MDAI, also known as5,6-methylenedioxy-2-aminoindane, is anentactogen of the2-aminoindane family which is related toMDMA and produces similar subjective effects.[4][5][6][1]
A 2024 study compared the effects of MDAI andMDMA in humans.[1] It found that MDAI produced comparable and very similar subjective effects to those of MDMA.[1] This included pleasurable drug effects,drug liking, stimulation, happiness, openness, trust, and closeness.[1] In addition, it included sense of well-being, emotional excitation, and extroversion, but not general activity or concentration, a profile of effects described as similar to that of MDMA.[1] Other effects included a blissful state, experience of unity, and changed meaning of percepts, also described as comparable to MDMA.[1] The effects of MDAI were slightly greater than those of 75mg MDMA and slightly lower than those of 125mg MDMA.[1] At the employed dose of 3.0mg/kg, with 125mg MDMA corresponding to 1.9mg/kg, it was estimated that MDAI had about 60% of MDMA's potency in producing comparable psychoactive effects (hence, roughly 200mg MDAI would be similar to 125mg MDMA).[1] Aside from subjective effects, MDAI also increasedblood pressure,cortisol levels, andprolactin levels similarly to MDMA.[1] Conversely, it did not increaseheart rate orbody temperature.[1]
Very high doses can be fatal in rats with a 50% fatality rate for those subcutaneously injected with 28 mg/kg of MDAI. This is a result of the way serotonin release interferes with thermoregulation.[12]
MDAI is only non-neurotoxic in isolation but may becomeneurotoxic when mixed with other drugs.[13] Three deaths were linked to MDAI use in theUnited Kingdom during 2011 and 2012, all involving symptoms consistent withserotonin syndrome. Two of these also involved other drugs while one death appeared to be from MDAI alone.[7]
The family of drugs typified byMDMA produce their effects through multiple mechanisms of action in the body, and consequently produce three distinct cues which animals can be trained to respond to: a stimulant cue typified by drugs such asmethamphetamine, a psychedelic cue typified by drugs such asLSD andDOM, and an "entactogen-like" cue which is produced by drugs such as MDAI andMBDB. These drugs cause drug-appropriate responses in animals trained to recognize the effects of MDMA, but do not produce responses in animals trained selectively to respond to stimulants or hallucinogens. Because these compounds selectively release serotonin in the brain but have little effect on dopamine or noradrenaline levels, they can produce empathogenic effects but without any stimulant action, instead being somewhat sedating.[22][23][24][25][26][27][28]
MDAI shows substantially lowerserotonergic neurotoxicity thanMDMA in animals and has been described as a "non-neurotoxic" analogue of MDMA.[7][8][9] However, MDAI still shows weak serotonergic neurotoxicity both alone and particularly incombination withamphetamine in animals.[7][8][9] As such, MDAI does not appear to be a fully non-neurotoxic alternative to MDMA.[7][8][9]
MDAI can be produced from 3-(3,4-methylenedioxyphenyl)propionic acid[29] which is converted to the acid chloride and then heated to produce 5,6-methylenedioxy-1-indanone. Treatment of the indanone with amyl nitrite in methanol with HCl afforded the hydroxyimino ketone. This is reduced to the 2-aminoindan following a modification of Nichols' earlier method from a paper discussingDOM analogues,[30] using aPd/C catalyst in glacialacetic acid with catalyticH2SO4.
MDAI has been advertised as adesigner drug. It started to be sold online from around 2007, but reached peak popularity between about 2010 to 2012, after bans onmephedrone came into effect in various countries. Many internet-sourced products claimed to be MDAI have been shown to containmephedrone or othercathinones, while generally containing no MDAI. The number of internet searches for MDAI has been considerably higher in theUnited Kingdom compared toGermany and theUnited States.[11]
^abSainsbury PD, Kicman AT, Archer RP, King LA, Braithwaite RA (2011). "Aminoindanes--the next wave of 'legal highs'?".Drug Testing and Analysis.3 (7–8). Wiley:479–482.doi:10.1002/dta.318.PMID21748859.
^abcdefCorkery JM, Elliott S, Schifano F, Corazza O, Ghodse AH (July 2013). "MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') toxicity: a brief overview and update".Human Psychopharmacology.28 (4):345–355.doi:10.1002/hup.2298.PMID23881883.S2CID12322724.
^abcdJohnson MP, Huang XM, Nichols DE (December 1991). "Serotonin neurotoxicity in rats after combined treatment with a dopaminergic agent followed by a nonneurotoxic 3,4-methylenedioxymethamphetamine (MDMA) analogue".Pharmacol Biochem Behav.40 (4):915–922.doi:10.1016/0091-3057(91)90106-c.PMID1726189.
