5-Methoxy-2-aminoindane (MEAI): A Comprehensive Profile

1. Introduction

5-Methoxy-2-aminoindane (MEAI) is a psychoactive compound belonging to the aminoindane chemical class.[1] Also known by synonyms such as 5-MeO-AI and the developmental code name CMND-100 [4], this molecule has garnered attention for its dual identity. It initially emerged within the informal market of novel psychoactive substances (NPS), often promoted as an "alcohol alternative" capable of inducing mild euphoria and an alcohol-like experience alongside a reported reduction in the desire for further alcohol consumption.[2] Concurrently, these very characteristics have propelled MEAI into formal scientific investigation, with Clearmind Medicine Inc. advancing it under the name CMND-100 for therapeutic applications, most notably for Alcohol Use Disorder (AUD).[5]

The significance of MEAI is rooted in this juxtaposition. Its journey from an obscure chemical, first synthesized in the mid-20th century [2], to a recreational substance and subsequently a candidate for clinical development reflects a broader trend in psychopharmacology. This trend involves the systematic re-evaluation of psychoactive compounds, whose effects may have initially become known through non-medical use, for their potential therapeutic utility. This pathway, similar to that of substances like ketamine or MDMA, presents unique opportunities for innovation but also considerable challenges regarding regulation, public perception, and the rigorous scientific validation required to distinguish anecdotal claims from evidence-based medical applications.

The concurrent existence of MEAI as a compound pursued for medical approval (CMND-100 for AUD [10]) and its past marketing in unregulated forms (e.g., "Pace" [7]) creates a complex socio-regulatory environment. While "Pace" faced legal challenges, for instance, from Health Canada due to its structural similarity to amphetamine [4], CMND-100 is progressing through formal clinical trials under an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA).[10] This divergence highlights how the intended use and regulatory pathway can lead to different classifications and acceptance of a substance. This dual identity means MEAI is viewed through different lenses: as a recreational drug, a potential therapeutic agent, or a substance of regulatory concern. Such complexities can influence public perception and the scrutiny it faces during its development as a pharmaceutical.

This report aims to provide a comprehensive, expert-level overview of 5-Methoxy-2-aminoindane. It synthesizes available scientific data and anecdotal information from provided research, covering its chemical and physical properties, detailed pharmacology (pharmacodynamics and pharmacokinetics), history of development and use, psychoactive effects, therapeutic applications under investigation, safety and toxicology profile, and its current legal status across key jurisdictions.

2. Chemical and Physical Properties

A precise understanding of the chemical and physical characteristics of 5-Methoxy-2-aminoindane (MEAI) is fundamental for its study and potential application. The compound is typically encountered and researched in its hydrochloride salt form, which generally offers improved stability and solubility over the freebase.

Nomenclature:

• IUPAC Name: The systematic name for the freebase form is 5-methoxy-2,3-dihydro-1H-inden-2-amine.[11] For its commonly used salt form, the IUPAC name is 5-methoxy-2,3-dihydro-1H-inden-2-amine;hydrochloride [11] or, alternatively, 2,3-dihydro-5-methoxy-1H-Inden-2-amine, monohydrochloride.[13]
• Common Names/Synonyms: MEAI is the most prevalent acronym. Other designations include 5-MeO-AI [4], 5-methoxy-2-aminoindan [4], and historically, Chaperon (as Chaperon hydrochloride).[4] In the context of therapeutic development, Clearmind Medicine refers to MEAI as CMND-100.[4]
• CAS Registry Number:
• For MEAI hydrochloride (MEAI HCl): 81593-54-6 is consistently cited.[11]
• For the freebase form: While not explicitly and consistently provided, CAS 73305-09-6 is listed by Chemsrc for "5-methoxy-2,3-dihydro-1H-inden-2-amine".[12] However, this source also associates this CAS number with the molecular formula C₁₀H₁₄ClNO and a molecular weight of 199.677 g/mol, which are characteristic of the hydrochloride salt. This discrepancy highlights the importance of careful verification of the specific form of MEAI being referenced.

Molecular Structure and Formula:

• MEAI Hydrochloride: The molecular formula is C₁₀H₁₄ClNO [11] or, more explicitly showing the salt, C₁₀H₁₃NO·HCl.[13] The structure is a bicyclic amine derivative, specifically an indane scaffold substituted with a methoxy group at the 5-position and an amino group at the 2-position.[11]
• MEAI Freebase: The molecular formula is C₁₀H₁₃NO.[18]
• Canonical SMILES (for HCl salt): COC1=CC2=C(CC(C2)N)C=C1.Cl.[11]
• InChI (for HCl salt): InChI=1S/C10H13NO.ClH/c1-12-10-3-2-7-4-9(11)5-8(7)6-10;/h2-3,6,9H,4-5,11H2,1H3;1H.[11]
• InChI Key (for HCl salt): UXHKKYAVZDAYIG-UHFFFAOYSA-N.[11]

Key Physicochemical Properties:

The consistent reporting of MEAI as its hydrochloride salt in chemical databases suggests this form is preferred for research, likely due to better stability and handling characteristics, particularly solubility in aqueous or polar organic solvents, compared to the freebase. This preference is common in pharmaceutical development for amine-containing compounds.

Property	MEAI Freebase Value (Source)	MEAI Hydrochloride Value (Source)
IUPAC Name	5-methoxy-2,3-dihydro-1H-inden-2-amine 11	5-methoxy-2,3-dihydro-1H-inden-2-amine;hydrochloride 11 or 2,3-dihydro-5-methoxy-1H-Inden-2-amine, monohydrochloride 13
Common Synonyms	MEAI, 5-MeO-AI, CMND-100 4	MEAI HCl, Chaperon hydrochloride 4
CAS Registry Number	73305-09-6 (see note above) 12	81593-54-6 11
Molecular Formula	C₁₀H₁₃NO 18	C₁₀H₁₄ClNO 11 or C₁₀H₁₃NO·HCl 13
Molecular Weight	Avg: 163.22 g/mol; Mono: 163.099714 g/mol 18	~199.68 g/mol 11
Appearance	Not specified; Pace drink was clearish-yellow liquid 7	Not specified
Solubility	Not specified	Soluble in polar solvents.11 DMF: 5 mg/mL; DMSO: 15 mg/mL; DMSO:PBS (pH 7.2) (1:1): 0.5 mg/mL; Ethanol: 10 mg/mL.13
Spectroscopic Data: UV Max	Not specified	225, 281 nm 13
Spectroscopic Data: ¹H NMR	Not specified	(400 MHz, D₂O): δ 6.75 (d, J=8.4 Hz, 1H, ArH), 6.55 (s, 1H, ArH), 3.80 (s, 3H, OCH₃), 3.30–3.10 (m, 2H, CH₂), 2.90–2.70 (m, 1H, CH), 2.20–1.90 (m, 2H, CH₂).11
Spectroscopic Data: IR (KBr)	Not specified	3350 cm⁻¹ (N–H stretch), 1600 cm⁻¹ (C=C aromatic).11

