2,5-Dimethoxy-4-ethylamphetamine (DOET) is a
psychedelic drug
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
of the
phenethylamine,
amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
, and
DOx families.
It is closely related to
DOM and is a
synthetic analogue of the
naturally occurring
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...
phenethylamine psychedelic
mescaline
Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...
.
The drug acts as a
selective agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
of the
serotonin 5-HT2 receptors, including of the serotonin
5-HT2A,
5-HT2B, and
5-HT2C receptors.
DOET was first discovered by
Alexander Shulgin in the 1960s.
It was clinically studied at low and sub-
hallucinogen
Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...
ic doses for potential use as a
pharmaceutical drug
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
acting as a "
psychic energizer" by
Dow Chemical Company in the 1960s.
However, its development was terminated after DOM emerged as a
street drug and caused a
public health crisis in
San Francisco
San Francisco, officially the City and County of San Francisco, is a commercial, Financial District, San Francisco, financial, and Culture of San Francisco, cultural center of Northern California. With a population of 827,526 residents as of ...
in 1967.
Nonetheless, DOET's effects at low doses were extensively characterized in small
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s.
The psychedelic effects of DOET at higher doses were subsequently described by Shulgin in his book
PiHKAL
''PiHKAL: A Chemical Love Story'' is a book by Alexander Shulgin and Ann Shulgin published in 1991. The subject of the work is Psychoactive drug, psychoactive phenethylamine Derivative (chemistry), chemical derivatives, notably those that act ...
in 1991.
DOET is taken
by mouth
Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications.
Oral administ ...
.
It has a slow
onset of 1 to 3hours, a delayed
peak of 3 to 5hours, and a
dose-dependent and potentially very long
duration of 5 to 20hours.
Effects at low doses include mild
euphoria
Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
, enhanced
self-awareness, and
talkativeness, among others.
Mild
closed-eye visuals can also occur.
At higher doses, DOET produces psychedelic effects including
heightened emotions,
sensory enhancement, rich closed-eye visuals, and
open-eye visuals, among others.
Physical effects include
pupil dilation, increased
heart rate
Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
, and increased
blood pressure
Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
.
Effects
In a 1968
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
, DOET at an
oral dose of 1.5mg (as the
hydrochloride salt
In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...
) produced mild
euphoria
Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
and enhanced
self-awareness, but no
hallucinogen
Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...
ic effects (in terms of perceptual distortions or
hallucination
A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s/
open-eye visuals), marked behavioral changes, or
intellectual impairment
Developmental disability is a diverse group of chronic conditions, comprising mental or physical impairments that arise before adulthood. Developmental disabilities cause individuals living with them many difficulties in certain areas of life, espe ...
.
Other reported effects included feeling
high, feelings of
insight
Insight is the understanding of a specific causality, cause and effect within a particular context. The term insight can have several related meanings:
*a piece of information
*the act or result of understanding the inner nature of things or of se ...
, feelings of
pleasantness,
body image awareness,
impatience, slight
difficulty concentrating,
talkativeness,
racing thoughts, mild
closed-eye visuals,
time dilation
Time dilation is the difference in elapsed time as measured by two clocks, either because of a relative velocity between them (special relativity), or a difference in gravitational potential between their locations (general relativity). When unsp ...
in some, feeling
alert, and feeling "washed out" after the drug.
Some of the effects of DOET in the study resembled those of
dextroamphetamine
Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
, including talkativeness, euphoria, and feeling alert.
The subjective effects began 1 to 1.5hours after dosing,
peaked around 3 to 4hours after administration, and the
duration was about 5 to 6hours.
Pupil dilation was also observed, but there were no marked changes in
heart rate
Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
or
blood pressure
Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
.
There were also changes on
cognitive tests of
association and
serial learning.
The effects of DOET were similar to those of low doses of DOM (2.7–3.3mg) but DOET appeared to be more
potent (with 2.0mg DOM being indistinguishable from
placebo
A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures.
Placebos are used in randomized clinical trials ...
).
In a subsequent 1971 clinical trial, DOET hydrochloride at oral doses of 0.75 to 4mg again produced pupil dilation (
dose-dependent), mild euphoria, feelings of enhanced self-awareness, and many of the other effects observed in the previous trial.
Once again, there were no hallucinogenic effects, aside from closed-eye visuals in a minority of individuals, and there was no
cognitive impairment.
New assessed and reported effects included feeling
relaxed, feelings of
unpleasantness in some,
lightheadedness, reduced
depressive feelings, and feeling
anxious or
restless.
The feelings of
nervousness and restlessness occurred more at the higher doses.
DOET appeared to show a greater apparent separation between threshold and hallucinogenic doses than had been documented for other psychedelics.
Other psychedelics like
LSD and DOM show a 2- to 3-fold separation, whereas DOET showed an at least 5-fold separation.
