LPH-5

LPH-5 is a novel, phenethylamine-derived psychedelic and therapeutic candidate developed by Lophora. It is a conformationally-restricted derivative of 2C-TFM but is considered a new chemical entity (NCE), not a prodrug or close analog of any known psychedelic[1][2][10]. LPH-5 acts as a highly potent and selective agonist at the serotonin 2A (5-HT2A) receptor, with an EC50 of 3.2 nM and Emax of 78%[1][3]. It demonstrates strong selectivity for the 5-HT2A receptor over other serotonin receptors, particularly showing negligible activity at the off-target serotonin 2B receptor, which reduces cardiac risk[1][2][10]. Preclinical studies have shown that LPH-5 produces persistent antidepressant effects in rodents after single administration without cytotoxicity or genotoxicity[6]. The drug has excellent pharmacokinetic properties and low promiscuity across other targets. Clinical development focuses on treatment-resistant depression (TRD) and major depressive disorder (MDD), with potential applications in broader CNS disorders[7][8][10].