Researchers from Osaka University in Japan have discovered that the body’s own cannabinoids – known as endocannabinoids – play a major role in regulating the formation of brain connections, and that smoking marijuana may interfere with this process. Appearing in the Journal of Neuroscience, this research not only sheds light on some of the potential dangers of regularly using cannabis while the brain is developing, but also helps to clear up the long-standing mystery of how neural circuits are created.

Scientists have known for some time that the young brain undergoes major structural changes before reaching maturity, and that during this formative period, the number and arrangement of connections between neurons – known as synapses – are extensively remodeled. This neural refurbishment occurs in two stages, the first of which involves the formation and strengthening of new synapses, while the second is characterized by synaptic pruning, whereby any unnecessary connections are erased in order to streamline neural circuits.

To investigate how this process is mediated, the study authors used fluorescent proteins that enabled them to track activity in the brains of newborn mice, focusing particularly on the development of thalamocortical axons (TCAs), which are the nerve fibers linking the neurons of the thalamus to those of the cortex.

Administration of THC caused a massive reduction in the number of TCAs, as indicated by the lower visibility of bright green proteins in the image on the right. Osaka University

From the day that the mice were born, the researchers began to see new TCAs extend from the thalamus and invade the cortex, although after a few days this process stopped and many of these new connections were subsequently pruned. The shift from the creation of new synapses to their deletion coincided with an increase in the expression of a type of brain receptor known as type 1 cannabinoid receptors (CB1Rs), suggesting that endocannabinoids may be involved in stimulating synaptic pruning.

To confirm this, the team then used mice that had been engineered to lack CB1Rs in this region of the brain, finding that this suppressed the normal development of new brain connections. They then injected the brains of mice with tetrahydrocannabinol (THC) – the psychoactive ingredient in marijuana –and discovered that when this binds to CB1Rs it too interferes with the proper formation of synapses.

In humans, much of this synaptic pruning occurs during adolescence, during which time the brain undergoes some drastic changes. Any disruptions to this process can lead to cognitive impairment, which is why many people tend to develop mental illnesses during this stage of their lives. In light of this new research, therefore, the dangers of smoking too much weed as a teenager are brought into sharp relief, suggesting that cannabis abuse during these years could prevent the formation of healthy neural circuits.