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Methallylescaline
Methallylescaline
Methallylescaline
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Methallylescaline
Clinical data
Other namesMAL; 4-Methylallyloxy-3,5-dimethoxyphenethylamine; 3,5-Dimethoxy-4-methylallyloxyphenethylamine; 4-Methylallyl-desmethylmescaline; MAD
Routes of
administration		Oral[1]
Drug classSerotonin 5-HT2 receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Onset of action≤1 hour[1]
Duration of action12–16 hours[1]
Identifiers
  • 2-{3,5-Dimethoxy-4-[(2-methylprop-2-en-1-yl)oxy]phenyl}ethan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H21NO3
Molar mass251.326 g·mol−1
3D model (JSmol)
  • CC(=C)COc1c(cc(cc1OC)CCN)OC
  • InChI=1S/C14H21NO3/c1-10(2)9-18-14-12(16-3)7-11(5-6-15)8-13(14)17-4/h7-8H,1,5-6,9,15H2,2-4H3 checkY
  • Key:FOXJFBFFGULACD-UHFFFAOYSA-N checkY
  (verify)

Methallylescaline (MAL), also known as 4-methylallyloxy-3,5-dimethoxyphenethylamine, is a psychedelic drug of the phenethylamine and scaline families related to mescaline.[1][3] It is taken orally.[1][3]

The drug acts as a serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A receptor.[4] It is closely structurally related to mescaline and to other scalines like escaline and allylescaline.[4]

Methallylescaline was first described by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[3][1] It was encountered as a novel designer drug by 2013.[5][6][7]

Use and effects

[edit]

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists the dose range of methallylescaline as 40 to 65 mg and its duration as 12 to 16 hours.[1][8][9] As such, its dose range is relatively narrow.[1][8][9] Moreover, the drug has been reported to have an unusually steep dose–response curve, such that a small increase in dose can result in an unexpectedly large increase in effects.[10] Methallylescaline has about 6 times the potency of mescaline, which has a much higher listed dose range of 200 to 400 mg.[8][9][1] Its onset is within 1 hour and peak effects occur within 2 hours.[1]

Shulgin has described methallylescaline as a "mixed bag" in terms of experience reports.[1] Its effects have been reported to include closed-eye visuals, "visual theater", open-eye visuals including visual distortions, visual depth and movement effects, kaleidoscopic neon colors, watercolors, fantasy, mental imagery, feelings of unreality, easy childhood memory recall, self-connectedness, eroticism, initial discomfort, overload, feeling overwhelmed, shades of possible amnesia, loss of contact, extreme restlessness, trouble sleeping, and enhanced dreams.[1] It was also reported to produce quite strong body effects, diuretic effects, and slightly reduced heart rate.[1] Some found it unpleasant and said that they would not repeat the experience, whereas others were impressed by it, found it enjoyable, and called it "beautiful".[1] Many expressed that the dose they tried was too strong for them and that a lower dose would be better.[1] Methallylescaline has been described as having relatively more visual imagery than other scalines like cyclopropylmescaline and allylescaline.[1]

Interactions

[edit]
See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

Pharmacology

[edit]

Pharmacodynamics

[edit]

Methallylescaline acts as a potent agonist of the serotonin 5-HT2A receptor.[4] It also interacts with certain other targets, such as the serotonin 5-HT2C receptor.[4]

Chemistry

[edit]

Methallylescaline, also known as 4-methylallyloxy-3,5-dimethoxyphenethylamine, is a substituted phenethylamine and scaline.[1][3][8][9] It is a synthetic derivative of mescaline (3,4,5-trimethoxyphenethylamine) with a methallyloxy group instead of methoxy group at the 4 position.[1][3][8][9]

Synthesis

[edit]

The chemical synthesis of methallylescaline has been described.[1]

Analogues

[edit]

Analogues of methallylescaline include mescaline, escaline, allylescaline, and cyclopropylmescaline, among others.[1][3][8][9]

History

[edit]

Methallylescaline was first described in the literature by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[3][1][8] It was first tried by Shulgin in 1981 and its hallucinogenic effects were discovered by him in 1982.[11][9] The drug has an entry in PiHKAL, but not in Shulgin's 2011 book The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds.[3] It was encountered as a novel designer drug in Europe by 2013.[5][6][7] Methallylescaline's pharmacology was described by Matthias Liechti and Daniel Trachsel and colleagues in 2021.[4]

