Yeah, I know it sounds heavy, but it really it isn’t. Brush up on your latin and biology - take a look at this:

CB1 and MOP

Hey! Come back here! I’ll work with ya on it. Promise.

It’s like this, the synergistic relationship between opiate pain relievers and cannabis has been anecdotally noted by western physicians from around 1850 until… Well, now that I think on it, I suppose docs are still seeing similar results in some patients.

The research study performed by Wilson-Poe, Morgan, Aicher and Hegarty (right here at WSU, Vancouver!) gives us a clue how that works from a biological standpoint. I love this stuff, man. Have I already told you that?

We’re all hip to the synapse/key thing, right? Agonists and antagonists? The analogy is, certain molecules act like keys tripping the locks in neurons. The agonist is responsible for the resulting electrical potential to momentarily… the nerve “fires,” okay? Toss a wad of putty into the key hole and the antagonist stands there giving you the raspberries. Nothing happens.

In this study the THC synthetic used was HU-210. Researchers are forced to use synthetic cannabinoids because the real stuff is, you know? – against the law.

They tell us the PAG (grey brain matter) has a lot to do with pain sensation (antinociception). They say if you pump a little cannabinoid into the gray matter, then less morphine is required to get the same result as you’d get without the cannabinoid.

Yeah, that’s not telling us anything. We’re already hip to that, right?

Their work gives us a good insight as to why. Though, I’ll admit to a bit of confusion near the conclusion.

A MOP (mu) receptor is an opioid receptor. Dorsolateral and ventrolateral are simply location. Immunocytochemical means they’ve “tagged” cells for identification. Somatodendritic just means there are receptors on both the cell body (soma) and on the tentacle looking things called dendrites.

Here, here’s a drawing of a neuron.

Nerve Cell

That oughta make things easier, eh?

That big red part with all of the cool different colored patterns in it would be the soma. Notice the flesh-colored dendrite (above the red) interfaces not only on the other dendrite, but on the soma as well. Cool.

Okay, now here is where I get a bit confused. I think what they’re telling us is 8% of the cells analyzed had both opioid and cannabis receptors. Pretty sure. If that’s the case then it would explain the synergy, eh? I mean, if a cannabinoid has a bunch of cells reacting already, then less opiate is required for the desired result. That’s pretty easy to grasp. I guess.

I dunno, I’m no rocket surgeon.

“These results indicate that behavioral interactions between cannabinoids and opioids may be the result of cellular adaptations…”

I’d like to see a similar study, only using methanandamide (synthetic ananamide) or 2-AG in place of HU-210. Anandamide and 2-AG are endocannabinoids – stuff our bodies manufacture.

This study gives us some idea how the relationship between opiates and cannabinoids operates at the cellular level. Very cool, eh?

I’m a nerve guy. I can talk about action potentials and sheaths and nodes and sodium/potassium pumps and axons and dendrites and synapses (both axoaxonic and axosomatic) and… stuff. My malady is nerve related.  Sorta.

The “sorta” didn’t dawn on me ’til an associate sent me a link about the roles played by the CB1 and 2 system in the remodeling of bone. You know… my pissed off nerves wouldn’t be, if it weren’t for the fucked up bone; stenosis, osteophytes, osteoarthritis?  It aint the nerves. They’re just the messengers. It’s the bone.

Bone.

The nerves would be fine if it weren’t for the bone.

I need to expand my studies.

Osteoblasts and osteoclasts. Remember those. Blasts make bone. Clasts absorb bone. This is going on within you. Right now. As you read this. Cool, huh?

Bone is important to people. The fact that it’s in constant rejuvenation is very important to the bone. Especially for bones of older folks; men whose testosterone levels drop off, women after menopause - when those hormones, too, drop to lower levels. Those hormones have a big influence on bone. Things can get out of kilter.

I’m reminded of a joke about how to make a hormone…
Never mind.

Osteoporosis. That’s what we’re talking about here: Osteoporosis and the endocannabinoid system.

