|Summary sheet: MDAI|
|Chemical class||Aminoindane / MDxx|
|Routes of Administration|
5,6-Methylenedioxy-2-aminoindane (also known as MDAI) is a lesser-known novel entactogen substance of the aminoindane class. It acts as a putatively non-neurotoxic and highly selective serotonin releasing agent (SSRA) with neglible effects on dopamine and norepinephrine.
MDAI was developed by the American medicinal chemist and pharmacologist David E. Nichols during the 1990s at Purdue University. in the 2010s, MDAI was marketed alongside novel entactogens like 5-MAPB, 5-APB, and 6-APB as a legal, grey-market alternative to MDMA in the online research chemical market. It is currently being investigated as a potential alternative to traditional entactogens in the treatment of mental health conditions like anxiety and depression.
Subjective effects include sedation, muscle relaxation, tactile enhancement, anxiety suppression, enhanced empathy and sociability and euphoria. It has been described as producing the non-stimulating effects of prototypical entactogens like MDMA and MDA. It has been suggested that the lack of dopamine and norepinephrine activity limits its ability to produce overtly invigorating, prosocial or euphoric effects but with the benefit of decreased neurotoxicity and side-effects. However, more research is required to validate these claims.
Very little data exists about the pharmacological properties, metabolism, and toxicity of MDAI, and it has a limited history of human use. It is highly advised to use harm reduction practices if using this substance.
MDAI, or 5,6-methylenedioxy-2-aminoindane, is a synthetic molecule of the aminoindane class with structural similarity to amphetamines. It features the R3 terminal carbon of the propane chain of amphetamine bound to the benzene ring. This creates an indane group, a bicyclic moeity containing a benzene ring fused to a pentane ring. MDAI contains an amino group NH2 bound to R2 of the indane ring. MDAI also contains two oxygen substitutions at R5 and R6 joined by a methylene bridge to form a methylenedioxy group.
MDAI is structurally related to 2-AI, differing by a methylenedioxy ring.
MDAI has been shown to inhibit the reuptake of serotonin and has a selective affinity for the serotonin receptor. Studies have shown that the brains of animals treated with MDAI have greater extracellular concentrations of monoamine neural transmitters, most significantly serotonin.
For comparison, MDAI is similar in potency with releasing serotonin to MDA, but significantly less potent than MDMA. This is done by inhibiting the reuptake and reabsorption of the neurotransmitters after they have performed their function of transmitting a neural impulse, essentially allowing them to accumulate, be reused and cause entactogenic effects.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
- Sedation - The largest reported difference between MDAI and MDMA is that MDAI primarily results in moderate sedation and can therefore discourage physical activities such as running, dancing or climbing.
- Spontaneous physical sensations - The "body high" of MDAI can be described as a moderate to extreme euphoric, soft and warm tingling sensation that encompasses the entire body. It is capable of becoming overwhelmingly pleasurable at higher doses. This sensation maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached.
- Tactile enhancement
- Vibrating vision - At high doses, a person's eyeballs may begin to spontaneously wiggle back and forth in a rapid motion, causing the vision to become blurry and temporarily out of focus. This is a condition known as nystagmus.
- Increased perspiration
- Temperature regulation suppression
- Dehydration - Feelings of dry mouth and dehydration are a universal experience with MDAI. This effect is a product of an increased heart rate and an extreme motivation to engage in strenuous physical activities. While it is important to avoid becoming dehydrated (especially when out dancing in a hot environment) there have been a number of users suffering from water intoxication through over-drinking, so it is advised that users simply sip at water and never over-drink.
- Difficulty urinating - Much like MDMA, higher doses of MDAI result in difficulty urinating. This is an effect that is completely temporary and harmless. It is most likely due to the promotion of the release of anti-diuretic hormone (ADH), which is the mechanism responsible for this side effect within MDMA. Anti-diuretic hormone is responsible for regulating urination. Difficulty urinating can be lessened by simply relaxing, but can be significantly relieved by placing a hot flannel over the genitals to warm them up and encourage blood flow. Some have reported that simply listening to the sound of running water also helps (such as a tap/faucet).
- Temporary erectile dysfunction
The cognitive effects of MDAI can be broken down into several components which progressively intensify proportional to dosage. The general head space of MDAI is described by many as one of euphoria and feelings of love or empathy. It contains a number of typical entactogenic cognitive effects.
The most prominent of these cognitive effects generally include:
- Anxiety suppression
- Cognitive euphoria - Strong emotional euphoria and feelings of happiness are present within MDAI and are a direct result of serotonin release.
- Empathy, affection, and sociability enhancement - This particular effect is not as pronounced, powerful and therapeutic as that of MDMA or 2C-B. It is the most obvious and noticeable effect within any MDAI experience and dominates the head space.
- Increased music appreciation
- Immersion enhancement
- Thought deceleration
- Time distortion
- The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
This toxicity and harm potential section is a stub.
As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
MDAI and other similar drugs have been widely used in scientific research as they are able to replicate many of the effects of MDMA, but without causing the associated neurotoxicity. No tests have been performed on cardiovascular toxicity.
There is currently no scientific data on the lethal dose of MDAI in humans and the exact toxic dosage is unknown. Due to its action as a serotonin reuptake inhibitor, overdoses of this substance would likely result in serotonin syndrome.
