TCB-2
Psychedelic drug
From Wikipedia, the free encyclopedia
TCB-2, also known as 2CBCB or 2C-BCB, is a putative psychedelic drug of the phenethylamine, 2C, and benzocyclobutene families related to 2C-B.[1][3][2][5] It is a cyclized phenethylamine and is the derivative of 2C-B in which the β position has been connected to the 6 position by a methylene bridge to form a benzocyclobutene ring system.[3][1][5] It is unclear whether TCB-2 produces hallucinogenic effects in humans and its route of administration and properties such as dose and duration are unknown.[1][2][3]
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 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; 2C-TCB |
| 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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| Pharmacokinetic data | |
| Duration of action | Unknown[1][2][3][4] |
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| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C11H14BrNO2 |
| Molar mass | 272.142 g·mol−1 |
| 3D model (JSmol) | |
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The drug is a highly potent serotonin receptor agonist, including of the serotonin 5-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 and selective enantiomer (R)-TCB-2 in scientific research.[3][1][5]
TCB-2 was first described in the scientific literature by Thomas McLean and colleagues of the lab of David E. Nichols at Purdue University in 2006.[1][5] It was encountered as a novel designer drug by 2018, though it appears to be very rare.[1][9][10] The drug is not an explicitly controlled substance in the United States and is fully legal for use in scientific research in this country.[2][1] TCB-2 was suggested as an alternative and replacement of the widely employed DOI for use in research in 2025.[2]
Use and effects
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 is psychoactive in the low-milligram range (route unspecified but presumably oral).[3] No additional details were provided, including notably with regard to the nature of the effects.[3] There are also a number of trip 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]
Interactions
Pharmacology
Pharmacodynamics
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 145 (Ki) 1.5–2,290 (EC50) 28–54% (Emax) |
| 5-HT1B | 49 (Ki) 1.9–13 (EC50) 87–100% (Emax) |
| 5-HT1D | 22 (Ki) 3.6–20 (EC50) 95–107% (Emax) |
| 5-HT1E | 62 (Ki) 4.7–98 (EC50) 100–112% (Emax) |
| 5-HT1F | ND (Ki) 25–331 (EC50) 96–110% (Emax) |
| 5-HT2A | 0.26–6.9 (Ki) 0.49–36 (EC50) 68–101% (Emax) |
| 5-HT2B | 2.2 (Ki) 4.3–8.7 (EC50) 82–90% (Emax) |
| 5-HT2C | 9.8 (Ki) 1.2–18 (EC50) 64–96% (Emax) |
| 5-HT3 | >10,000 |
| 5-HT4 | ND |
| 5-HT5A | >10,000 (Ki) 28–135 (EC50) 38–40% (Emax) |
| 5-HT6 | 40 (Ki) 30 (EC50) 80% (Emax) |
| 5-HT7 | 42 (Ki) 1,740 (EC50) 79% (Emax) |
| α1A–α1D | >10,000 |
| α2A | 661 |
| α2B | 1,550 |
| α2C | 447 |
| β1–β3 | >10,000 |
| D1, D2 | >10,000 |
| D3 | 186 |
| D4 | 2,290 |
| D5 | >10,000 |
| H1 | >10,000 |
| H2 | 5,620 |
| H3, H4 | >10,000 |
| M1–M5 | >10,000 |
| TAAR1 | ND |
| I1 | ND |
| σ1 | 603 |
| σ2 | >10,000 |
| SERT | >10,000 (Ki) ND (IC50) |
| NET | >10,000 (Ki) ND (IC50) |
| DAT | >10,000 (Ki) ND (IC50) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [6][5][11] | |
TCB-2 acts as a potent agonist of the serotonin 5-HT2A and 5-HT2C receptors.[1][3][5] Its affinity (Ki) for the serotonin 5-HT2A receptor has been reported to be 0.75 nM and to be similar to that of 2C-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 higher activational potency at this receptor.[1][3][5] TCB-2 is a biased agonist of the serotonin 5-HT2A receptor, showing 65-fold higher potency in stimulating phosphoinositide turnover than in activating arachidonic acid release.[1][3][5] Besides the serotonin 5-HT2 receptors, TCB-2 might importantly stimulate the serotonin 5-HT1A receptor.[1][12] The comprehensive receptor 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 for LSD and DOI in rodent drug discrimination tests.[1][3][5] It showed similar potency in this regard as LSD and 11- to 13-fold greater potency than DOI, making it one of the most potent known psychedelic drugs in this assay.[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 the head-twitch response, another behavioral proxy of psychedelic effects, in rodents.[1][7][8][12] 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][13] 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 produce hyperlocomotion at lower doses and hypolocomotion at higher doses in rodents.[1][7][8][14] The drug produces rapid antidepressant-, anti-anhedonic-, and anxiolytic-like effects in animals.[15] TCB-2 shows anti-inflammatory effects in preclinical research, albeit with lower potency and efficacy than non-cyclized analogues.[16][17] Unlike other psychedelic phenethylamines, TCB-2 produces some behavioral serotonin syndrome-like effects in rodents.[1][12] Other animal studies have also been done.[8][18][19][20]
Chemistry
Synthesis
The chemical 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 in scientific research.[21]
Analogues
Analogues of TCB-2 include 2C-B, DOB, β-methyl-2C-B (BMB), tomscaline, 2CB-Ind, jimscaline, LPH-5, 2CBCB-NBOMe (NBOMe-TCB-2), and ZC-B, among others.[3] 2CBCB-NBOMe, the NBOMe derivative of TCB-2, shows 2.7-fold higher affinity for the serotonin 5-HT2A receptor than TCB-2 itself.[11]
History
TCB-2 was first described in the scientific literature by Thomas McLean and colleagues of the lab of David E. Nichols at Purdue University in 2006.[1][5] At the time of its discovery, it was the most potent known phenethylamine psychedelic, with (R)-TCB-2 having similar potency as the better-known LSD, at least on the basis of rodent drug discrimination assays.[5] However, subsequent studies using the head-twitch response found it to be much less potent.[1][7][8][12] TCB-2 was reported to have been encountered as a novel designer drug by 2018, although it appears to be very rare.[1][9][10] In late 2025, TCB-2 was suggested as an alternative and replacement of the widely employed DOI for use in research.[2] This was due to DOI being poised to become a restricted Schedule I controlled substance in the United States.[2][22][23]
Society and culture
Availability
TCB-2 is commercially available for use in scientific research.[21]
Legal status
Canada
TCB-2 is not a controlled substance in Canada as of 2025.[24]
United States
TCB-2 is not a controlled substance in the United States.[2][1][25] However, it could be considered an analogue of 2C-B under the Federal Analogue Act.[2] In any case, as it is not an explicitly controlled substance, there are no restrictions on use of TCB-2 for scientific research purposes.[2][1]