Activation of Cannabinoid receptor inhibits GABA activity??

[JohnBoy2000]

Cannabinoid receptor - Wikipedia

en.wikipedia.org

Anyone well up to speed on cannabinoid transmission can confirm this?

 

[plumbus-nine]

From subjective experience, I'd confirm this. Having generalized anxiety and sensitive to anything anxiogenic like (unfortunately) 5ht2a agonists, I don't tolerate THC at all. Just two puffs and 10 mins later my heart would race, panic attack ... reversible by high dose CBD. On dissociatives, which are strangely anxiolytic but pro-glutamatergic, I tolerate low-strength outdoor weed but strong stuff induces heavy vertigo, nausea and other nasty stuff, together with a weeeiiird feeling. Had to lie down after also just a few puffs, bad mistake. People looked soo strange at me (unfortunately didn't tell them that I'm on a disso, cause nature freaks and stuff..)

 

[jambabomba]

From subjective experience, I'd confirm this. Having generalized anxiety and sensitive to anything anxiogenic like (unfortunately) 5ht2a agonists, I don't tolerate THC at all. Just two puffs and 10 mins later my heart would race, panic attack ... reversible by high dose CBD. On dissociatives, which are strangely anxiolytic but pro-glutamatergic, I tolerate low-strength outdoor weed but strong stuff induces heavy vertigo, nausea and other nasty stuff, together with a weeeiiird feeling. Had to lie down after also just a few puffs, bad mistake. People looked soo strange at me (unfortunately didn't tell them that I'm on a disso, cause nature freaks and stuff..)

Yes indeed. I have had the same thing. I remember I liked to smoke weed and even eat strong hash when I was something like 20y old. I enjoyed it but I didn't had much ego back then so nothing to fear. Many years later and after using years of gabaergic substances the situation had changed completely. THC just caused panic attacks and even hellish states. Gone were the days I could enjoy cannabis..

And I gues it is directly correlated with the development of ego which is based on fear mostly. What I've understood it might have something to do with brain dominance too. What I mean is that with left brain dominance one might have more ego based fearful thinking and with right brain dominance one is more easygoing, accepting and not so focused on linear world and that might be one factor contributing to experience with drugs too. If perception is mainly dominated by the ego then loosing control is very fearful and excitation gives anxiety and fear of death. But on the other hand, if perception is more on the right side of the brain and connected to the whole, or to God, or to quantum field of potentiality (love) the same excitation and loose of control might be seen just as a positive relaxation or arousal.

 

[Jabberwocky]

Yes indeed. I have had the same thing. I remember I liked to smoke weed and even eat strong hash when I was something like 20y old. I enjoyed it but I didn't had much ego back then so nothing to fear. Many years later and after using years of gabaergic substances the situation had changed completely. THC just caused panic attacks and even hellish states. Gone were the days I could enjoy cannabis..

I relate, and I've never actually made that connection before. I smoked weed daily for 15 years and never had any anxiety at all. At some point, that changed, and looking back it was a few years after my gabaergic addictions became severe, particularly alcohol.

I cannot enjoy cannabinoids at any dose anymore unless I have alcohol or benzos in my system.

I've always blamed this on my psychedelic use, but looking back this makes more sense, referring to the anxiety and not the intensity of the high.

 

[Pissed_and_messed]

weirdly enough I get generally less anxiety of weed nowadays almost 4 months off of benzos (for god's sake thats almost half a year). I guess being numb'n'dumb all the time doesn't really promote content high but brings every intentionally forgotten cognition too close to my face.

 

[ex-amine]

your endocannabinoid system is almost always working towards homostasis, so if there is too much excitort glutamate , the CB1 receptor will release Gaba till a kind of balance is found.
(there is much more going on ,but don't feel like typing this all down right now.

 

[PtahTek]

idk
petsonally i love weed with any gaba drug but my brain is scrambled anyway, so take it with that lucky penny ya found on the side walk.

 

[izo]

i had a serious neurological issue last autumn. was energy deprived in the head and therefore awake for 17 days! during that time i took bdo 2ml 2 times for sleeping. mistake. because afterwards my brain woulnt handle ghb as it normally would. have to get off ghb 3 days after starting, otherwise too big side effects arise. also antihistamines like dph and doxylamine give me a big hangover nowadays.

so i took bdo for sleeping in march this year for sleeping, woke up with a headache, which is quite unusual but nothing unusual for me after last autumn. i took 1g pcm against the headache and got the same energy deprived state i was in last autunm. not really that hard but similar. so endocannabinoids and bdo hangover produce energy deprivation in my head now. had the feeling the whole day. didnt know what to do. i took a massive dose of ritalin then and the feeling was gone. long story short. dont let imbeciles handle a machine for idiots fun time. but what can i say? twat?

 

[Skorpio]

Cb1 receptors are the most common GPCR in the brain. They act to provide negative feedback at GABAergic (more often) or glutaminergic synapeses.

A key thing to remember is that the brain is not just a giant tank of neurotransmitters, where an increase in GABA is going to mean the same thing across the brain. Neurons are discretely involved in circuits that vary in composition across the brain, and receptor expression varies. Having GABAergic neurons inhibited by their cb1 receptors only inhibits GABA receptors which happen to have these receptors, and would produce a different effect than taking a drug like picrotoxin which blocks all GABA receptors.

At their simplest, neural circuits are composed of neurons that release GABA or glutamate. Both of these open ion channels, where glutamate receptors let in positively charged sodium ions and GABA receptors let in negatively charged chloride ions. The sum of the charges of the ions is the voltage of the cell, and when the voltage reaches a threshold, voltage-gated sodium channels open up further increasing the voltage to open up voltage gated calcium channels that cause neurotransmitter release due to the interaction of calcium with proteins.



Cells can receive multiple inputs simultaneously, and act due to the sum of common inputs. Neurotransmitters that bind to G -protein coupled receptors (opioids, cannabinoids, serotonin, dopamine etc etc) cause downstream second messenger pathways to be activated or repressed and will regulate different molecular aspects of a neuron via reversible protein modification. This can even include changing the voltage of a cell by modifying the state of ion channels.

Using the more common example of a GABAergic synapse, endocannabinoids are released by the postsynaptic neuron back onto the presynaptic neuron simultaneously while the postsynaptic neuron is releasing GABA onto the next neuron in the circuit. This hyperpolarizes the presynaptic neuron (indirectly by releasing PKA inhibition of some ion channels), causing it to need a stronger stimulus (ie more glutamate being fired at it) to fire again.

Retrograde endocanabinoid signaling is another level of control of neural circuits, as the amount of endocannabinoid release can be dialed back to intensify the gain of GABA release. Life tends to develop systems with many layers of regulatory control.

 

[cdin]

Yep. This is why massive overdose on potent cb1 synth noids results in death from seizure, hyperthermia and multi organ failure - GABA blockade