Society and culture

[edit]

Names

[edit]

Alexander Shulgin described the name of methallylescaline (MAL) as "completely unsound".[1] This was because there was no union of a methallyl group with escaline.[1] Instead, methallylescaline is mescaline with a 2-propene group attached to the methyl of the methoxy group at the 4 position.[1] However, Shulgin expressed that there is no way of naming the compound in that manner.[1] The only corresponding proper name would be 4-methylallyldesmethylmescaline (MAD).[1] However, Shulgin found the acronym MAD to be disagreeable and ultimately preferred MAL.[1]

[edit]

Sweden

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Methallylescaline is illegal in Sweden as of 26 January 2016.[12]

United States

[edit]

Methallylescaline is not directly scheduled under the Controlled Substances Act. However, due to its structural similarities with mescaline, it could potentially be prosecuted under the Federal Analogue Act if sold for human consumption.

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Methallylescaline

View on Grokipedia
from Grokipedia
Methallylescaline (MAL), chemically known as 4-(2-methylallyloxy)-3,5-dimethoxyphenethylamine, is a synthetic phenethylamine compound with the molecular formula C₁₄H₂₁NO₃, classified as a psychedelic hallucinogen structurally derived from mescaline by substitution of a methallyloxy group at the 4-position. As a serotonin 5-HT receptor agonist, it produces psychoactive effects including visual hallucinations, stimulation, and altered perception akin to mescaline, though empirical data on its pharmacology remains limited primarily to in vitro studies and user reports. Recent monitoring by drug early warning systems has noted its emergence in online discussions as a novel psychoactive substance, often compared to traditional psychedelics for its long duration of action, estimated at 12-16 hours based on anecdotal dosing of 40-65 mg. Analytical reference standards confirm its categorization within the scaline subfamily of phenethylamines, with potential for metabolism into active compounds, as explored in recent mass spectrometry research.

Chemistry

Chemical Structure and Properties

Methallylescaline, systematically named 3,5-dimethoxy-4-(2-methylallyloxy)phenethylamine, is a synthetic featuring a phenethylamine backbone with methoxy groups at the 3- and 5-positions of the phenyl ring and a 2-methylallyloxy substituent at the 4-position. Its molecular formula is C14_{14}H21_{21}NO3_{3}, with a of 251.32 g/mol. This structure positions methallylescaline within the scaline family of compounds, defined as 4-alkoxy derivatives of 3,5-dimethoxyphenethylamine, which modify the 4-methoxy group of (3,4,5-trimethoxyphenethylamine) to potentially enhance and receptor affinity. The methallyl modification—a 2-methylprop-2-en-1-yl chain—replaces the found in , conferring structural similarity to other synthetic psychedelics like proscaline while altering steric and electronic properties at the 4-position. Compared to , methallylescaline exhibits greater potency on a per-milligram basis, with effective doses approximately 40–65 mg versus 's 200–400 mg, reflecting about a sixfold increase attributable to the extended alkoxy chain. Physically, methallylescaline is typically encountered as its , a white to off-white crystalline solid with a of 159–160 °C. It demonstrates solubility in organic solvents such as and , but limited solubility in water, consistent with its amphiphilic structure. Predicted physicochemical parameters include a around 363 °C and a pKa of approximately 9.6, indicating basic character suitable for salt formation.

Synthesis Methods

Methallylescaline, chemically 3,5-dimethoxy-4-(2-methylallyloxy)phenethylamine, is synthesized via a two-step process starting from homosyringonitrile (3,5-dimethoxy-4-hydroxyphenylacetonitrile). The phenolic hydroxyl group of homosyringonitrile is alkylated using methallyl chloride in the presence of a base such as potassium carbonate, yielding the intermediate 3,5-dimethoxy-4-methallyloxyphenylacetonitrile. This ether formation protects the position and sets the 4-substituent characteristic of scaline derivatives. The intermediate is then reduced to the primary amine using lithium aluminum hydride, producing methallylescaline after acidification and basification . Purification involves of the freebase followed by of the salt from and . This route, documented by , exemplifies adaptations of analog syntheses where ether substitution precedes nitrile reduction to minimize side reactions involving the amine functionality. Challenges in this method include ensuring complete to avoid phenolic impurities and managing reduction selectivity, as incomplete reactions can lead to lower yields and require rigorous purification for analytical purity. The process draws from established chemistry but demands controlled conditions to handle reactive reagents like lithium aluminum hydride, which poses fire hazards in non-laboratory environments. Shulgin's approach underscores the scalability limitations and purity demands for such compounds outside specialized facilities.

