Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway

Trippy man

8 Likes

Just got this in my inbox yesterday, haven’t even had a chance to read them yet. My current project is looking at binding of cannabinoids to the HT2b receptor I finally got the software to validate it so hopefully I’ll get to it soon. Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors
Related work Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells - PubMed
CB1-5-HT2A heteromers in schizophrenia patients: Human studies in pro-neurons of the olfactory epithelium - ScienceDirect

8 Likes

Man… testing in mice. There’s some good research that says what kind of mice to use…and it doesn’t look like they selected it.

I think its a bit weird also that they indicated 10mg/kg/day as a “chronic” level. That just seems ridiculous - as that would be the equivalent of 32 joints per day for an average male. I mean - I guess that’s realistic for someone… but who has the money to smoke that much all the time? That’s like 500$ a day in weed where I live.

Wouldn’t it be nice if instead of poisoning mice and then saying they saw psychotic effects. That they could instead not poison people, monitor them and then not see any psychotic effects. x.X

5 Likes

I bet a few dabs are equivalent to 32 joints lol

6 Likes

I find it just interesting that it acts on the 5-HT2A receptor, the same receptors known to light up with classical psychedelics

1 Like

Myself and @Killa12345 partakes more than most. I kill 1g distillate and 1g diamonds/sauce a week. I ate a 300mg edible and felt nothing. This was a buddies edible package. But my 80mg will floor me.

7 Likes

I eat 500mg at a time. I smoke for 16 hours straight every single day.

I’d imagine I come close to the thc found in 32 joints daily in dabs.

17 Likes

We NEED to have a sash! If fla wasnt to hard on herb, I’d move back. Wife found a bad ass house on clearwater beach. My old stomping grounds gor picking up chicks. This was back in 95.

@Killa12345 is bubba the love sponge still on air (93.1), or the pirate EDM radio channel? They used to broadcast from a boat in the gulf of Mexico

2 Likes

I used to make my edibles 500 mg. It put people into a zombie state. Now I make them 1/10th as strong, same recipe smaller molds .its all untested and im presuming the oil is 80 percent?

2 Likes

I don’t know. I need about 4000-5000mg of Thc/thca daily. Blessed I get to smoke that much.

500mg just get the party started right in the AM

6 Likes

i drink too much beer to smoke that much weed daily

1 Like

I don’t drink or really do any other stimulants than coffee.

I really don’t even eat aspirin. I use cannabis to heal all ailments. It’s like robitussin or windex

20 Likes

I think this further highlights cannabis as a potential tool to use in psychotheraputic settings
Especially now that other drugs that primarily act on that same receptor are being studied for psychotherapeutic use

1 Like

I partake nightly. Either 4 beers or 2 big margaritas. Plus smoke.

4 Likes

Despite being a cannabis scientist, I actually barely smoke. Maybe 3 tokes every 3rd day in the evenings. However, a few weeks ago I just decided to get ripped. So I smoked like 4 bowls over an hour. What surprised me and maybe yall will have a hard time believing this, but I was having open eye visuals that were very reminiscent of DMT. They were not as strong but they were very real. I’ve always considered cannabis mildly psychedelic, especially when eaten. When I OD on D9 edibles, I enter an uncomfortable visionary state that last 8 hrs plus. Not like super visual typically (tho my visual field is altered) but I’m somewhere between reality amd a very vivid day dream. Side note: I find d8 to be more visual when eaten vs d9.

Lastly, for anyone wanting to do receptor affinity and docking computation/modeling, there is a relatively new website that allows you construct a molecule, and it predicts probabilities of binding at all of the different receptor systems. It also predicts if a molecule is a CYP enzyme inhibitor. I plugged CBG into it amd tho I dont remember seeing any strong affinity for 5HT2A receptor, I did notice it is likely an inhibitor of several CYP enzymes.

Just google “swiss target prediction” to find the website. It’s very addicting lol

5 Likes

XD chronic haha

1 Like

So I have a psychedelic therapist that works with PTSD vets and he claims that cannabis, when used properly, alleviates PTSD more effectively than any psychedelic or ketamine. But it requires a strong dose and basically a guide that encourages you to follow any acute body sensations however uncomfortable and somehow this can lead you back to the experience that was traumatic in the first.place, while allowing you to view it from a more objective based viewpoint. Pretty cool stuff…

6 Likes

I’ve been doing much of the same stuff with the docking however there’s way more going on that has to be accounted for. Knowing something could dock only tells us one thing. is it allosteric, is it an agonist, antagonist, is it competitive or non competitive? Is the binding site realistic? Can the molecule get to that site? Does the molecule even get to the blood to be transported to that site. How long is it active?

4 Likes

I agree that the software has limitations and becomes less and less reliable the farther your compound is from something known. And yes it doesnt distinguish agonist vs antagonist sadly. However occasionally I will hit 100% probability of am experimental analogue hitting 5HT2A. Based on the SAR of that to known analogues I can have a pretty good idea however.

1 Like

True, there’s so much we don’t know, I’m thinking of emailing the professor who just published this paper, on htr2b interaction in the gut. DEFINE_ME

1 Like