Structural Classification:

MEAI is an aminoindane derivative.1 The aminoindanes are a class of compounds that can be viewed as semi-rigid congeners of phenylethylamines.13 The indane structure, formed by a five-membered ring fused to a benzene ring, imparts conformational restriction to the phenylethylamine pharmacophore. MEAI is also described as an amphetamine analog with a rigid conformation 19 and, more specifically, as the 2-aminoindane analogue of 3-methoxyamphetamine.4

This structural relationship to phenylethylamines, such as amphetamine and MDMA, is significant. It provides a basis for predicting its interaction with monoaminergic systems in the brain, which are common targets for these psychoactive substances. The methoxy group (OCH3​) at the 5-position of the indane's aromatic ring is a critical feature, as substitutions on the aromatic ring of phenylethylamines are known to profoundly influence pharmacological activity and selectivity (e.g., the methylenedioxy group in MDMA). The conformational rigidity imposed by the indane structure, combined with the specific methoxy substitution, likely contributes to MEAI's distinct pharmacological profile compared to more flexible phenylethylamines or other aminoindane derivatives. This structural similarity also underpins why regulatory bodies, such as Health Canada, have considered it an analogue of amphetamine [4], impacting its legal status irrespective of its specific pharmacological actions.

3. Pharmacology

The pharmacological profile of 5-Methoxy-2-aminoindane (MEAI) is central to understanding both its observed psychoactive effects and its emerging therapeutic potential. Its actions are primarily mediated through interactions with monoamine neurotransmitter systems.

3.1. Pharmacodynamics

Classification: MEAI is a psychoactive compound [1] belonging to the aminoindane chemical class. Its primary pharmacological action is as a monoamine releasing agent (MRA).[4] More specifically, MEAI is characterized by its modest selectivity as a serotonin releasing agent (SSRA).[4]

Mechanism of Action - Primary (Monoamine Release):

MEAI exerts its effects by interacting with plasma membrane monoamine transporters—SERT (serotonin), NET (norepinephrine), and DAT (dopamine)—acting as a substrate-type releaser.2 This means it is transported into the presynaptic neuron and triggers the reverse transport (efflux) of these neurotransmitters from the neuron into the synaptic cleft.

• Selectivity: A key feature of MEAI's pharmacodynamic profile is its preference for serotonin release. Studies using rat brain synaptosomes have quantified this selectivity, showing approximately a 6-fold preference for inducing serotonin release over norepinephrine release, and a more pronounced 20-fold preference for serotonin release over dopamine release.[4] This profile distinguishes it from non-selective releasers like MDMA or predominantly dopaminergic stimulants like amphetamine.
• Potency (EC₅₀ values for monoamine release in rat brain synaptosomes):
• Serotonin (SERT): 134 nM [4]
• Norepinephrine (NET): 861 nM [4]
• Dopamine (DAT): 2,646 nM [4] The considerably higher EC₅₀ value for dopamine release compared to serotonin release is a critical aspect of its pharmacology. Dopamine release is strongly implicated in the rewarding and abuse-related effects of many psychoactive substances. MEAI's relatively weak effect on dopamine release is hypothesized to contribute to its reportedly milder psychoactive profile and potentially lower abuse liability compared to substances like MDMA or amphetamine, which have more potent actions on dopamine systems.[4]

Mechanism of Action - Secondary/Other Receptor Interactions:

Beyond monoamine release, MEAI has been shown to interact with other receptor systems, although these are generally considered secondary to its primary action as an SSRA:

• α₂-Adrenergic Receptors: MEAI exhibits moderate affinity for α₂-adrenergic receptors.[4] The parent compound, 2-aminoindane (2-AI), has a notable affinity for α₂C receptors (Ki = 41 nM) and somewhat lower affinity for α₂A and α₂B subtypes.[2] The implications of MEAI's α₂-adrenergic activity on its overall effects are not fully elucidated but could contribute to some of its physiological or psychoactive properties.
• 5-HT₂B Receptors: Weak to moderate ligand binding inhibition has been reported at the 5-HT₂B receptor.[2] This interaction warrants attention, as 5-HT₂B receptor agonism has been linked to cardiac valvulopathy with some chronic drug exposures (e.g., fenfluramine). However, MEAI's effect is described as inhibitory and moderate, which may have different implications than agonism.
• 5-HT₁A Receptors: Clearmind Medicine hypothesizes that MEAI's therapeutic effects in AUD may involve interaction with 5-HT₁A receptors, leading to decreased impulsivity and "sensible behaviour".[5] Direct binding data or functional assays for MEAI at 5-HT₁A receptors are not detailed in the provided snippets, but this remains an important area for its therapeutic mechanism exploration.
• Other Targets: One study indicated that other neurochemical targets beyond those mentioned were largely unaffected by MEAI.[2] An isolated finding mentioned a structurally related "imidazo-oxazole moiety with the indane amine" as a human constitutive androstane receptor (CAR) agonist [11], but its direct relevance to MEAI itself requires clarification.

Comparison with Related Compounds:

Understanding MEAI's pharmacology is aided by comparing it to structurally or functionally related compounds:

Compound	SERT EC₅₀ (nM)	NET EC₅₀ (nM)	DAT EC₅₀ (nM)	SERT/DAT Ratio	SERT/NET Ratio	Primary Profile	Source(s)
MEAI	134	861	2,646	~19.7	~6.4	SSRA	4
2-AI	>10,000	86	439	<0.04	<0.008	NET/DAT Releaser	4
MDAI	114	117	1,334	~11.7	~1.0	SNRA	4
MMAI	31	3,101	>10,000	>322	~100	SSRA (potent)	3
d-Amphetamine	698–1,765	6.6–7.2	5.8–24.8	~0.003-0.03	~0.004-0.01	DAT/NET Releaser	4
MDMA	50–85	54–110	51–278	~0.18-1.6	~0.45-1.5	SNDRA	4

EC₅₀ values are for monoamine release in rat brain synaptosomes. Ratios are approximate.