^abJohnson MP, Conarty PF, Nichols DE (July 1991). "[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues".European Journal of Pharmacology.200 (1):9–16.doi:10.1016/0014-2999(91)90659-e.PMID1685125.
^abGallagher CT, Assi S, Stair JL, Fergus S, Corazza O, Corkery JM, et al. (March 2012). "5,6-Methylenedioxy-2-aminoindane: from laboratory curiosity to 'legal high'".Human Psychopharmacology.27 (2):106–112.doi:10.1002/hup.1255.PMID22389075.S2CID205924978.
^Páleníček T, Lhotková E, Žídková M, Balíková M, Kuchař M, Himl M, et al. (August 2016). "Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats".Progress in Neuro-Psychopharmacology & Biological Psychiatry.69:49–59.doi:10.1016/j.pnpbp.2016.04.004.PMID27083855.S2CID33032545.
^Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain".European Journal of Pharmacology.559 (2–3):132–137.doi:10.1016/j.ejphar.2006.11.075.PMID17223101.
^Steele TD, Nichols DE, Yim GK (July 1987). "Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain".Biochemical Pharmacology.36 (14):2297–303.doi:10.1016/0006-2952(87)90594-6.PMID2886126.
^Nichols DE (1986). "Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens".Journal of Psychoactive Drugs.18 (4):305–13.doi:10.1080/02791072.1986.10472362.PMID2880944.
^Oberlender R, Nichols DE (December 1990). "(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine as a discriminative stimulus in studies of 3,4-methylenedioxy-methamphetamine-like behavioral activity".The Journal of Pharmacology and Experimental Therapeutics.255 (3):1098–106.doi:10.1016/S0022-3565(25)22947-0.PMID1979813.
^Oberlender R, Nichols DE (March 1991). "Structural variation and (+)-amphetamine-like discriminative stimulus properties".Pharmacology, Biochemistry, and Behavior.38 (3):581–6.doi:10.1016/0091-3057(91)90017-V.PMID2068194.S2CID19069907. PMID
^abNichols DE, Brewster WK, Johnson MP, Oberlender R, Riggs RM (February 1990). "Nonneurotoxic tetralin and indan analogues of 3,4-(methylenedioxy)amphetamine (MDA)".Journal of Medicinal Chemistry.33 (2):703–10.doi:10.1021/jm00164a037.PMID1967651.
^Nichols DE, Barfknecht CF, Long JP, Standridge RT, Howell HG, Partyka RA, et al. (February 1974). "Potential psychotomimetics. 2. Rigid analogs of 2,5-dimethoxy-4-methylphenylisopropylamine (DOM, STP)".Journal of Medicinal Chemistry.17 (2):161–6.doi:10.1021/jm00248a004.PMID4809251.
^Nichols DE, Oberlender R (1989). "Structure-activity relationships of MDMA-like substances".NIDA Research Monograph.94:1–29.PMID2575223.
^"关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived fromthe original on 1 October 2015. Retrieved1 October 2015.
^"812.121.11"(PDF).Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien (Regulation of the EDI about the directories of drugs, psychotropic substances, precursors and auxiliary chemicals) (in German). Das Eidgenössische Departement des Innern (EDI). December 2011.
^Johnson MP, Frescas SP, Oberlender R, Nichols DE (May 1991). "Synthesis and pharmacological examination of 1-(3-methoxy-4-methylphenyl)-2-aminopropane and 5-methoxy-6-methyl-2-aminoindan: similarities to 3,4-(methylenedioxy)methamphetamine (MDMA)".Journal of Medicinal Chemistry.34 (5):1662–8.doi:10.1021/jm00109a020.PMID1674539.
^Johnson MP, Huang XM, Nichols DE (December 1991). "Serotonin neurotoxicity in rats after combined treatment with a dopaminergic agent followed by a nonneurotoxic 3,4-methylenedioxymethamphetamine (MDMA) analogue".Pharmacology, Biochemistry, and Behavior.40 (4):915–22.doi:10.1016/0091-3057(91)90106-c.PMID1726189.S2CID7199902.
^Sprague JE, Johnson MP, Schmidt CJ, Nichols DE (October 1996). "Studies on the mechanism of p-chloroamphetamine neurotoxicity".Biochemical Pharmacology.52 (8):1271–7.doi:10.1016/0006-2952(96)00482-0.PMID8937435.
^Cozzi NV, Frescas S, Marona-Lewicka D, Huang X, Nichols DE (March 1998). "Indan analogs of fenfluramine and norfenfluramine have reduced neurotoxic potential".Pharmacology, Biochemistry, and Behavior.59 (3):709–15.doi:10.1016/s0091-3057(97)00557-1.PMID9512076.S2CID41048219.
