Cannabis: Lack of High for Some New Users/Anxiety in Veterans?

[AlphaMethylPhenyl]

So, the title says it all.

It just dawned on me yesterday how strange this dynamic is, and thought it strange that it hasn't been covered yet in terms of neurology (according to what I've searched and seen).


And similarly, how people grow this reverse-tolerance in that after years of use, many people find it too potent to take a bowl, lest they get super anxious. So it's sobriety while new to the drug, and lack of (typically seen) tolerance in most users as the years go by.


Weird, not getting high on a drug when new to it. Then later down the line many people get high with so little.


What is up with these two things?

 

[Captain.Heroin]

cb-1 agonism -> mu agonism through downstream effects

takes a while for some peoples brains to get this process going

i didnt get stoned for 2 weeks then it slowly started to effect me.

 

[AlphaMethylPhenyl]

Almost every main recreational drug has legitimate data on how it somehow increases mu activity. People have even stated that mu agonism, and not d2 agonism, is behind reward most primarily.

Any pros out there?

 

[Captain.Heroin]

Indeed this is the euphoria; it is also going to downstream effect dopamine IIRC, which is why people like me LITERALLY cannot stop smoking weed. The reinforcement is too strong; even if I can get off it for a short while my brain just WANTS IT incessantly.

I am interested to hear from others more well read on these subjects. I am just an amateur.

 

[AlphaMethylPhenyl]

As implied, likely a CB1 and Mu heteromer at work there.

 

[atara]

The idea that tolerance acts like a rubber band always opposing drugs' effects is naive. It's not just cannabis that shows this effect, also nicotine:

https://www.ncbi.nlm.nih.gov/pubmed/22775443

Tolerance can only be understood IMHO as a component of what the brain does naturally, learning. It is because of learned expectations that alcohol has different effects in different cultures:

http://www.sirc.org/publik/drinking3.html

It is also IMHO a result of learning that people start to get anxiety from cannabis that they hadn't before. If you expect to become anxious, your brain will happily comply.

 

[AlphaMethylPhenyl]

^It's reasonable, as that's what tends to happen.

Setting and trying not to become anxious (through whatever means save another drug) can't always conquer this anxiety, imho. This is by my concerted experience, telling myself 1,000 times before that I won't be anxious and doing everything beforehand to prevent it.

It's really an anomaly.

 

[Cheshire_Kat]

I think I tried dozens of times to get stoned when I first started before I succeeded. Fifty years later, I'm still good to go, no anxiety.


Maybe I'm just lucky

 

[AlphaMethylPhenyl]

^maybe there's a significant associations between times tried before getting high and anxiety down the line.

Yeah I wan't saying that it happens to everyone. But I was saying that it happens to enough people to be considered a regular effect. Tons of people I know say that they used to be able to smoke a bowl no problem and be happy, but a few years down the line get way too messed up to enjoy the experience if they take more than a few puffs. Anecdotes upon anecdotes.

But this sort of reverse-tolerance may be unique, as many who eventually get the anxiety simply are bored when high, or otherwise don't get much magic from the experience.

This dynamic and kind of tolerance seems particular here. I wonder if in coincides somehow with regular alcohol use that's otherwise safe/non-abused. I know that weed can lower GABA by itself. Just thinking now that part of how it might treat opioid addiction is through classical conditioning regarding GABA reduction.

And (more so off topic) reducing Substance P would be behind the classical conditioing of gabapentin in treating opiod addiction, as opioids reduce Susbtance P--I know of no other direct Substance P reducers (save gabapentin/pregabalin and opioids).

But CBD-rich products are awesome. Further, the entourage effect really is medicinal.

But here's an interesting thing:

I was put on opioids while young for pain due to a serious illness. Took several years to get wise and I quit just before chipping would become addiction that I couldn't handle. I loved that effect, just loved it.

But it seems that since, my natural tolerance to them has skyrocketed, and it takes a boatload for me to actually feel something. No tolerance and 25 mg oxycodone did about nothing for me. Sub the first time with no tolerance at 1 mg made me a bit happier, but it really felt euthymic, not euphoric. But I don't hear repeat reports of this.

I definitely stray towards stimulating substances (strange as, from what I understand, oxy is a more stimulating opioid).