3,4-Methylenedioxyamphetamine

MDA is bought, sold, and used as a recreational drug due to its enhancement of mood and empathy. It produces MDMA-like effects, including entactogenic and stimulant effects, as well as mild psychedelic effects. The dose range of MDA is very similar to that of MDMA. It does not produce profound sensory disruption or overt hallucinations. Enantiopure (R)-MDA at high doses produces more robust psychedelic effects than typical doses of racemic MDA. The duration of MDA is about 5 to 8hours and is about 2hours longer than that of MDMA (3–6hours). Shulgin originally gave a duration of MDA of 8 to 12hours in PiHKAL, but he later revised this down to only 3 to 6hours. Modern clinical studies have given an average duration of 6 to 8hours with a range of 0.9 to 10hours. The drug's onset is 0.7hours (range 0.3 to 1.1hours) and its time to peak effects is 2.0hours (range 1.0 to 3.5hours). ==Side effects==

Side effects of MDA include sympathomimetic effects like increased heart rate and blood pressure as well as increased cortisol and prolactin levels. ==Overdose==

Symptoms of acute toxicity may include agitation, sweating, increased blood pressure and heart rate, dramatic increase in body temperature, convulsions, and death. Death is usually caused by cardiac effects and subsequent hemorrhaging in the brain (stroke). A 450mg intravenous injection of MDA was found to result in death in one case. ==Interactions==

Pharmacodynamics MDA is a substrate of the serotonin, norepinephrine, dopamine, and vesicular monoamine transporters, and in relation to this, acts as a reuptake inhibitor and releasing agent of serotonin, norepinephrine, and dopamine (that is, it is an ). It is also an agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors and shows affinity for the α2A-, α2B-, and α2C-adrenergic receptors and serotonin 5-HT1A and 5-HT7 receptors. In addition to its actions as a monoamine releasing agent, MDA is a potent high-efficacy partial agonist or full agonist of the rodent TAAR1. Moreover, MDA acts as a very weak partial agonist or antagonist of the human TAAR1 rather than as an efficacious agonist. MDA fully substitutes for MDMA in rodent drug discrimination tests. MDA also substitutes for stimulants like dextroamphetamine and cocaine in drug discrimination tests. However, the head-twitch response they produce is very weak in magnitude compared to other related psychedelics such as the DOx drugs. This might in part be due to metabolism of MDA. In addition, MDA activates a response of the neuroglia, though this subsides after use. Its duration of action has been reported to be about 6 to 8hours. The duration of MDA is longer than that of MDMA, about 8hours for MDA versus 6hours for MDMA. The elimination half-life of MDA is 10.9hours. Differences in the duration of MDA versus MDMA may be due pharmacodynamics rather than pharmacokinetics. ==Chemistry==

MDA is a substituted methylenedioxylated phenethylamine and amphetamine derivative. Synonyms In addition to 3,4-methylenedioxyamphetamine, MDA is also known by other chemical synonyms such as the following: • α-Methyl-3,4-methylenedioxy-β-phenylethylamine • 1-(3,4-Methylenedioxyphenyl)-2-propanamine • 1-(1,3-Benzodioxol-5-yl)-2-propanamine Synthesis MDA is typically synthesized from essential oils such as safrole or piperonal. Common approaches from these precursors include: • Reaction of safrole's alkene functional group with a halogen containing mineral acid followed by amine alkylation. • Wacker oxidation of safrole to yield 3,4-methylenedioxyphenylpropan-2-one (MDP2P) followed by reductive amination or via reduction of its oxime. • Henry reaction of piperonal with nitroethane followed by nitro compound reduction. This gives MDP2P, which was then subjected to a Leuckart reaction. • The "two dogs" or "dopeboy" clandestine method, starting with helional as a precursor. First, an oxime is created using hydroxylamine. Then, a Beckmann rearrangement is performed with nickel acetate to form the amide. Then a Hofmann rearrangement is done to form the freebase amine of MDA. Then it is purified with an acid base extraction. Detection in body fluids MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDA and major metabolites of MDMA, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug. Analogues and derivatives Analogues of MDA include its positional isomer 2,3-methylenedioxyamphetamine (2,3-MDA) and others. MDMA is the N-methyl derivative of MDA. Some other analogues of MDA include 5-APB, 6-APB, 5-APDB, 6-APDB, 5-APBT, 6-APBT, and SDA (3T-MDA), among others. MDA constitutes part of the core structure of the β-adrenergic receptor agonist protokylol. ==History==

MDA was first synthesized by Carl Mannich and Willy Jacobsohn in 1910. MDA was first used in animal tests in 1939, and human trials began in 1941 in the exploration of possible therapies for Parkinson's disease. MDA was patented as an ataractic by Smith, Kline & French in 1960, and as an anorectic under the trade name "Amphedoxamine" in 1961. MDA began to appear on the recreational drug scene around 1963 to 1964. It was then inexpensive and readily available as a research chemical from several scientific supply houses. Several researchers, including Claudio Naranjo and Richard Yensen, have explored MDA in the field of psychotherapy. The International Nonproprietary Name (INN) tenamfetamine was recommended by the World Health Organization (WHO) in 1986. It was recommended in the same published list in which the INN of 2,5-dimethoxy-4-bromoamphetamine (DOB), brolamfetamine, was recommended. Matthew J. Baggott and colleagues conducted some of the first modern clinical studies of MDA in humans and published their findings in the 2010s. ==Society and culture==

Names When MDA was under development as a potential pharmaceutical drug, it was given the International Nonproprietary Name (INN) of tenamfetamine. Legal status Australia MDA is schedule 9 prohibited substance under the Poisons Standards. A schedule 9 substance is listed as a "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities." European Union MDA is individually classified by countries in the European Union, but generally the countries follow the Convention on Psychotropic Substances. United States MDA is a Schedule I controlled substance in the United States. ==Research==

MDA has been studied in entactogen-assisted psychotherapy. ==See also==