[highonmt]

Some interesting posts here regarding 'cannabinoid free' [chemotype v] cannabis got me thinking about cannabinoids as a class and the distinctions between cannabinoids as compounds that show affinity for cb1 and cb2 and the benzo chromene type compounds produced by cannabis that are the 'classic' cannabinoids. Many people use the term cannabinoid to refer specifically to these benzo cromene




and acyclic benzo terpenens




type compounds produced in cannabis.

In reality there are a number of compounds found in cannabis that are indeed cannabinoids due simply to their affinity for the cb1 and 2 receptors. Terpenes such as beta caryophyllene [cb2]





could be present in a strain lacking the active enzyme system responsible for the production of the benzo chromene class of cannabinoids. If anyone has a more complete list of phyto cannabiniods present in cannabis could you please post it up or link to it here thanks.

[mofeta]

Brenneisen's chapter from ElSohly's book is the most comprehensive paper on the chemical constituents of pot that I know of:

Chemistry and Analysis of Phytocannabinoids and Other Cannabis Constituents

The link is to the stand-alone chapter hosted on the Medical Genomics website.

[highonmt]

Originally Posted by mofeta

Brenneisen's chapter from ElSohly's book is the most comprehensive paper on the chemical constituents of pot that I know of:

Chemistry and Analysis of Phytocannabinoids and Other Cannabis Constituents

The link is to the stand-alone chapter hosted on the Medical Genomics website.

Thanks great link I will search further for reports of cb1 and 2 affinity in the various and sundry compounds. HM

[Chimera]

That's a really good point Highonmt. Classically, we referred to cannabinoids as compounds that are derived from and including CBG.

However, as you state we are considering terpenes as putative cannabinoids now, so the previous definition doesn't really make sense since as you say chemotype V plants that are deficient in CBG and its derivatives may still contain putative cannabinoids (ie terpenes).

This whole science is really very young, and we are tripping over ourselves now as it expands and we learn that our previous definitions are insufficient to tell a complete and accurate story.

Good post.

-Chimera

[paladin420]

Great post.. Please try to keep this as simple as possible for those of us in the field( as it where) ... Just white trash Tryin to help sick folk...

[highonmt]

Thanks for the kind words, if anyone here has access to scifinder or similar data base software please do some searching for cb1 and 2 affinity if I had access anymore I would do it myself but I threw the shackles of corporate America quite a while ago... I would also like to find info on any papers on the structure of the two receptors and any structural activity relationship [sar] information on the known cannabiniods.

[mofeta]

Originally Posted by highonmt

Thanks for the kind words, if anyone here has access to scifinder or similar data base software please do some searching for cb1 and 2 affinity if I had access anymore I would do it myself but I threw the shackles of corporate America quite a while ago... I would also like to find info on any papers on the structure of the two receptors and any structural activity relationship [sar] information on the known cannabiniods.

LOL! That is a tall order! This is one of the hottest subjects in neuropharmacology today, and there are important papers coming out every week it seems. As a chemist, you should have no problem reading these papers once you learn the specialized terms molecular neuropharmacologists use. The thing is is that there is A LOT to read.

Our understanding of the lipid neurotransmitters is still in it's infancy, but that is changing rapidly.

One thing I would point out is that it is becoming apparent that the CB1 and CB2 are just the tip of the iceberg. There are an increasing number of "orphan" GPCRs that are likely bound mainly by cannabinoids. Cannabinoids also exert their influence through mechanisms other than the GPCRs, like TPRV1 cation channel.(EDIT: forgot to mention that cannabinoids also bind the better known receptors, like 5HT etc. Also, here is a post I made about a watershed paper that shows how important cannabinoids are in modulating the more well-known neurotransmitters.)

As you know, most papers are behind a paywall, and subscriptions aren't cheap. There are, however, a lot of really good papers/books available in full-text for free.

You could do worse than start with these:

Cannabinoid pharmacology: the first 66 years-This is an overview by Pertwee, he is the man when it comes to cannabinoid pharmacology

The diverse CB1 and CB2 receptor pharmacology of
three plant cannabinoids: D9-tetrahydrocannabinol,
cannabidiol and D9-tetrahydrocannabivarin-another good one by Pertwee

Novel cannabinoid receptors-good one on cannabinoid receptors other than CB1 and CB2.

If you are just looking for Ki for various ligands of the well-known cannabinoid receptors, the PDSP database is real good (and free). Here is a link to the CB1 page:

PDSP CB1 binding affinity page

There are a lot more good resources free on the web, but the real world beckons, and I have to go now. I think the stuff above is a good start, I will post more later.

[highonmt]

Neuropharma research was my forte for a good while. Worked down in california for a huge mutinational reseach firm. We were working on TRI's which by the way we named in our lab. Dopamine is a tough one to work into the equation tho lol. I remember when we added the cannabiniod system to the huge recptor poster wall. These are going to be tough targets to characterize given the lipid soluble nature of the receptors. I appriciate the links I suspect there are allosteric binding sights on the recptor protien as well.
HM

Originally Posted by mofeta

LOL! That is a tall order! This is one of the hottest subjects in neuropharmacology today, and there are important papers coming out every week it seems. As a chemist, you should have no problem reading these papers once you learn the specialized terms molecular neuropharmacologists use. The thing is is that there is A LOT to read.

Our understanding of the lipid neurotransmitters is still in it's infancy, but that is changing rapidly.

One thing I would point out is that it is becoming apparent that the CB1 and CB2 are just the tip of the iceberg. There are an increasing number of "orphan" GPCRs that are likely bound mainly by cannabinoids. Cannabinoids also exert their influence through mechanisms other than the GPCRs, like TPRV1 cation channel.(EDIT: forgot to mention that cannabinoids also bind the better known receptors, like 5HT etc. Also, here is a post I made about a watershed paper that shows how important cannabinoids are in modulating the more well-known neurotransmitters.)

As you know, most papers are behind a paywall, and subscriptions aren't cheap. There are, however, a lot of really good papers/books available in full-text for free.

You could do worse than start with these:

Cannabinoid pharmacology: the first 66 years-This is an overview by Pertwee, he is the man when it comes to cannabinoid pharmacology

The diverse CB1 and CB2 receptor pharmacology of
three plant cannabinoids: D9-tetrahydrocannabinol,
cannabidiol and D9-tetrahydrocannabivarin-another good one by Pertwee

Novel cannabinoid receptors-good one on cannabinoid receptors other than CB1 and CB2.

If you are just looking for Ki for various ligands of the well-known cannabinoid receptors, the PDSP database is real good (and free). Here is a link to the CB1 page:

PDSP CB1 binding affinity page

There are a lot more good resources free on the web, but the real world beckons, and I have to go now. I think the stuff above is a good start, I will post more later.

[mofeta]

Originally Posted by highonmt

I suspect there are allosteric binding sights on the recptor protien as well.
HM

Here you go:

Allosteric Modulation of the Cannabinoid CB1 Receptor

[mofeta]

Originally Posted by highonmt

Neuropharma research was my forte for a good while. Worked down in california for a huge mutinational reseach firm. We were working on TRI's which by the way we named in our lab.

You should have an easy go at it with the cannabinoids then.

My interest in the TRIs has been rekindled recently, as they finally have some in clinical trials. I have an interest in anxiety/panic disorders, and how they relate to personality disorders. I am interested in the interplay between the locus coeruleus, hypothalamus, amygdala and the cingulate gyrus. I hope what we learn from the TRI clinical trials will help elucidate these relationships.

When I think of the firm you are referencing, I think of the name of the road it is on- it always reminds me of the science fiction I read as a kid! (if it's the place I'm thinking of in SD)