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3,4-Methylenedioxyamphetamine
INN: Tenamfetamine

Clinical data
Other names	MDA; Tenamfetamine; Amphedoxamine; Sally; Sassafras; Sass-a-frass; Sass; Mellow Drug of America; Hug drug; Love; 3,4-Methylenedioxy-α-methylphenethylamine; 5-(2-Aminopropyl)-1,3-benzodioxole; EA-1298; NSC-9978; NSC-27106; SKF-5
Routes of administration	By mouth, sublingual, insufflation, intravenous
Drug class	Empathogen–entactogen; Stimulant
ATC code	None
Legal status
Legal status	AU: S9 (Prohibited substance) BR: Class F2 (Prohibited psychotropics) CA: Schedule I DE: Anlage I (Authorized scientific use only) UK: Class A US: Schedule I UN: Psychotropic Schedule I
Pharmacokinetic data
Metabolism	Hepatic (CYP extensively involved)
Duration of action	6–8 hours
Excretion	Renal
Identifiers
IUPAC name 1-(2H-1,3-Benzodioxol-5-yl)propan-2-amine
CAS Number	4764-17-4
PubChem CID	1614
DrugBank	DB01509
ChemSpider	1555
UNII	XJZ28FJ27W
KEGG	D12715
ChEMBL	ChEMBL6731
CompTox Dashboard (EPA)	DTXSID40859958
ECHA InfoCard	100.230.706
Chemical and physical data
Formula	C10H13NO2
Molar mass	179.219 g·mol
3D model (JSmol)	Interactive image
SMILES NC(C)CC1=CC2=C(C=C1)OCO2
InChI InChI=1S/C10H13NO2/c1-7(11)4-8-2-3-9-10(5-8)13-6-12-9/h2-3,5,7H,4,6,11H2,1H3 Key:NGBBVGZWCFBOGO-UHFFFAOYSA-N
(verify)

3,4-Methylenedioxyamphetamine (MDA), sometimes referred to as “sass,” is an empathogen-entactogen, stimulant, and psychedelic drug of the amphetamine family that is encountered mainly as a recreational drug. In its pharmacology, MDA is a serotonin–norepinephrine–dopamine releasing agent (SNDRA). In most countries, the drug is a controlled substance and its possession and sale are illegal.

MDA is rarely sought as a recreational drug compared to other amphetamines; however, it remains widely used due to it being a primary metabolite, the product of hepatic N-dealkylation, of MDMA. It is also a common adulterant of illicitly produced MDMA.

Uses

Medical

MDA currently has no accepted medical use.

Recreational

MDA is bought, sold, and used as a recreational drug due to its enhancement of mood and empathy. A recreational dose of MDA is sometimes cited as being between 100 and 160 mg.

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).

Pharmacology

Pharmacodynamics

MDA is a substrate of the serotonin, norepinephrine, dopamine, and vesicular monoamine transporters, as well as a TAAR1 agonist, and for these reasons acts as a reuptake inhibitor and releasing agent of serotonin, norepinephrine, and dopamine (that is, it is an SNDRATooltip serotonin–norepinephrine–dopamine releasing agent). It is also an agonist of the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors and shows affinity for the α_2A-, α_2B-, and α_2C-adrenergic receptors and serotonin 5-HT_1A and 5-HT₇ receptors.

The (S)-optical isomer of MDA is more potent than the (R)-optical isomer as a psychostimulant, possessing greater affinity for the three monoamine transporters.

In terms of the subjective and behavioral effects of MDA, it is thought that serotonin release is required for its empathogenic effects, dopamine release is required for its euphoriant (rewarding and addictive) effects, dopamine and norepinephrine release is required for its psychostimulant effects, and direct agonism of the serotonin 5-HT_2A receptor is required for its mild psychedelic effects.

Pharmacokinetics

The duration of the drug has been reported to be about 6 to 8 hours.

Chemistry

MDA is a substituted methylenedioxylated phenethylamine and amphetamine derivative. In relation to other phenethylamines and amphetamines, it is the 3,4-methylenedioxy, α-methyl derivative of β-phenylethylamine, the 3,4-methylenedioxy derivative of amphetamine, and the N-desmethyl derivative of MDMA.

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.
• Darzens reaction on heliotropin was also done by J. Elks, et al. 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 hydoxylamine. 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.

Derivatives

MDA constitutes part of the core structure of the β-adrenergic receptor agonist protokylol.

History

MDA was first synthesized by Carl Mannich and W. Jacobsohn in 1910. It was first ingested in July 1930 by Gordon Alles who later licensed the drug to Smith, Kline & French. 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. From 1949 to 1957, more than five hundred human subjects were given MDA in an investigation of its potential use as an antidepressant and/or anorectic by Smith, Kline & French. The United States Army also experimented with the drug, code named EA-1298, while working to develop a truth drug or incapacitating agent. Harold Blauer died in January 1953 after being intravenously injected, without his knowledge or consent, with 450 mg of the drug as part of Project MKUltra. 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. These events suggest that MDA and DOB were under development as potential pharmaceutical drugs at the time.

Society and culture

Name

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."

United States

MDA is a Schedule I controlled substance in the US.

Research

In 2010, the ability of MDA to invoke mystical experiences and alter vision in healthy volunteers was studied. The study concluded that MDA is a "potential tool to investigate mystical experiences and visual perception".

A 2019 double-blind study administered both MDA and MDMA to healthy volunteers. The study found that MDA shared many properties with MDMA including entactogenic and stimulant effects, but generally lasted longer and produced greater increases in psychedelic-like effects like complex imagery, synesthesia, and spiritual experiences.

Adverse effects

MDA can produce serotonergic neurotoxic effects in rodents, thought to be activated by initial metabolism of MDA. In addition, MDA activates a response of the neuroglia, though this subsides after use.

See also

• MDMA
• 2,3-Methylenedioxyamphetamine
• 4,4'-Methylenedianiline
• Malondialdehyde

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External links

• Erowid MDA Vault
• MDA entry in PiHKAL
• MDA entry in PiHKAL • info