Cannabis causes social isolation due to dysfunction of a non-neuronal star-shaped cell in the brain

Cannabis (Marijuana) is a drug obtained from the hemp plant such as Cannabis sativa and Cannabis indica. The principal psychoactive component is tetrahydrocannabinol (THC). It is the popular recreational drug around the world coming behind alcohol, tobacco. People taking the drug for a long period are facing the side effects like depression, less viability towards social action, and it finally leads to the withdrawal of drugs.

The mechanism of how the drug acts in the brain and causes social abnormality lied unclear over the decades. Researchers now gave a biochemical idea of explaining it. The study published in journal Nature shows that the active drug binds to the cannabinoid receptor, which is present in star-shaped cells of the CNS called astrocytes, that would likely be a cause for the behavioral change of the humans.

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Cannabis – molecular level of action

An active component of cannabis is known to disrupt the metabolic balance between neurons and astrocytes. Previous research has enlightened that the cannabinoid receptors not only present on the cell membrane of the astrocyte, but also on the mitochondrial are membrane. This finding provides a clue of causing social disability when someone gets intoxicated.

Astrocytes, besides acting as a “Blood-Brain-Barrier,” plays an important role in the energy metabolism of the brain. The significance of lactate production in the neurons has been studied for years, and it is established to have a role in energy metabolism other than glucose. The star-shaped cell is likely to take the glucose from the blood and metabolize it into lactate, which will be utilized as food for the neurons present in the vicinity.

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Having this idea, Marsicano and his team did a trial in the mice to understand the action more clearly. They observed that the cannabinoid attaches to the mtCB1 receptor which is located in the mitochondrial membrane of astrocytes. This leads to a cascade of events with a reduction of lactate in the cell, thereby causing the death of the surrounding neuron.

The cascade event includes a decreased level of reactive active species (ROS) in the cell, which downregulates the amount of lactate that is shuttled to neurons through a protein mtCB2. Due to the less energy intake by the neuron, their function becomes impaired resulting in the harmful behavior of the animals. They also said that the social interactions were reduced for up to 24 hours after exposure to THC.

This finding helps us to know about the astrocyte’s efficient functions in the brain, and it will be the beginning of further research to tackle the behavioral problems due to cannabis and other related drugs.

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Source: MedicalXpress

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