First reported cases of VHD were associated with ergot derivatives acting as 5-HT2B agonists, especially in Parkinson’s disease treatment. These were discontinued due to development of pulmonary hypertension and VHD. Mechanisms involve increased myofibroblast mitogens and deposition of glycosaminoglycans in heart valves. In line with FDA draft guidance, comprehensive assessment of drug-induced VHD risk is recommended. If psychedelics demonstrate efficacy and gain regulatory approval, long-term cardiovascular safety must be monitored using systems like FAERS. Here, HTR2B is linked to pulmonary hypertension.