Here, check this out:

Osteo-whatever

I think what that reads is there’s strong evidence manipulating the CB1 and CB2 systems can interfere with an osteoblast kicking off the precursors to form osteoclasts and, also, induce apoptosis (cell death) in osteoblasts.

Finding the CB1 system associated with bone confused me at first. I typically associate the CB1 with the brain, major organs, and the peripheral nerves. Then I considered bones as organs. Then I remembered the thigh bone is connected to the knee bone connected to the shin bone…

Where the hell did that come from? Heh!

Hormones. CB1 & 2. Neuroactive receptors… bone physiology.

Homeostasis.

The article is rather heavy. In reviewing it I’ve spent several hours with a search engine running in the background. Like, everyone knows what RANKL is, right? Yeah, right. If you find yourself with some free time and wouldn’t mind taking a quick biology course, check it out in-depth. Have your reference materials handy.

…weird it starts out talking about treating addiction with THC.

In this post I’m going to cheat. I’m going to offer a link to a Washington Post opinion page from a year ago. How I got there is a bit interesting. I think, anyway.

On a popular activist blog there was a post about an Air Force vet supporting a medicinal cannabis effort in Arkansas. The vet appears in a T.V. commercial. The 30 second spot can be seen here on the YouTube:

Dan Hankins

On the blog it mentioned an article on the subject had appeared in Stars and Stripes (a military news media). And I’ll be darned… there it was. At the end of the S & S article it credited the Washington Post. At the end of my scavenger hunt I tapped the Post article:

The Post

You might find it of interest.

Cannabibidivarin.
Yeah, I didn’t have a clue either. My ninety-year-old aunt sent me a newspaper article about a lab study and epilepsy. I mean, like cut it from the paper, put it in an envelope… stamp.  Hey, I still pay my bills via postal. Someone’s gotta keep those wheels turning. Anyway, the researchers did in vitro and in vivo studies. Rats and mice were used on the vivo side.

How bout I give you a “link” to the article? Not that four stamps would break me, but I don’t have your postal address. Heh.

CBDV (L.A. Times)

Yeah, GW Pharmaceuticals again. Before I go all off on the pharm thing read the article. I think it was rather well written. The author does make mention of there being over 100 phytocannabinoids… I thought there were about 66, but then I have been a bit remiss in my studies of late.

Here’s a link that’ll get you to the study’s abstract. I think you can load the whole study from there. You know, for you nerds?

BJP (via Wiley)

In Lee Romney’s article there’s mention of medicinal cannabis folks balking at the profit driven motives of big pharmaceutical industry. Yeah, yeah, I know this is the “medicinal” category. I do think my following commentary is applicable however.

We can have our cake and eat it, too, folks. The answer is simple The answer is cannabis legalization with provisions for home cultivation. With that done the whole plant administration can simply keep plugging along. Grow your stuff. Trade your stuff with fellow “patients.” Breed your own stuff. No harm no foul.

And the big pharms can do the science. I mean, c’mon do you have a lab? Hell, I don’t even have a rat much less a gas chromatograph. Did you even know there was a cannabidivarin? What if GW’s little stumble-upon manages to give epileptics some serious relief? I don’t see that as a bad thing. Do you?

I can’t help, but have a whole new industry come to mind. One where the phyto- breeders chase the pharms.  You know, like that whole CBD thing down in California?

Canabidivarin… whip that out on your med-head friend during conversation. I’d read the article and study first though.

I don’t know if taking a bunch of studies, evaluating them and then announcing the results is some sort of research cheat or a valid scientific method.  I’ll query the next research scientist I come across.

This one’s from Germany.
I’ll be honest with you, under methods, “Selective literature review,” is posited. I’m not real sure “selective” was a good word to use. Though it appears a tad over 100 research papers are cited. Maybe I’m missing something. Maybe the work tells us the criteria involved in picking the studies for analysis?

Regardless, they appear to be an accredited bunch and the conclusion was positive. here, take a look for yourself:  study

That’s it. That’s all I’ve got this day.

