 Racemic TCB-2 structure | |
 TCB-2 ball-and-stick model | |
| Clinical data | |
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| Other names | 2CBCB; 2C-BCB; 6,β-Methylene-2C-B |
| Routes of administration | Unknown[1][2][3][4] |
| Drug class | Serotonin receptor agonist;Serotonin 5-HT2A receptor agonist;Serotonergic psychedelic;Hallucinogen |
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| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Duration of action | Unknown[1][2][3][4] |
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| ChEBI | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C11H14BrNO2 |
| Molar mass | 272.142 g·mol−1 |
| 3D model (JSmol) | |
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TCB-2, also known as2CBCB or2C-BCB, is a putativepsychedelic drug of thephenethylamine,2C, andbenzocyclobutene families related to2C-B.[1][3][2][5] It is acyclized phenethylamine and is thederivative of 2C-B in which the β position has been connected to the 6 position by amethylene bridge to form a benzocyclobutenering system.[3][1][5] It is unclear whether TCB-2 produceshallucinogenic effects in humans and itsroute of administration and properties such asdose andduration are unknown.[1][2][3]
The drug is a highlypotentserotonin receptor agonist, including of the serotonin5-HT2A receptor among others.[3][6][1][5] TCB-2 produces psychedelic-like effects in animals.[3][1][7][8][5] It may be among the most potent known serotonin 5-HT2A receptor agonists and psychedelic phenethylamines.[3][5] TCB-2 is often employed as its more potent andselectiveenantiomer (R)-TCB-2 inscientific research.[3][1][5]
TCB-2 was first described in thescientific literature by Thomas McLean and colleagues of the lab ofDavid E. Nichols atPurdue University in 2006.[1][5] It is not an explicitlycontrolled substance in theUnited States and is fully legal for use in scientific research in this country.[2][1] In 2025, TCB-2 was suggested as an alternative and replacement of the widely employedDOI for use in research.[2]
TCB-2 does not appear to have been formally tested in humans and its properties and effects are unknown.[1][2][3][4] However,Daniel Trachsel has reported based on anonymous personal communication in 2009 that TCB-2 ispsychoactive in the low-milligram range (route unspecified but presmablyoral).[3] No additional details were provided, including notably with regard to the nature of the effects.[3] There are also a number oftrip reports of TCB-2 on online forums, but such reports are unconfirmed and may not be reliable.[1] In relation to the preceding, it has been said that there are no valid data on TCB-2 in humans.[1]
TCB-2 acts as apotentagonist of theserotonin5-HT2A and5-HT2C receptors.[1][3][5] Itsaffinity (Ki) for the serotonin 5-HT2A receptor has been reported to be 0.75 nM and to be similar to that of2C-B (Ki = 0.88 nM).[1][3][5] The (R)-enantiomer shows 3-fold higher affinity for the serotonin 5-HT2A receptor as well as 2-fold higheractivational potency at this receptor.[1][3][5] TCB-2 is abiased agonist of the serotonin 5-HT2A receptor, showing 65-fold higher potency in stimulatingphosphoinositide turnover than in activatingarachidonic acid release.[1][3][5] Besides the serotonin5-HT2 receptors, TCB-2 might importantly stimulate the serotonin5-HT1A receptor.[1][9] The comprehensivereceptor interactions of TCB-2 have been studied.[6] It is a potent agonist of the serotonin 5-HT1A,5-HT1B,5-HT1D,5-HT1E,5-HT1F, 5-HT2A, 5-HT2B, and 5-HT2C receptors, with the highest activity at the serotonin 5-HT2A receptor.[6]
(R)-TCB-2 has been found to substitute forLSD andDOI in rodentdrug discrimination tests.[1][3][5] It showed similar potency in this regard as LSD and 11- to 13-fold greater potency thanDOI, making it one of the most potent known psychedelic drugs in thisassay.[1][3][5] In contrast to (R)-TCB-2, (S)-TCB-2 was inactive in the test even at a more than 10-fold higher dose.[3][5] TCB-2 also produces thehead-twitch response, another behavioral proxy of psychedelic effects, in rodents.[1][7][8][9] However, in contrast to drug discrimination, the drug required surprisingly high doses to produce the head-twitch response, showing similar potency to that of DOI in this assay.[1][8][10] This might be related to TCB-2's biased serotonin 5-HT2A receptor agonism.[1][8] In addition to its psychedelic-like effects, TCB-2 has been found to producehyperlocomotion at lower doses andhypolocomotion at higher doses in rodents.[1][7][8][11] The drug produces rapidantidepressant-,anti-anhedonic-, andanxiolytic-like effects in animals.[12] TCB-2 showsanti-inflammatory effects inpreclinical research, albeit with lower potency and efficacy than non-cyclizedanalogues.[13][14] Unlike other psychedelic phenethylamines, TCB-2 produces some behavioralserotonin syndrome-like effects in rodents.[1][9] Otheranimal studies have also been done.[8][15][16][17]
Thechemical synthesis of TCB-2 has been described.[5] The synthesis of TCB-2 has been described as tedious, such that its manufacture has been prevented from being economical, although it is still available commercially for use inscientific research.[18]
Analogues of TCB-2 include2C-B,DOB,β-methyl-2C-B (BMB),tomscaline,2CB-Ind,jimscaline,LPH-5,2CBCB-NBOMe (NBOMe-TCB-2), andZC-B, among others.[3] 2CBCB-NBOMe, theNBOMederivative of TCB-2, shows 2.7-fold higheraffinity for theserotonin5-HT2A receptor than TCB-2 itself.[19]
TCB-2 was first described in thescientific literature by Thomas McLean and colleagues of the lab ofDavid E. Nichols atPurdue University in 2006.[1][5] At the time of its discovery, it was the mostpotent knownphenethylaminepsychedelic, with (R)-TCB-2 having similar potency as the better-knownLSD, at least on the basis of rodentdrug discrimination assays.[5] However, subsequent studies using thehead-twitch response found it to be much less potent.[1][7][8][9] In late 2025, TCB-2 was suggested as an alternative and replacement of the widely employedDOI for use inresearch.[2] This was due to DOI being poised to become a restrictedSchedule Icontrolled substance in theUnited States.[2][20][21]
TCB-2 is commercially available for use inscientific research.[18]
TCB-2 is not acontrolled substance inCanada as of 2025.[22]
TCB-2 is not acontrolled substance in theUnited States.[2][1][23] However, it could be considered ananalogue of2C-B under theFederal Analogue Act.[2] In any case, as it is not an explicitly controlled substance, there are no restrictions on use of TCB-2 forscientific research purposes.[2][1]
A potent molecule that was developed by constraint of the side chain is TCB-2 (McLean et al., 2006), now commercially available as a 5-HT2A/2C agonist for experimental laboratory studies. Although its synthesis is tedious enough to prevent its manufacture from being economical, it does exemplify the fact that relatively modest structural changes can lead to active compounds.
