TWEETIO (psychedelics)

File:Tweetio-examples.png (left), 2CE-5-ETO (center), and 2CT2-5-ETO (right).]]

TWEETIO is a family of phenethylamine psychedelic drugs.{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 | access-date=1 February 2025 | quote=I learned of a remarkable study that had been methodically carried out but never published, in which the methoxy groups of a number of the 2C- family replaced with ethoxy groups. As there are two methoxy groups, there are three possible homologues: the 2-methoxy-, the 5-methoxy- or both methoxys an be lengthened. These compounds were called the TWEETIO compounds in a humorous way of pronouncing the simplest of them, a compound with an ethoxy (or EtO-) group at the 2-position, vis., 2-EtO-something. (See Table 3.11.) [...] Table 3.11 The TWEETIO homologues of several 2C- compounds [...] In most of these listings the human studies involved only two subjects, never more than six. For this reason, ranges are not given, only typical dosages, and the short statement of effect is simply a terse abstract of the reports that were written. Some generalities are possible. Homologation at the 2-position appears to lead to a shorter duration and a decrease in potency. Homologation at the 5-position can enhance the potency and increase the duration to a remarkable degree. With 2CE-5-ETO for example, the administration of Valium or Halcion allowed sleep, but did not abort the long duration of action. Longer ether chains such as the propoxy groups have not been synthesized as yet.}}{{cite journal | vauthors = Jacob P, Shulgin AT | title = Structure-activity relationships of the classic hallucinogens and their analogs | journal = NIDA Res Monogr | volume = 146 | issue = | pages = 74–91 | date = 1994 | pmid = 8742795 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 | quote = Two additional centrally active structural variations of the prototype 2C-D have been observed and explored to a small degree. The p-oxygenated analogs are known as the β-methoxy-β-arylethylamine (BOX) series, and the materials with ethoxy groups in place of either of the methoxy groups are called the tweetios. Neither family is entered in table 3, but both are logical extensions of it. [...] The two tweetio analogs (2-ethoxy and 5-ethoxy) of both 2C-D and 2C-B have been explored and have dramatically reduced activity. The 5-tweetio (5-ethoxy) compounds are of twofold lessened potency, and the 2-tweetio (2-ethoxy) materials are down by another factor of five. The bis-etios (2,5-diethoxy homologs of 2C-D and 2C-B) are not known to be active at all.}}{{cite journal | vauthors = Catalani V, Corkery JM, Guirguis A, Napoletano F, Arillotta D, Zangani C, Vento A, Schifano F | title = Psychonauts' psychedelics: A systematic, multilingual, web-crawling exercise | journal = Eur Neuropsychopharmacol | volume = 49 | issue = | pages = 69–92 | date = August 2021 | pmid = 33857740 | doi = 10.1016/j.euroneuro.2021.03.006 | url = https://cronfa.swan.ac.uk/Record/cronfa55715| quote = Table 1 NPSfinder® psychedelic phenethylamines and comparisons with EMCDDA and UNODC databases. [...]}}{{cite book | last1=Trachsel | first1=D. | last2=Lehmann | first2=D. | last3=Enzensperger | first3=C. | chapter=8.5.21. Modifikation der 2,5-Dimethoxysubstituenten | pages=820–826 | title=Phenethylamine: von der Struktur zur Funktion | trans-title = Phenethylamines: From Structure to Function | edition = 1 | publisher=Nachtschatten-Verlag | location = Solothurn | series=Nachtschatten-Science | year=2013 | isbn=978-3-03788-700-4 | oclc = 858805226 | url=https://books.google.com/books?id=-Us1kgEACAAJ | language=de }} They are analogues of the 2C drugs (4-substituted 2,5-dimethoxyphenethylamines) in which one or both of the methoxy groups at positions 2 and 5 of the phenyl ring have been lengthened to ethoxy groups. Examples include 2CD-2-ETO (a TWEETIO of 2C-D), 2CE-5-ETO (a TWEETIO of 2C-E), and 2CT2-5-ETO (a TWEETIO of 2C-T-2).

The TWEETIO drugs are said to have been named in a humorous way by pronouncing the simplest structural form of "2-EtO-X". Limited human data are available on the TWEETIO compounds. In any case, some generalizations have been made, including that the 2-ETO compounds tend to have a shorter duration and decreased potency, the 5-ETO drugs tend to have enhanced potency and remarkably increased durations, and the 2,5-Di-ETO drugs tend to be inactive.

The TWEETIO compounds were not the work of psychedelic chemist Alexander Shulgin, but were communicated to and reported by Shulgin in the scientific literature in the 1990s and 2000s. It was said by Shulgin in 2003 that the propoxy analogues had not yet been synthesized. In 2023, a propoxy derivative, ASR-2001 (2CB-5PrO), was first reported.