3,4-Methylenedioxyamphetamine
Encyclopedia
3,4-Methylenedioxyamphetamine (MDA; "Sassafras"), also known as tenamfetamine (INN
), is a psychedelic
and entactogen
ic drug of the phenethylamine
and amphetamine
chemical classes. It is mainly used as a recreational drug, an entheogen
, and a tool
in use to supplement various types of practices for transcendence
, including in meditation
, psychonautics
, and as an agent in psychedelic psychotherapy
. It was first synthesized
by G. Mannish and W. Jacobson in 1910. There are about 20 different synthetic routes described in the literature for its preparation.
who then licensed the drug to Smith Kline and 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 500 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. One human subject died in January 1953 after being intravenously injected with 450 mg of the drug. MDA was patented as a cough suppressant
by H. D. Brown in 1958, as an ataractic by Smith, Kline & French in 1960, and as an anorectic
under the trade name “Amphedoxamine” in 1961. Several researchers, including Claudio Naranjo
and Richard Yensen, have explored MDA in the field of psychotherapy
.
into isosafrole
via isomerization. The isosafrole is then oxidized, using a peroxyacid, to produce MDP2P
(methylenedioxyphenylacetone
). Finally, it is converted to MDA via reductive amination
with ammonia
. This synthesis is very similar to that of MDMA
(Ecstasy) and of MDEA. Only disavantage is that this method, when used to produces MDA, gives extremely low yield. To achieve decent yield, MDP2P should first be reacted with hydroxylamine to produce Isosafrole Ketoxime (MDP2P Oxime). The oxime can then be reduced to MDOH, then MDA. Both reductions can be performed at the same time if the reactants are adjusted accordingly. The most common route is by starting from piperonal, and condensing it with nitroethane
. The resulting nitro-isosafrole can then be reduced to MDA with a suitable reducing agent.
scene around 1963 to 1964. It was then inexpensive and readily available as a research chemical from several scientific supply houses. Although now illegal, MDA continues to be bought, sold, and used for recreational'love drug', due to its enhancement of sex. Unlike many amphetamine related drugs it did not reduce a man's ability to maintain an erection. It was often taken in conjunction with LSD to complement its largely physical effects with the mental effects of the LSD.
A recreational dose of MDA is commonly between 100 and 160 mg. The “S” optical isomer of MDA is more potent than the “R” optical isomer as a psychostimulant, possessing greater affinity for the three monoamine transporter
proteins (SERT
, NET
and DAT
). Although there is some debate, the duration of the drug is now generally believed to be roughly 6 to 10 hours; but most individuals report the duration of the drug's effects to be around 5–6 hours, slightly longer than that of MDMA. (In the late 1990s, Alexander Shulgin
changed his opinion of the duration to 3–6 hours).
MDA is thought to be similar in pharmacological mechanism of action and phenomenological effects to its more widely used N-methyl analogue MDMA (Ecstasy). Like MDMA, MDA causes serotonin and dopamine release by acting as a substrate at the SERT and DAT, respectively. This may explain the similar euphoric and empathogenic effects of the two compounds. However, (S)-MDA has a higher efficacy in stimulating the 5-HT2A receptor
than (R)-MDMA; thus MDA tends to cause more psychedelic-like effects, such as visual hallucination
s. MDMA can also produce psychedelic-like visual effects, though these are generally less pronounced than those of MDA, or require a heavier dose to become apparent.
MDA is said to share the empathogen/entactogenic
effects of MDMA. While it is generally similar to MDMA, users report that MDA has more stimulant, or psychedelic
hallucinogenic
qualities and slightly less intense empathogen/entactogenic
effects than MDMA. MDA is also considered less predictable than MDMA, with effects varying greatly from person to person. However, no properly controlled experiments have compared these drugs in humans. MDA was best known for its enhancement of the experiences of dancing and sex.
MDA also differs from its methylated cousin MDMA in its acute toxicity—it is clearly more toxic, with toxicity indicative of overstimulation of the central nervous system
and the cardiovascular system. 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). The website erowid
.org lists the fatality rate at roughly 2 in 100,000 users, assuming it has similar rates as MDMA. The median lethal dose (LD50) in mice has been reported as 92 mg/kg by intraperitoneal injection
.
was enacted in the United States, placing MDA into Schedule I. It is similarly controlled in other nations. In Canada
MDA is a Schedule III
drug. Internationally, MDA is a Schedule I drug under the Convention on Psychotropic Substances
. Many similar unscheduled MDXX chemicals can be prosecuted under the Federal Analog Act
.
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
), is a psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...
and entactogen
Empathogen-entactogen
The terms empathogen and entactogen are used to describe a class of psychoactive drugs that produce distinctive emotional and social effects similar to those of MDMA. Putative members of this class include 2C-B, 2C-I, MDMA, MDA, MDEA, MBDB, 2C-T-7, and 2C-T-2, among others...
ic drug of the phenethylamine
Substituted phenethylamine
The substituted phenethylamines are chemical compounds with the 2-phenethylamine chemical structure modified at the phenyl ring, sidechain, and/or amino group. Some of them are psychoactive drugs, including stimulants, psychedelics, opioids, and entactogens, which exert their effects primarily...
and amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...
chemical classes. It is mainly used as a recreational drug, an entheogen
Entheogen
An entheogen , in the strict sense, is a psychoactive substance used in a religious, shamanic, or spiritual context. Historically, entheogens were mostly derived from plant sources and have been used in a variety of traditional religious contexts...
