2,5-Dimethoxy-4-iodoamphetamine

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists DOI's dose as 1.5 to 3mg orally and its duration as 16 to 30hours. The effects of DOI have been reported to include feelings of unreality, strangeness, closed-eye imagery, time dilation, having none of LSD's sparkle, depression and sadness, enhanced eroticism, lightheadedness, and spaciness, among others. It was said to have little or no body load. The (R)-enantiomer, (R)-DOI, was active at doses of 1.0 to 2.3mg orally, whereas the (S)-enantiomer, (S)-DOI, was active at a dose of 6.3mg orally. == Interactions ==

It is unclear whether DOI may interact with monoamine oxidase inhibitors (MAOIs). ==Pharmacology==

Pharmacodynamics Actions DOI is a serotonin 5-HT2A, 5-HT2B and 5-HT2C receptor agonist. The drug shows biased agonism at the serotonin 5-HT2C receptor. The drug is not a monoamine releasing agent of serotonin or dopamine. The compound has a stereocenter, and R-(−)-DOI is the more active stereoisomer. (R)-DOI was the most active of the assessed drugs and showed extremely high potency that was in the picomolar range and was an order of magnitude more potent than its action as a hallucinogen. TNFα may play a mediating role in the pathophysiology of degenerative inflammatory conditions like rheumatoid arthritis and Alzheimer's disease. (R)-DOI has also been found to block pulmonary inflammation, mucus hyperproduction, airway hyperresponsiveness, and to turn off key genes in pulmonary immune response, effects which block the development of allergic asthma in animal models. These findings could make DOI and other serotonin 5-HT2A agonists novel treatments for inflammatory conditions. DOI has been shown to induce rapid growth and reorganization of dendritic spines and synaptic connections with other neurons, processes known to underlie neuroplasticity, and hence to be a psychoplastogen. DOI, along with other psychedelics, has been reported to produce serotonergic neurotoxicity in vitro and in rodents in vivo at high doses given repeatedly. Serotonin 5-HT2A receptor antagonism or knockdown could partially but greatly block this neurotoxicity in vitro. ==Chemistry==

DOI, also known as 2,5-dimethoxy-4-iodoamphetamine or as 2,5-dimethoxy-4-iodo-α-methylphenethylamine, is a substituted phenethylamine and amphetamine derivative and a member of the DOx family of drugs. It is structurally related to the naturally occurring phenethylamine psychedelic mescaline (3,4,5-trimethoxyphenethylamine). Synthesis The chemical synthesis of DOI has been described. Analogues Analogues of DOI include 2C-I, 4C-I, DOB, DOC, DOF, and DOM, among many others. Other analogues include N-methyl-DOI, IDNNA (N,N-dimethyl-DOI), DOI-NBOMe, and 25I-NBOMe, among others. ==History==

DOI was first described in the scientific literature by Ronald Coutts and Jerry Malicky in 1973. Subsequently, it was described in greater detail by Alexander Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). South Australian man Cody Edwards who brutally murdered Synamin Bell controversially plead guilty to the lesser sentence of manslaughter after attesting that the drug DOI had induced paranoia, and that he had subsequently acted in 'self-defence' when he had beaten the mother-of-three to death with a dumbbell, resulting in over fifty wounds. As of late 2025, DOI is expected to become a Schedule I controlled substance in the United States. ==Society and culture==

Scientific research DOI is widely used in scientific research to study serotonergic psychedelics and the serotonin 5-HT2 receptors. Legal status Australia The Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) of Australia does not list DOI as a prohibited substance. Canada Listed as a Schedule 1 as it is an analogue of amphetamine. The CDSA was updated as a result of the Safe Streets and Communities Act, changing amphetamines from Schedule 3 to Schedule 1. Denmark Illegal since 8 April 2007. Finland DOI is classified as a psychoactive substance banned from the consumer market in Finland. Sweden 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 As of 2023, DOI is not scheduled in the United States. However, DOI may be considered an analog of other controlled DOx drugs like DOB, in which case, sales or possession could be prosecuted under the Federal Analogue Act. The drug's non-controlled status has made it usefully accessible for use in scientific research, which has contributed to its popularity for such uses. However, in May 2024, it was reported that the DEA's June 10, 2024 hearing on scheduling of DOI and DOC had been postponed. This followed opposition to the proposal by psychedelic researchers. DOI is a Schedule I controlled substance in the state of Florida. == See also ==