The lesser influence of DOET on perceptual processes than equivalent doses of DOM was in spite of the greater potency of DOET than DOM in producing subjective effects in general.
A third and final 1974 clinical trial assessed oral doses of 1 to 4mg (''S'')-(+)-DOET, 1 to 2mg (''R'')-(–)-DOET, and 2 to 4mg (''RS'')-(±)-DOET.
It was found that 1mg (''R'')-(–)-DOET was equivalent to 4mg (''S'')-(+)-DOET in producing psychoactive effects and hence that (''R'')-(–)-DOET was about 4times as potent as (''S'')-(+)-DOET.
The onset was 1.5 to 3hours, peak effects were at 4 to 5hours, and the duration was 6 to 10hours.
The subjective effects were similar to the earlier trials, but new reported effects included
enhanced perception of all
sense
A sense is a biological system used by an organism for sensation, the process of gathering information about the surroundings through the detection of Stimulus (physiology), stimuli. Although, in some cultures, five human senses were traditio ...
s, difficult-to-describe
cognitive alteration, relaxed
well-being
Well-being is what is Intrinsic value (ethics), ultimately good for a person. Also called "welfare" and "quality of life", it is a measure of how well life is going for someone. It is a central goal of many individual and societal endeavors.
...
, and
heightened emotions with rapid
mood changes.
No hallucinogenic effects or
visual distortions with eyes open occurred, but
vivid imagery with eyes closed could be experienced at the higher doses.
Based on the preceding clinical trials, DOET does not produce clear hallucinogenic effects, aside from closed-eye visuals, at doses of up to 4mg.
However,
Alexander Shulgin has stated that DOET is psychedelic at doses of 3mg and above.
In
PiHKAL
''PiHKAL: A Chemical Love Story'' is a book by Alexander Shulgin and Ann Shulgin published in 1991. The subject of the work is Psychoactive drug, psychoactive phenethylamine Derivative (chemistry), chemical derivatives, notably those that act ...
, Shulgin listed the dosage of DOET as 2 to 6mg and its duration as 14 to 20hours.
In experience reports of 1 to 7mg DOET in different individuals, 1mg produced relaxation but no psychedelic effects; 2.5mg produced both open- and closed-eye visuals; 4mg produced mood-energizing effects but very little or no hallucinogenic effect; 6mg produced sensory enhancement, rich closed-eye visuals, and no open-eye visual movement; and 7mg produced strong feelings with themes of
love,
eroticism
Eroticism () is a quality that causes sexual feelings, as well as a philosophical contemplation concerning the aesthetics of sexual desire, sensuality, and romantic love. That quality may be found in any form of artwork, including painting, scul ...
, and
divinity
Divinity (from Latin ) refers to the quality, presence, or nature of that which is divine—a term that, before the rise of monotheism, evoked a broad and dynamic field of sacred power. In the ancient world, divinity was not limited to a single ...
,
openness, not much visually, closed-eye visuals, and
body load symptoms.
There was considerable variation in subjective effects between individuals.
Shulgin has described both DOET and DOM as being effective
antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...
s at lower doses and DOET as being a
cognitive enhancer at modest doses.
In line with notions that DOET is a "psychic energizer", the related psychedelic
DOPR has shown
pro-motivational effects in rodents at sub-hallucinogenic doses
and the related drug
Ariadne (4C-DOM) has reportedly shown pro-motivational effects in monkeys despite being non-hallucinogenic.
ASR-2001 (2CB-5PrO), a non-hallucinogenic analogue of the related psychedelic
2C-B, is under development for use as a
stimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
-like
medication
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
for the treatment of
psychiatric disorder
A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...
s.
Interactions
Pharmacology
Pharmacodynamics
DOET acts as a
selective serotonin 5-HT2 receptor agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
, including of the serotonin
5-HT2A,
5-HT2B, and
5-HT2C receptors.
In one study, its
affinities (K
i) were 12nM for the serotonin 5-HT
2A receptor, 108nM for the serotonin 5-HT
2C receptor (9-fold lower than for 5-HT
2A), and 9,727nM for the serotonin
5-HT1A receptor (811-fold lower than for 5-HT
2A).
The drug's for activation of the serotonin 5-HT
2A receptor was 1.7 to 8.1nM depending on the
intracellular signaling cascade, while its was 99%.
At the serotonin 5-HT
2B receptor, its was 68nM (8- to 40-fold lower than for 5-HT
2A) and its was 73%.
DOET is a
full agonist of the serotonin 5-HT
2A receptor and a high-
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...
of the serotonin 5-HT
2B and 5-HT
2C receptors.
The drug is a very weak or inactive agonist of the human
trace amine-associated receptor 1 (TAAR1) and is inactive at the
rhesus monkey TAAR1.
