C-iBu include

2C-Bu 2C-Bu, also known as 2,5-dimethoxy-4-butylphenethylamine, is a chemical compound of the phenethylamine and 2C families. It has been said by Daniel Trachsel to be completely unknown. 2C-Bu is the 2C analogue of the DOx derivative DOBU, which ...

(the butyl analogue), 2C-tBu (the ''tert''-butyl analogue), 2C-sBu (the ''sec''-butyl analogue), and 2C-CPM (the cyclopropyl methyl 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. Moreover, DOTFM has potent psychedelic effects with no anti-inflammatory activity. 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 Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...

of 2C-iBu has been described.

Clinical development

2C-iBu was developed as a novel anti-inflammatory drug by Charles D. Nichols and colleagues at

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. The drug has reached the preclinical research stage of development, but no recent development has been reported as of October 2023. Eleusis has licensed

surrounding 2C-iBu and has patent protection for 2C-iBu.

Legal status

2C-iBu is not a controlled substance in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

as of 2020.

References

External links