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cannabis impact on gaba

strgchris

Greenlighter
Joined
Jun 5, 2015
Messages
19
So does it lower it or raise it? I've read research that implies gaba is blocked, others state it is raised, and some that seem to think it balances glutamate and gaba raising neither via the ndma receptor. So which is it? If it blocks gaba how does it help with sleep/anxiety or seizure? Wouldn't ingesting a substance that blocks gaba induce greater nerve pain? if you indeed suffer from nerve pain. Which I can with me it most definitely helps with all of this things. Just curious if some pot experts fill in the gaps.
 

adder

Bluelighter
Joined
Mar 28, 2006
Messages
2,852
After I quit benzodiazepines, weed became extremely anxiogenic for me. And I used to smoke it quite often, weed helped me a lot with insomnia and restless legs during the first 2 months after I quit methadone but now I can't stand it at all, so I guess THC blocks GABA release, but different strains may produce different effects. It's actually nearly impossible to find a chilled out weed right now here, all that is around seem to be strains with super high THC content.

http://www.ncbi.nlm.nih.gov/pubmed/22133429
 

rakketakke

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Aug 31, 2010
Messages
469
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Geospatial Inversion.
**Nora Laaris et. al., "Δ9-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus." Neuropharmacology, Vol. 59, No. 1-2, 121-127. 2010.[

**A. Hoffman, "Mechanisms of Cannabinoid Inhibition of GABA-A Synaptic Transmission in the Hippocampus." J. Neurosci., 20(7):2470-2479. 2000.

Marijuana causes a physiological reaction that causes anxiety.

Depression of growth hormone and cortisol response to insulin-induced hypoglycemia after prolonged oral delta-9-tetrahydrocannabinol administration in man.

Six hospitalized volunteer male subjects were given insulin, 0.15 U/kg, before and after 14 days of administration of delta-9-tetrahydrocannabinol (THC) at a dose of 210 mg/day. A diminished maximal serum human growth hormone (GH) increase followed the prolonged THC ingestion. The mean maximal GH response was: 52.6 ng/ml /- 8.7 ( /-SE) before THC and 18.8 ng/ml /- 6.7 ( /-SE) during THC, P less than 0.01; corresponding cortisol responses were 20.1 mug/dl /- 3.0 before THC and 10.0 mug/dl /- 1.1 during THC, P less than 0.05. The data suggest suppression of the hypothalamic-pituitary axis after prolonged high dose THC use. This is consistent with other reported endocrine effects of marijuana in man.



Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence.

Department of Psychiatry, Psychiatric Institute, University of Illinois, Chicago, IL 60612, USA.

In addition to their physiological function, metabotropic receptors for neurotransmitter gamma-aminobutyric acid (GABA), the GABA(B) receptors, may play a role in the behavioral actions of addictive compounds. Recently, GABA(B) receptors were cloned in fruit flies (Drosophila melanogaster), indicating that the advantages of this experimental model could be applied to GABA(B) receptor research. RNA interference (RNAi) is an endogenous process triggered by double-stranded RNA and is being used as a tool for functional gene silencing and functional genomics. Here we show how cell-nonautonomous RNAi can be induced in adult fruit flies to silence a subtype of GABA(B) receptors, GABA(B)R1, and how RNAi combined with pharmacobehavioral techniques (including intraabdominal injections of active compounds and a computer-assisted quantification of behavior) can be used to functionally characterize these receptors. We observed that injection of double-stranded RNA complementary to GABA(B)R1 into adult Drosophila selectively destroys GABA(B)R1 mRNA and attenuates the behavioral actions of the GABA(B) agonist, 3-aminopropyl-(methyl)phosphinic acid. Moreover, both GABA(B)R1 RNAi and the GABA(B) antagonist CGP 54626 reduced the behavior-impairing effects of ethanol, suggesting a putative role for the Drosophila GABA(B) receptors in alcohol's mechanism of action. The Drosophila model we have developed can be used for further in vivo functional characterization of GABA(B) receptor subunits and their involvement in the molecular and systemic actions of addictive substances.

