2,5-Dimethoxy-3,4-methylenedioxyamphetamine (DMMDA) is a
psychedelic
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science of ...
drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
of the
phenethylamine
Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amin ...
and
amphetamine
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
chemical class Chemical classification systems attempt to classify elements or compounds according to certain chemical functional or structural properties. Whereas the structural properties are largely intrinsic, functional properties and the derived classificat ...
es.
It was first
synthesized by
Alexander Shulgin
Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. He is credited with introducing 3,4-methylenedioxymethamph ...
and was described in his book ''
PiHKAL''.
Shulgin listed the
dosage as 30–75 mg and the
duration
Duration may refer to:
* The amount of time elapsed between two events
* Duration (music) – an amount of time or a particular time interval, often cited as one of the fundamental aspects of music
* Duration (philosophy) – a theory of time and ...
as 6–8 hours.
He reported DMMDA as producing
LSD
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
-like
image
An image is a visual representation of something. It can be two-dimensional, three-dimensional, or somehow otherwise feed into the visual system to convey information. An image can be an artifact, such as a photograph or other two-dimensiona ...
s,
mydriasis
Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs.
Normally, as ...
,
ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
, and time dilation.
Pharmacology
The mechanism behind DMMDA's hallucinogenic effects has not been specifically established, however Shulgin describes that a 75
milligram
The kilogram (also kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially. ...
dose of DMMDA is equivalent to a 75–100 microgram dose of
LSD
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
. LSD is a known
5-HT2A partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...
.
DMMDA also has an affinity for the
5-HT2A receptor in the human brain.
Because similiar chemicals, such as
MDA
MDA, mda, or ''variation'', may refer to:
Places
* Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics
* Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...
and
MMDA, are act as agonists on the
5-HT2A, it is likely that DMMDA also acts as an agonist of the
5-HT2A receptor.
This may suggest that the hallucinogenic effects of DMMDA result from its
agonism
Agonism (from Greek ἀγών '' agon'', "struggle") is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks ...
of the
5-HT2A receptor in the
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
brain. DMMDA also has lower affinities for other
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
receptors, such as the
5-HT2B,
5-HT2C and
5-HT1B receptor as well as
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
,
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
and
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
transporters, which may contribute to DMMDA's
psychoactive
A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior.
Th ...
effects.
DMMDA-2's and DMMDA-3’s affinities for the
5-HT2A receptor are almost the same as DMMDA’s.
4,5-dimethoxy-2,3-methylenedioxyamphetamine's affinity for the
5-HT2A is slighly lower than DMMDA's; the affinity for the receptor stands at around 70% that of DMMDA.
The two remaining isomers of DMMDA are 4,6-dimethoxy-2,3-methylenedioxyamphetamine and 5,6-dimethoxy-2,3-methylenedioxyamphetamine, which both have an affinity for the
5-HT2A receptor of around 65-70% that of DMMDA.
Chemistry
Shulgin explains in his book that DMMDA has 6 isomers similar to
TMA.
DMMDA-2
DMMDA-2 is a psychedelic phenethylamine discussed by Alexander Shulgin in his book '' PiHKAL (Phenethylamines i Have Known And Loved)''; however, he was not the first to synthesize it. Shulgin comments in his book that a 50 milligram dose of DMMD ...
is the only other isomer that has been synthesized as of yet. DMMDA-3 could be made from
exalatacin (1-allyl-2,6-dimethoxy-3,4-methylenedioxybenzene). Exalatacin can be found in the
essential oil
An essential oil is a concentrated hydrophobic liquid containing volatile (easily evaporated at normal temperatures) chemical compounds from plants. Essential oils are also known as volatile oils, ethereal oils, aetheroleum, or simply as the o ...
of both
Crowea exalata and
Crowea angustifolia var. angustifolia.
In other words, exalatacin is an isomer of both
apiole
Apiole is a phenylpropene, also known as apiol, parsley apiol, or parsley camphor. Its chemical name is 1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene. It is found in the essential oils of celery leaf and all parts of parsley. Heinrich Christoph ...
and
dillapiole
Dillapiole is an organic chemical compound and essential oil commonly extracted from dill weed, though it can be found in a variety of other plants such as fennel root. This compound is closely related to apiole, having a methoxy group positioned ...
, which can be used to make DMMDA and DMMDA-2 respectively. Exalatacin is almost identical to apiole and dillapiole, but differs from them in its positioning of its
methoxy
In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula .
On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position as ...
groups, which are in the 2 and 6 positions.
Additionally, yet another isomer of DMMDA could be made from pseudo-dillapiole or 4,5-dimethoxy-2,3-methylenedioxyallylbenzene.
:
Synthesis
Shulgin describes the synthesis of DMMDA from
apiole
Apiole is a phenylpropene, also known as apiol, parsley apiol, or parsley camphor. Its chemical name is 1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene. It is found in the essential oils of celery leaf and all parts of parsley. Heinrich Christoph ...
in his book
PiHKAL.
Apiole
Apiole is a phenylpropene, also known as apiol, parsley apiol, or parsley camphor. Its chemical name is 1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene. It is found in the essential oils of celery leaf and all parts of parsley. Heinrich Christoph ...
is subjected to an isomerization reaction to yield isoapiole by adding to solution of ethanolic
potassium hydroxide
Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash.
Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which exp ...
and holding the solution at a steam bath.