History

Discovery and Early Research

Methallylescaline, a analog of , was first synthesized by chemist Alexander T. Shulgin during his exploration of alkoxy-phenethylamines in the early 1980s. The synthesis involved O-alkylation of homosyringonitrile with methallyl chloride in the presence of and a , followed by reduction with lithium aluminum hydride and acidification to yield the hydrochloride salt. This work built on Shulgin's broader program of preparing and evaluating structural variants of , aiming to identify modifications that enhance potency or alter qualitative effects. Shulgin conducted initial human bioassays of methallylescaline, reporting threshold effects at 40 mg and stronger responses at 50-65 mg orally, with durations extending 12-16 hours—substantially shorter than 's typical 11-12 hours but at roughly one-fifth to one-tenth the dose (: 200-400 mg). Early qualitative reports from these trials described visual distortions, , and enhanced fantasy, though outcomes varied, with some assays yielding predominantly and others vivid erotic or kaleidoscopic imagery. These findings, derived from self-experimentation and small-group testing, provided preliminary potency estimates but lacked controlled pharmacological screening. Prior to the 2000s, no formal clinical trials or peer-reviewed studies on methallylescaline appear in scientific literature, reflecting the compound's status as a research chemical outside mainstream pharmaceutical development. Shulgin documented the synthesis and effects in PiHKAL (1991), serving as the primary reference for its properties, but empirical gaps persisted, including detailed receptor binding data or comparative toxicology. This scarcity underscores the reliance on anecdotal and exploratory assays in early phenethylamine research, constrained by regulatory barriers to systematic investigation.

Emergence as a Novel Psychoactive Substance

Methallylescaline, a synthetic analog of the controlled , first appeared in forensic detections of psychoactive substances (NPS) on blotter papers as early as 2015. By 2020, it was characterized in preclinical studies as a newly emerging , reflecting its gradual introduction into niche markets via online vendors seeking alternatives to regulated psychedelics. This analog design, featuring a methallyloxy substitution at the 4-position of the scaffold, facilitated its positioning outside immediate legal prohibitions on analogs in jurisdictions like the , where scheduling often lags behind chemical innovation. Surveillance data indicate limited evidence of widespread recreational use prior to recent years, with market dynamics driven by suppliers rather than established illicit distribution networks. Online monitoring by the National Drug Early Warning System (NDEWS) revealed a surge in discussions, particularly on platforms like , starting in late 2023, focusing on its availability and purported psychedelic properties. This prompted a dedicated NDEWS alert on May 10, 2024, highlighting increased web mentions and the substance's status as a agonist with mescaline-like effects, underscoring the challenges of real-time tracking in decentralized online marketplaces. Regulatory responses have trailed synthesis advancements, as evidenced by a 2025 , , and metabolism study on methallylescaline and the related NPS proscaline, which addressed gaps in toxicological data amid rising detections. Such research highlights the causal disconnect between rapid NPS proliferation—fueled by structural tweaking to exploit legal ambiguities—and the slower pace of empirical validation and control measures. NDEWS continues to flag methallylescaline in ongoing web surveillance, with follow-up reports in early 2025, indicating persistent but niche interest without indicators of broad epidemiological spread.

