Cannabinoid receptors, through which marijuana exerts its effects, have been found in a key emotional hub in the brain involved in regulating anxiety and the flight-or-fight response. This is the first time cannabinoid receptors have been identified in the central nucleus of the amygdala in a mouse model.
- The natural endocannabinoid system regulates anxiety and the response to stress by dampening excitatory signals that involve the neurotransmitter glutamate.
- Chronic stress or acute, severe emotional trauma can cause a reduction in both the production of endocannabinoids and the responsiveness of the receptors. Without their “buffering” effect, anxiety goes up.
- While marijuana’s “exogenous” cannabinoids also can reduce anxiety, chronic use of the drug down-regulates the receptors, paradoxically increasing anxiety. This can trigger “a vicious cycle” of increasing marijuana use that in some cases leads to addiction.
The researchers at Vanderbilt involved in this study used high-affinity antibodies to label or mark the cannabinoid receptors so that they could be relatively easily seen using the various microscopy techniques utilized, including electron microscopy, which allowed for very detailed visualization at individual synapses between nerve cells.
“We know where the receptors are, we know their function, we know how these neurons make their own cannabinoids,” Patel said. “Now can we see how that system is affected by … stress and chronic (marijuana) use? It might fundamentally change our understanding of cellular communication in the amygdala.”
Sachin Patel, M.D., Ph.D., right, with Teniel Ramikie. The team found cannabinoid receptors in a part of the brain involved in regulating anxiety. Photo Credit: Joe Howell and Vanderbilt University Press Release.