TCB-2
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. 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. 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.
The drug is a highly potent receptor agonist">receptor (biochemistry)">receptor agonist, including of the serotonin 5-HT2A receptor among others. TCB-2 produces psychedelic-like effects in animals. It may be among the most potent known serotonin 5-HT2A receptor agonists and psychedelic phenethylamines. TCB-2 is often employed as its more potent and selective enantiomer -TCB-2 in scientific research.
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. It is not an explicitly controlled substance in the United States and is fully legal for use in scientific research in this country. In 2025, TCB-2 was suggested as an alternative and replacement of the widely employed DOI for use in research.
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. 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.Pharmacology
Pharmacodynamics
TCB-2 acts as a potent agonist of the serotonin 5-HT2A and 5-HT2C receptors. Its affinity for the serotonin 5-HT2A receptor has been reported to be 0.75nM and to be similar to that of 2C-B. The -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.-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 -TCB-2, -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.