The fight against multiple sclerosis, epilepsy and stroke could also involve controversial molecules such as CBD and futuristic biotechnologies.
The brain has enormous resilience. If it loses neurons, for example with aging, others can replace its functions thanks to the so-called “neuronal reserve”. But it is not an infinite superpower: at a certain point the loss of cells becomes so severe that it can no longer be compensated for. It happens in neurodegenerative diseases such as Alzheimer’s, Parkinson’s or after a stroke. These pathologies are under the lens of Spoke 6 researchers (Neurodegeneration, trauma and stroke) coordinated by Tullio Florio of the University of Genoa. Their aim is to understand the mechanisms of alteration of brain cells and identify new biomarkers for early diagnosis and new targets for drugs. Sometimes, the solutions to these problems are found in surprising places.
This is the case of the studies by Domenico Pellegrini-Giampietro and Elisa Landucci, from the University of Florence, who are investigating the role of cannabinoids in neurodegenerative diseases. These molecules that are extracted from the Cannabisof the sativa and indica varieties, from which marijuana and hashish are prepared, have in fact a “double face” that could open up new therapeutic avenues. «The two best-known substances are tetrahydrocannabinol (THC) and cannabidiol (CBD): the first is responsible for the narcotic effects of cannabis, the second is not and also for this reason it is sold freely in many countries and, unlike THC, it is not considered doping in sport», explains Pellegrini-Giampietro, who has been studying these molecules for years on experimental models of cerebral ischemia. Research recently published by the Mnesys team has shown that THC accentuates damage to neurons in several ways; in particular by altering the function of mitochondria (the cell’s energy plants) and synapses. But, on the contrary, CBD shows a protective potential in ischemia, similar to what is observed in other diseases such as multiple sclerosis and epilepsy. In the latter case, it is already used successfully in infantile forms that do not respond to traditional drugs. «CBD also slightly attenuates the negative effects of THC in those who abuse cannabis products», specifies Pellegrini-Giampietro. «Cbd is therefore protective in pathological conditions, i.e. in the presence of neurological diseases or in case of chronic abuse of joints and the like. In healthy people, however, it is not such a “quiet” molecule as many think, especially when the nervous system is developing: during pregnancy and adolescence, great care is needed even with CBD alone, because it has been observed that it can have negative consequences on the brain of unborn children and young people.”
chaos and caution
In short, CBD is a substance to be handled with care. On the one hand, it could prove to be a resource for protecting neurons; on the other, it is at the center of misunderstandings, fueled by confusing legislation (in Italy since July 2024 it has been included among narcotic substances and in pharmacies it can only be sold with a medical prescription) and by often superficial consumption. «In Italy there are two drugs, one with pure CBD for refractory childhood epilepsy, the other that contains THC and CBD in equal doses for multiple sclerosis and cancer pain, as an adjunct to therapy that can reduce the need for opioids», informs Pellegrini-Giampietro. «Alongside official drugs, however, there exists a chaotic and unregulated world of extracts whose true composition is difficult to know. The cannabis plant is a “Pandora’s box”: it contains many cannabinoids and, depending on how they are extracted, very different products are obtained. Today we have some more clinical information only for THC and CBD. To complicate the picture, plants are not all the same. In short, the objective of the research is to best characterize this set of molecules to identify the most useful combinations in different conditions.” However, a crucial challenge remains: how to bring these molecules into the brain with maximum effectiveness? In fact, it is protected by the blood-brain barrier, an almost impassable “gate” that blocks 98% of drugs. To overcome it, Anna Rita Bilia, a chemist at the University of Florence, is developing tiny nano-vesicles, infinitely small lipid bubbles. These “ships” can be loaded with drugs, cross the barrier and release them in a controlled manner. Tests are underway specifically for CBD, but the technology could make many neurological therapies more efficient.