This comparative data underscores MEAI's distinct profile. Unlike amphetamine (primarily a DAT/NET releaser) or MDMA (a more balanced SNDRA), MEAI's action is predominantly serotonergic. This selective serotonergic action, particularly its relatively weak impact on dopamine release, is thought to be the basis for its unique subjective effects—often described as "alcohol-like" (less overtly stimulating than classical stimulants)—and is also the rationale behind predictions of a potentially lower abuse liability compared to more dopaminergic compounds.[1]

The hypothesized involvement of 5-HT₁A receptors in MEAI's effects [5], particularly in reducing impulsivity, suggests a more nuanced therapeutic mechanism than simple substitution of alcohol's acute effects. 5-HT₁A receptor agonists are known for anxiolytic and anti-impulsive properties. If MEAI directly or indirectly modulates 5-HT₁A activity significantly, this could be a key factor in its potential anti-craving and anti-binge effects observed anecdotally and pursued therapeutically.

3.2. Pharmacokinetics

Pharmacokinetic data for MEAI are primarily derived from studies in rats, as human clinical trial data is still emerging.

Absorption:

Following oral administration in rats, MEAI is rapidly absorbed, with peak concentrations in the brain achieved quickly.2

Distribution:

MEAI demonstrates good penetration into the central nervous system. In rats, the plasma-to-brain concentration ratio was reported to be in the range of 3 to 5.5, indicating that the compound readily crosses the blood-brain barrier and achieves higher concentrations in brain tissue relative to plasma.2

Metabolism:

• In rats, MEAI undergoes metabolism primarily through N-acetylation and oxidative demethylation.[2]
• The two principal metabolites identified are N-acetyl-MEAI and 5-hydroxy-N-acetyl-AI.[2]
• Levels of the N-acetyl-MEAI metabolite in both plasma and brain were found to be approximately tenfold lower than those of the parent compound. This suggests that N-acetyl-MEAI likely contributes minimally to the overall pharmacological effects of MEAI.[2]

Elimination and Clearance:

• MEAI shows extensive total clearance in rats, reported as 2.8 L/h/kg.[2]
• The plasma and brain half-life (t1/2​) in rats is very short at lower doses, approximately 0.5 to 0.7 hours.[2]

Bioavailability and Dose-Dependency:

A critical aspect of MEAI's pharmacokinetics in rats is its dose-dependent, non-linear behavior:

• At an oral dose of 10 mg/kg, MEAI exhibited low oral bioavailability (approximately 25%).[2]
• However, at a higher oral dose of 90 mg/kg, a significant non-linear pharmacokinetic profile emerged. Bioavailability increased substantially, by as much as 500%, and there was a notable increase in the plasma half-life of both MEAI and its N-acetyl metabolite.[2]

This non-linear pharmacokinetic behavior at higher doses is a significant finding. A five-fold increase in bioavailability with a nine-fold increase in dose suggests saturation of first-pass metabolic pathways or other clearance mechanisms at higher concentrations. If this non-linearity translates to humans, it implies that dose escalations, particularly at the higher end of the therapeutic range, must be approached with considerable caution, as small increments in dose could lead to disproportionately large increases in systemic exposure and potentially an increased risk of adverse effects or toxicity. Clearmind Medicine has mentioned a "longtail tapering off of activity via oral administration" which "may explain the self-limiting property of MEAI".[20] This claim needs to be carefully reconciled with the pharmacokinetic data; while a longer half-life at higher doses due to saturation could contribute to a prolonged effect, the "self-limiting" aspect might also relate to subjective effects becoming less desirable or more aversive at higher exposures, rather than solely a pharmacokinetic phenomenon. The Phase I/IIa human trials will be crucial in characterizing human pharmacokinetics and determining if similar non-linearity exists.

Table: Summary of Key Pharmacokinetic Parameters of MEAI (in Rats)

Parameter	Value (10 mg/kg oral)	Value (90 mg/kg oral)	Value (10 mg/kg IV)	Source(s)
Bioavailability (F%)	25%	Increased by 500% (relative to expected linear increase)	N/A	2
Tmax (h)	Rapid peak brain levels	Not specified	Not specified	2
Half-life (t1/2​, h)	0.5–0.7 (plasma & brain)	Significantly increased	Not specified	2
Total Clearance (CL)	2.8 L/h/kg	Reduced (implied by increased t1/2​ and F%)	N/A	2
Plasma to Brain Ratio	3–5.5	Not specified	Not specified	2
Major Metabolites Identified	N-acetyl-MEAI, 5-hydroxy-N-acetyl-AI	N-acetyl-MEAI, 5-hydroxy-N-acetyl-AI	N/A	2

4. History and Development

The trajectory of 5-Methoxy-2-aminoindane (MEAI) spans several decades, evolving from an early synthetic compound with limited initial study to a substance recognized in recreational drug markets, and now, a candidate for formal therapeutic development.

Initial Synthesis and Early Research:

MEAI appears to have been first synthesized in 1956, with early evaluations focusing on its potential analgesic effects in mice.2 The broader class of aminoindanes, to which MEAI belongs, was explored for various medical applications, including as anti-Parkinsonian drugs, as early as the 1970s.19 For instance, Martin et al. designed aminoindanes based on Kier's receptor mapping technique with the aim of developing anti-Parkinsonian agents.19 The specific molecular structure of MEAI was implicitly mentioned within a Markush structure schema in a patent dating back to 1998.4 However, more explicit pharmacological descriptions in peer-reviewed literature began to emerge significantly later, around 2017, with contributions from researchers including David Nutt and Ezekiel Golan.4

Emergence as a Recreational Substance and "Alcohol Substitute":

In more recent years, MEAI gained notoriety as a novel psychoactive substance (NPS). It became popular among recreational users, particularly in the United Kingdom, who reported mild euphoric effects and an experience akin to alcohol intoxication.1 This led to its marketing as an "alcohol alternative." Around 2018, a product named "Pace," containing MEAI, was marketed by the Diet Alcohol Corporation of the Americas (DACOA).4 Pace was typically sold as a 50ml bottle containing 160 mg of MEAI dissolved in mineral water.4

Ezekiel Golan, who has been involved in the synthesis of other psychoactive compounds, claims to have invented MEAI in 2008 and was associated with the Pace product.[7] His initial intentions for MEAI may have included its sale as a "legal high," but he later expressed interest in developing it as a "binge behaviour regulator".[4] The distribution of Pace, however, encountered regulatory obstacles; Health Canada issued a warning that MEAI was considered illegal due to its structural similarity to amphetamine, effectively halting its sale in Canada.[4] This shift from individual invention and NPS marketing towards a more structured development path is notable. It reflects a potential pathway for some psychoactive compounds with interesting anecdotal effects to be brought into mainstream pharmaceutical research and development, provided they can navigate the complex IP and regulatory landscapes.

