International Medical Cannabis Conference, University of Bern 2025, IMCCB-25

My lecture will recount three forgotten moments in the history of endocannabinoid research.The first took place in 1996, when the newly discovered anandamide, the first endocannabinoid substance to be identified, came dangerously close to an untimely death.It may seem odd now, but back then, the idea that an unusually looking lipid molecule could transmit signals from one brain cell to another was viewed by many with a great deal of disbelief.So much that one bizarre circumstance almost consigned anandamide to the trash bin of science.The next story bears witness to the difficulties early researchers experienced in identifying the biochemical mechanisms through which anandamide is produced.Some of those difficulties are still with us today and await to be resolved.The last part of the lecture will describe the discovery of the second endocannabinoid, 2-arachidonoylglycerol, which until then had been considered a rather mundane intermediate in lipid metabolism but turned out to be one of the most pervasive modulatory transmitters in the mammalian brain.The lecture will mostly rely on published articles, lab notebooks, and personal correspondence and its main objective is to show that each of the events recounted was an important juncture in the progress of endocannabinoid studies, which is worth remembering along with its many protagonists and learned lessons.It is also my hope that the lecture will help the audience to acquire a deeper understanding of the endocannabinoid system, which will allow them to bring into focus the many open questions that need to be addressed by future research.