Cannabis has been known to inhibit GABA-A transmission. This would be the same as the anxiety one would get if your blood level of benzos got low and you are dependent. There would not be enough GABA to cover the receptors that manage fear and anxiety.

Then again if you want to dismiss oral consumption there is still the fact of shortness of breath and anxiolytics (sp?) that are in tobacco smoke or your method of smoking induces shortness of breath.

Other then that I believe its likely much more complex than that, both anxiety and paranoia, are a result of your brain reacting to the abstinence of the drug you've so frequently "flooded" it with. With cannabis, smoking it would typically induce positive feelings. excessive drug use will trick your brain into relying on exogenous rather than endogenous sources. Therefore, cessation of whatever drug you typically used will leave your body without feeling comfortable, and thus responds with the opposite feeling (i.e. paranoia in the absence of calmness).

benzos respectively, are of course antianxiety/sleep aids etc, and help with such anxious/paranoid thinking. On the flip side though, CB1 induced suppresion of inhibiton at GABA receptors will lead to increased dopamine release. Both rewarding and perhaps, like other DA releasers could cause paranoia/anxiety. I guess suppression of inhibition induced DA relese is of a far smaller magnitude than that caused by stimulants and such.

Everyone is diffirent but still I think long-term smokers can expect a little bit of anxiety. Who doesn't though?
 

strgchris

Greenlighter
Joined
Jun 5, 2015
Messages
19
Thanks nice w write up! So if cannabis inhibits gaba a transmission, wouldn't intern make nerve pain and sleep more difficult? Do you think the pain reduction is a result of increased dopamine? Does cannabis also inhibit glutamate? which why people use it for sleep but results in poor sleep quality? Or is it possible your brain produces a surplus of gaba to counter inhibition from the initial onset of the psychoactive components of cannabis so when the gaba a transmission is resumed as thc where's off the brain is flooded with more gaba than usual?
 

ImTooHighToType

Greenlighter
Joined
Jan 13, 2017
Messages
1
It might have to do with the contradictory effects of CB1 agonism and GABA antagonism, as THC affects both receptors to varying degrees and that we have all our own unique neurochemistry.

GABA antagonism results in elevated dopamine and adrenaline (excitement and anxiety), and lowering the seizure threshold. CB1 agonism lowers the seizure threshold, and does NOT particularly affect dopamine outside food-related motivation.

This explains the cases of seizures in synthetic cannabis overdoses. The receptor activity becomes so extreme that the small differences in neural expression leads to either one of the contradictory effects out-compeeting the other. You can also see this effect occuring in situations with lower doses. Say if John was 2x more sensitive to say alcohol than Jack, then you could predict that he would begenerally more anxious with weed than Jack. I can also chip in a personal anecdote while we're at it. A friend of mine always liked to get super drunk, and he is also the more paranoid type with weed, aswell as him just being a bit of an anxious person in general (I've known this dude for all my life).

Without blatantly contradicting myself, you never know how somebody might react to a substance before they try it. My buddy's reaction to MDMA on an occasion with one other buddy turned out to be many times stronger than mine and later said buddy. He said he was basically tripping out (he has tried 2CB), and his face just couldn't stop looking like a "roll"ercoaster going off the rails. It took some time before he could actually walk without falling all over the place.

(Very longwinded quote from later said buddy): "lets go outside for a wal-"My buddy immediatly stands up on top of a quick "yes" with a tone that can only be described as limitless motivation. He proceeds to walk forward, but ends up stumbling all around like a drunk ballerina* ... - but let's wait untill you stop "falling around" while everybody giggles.



I also want to add that I wrote this on a phone outside in the cold on top of being baked, so I kinda just went for it without really double-checking that I actually remembered the correct version of all of my claims about the neuropharmacology of THC, but ohwell, I can always edit later (and then you probably wouldn't see this paragraph, or maybe even the whole post is deleted). Whatever, I had a blast.
 

xbandit07x

Bluelighter
Joined
Aug 19, 2016
Messages
557
Guys isnt it obvious. Marijuana Suppresses Gaba but also suppresses Glutamte.
 
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