MEAI, also known as 5-methoxy-2-aminoindane (5-MeO-AI), is a

monoamine releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrati ...

of the 2-aminoindane group. It specifically acts as a

selective serotonin releasing agent A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter ...

(SSRA). The drug is under development for the treatment of

alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...

cocaine use disorder Cocaine dependence is a neurological disorder that is characterized by withdrawal symptoms upon cessation from cocaine use. It also often coincides with cocaine addiction which is a biopsychosocial disorder characterized by persistent use of coc ...

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...

, and

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

under the developmental code name CMND-100.

Effects

When used recreationally, MEAI is reported to produce mild

psychoactive A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

effects and

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

Pharmacology

Pharmacodynamics

MEAI is a

(MRA). It is a modestly selective

serotonin releasing agent A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter ...

(SSRA), with 6-fold preference for induction of

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, ...

release over

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

release and 20-fold preference for induction of serotonin release over

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

release. In addition to inducing

monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ...

release, MEAI has moderate

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 ...

for the α₂-adrenergic receptor. Based on these findings, MEAI might produce

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

-like

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

ic and sympathomimetic effects but may be expected to have reduced

misuse liability Substance misuse, also known as drug misuse or, in older vernacular, substance abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder, differing definitions ...

in comparison.

Chemistry

MEAI, also known as 5-methoxy-2-aminoindane, is a 2-aminoindane

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 ...

. It is the 2-aminoindane analogue of the

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

3-methoxyamphetamine 3-Methoxyamphetamine (3-MA), also known as ''meta''-methoxyamphetamine (MMA), is a monoamine releasing agent (MRA) of the amphetamine family. It is a positional isomer of ''para''-methoxyamphetamine (PMA; 4-methoxyamphetamine). Effects Accord ...

History

MEAI appears to have been first synthesized in 1956. Its molecular structure was first mentioned implicitly in a

markush structure A Markush structure, Markush group, or a Markush claim is a representation of alternatively useable members. Markush structures are frequently used with chemical structures to indicate a group of related chemical compounds. They are commonly used ...

schema appearing in a patent from 1998. It was later explicitly and pharmacologically described in a peer reviewed paper in 2017 by

David Nutt David John Nutt (born 16 April 1951) is an English neuropsychopharmacologist specialising in the research of drugs that affect the brain and conditions such as addiction, anxiety, and sleep. He is the chairman of Drug Science, a non-profit ...

and Ezekiel Golan et al. followed by another in February 2018 which detailed the

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

and metabolism of MEAI by Shimshoni, David Nutt, Ezekiel Golan et al. One year later it was studied and reported on in another peer reviewed paper by Halberstadt et al. The aminoindane family of molecules was, perhaps, first chemically described in 1980.

Alcohol substitute

MEAI was an early candidate of

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

replacement drugs that came to market during a late 2010s movement to replace alcohol with less-toxic alternatives spearheaded by British psychopharmacologist

rippling to the rest of Europe. In an act of

gonzo journalism Gonzo journalism is a style of journalism that is written without claims of objectivity, often including the reporter as part of the story using a first-person narrative. The word "gonzo" is believed to have been first used in 1970 to descri ...

, Michael Slezak writing for

New Scientist ''New Scientist'' is a popular science magazine covering all aspects of science and technology. Based in London, it publishes weekly English-language editions in the United Kingdom, the United States and Australia. An editorially separate organ ...

, tried and reported on his experience with MEAI after being provided with it by Dr Zee ( Ezekiel Golan) following an interview. Golan claimed that he invented MEAI and originally intended for it to be sold as a legal high but changed his mind, indicating plans to work with Nutt and his compan
DrugScience
The goal was to develop MEAI further based on Golan's patents as a "binge behaviour regulator" and "alcoholic beverage substitute". In 2018, a company named Diet Alcohol Corporation of the Americas (DACOA) began openly marketing an MEAI-based drink called "Pace" for sale in the USA and Canada. Pace was described as a 50ml bottle containing 160 mg of MEAI in mineral water. Distribution halted after

Health Canada Health Canada (HC; )Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary units, department of the Gove ...

released a warning indicating the substance was considered illegal to market for consumption in Canada due to structural similarity to amphetamine. In a December 2018 article by

CBC News CBC News is the division of the Canadian Broadcasting Corporation responsible for the news gathering and production of news programs on the corporation's English-language operations, namely CBC Television, CBC Radio, CBC News Network, and CBC ...

, Dr Zee ( Ezekiel Golan) was interviewed and publicly came out as the "lead scientist" of Pace claiming "tens of thousands" of bottles were already sold in Canada. Golan claimed the MEAI featured in Pace was "manufactured in India" and "bottled in Delaware".

provided a statement to CBC News stating "Pace is an illegal and unauthorized product in Canada."

Pharmaceutical development

On May 26, 2022, MEAI was prepared for

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

registration b
Clearmind Medicine Inc.
Clearmind Medicine claims wide intellectual property holdings to Ezekiel Golan's patents. In March 2022 Clearmind Medicine announced supportive evidence from animal studies in mice attesting to suppression of alcohol consumption. In June 2022 Clearmind Medicine announced promising results from animal studies that showed promise for treating cocaine addiction with MEAI. MEAI, under the developmental code name CMND-100, is under development by Clearmind Medicine for the treatment of

, and

. As of October 2024, it is in the preclinical stage of development for these indications.

References

External links

Information Video About Alcohol Consumption
{{Monoamine releasing agents 2-Aminoindanes Designer drugs Entactogens Experimental entactogens Experimental psychiatric drugs Methoxyphenethylamines Monoamine releasing agents Phenol ethers