4-Methylthioamphetamine (4-MTA) is a compound structurally similar to amphetamine. 4-MTA is reported to have physiological effects similar to that of 3,4 methylenedioxyamphetamine (MDA) and 3,4-methylene-dioxymethamphetamine (MDMA/ecstasy).

There are no accepted medical uses for 4-MTA. 4-MTA was synthesized as a compound with selective serotonergic activity for use in research.

4-MTA is structurally similar to amphetamine, para-chloroamphetamine (PCA) and MDA. Manipulations of the 4th position on the phenyl ring of amphetamine compounds enhance their serotonergic properties. 4-MTA has a methylthio group at the 4th position where PCA has a cloro group, and MDA has a methylenedioxy group at the 3,4 positions of amphetamine. PCA is the prototype serotonergic compound used in basic science research. PCA blocks the uptake of serotonin into neruons and increases the release of serotonin from neurons. However, PCA also has effects on dopamine and norepinephrine systems in the brain and these effects may be responsible for its neurotoxicity. 4-MTA is a more selective serotonergic compound. 4-MTA blocks the uptake of serotonin into neurons and increases the release of serotonin from neurons, but unlike PCA, 4-MTA is an inhibitor of monoamine oxidase, the enzyme that metabolizes serotonin. The major side effects of 4-MTA have not been determined in humans. The pronounced increase in serotonin activity produced by 4-MTA could possibly lead to the "serotonin syndrome" which can occur clinically when serotonin uptake blockers and MAO inhibitors are used in combination. These symptoms include restlessness, muscle twitches, involuntary muscle contractions, exaggerated reflex responses, sweating, shivering, tremor, and ultimately convulsions, coma and death. 4-MTA has been reported by the London Toxicology Group to be responsible for three deaths as of November 1998. An additional report in December 1998 indicated that a student died at a "rave" party after taking seven tablets of 4-MTA.

4-MTA is most likely taken for its stimulant/euphoric properties or accidently as a substitute for Ecstasy. Anecdotal reports suggest that 4-MTA produces a prolonged (12 hr.) but somewhat less euphoric effect compared with Ecstasy.

4-MTA use has been reported in Europe. The National Criminal Intelligence Service (NCIS) of the United Kingdom (UK) has suggested that the success among law enforcement agencies in controlling "Ecstasy-type" drugs may lead to the production and abuse of a variety of other Ecstasy derivatives. It is anticipated that because of this, 4-MTA may be sold as Ecstasy or as a substitute for Ecstasy on the street. Recent reports also indicate that MDMA may produce damage to serotonergic neurons in humans. Since 4-MTA produces no neurotoxicity in animal studies, it may ultimately become a more preferred drug of abuse for individuals seeking a safer Ecstasy-type experience.

Three reports of 4-MTA analysis appear in Microgram, and one report on the Internet site of the London Toxicology Group. The drug appears to be popular in the UK, The Netherlands and Belgium. 4-MTA was found in white or cream-colored tablets ranging from 9.1 to 14.0 mm in diameter, 4.1 to 4.7 mm thick, weighing 299 to 710 mg, and half-scored with no other markings. In two cases, each tablet was packaged and labeled "S5 The One And Only Dominator". The package label claimed that the tablets contained caffeine, vitamins, and herbal ingredients. Analysis of the tablets found 100 to 140 mg 4-MTA per tablet.

4-MTA is not specifically listed as a controlled substance in the United States. However, it can be treated as a Schedule I controlled substance analog of either MDA or MDMA under the Analog Provisions of the Controlled Substances Act [21 USC 802(32)(A)] to the extent that it is intended for human consumption. At the recommendation of the W.H.O., the Commission on Narcotic Drugs on 20 March 2001, added 4-MTA to Schedule I of the 1971 Convention on Psychotropic Substances. DEA/DHHS will take the necessary steps to place 4-MTA under the CSA.

Comments and additional information are welcomed by the Drug and Chemical Evaluation Section, FAX 202-307-8570 or telephone 202-307-7183.

August, 2001