In contrast to many other amphetamines, but like other
DOx drugs, DOET does not bind to the
monoamine transporters.
DOET produces the
head-twitch response (HTR), a behavioral proxy of psychedelic effects, in rodents.
As with other psychedelics, DOET shows a biphasic or
inverted U-shaped dose–response curve for production of the HTR.
The drug induces the HTR to a similar maximal extent as other related psychedelics like
DOM and
DOI.
DOET substitutes for the
phenethylamine psychedelics
mescaline
Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...
and DOM, partially substitutes for the
tryptamine psychedelic
5-MeO-DMT, and does not substitute for the
psychostimulant dextroamphetamine
Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
in animal
drug discrimination tests.
DOET produces
hyperlocomotion in mice.
However, like other psychedelics, it shows a biphasic or inverted U-shaped dose–response curve, increasing
locomotor activity at low to moderate doses and reducing it at high doses.
DOET produces
serotonin receptor-dependent
pressor and
hyperthermic effects in rodents.
Pharmacokinetics
In terms of effects in humans, the
onset of lower doses of DOET and its individual
enantiomer
In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...
s (0.75–4mg) is 1 to 3hours,
peak effects occur after 3 to 5hours, and the
duration is 5 to 10hours.
At higher doses of DOET (2 to 6mg), the duration was reported to be 14 to 20hours.
DOET, like other
DOx drugs, has an unusually slow onset and long duration.
In rodents, DOET is
metabolized by
oxidation
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
of the
ethyl group
In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry
The International Union of Pure and Applied ...
at the 4 position.
It appears to be metabolized more quickly than
DOM.
In humans, DOET is
excreted 10 to 40% in
urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
unchanged within 24hours.
The greatest excretion rate occurred between 3 and 6hours.
Chemistry
DOET, also known as 2,5-dimethoxy-4-ethylamphetamine or as 2,5-dimethoxy-4-ethyl-α-methylphenethylamine, is a
substituted phenethylamine and
amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
and is a member of the
DOx group of drugs.
It is
structurally related to the
naturally occurring
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...
phenethylamine psychedelic
mescaline
Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...
(3,4,5-trimethoxyphenethylamine).
Analogues of DOET include other
DOx drugs such as
DOM,
DOPR,
DOBU,
DOAM,
DOB, and
DOI.
The α-desmethyl or phenethylamine analogue of DOET is
2C-E.
Ariadne is the α-ethyl or
phenylisobutylamine analogue of DOM.
History
DOET was discovered by
Alexander Shulgin in the 1960s.
He assessed DOET after
synthesizing DOM in 1963 and discovering DOM's
psychedelic effects in 1964.
Shulgin found that DOET was a remarkable "
psychic energizer" at low doses without producing psychedelic effects at these doses.
The effects that he experienced included
positive mood,
talkativeness, and
disinhibition that lasted the whole day.
In contrast to Shulgin however, a friend and colleague of Shulgin's that he had try DOET a month later only experienced intense
lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness, or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overw ...
followed by profound
depression after taking the drug.
Nonetheless, Shulgin's enthusiasm was not dissuaded, and he felt that the drug should be exploited.
Shulgin was working at
Dow Chemical Company at the time, and he pitched DOET to the company.
They selected DOET as a promising compound and decided to move forward with
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s for potential use as a
pharmaceutical drug
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
.
Shulgin and the company filed a
patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an sufficiency of disclosure, enabling discl ...
for DOET in 1966, which was published in 1970.
Dow Chemical Company tasked
neuroscientist
A neuroscientist (or neurobiologist) is a scientist specializing in neuroscience that deals with the anatomy and function of neurons, Biological neural network, neural circuits, and glia, and their Behavior, behavioral, biological, and psycholo ...
Solomon H. Snyder at
Johns Hopkins University
The Johns Hopkins University (often abbreviated as Johns Hopkins, Hopkins, or JHU) is a private university, private research university in Baltimore, Maryland, United States. Founded in 1876 based on the European research institution model, J ...
with clinically studying DOET.
In 1967,
DOM emerged as a
street drug and
LSD replacement with the name "STP" in
San Francisco
San Francisco, officially the City and County of San Francisco, is a commercial, Financial District, San Francisco, financial, and Culture of San Francisco, cultural center of Northern California. With a population of 827,526 residents as of ...
and caused a
public health crisis.
This occurred after LSD distributor
Owsley Stanley learned of DOM from Shulgin and began distributing very-high-dose DOM
tablets for free.
LSD had become illegal in
California
California () is a U.S. state, state in the Western United States that lies on the West Coast of the United States, Pacific Coast. It borders Oregon to the north, Nevada and Arizona to the east, and shares Mexico–United States border, an ...
in 1966 and an alternative had been sought by Stanley.
The DOET tablets he distributed could have very long
durations (up to 3–4days) and resulted in intense experiences, worrying physical
side effect
In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects.