, and a tool
Tool
A tool is a device that can be used to produce an item or achieve a task, but that is not consumed in the process. Informally the word is also used to describe a procedure or process with a specific purpose. Tools that are used in particular fields or activities may have different designations such...
in use to supplement various types of practices for transcendence
Transcendence (philosophy)
In philosophy, the adjective transcendental and the noun transcendence convey the basic ground concept from the word's literal meaning , of climbing or going beyond, albeit with varying connotations in its different historical and cultural stages...
, including in meditation
Meditation
Meditation is any form of a family of practices in which practitioners train their minds or self-induce a mode of consciousness to realize some benefit....
, psychonautics
Psychonautics
Psychonautics refers both to a methodology for describing and explaining the subjective effects of altered states of consciousness, including those induced by mind altering substances, and to a research paradigm in which the researcher voluntarily immerses him/herself into an altered...
, and as an agent in psychedelic psychotherapy
Psychedelic psychotherapy
Psychedelic therapy refers to therapeutic practices involving the use of psychedelic drugs, particularly serotonergic psychedelics such as ergine, LSD, psilocin and DMT...
. It was first synthesized
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
by G. Mannish and W. Jacobson in 1910. There are about 20 different synthetic routes described in the literature for its preparation.
Medical use
There are no currently accepted medical uses for MDA. However, researchers have investigated many possible uses in the past. It was first ingested in July 1930 by Gordon AllesGordon Alles
Gordon A. Alles , was an American chemist and pharmacologist who did much research on the isolation and properties of insulin for the treatment of diabetics. He is also credited with discovering and publishing the psychological effects of amphetamine, as well as for MDA...
who then licensed the drug to Smith Kline and French. MDA was first used in animal tests
Animal testing
Animal testing, also known as animal experimentation, animal research, and in vivo testing, is the use of non-human animals in experiments. Worldwide it is estimated that the number of vertebrate animals—from zebrafish to non-human primates—ranges from the tens of millions to more than 100 million...
in 1939, and human trials began in 1941 in the exploration of possible therapies for Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. From 1949 to 1957, more than 500 human subjects were given MDA in an investigation of its potential use as an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
and/or anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
by Smith, Kline & French. The United States Army
United States Army
The United States Army is the main branch of the United States Armed Forces responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military, and is one of seven U.S. uniformed services...
also experimented with the drug, code named EA-1298, while working to develop a truth drug
Truth drug
A truth drug or truth serum is a psychoactive medication used to obtain information from subjects who are unable or unwilling to provide it otherwise. The unethical use of truth drugs is classified as a form of torture according to international law. However, they are properly and productively...
or incapacitating agent. One human subject died in January 1953 after being intravenously injected with 450 mg of the drug. MDA was patented as a cough suppressant
Cough medicine
A cough medicine is a medicinal drug used in an attempt to treat coughing and related conditions. For dry coughs, treatment with cough suppressants may be attempted to suppress the body's urge to cough...
by H. D. Brown in 1958, as an ataractic by Smith, Kline & French in 1960, and as an anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
under the trade name “Amphedoxamine” in 1961. Several researchers, including Claudio Naranjo
Claudio Naranjo
Claudio Naranjo is a Chilean psychiatrist who is considered a pioneer in integrating psychotherapy and the spiritual traditions. He is one of the three successors named by Fritz Perls , and a developer of the Enneagram of Personality and founder of the Seekers After Truth Institute...
and Richard Yensen, have explored MDA in the field of psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...
.
Synthesis
One method of MDA synthesis is to turn safroleSafrole
Safrole, also known as shikimol, is a phenylpropene. It is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil , or synthesized from other related methylenedioxy...
into isosafrole
Isosafrole
Isosafrole is a phenylpropene, a type of aromatic organic chemical with a smell similar to anise or licorice. It is found in small amounts in various essential oils, but is most commonly obtained by isomerizing the plant oil safrole....
via isomerization. The isosafrole is then oxidized, using a peroxyacid, to produce MDP2P
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...
(methylenedioxyphenylacetone
Phenylacetone
Phenylacetone , is an organic compound. It is a clear oil with a refractive index of 1.5168. This substance is used in the manufacture of methamphetamine and amphetamine as a starting material or intermediate, where it is commonly known as P2P...
). Finally, it is converted to MDA via reductive amination
Reductive amination
Reductive amination is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine...
with ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
. This synthesis is very similar to that of MDMA
Methylenedioxymethamphetamine
MDMA is an entactogenic drug of the phenethylamine and amphetamine class of drugs. In popular culture, MDMA has become widely known as "ecstasy" , usually referring to its street pill form, although this term may also include the presence of possible adulterants...