Therapeutic Development (CMND-100):

The therapeutic potential of MEAI, particularly for addiction-related disorders, is now being formally investigated by Clearmind Medicine Inc., which is developing MEAI under the code name CMND-100.4

• Primary Indication (AUD): The main focus of Clearmind's CMND-100 program is the treatment of Alcohol Use Disorder (AUD).[5] The rationale is based on MEAI's reported ability to reduce alcohol cravings and its potential to modulate neural pathways, such as those involving 5-HT1A receptors, to decrease impulsivity.[20]
• Other Investigated Indications:
• Cocaine Addiction: Preclinical studies, in collaboration with SciSparc Ltd., have explored MEAI in combination with Palmitoylethanolamide, showing a significant reduction in cocaine-induced craving in animal models. A European patent application for this combination therapy has been published.[4]
• Metabolic Syndrome and Obesity: Clearmind is also developing MEAI for these conditions.[4] Supporting this, one preclinical study demonstrated that MEAI can reverse diet-induced obesity and improve metabolic parameters in mice.[1]
• Binge Eating: Collaborative research with the Hebrew University of Jerusalem's Obesity and Metabolism Laboratory is underway to study MEAI for binge eating disorders.[8]
• Clinical Trial Progress: Clearmind Medicine received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) for a Phase I/IIa clinical trial of CMND-100 for AUD.[10] This multinational, multi-center trial includes prestigious sites such as Yale School of Medicine and Johns Hopkins University School of Medicine in the USA, as well as the IMCA in Israel.[10] The first patient was reported to be enrolled in June 2025.[14]
• Intellectual Property and Collaborations: Clearmind Medicine states it owns the rights to MEAI and related patents, including intellectual property holdings from Ezekiel Golan's patents.[4] The company is also pursuing novel delivery mechanisms, such as the ActivCrystal™ technology in collaboration with Dr. Glitter Pty Ltd, for an MEAI-based alcohol substitute product.[6] This multi-pronged strategy, exploring various indications and formulations, suggests a comprehensive approach to maximizing MEAI's therapeutic and commercial potential, diversifying risk, and addressing multiple unmet medical needs.

Key Developers and Commercial Entities:

• Ezekiel Golan: Claimed inventor of MEAI, involved with "Pace".[4]
• David Nutt: Involved in research collaborations related to MEAI.[4]
• Clearmind Medicine Inc.: The primary entity spearheading the therapeutic development of MEAI as CMND-100.[4]
• Diet Alcohol Corporation of the Americas (DACOA): Former marketer of the MEAI-based drink "Pace".[4]
• Dr. Glitter Pty Ltd: Collaborating with Clearmind on novel delivery technology.[6]
• SciSparc Ltd.: Collaborating with Clearmind on MEAI for cocaine addiction.[8]

The progression of MEAI from an NPS with associated legal challenges to a compound under formal FDA-regulated clinical trials signifies that regulatory bodies are open to evaluating such substances based on scientific merit and their potential to address significant unmet medical needs, provided a rigorous and compliant development pathway is followed. This path underscores the potential for other NPS with interesting anecdotal effects to be formally investigated, but also highlights the complexities involved.

5. Psychoactive Effects and User Experiences

The psychoactive effects of 5-Methoxy-2-aminoindane (MEAI) are central to both its recreational use and its therapeutic investigation. Reports stem from scientific literature, marketing claims for products like "Pace," and anecdotal user experiences.

Reported Subjective Effects (from Scientific Literature and Product Marketing):

• Euphoria: MEAI is reported to produce mild euphoric effects.[1]
• Alcohol-like Experience: A frequently cited characteristic is an "alcohol-like tipsy experience" or a feeling of mild inebriation.[1] This has led to its marketing as an "alcohol alternative" or "substitute" [4], with the aim of replicating some of alcohol's desirable sensations without the associated health risks or hangover.[6]
• Contentedness: A feeling of contentedness has also been described.[7]
• Empathogenic Effects: Some sources mention potential empathogenic effects [3], although this is less emphasized in the available material compared to its alcohol-like properties.
• Reduced Desire for Alcohol / Binge Mitigation: A key reported effect, and one driving therapeutic interest, is a reduced desire to consume alcoholic beverages or a binge-mitigating effect on alcohol consumption.[2] This effect, noted by recreational users and forming a cornerstone of Clearmind's therapeutic rationale [20], is particularly interesting as it suggests MEAI might not just substitute alcohol's effects but actively reduce the drive to consume it.
• Mild Psychostimulant Effects: Some reports suggest mild psychostimulant properties [3], though its overall profile appears distinct from classical stimulants due to its primary serotonergic action.

Comparison with Related Compounds:

• Alcohol: The "alcohol-like" description is pervasive. The crucial question, which user reports may help clarify, is precisely how it mimics and differs from ethanol. Does it provide disinhibition and sociability without significant cognitive or motor impairment, or severe hangovers? The product "Pace" was marketed with claims of "zero hangover" [7], though this lacks independent scientific verification.
• MDMA: MEAI shares structural similarities with MDMA.[9] It is suggested that MEAI might produce MDMA-like entactogenic effects, but potentially with reduced misuse liability due to its significantly weaker impact on dopamine release compared to MDMA's balanced SNDRA profile.[4]
• MDAI (5,6-Methylenedioxy-2-aminoindane): Another aminoindane, MDAI, also produces MDMA-like entactogenic effects.[19] MEAI and MDAI differ in their specific monoamine release profiles; MEAI is more serotonin-selective, while MDAI is a more balanced serotonin-norepinephrine releasing agent (SNRA).[4]

Analysis of User Reports 29:

Anecdotal user reports from online forums such as Bluelight, while not controlled scientific data, can offer valuable qualitative insights into the real-world consumption patterns and subjective experiences of MEAI. Based on the nature of such forums and the pharmacology of MEAI, reports likely describe a spectrum of effects:

• Positive Effects Often Reported for Serotonergic Agents: These might include mood elevation, increased sociability, feelings of relaxation or mild euphoria, an altered sense of perception, and potentially the reported alcohol-like buzz. Some users might experience reduced anxiety or increased empathy.
• Negative Effects Often Reported: As with many psychoactive substances, negative effects could include nausea, headache, dizziness, fatigue, or jitteriness. Some individuals might experience anxiety, particularly at higher doses or if predisposed. Comedown effects such as low mood or tiredness after the primary effects wear off are also possible. Physiological effects like increased heart rate or blood pressure might be noted.
• Dosage Information: Recreational doses mentioned in such forums vary and are often unverified.
• Duration of Effects: Users typically report onset time, peak duration, and overall length of the experience, including any after-effects.
• Route of Administration: Oral consumption is the most likely route discussed.
• Comparisons: Users often compare new substances to more well-known ones, so comparisons to alcohol, MDMA, or other stimulants/entactogens would be expected.
• Hangover/After-effects: Reports on the presence or absence of a "hangover," especially in comparison to alcohol, would be particularly relevant given its marketing.
• Desire to Re-dose/Addiction Potential: User perceptions of its addictiveness or the compulsion to re-dose are important indicators, though subjective.
• Self-Limiting Property: Any anecdotal corroboration of the "self-limiting" property mentioned by Clearmind [20]—whereby further consumption becomes less desirable after a certain point—would be noteworthy.

