PDA

View Full Version : Pot thread / THC is only a PARTIAL agonist!


resorcinol
11-13-2008, 05:37 AM
We've prolly had one before, but it's been a good long while since us 'philes have talked about the 'ol smokey stuff.

How many of y'all like it / dislike it?

I like it, but I have to take care to not overdo it, because overdoing it for me is an INSTANT panic attack, absolutely for sure. I don't just zone out and get glued to the spot I'm in if I overdo it, i fucking flip out if I overdo it.

But in doses below this threshold, I enjoy the high. I prefer sativa strains, as they're more heady, more euphoic, cause more of the interesting thought changes, and don't immobilize by body as much. The sativa strains, I believe, have a higher THC:CBD ratio (IE, more THC compared to a constant amount of CBD).

Taking a more chemical standpoint, what surprised me was that d-9-THC is only a partial agonist at CB1 receptors. CB1 receptors are the target that causes the psychoactive effects of marijuana and synthetic cannabinoids.

A synthetic full CB1 agonist, WIN 55-212-2, received glowing reviews in a thread over at bluelight.

There are other similar threads about other synthetic cannabinoids, and more are popping up everyday.

Just a note for those of you who plan on looking to the RC market for synthetic cannabinoids; you want the compounds that have a higher affinity for CB1 than CB2. CB2 receptors are barely even found in the brain... their conc there is extremely low... most CB2 receptors are found on immune system cells, and their function is pretty unknown.

So you want compounds that have a higher binding affinity for CB1 than CB2.

It really shocked me that d-9-THC, the primary active in weed, is only a PARTIAL agonist of CB1. Weed is the bupe of cannabinoids!

Anecdotal evidence from people trying these synthetic cannabinoids that are FULL CB1 agonists rather than partial CB1 agonists seems to suggest that they're:
1)more euphoric than marijuana / d-9-THC
2)more like SATIVA strains of weed than indica strains
3)cause less anxiety for the same amount of high

The WIN 55 compound, in particular, sounds like it has more EUPHORIA than weed does as a cannabinoid.

There's also some evidence on BL that these synthetic full CB1 agonists are better at getting people with very high weed tolerances high than weed is. This makes sense because full agonists activate the receptor more fully (obviously) so there's less of a wall / ceiling effect.

The synthetics that are water soluble, like WIN 55, also seem to cause less "burnout", probably because they're "in and out", they're more easily metabolized and excreted than compounds like THC which are stored in fatty tissue.

Out of all the synthetics, WIN 55 is the one I'm most interested in getting my hands on. Someday, someone who certainly is NOT me may indeed do just that :P

Edit: I forgot to mention: there's some evidence that the fact that THC is only a partial agonist is part of the reason that it's so hard to overdose on. The relative lack of CB1 receptors in the brainstem is part of the reason, but it can't be all of the reason.

It is likely that these synthetics that are FULL agonists of CB1, while almost certainly more fun than weed, are also more able to cause an overdose via respiratory depression. It would take a higher dose than with opioids still, but there's evidence that it's possible to OD of FULL CB1 agonists. So be careful if you try these drugs.

resorcinol
11-13-2008, 06:15 AM
Something else cannabinoids have in common with opioids....

The endogenous cannabinoid and opioid systems are both neuromodulatory and modulate GABAergic neurotransmission.

The only reason that cannabinoids aren't as mega euphoric as opioids is that CB1 receptors are only found in very low concentrations in the VTA, whereas mu opioid receptors are densely concentrated there (in the VTA). GABAergic neurotransmission needs to be throttled in the VTA to cause intense euphoria. The throttling of GABA where CB1 in densely concentrated is probably responsible for the thought altering and perception altering "psychedelic" aspects of weed intoxication.

There are, however, some CB1 receptors in the VTA (just nowhere near the number of mu opioid receptors that exist there), and that's probably behind the "mild" euphoria that weed has, and why weed is such a good drug to combine with opioids.

Full CB1 agonists may have greater potential to cause psychological dependence than partial CB1 agonists like weed. All of this remains to be seen.

cactus31
11-20-2008, 04:13 PM
Wow, that's really interesting. I had no idea it was only a partial agonist (delta-9).

Damn, I wish I could enjoy weed. My fucking GF, she's been smoking weed for probably 7-8 plus years, and for her, every time is practically like the first. She gets all giggly, happy, paranoid, hungry. A constellation of effects off of a couple bong hits. Every single time, too!

If I take one little hit, bong or pipe, I can't even function. All I can do is sit and stare at the TV or whatever. I get a really dis-jointed though pattern going on, and all I can think about is everything I don't like about my life. In no way is it relaxing or fun for me :(

marshalldylan1
11-20-2008, 04:27 PM
Give me a nice heavy indica strain with some opies and I'm the happiest I can be.