Tetrahydrocannabinol (THC), the main cannabinoid in marijuana, may cause memory loss by inhibiting the energy-producing components of brain cells, known as mitochondria, according to a newly published study in the journal Nature.
Cannabinoids such as THC bind to cannabinoid receptors throughout the central nervous system (CNS) in order to produce a range of effects, some of which lead to the sensation of feeling stoned. It was recently discovered that the mitochondria inside neurons also have cannabinoid receptors on their membranes, raising the possibility that certain substances may alter energetic activity in the brain.
Researchers therefore decided to investigate whether this causes memory deficits. First, they placed mice in a maze along with a series of objects. Once the mice had familiarized themselves with these items, the team injected THC into their brains, specifically targeting the hippocampus, which controls memory formation.
As a consequence, the mice appeared to forget their previous encounters with the maze and its contents, indicated by the fact that they spent a significant amount of time re-familiarizing themselves with these items.
However, mice that were engineered to lack cannabinoid receptors in the mitochondria of their hippocampal neurons did not experience the same level of amnesia, suggesting that this memory loss may be mediated by the way that THC interacts with these mitochondria.
The researchers then extracted neurons from the hippocampus of both sets of mice, and observed what happened when they were introduced to THC in a petri dish. In the brain cells taken from regular mice, the addition of cannabinoids interrupted the electron transport system of mitochondria, leading to a decrease in synthesis of a molecule called ATP, which acts as the major cellular energy store.
As a consequence, cellular respiration dropped, causing a decrease in communication among the neurons of the hippocampus.
In contrast, cells taken from mice that lacked cannabinoid receptors in their mitochondria did not show any signs of reduced energy or connectivity, which the researchers say probably explains why memory formation was not impaired in these mice.
In a statement, study co-author Pedro Grandes said that this new information could one day help to create new therapeutic cannabinoids that target “specific cannabinoid receptors located in the brain in certain specific neurone compartments,” in order to avoid any unwanted side effects like memory loss.