Cannabis Damages Cells Essential for Brain Development in Adolescents

cannabis-brain effect

Researchers have discovered that tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, damages brain microglia, thereby exposing adolescents to an increased risk of psychiatric disorders, including schizophrenia, and learning difficulties. In experiments conducted on mouse models, the compound notably increased genetic predisposition to these disorders and hindered brain development. Therefore, researchers are urging caution regarding its consumption, which is on the rise among adolescents.

In recent years, recreational and medical cannabis use has significantly increased worldwide. THC, a psychoactive substance that causes euphoria in users, and CBD, a compound known for its calming effects, are the main mediators of its effects.

As adolescents’ nervous systems and brains are still developing, they are particularly vulnerable to the negative effects of THC. According to Atsushi Kamiya, a professor of psychiatry and behavioral sciences at Johns Hopkins University, “its concentration in marijuana plants has increased four times in the last 20 years, posing a particular danger for adolescents who are genetically predisposed to psychoactive disorders including schizophrenia.”

Previous studies have reported that cannabis use in adolescents is associated with an increased risk of psychiatric disorders and cognitive abnormalities. These effects result from the presence of type 1 cannabinoid receptors (Cnr1) in the brain, which specifically bind to THC. While it was previously believed that these receptors were located only at presynaptic terminals, recent research has revealed that they are also expressed in astrocytes and microglia.

Microglial cells are a subset of macrophages that play a crucial role in communication between neurons, immune responses, and brain development. In adolescents, they play a key role in synaptic pruning during brain maturation and in neuronal processes related to social and cognitive functions. Kamiya and his colleagues already suspected that THC could induce structural changes in microglia, thereby altering brain development and cognitive functioning in adolescents.

Increased Microglial Apoptosis

To test their hypothesis, researchers from the new study selected genetically modified adolescent mice to exhibit a mutation characteristic of a predisposition to psychiatric disorders in humans, such as schizophrenia. These mutations induce brain changes in regions responsible for emotion control, learning, and memory. Indeed, previous research has suggested that cannabis’s involvement in psychiatric disorders is modulated by genetic predisposition to these conditions (gene-environment interaction).

Both genetically modified and non-modified animals received daily single injections of THC for 30 days, while the control group received a saline solution. After this administration, the rodents had a 3-week resting period before behavioral tests. These tests included odor detection, object recognition, social interaction, and memory. Fluorescent markers were also used to quantify microglia and assess morphological differences with healthy microglia.

The results revealed that mice exposed to THC showed increased microglial apoptosis (programmed cell death). However, the loss of microglia was 33% higher in those with the genetic mutation. This reduction was particularly pronounced in the prefrontal cortex, the brain region responsible for memory, social behavior, decision-making, and other executive functions.

Since microglia are involved in the maturation of the developing brain, their reduction could lead to abnormal cellular signaling and communication, according to the researchers. This hypothesis is consistent with the fact that genetically modified mice receiving THC scored 40% lower on social memory compared to their counterparts receiving a saline solution.

Overall, the results suggest that cannabis consumption in adolescence could lead to long-term negative effects. “This kind of study is critical right now because marijuana is becoming more mainstream, and we are just beginning to understand how it affects the brain immune cells,” says the study’s lead author, Yuto Hasegawa of Johns Hopkins University, published in the journal Nature Communications.

However, further research is needed to confirm the reproducibility of these results in humans. Additionally, an essential step is to determine the exact way in which microglial abnormalities affect brain functions at the molecular level. Nevertheless, these findings can already contribute to raising awareness of adolescents’ exposure to cannabis.

Featured Image:  Michael S. Helfenbein.