2,5-dimethoxy-4-iodoamphetamine (DOI) is a psychedelicdrug and a substituted amphetamine of the phenethylamine family. It is also a powerful anti-inflammatory that is effective at doses on the order of 100 micrograms in humans, far below its effective dose as a psychedelic. Despite being a substituted amphetamine, it is not a stimulant. DOI has a stereocenter and R-(-)-DOI is the more active stereoisomer. In neuroscience research, [125I]-R-(-)-DOI is used as a radioligand and indicator of the presence of 5-HT2A serotonin receptors. When ingested recreationally, DOI is active at a dosage of 1.5 - 3.0 mg (orally) and has a duration of 16 – 30 hours (approximately twice as long as LSD). DOI's effects have been compared to LSD, 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 and a different subjective visual experience. The after effects include residual stimulation and difficulty sleeping, which, depending on the dose, may persist for days. 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. Psychedelic amphetamines such as DOI have a much lower therapeutic index when compared to psychedelic tryptamines including naturally derived materials such as psilocybin and ergolines, perhaps most famously LSD. There is little data currently available on the pharmaceutical and therapeutic effects of DOI.
The solubility of DOI hydrochloride in H2O is 10 mg/ml, and in ethanol 2 mg/ml.
DOI has also recently been shown to be an extremely potent inhibitor of tumor necrosis factor-alpha, an inflammatory mediator which is an important target for current research into degenerative conditions such as arthritis and Alzheimer's disease, where the disease process involves tissue damage through chronic inflammation. This could make DOI and other 5-HT2A agonists an entirely new area for development of novel treatments for these conditions.
DOI was first synthesized by Alexander Shulgin. The radioactiveiodine-125 form of DOI was first developed in the lab of David E. Nichols. In January 2007, British Police reported that 3 young men had fallen ill, reportedly, after taking DOI at a rave in Biggleswade, near Milton Keynes, 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 in the UK. Given that it is structurally derived from phenethylamine through methoxy substitutions on the ring, it is a Class A drug in the UK.
An extremely large increase of the hallucinogenic drug has been seen in sales in Adelaide, Australia. It is commonly sold as LSD or just "trips".
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 Aug 30, 2007, published by Medical Products Agency in their regulation LVFS 2007:10 listed as DOI, 4-jod-2,5-dimetoxi-amfetamin.