Okay if you were a pretty smart 7-10 year old…

Humans and animals have a part of the brain called the “lateral habenula” (LHb). The LHb is really important for a lot of things, especially for helping us recognize when things are upsetting or unpleasant and for learning how to avoid those things; it’s also important for helping us recognize when good things we expected end up not happening, called “negative reward.”

In some people, their LHb has too much or majorly altered activity, which can contribute to mental health problems like addiction and depression. Lots of doctors and scientists that are familiar with the LHb think that figuring out how we can change LHb activity back to a more normal pattern might be an effective treatment for these problems, especially depression.

In order to figure out how to do this, we need a better understanding of how the brain cells in the LHb communicate with each other and with other parts of the brain. Brain cells use lots of different types of molecules to send messages, including endocannabinoids (eCBs).

eCBs are basically specialized fat molecules that have specific receptors all over the brain. Type 1 cannabinoid receptors (CB1) are the target of THC from marijuana, for reference. Very little research has been done on understanding eCB function in the LHb. However, one study showed that blocking CB1 receptors in the LHb could make rats behave in a way where they appeared to be less depressed and less anxious- that is super interesting because if we give rats that same drug by an injection to the whole body (instead of just the LHb), it makes them more depressed and anxious. So the effects in the LHb seem to be opposite to what would be expected from other parts of the brain!

But why? What kinds of signals are eCB molecules sending in the LHb? That was the purpose of the study - to understand how eCB signaling is regulating cellular communication within the LHb, at a cellular and molecular level. Generally, eCBs decrease neurotransmitter release.

They found that in the LHb, eCBs seem to decrease GABA release, as expected; decrease glutamate release (in some contexts), as expected; but also increase glutamate release in some other specific contexts, which is opposite from their normal predicted function. They found this unexpected increase required cannabinoid receptors on astrocytes, and hypothesize that this mechanism could potentially increase LHb excitation and explain the backwards behavioral effects of cannabinoids mentioned above. To be determined in future studies.

If I’m reading this right, it looks like they’re saying cannabis can make you anxious/depressed by suppressing glutamate and GABA production in your brain.

Edit: I was not reading it right.

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