The
isoapiole is then
nitrated
In organic chemistry, nitration is a general class of chemical processes for the introduction of a nitro group into an organic compound. The term also is applied incorrectly to the different process of forming nitrate esters between alcohols and ...
to 2-nitro-isoapiole or 1-(2,3-dimethoxy-3,4-methylenedioxyphenyl)-2-nitropropene by adding it to a stirred solution of
acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
and
pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a d ...
at ice-bath temperatures and treating the solution with
tetranitromethane
Tetranitromethane or TNM is an organic oxidizer with chemical formula . Its chemical structure consists of four nitro groups attached to one carbon atom. In 1857 it was first synthesised by the reaction of sodium cyanoacetamide with nitric acid.
...
. The
pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a d ...
acts as a catalyst in this reaction.
The 2-nitro-isoapiole is finally
reduced to
freebase
Freebase may refer to:
*Free base or freebase, the pure basic form of an amine, as opposed to its salt form
*Freebase (database), a former online database service
*Freebase (mixtape), ''Freebase'' (mixtape), 2014 mixtape by 2 Chainz
*An original ...
DMMDA by adding it to a well-stirred and
refluxing
Reflux is a technique involving the condensation of vapors and the return of this condensate to the system from which it originated. It is used in industrial and laboratory distillations. It is also used in chemistry to supply energy to Chemical ...
suspension of
diethylether
Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable liq ...
and
lithium aluminum hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic sy ...
under an inert atmosphere (e.g.
helium
Helium (from el, ἥλιος, helios, lit=sun) is a chemical element with the symbol He and atomic number 2. It is a colorless, odorless, tasteless, non-toxic, inert, monatomic gas and the first in the noble gas group in the periodic table. ...
).
Finally, the freebase DMMDA converted into its
hydrochloride
In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative na ...
salt.
Shulgin's synthesis of DMMDA is reasonably unsafe, since it involves the use of
tetranitromethane
Tetranitromethane or TNM is an organic oxidizer with chemical formula . Its chemical structure consists of four nitro groups attached to one carbon atom. In 1857 it was first synthesised by the reaction of sodium cyanoacetamide with nitric acid.
...
, which is toxic, carcinogenic and prone to detonating.
DMMDA can be made from apiole via other safer methods. Among other methods, DMMDA can be synthesize from apiole via the intermediate chemical 2,5-dimethoxy-3,4-methylenedioxyphenylpropan-2-one or DMMDP2P in the same manner as
MDA
MDA, mda, or ''variation'', may refer to:
Places
* Moldova, a country in Europe with the ISO 3166-1 country code MDA Politics
* Meghalaya Democratic Alliance (2018), ruling coalition government in the Indian State of Meghalaya led by National Pe ...
is made from
safrole
Safrole is an organic compound with the formula CH2O2C6H3CH2CH=CH2. It is a colorless oily liquid, although impure samples can appear yellow. A member of the phenylpropanoid family of natural products, it is found in sassafras plants, among oth ...
. DMMDP2P can be made from apiole via a
Wacker oxidation
The Wacker process or the Hoechst-Wacker process (named after the chemical companies of the same name) refers to the oxidation of ethylene to acetaldehyde in the presence of palladium(II) chloride as the catalyst. This chemical reaction was one of ...
with
benzoquinone Benzoquinone (C6H4O2) is a quinone with a single benzene ring. There are 2 (out of 3 hypothetical) benzoquinones:
* 1,4-Benzoquinone, most commonly, right image (also ''para''-benzoquinone, ''p''-benzoquinone, ''para''-quinone, or just quinone)
* 1 ...
. DMMDP2P can be alternatively made by subjecting apiole to an
isomerisation
In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...
reaction to yield isoapiole followed by a
Peracid oxidation and finally a
hydrolytic dehydration.
Then the DMMDP2P can then be subjected to a
reductive amination
Reductive amination (also known as reductive alkylation) is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde. It is considered ...
with a source of
nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
, such as
ammonium chloride, and a reducing agent, such as
sodium cyanoborohydride
Sodium cyanoborohydride is the chemical compound with the formula Sodium, NaBoron, BHydrogen, H3cyanide, CN. It is a colourless salt, but commercial samples can appear tan. It is widely used in organic synthesis for the reduction of imines. The sal ...
or an
amalgam
Amalgam most commonly refers to:
* Amalgam (chemistry), mercury alloy
* Amalgam (dentistry), material of silver tooth fillings
** Bonded amalgam, used in dentistry
Amalgam may also refer to:
* Amalgam Comics, a publisher
* Amalgam Digital
...
of
mercury
Mercury commonly refers to:
* Mercury (planet), the nearest planet to the Sun
* Mercury (element), a metallic chemical element with the symbol Hg
* Mercury (mythology), a Roman god
Mercury or The Mercury may also refer to:
Companies
* Merc ...
and
aluminium
Aluminium (aluminum in American and Canadian English) is a chemical element with the symbol Al and atomic number 13. Aluminium has a density lower than those of other common metals, at approximately one third that of steel. I ...
, to yield freebase DMMDA.
DMMDA-synthesis.png, Alexander Shulgin's synthesis of DMMDA.
References
{{DEFAULTSORT:Dimethoxy-3,4-methylenedioxyamphetamine, 2,5-
Substituted amphetamines
Benzodioxoles
Hydroxyquinol ethers
Mescalines
2,5-Dimethoxyphenethylamines
Entactogens and empathogens