It is strongly recommended that one use harm reduction practices when using this substance.
Dependence and abuse potential
Although no formal studies have been conducted, MDAI can be considered somewhat habit-forming with a low potential for abuse and is unlikely to be capable of causing psychological dependence among most users. This is because unlike traditional stimulants, MDAI does not increase concentrations of dopamine. If addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Tolerance to many of the effects of MDAI develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption).
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- 25x-NBOMe & 25x-NBOH - 25x compounds are highly stimulating and physically straining. Combinations with MDAI should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
- Alcohol - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
- DXM - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
- MDMA - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
- MXE - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
- Dissociatives - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
- Stimulants - MDAI may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
- Tramadol - Tramadol is known to lower the seizure threshold and combinations with stimulants may further increase this risk.
- MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants.
- Cocaine - This combination may increase strain on the heart to a dangerous degree.
Serotonin syndrome risk
- Austria: MDAI is illegal to possess, produce and sell under the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich).
- Brazil: MDAI is illegal to possess, produce and sell under Portaria SVS/MS nº 344.
- China: As of October 2015, MDAI is a controlled substance in China.
- Denmark: MDAI is illegal in Denmark as of September 2015.
- Germany: MDAI is controlled under the NpSG (New Psychoactive Substances Act) as of November 26, 2016. Production and import with the aim to place it on the market, administration to another person and trading is punishable. Possession is illegal but not penalized.
- Japan: MDAI is a controlled substance in Japan effective March 30th, 2013.
- Switzerland: MDAI is a controlled substance specifically named under Verzeichnis E. It is a controlled substance since December 2011.
- Turkey: MDAI is a classed as drug and is illegal to possess, produce, supply, or import. 
- United Kingdom: MDAI is illegal to produce, supply, or import under the Psychoactive Substance Act, which came into effect on May 26th, 2016.
- Johnson, M. P., Conarty, P. F., Nichols, D. E. (23 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. ISSN 0014-2999.
- Nichols, D. E., Brewster, W. K., Johnson, M. P., Oberlender, R., Riggs, R. M. (February 1990). "Nonneurotoxic tetralin and indan analogues of 3,4-(methylenedioxy)amphetamine (MDA)". Journal of Medicinal Chemistry. 33 (2): 703–710. doi:10.1021/jm00164a037. ISSN 0022-2623.
- Nichols, D. E., Johnson, M. P., Oberlender, R. (January 1991). "5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine". Pharmacology, Biochemistry, and Behavior. 38 (1): 135–139. doi:10.1016/0091-3057(91)90601-w. ISSN 0091-3057.
- MP, J., SP, F., ((R, O.)), DE, N. (1 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): 1662–1668. doi:10.1021/JM00109A020.
- Johnson, M. P., Huang, X. M., Nichols, D. E. (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): 915–922. doi:10.1016/0091-3057(91)90106-c. ISSN 0091-3057.
- Nichols, D. E., Marona-Lewicka, D., Huang, X., Johnson, M. P. (1993). "Novel serotonergic agents". Drug Design and Discovery. 9 (3–4): 299–312. ISSN 1055-9612.
- Sprague, J. E., Johnson, M. P., Schmidt, C. J., Nichols, D. E. (25 October 1996). "Studies on the mechanism of p-chloroamphetamine neurotoxicity". Biochemical Pharmacology. 52 (8): 1271–1277. doi:10.1016/0006-2952(96)00482-0. ISSN 0006-2952.
- Cozzi, N. V., Frescas, S., Marona-Lewicka, D., Huang, X., Nichols, D. E. (March 1998). "Indan analogs of fenfluramine and norfenfluramine have reduced neurotoxic potential". Pharmacology, Biochemistry, and Behavior. 59 (3): 709–715. doi:10.1016/s0091-3057(97)00557-1. ISSN 0091-3057.
- Talaie, H.; Panahandeh, R.; Fayaznouri, M. R.; Asadi, Z.; Abdollahi, M. (2009). "Dose-independent occurrence of seizure with tramadol". Journal of Medical Toxicology. 5 (2): 63–67. doi:10.1007/BF03161089. eISSN 1937-6995. ISSN 1556-9039. OCLC 163567183.
- Gillman, P. K. (2005). "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity". British Journal of Anaesthesia. 95 (4): 434–441. doi: . eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647.
- 关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | http://www.sfda.gov.cn/WS01/CL0056/130753.html
- "Lists of euphoriant substances subject to control in Denmark". The Danish Medicines Agency. September 2015. | http://laegemiddelstyrelsen.dk/en/licensing/company-authorisations-and-registrations/euphoriant-substances/lists
- "Anlage NpSG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 15, 2019.
- "Gesetz zur Bekämpfung der Verbreitung neuer psychoaktiver Stoffe" (PDF) (in German). Bundesanzeiger Verlag. Retrieved December 15, 2019.
- "§ 4 NpSG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 15, 2019.
- "新たに指定された指定薬物の名称" (PDF, in Japanese). 厚生労働省 [Ministry of Health, Labour and Welfare (MHLW)]. Retrieved on May 2, 2022.
- "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.
- Başbakanlık Mevzuatı Geliştirme ve Yayın Genel Müdürlüğü
- Psychoactive Substances Act 2016