Pharmacology

Pharmacodynamics

Methallylescaline functions primarily as a , with its hallucinogenic effects attributable to activation of 5-HT2A receptors, consistent with the pharmacodynamic profile of analogs in the class. assays using human receptors demonstrate moderate binding affinity at 5-HT2A (Ki = 550 ± 190 nM), where it acts as a full (EC50 = 79 ± 12 nM; = 85 ± 5%). Affinity at 5-HT2C receptors is comparable (Ki = 520 ± 150 nM), suggesting potential contributions to downstream signaling, though with lower potency relative to some fluorinated analogs in the series. These interactions align with structure-activity trends among 4-alkoxy-3,5-dimethoxyphenethylamines, where alkoxy chain modifications enhance serotonergic potency over itself (Ki ≈ 6,000–9,000 nM at 5-HT2A). Negligible binding (Ki > 1,000 nM or undetectable) occurs at 5-HT1A, dopamine D2, trace amine-associated receptor 1 (TAAR1), and monoamine transporters (NET, DAT, SERT), indicating minimal stimulant-like modulation via dopaminergic or reuptake mechanisms. Empirical data remain limited to in vitro radioligand binding and functional assays, precluding definitive in vivo causal attributions without additional behavioral or neuroimaging studies.

Pharmacokinetics and Metabolism

Methallylescaline is orally active, with onset of psychoactive effects typically occurring 1 to 2 hours post-ingestion, consistent with patterns observed in mescaline analogs such as , where onset ranges from 10 to 50 minutes and peak effects emerge around 1 to 1.25 hours. The overall duration of action is estimated at 12 to 16 hours, based on qualitative human trials documented by , who tested dosages of 40 to 65 mg. Oral bioavailability data specific to methallylescaline are unavailable, but extrapolation from indicates substantial absorption, with at least 53% of an oral dose excreted unchanged in urine, suggesting minimal first-pass inactivation beyond partial to trimethoxyphenylacetic acid. Distribution details remain uncharacterized due to sparse , though as a lipophilic , it likely crosses the blood-brain barrier efficiently to elicit central effects, akin to related psychedelics. Metabolism is predominantly hepatic, involving phase I reactions that produce oxygenated derivatives. incubation with human hepatocytes via liquid chromatography-high-resolution has revealed primary metabolites including three isomeric monohydroxy-methallylescalines (M1–M3) and one dihydroxylated form (M4), confirming cytochrome P450-mediated oxidation as the key pathway. A comprehensive 2025 investigation integrating predictions, rodent models, and assays identified 11 distinct methallylescaline metabolites, the majority featuring aromatic or aliphatic , underscoring conserved routes among substituted . Excretion occurs mainly via the kidneys, mirroring mescaline’s profile where over half the dose appears unmetabolized in urine, though precise elimination , clearance rates, and potential for accumulation in chronic use are unknown, reflecting the absence of dedicated human pharmacokinetic trials. These gaps highlight reliance on analog data and preclinical models for inference, with no evidence of significant enterohepatic recirculation or alternative routes.

Subjective and Physiological Effects

Reported Subjective Effects

User reports, primarily from psychonaut forums and experience vaults, describe methallylescaline as eliciting mescaline-like hallucinogenic effects, including visual distortions such as enhanced colors, swirling patterns on surfaces, and kaleidoscopic imagery with open or closed eyes, often requiring focused attention to perceive fully. These perceptual alterations are frequently accompanied by cognitive , increased , and introspective insights, with some individuals reporting emotional openness manifesting as tears or a profound of connection to the world. , in documenting the compound in , noted active doses of 40-60 mg yielding such effects, portraying it as more potent than with a subtly stimulating quality rather than purely . A distinguishing feature in accounts is a stimulant-like component, including mental and physical energy, heightened tactile sensitivity, and reduced anxiety or pain perception, which contrasts with the heavier of traditional . Positive reports emphasize variability, with effects ranging from subtle, long-persisting perceptual shifts to immersive fostering empathy and clarity, though these remain anecdotal and unverifiable, potentially confounded by polydrug use or individual physiology. Conversely, negative subjective experiences highlight dysphoric elements, such as anxiety in sensitive users, intense prompting , or underwhelming intensity at lower thresholds (e.g., 40 mg), leading to disappointment and emphasis on precise dosing. Such variability underscores the compound's unpredictable nature across reports, where stimulating aspects may tip into discomfort for some, without controlled empirical validation.

