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> THC/Anandamide Mechanism of action, A few questions of the endogenous cannabinoid system (NOT "DUDE, how do weed get you high?")
post Jan 30, 2009, 12:57 AM
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So, pretty much every explanation Ive been able to find in journal articles, wikipedia etc. has me pretty confused. It is to my understanding that the endocannabinoid system works as follows...

1. Glutamic acid binds to the post-synaptic neuron (NMDA receptor) and depolarizes it by opening ligand gated ion chanels and letting in Ca++ etc.

2. The depolarized post-synaptic neuron releases the endocannabinoid anandamide (Because of a calcium ion, energy independent reaction that involves various enzymes that end up creating the anandamide).

3. The anandamide then binds to the CB1 receptor on the pre-synaptic neuron (through retrograde signaling).

4. Those endocannabinoids then decrease GABA release through DSI (depolarization induced suppression of inhibition).

First of all, do I have any of this wrong? I'm confused as to weather or not the anandamide binding to the CB1 receptor depolarizes the pre-synaptic neuron (is the "D" in DSI refering to the depolarization of the post synaptic neuron by the glutamate or that of the pre-synaptic neuron due to anandamide?).

Second of all, Ive read that CB1 agonists such as anandamide and THC inhibit adenyl cyclase (which has SOMETHING to do with G-coupled protein action I THINK), where is this occuring?.

Is it that the CB1 receptors (which are G-protein bound) are agonized by either anandamide or THC, then the G-protein inhibits adenyl cyclase (and is adenyl cyclase part of the g-protein)? Also, when the CB1 receptor is antagonized, are any ion channels opened (this could be answered by my depolarization question)?

Finally, is it right to assume that THC does the same thing I described in steps 1-4 without including steps 1 and 2 (which is simply the trigger of creation/release of anandamide)?

Sorry, I know that I am asking for a lesson in basic neuron/receptor function as well as specific circumstantial explanations but I would really like to figure this out. Obviously I am no neurologist, I'm simply a 17 year old who is fascinated by neuroscience and cant take any legit classes yet (woohoo college next year).
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