TWEETIO

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Examples of major TWEETIO drugs. These are 2CD-2-ETO (left), 2CE-5-ETO (center), and 2CT2-5-ETO (right). Tweetio-examples.png
Examples of major TWEETIO drugs. These are 2CD-2-ETO (left), 2CE-5-ETO (center), and 2CT2-5-ETO (right).

TWEETIO is a family of phenethylamine psychedelic drugs. [1] [2] [3] [4] 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. [1] [2] [4] 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), among many others. [1] [2] [3] [4]

Contents

The TWEETIO drugs are said to have been named in a humorous way by pronouncing the simplest structural form of "2-EtO-X". [1] [5] Limited human data are available on the TWEETIO compounds. [1] [2] [5] [4] 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. [1] [2] [5]

The TWEETIO compounds were developed by Darrell Lemaire as potential "smart drugs" in the 1970s or 1980s. [6] [7] [8] [9] The compounds were described in the scientific literature by Alexander Shulgin via personal communication with Lemaire in the 1990s and 2000s. [5] [1] [2] [4] It was said by Shulgin in 2003 that the propoxy analogues had not yet been synthesized. [1] In 2023, the propoxy derivative ASR-2001 (2CB-5PrO) was reported by Nick Cozzi and Paul F. Daley of the Alexander Shulgin Research Institute. [10] [11] [12] [13] [14] It is under development for potential medical use. [10] [11] [12] [13]

List and properties of TWEETIO drugs

TWEETIO analogues of selected 2C drugs [1] [2] [3] [4]
R4Dosage (parent)R2R5Code nameTrial doseComments of trial
Br-12–24 mgEt-Me- 2CB-2-ETO 15 mg"30–50 [mg] prolongs action"
Et-Et- 2CB-DI-ETO >55 mg"restless sleep, only"
Me-20–60 mgEt-Me- 2CD-2-ETO 60 mg"intimate, no intox, 4 hrs"
Me-Et- 2CD-5-ETO 50 mg"12 hour duration"
Et-Et- 2CD-DI-ETO >55 mg"mild, 4 hr duration"
Et-10–15 mgMe-Et- 2CE-5-ETO 15 mg"16–24 hr duration"
14–22 mgEt-Me- 2CI-2-ETO 5 mg"50 mg longer duration only"
MeS-60–100 mgEt-Me- 2CT-2-ETO 50 mg"mild, 4 hr duration"
Me-Et- 2CT-5-ETO 30 mg"15 hr duration"
EtS-12–25 mgEt-Me- 2CT2-2-ETO 50 mg"9 hr duration"
Me-Et- 2CT2-5-ETO 20 mg"16 hr duration"
Et-Et- 2CT2-DI-ETO 50 mg"only longer with higher dose"
iPrS-8–20 mgEt-Me- 2CT4-2-ETO 25 mg"dosage affects duration only"
PrS-10–30 mgEt-Me- 2CT7-2-ETO 20 mg"fast, out at 5 hrs"

Alexander Shulgin also described some of these compounds in additional detail in his book PiHKAL (Phenethylamines I Have Known and Loved). [5]

According to Shulgin in 2011, 2CB-5-EtO is not in the published scientific literature. [15] In a 1994 literature review however, Shulgin described 2CB-5-EtO as being active but 2-fold less potent than 2C-B. [2]

ASR-2001 (2CB-5PrO), a non-hallucinogenic TWEETIO analogue of 2C-B with a 5-propoxy group, is under development by the Alexander Shulgin Research Institute for use as a mild stimulant-like medication for the treatment of psychiatric disorders. [10] [11] [12] [13] [14]

Another known TWEETIO-related drug, a 2C-E analogue with a 5-isopropoxy group, is 2CE-5iPrO. [16]

DOx compounds

Various DOx compounds featured extended methoxy groups. [5] [15] These include Florence (DOM-2ETO), Iris (DOM-5ETO), DOM-2,5-DiEtO, MEM, MME, MEE, EMM, EME, EEM, and EEE, among others. [5] [15] They are derivatives of DOM and/or TMA-2. [5] [15]

Scalines

Various scalines, or mescaline analogues, featured extended methoxy groups. [5] [15] These include asymbescaline, escaline, metaescaline, metaproscaline, proscaline, symbescaline, and trisescaline (trescaline), among others. [5] [15]

