2,5-Dimethoxy-4-iodoamphetamine (DOI) is a

psychedelic drug 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 o ...

and a

substituted amphetamine Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with s ...

. Unlike many other substituted amphetamines, however, it is not primarily a

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

. DOI has a

stereocenter In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups c ...

and ''R''-(−)-DOI is the more active

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

. In neuroscience research, sup>125I''R''-(−)-DOI is used as a

radioligand A radioligand is a radioactive biochemical substance (in particular, a ligand (biochemistry), ligand that is radioactive tracer, radiolabeled) that is used for diagnosis or for research-oriented study of the receptor (biochemistry), receptor system ...

and indicator of the presence of 5-HT_2A serotonin receptors. DOI's effects have been compared to

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 ...

, although there are differences that experienced users can distinguish. Besides the longer duration, the trip tends to be more energetic than an LSD trip, with more

body load Body load is the specific physical or tactile sensations brought on by psychoactive drugs, especially psychedelics. Generally, body load is an unpleasant physical sensation that is difficult to describe objectively either in terms of other sensation ...

and a different subjective visual experience. The after effects include residual stimulation and difficulty sleeping, which, depending on the dose, may persist for days. While rare, it is sometimes sold as a substitute for LSD, or even sold falsely as LSD, which may be dangerous because DOI does not have the same established safety profile as LSD.

Research

Research suggests that administration of (''R'')-DOI blocks pulmonary inflammation, mucus hyper-production, airway hyper-responsiveness and turns off key genes in in-lung immune response. These effects block the development of allergic asthma in a mouse model. Several 5-HT_2A agonist

hallucinogen Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorize ...

s including (''R'')-2,5-dimethoxy-4-iodoamphetamine DOI,

TCB-2 TCB-2 is a hallucinogen discovered in 2006 by Thomas McLean working in the lab of David Nichols at Purdue University. It is a conformationally-restricted derivative of the phenethylamine 2C-B, also a hallucinogen, and acts as a potent agonist ...

and LA-SS-Az have unexpectedly also been found to act as potent inhibitors of

TNF Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

, with DOI being the most active, showing TNF inhibition in the

picomolar Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of sol ...

range, an order of magnitude more potent than its action as a hallucinogen.

Pharmacology

DOI is a 5-HT_2A, 5-HT_2B and 5-HT_2C receptor agonist. DOI has been shown to be an extremely potent

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

of tumour necrosis factor-alpha inflammation at picomolar concentrations in cell studies. TNF-alpha is an important target for research into degenerative conditions such as

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As ...

, where the disease process involves tissue damage through chronic inflammation. This could make DOI and other 5-HT_2A agonists an entirely new area for development of novel treatments for these conditions. DOI has also been shown to induce rapid growth and reorganization of

dendritic spines A dendritic spine (or spine) is a small membranous protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical si ...

and synaptic connections with other

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...

, processes known to underlie

neuroplasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...

History

DOI 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-methylenedioxymetha ...

. The

radioactive Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is consi ...

iodine-125 Iodine-125 (125I) is a radioisotope of iodine which has uses in biological assays, nuclear medicine imaging and in radiation therapy as brachytherapy to treat a number of conditions, including prostate cancer, uveal melanomas, and brain tumor ...

form of DOI for PET imaging was first developed in the lab of David E. Nichols. In January 2007, British police reported that three young men had fallen ill, reportedly, after taking DOI at a rave in

Biggleswade Biggleswade ( ) is a market town and civil parish in Central Bedfordshire in Bedfordshire, England. It lies on the River Ivel, 11 miles (18 km) south-east of Bedford. Its population was 16,551 in the 2011 United Kingdom census, and its e ...

, near

Milton Keynes Milton Keynes ( ) is a city and the largest settlement in Buckinghamshire, England, about north-west of London. At the 2021 Census, the population of its urban area was over . The River Great Ouse forms its northern boundary; a tributary ...

, and warned others who had taken it to seek medical attention. This would appear to be the first indication that DOI has found more widespread use as a

recreational drug Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...

in the UK.

Legal status

Australia

The

Standard for the Uniform Scheduling of Medicines and Poisons The Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) is an Australian legislative instrument produced by the Therapeutic Goods Administration (TGA)., subsection 4A. Before 2010, it was known as the ''Standard for the Unifo ...

(SUSMP) of Australia does not list DOI as a prohibited substance.

Canada

Listed as a

Schedule 1 Schedule 1 may refer to: * Schedule I Controlled Substances within the US Controlled Substances Act * Schedule I Controlled Drugs and Substances within the Canadian Controlled Drugs and Substances Act * Schedule I Psychotropic Substances within t ...

as it is an analogue of amphetamine. The CDSA was updated as a result of the ''

Safe Streets Act The ''Safe Streets Act, 1999'' (SSA) (the Act) is a statute in the province of Ontario, Canada. The Act prohibits aggressive solicitation of persons in certain public places. It also prohibits the disposal of "certain dangerous things" such as u ...

'' changing amphetamines from Schedule 3 to

Denmark

Illegal since 8 April 2007.

Sweden

Riksdag, ''Sveriges riksdag'' added DOI to schedule I (''"substances, plant materials and fungi which normally do not have medical use"'') as narcotics in Sweden as of August 30, 2007, published by ''Medical Products Agency'' in their regulation LVFS 2007:10 listed as DOI, 4-jod-2,5-dimetoxi-amfetamin.

United States

DOI is not scheduled in the United States, but it is likely that DOI would be considered an analog (of DOB), in which case, sales or possession could be prosecuted under the

Federal Analogue Act The Federal Analogue Act, , is a section of the United States Controlled Substances Act passed in 1986 which allows any chemical "substantially similar" to a controlled substance listed in Schedule I or II to be treated as if it were listed in ...

. DOI is regularly used in animal and in vitro research. Scheduling DOI could cause problems for medical researchers.

US State of Florida

DOI is a Schedule I controlled substance in the state of Florida.

References

External links

Erowid about DOI

The Lycaeum about DOI

PiHKAL entry

DOI Entry in PiHKAL • info
{{DEFAULTSORT:Dimethoxy-4-Iodoamphetamine, 2,5- Substituted amphetamines Iodoarenes 2,5-Dimethoxyphenethylamines Designer drugs Serotonin receptor agonists TNF inhibitors PET radiotracers