The variability typically found in such user reports underscores the importance of controlled clinical settings for administration. Factors like dose, individual neurochemistry, setting, and co-ingestion of other substances can significantly influence outcomes. These anecdotal accounts highlight potential effects and risks but cannot substitute for rigorous scientific evaluation through clinical trials [10], which are essential for establishing a reliable safety and efficacy profile and standardized dosing.

6. Therapeutic Potential and Clinical Research

The unique psychoactive profile of 5-Methoxy-2-aminoindane (MEAI), particularly its reported alcohol-like effects coupled with a reduction in the desire to consume alcohol, has spurred significant interest in its therapeutic applications. Clearmind Medicine Inc. is at the forefront of this research, developing MEAI under the code name CMND-100.

Investigated Indications:

• Alcohol Use Disorder (AUD) / Binge Drinking Mitigation: This is the primary therapeutic target for CMND-100.[4] The hypothesis is that MEAI can disrupt the cycle of binge drinking, potentially by modulating neural pathways involving serotonin, such as the 5-HT1A receptor system, which is associated with impulsivity and craving control.[20]
• Cocaine Addiction: Preclinical research, conducted in collaboration with SciSparc Ltd., has shown that MEAI, when combined with Palmitoylethanolamide (PEA), significantly reduces cocaine-seeking behavior in animal models without affecting natural reward responses. A European patent application covers this combination therapy.[4]
• Metabolic Syndrome and Obesity: Clearmind Medicine is also exploring MEAI for these conditions.[4] This is supported by preclinical findings where MEAI was shown to reverse diet-induced obesity and improve various metabolic parameters in mice.[1]
• Binge Eating Disorders: In collaboration with the Hebrew University of Jerusalem's Obesity and Metabolism Laboratory, Clearmind is investigating MEAI's potential for treating binge eating.[8]

The investigation of MEAI across multiple "binge" or compulsive behaviors (alcohol, cocaine, food) suggests a therapeutic hypothesis centered on a common underlying neurobiological mechanism. This likely involves the modulation of serotonergic pathways that regulate reward processing, impulse control, and satiety. If MEAI proves effective across these varied conditions, it would lend strong support to a transdiagnostic approach targeting serotonergic dysregulation in a spectrum of addictive and compulsive disorders.

Summary of Preclinical Research Findings:

Preclinical studies have provided initial support for MEAI's therapeutic potential:

• Alcohol Consumption: In murine models, CMND-100 (MEAI) administered as monotherapy, and also in combination with SciSparc's CannAmide (PEA), demonstrated a significant reduction in alcohol consumption.[8]
• Cocaine Seeking: The MEAI-PEA combination effectively reduced cocaine-seeking behavior in animal models, notably without blunting natural reward responses, suggesting specificity for drug-related compulsions.[27]
• Obesity/Metabolic Effects: MEAI administration in mice led to a reversal of diet-induced obesity and improvements in metabolic markers.[1]
• Pharmacology: As detailed previously, MEAI acts primarily as a selective serotonin releasing agent with good brain penetration in rats.[2]
• Safety/Toxicology: Preclinical studies in rats indicated that MEAI is generally well-tolerated at lower to moderate doses, though non-linear pharmacokinetics emerge at higher doses. In vitro cytotoxicity was low at therapeutically relevant concentrations.[3]

Overview of Clinical Trials (CMND-100 for AUD):

The progression of MEAI into human clinical trials is a critical step in evaluating its therapeutic utility.

Trial Attribute	Details	Source(s)
Trial Identifier	NCT05913752	15
Phase	Phase I/IIa (First-in-Human)	9
Status	Enrolling (First patient enrolled June 2025)	14
Indication	Alcohol Use Disorder (AUD)	5
Sponsor	Clearmind Medicine Inc.	10
Locations	Multinational, Multi-center (USA: Yale School of Medicine, Johns Hopkins University School of Medicine; Israel: IMCA)	10
Design Notes	Single and multiple dose administration; tolerability, safety, and pharmacokinetic trial. Likely includes double-blind, placebo-controlled elements for efficacy.	9
Population	Healthy volunteers and subjects with AUD. Eligible: 18-60 years, reporting heavy binge drinking or diagnosed with AUD, expressing a desire to reduce/stop drinking.	10
Primary Endpoints	Determination of tolerable dose(s); characterization of safety and pharmacokinetics/pharmacodynamics of single and repeated doses.	10
Secondary Endpoints	Preliminary evaluation of efficacy in reducing drinking patterns and alcohol cravings in individuals with moderate-to-severe AUD.	10
Route of Admin.	Oral capsules	10

The initiation of this Phase I/IIa trial, despite MEAI's history as an NPS and the legal issues faced by unregulated products like "Pace" [7], demonstrates that regulatory bodies such as the FDA are prepared to evaluate such compounds based on their scientific merit and potential to address unmet medical needs. This is contingent upon a rigorous, compliant development pathway. This situation may serve as a precedent for other NPS-derived compounds with anecdotal therapeutic effects, emphasizing the FDA's role in data-driven evaluation.

A particularly noteworthy aspect of MEAI's therapeutic profile is the "self-limiting" property alluded to by Clearmind Medicine.[20] If this property—whereby further consumption becomes less desirable after a certain effect level is reached—is validated in human trials, it could be a crucial differentiator from alcohol and other addictive substances. Such an effect could inherently reduce the abuse liability of MEAI itself when used as a therapeutic, a significant advantage for any addiction treatment. The non-linear pharmacokinetics observed in rats at higher doses [2] might contribute to this, potentially leading to less predictable or less pleasant effects, or an increase in side effects at higher exposures, thereby naturally discouraging excessive intake. This hypothesis requires careful evaluation in the ongoing human trials.

7. Safety and Toxicology

The safety and toxicology profile of 5-Methoxy-2-aminoindane (MEAI) is a critical area of investigation, given its psychoactive nature and potential for human consumption, both recreationally and therapeutically. Current data are primarily from preclinical studies.

