DOI: Difference between revisions

'''2,5-Dimethoxy-4-iodoamphetamine''' (also known as '''DOI''') is a lesser-known [[Psychoactive class::psychedelic]] substance of the [[chemical class::phenethylamine]] class. It is a member of the [[DOx]] family of psychedelic amphetamines.  

The synthesis of DOI was first reported in 1972<ref>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</ref> and its usage in humans was first documented by [[Alexander Shulgin]] in the 1991 book [[PiHKAL]] ("Phenethylamines I Have Known and Loved").{{citation needed}} DOI is very well-researched compared to most psychedelics. It is regularly used in research as a radioligand to map [[Serotonin#The 5-HT System|serotonin-2A]] [[receptors]] in the brain.{{citation needed}}

The effects of DOI are often compared to those of [[LSD]], although notable differences can be distinguished. Besides the significantly longer duration, the experience is commonly reported to be more [[stimulating]] than LSD, with a more pronounced [[body load]] and a less complex head space. The after effects include long-lasting residual stimulation and [[wakefulness|difficulty sleeping]], which, depending on the dose and time taken during the day, may persist for days afterwards.<ref name="DOI TiHKAL" />

DOI is sometimes sold as a substitute for LSD, or even sold falsely as LSD. This can be dangerous because DOI does not have the same established safety profile as LSD.<ref>LSD BLOTTER ACID MIMICS (ACTUALLY CONTAINING

4-IODO-2,5-DIMETHOXYAMPHETAMINE (DOI) AND 4-CHLORO-2,5-DIMETHOXYAMPHETAMINE (DOC)) IN LANTANA, FLORIDA | http://web.archive.org/web/20090204025435/http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg0608/mg0608.html</ref>

DOI was first synthesized by a team at the University of Alberta in 1972.<ref>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</ref>

 

 

====Neuroplasticity====

One study demonstrated that [[DOI]], [[DMT]], [[LSD]], and noribogaine (a metabolite of [[ibogain]]) promotes neuritogenesis both ''in vitro'' and ''in vivo''.<ref>https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30755-1</ref>

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 OCH₃ 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]].<ref>http://isomerdesign.com/PiHKAL/read.php?domain=pk&id=67</ref>

DOI's [[psychedelic]] effects are believed to come from its efficacy as an [[agonist]] at the [[Serotonin#The 5-HT System|5-HT_2A]], [[Serotonin#The 5-HT System|5-HT_2B]] and [[Serotonin#The 5-HT System|5-HT_2C]] [[receptor]]s.<ref name="head twitch">Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/22517680</ref> However, the role of these interactions and how they result in the [[psychedelic]] experience continues to remain the subject of ongoing scientific inquiry.  

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.<ref>Serotonin 5-Hydroxytryptamine2A Receptor Activation Suppresses Tumor Necrosis Factor-α-Induced Inflammation with Extraordinary Potency | Journal of Pharmacology and Experimental Therapeutics (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/18708586 </ref>

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.<ref>Jones, K. A., Srivastava, D. P., Allen, J. A., Strachan, R. T., Roth, B. L., & Penzes, P. (2009). Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling. Proceedings of the National Academy of Sciences, 106(46), 19575-19580. PMID: 19889983. https://doi.org/10.1073/pnas.0905884106</ref>

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

 

*'''[[Tramadol]]''' - Tramadol lowers the seizure threshold<ref>Talaie, H., Panahandeh, R., Fayaznouri, M. R., Asadi, Z., & Abdollahi, M. (2009). Dose-independent occurrence of seizure with tramadol. Journal of medical toxicology, 5(2), 63-67. doi:10.1007/BF03161089</ref> and [[psychedelics]] may act as triggers for seizures, particularly in those who are predisposed to them.{{citation needed}}

*'''[https://en.wikipedia.org/wiki/Lithium_(medication) Lithium]''' - Lithium is often used as treatment for bipolar disorder. It may possibly cause elevated risk of seizures and psychosis due to its [[Glutamate|glutaminergic]] and [[GABA|GABAergic]] effects.{{citation needed}}

 

*'''Austria:''' DOI is illegal to possess, produce and sell under the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich).{{citation needed}}

*'''Australia:''' DOI is not listed as a prohibited substance in The Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).<ref>Therapeutic Goods Administration. Australian Government Department of Health and Ageing | http://www.comlaw.gov.au/Details/F2013L01607/229bdf2e-7014-4379-b751-0b584f55d699</ref>

*'''Brazil:''' DOI is illegal to possess, produce and sell as it is listed on Portaria SVS/MS nº 344.<ref>http://portal.anvisa.gov.br/documents/10181/3115436/%281%29RDC_130_2016_.pdf/fc7ea407-3ff5-4fc1-bcfe-2f37504d28b7</ref>

*'''Canada:''' DOI is listed as a Schedule 1<ref>Canadian Legal Information Institute (CanLII). Controlled Drugs and Substances Act, S.C. 1996, c. 19, as amended | http://isomerdesign.com/Cdsa/schedule.php?schedule=1&section=18.5&structure=C</ref> drug as it is an analogue of amphetamine.<ref>Canadian Legal Information Institute (CanLII). Controlled Drugs and Substances Act, S.C. 1996, c. 19, as amended | http://isomerdesign.com/Cdsa/definitions.php?structure=C</ref> The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1.

*'''Denmark:''' DOI became illegal on April 8, 2007.{{citation needed}}

*'''Germany:''' DOI is controlled under BtMG Anlage II, making it illegal to manufacture, import, possess, sell, or transfer it without a license.<ref>http://www.gesetze-im-internet.de/btmg_1981/anlage_ii.html</ref>

*'''Latvia:''' DOI is a Schedule I controlled substance.<ref>Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem (2,5-Dimetoksifeniletānamīni) | http://likumi.lv/doc.php?id=121086</ref>

*'''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.<ref>Läkemedelsverkets författningssamling | http://www.lakemedelsverket.se/upload/lvfs/LVFS_2007-10.pdf</ref>

*'''United Kingdom:''' DOI is illegal to produce, supply, or import under the Psychoactive Substance Act, which came into effect on May 26th, 2016.<ref>Psychoactive Substances Act 2016 (Legislation.gov.uk) | http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted</ref>

*'''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.{{citation needed}}

**'''Florida:''' DOI is a Schedule I controlled substance in the state of Florida.<ref>The 2015 Florida Statutes Title XLVI CRIMES Chapter 893 DRUG ABUSE PREVENTION AND CONTROL | http://leg.state.fl.us/statutes/index.cfm?App_mode=Display_Statute&URL=0800-0899/0893/0893.html</ref>

 

[[Category:Amphetamine]]

[[Category:Hallucinogen]]

[[Category:Phenethylamine]]

[[Category:Psychoactive substance]]