The endocannabinoid system.....

[WVUPharm2007]

...keep up with this stuff. With a greater understanding of the role of endogenous cannabinoid system that has come to light relatively recently...some interesting stuff might happen when we figure out how innervating/antagonizing the various subreceptors affects humans. But right now...potential for cancer apoptosis....roles in liver disease...roles in Parkinson's....roles in obesity (via the underappreciated and underresearched PPAR-delta...crazy ****, man...)....roles in nicotine addiction...potential for neuroprotection in MS (via PPAR-alpha)....suppression of neuropathic nociception.

It's the future...big pharma is on the weed wagon...er, well, kinda....

 

[Priapism321]

...keep up with this stuff. With a greater understanding of the role of endogenous cannabinoid system that has come to light relatively recently...some interesting stuff might happen when we figure out how innervating/antagonizing the various subreceptors affects humans. But right now...potential for cancer apoptosis....roles in liver disease...roles in Parkinson's....roles in obesity (via the underappreciated and underresearched PPAR-delta...crazy ****, man...)....roles in nicotine addiction...potential for neuroprotection in MS (via PPAR-alpha)....suppression of neuropathic nociception.

It's the future...big pharma is on the weed wagon...er, well, kinda....

Ask Sanofi how they feel about the first "big breakthrough" drug to be developed based on research of the endocannabinoid system.......

People lose weight, but tend to kill themselves and become depressed more often despite effective treatment for their obesity. Whoops, that's not supposed to happen is it?

R.I.P. rimonabant

I wouldn't get so excited over this stuff just yet...

 

[WVUPharm2007]

Ask Sanofi how they feel about the first "big breakthrough" drug to be developed based on research of the endocannabinoid system.......

People lose weight, but tend to kill themselves and become depressed more often despite effective treatment for their obesity. Whoops, that's not supposed to happen is it?

R.I.P. rimonabant

I wouldn't get so excited over this stuff just yet...

It's out in Europe.

It's not stopping a certain other Pharma company from trying to get their own CB1 blocker through. It makes sense when you think about it. CB agonist --> euphoria.....CB antagonist--->?

What they need to do is go back into the labs and create a CB1 blocker that doesn't cross the BBB.

 

[Priapism321]

It's out in Europe.

It's not stopping a certain other Pharma company from trying to get their own CB1 blocker through. It makes sense when you think about it. CB agonist --> euphoria.....CB antagonist--->?

What they need to do is go back into the labs and create a CB1 blocker that doesn't cross the BBB.

Europe is not where the money is; the U.S. is the only country that lets Big Pharma perpetually bend them over (primarily because they basically run congress and the FDA). I would be interested to see how widespread its use is across the Atlantic.

Nothing stops these companies once they get to a certain point in testing (I think they smell the money and certainly are not truly concerned with the safety and welfare of the people who are prescribed these damn drugs). I mean, give me a break, Merck was trying to gain approval of ANOTHER COX-II inhibitor after the rofecoxib travesty.

 

[WVUPharm2007]

I'm shocked the FDA decided to grow something resembling a backbone.

The pharma companies are kinda dumb though. They make changes in intrinsic human physiology on a gigantic scale that have never been attempted before without ever contemplating the consequences.

As an example, look at the DPP-IV inhibitor Januvia. Yeah, sure....it inhibits incretin metabolism. But that ain't all DPP-IV does...it does TONS of other ****. But they surely don't give a flying ****. It's like they don't even consider what else might happen. In 15 years when a meta-analysis shows that it causes cancer (rather, allows endogenous cancer to proliferate unchecked) or has caused a bunch of deaths in immunocompromised patients they'll sit there all dumbfounded....."how could we have known?" You could have known by studying your f'n biochemical pathways better, dummy!

And that's why I'm thinking about forgoing the pharmacist thing and going into drug development. Long term, this **** ****s these companies over, too. Legal bills and all. There needs to be some sort of bridge between nerds in a lab going around figuring out what inhibits what and the clinical folks who don't understand biochemical pathways to the extent said nerds do.

Is there such thing as a clinical pharmacologist that specifically specializes in determining the amount of things that can and will go wrong when newly discovered mechanisms of altering human physiological function are discovered? I need to figure out how to pursue THAT ****....cause whoever is in charge of that entire area kinda sucks. I think I could take their job.

With cannabinoids, I'm not sure what to think. The POTENTIAL is so there. It's very exciting. The fact that they are apparently so intertwined with PPAR expression may be worrysome...or it might be encouraging. Agonists appear to increase alpha and gamma expression, lower delta expression. Antagonists the opposite. I can just see the first guy who has CHF and goes on some super selective CB agonist dying due to a sudden influx of angioedema that decided to "magically appear due to an unknown mechanism" that any idiot who knows common drug class side effect would consider a possibility.

But, hey...to make an omelet, you need to break some eggs....kinda the sad part about new pharmacotherapy....

 

[Braddyp]

An interesting exercise:

1. Review some of the anectodal news reports and internet postings of people who have used high potency cannabis oil to treat their cancer. A common thread emerges: The importance of titrating the dose quickly to establish the tolerance necessary to use very high doses. There's no way to know how much THC, CBD, etc is present in these products but the patients generally describe symptoms you would see with extremely high doses of THC.

2. Search pubmed for GPR55, CB1, CB2, heteromization, and cancer. You will find a number of recent mechanistic studies which describe the biphasic action of cannabinoid agonists on cancer cells that express GPR55-CB heteromers. At low concentrations, THC (but not CBD) seems to act via GPR55 associated pathways with oncogenic downstream effects. Conversely, THC triggers Cannabinoid receptor mediated apoptosis in these same cells when present in higher concentrations. The effect of upward titrating cannabis oil doses in treatment of Ph+ T-Cell-ALL in a human being has been documented in one case report in "Case Reports in Oncology" published by Karger.

Put simply, patients using cannabis or THC for palliative reasons only use small doses, while the complementary/herbal medicine community seems to think that very high doses are necessary if the patient is trying to treat their cancer (induce remission). Moreover, the patients who claim cannabis oil helped to "cure" their cancer invariably report they used very high doses. These cases all predated the discovery of THC's biphasic action on cancer cells. In other words, there is now a pharmacologic explanation for a phenomenon that has been reported within the alternative medicine community. Could all be coincidence, but definitely suggests to me that high dose cannabis as a potential chemotherapy drug needs to be studied in randomized trials.

There is also something called "the entourage effect" which may be unique to eicosanoid signalling (and hence endocannabinoid signaling). In basic terms, the presence of various endocannabinoid analogues at one receptor site seem to influence it's action. While it hasn't been studied yet, one might postulate that the 60 different cannabinoids in Cannabis help shift THC signaling toward activation of CB1 and CB2 apoptotic pathways and away from GPR-55 mediated proliferation.

 

[WVUPharm2007]

I used to be smart as all hell...