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PaperclipPerfector  1yr ago (text post)   3089 thread views

Small-Scale Question Sunday for September 3, 2023

Do you have a dumb question that you're kind of embarrassed to ask in the main thread? Is there something you're just not sure about?

This is your opportunity to ask questions. No question too simple or too silly.

Culture war topics are accepted, and proposals for a better intro post are appreciated.

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Honestly the endogenous endocannabinoid system is the only neurotransmitter I haven't rigorously studied (along with sigmaergy) but IIRC THC has many neurotoxic effects and can lead to both reduced synaptic plasticity and anhedonia induced by e.g. depleted dopamine https://www.frontiersin.org/articles/10.3389/fpsyt.2021.623403/full https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123717/ Of course like for 90% of drugs the major causative factor of toxicity must be related to oxidative stress and therefore this damage can be prevented, the interesting question being what are the other mechanisms and causes of thc toxicity? There are however mixed effects IIRC e.g. thc has neurotrophic effects too? annectodically, I don't have much IRL experience with thc but when I did I noticed a strong nocitropic/brain fog effect. But there might be a sweet spot with lower doses?

other things I remember: CB2 is fairly useless as a psychotrope

oleamide is a weird endocannabinoid which induced strong insomnia in me (paradoxal effect given research, I wonder what this denote about my brain)

there are other cannabinoid receptors than CB1 and CB2 but the research on them is very scarce

There are altenatives to thc, such as Delta 8 which has the merit to be less anxiogenic.

IIRC direct agonists lead to too fast tolerance and are considered dangerous versus the PAMs, however IIRC there are some new synthethic with claims of being viable so?

The toxicity of the alternative allosteric modulators (PAMs) such as delta 8 is understudied but IMO is likely not much stronger than thc unless they create currently unknown toxic metabolites. Their toxicity "should" be proportional to their dose potency relative to thc but alas the reddit evidence is that most lead to slighly-to highly faster tolerance buildup than thc and tolerance buildup is a not too shitty measure of toxicity, despite potency relative normalization.

The same hold true for many research stims btw, for very unclear and underresearched scientific reasons not are all the same bargain on the homeostatic response strength.

btw another thing strongly understudied is the effects and cross tolerance mechanisms of thc combination with dopaminergics and noradrenergics. btw if anyone know the mechanisms of thc induced tachychardia, I'm interested besides, is there an equivalent to MAOIs for CB1?

BTW anyone know a decent subreddit or forum to discuss pharmacology, that isn't related to nootropics?

Also when someone will wake the fuck up and synthethize mesocarb as a legal stim? https://en.wikipedia.org/wiki/Mesocarb

I need to ask the ukrainian

So to put in layman’s terms- THC is bad for your brain, there’s not enough studies to say exactly how bad, but it causes a dopamine deficiency(which would explain the depression-like symptoms of heavy marijuana use), and non-THC ingredients are especially not studied but what evidence exists mostly points to them being bad too. The recent rise in THC content in street level weed probably makes it a lot worse from a mental effects perspective.

Do I have that right?

yes you got it right but as usual, nothing is poison, everything is poison, it is the dose (and frequency) that makes the poison. Also hormesis can be a thing https://en.wikipedia.org/wiki/Hormesis Anyway my speculation is that taking frequent weed before the age of 18 (or maybe up to the twenties) is a scary risk factor to permanent brain damage/altered development

The legalization or de-demonization of thc might accelerate the reversal of the flynn effect https://en.wikipedia.org/wiki/Flynn_effect and accelerate the downfall of society. Or maybe not? Anyway I don't believe that infrequent use at adult age is a big deal, especially when concomittant with e.g. skq1 But the greater point is that we are very lucky to have drugs that have in large parts, observable toxicity.

We could very well live in a world where people take drug X and the toxicity is only revealed by e.g. a sudden death rate of 70%, 30 years later. Many kinds of toxicities are non-observable (except in a lab) or low observable, which are so called, subchronic toxicities. Neuron death, dysregulation, oxidative stress and teratogeny (mutations) are in large parts non-observable. In addition to those, the popular drugs just so happen to have observable toxicities too.

Given that we live in a era of contingent extreme ignorance (no standard database to correlate human's diseases rates with the prescriptions and drugs they take in their lifetimes) It is a fact that some horryfing quality of life reductions are happening silently for many people because of subchronic toxicities. E.g. IIRC chronic coffee use leads to white matter shrinkage (but conversely considerably reduce the rate of neurodegenerative diseases)

Seems correct. Honestly I think it will be seen as a huge mistake not to cap legal weed at a low THC potency. ‘70s weed was like 2%, modern US legal weed is shooting past 23%, there’s substantial evidence that psychosis risk goes up several-fold with higher strength stuff. There’s an ingrained societal knowledge that liquor and beer have very difference alcohol content, the same isn’t true for weed which often looks the same regardless of potency.

As it is, it’s all legal and mostly taxed the same way. New York was moderately smart and has a potency-based tax system, but it’s not enough to make a big difference in purchase decisions.

Indeed toxicity can be non-linear with the dose. Btw I made this comment on the point that thc has less observable toxicity than alcohol https://www.themotte.org/post/658/smallscale-question-sunday-for-september-3/136506?context=8#context

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