MDAI
MDAI, also known as 5,6-methylenedioxy-2-aminoindane, is an entactogen of the 2-aminoindane family which is related to MDMA and produces similar subjective effects.
It acts as a selective serotonin and norepinephrine releasing agent. The drug shows greatly reduced serotonergic neurotoxicity in comparison to MDMA in animals, although it still shows weak capacity for neurotoxicity with chronic use or in combination with amphetamine.
MDAI was developed in the 1990s by a team led by David E. Nichols at Purdue University. It has been encountered as a designer drug and has been used recreationally with reported street names such as "sparkle" and "mindy". In addition to its recreational use, there has been interest in MDAI for potential use in medicine, for instance in drug-assisted psychotherapy.
Use and effects
A 2024 study compared the effects of MDAI and MDMA in humans. It found that MDAI produced comparable and very similar subjective effects to those of MDMA. This included pleasurable drug effects, drug liking, stimulation, happiness, openness, trust, and closeness. 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. Other effects included a blissful state, experience of unity, and changed meaning of percepts, also described as comparable to MDMA. The effects of MDAI were slightly greater than those of 75mg MDMA and slightly lower than those of 125mg MDMA. 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. Aside from subjective effects, MDAI also increased blood pressure, cortisol levels, and prolactin levels similarly to MDMA. Conversely, it did not increase heart rate or body temperature.Toxicity
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.MDAI is only non-neurotoxic in isolation but may become neurotoxic when mixed with other drugs. Three deaths were linked to MDAI use in the United Kingdom during 2011 and 2012, all involving symptoms consistent with serotonin syndrome. Two of these also involved other drugs while one death appeared to be from MDAI alone.
Pharmacology
Pharmacodynamics
MDAI acts as a selective and well-balanced serotonin and norepinephrine releasing agent with much less effect on dopamine release. In addition to inducing the release of the monoamine neurotransmitters, MDAI also inhibits their reuptake. For comparison to MDAI, MDA and MDMA are well-balanced releasing agents of serotonin, norepinephrine, and dopamine. Conversely, the profile of monoamine release with MDAI is very similar to that of (R)-MDMA, which like MDAI is also a well-balanced SNRA with about 10-fold reduced impact on dopamine release, though MDAI is several-fold more potent than -MDMA in vitro.In contrast to MDMA, MDAI shows no affinity for any of the serotonin receptors. This notably includes the serotonin 5-HT2A receptor, which is implicated in producing psychedelic effects, and the serotonin 5-HT2B receptor, which is implicated in causing cardiac valvulopathy. However, MDAI shows significant affinity for all three of the α2-adrenergic receptors.
The family of drugs typified by MDMA 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 as methamphetamine, a psychedelic cue typified by drugs such as LSD and DOM, and an "entactogen-like" cue which is produced by drugs such as MDAI and MBDB. 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.
MDAI shows substantially lower serotonergic neurotoxicity than MDMA in animals and has been described as a "non-neurotoxic" analogue of MDMA. However, MDAI still shows weak serotonergic neurotoxicity both alone and particularly in combination with amphetamine in animals. As such, MDAI does not appear to be a fully non-neurotoxic alternative to MDMA.