Psychedelic drugs have been highly investigated in recent years due to apparent effects on depression, but are limited by side effects related to hallucinations. We have conducted mechanistic studies of psychedelic drug effects on downstream second messenger systems, and have identified counteracting receptor pathways. We will advance a drug combination which reduces psychedelic hallucinogenic effects by continuing these mechanistic and dose-finding studies, and thus enable drug development for a novel drug-combination with improved tolerability.