A drug or procedure usually use ...
s, and
hospitalizations.
DOM was first described in the media and
scientific literature in 1967 as a result of the crisis.
The drug became illegal in the
United States
The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
in 1968.
It is unclear why Shulgin told Stanley about DOM and risked his professional career as well as the DOET
clinical development.
However, it might have been because Shulgin felt that DOM was a promising compound but was not being further pursued by Dow Chemical Company and would otherwise be forgotten.
Dow Chemical Company terminated its clinical research program on DOET due to the DOM public health crisis.
DOET was subsequently first described in the scientific literature by Snyder and colleagues in 1968.
Snyder continued to be interested in DOET as a potential medicine, but it was never further developed.
Snyder conducted and published a series of three
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s of low-dose DOET between 1968 and 1974.
In these trials, he compared DOET with DOM,
dextroamphetamine
Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...
, and
placebo
A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures.
Placebos are used in randomized clinical trials ...
.
As with Shulgin, he found DOET to produce
amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
-like mild
euphoria
Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
and talkativeness, among other effects, without producing significant
hallucinogen
Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...
ic effects at the assessed doses.
Snyder also studied the individual
enantiomer
In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...
s of DOET.
Shulgin first discussed DOET in publications in 1969 and 1970.
DOET became a
Schedule I controlled substance in the
United States
The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
in February 1973.
Ariadne (4C-D, 4C-DOM, BL-3912, Dimoxamine), the α-
ethyl or
phenylisobutylamine analogue of DOM, was developed by Shulgin in the 1970s.
He found it to be
psychoactive and to produce "the alert of a psychedelic, with none of the rest of the package".
This threshold psychoactivity without psychedelic effects was reminiscent of low doses of DOET.
However, in contrast to DOET and other
DOx drugs like DOM, Ariadne remained completely non-hallucinogenic even at very high doses, showing a hard
ceiling to its psychoactive effects and a lack of
recreational potential.
Ariadne was patented and developed by Shulgin and
Bristol Laboratories for potential use as an
antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...
and for a variety of other clinical indications in the 1970s.
(''R'')-Ariadne (BL-3912A) completed
phase 2 clinical trials and showed promising initial clinical benefits.
However, further clinical development was halted for strategic economic reasons.
In 2023, Ariadne was found to exhibit reduced-
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...
partial agonism of the serotonin 5-HT
2A receptor compared to DOM, and this was considered to account for its dramatically reduced hallucinogenic potential.
Shulgin first synthesized
2C-E, the α-
desmethyl or
phenethylamine analogue of DOET, in 1977.
Shulgin first published reports describing the psychedelic effects of higher doses of DOET in
PiHKAL
''PiHKAL: A Chemical Love Story'' is a book by Alexander Shulgin and Ann Shulgin published in 1991. The subject of the work is Psychoactive drug, psychoactive phenethylamine Derivative (chemistry), chemical derivatives, notably those that act ...
in 1991.
Prior to this, no reports had clearly been published of hallucinogenic effects of DOET, although Snyder had observed some closed-eye visuals with low-dose DOET in his clinical trials.
Shulgin also described 2C-E as producing robust psychedelic effects in PiHKAL, though with much higher doses required than DOET.
Society and culture
Names
DOET was originally named DOE by
Alexander Shulgin.
However, he subsequently recalled that this was also an acronym for
desoxyephedrine (methamphetamine).
As a result, he changed his name for the drug from DOE to DOET or DOEt.
Other names that Shulgin has given DOET have included HECATE or Hecate (after the
Greek goddess) and DMEA (short for dimethoxyethylamphetamine).
Legal status
Internationally, DOET is a Schedule I controlled drug; under the
Convention on Psychotropic Substances, it is legal only for medical uses or scientific research.
[https://web.archive.org/web/20070302130637/http://www.incb.org/pdf/e/list/green.pdf]
United States
DOET is classified as a
Schedule I substance in the United States and is similarly controlled in other parts of the world.
Australia
DOET is considered a Schedule 9 prohibited substance in Australia under the
Poisons Standard (October 2015).
A Schedule 9 substance is a substance 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.
References
External links
DOET - Isomer DesignDOET Experience Reports - ErowidDOET - PiHKAL - ErowidDOET - PiHKAL - Isomer DesignDOET: Exploring This Rare DOX Psychedelic - Tripsitter
{{DEFAULTSORT:Dimethoxy-4-ethylamphetamine, 2,5-
5-HT2A agonists
5-HT2B agonists
5-HT2C agonists
Abandoned drugs
Alexander Shulgin
Designer drugs
DOx (psychedelics)
Experimental antidepressants
Experimental hallucinogens
Nootropics
Pro-motivational agents
Psychedelic phenethylamines
TAAR1 agonists