MDxx compounds

EMDA-2 (2-ethoxy-4,5-methylenedioxyamphetamine) has been described by Alexander Shulgin as the "TWEETIO" analogue of MMDA-2. [5] It is active as a psychedelic, producing closed-eye visuals and other effects, with a potency of about one-third that of MMDA-2 and a duration of 10 to 12 hours. [5]

See also

References

  1. 1 2 3 4 5 6 7 8 9 Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN   978-0-12-433951-4 . Retrieved 1 February 2025. 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.
  2. 1 2 3 4 5 6 7 8 Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Res Monogr. 146: 74–91. PMID   8742795. Archived from the original (PDF) on August 5, 2023. 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.
  3. 1 2 3 Catalani V, Corkery JM, Guirguis A, Napoletano F, Arillotta D, Zangani C, Vento A, Schifano F (August 2021). "Psychonauts' psychedelics: A systematic, multilingual, web-crawling exercise". Eur Neuropsychopharmacol. 49: 69–92. doi:10.1016/j.euroneuro.2021.03.006. PMID   33857740. Table 1 NPSfinder® psychedelic phenethylamines and comparisons with EMCDDA and UNODC databases. [...]
  4. 1 2 3 4 5 6 Trachsel, D.; Lehmann, D.; Enzensperger, C. (2013). "8.5.21. Modifikation der 2,5-Dimethoxysubstituenten". Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 820–826. ISBN   978-3-03788-700-4. OCLC   858805226.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN   0-9630096-0-5. OCLC   25627628. "The Tweetio homologue of MMDA-2 has been tasted, however. This is 2-ethoxy-4,5-methylenedioxyamphetamine, or EMDA-2. [...] At 135 milligrams, there have been reported eyes-closed visual phenomena, with intense colors. The overall duration is similar to MMDA-2 (some 10 hours) and there are reported sleep disturbances. At 185 milligrams, the feelings were intensified, there were “marvelous eyes-closed visuals (the colors were incredible), good concentration, but distinct body-tingles and rushes.” The time span was about 12 hours from start to finish, but it proved to be impossible to sleep afterwards. This homologue is thus about a third the potency of MMDA-2."
  6. ↑ "Erowid Darrell Lemaire Vault". erowid.org. Retrieved 14 November 2025.
  7. ↑ Morris H (7 December 2016). "The Lazy Lizard School of Hedonism". Hamilton's Pharmacopeia . Season 1. Episode 6. Vice Media. Viceland.
  8. ↑ Hosteen Nez (Darrell Lemaire) (2010). "Notes About Psychoactive Compounds" (PDF). In Targ, Russell; Radin, Dean (eds.). Radiant Minds: Scientists Explore the Dimensions of Consciousness. Millay. pp. 201–207. ISBN   978-0-615-29633-3.
  9. ↑ Lazar (Darrell Lemaire); Hosteen Nez (1990), Certain Exotic Transmitters as Smart Pills or Compounds that Increase the Capacity for Mental Work in Humans: A Story About LAZAR as Told by Hosteen Nez (2 ed.), archived from the original (PDF) on 9 July 2001
  10. 1 2 3 Busby M (2 November 2023). "The Heirs to a Vault of Novel Psychedelics Take a Trip Into the Unknown". DoubleBlind Mag. Retrieved 19 April 2025.
  11. 1 2 3 Busby M (30 March 2025). "What Happens When You Inherit 500 Psychedelic Compounds?". DoubleBlind Mag. Retrieved 19 April 2025.
  12. 1 2 3 Kargbo RB (April 2025). "Innovative Approaches in Psychedelics, AI, and Communication: A Multi-Domain Perspective". ACS Med Chem Lett. 16 (4): 514–516. doi:10.1021/acsmedchemlett.5c00114. PMID   40236531.
  13. 1 2 3 Goldstein L (10 July 2023). "Pioneering Psychedelics Scientist Alexander "Sasha" Shulgin's Legacy Lives On Via New Compounds And Research". Benzinga. Retrieved 19 April 2025.
  14. 1 2 WOpatent 2024243599A1,Mark J. Martini; Nicholas V. Cozzi& Paul F. Daleyet al.,"Asymmetric phenylalkylamines",published 28 November 2024, assigned to Alexander Shulgin Research Institute
  15. 1 2 3 4 5 6 Shulgin A, Manning T, Daley PF (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds . Vol. 1. Berkeley, CA: Transform Press. ISBN   978-0-9630096-3-0. OCLC   709667010.
  16. ↑ Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacology & Translational Science. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC   8033619 . PMID   33860179.
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