Duration and Dosage Considerations

Methallylescaline is typically administered orally, with reporting effective dosages ranging from 40 to 65 mg based on human trials conducted in the late . Doses below 40 mg may produce threshold or mild effects, while those exceeding 65 mg have been associated with increased physical discomfort and restlessness, indicating non-linear scaling of intensity with dose increments. The onset of effects occurs within approximately 1 hour, with peak intensity reached by 1 to 2 hours post-ingestion, followed by a plateau that extends the total duration to 12 to 16 hours. This timeline reflects empirical observations from controlled self-experiments rather than large-scale , and individual variability in metabolism, body weight, and prior exposure can alter the precise progression. Compared to , which requires 200 to 400 mg for comparable potency and exhibits a similar overall duration of 10 to 12 hours, methallylescaline demonstrates roughly sixfold greater potency but no established pharmacokinetic superiority in onset or offset kinetics. Effects are influenced by psychological factors such as mindset and environment (set and setting), which can amplify or mitigate intensity independent of dose. Cross-tolerance develops rapidly with other phenethylamine psychedelics, reducing responsiveness upon repeated or sequential use within days, necessitating dose adjustments or abstinence periods for consistent outcomes. As a novel psychoactive substance often obtained from unregulated sources, variability in purity and accurate measurement poses risks of under- or overdosing, with no standardized pharmaceutical-grade product available for verification.

Risks and Safety Profile

Acute and Chronic Toxicity

Methallylescaline, a synthetic analog of , lacks comprehensive empirical data on due to limited human and . No 50 (LD50) has been established, and overdose case reports are absent from the literature, though its serotonergic agonism at 5-HT2A receptors suggests potential for , particularly when combined with other serotonergic agents, as observed in related phenethylamines like . Acute physiological effects may include cardiovascular strain, such as elevated and , extrapolated from studies where doses of 500 mg increased systolic , , and body temperature in healthy participants. and gastrointestinal distress are commonly reported in class compounds, though specific incidence for methallylescaline remains undocumented. Chronic toxicity data for methallylescaline is even scarcer, with no long-term human studies available to assess cumulative harms. Repeated activation of serotonergic pathways could theoretically contribute to , including potential downregulation of 5-HT receptors or , mechanisms implicated in chronic use of other hallucinogenic phenethylamines, though itself shows minimal evidence of such damage in traditional low-dose contexts. studies on methallylescaline indicate possible alterations in wave activity and involvement, raising concerns for abuse liability but not directly confirming neurotoxic outcomes. Without longitudinal evidence, assumptions of safety based on precedents are unwarranted, as structural modifications like the methallyloxy group may alter metabolic profiles and toxicity thresholds via and other enzymes. Overall, the evidential void underscores the need for caution in repeated exposure, prioritizing empirical gaps over analogical inference.

Psychological and Physiological Risks

Methallylescaline poses psychological risks akin to those of other serotonergic psychedelics, including acute episodes of , anxiety, , and that can escalate into challenging or traumatic experiences. User reports document psychosis-like states and self-harm attempts during intoxication, particularly in suboptimal environments or with predisposing factors such as genetic vulnerability to . These effects stem from potent agonism at 5-HT2A receptors, disrupting normal perceptual and emotional processing, though no controlled studies quantify incidence for methallylescaline specifically. Persistent psychological sequelae, such as (HPPD), occur rarely with psychedelics but remain undocumented in peer-reviewed data for methallylescaline; from related compounds suggests visual disturbances may linger post-use. Psychological dependence is possible with repeated recreational dosing, driven by and novelty-seeking, though physical appears absent. Physiologically, methallylescaline induces sympathomimetic effects like elevated heart rate, blood pressure, and body temperature, compromising thermoregulation and heightening dehydration or hyperthermia risks, especially during physical activity. Nausea, vomiting, and pronounced body load—manifesting as discomfort or heaviness—frequently precede peak effects, with isolated cases requiring medical intervention. Urinary retention is commonly reported, and high doses (above 50 mg) have been associated with temporary renal impairment in user accounts. Drug interactions amplify hazards: combining with inhibitors risks due to structure, while stimulants or alcohol exacerbate cardiovascular strain and seizure potential. Limited empirical data, derived primarily from self-reports on niche platforms, likely understates harms, as negative outcomes are less disseminated than favorable ones amid the substance's obscurity and illicit status.

