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Cannabinoid induced anxiogenesis mediated by gaba

^ Yea, all those other effects come indirectly from stimulation of cannabinoid receptors. Just like nicotine (cholinergic) indirectly causes release of catecholamines, vasopressin, serotonin, and b-endorphin.
 
I didn't find said compound to be anxiogenic at all, fastandbulbous. I have been prone to anxiety when smoking cannabis, sometimes suffering full blown panic attacks. I smoked the 1-pentyl for breakfast one morning at 6-8mg and had an overly intense experience but it lacked any anxiety at all. I sat on the corner of the bed staring at the wall, thoughts started racing through my head accompanied by an ecstatic emotional state, went into a complete trance and snapped out of it about 20 minutes later. The 20 minutes took only a blink of the eyes, but when snapping out of it I recall experiencing racing thoughts for an extreeeeemely dilated period of time. My first thought was that I may have passed out and missed work, but even this thought didn't give me any anxiety whatsoever.

If anything I find the 1-pentyl to be very anxiolytic. I find indica strains to be anxiolytic usually and sativa strains to have a potential for a lot more anxiety.

P.S. how do you do rectal administration with said compound, specifically? Make a solution and use a syringe? If so, how's the solution made?
 
Make solution in isopropanol (or ethanol) - keep it below 1ml - and add the alcohol to 5-10x the volume of full fat milk. That gives a stable emulsion that is ideal for rectal admin. The emulsion technique also works for THC & co; not tried it with salvinorin A, but should work
 
fastandbulbous said:
^ Seems reasonable - nothing induces anxiety/panic like cannabis (well maybe yohimbine)
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Funny you should mention -- Back in my heavy fitness days, I once took a diet supplement containing large amounts of caffeine, synephrine, guggulsterones, and yohimbine (a supplement called Lipo 6). All went well until I decided to take a few bong rips.

I have never felt such anxiety. I was with a group of friends, and for a second I seriously considered getting up and just randomly running away. :D Wasn't funny at the time, though.
 
Me & mrs f&b tried yohimbine for it's aphrodisiac effect - took too much and ended up anxious & sweaty (& dreaming of wolverotterpillars - very strange dreams with animal spirits)

wolverotterpillars : An otter like creature witha wolverine's appetite and lots of legs!
 
fastandbulbous, what's your favorite tool to use for anal administration of emulsions? A regular insulin syringe with the needle removed? A turkey baster? Something in between?

The only thing I've ever taken via that route is whole pills, which are a bit easier to manage than liquids.
 
interesting, gonna try smoking againt with some xanax or something, maybe then i find it enjoyable
 
Coolio said:
If anything I find the 1-pentyl to be very anxiolytic. I find indica strains to be anxiolytic usually and sativa strains to have a potential for a lot more anxiety.
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That makes sense, as an indica strain is a more physical high while sativa is more mental goofy, does anyone know the neurochemistry behind that?
 
Sorry to revive this old thread, but does anyone have any sources for the claims made here?
Regarding GABA, NE and Dopamine. Couldn't find it so far.
 
I think that the evidence behind THC's downstream effects at GABA playing a significant role in inducing anxiety is speculative...we know that THC has this comparatively weak, or at least localized effect, but we haven't linked it to behavioral consequences. I mean, cannabinoids don't share many subjective effects in common w/ stuff like flumazenil.

ebola
 
Good bump The Happy Wanderer, this seems very plausible like ebola mentioned it hasn't been linked to behavioral consequences, however i share the experience of having cannabinoids and/or cannabimimetics to become anxyolitic after a prolonged period of use.
 
Just found this


This part is interesting
THC begins this process by binding to the CB1 receptors for anandamide. These receptors then modify the activity of several intracellular enzymes, including cAMP, whose activity they reduce. Less cAMP means less protein kinase A. The reduced activity of this enzyme affects the potassium and calcium channels so as to reduce the amount of neurotransmitters released. The general excitability of the brain’s neural networks is thus reduced as well.

However, in the reward circuit, just as in the case of other drugs, more dopamine is released. As with opiates, this paradoxical increase is explained by the fact that the dopaminergic neurons in this circuit do not have CB1 receptors, but are normally inhibited by GABAergic neurons that do have them. The cannabis removes this inhibition by the GABA neurons and hence activates the dopamine neurons.
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Though I don't know how valid this source is. However, it obviously says that if CB1-receptors at a GABAergic neuron is activated, the neuron is less likely to fire.
We have do find more and better sources for this.

EDIT: This one seems legit:
[...] indicating that Delta(9)-THC is a full agonist at CB1Rs on GABA axon terminals. These results suggest that Delta(9)-THC inhibits GABA release, but does not directly alter GABA(A) receptors or GABA uptake in the hippocampus. Furthermore, full agonist effects of Delta(9)-THC on IPSCs likely result from a much higher expression of CB1Rs on GABA versus glutamate axon terminals in the hippocampus.
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EDIT2: And we're going deeper

While having THC on board and acting in the brain does reduce GABA release from the subset of pre-synaptic terminals that do contain CB1 receptors, this is not nearly as universal of an effect as something that targets GABA receptors. To make this more clear, yes, there are a LOT of CB1 receptors, and they are spread around many parts of the brain. But not all GABA terminals contain CB1 receptors, and not every instance of GABA release is suppressed by THC. This is in contrast to the situation with sleep drugs that target GABA(A) receptors, which are pretty much universally present at GABA synapses.
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Now, next I'll see how this is all connected to norepinephrine.
 
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Ok, from what I have found the connection to different other neurotransmitter systems is obviously there, but it seems it is very specific different regions of the brain, so it would need a lot more work to really learn more about it.
I was mostly interested in it because I strongly tend to get anxious from weed. I'd guess that's from NE release (or inhibtion of NEic neuron inhibiting neurons... oh boy), but why do some people get anxiolytic effects. Really hard to say. Would like some CBD oil, should work in the other direction for me.
 
One thing I know is that weed has started inducing terrible paranoia in me after I quit benzodiazepines. Lately I even got CEVs about demons after smoking very similar to what I was experiencing during first 2 months of benzodiazepine withdrawal. I started controlling the paranoia after weed in a similar manner as I've learnt to control benzodiazepine withdrawal derealisation to an extent, but I never was paranoid after weed before I quit BZDs. If it hadn't been for weed, I probably wouldn't have made it through methadone withdrawal. So it used to be an anxiolytic for me, now it's an anxiogenic. :/
 
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adder said:
One thing I know is that weed has started inducing terrible paranoia in me after I quit benzodiazepines. Lately I even got CEVs about demons after smoking very similar to what I was experiencing during first 2 months of benzodiazepine withdrawal. I started controlling the paranoia after weed in a similar manner as I've learnt to control benzodiazepine withdrawal derealisation to an extent, but I never was paranoid after weed before I quit BZDs. If it hadn't been for weed, I probably wouldn't have made it through methadone withdrawal. So it used to be an anxiolytic for me, now it's an anxiogenic. :/
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After BZD withdrawl you need every last bit of GABA, and weed takes a good portion of that away.
 
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