Damn, but I love that word, “phytocannabinoid.”  It’s true, I had to check the spelling ’cause it just doesn’t look right, but maybe that’s why I like it? It’s a weird word. Birds of a feather…

I’ve written before about the neuroprotectant (‘nother cool word) properties of the chemical compounds found in the plant. Still, when another study – by folks with all of those cool letters after their name – is released, I feel it gives further validity to the previous studies.

Some folks in the U.K. did one on the efficacy of cannabis extracts in the palliative treatment of MS. The abstract can be found in the Journal of Neurology, Neurosurgery and Psychiatry. unfortunately, to read the whole thing you best be ready to pony up some bones. But, for the meat of it:

MS and Phytos

Is 30% significant? I’m not sure. Oh, I’d guess that near a third would think so, but in the world of science… I dunno. Hell, the conclusion merely states that cannabis extracts are more effective than a placebo in relieving stiffness in MS patients.

Oh, but wait… Doesn’t GW Pharmaceuticals have an extract derived product on the market (in several countries) to treat MS ?

Sigh, move along here. There’s nothing to see - I guess. Hell, the U.S. Government has known of those properties since 2003 (earlier, actually).

See: 6,630,507

Sorry for wasting your time.

This might be old news for some. Okay, one of the three of ya. It was prepared Feb. of ’10.

“In 1999, the California legislature passed and Governor Gray Davis signed SB847, which commissioned the University of California to establish a scientific research program to expand the public scientific knowledge on purported therapeutic usages of marijuana.

“We hereby submit this report of our scientific findings pursuant to this objective.”

Wanna read the synopsis? CMCR

Have you noticed how cannabis comes up again and again as an agent for relief in neurological disorders? And I’m not just speaking of neuropathic pain. I’ve an acquaintance with the onset of Parkinson’s who’s  begun taking a canna-cap every other night. He’s experiencing a significant decline in tremors.

I find it interesting there appears to be a “correct” dose of cannabis for analgesia. One of the studies indicates a “Goldilocks” effect (my words). It seems lower doses don’t get it done. High doses make things worse. A medium dose… works.

The brief report is just that. It only takes ten minutes or so to run through. There aren’t any in-depth studies, just conclusions with a bit of background. Hell, if you have the time to read this, you’ve the time to skim that. Check it out!

“Results of CMCR studies support the likelihood that cannabis may represent a possible adjunctive avenue of treatment for certain difficult-to-treat conditions like neuropathic pain and spasticity. In establishing the University of California CMCR, the California Legislature enabled the creation of what is now arguably a world-class resource both for state-of-the-art clinical trials on medicinal cannabis and its derivatives, and for developing knowledge on the potential and limitations of cannabinoid therapeutics for selected indications. By facilitating high caliber clinical trials, whose results are published in leading peer-reviewed scientific journals, the CMCR is providing physicians and policy makers with solid scientific data to inform both medical research and policy decisions. As a seasoned and unique resource, the CMCR is well-positioned to inform public health and policy decision-makers.”

The Journal of Cannabis in Clinical Practice

Are you guys hip to this? I wasn’t ’til just the other day when a friend of mine dropped off a copy of the Autumn 2011 edition. There’s some good stuff in there, man. If you are an individual administering cannabis medicinally I’d highly recommend you get your hands on one.

CBD and “minor” cannabinoids are a big topic in the issue (which I’m not done with yet, by the way). The SCC (Society of Cannabis Clinicians) has begun what they call “Project CBD.” It’s a survey, of sorts, to be answered by folks who use cannabis medicinally and know the average CBD content of the strain they’re utilizing.

I’m beginning to understand how difficult it is to do science with a substance containing (at least) 66 active molecules (compounds?). And it doesn’t stop there.

Terpenes (or terpenoids) are suspected to be a player, too. O’Shaughnessy’s gets into this whole “entourage effect” thing. That is, a single cannabinoid can be administered and an effect observed. This effect can be positive or negative (see Rimonabant). Add another cannabinoid in the mix and results could very well differ. The cannabinoids are like a crew, man. One can bang away on this or that, but without shoring, support, procurement… This is why (in my opinion) phytocannabinoids are such a bitch for big pharma. At least GW pharmaceuticals had enough sense to use two cannabinoids, eh?