Preclinical Toxicity Studies (chiefly in rats):

• Acute Toxicity:
• Single oral administration of MEAI at a dose of 10 mg/kg was reported to be well tolerated in Sprague Dawley rats.[3]
• At a higher acute dose of 100 mg/kg, rats exhibited transient adverse clinical signs, including tremor, Straub tail (a characteristic stiffening and erection of the tail often seen with opioid or stimulant administration), dyspnea, piloerection, hunched posture, and decreased motor activity.[3] These signs suggest central nervous system and autonomic effects at high doses.
• Subacute Toxicity:
• Repeated oral administration of MEAI for 5 days at dose levels of 10 mg/kg and 30 mg/kg in rats did not elicit significant adverse clinical effects.[20]
• Hematological assessments (complete blood count) revealed no significant changes compared to control groups, indicating a lack of toxicity on the hematopoietic system after this period of subacute exposure.[20]
• Pathological and histopathological examinations in these subacute studies reportedly showed no evidence of liver or kidney toxicities.[20]
• In Vitro Cytotoxicity:
• MEAI demonstrated low cytotoxicity in in vitro assays at concentrations likely relevant to its pharmacological activity.[20]
• However, cytotoxic effects were observed at higher concentrations. Calculated IC₅₀ values were approximately 400 mg/L (which translates to roughly 2 mM for the freebase). Specifically, IC₅₀ values were reported as 368.2 mg/L for rat brain striatum primary neurons and 403.1 mg/L for human primary healthy hepatocytes.[3] Cytotoxicity was evident at concentrations of 500 mg/L and 1000 mg/L.[3]
• Mutagenicity: The potential for in vitro mutagenic effects was evaluated as part of its preliminary drug development route.[20] The available snippets suggest these studies were conducted, but specific results regarding mutagenicity are not detailed beyond general statements of a favorable safety profile at lower doses.
• Neurotoxicity:
• Direct, long-term neurotoxicity studies for MEAI are not extensively detailed in the provided snippets. However, inferences can be drawn from related compounds and its mechanism of action. MEAI is a derivative of MMAI (5-methoxy-6-methyl-2-aminoindane), which is reported to inhibit serotonin uptake and stimulate its release without inducing the serotonergic neurotoxicity commonly associated with MDMA.[13] This suggests MEAI might share a more favorable neurotoxicity profile compared to MDMA.
• MDAI (5,6-methylenedioxy-2-aminoindane), another aminoindane, also shows greatly reduced serotonergic neurotoxicity in animal models compared to MDMA, although some weak capacity for neurotoxicity with chronic use or in combination with amphetamine might exist.[22]
• MEAI's primary action as a selective serotonin releasing agent (SSRA), with considerably less dopamine involvement than MDMA, is generally associated with a lower risk of the kind of excitotoxic damage linked to potent, combined dopamine and serotonin releasers. This characteristic, if confirmed by specific long-term studies on MEAI, would be a significant safety advantage.

Interaction with Ethanol:

Given MEAI's proposed use as an alcohol substitute or as a treatment for AUD, its interaction with ethanol is of paramount importance.

• In vitro studies exploring the combination of MEAI (at 100 mg/L, described as the highest non-toxic concentration in those assays) with cytotoxic levels of ethanol (6% and 7.5%) revealed no statistically significant increase in cytotoxic effect.[20] This suggests a lack of synergistic or additive neurotoxicity at the cellular level when MEAI and ethanol are combined under these specific conditions. This finding is a positive initial safety signal, reducing concerns about acute toxic interactions if MEAI were consumed concurrently with alcohol. However, these are in vitro results, and in vivo studies, as well as human clinical data, are necessary to confirm this lack of adverse interaction and to assess potential behavioral or physiological compounding effects from co-administration.

Reported Adverse Effects in Humans (Anecdotal/Recreational Use):

Information on human adverse effects primarily stems from anecdotal reports related to its recreational use, as formal clinical trial data is still emerging.

• The most commonly reported subjective effects include a mild euphoric, alcohol-like tipsy experience.[3]
• Based on its pharmacology as an SSRA and reports from users of similar substances (e.g., from forums like Bluelight [29]), potential adverse effects could include nausea, headache, dizziness, fatigue, anxiety (especially at higher doses), and transient cardiovascular effects (e.g., increased heart rate). Comedown effects like temporary low mood or tiredness are also plausible.
• The product "Pace," which contained MEAI, was marketed with the claim of "zero hangover" [7], but this has not been scientifically substantiated.

Overdose Information:

Specific case reports of MEAI overdose are not detailed in the provided research snippets.30 However, based on its known pharmacology as an SSRA and the non-linear pharmacokinetics observed in rats at high doses 2, an overdose in humans could theoretically lead to:

• Serotonergic overstimulation, potentially resulting in symptoms of serotonin syndrome (e.g., confusion, agitation, hyperthermia, autonomic instability, neuromuscular hyperactivity).
• Exacerbated psychoactive effects, including anxiety or panic.
• Cardiovascular stress. It is critical that human clinical trials carefully establish safe dosing ranges.

Human Clinical Trial Safety (CMND-100):

The Phase I/IIa clinical trial for CMND-100 (NCT05913752) is designed to primarily evaluate the safety and tolerability of MEAI in healthy volunteers and in individuals with AUD.10 As of the latest information (first patient enrolled June 2025), detailed safety data from this trial are not yet available. The study will systematically collect adverse event data, which will be crucial for understanding MEAI's safety profile in humans under controlled conditions.

The preclinical safety data, particularly the good tolerability in rats at doses up to 30 mg/kg (corresponding to human equivalent doses of 1.6 mg/kg and 4.8 mg/kg, respectively [20]), provides a basis for initiating human trials. However, the non-linear pharmacokinetics observed at higher doses in rats [2] remains a pivotal safety consideration. This necessitates a cautious dose-escalation strategy in human studies to avoid unexpectedly high systemic exposures that could lead to toxicity. The dose-finding component of the Phase I/IIa trial is therefore essential for establishing a safe therapeutic window in humans.

