Disovery of the endocannabinoid system

This page delves into the endocannabinoid system (ECS), exploring its scientific discovery in the late 1980s and the identification of key components like receptors and endogenous cannabinoids.

Research into the ECS and its functions was initially slow, as the nature of the ECS as a lipid-transmitter-based system and its homeostatic actions introduced a new type of regulatory biological system not based on e.g., peptides.

Today, the body’s fascinating endocannabinoid system is known to be one of the most extensive biological systems in mammals (Maccarrone, 2017; Scherma et al., 2019; Lu and Mackie, 2021). Nevertheless, the ECS and its many functions still need to be further elucidated. 

Studies are providing increasing evidence that the ECS is paramount in the treatment of neurological, neuropsychiatric and psychiatric conditions. Such conditions appear treatable through modulating the ECS with far fewer side effects than current treatments. As such, this is one of the most exciting areas of research in mental health today. However, further research and high-quality clinical trials are needed to fully demonstrate the efficacy and safety of therapies targeting the ECS.  

The Evolution of Understanding: A Chronology of Discoveries in the Endocannabinoid System.

  • Late 1980's

    In the late 1980s, research conducted at Allyn Howlett’s lab at St. Louis University provided the first concrete evidence for the existence of cannabinoid receptors (Howlett et al., 1986). In 1988, Allyn Howlett and her graduate student, William Devane, discovered a large group of receptors that responded to THC (delta-9-tetrahydrocannabinol, the psychoactive cannabinoid found in the Cannabis plant) (Devane et al., 1988).

  • 1990

    Confirmation came in 1990 and 1991 with the cloning and expression of complementary DNA encoding the cannabinoid receptor 1 (CB1R) by Tom Bonner’s research group at the National Institutes of Mental Health, Bethesda, Maryland, USA (Matsuda et al., 1990) and Gérard and colleagues at the Institut de Recherche Interdisciplinaire, Université Libre de Bruxelles, Belgium. The second cannabinoid receptor (CB2R) was identified a few years later in Sean Munro’s laboratory in Cambridge, UK (Munro et al., 1993; Gerard et al., 1991).

  • 1992

    Once it became evident that human cannabinoid receptors exist, the search for endogenous cannabinoids began. The first endocannabinoid – anandamide – was identified in 1992 by William Devane, who by then was working in Jerusalem in a lab led by Raphael Mechoulam, a renowned chemist who has devoted much of his long life to the Endocannabinoid System (ECS) (Devane, 1992).

  • 1995

    In 1995 Mechoulam’s lab and Sugiura and colleagues (Teikyo University, Sagamiko, Kanagawa, Japan) discovered a second endocannabinoid – 2-arachidonoylglycerol (Sugiura et al., 1995; Mechoulam et al., 1995).

    Together these findings resulted in the discovery of the ECS. The importance attributed to the ECS in recent research was cited as early as the 90s. The ECS appears to be involved in several disorders, including a number of psychiatric conditions (for review see, Parolaro et al., 2010) and among them schizophrenia (Leweke et al. 1999), post-traumatic stress disorder (e.g., Schaefer et al., 2013) and social anxiety disorder.

  • 1997

    In 1997, Hinderk M. Emrich, F. Markus Leweke and Udo Schneider established the cannabinoid hypothesis of schizophrenia and two years later, Leweke et al. (1999) reported on the first study linking anandamide, one of the main endogenous transmitters of the ECS, to schizophrenia.

    Further, the group investigated the link of the ECS to other mental health conditions as well. This led to the development of new psychopharmacological approaches in psychiatric conditions that target this system.