Is 2C-B a Psychedelic Drug?

2C-B causes psychedelic effects via the serotonin 5-HT2A receptor.

April 15, 2019 -

2C-B is a drug that belongs to the phenethylamine family. Figure 1 shows its chemical structure. Alexander Shulgin first synthesized 2C-B in 1974. This synthetic drug has been receiving a lot of attention recently due to its increasing popularity in the club scene along with ketamine, MDMA, and cocaine.

Drugs in the phenethylamine family are stimulants of the central nervous system. Because of this, it makes sense that at first glance compounds like 2C-B are not considered psychedelic drugs like tryptamine compounds (e.g., psilocin, bufotenin). However, further examination of 2C-B shows it is indeed psychedelic in terms of its effects and receptor binding.

The subjective effects of 2C-B are similar to other psychostimulants like MDMA and amphetamine and psychedelics such as ayahuasca, salvinorin A, and Salvia divinorum.1 The effects include euphoria, mood changes more than perceptual changes, and a psychedelic experience with an altered state of consciousness.

Figure 1: The chemical structure of 2C-B. Its chemical name is 2-(4-bromo-2,5-dimethoxyphenyl)ethanamine.

Scientists classify a drug as psychedelic if its effects are caused by agonist or partial agonist binding to serotonin 5-HT2A receptors.1,2 No fMRI studies have been done to confirm 2C-B binding to 5-HT2A receptors in the human brain correlates with subjective effects. However, testing using 5-HT2A in in vitro receptor affinity studies confirms this theory. In 2010, the Psychoactive Drug Screening Program (PDSP) at the National Institute of Mental Health assayed 25 drugs including 2C-B at 51 receptors.3 The results showed 2C-B is an agonist of 5-HT2A.

In addition, the affinity of 2C-B for 5-HT2A has been shown in oocytes from the frog Xenopus laevis (African clawed frog)4 and Chinese hamster ovary K1 cells5 expressing the human 5-HT2A receptor. These studies categorized 2C-B as a partial agonist of 5-HT2A. There is also experimental evidence indicating 2C-B is a partial agonist of 5-HT2B and 5-HT2C.6,7 However, it is unknown how the agonist activity at these two receptors influences the psychedelic effects of 2C-B.

Although it is not a tryptamine, 2C-B is a psychedelic drug. The evidence for this comes from scientific studies showing its affinity for the 5-HT2A receptor. Also, experience reports from users of 2C-B have documented its effects which include a psychedelic experience. Further research into 2C-B would provide insight into the possible therapeutic potential of this compound.

    References
  1. Papaseit E, Farré M, Pérez-Mañá C, et al. Acute Pharmacological Effects of 2C-B in Humans: An Observational Study. Frontiers in Pharmacology. 2018;9:206. doi:10.3389/fphar.2018.00206
  2. Nichols DE, Nichols CD. Serotonin Receptors. Chem Rev. 2008;108(5):1614-1641. doi:10.1021/cr078224o
  3. Ray TS. Psychedelics and the Human Receptorome. PLoS ONE. 2010;5(2):17. doi:10.1371/journal.pone.0009019
  4. Villalobos CA, Bull P, Sáez P, Cassels BK, Huidobro‐Toro JP. 4‐Bromo‐2, 5‐dimethoxyphenethylamine (2C‐B) and structurally related phenylethylamines are potent 5‐HT2A receptor antagonists in Xenopus laevis oocytes. British Journal of Pharmacology. 2004;141(7):1167-1174. https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0705722.
  5. Moya PR, Berg KA, Gutierrez-Hernandez MA, et al. Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT) 2A and 5-HT2C receptors. Journal of Pharmacology and Experimental Therapeutics. 2007;321(3):1054-1061. doi:10.1124/jpet.106.117507.
  6. Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME. Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology. 2015;99:546-553. doi:10.1016/j.neuropharm.2015.08.034
  7. Luethi D, Trachsel D, Hoener MC, Liechti ME. Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs). Neuropharmacology. 2018;134:141-148. doi:10.1016/j.neuropharm.2017.07.012