Table: Summary of Preclinical Safety and Toxicology Findings for MEAI

Study Type	Species/System	Key Findings (Dose, Effects)	Source(s)
Acute Oral Toxicity	Sprague Dawley Rats	10 mg/kg: Well tolerated. <br> 100 mg/kg: Transient adverse clinical signs (tremor, Straub tail, dyspnea, piloerection, hunched back, decreased motor activity).	3
Subacute Oral Toxicity (5-day)	Sprague Dawley Rats	10 mg/kg & 30 mg/kg: No significant adverse clinical effects. No toxicity on hematopoietic system. No liver or kidney toxicities observed via pathology/histopathology.	20
In Vitro Cytotoxicity	Rat Brain Striatum Primary Neurons	IC₅₀: 368.2 mg/L. Cytotoxic effects at 500 & 1000 mg/L.	3
In Vitro Cytotoxicity	Human Primary Healthy Hepatocytes	IC₅₀: 403.1 mg/L. Cytotoxic effects at 500 & 1000 mg/L.	3
In Vitro Ethanol Interaction (Cytotoxicity)	Rat Brain Striatum Primary Neurons / Human Hepatocytes	MEAI (100 mg/L) combined with ethanol (6% or 7.5%) showed no statistically significant increase in cytotoxic effect (no synergistic/additive neurotoxicity).	20
Mutagenicity	In vitro assays	Evaluated; suggested low concern but specific results not detailed.	20
Neurotoxicity (Inferred)	Comparative (vs. MDMA, based on related compounds)	MEAI, as an SSRA and derivative of less neurotoxic aminoindanes (MMAI, MDAI), is hypothesized to have a better neurotoxicity profile than MDMA. Requires direct long-term study for MEAI.	13

8. Legal Status and Regulatory Landscape

The legal status of 5-Methoxy-2-aminoindane (MEAI) is complex and varies significantly across jurisdictions, reflecting its dual nature as a compound with recreational use history and emerging therapeutic potential. It is often not explicitly scheduled but may fall under broader controls for novel psychoactive substances (NPS) or analogue legislation.

United States:

• Food and Drug Administration (FDA): An Investigational New Drug (IND) application for CMND-100 (MEAI) for a Phase I/IIa clinical trial targeting Alcohol Use Disorder has been approved by the FDA. This trial is sponsored by Clearmind Medicine.[10] Clearmind Medicine had prepared MEAI for FDA registration as of May 2022.[4] This approval allows for legitimate research and development as a potential pharmaceutical.
• Drug Enforcement Administration (DEA) / Controlled Substances Act (CSA): MEAI is generally unscheduled at the federal level.[4] It is not explicitly listed in Schedule I of the CSA.[32] However, its structural similarity to amphetamine (a Schedule II substance) could potentially bring it under the purview of the Federal Analogue Act if intended for human consumption outside of FDA-approved research or therapeutic channels. The DEA has previously scheduled other methoxy-substituted psychoactive compounds like 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) into Schedule I [33], demonstrating a precedent for controlling such substances, although MEAI is structurally distinct from tryptamines. The related aminoindane MDAI is also not explicitly listed as Schedule I in the US.[22]

United Kingdom:

• MEAI falls under the scope of the Psychoactive Substances Act 2016.[4] This Act provides a blanket ban on the production, supply, and importation of any substance capable of producing a psychoactive effect, unless it is an exempted substance (e.g., alcohol, caffeine, nicotine, approved medicines). Aminoindanes, including MEAI, gained popularity as NPS in the UK, particularly after other substances like mephedrone were banned in 2010.[25] The UK has not specifically scheduled aminoindanes under the Misuse of Drugs Act 1971 beyond the general controls of the Psychoactive Substances Act.[25]

European Union:

• MEAI is recognized as an NPS and is monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).[21] The EMCDDA reported encounters with the related aminoindane MDAI in 2010.[21]
• The EU has a framework (Council Decision 2005/387/JHA) for information exchange, risk assessment, and control of new psychoactive substances, under which MEAI would be considered.[36]
• Germany: MEAI, like MDAI, is subject to the Neue-psychoaktive-Stoffe-Gesetz (NpSG), which restricts its use to industrial and scientific purposes only.[4]
• A European patent application has been published for a combination therapy involving MEAI for cocaine addiction, indicating research and development interest within Europe.[27]

Canada:

• Health Canada has stated that MEAI is considered a Controlled Substance, analogous to amphetamine (Schedule I of Canada's Controlled Drugs and Substances Act), making the unapproved sale of products like "Pace" illegal.[4]

Australia:

• The legal status of MEAI in Australia is likely as a prohibited substance or controlled drug, potentially under generic analogue provisions or specific listings for aminoindanes.
• The Criminal Code (Controlled Drugs) Legislation Amendment Regulation 2014 expanded the list of illicit substances, including classes like phenethylamines.[37]
• Tasmania's Misuse of Drugs Act 2001 lists "5-(2-aminopropyl)indan and substituted 5-(2-aminopropyl)indans" in Schedule 1.[38] While MEAI is a 2-aminoindane, this indicates control over related indane structures.
• 2-aminoindane itself has defined small and indictable quantities under New South Wales law.[39]
• Unapproved therapeutic goods, which MEAI would be considered if imported for therapeutic use without specific approval, can only be accessed under strict schemes regulated by the Therapeutic Goods Administration (TGA).[40]

General Status:

MEAI is widely recognized as an NPS or "designer drug".2 Its legal status is often not defined by specific scheduling of MEAI itself but by broader NPS legislation, analogue acts (based on structural similarity to controlled substances like amphetamine), or general medicines regulations if intended for therapeutic use.

The primary driver for legal controls in jurisdictions like Canada (analogue to amphetamine) and the UK (Psychoactive Substances Act) appears to be MEAI's psychoactive nature and its structural relationship to known controlled substances, rather than extensive epidemiological data on specific harms attributed directly to MEAI at the time of control. This precautionary approach is common for NPS.

The FDA's IND approval for CMND-100 in the US, despite Health Canada's stricter stance on its unregulated sale, illustrates how different regulatory frameworks and intended uses (therapeutic vs. recreational) can lead to divergent legal treatments of the same compound. This underscores that a substance might be illegal for recreational sale but permissible for controlled research and therapeutic development if a rigorous scientific and regulatory pathway is followed.

The active patenting strategy by Clearmind Medicine for MEAI's therapeutic uses [4] is standard pharmaceutical practice to secure commercial exclusivity. However, the compound's early synthesis date (1956) [2] and its history of recreational use could present challenges for broad composition-of-matter patents, making patents for specific uses, formulations (e.g., with ActivCrystal™ [6]), or combination therapies (e.g., with PEA for cocaine addiction [27]) particularly important.

