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Cannabinoid induced anxiogenesis mediated by gaba

wungchow

wungchow

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Dec 12, 2006
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I found this interesting snippet in an article on cb1 receptors.

CB1 receptors are thought to be the most widely expressed G protein-coupled receptors in the brain. This is key to endocannabinoid-mediated depolarization-induced suppression of inhibition, a very common form of short-term plasticity in which the depolarization of a single neuron induces a reduction in GABA-mediated neurotransmission. Endocannabinoids released from the depolarized neuron bind to CB1 receptors in the pre-synaptic neuron and cause a reduction in GABA release.
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So cannabinoids are actually directly anxiogenic? This would explain why I can't smoke pot anymore without panicking.
 
^ Seems reasonable - nothing induces anxiety/panic like cannabis (well maybe yohimbine)
 
It does? Heard about it several times but even with a full CB1/2-agonist I never managed to get there... Ummm...Maybe not in all people...
 
^the effects are more pronounced if you're a chronic pot smoker....i effectively "burned out" on it after smoking daily for 3 years...nothing but anxiety
 
^ A while ago I underestimated the efficiency of the rectal route (used an oral dose when rectally it only needs half the oral dose) for one of the Huffman cannabinoid analogues (1-pentyl-3-naphthoylindole) and had one of the worst drug induced bouts of anxiety I've ever had. If you have access to said compound, try smoking/vapourizing about 10mg to discover the world of cannabinoid panic (actually, don' unless you really want to experience it - it's pretty unpleasant to put it mildly)

Maybe not in all people
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Maybe you're just too laid back! =D =D ;)
 
See, I've experimented with these too, but I never had any issues with anxiety at any dose (technically, a little on my first dose that ended quickly.)
 
Maybe it's just me being too tightly wrapped (but there seems to be enough people who do get severe anxiety from cannabis to make the O/Ps post seem quite feasable)!
 
Oh no, please don't get me wrong! I wasn't doubting the OPs post in any way!!!! I just stated that this never happened to me... And btw, I am what one would call "a chronic pot smoker". Anyway.

Actually, was talking about exactly that one compound that FnB mentioned (=1-pentyl-3-naphthoylindole = JWH-018 ). Unfortunately, there's not enough left for a 10 mg experiment up into my ass. It was a present , consisting only of some milligrams that I don't wanna waste with finding my personal frontier.
BUT: Just for the case, what would the people who actually experience(d) this anxiety recommend to do??? I know that for example with psychedelic-induced horror/panic (e.g. with psilocybine, LSD) "talking down", holding the hand of a friend or other closely related person etc. is still the best way to go. What about cannabinoid-induced panic/anxiety?
Looking at the opening post, a GABA-agonist (at low dose!!!) could be the answer, maybe some diluted GBL (acts quite fast IMO, within ca. 10 min)

Thx (in advance) for your responses. Peace!

Murphy
 
Does the reduced release of GABA have a ceiling effect? or does that imply, that full agonists like HU-210, would, in an overdose situation of sufficient magnitude, cause seizures?

And, I wonder, possibly, as they are said to be dissociative more than stoning, if that could have some likeness to the effects of muscimol, that initially acts as a stimulant, by booting GABA itself off the GABA binding site on GABAaRs?

Or am I both barking up the wind, and pissing in the wrong tree entirely on both points?

Only in respect of full agonists of course, not partial ones like THC.
 
I believe the norepinephrine is the main cause. It's also responsible for the rapid heart beat. I think it maycounterbalance GABA.
 
Limpet_Chicken said:
And, I wonder, possibly, as they are said to be dissociative more than stoning, if that could have some likeness to the effects of muscimol, that initially acts as a stimulant, by booting GABA itself off the GABA binding site on GABAaRs?
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Not impossible, but I don't see any structural similarities that would suggest that to me. So, a bit far-fetched IMO.


MM2-minimized structures.

About your first questions, I have really no idea.

Murphy
 
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What about cannabinoid-induced panic/anxiety?
Looking at the opening post, a GABA-agonist (at low dose!!!) could be the answer, maybe some diluted GBL (acts quite fast IMO, within ca. 10 min)
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That works wonders, as does rectal admin of diazepam emulsion (I was given some vet products that consisted of a plastic toothpaste tube tube filled with diazepam emulsion - 10mg dose - for rectal admin to animals having a seizure and in a moment of rather high anxiety I grabbed at what I thought would be the quickest acting treatment in the absence of GBL) both really fast acting which gives decent relief of the nightmareish anxiety of a 'total freakout' in 5 minutes. Oral diazepam, by comparison would seem to take an eternity to start working when in that state
 
So, may I assume that you speak out of own experience, concerning the GBL? I have no benzos at hand and the diluted GLB would be my "antidot" of choice...

@Wungchow: Can you please tell me in which article you found this statement? (journal, year, 1st page) THANKS!!!
 
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Tsukasa said:
I believe the norepinephrine is the main cause. It's also responsible for the rapid heart beat. I think it maycounterbalance GABA.
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Norepinephrine?! We were discussing cannabinoids, later then GABA-agonists?! How do you come to norepinephrine? I don't see the connection here...
 
Hammilton said:
See, I've experimented with these too, but I never had any issues with anxiety at any dose (technically, a little on my first dose that ended quickly.)
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I've had a horrendous panic attack on said compound even with a normal dose.

And yes, Diazepam was the answer.

Btw, FnB... I seriously hope that you had not used that diazepam tube on one of your cats before using it on yourself ;).
 
I assume, a "normal dose" is something like 1-3 mg, smoked.
Yeah, not everybody reacts equally. I already noticed the same with weed: While some people can stand (and actually enjoy) "huge" amounts, there are others who totally freak out after one joint...
 
MurphyClox said:
Norepinephrine?! We were discussing cannabinoids, later then GABA-agonists?! How do you come to norepinephrine? I don't see the connection here...
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Experiments have shown that THC can affect two neurotransmitters: norepinephrine and dopamine. Serotonin and GABA levels may also be altered.
 
Tsukasa said:
Experiments have shown that THC can affect two neurotransmitters: norepinephrine and dopamine. Serotonin and GABA levels may also be altered.
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likely indirectly...but notably it appears to
 
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