O’Shaugnessy’s is real world, too. I mean, the group understands that people are medicating with whole plant cannabis; smoking it, vaporizing, eating it… They don’t shy away from that “stigma”.

Somehow I got the impression if I used young flowers for my capsules I’d have a higher CBD content. Nope. It doesn’t work that way. I haven’t the equipment (nor the money) to do the testing, but I might be harvesting CBG (cannabigerol) rich material. I’m okay with that. CBG acts as a GABA reuptake inhibitor. That works as a muscle relaxant, spasm relief, an analgesic and stuff.

Side effects can result in lethargy, confusion, cognitive and memory impairment… I’ve experienced that. That’s why I take the caps every third night and I’m still experimenting with the formulation. I do wish I had the equipment to test both me and the material I’m using sigh.

Oh! And did you know that CBD isn’t really active at the CB receptors? What it does is suppress FAAH (Fatty Acid Amide Hydroxylase). FAAH is the enzyme that breaks down anandamide.

I love this shit, man.

Transient Receptor Potential cation channel subfamily V (TRPV).  Grab a copy of “O’s” and you’ll know why you might have some interest in TRPV’s.

Love this shit…

O’Shaughn’s

Okay, this isn’t really about Leukemia (RIP, Clay).  It’s about science. It’s about new discoveries and learning. Tangentially, perhaps, how science can be oh-so serendipitous.

If you really do want to read a rather lengthy paper on Leukemia and CBD click here:   Molecular Pharmacology.

The title scare ya? It is rather heavy, man. There’s two-bit words (in latin) and stuff I don’t have a clue what is. Stuff I don’t think this program will let me type even if I did know what the Hell it was.

The short story is, the CB2 system appears to control cell death. It’s called “apoptosis.” It’s an easy word to remember. I did, though I had to check the spelling. Cell death is important.

This day you can say good-bye to somewhere around 60 billion of them.

Don’t confuse apoptosis with necrosis. Don’t confuse necrosis with Alice Cooper (RIP Ethyl). Without apoptosis you wouldn’t have fingers. You started with flippers.

Wow, I’m all over the place here. Someone help me out… where was I?

Ah! Science, serendipity, systems…

See, it was back in ’64 when Mechoulam isolated THC from the plant. He had wondered what molecule could be providing the psychotropic effect. So then he wondered how/why THC could bind in the biology. It wasn’t until ’92 that Mechoulam (again) found it; Anandamide. Other molecules have been discovered since, and others are suspected.

We make chemicals (endocannabinoids) that are very similar to those found in cannabis (phytocannabinoids). The physiological systems, CB1 and CB2 can be manipulated.

We can tell cells to die. Cancer cells. Leukemia cells. Science moves slow. It’s coming though, man. The science is very encouraging.

And it’s ‘cuz’a cannabis, man.
We’d have not realized the systems involved, not at this time anyway, if Ol’ Raphael hadn’t wondered why/how people get stoned.

It’s a nasty day out today. It’s 40 degrees (F), wet and blustery. So, I’m hanging out in this warm shack surfin’ the inter-tubes. As a result, I came across a study on studies. It’s titled;

Cannabinergic Pain Medicine: A Concise Clinical Primer and Survey of Randomized-controlled Trial Results.

“Cannabinergic.” A new cool word! The title is “hot” by the way. It’ll take you to the PubMed page. Oh, and if you do take a look you might notice another study listed over on the right, Adverse Effects of Medical Cannabinoids. I’ll spoil it for you: dizziness.

Where was I…? Oh, yeah.

The researcher took a look at 38 rondomized-controlled trials. Of those 38, 27 concluded cannabis works, 11 came up negative. That’s 71% to 29%. In the world of science that’s significant.

I just thought I’d pass that along. Now I’m off to YouTube to watch cute kitten videos. Snork.