Table: Legal Status of 5-Methoxy-2-aminoindane (MEAI) in Key Jurisdictions

Jurisdiction	Legal Status/Classification	Key Legislation/Regulatory Body	Notes/Source(s)
United States	Generally unscheduled (federal). IND approved for clinical trials (CMND-100). Potentially falls under Federal Analogue Act if sold for consumption.	FDA (for IND), DEA (for CSA)	4
United Kingdom	Covered under the Psychoactive Substances Act 2016.	Psychoactive Substances Act 2016	4
European Union (General)	Monitored as an NPS. Subject to Council Decision 2005/387/JHA.	EMCDDA, National drug agencies	21
Germany (EU Member)	NpSG (Industrial and scientific use only).	Neue-psychoaktive-Stoffe-Gesetz (NpSG)	4
Canada	Controlled Substance (analogue to amphetamine, Schedule I).	Health Canada, Controlled Drugs and Substances Act	4
Australia	Likely prohibited/controlled, potentially under analogue provisions or specific indane listings. Unapproved therapeutic good.	State/Territory Criminal Codes, Misuse of Drugs Acts, Therapeutic Goods Administration (TGA)	.37 Note: 5-(2-aminopropyl)indan is scheduled; 2-aminoindane has defined quantities. MEAI is a 2-aminoindane derivative. Specific listing for MEAI not found.

9. Discussion

5-Methoxy-2-aminoindane (MEAI) presents a fascinating case study of a compound navigating the complex interface between recreational psychoactive use and formal therapeutic development. Its primary pharmacological action as a modestly selective serotonin releasing agent (SSRA), with significantly less impact on dopamine systems compared to substances like MDMA or amphetamine, underpins its reported alcohol-like subjective effects and its potential for a relatively lower abuse liability.[4] This profile has led to its investigation by Clearmind Medicine as CMND-100, primarily for Alcohol Use Disorder (AUD), but also for other conditions involving compulsive behaviors such as cocaine addiction and binge eating, and for metabolic disorders like obesity.[1]

The dual nature of MEAI—a substance with a history of unregulated recreational sale (e.g., as "Pace" [7]) and a candidate for legitimate medical use—poses distinct challenges and opportunities. Its perception as an "alcohol substitute" could influence public and regulatory views, potentially creating hurdles for its acceptance as a medicine, even if clinical efficacy and safety are demonstrated. Conversely, the anecdotal reports of reduced desire for alcohol consumption by recreational users [2] have provided a unique impetus for its therapeutic investigation. Clearmind's hypothesis that MEAI may act via 5-HT1A pathways to decrease impulsivity [20] suggests a targeted mechanism beyond simple effect substitution, which, if validated, could represent a novel approach to addiction treatment. The investigation of MEAI for multiple "binge" or compulsive behaviors further hints at a potential common serotonergic modulatory mechanism underlying these conditions. Success in these diverse areas could validate a transdiagnostic approach for a spectrum of related behavioral health issues.

A critical aspect of MEAI's profile is the "self-limiting" property suggested by Clearmind Medicine.[20] If human studies confirm that MEAI's effects become less desirable or more aversive beyond a certain intake level, this could inherently reduce its own abuse potential as a therapeutic agent—a significant advantage for an addiction treatment. The non-linear pharmacokinetics observed in rats at higher doses, leading to disproportionately increased exposure [2], might contribute to such a self-limiting effect by altering the subjective experience or increasing side effects, thus naturally discouraging excessive consumption.

Despite promising preclinical data, including good tolerability in rats at lower doses and a lack of synergistic neurotoxicity with ethanol in vitro [20], several research gaps remain. Chief among these is the need for comprehensive human pharmacokinetic data, particularly to determine if the dose-dependent non-linearity seen in rats occurs in humans, as this has significant implications for safe dosing. The ongoing Phase I/IIa clinical trial (NCT05913752) is crucial for addressing this and for establishing the safety, tolerability, and preliminary efficacy of MEAI in humans.[10] Furthermore, the precise neurobiological mechanisms underlying its reported binge-mitigating effects require deeper investigation. Long-term safety in humans, including potential neurotoxicity (though inferred to be lower than MDMA) and cardiovascular effects, must be thoroughly evaluated. Systematic human abuse liability studies are also essential to objectively assess its misuse potential.

The development of MEAI could serve as an important test case for how society and regulatory agencies manage substances that straddle the line between recreational psychoactives and potential therapeutics, particularly those offering harm reduction possibilities. Its journey highlights the potential for NPS-derived compounds to enter legitimate drug development pipelines, but also the intricate scientific, ethical, and regulatory navigation required. The research stimulated by MEAI, especially into its effects on binge behaviors, may also contribute to a broader understanding of addiction neurobiology, potentially uncovering novel therapeutic targets beyond MEAI itself.

10. Conclusion

5-Methoxy-2-aminoindane (MEAI), also known by its developmental code CMND-100, is an aminoindane derivative with a distinct pharmacological profile as a modestly selective serotonin releasing agent. This neurochemical action is believed to underlie its reported psychoactive effects, which include mild euphoria and an alcohol-like experience, often accompanied by a reduced desire for alcohol consumption. These characteristics have led to its exploration both as a recreational "alcohol alternative" and, more formally, as a potential therapeutic agent for Alcohol Use Disorder, cocaine addiction, and certain metabolic and eating disorders.

Preclinical studies in animals have indicated some positive safety signals at lower doses and promising efficacy in models of addiction and obesity. However, non-linear pharmacokinetics at higher doses in rats highlight the need for cautious dose-finding in human trials. The ongoing Phase I/IIa clinical trial of CMND-100 for AUD is a critical step in determining its safety, tolerability, pharmacokinetics, and preliminary efficacy in humans.

MEAI's development is characterized by the complexities arising from its dual identity: a compound with a history of unregulated use and a candidate for legitimate pharmaceutical development. Its legal status varies globally, often falling under broad NPS or analogue legislation. The successful progression of MEAI as a therapeutic will depend on rigorous scientific validation through clinical trials to definitively establish its benefit-risk profile. If proven effective and safe, MEAI could offer a novel therapeutic option for significant unmet medical needs, particularly in the realm of addiction. Its journey underscores the evolving landscape of psychopharmacology, where substances with psychoactive properties are increasingly being investigated for their therapeutic potential, requiring careful navigation of scientific, regulatory, and societal considerations.

11. References

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• [18] U.S. Environmental Protection Agency. (n.d.). 5-Methoxy-2,3-dihydro-1H-inden-2-amine. Comptox Chemicals Dashboard.
• [13] Cayman Chemical. (n.d.). MEAI (hydrochloride).
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• [9] Yale School of Medicine. (n.d.). A Phase I/II Single and Multiple Dose Tolerability, Safety and Pharmacokinetic Study of CMND-100 in Healthy Volunteers and Subjects with Binge Drinking/ Alcohol Use Disorder (AUD). Yale ADDICTION RECOVERY research Program (ABN Lab).
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