Long-Term Health Implications

Due to the novelty of methallylescaline (MAL) as a , no longitudinal clinical studies exist on its long-term health implications, leaving potential risks speculative and inferred primarily from the broader class of serotonergic phenethylamine psychedelics. Recreational use patterns, often sporadic rather than chronic, limit direct evidence, but repeated exposure carries theoretical concerns for persistent perceptual disorders such as (HPPD), involving ongoing visual disturbances like trails, halos, or geometric patterns, documented in a small subset of users. These effects, while rare (prevalence estimates below 5% in surveyed populations), can endure for months or years and may exacerbate underlying vulnerabilities, though specific incidence with MAL remains unquantified. Serotonin system alterations represent another inferred risk, as MAL acts primarily as a agonist akin to ; chronic or frequent use of analogous psychedelics has been associated with downregulation of serotonin binding sites, as observed in of long-term ayahuasca users showing reduced 5-HT2A availability persisting beyond acute intoxication. Such changes could theoretically contribute to cognitive deficits, , or heightened susceptibility to mood disorders in predisposed individuals, though evidence from psychedelic cohorts often highlights adaptive rather than uniform harm, with causality unestablished due to confounding factors like . No data confirm serotonin neurotoxicity specific to MAL, distinguishing it from amphetamine-like phenethylamines, but absence of targeted research precludes dismissal of cumulative receptor desensitization risks. MAL's synthetic profile introduces additional uncertainties compared to natural , whose traditional ceremonial use over centuries reports no widespread chronic physical sequelae beyond tolerance buildup. Recent metabolic profiling via , , and models identified 11 unique metabolites for MAL, including hydroxylated and N-acetylated forms not prominent in , potentially yielding novel bioactive compounds with untested toxicities. Clandestine production amplifies this via impurities from incomplete synthesis routes, as seen in other synthetic phenethylamines where contaminants correlate with acute organ strain or idiosyncratic reactions. Absent empirical validation of safety or therapeutic persistence, prolonged MAL exposure lacks justification over verified alternatives with established risk profiles, underscoring the need for precautionary restraint.

United States

Methallylescaline is not explicitly listed in any schedule of the , and the has taken no specific scheduling action against it as of 2025. Nonetheless, it qualifies as a controlled substance analog under the (21 U.S.C. § 813) due to its substantial structural similarity to —a Schedule I —as a 4-(2-methylallyloxy)-3,5-dimethoxyphenethylamine derivative with comparable serotonergic effects. This renders possession, distribution, or manufacture prosecutable as a federal equivalent to Schedule I offenses when intended for human consumption, emphasizing prosecutorial focus on intent rather than chemical novelty alone. The Act's application to methallylescaline exemplifies its broad scope in addressing novel psychoactive substances (NPS), intended to prevent circumvention of controls through minor modifications, though critics argue this constitutes overreach by imposing criminal liability on structurally similar compounds absent of harm or abuse potential. Enforcement remains challenging given the substance's rarity, with no recorded mentions in DEA forensic databases like the National Forensic Laboratory Information System (NFLIS) or seizure reports, indicating limited domestic prevalence. State-level regulations show minimal variation, typically deferring to federal analog provisions without independent bans or scheduling, as most states align with the for derivatives. (analogous alignment for NPS) Monitoring efforts underscore precautionary intent amid low empirical risk signals: In May 2024, the National Drug Early Warning System (NDEWS) issued an alert on increasing online mentions of methallylescaline since late 2023, primarily on , discussing its visual hallucinogenic effects akin to alongside reports of and dose sensitivity, but without associated data on overdoses, trafficking, or clinical harms. This reflects proactive surveillance of NPS discussions rather than reactive enforcement driven by widespread use.

