DOI

Summary sheet: DOI

DOI
Chemical Nomenclature
Common names	DOI
Substitutive name	2,5-Dimethoxy-4-iodoamphetamine
Systematic name	1-(4-Iodo-2,5-dimethoxyphenyl)-2-propanamine
Class Membership
Psychoactive class	Psychedelic
Chemical class	Amphetamine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Threshold 0.5 mg Light 0.5 - 1 mg Common 1 - 2 mg Strong 2 - 3 mg Heavy 3 mg + Duration Total 16 - 24 hours Onset 1 - 2 hours Come up 1.5 - 3 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions

2,5-Dimethoxy-4-iodoamphetamine (abbreviated DOI) is a synthetic psychedelic substance of the phenethylamine and substituted amphetamine chemical classes that produces notably dose-sensitive, long-lived psychedelic and stimulating effects when administered. Unlike other substituted amphetamines, however, it is not a traditional stimulant. DOI was first synthesized by a team at the University of Alberta in 1972. Its usage in humans was first documented by Alexander Shulgin in the 1991 book PiHKAL ("Phenethylamines I Have Known and Loved").

DOI is very well-researched in comparison to many drugs despite being relatively uncommon in terms of its recreational use. This is because it is often used in research as a radioligand and indicator of the presence of 5-HT2A serotonin receptors.

In humans, DOI's reported effects have often drawn comparisons to those of LSD, although there are notable differences that experienced users can distinguish. Besides the significantly longer duration, the experience is commonly reported to be more energetic than an LSD experience with a more pronounced body load and a different subjective visual and auditory effects profile. The after effects include long-lasting residual stimulation and difficulty sleeping, which, depending on the dose and time taken during the day, may persist for days afterwards. 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.

Today, DOI finds rare use as a recreational drug and an entheogen, and rarely sold on the streets (unless in the form of misrepresented LSD) and typically obtained as a research chemical through online vendors. Along with its sensitive dose-response and unusually long duration, many reports also suggest that this substance may be overly difficult to use safely for those who are not already very experienced with hallucinogens. Therefore it is highly advised to approach this highly dose-sensitive, and long-lasting psychedelic substance with the proper amount of precaution and harm reduction practices if choosing to use it.

History and culture

This History and culture section is a stub. As a result, it may contain incomplete or wrong information. You can help by expanding it.

Chemistry

DOI, or 2,5-Dimethoxy-4-iodoamphetamine, is a molecule of the amphetamine class. Amphetamines are substituted phenethylamines containing a phenyl ring bound to an amino (NH₂) group through an ethyl chain and a methyl group bound to the alpha carbon R_α. DOI contains methoxy functional groups CH₃O- attached to carbons R₂ and R₅ as well as an iodine atom attached to carbon R₄ of the phenyl ring. DOI is the amphetamine, or alpha-methylated analogue, of the phenethylamine 2C-I.

Pharmacology

Further information: Serotonergic psychedelic

DOI's psychedelic effects are believed to come from its efficacy as an agonist at the 5-HT_2A, 5-HT_2B and 5-HT_2C receptors. However, the role of these interactions and how they result in the psychedelic experience continues to remain the subject of ongoing scientific inquiry.

DOI and its isomers binding profiles to specific 5HT receptor sets can be seen in the chart below:

Binding Profile of DOI and its isomers

Receptor	Ki (racemic DOI)	Ki (R-DOI)	Ki (S-DOI)	Intrinsic activity
5-HT1A	2355 nM	3843 nM	ND	ND
5-HT1B	1261 nM	ND	ND	ND
5-HT1D	1241.3 nM	ND	ND	ND
5-HT1E	2970 nM	ND	ND	ND
5-HT1F	2125.44 nM	ND	ND	ND
5-HT2A	0.68 nM	0.65 nM	0.65 nM	Partial agonist.
5-HT2B	20.03 nM	53.70318 nM	28.183829 nM	Partial agonist/full agonist
5-HT2C	2.38 nM	5.370318 nM	8.317638 nM	Full agonist when coupled to phospholipase A. Partial agonist (intrinsic efficacy = 53%) when coupled to phospholipase C.
5-HT5A	1000 nM	ND	ND	ND
5-HT5A	1000 nM	ND	ND	ND
5-HT6	>10000 nM	ND	ND	ND

Besides its action as a psychedelic, DOI has been shown to be an extremely potent inhibitor 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 and Alzheimer's disease 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 and synaptic connections with other neurons, processes known to underlie neuroplasticity.

