Medicinal marijuana

Marijuana is the most widely used illegal drug throughout the world and has aroused great controversies. Nowadays you can buy marijuana (the so-called ‘MediWiet’) on prescription in the drug store. It may help to relieve the symptoms of patients suffering from multiple sclerosis, restore appetite or suppress nausea in cancer patients treated with chemotherapy. Marijuana (bangh, hashish) is an extract from the plant Cannabis Sativa that contains at least 400 chemical components of which 60 belong to the class of cannabinoids.

The notion that marijuana can be used for the treatment of various diseases is not new. Already in 2000 years BC the Chinese had discovered its therapeutic properties, but it took until 1964 before ∆9-tetrahydrocannabinol, the main psychoactive principle in marijuana, was isolated and characterized by professor Raphael Mechoulam from the Hebrew University of Jerusalem. The mechanism of action of THC has also been subject of discussion. At first it was thought that cannabinoids perturbed the membrane due to their lipophilic nature, thereby producing cellular effects. However, the requirement of one enantiomer and stringent structural features of THC to produce its pharmacological response led to the search for dedicated membrane proteins responsible for its biological effects.

In the early nineties two proteins were identified and cloned: the cannabinoid CB1 and CB2 receptors, which could be activated by THC. The cannabinoid CB1 receptor is highly expressed in the brain, whereas the CB2 receptor is mainly found in cells of the immune system. It was found that the activation of the CB1 receptor in the brain is responsible for the typical effects of being ‘high’ after smoking a joint or eating space-cake.

Faculty of Science Profile Programme: “Endocannabinoids”

Recently, the Faculty of Science at the Leiden University has started a program to investigate the role of proteins responsible for the biosynthesis of the Endocannabinoids. In this multi-disciplinary project researchers from the Leiden Institute of Chemistry (LIC), Leiden Academic Center for Drug Research (LACDR) and Institute for Biology Leiden (IBL) will collaborate to address the fundamental questions: “Why does the cannabinoid CB1 receptor use two endogenous ligands in the central nervous system?” and “How does this affect its molecular interaction with the stress pathway?”

Endocannabinoids in health and disease

Endocannabinoids are signalling molecules formed by the human brain; they activate a protein called the cannabinoid CB1 receptor. This protein can be hijacked by the main component of marijuana (Δ9-THC) and is responsible for a person becoming “high” or “stoned”, and is also linked to binge eating (i.e. having the munchies). Continuous stimulation of the CB1 receptor by the endocannabinoids is associated with nicotine addiction, obesity and metabolic syndrome; these are all major risk factors for illness and death in Europe.

Endocannabinoids: the body’s own marijuana

The presence of cannabinoid receptors in mammals suggested the existence of endogenous molecules in the brain, which bind and activate these proteins. In 1992, almost 30 years after his discovery of THC, professor Mechoulam isolated the first endogenous compound for these receptors from porcine brain. This component proved to be a lipid: N-arachidonoylethanolamine. The compound was called anandamide ("ananda" is Sanskrit for internal bliss).