Cannabis intoxication is certainly not the original purpose of the cannabinoid receptors in the human brain. Nowadays, there are known body substances which dock to the receptor molecules of nerve cells in a similar way to cannabis. A group of researchers led by pharmacologist Prof. Dr. med. Bela Szabo at the University of Freiburg is investigating the role of this molecular system in the human brain. Their research reveals a neuronal feedback mechanism that might be important for the brain, amongst other things.
The CB1 receptor and the endocannabinoids are part of what is known as a retrograde signalling system. A negative feedback loop, which also involves endocannabinoids, registers when the stimulatory synaptic activity is too high and needs to be lowered. “This is most likely the most common type of retrograde signal transmission in the brain,” assumes Szabo. The endocannabinoid-based principle is important for the permanent modification of the strength of synaptic contacts; it is used to mediate synaptic plasticity. For example, a specific initial activity of synapses can lead to the long-term depression (LTD) of synapses (this can last for several hours), a phenomenon that is regarded as an important neuronal basis of memory. In many areas of the brain, endocannabinoids are important prerequisites for the occurrence of LTD. Szabo and his colleagues have also investigated the role of cannabinoid receptors in other areas of the nervous system, for example in the peripheral nervous system where the cannabinoids can have an effect on blood pressure. At present, the Freiburg researchers are investigating the mechanisms that control the endocannabinoid production in the nerve cells. The field of cannabinoid biology and pharmacology is not only interesting from the perspective of basic researchers, the pharmaceutical industry might also benefit from this research. For example, there is evidence that cannabinoid agonists have a pain relieving effect. Another example is stroke patients who might benefit from cannabinoid receptors that are able to maintain a low activity of nerve cells in risk areas and thus prevent the neurones from suffering long-term damage. The CB2 receptor also attracts the scientists’ attention. As it is found on the cell membrane of immune system cells, its activation might lead to the inhibition of certain inflammatory reactions. However, it is difficult to use these approaches for therapeutic applications. “The problem is the ubiquitous localisation of the cannabinoid receptors,” said Szabo. “It is a challenge to find substances that are able to activate or inhibit specific cannabinoid receptors in specific areas, thereby creating fewer side effects.