Subjective effects

This subjective effects section is a stub. As such, it is still in progress and may contain incomplete or wrong information. You can help by expanding or correcting it.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects

• Stimulation - In terms of its effects on the physical energy levels of the user, DOI is usually considered to be extremely stimulating at levels which are capable of become uncomfortable and overwhelming. This can result in a shakiness and unsteadiness of the hands but encouraging one to move around, run, dance, climb and generally engage in physical activities. In comparison, other more commonly used psychedelics such as psilocin are generally sedating and relaxed.
• Spontaneous physical sensations - The "body high" of DOI often described as being notably more intense in comparison to most classical psychedelics such as LSD. The sensation itself can be described as a constantly present yet somewhat mild energetic pins and needles sensation that encompasses a person’s entire body. It is usually felt over every square inch of the skin but occasionally manifests itself in the form of a continuously shifting tingling sensation that travels up and down the body in spontaneous waves. However, this effect is reported to be very dose-dependent, as even slight increases in one's dose can result in persisting unpleasant feelings of over-stimulation.
  • Physical euphoria - It should be noted that this effect is not as reliably induceable as it is with substances like stimulants or entactogens, and can just as easily manifest as physical discomfort without any apparent reason.
• Bodily control enhancement
• Tactile enhancement - Feelings of enhanced tactile sensation are consistently reported at low to moderate levels throughout most DOI experiences.
• Nausea - Mild to extreme nausea is reported when consumed in moderate to high dosages and either passes once the person has vomited or gradually fades by itself as the peak sets in.
• Increased blood pressure
• Increased heart rate
• Muscle contractions
• Muscle spasms
• Vasoconstriction - This effect is usually only present at higher dosages, but can be particularly uncomfortable when it manifests, and may persist throughout the main duration of the experience.
• Appetite suppression
• Dehydration
• Increased perspiration
• Difficulty urinating
• Pupil dilation
• Salivation
• Seizure - This is a rarely observed effect but is known to happen in those who are presumably predisposed to them, especially while in physically taxing conditions such as being dehydrated, undernourished, overheated, or generally fatigued.

Cognitive effects

The cognitive effects of DOI are described by many as characterized as extreme mental stimulation combined with a powerful amplification of the user's current mental state.

The total sum of these cognitive components regardless of the setting generally includes:

• Conceptual thinking
• Thought acceleration
• Thought connectivity
• Anxiety & Paranoia - This effect is not as common at low to moderate doses and is less likely to occur when the basic rules of set and setting are taken into account. It should be noted that this inconsistently induced effect is seemingly more likely to manifest when used with cannabis. This combination should be used with extreme caution if one is not experienced with psychedelics, meaning that the user should adequately pace themselves with a fraction of their usual amount. It is commonly reported that psychedelics can to a certain extent counteract some of the perceived mental cloudiness or intoxicating effects of THC causing the user to in turn use more cannabis than is needed which can often lead to an overwhelmingly anxious and paranoid headspace which can trigger a "bad trip".
• Empathy, affection, and sociability enhancement - This component is typically manifested only in the context of social settings in which one is within the company of others, and only at lower, non-impairing doses. These feelings of sociability, affection and empathy tend to be weaker and less consistent than those found on substances such as MDMA and 2C-B, but can still prove strong enough to provide long-lasting therapeutic effects.
• Cognitive euphoria
• Delusions
• Analysis enhancement - This effect is consistent in its manifestation and outrospection dominant.
• Emotionality enhancement
• Novelty enhancement
• Personal bias suppression
• Personal meaning enhancement
• Immersion enhancement
• Increased libido
• Increased music appreciation
• Increased sense of humor
  • Laughter fits - This can manifest prominently during a DOI experience, particularly during the come up phase, often resulting in bouts of uncontrollable giggles and laughter that can form a feedback loop if around others who are also under the influence.
• Memory suppression
  • Ego death
• Thought loops
• Time distortion
• Wakefulness

Visual effects

Enhancements

• Colour enhancement
• Pattern recognition enhancement
• Visual acuity enhancement

