TCB-2

Use and effects

TCB-2 does not appear to have been formally tested in humans and its properties and effects are unknown. 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 presmably oral). No additional details were provided, including notably with regard to the nature of the effects. There are also a number of trip reports of TCB-2 on online forums, but such reports are unconfirmed and may not be reliable. In relation to the preceding, it has been said that there are no valid data on TCB-2 in humans.

Interactions

Pharmacology

Pharmacodynamics

TCB-2 acts as a potent agonist of the serotonin 5-HT2A and 5-HT2C receptors. Its affinity (Ki) for the serotonin 5-HT2A receptor has been reported to be 0.75nM and to be similar to that of 2C-B (Ki = 0.88nM). 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. 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. Besides the serotonin 5-HT2 receptors, TCB-2 might importantly stimulate the serotonin 5-HT1A receptor. The comprehensive receptor interactions of TCB-2 have been studied. 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.

(R)-TCB-2 has been found to substitute for LSD and DOI in rodent drug discrimination tests. 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. In contrast to (R)-TCB-2, (S)-TCB-2 was inactive in the test even at a more than 10-fold higher dose. TCB-2 also produces the head-twitch response, another behavioral proxy of psychedelic effects, in rodents. 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. This might be related to TCB-2's biased serotonin 5-HT2A receptor agonism. 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. The drug produces rapid antidepressant-, anti-anhedonic-, and anxiolytic-like effects in animals. TCB-2 shows anti-inflammatory effects in preclinical research, albeit with lower potency and efficacy than non-cyclized analogues. Unlike other psychedelic phenethylamines, TCB-2 produces some behavioral serotonin syndrome-like effects in rodents. Other animal studies have also been done.

Chemistry

Synthesis

The chemical synthesis of TCB-2 has been described. 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.

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. 2CBCB-NBOMe, the NBOMe derivative of TCB-2, shows 2.7-fold higher affinity for the serotonin 5-HT2A receptor than TCB-2 itself.

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. 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. However, subsequent studies using the head-twitch response found it to be much less potent. In late 2025, TCB-2 was suggested as an alternative and replacement of the widely employed DOI for use in research. This was due to DOI being poised to become a restricted Schedule I controlled substance in the United States.

Society and culture

Availability

TCB-2 is commercially available for use in scientific research.

Legal status

Canada

TCB-2 is not a controlled substance in Canada as of 2025.

United States

TCB-2 is not a controlled substance in the United States. However, it could be considered an analogue of 2C-B under the Federal Analogue Act. In any case, as it is not an explicitly controlled substance, there are no restrictions on use of TCB-2 for scientific research purposes.

References

References

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