2C-C

2C-C (4-chloro-2,5-dimethoxyphenethylamine) is a ring-substituted phenethylamine psychedelic of the 2C series, bearing a chlorine atom at the 4-position of the 2,5-dimethoxyphenethylamine scaffold. The compound was first synthesized by Cheng and Castagnoli in 1984 as an intermediate in a structure-activity investigation of 6-hydroxydopamine neurotoxicity analogs and was subsequently characterized for human psychoactive effects by Alexander Shulgin in the 1991 compendium PiHKAL, where it was assigned entry number 22 with an oral dose range of 20 to 40 milligrams and a duration of 4 to 8 hours. Within the halogen-substituted 2C series (2C-F, 2C-C, 2C-B, 2C-I), 2C-C occupies a position of moderate potency: its 5-HT2A receptor binding affinity (Ki approximately 5.5 nanomolar in radioligand displacement assays against [125I]DOI) is comparable to that of 2C-B and 2C-I, but its functional efficacy at the 5-HT2A receptor (approximately 40 to 64 percent of maximal serotonin response in inositol phosphate accumulation assays) places it as a partial agonist with lower intrinsic activity than several congeners. The compound shows high-affinity binding at 5-HT2C receptors (Ki approximately 102 nanomolar) with near-full agonist efficacy (approximately 94 percent) and moderate activity at 5-HT2B receptors (EC50 approximately 280 nanomolar, 81 percent efficacy), while showing negligible affinity for monoamine transporters and no monoamine releasing activity. In behavioral pharmacology, 2C-C fully substitutes for DOM and MDMA in rat drug discrimination paradigms, suppresses locomotor activity in mice at doses of 30 to 100 mg/kg, and produces the head-twitch response characteristic of 5-HT2A receptor activation. Metabolism proceeds predominantly through monoamine oxidase A and B catalyzed deamination, with minor contributions from cytochrome P450 2D6 and O-demethylation pathways. Kim et al. (2021) demonstrated that 2C-C produces dose-dependent conditioned place preference in mice and self-administration in rats, indicating abuse liability, and induces neurotoxicity at high doses through neuroinflammatory mechanisms including decreased dopamine transporter expression, increased dopamine transporter phosphorylation, and elevated c-Fos expression in the nucleus accumbens and medial prefrontal cortex. The compound is classified as a Schedule I controlled substance in the United States (since July 2012) and is controlled in multiple additional jurisdictions. This monograph reviews the chemistry, synthesis, and structural class of 2C-C; the receptor pharmacology and mechanism of action in molecular and behavioral detail; the available pharmacokinetic record; the preclinical evidence base including neurotoxicity and abuse potential; the limited human observational literature; sourcing and quality verification considerations for research applications; reconstitution and handling; stack interaction considerations; adverse events and safety signals; and a comparative assessment of five structurally or pharmacologically related compounds (2C-B, 2C-I, mescaline, DOC, 25C-NBOMe) against 2C-C on five competency standards. The compound is a research tool for serotonergic pharmacology and structure-activity investigations; it is not approved for any therapeutic indication and is classified as a controlled substance in most jurisdictions where its legal status has been addressed.