Distortions

• Drifting (melting, breathing, morphing and flowing)
• Colour shifting
• Depth perception distortions
• Perspective distortions
• Symmetrical texture repetition
• Tracers
• After images
• Brightness alteration
• Diffraction

Geometry

Hallucinatory states

DOI and other psychedelic substituted amphetamines produce a full range of high level hallucinatory states in a fashion that is more consistent and reproducible than that of many other commonly used psychedelics. This holds particularly true in comparison to other substances within the phenethylamine class. These effects include:

• Transformations
• Internal hallucinations (autonomous entities; settings, sceneries, and landscapes; alterations in perspective and scenarios and plots) - In comparison to other psychedelics such as LSD, DOI is extremely high in internal hallucinations. They are more common within dark environments and can be comprehensibly described through its variations as lucid in believability, interactive in style, new experiences in content, autonomous in controllability, geometry-based in style and almost exclusively of a personal, religious, spiritual, science-fiction, fantasy, surreal, nonsensical or transcendental nature in their overall theme.
• External hallucinations - These are often present during the comedown and can include shadow people, among other indescribable beings. These external hallucinations are often lucid, interactive, autonomous, and robust. As sleep deprivation and stimulant psychosis surface, a trip sitter should accompany individuals sensitive to stimulants for the last part of the comedown. The visual effects of psychosis have been reported to blend into the psychedelic visuals around the 16-24 hour mark, sometimes accompanied by auditory hallucinations.

Auditory effects

• Enhancements
• Distortions
• Hallucinations

Transpersonal effects

• Existential self-realization
• Unity and interconnectedness

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

• Erowid Experience Vaults: DOI

Toxicity and harm potential

Further information: Research chemicals § Toxicity and harm potential, and Responsible use § Hallucinogens

The toxicity and long-term health effects of recreational DOI do not seem to have been studied in any scientific context and the exact toxic dose is unknown. This is because DOI is a research chemical with very little history of human usage. Anecdotal evidence from those within the community who have tried DOI suggests that there are no negative health effects attributed to simply trying the substance by itself at low to moderate doses and using it very sparingly (but nothing can be completely guaranteed). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

It is strongly recommended that one use harm reduction practices when using this substance.

Tolerance and addiction potential

DOI is not habit-forming and the desire to use it can actually decrease with use. It is most often self-regulating.

Tolerance to the effects of DOI are built almost immediately after ingestion. After that, it takes about 5-7 days for the tolerance to be reduced to half and 10-14 days to be back at baseline (in the absence of further consumption). DOI presents cross-tolerance with [[Cross-tolerance::all psychedelics]], meaning that after the consumption of DOI all psychedelics will have a reduced effect.

Legality

This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it.

• Australia - The Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) of Australia does not list DOI as a prohibited substance.
• Brazil - Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344.
• Canada - DOI is listed as a Schedule 1 drug as it is an analogue of amphetamine. The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1.
• Denmark - It has been illegal since April 8, 2007.
• Latvia - DOI is a Schedule I controlled substance.
• Sweden - DOI is a Schedule I substance as of August 30, 2007; this was published by the Medical Products Agency in their regulation LVFS 2007:10.
• United Kingdom - It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.
• United States - DOI is not scheduled in the United States, but it is likely that it would be considered an analog (of DOB) in which case sales or possession could be prosecuted under the Federal Analogue Act. DOI is regularly used in animal and in vitro research. Scheduling DOI could cause problems for medical researchers.
  • Florida - DOI is a Schedule I controlled substance in the state of Florida.

See also

• Responsible use
• Psychoactive substance index
• Psychedelics
• Phenethylamines
• DOx
• DOM
• DOC

External links

• DOI (Wikipedia)
• DOI (PiHKAL)
• DOI (TripSit)
• DOI (Bluelight)

Literature

• Nichols, D. E. (2016). Psychedelics. Pharmacological Reviews, 68(2), 264-355. https://doi.org/10.1124/pr.115.011478
• Coutts, R. T., & Malicky, J. L. (1973). The synthesis of some analogs of the hallucinogen 1-(2, 5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Canadian Journal of Chemistry, 51(9), 1402-1409. https://doi.org/10.1139/v73-210