(Ecstasy) and of MDEA. Only disavantage is that this method, when used to produces MDA, gives extremely low yield. To achieve decent yield, MDP2P should first be reacted with hydroxylamine to produce Isosafrole Ketoxime (MDP2P Oxime). The oxime can then be reduced to MDOH, then MDA. Both reductions can be performed at the same time if the reactants are adjusted accordingly. The most common route is by starting from piperonal, and condensing it with nitroethane
Nitroethane
Nitroethane is an organic compound having the chemical formula C2H5NO2. Similar in many regards to nitromethane, nitroethane is an oily liquid at standard temperature and pressure. Pure nitroethane is colourless and has a fruity odor.- Preparation :...
. The resulting nitro-isosafrole can then be reduced to MDA with a suitable reducing agent.
Recreational use
MDA began to appear on the recreational drugRecreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...
scene around 1963 to 1964. It was then inexpensive and readily available as a research chemical from several scientific supply houses. Although now illegal, MDA continues to be bought, sold, and used for recreational'love drug', due to its enhancement of sex. Unlike many amphetamine related drugs it did not reduce a man's ability to maintain an erection. It was often taken in conjunction with LSD to complement its largely physical effects with the mental effects of the LSD.
Effects
Monoamine transporter
Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...
proteins (SERT
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
, NET
Norepinephrine transporter
The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
and DAT
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
). Although there is some debate, the duration of the drug is now generally believed to be roughly 6 to 10 hours; but most individuals report the duration of the drug's effects to be around 5–6 hours, slightly longer than that of MDMA. (In the late 1990s, Alexander Shulgin
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...
changed his opinion of the duration to 3–6 hours).
MDA is thought to be similar in pharmacological mechanism of action and phenomenological effects to its more widely used N-methyl analogue MDMA (Ecstasy). Like MDMA, MDA causes serotonin and dopamine release by acting as a substrate at the SERT and DAT, respectively. This may explain the similar euphoric and empathogenic effects of the two compounds. However, (S)-MDA has a higher efficacy in stimulating the 5-HT2A receptor
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
than (R)-MDMA; thus MDA tends to cause more psychedelic-like effects, such as visual hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
s. MDMA can also produce psychedelic-like visual effects, though these are generally less pronounced than those of MDA, or require a heavier dose to become apparent.
MDA is said to share the empathogen/entactogenic
Empathogen-entactogen
The terms empathogen and entactogen are used to describe a class of psychoactive drugs that produce distinctive emotional and social effects similar to those of MDMA. Putative members of this class include 2C-B, 2C-I, MDMA, MDA, MDEA, MBDB, 2C-T-7, and 2C-T-2, among others...
effects of MDMA. While it is generally similar to MDMA, users report that MDA has more stimulant, or psychedelic
Psychedelic
The term psychedelic is derived from the Greek words ψυχή and δηλοῦν , translating to "soul-manifesting". A psychedelic experience is characterized by the striking perception of aspects of one's mind previously unknown, or by the creative exuberance of the mind liberated from its ostensibly...
hallucinogenic
Psychedelics, dissociatives and deliriants
This general group of pharmacological agents can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness...
qualities and slightly less intense empathogen/entactogenic
Empathogen-entactogen
The terms empathogen and entactogen are used to describe a class of psychoactive drugs that produce distinctive emotional and social effects similar to those of MDMA. Putative members of this class include 2C-B, 2C-I, MDMA, MDA, MDEA, MBDB, 2C-T-7, and 2C-T-2, among others...
effects than MDMA. MDA is also considered less predictable than MDMA, with effects varying greatly from person to person. However, no properly controlled experiments have compared these drugs in humans. MDA was best known for its enhancement of the experiences of dancing and sex.
MDA also differs from its methylated cousin MDMA in its acute toxicity—it is clearly more toxic, with toxicity indicative of overstimulation of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and the cardiovascular system. 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). The website erowid
Erowid
Erowid, also called The Vaults of Erowid, is an online library of information about psychoactive plants and chemicals and other topics on altered states of consciousness such as meditation and lucid dreaming. It provides information about legal and illegal substances, including their desired and...
.org lists the fatality rate at roughly 2 in 100,000 users, assuming it has similar rates as MDMA. The median lethal dose (LD50) in mice has been reported as 92 mg/kg by intraperitoneal injection
Intraperitoneal injection
Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum . IP injection is more often applied to animals than humans...
.
Legality
In 1970, the Controlled Substances ActControlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
was enacted in the United States, placing MDA into Schedule I. It is similarly controlled in other nations. In Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
MDA is a Schedule III
Controlled Drugs and Substances Act
The Controlled Drugs and Substances Act is Canada's federal drug control statute. Passed in 1996 by the Chrétien government, it repeals the Narcotic Control Act and Parts III and IV of the Food and Drug Act and establishes eight Schedules of controlled substances and two Classes of precursors...
drug. Internationally, MDA is a Schedule I drug under the Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
. Many similar unscheduled MDXX chemicals can be prosecuted under the Federal Analog Act
Federal Analog Act
The Federal Analog Act, , is a controversial section of the United States Controlled Substances Act which allowed any chemical "substantially similar" to a controlled substance listed in Schedule I or II to be treated as if it were also listed in those schedules, but only if intended for human...
.