International Controls and Analog Provisions

Methallylescaline is classified as illegal in , where it was added to the list of health hazard substances effective January 26, 2016, prohibiting its manufacture, possession for sale, import, export, and use in consumer products. In the broader European context, it has been identified and monitored as a new psychoactive substance (NPS) through the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) , with analytical confirmations reported in member states' forensic data since at least 2013, though it lacks EU-wide scheduling under the 2005 Decision framework. In the , methallylescaline is controlled under the , which imposes penalties for producing, supplying, offering to supply, possessing with intent to supply, importing, or exporting any psychoactive substance intended for human consumption, excluding exempted categories like alcohol or medicinal products; this blanket provision captures structural analogs without requiring specific listing. Canada's does not explicitly schedule methallylescaline, classifying it instead as an uncontrolled NPS alongside other phenethylamines like , though may invoke analog clauses based on its close structural relation to Schedule III if intent for human consumption is demonstrated. These international controls frequently hinge on analog provisions or generic psychoactive bans—emphasizing chemical similarity to established phenethylamines such as —rather than substance-specific empirical data on or , as evidenced by limited reports, including initial detections in in 2013 and sporadic powder identifications in EMCDDA alerts. Such precautionary measures, while addressing potential risks from class-wide pharmacological profiles, overlook the scarcity of documented acute harms or widespread use, potentially impeding evidence-based evaluation and research into low-incidence psychedelics where preclinical metabolism studies indicate demethylation and pathways akin to safer congeners. This structural prioritization over causal harm data underscores regulatory inconsistencies across jurisdictions, where low empirical threat contrasts with prohibitive stances that may reflect broader institutional caution toward novel phenethylamines irrespective of differentiated risk profiles.

Societal Impact and Research Developments

Recreational and Research Use

Methallylescaline has seen limited recreational use, mainly among experimenting with synthetic analogs as substitutes for , due to its reported milder potency and availability through online vendors. Discussions in niche online communities emphasize its psychedelic profile for personal exploration, though prevalence remains low compared to established substances like or , with isolated detections on blotter papers suggesting sporadic, non-mainstream consumption patterns. Proponents in these circles argue for its value in introspective experiences, while analyses underscore uncontrolled risks from black-market sourcing, including potential adulteration with unidentified contaminants that could exacerbate physiological strain. Scientific research on methallylescaline is sparse and confined to preclinical investigations, such as metabolic profiling and receptor binding assays, rather than human trials or therapeutic applications. A March 2025 study employed , , and approaches to identify 11 metabolites, including hydroxylated and N-acetylated forms, providing biomarkers for forensic detection and insights into its in biological systems. Additional work has mapped its interactions with serotonin receptors, positioning it within structure-activity relationships of 4-alkoxy-3,5-dimethoxyphenethylamines, but without advancing to clinical evaluation amid the broader psychedelic research surge focused on classics like . This narrow scope highlights evidentiary gaps, prioritizing over claims in self-reported recreational contexts. The National Drug Early Warning System (NDEWS) detected a notable increase in online mentions of methallylescaline, particularly on Reddit, during late 2023 and into 2024, prompting an alert on May 10, 2024, that highlighted the substance's emergence as a synthetic mescaline analog with potential psychedelic effects via 5-HT receptor agonism. This surge in discussions, tracked through web monitoring, suggested heightened interest or availability among niche online communities focused on research chemicals, yet lacked corroboration from traditional indicators like emergency department visits or overdose reports in NDEWS surveillance data up to that point. A follow-up NDEWS update on February 21, 2025, reiterated ongoing monitoring of terms like "MAL" and "methallylescaline," indicating sustained but not exponentially growing signals without associated harm metrics. In 2025, research advanced on methallylescaline's metabolic profile, with a March publication detailing predictions, rat studies, and human hepatocyte assays that identified primary phase I metabolites, including hydroxy- and dihydroxy-variants, via cytochrome P450-mediated oxidation. These findings elucidated potential pharmacokinetic pathways but emphasized persistent gaps in human-specific data, such as profiles and long-term accumulation risks, limiting causal inferences about toxicity or therapeutic windows. Complementary work confirmed metabolism to hydroxylated forms without quantifying systemic exposure in users. Surveillance trends through mid-2025 reveal a pattern where online visibility precedes verifiable or adverse outcomes, as no NDEWS or international early warning systems reported clustered intoxications or fatalities attributable to methallylescaline by October 2025. This disconnect implies that regulatory pursuits, often analog-based, may lag of harm, with monitoring underscoring the challenges of preempting risks in rapidly iterating psychoactive substance landscapes absent robust .

References

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