Naked Science Forum

Life Sciences => Physiology & Medicine => Topic started by: deanb on 01/10/2018 21:57:14

Title: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: deanb on 01/10/2018 21:57:14
Hi,

I am learning about how cannabinoids work and different effects they may have on humans and animals.
I know THC and, to a lesser extent, CBD have been studied for decades but how far have we got on reliable data on other cannabinoids?

I have seen it said various times that certain cannabinoids are better for certain requirements. How much is there to back this up as it pertains to CBDa, THCa, CBCa etc.  I have seen pie charts stating XYZ cannabinoids can be used for XYZ illnesses and am curious as to what this is based on.

Also, to what extent has the 'entourage effect' been studied?
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: evan_au on 01/10/2018 22:20:04
Quote from: deanb
to what extent is 'entourage effect' been studied?
The entourage effect seems to be more "magical incantation" rather than  "scientific evidence"..

As you say, CBD has very different effects than THC, and this has been well-researched. But it is harder to study minor components which vary greatly between strains of cannabis.

Medical regulatory authorities require a very high threshold of proof of safety and effectiveness before a therapeutic drug is approved.
This means that a therapeutic drug vendor must outlay a considerable amount of money to have just one compound approved. It is only in the case of lethal and resistant diseases like TB will multiple compounds be approved.

The costs are so high that a pharmaceutical company won't even bother unless they have patent protection, which won't be possible on a natural chemical soup like cannabis.

See: https://en.wikipedia.org/wiki/Entourage_effect

This team at Sydney University address the Entourage Effect:
https://sydney.edu.au/lambert/our-research/cannabis-research.html
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: deanb on 01/10/2018 22:51:08
Quote from: deanb
to what extent is 'entourage effect' been studied?
The entourage effect seems to be more "magical incantation" rather than  "scientific evidence"..

As you say, CBD has very different effects than THC, and this has been well-researched. But it is harder to study minor components which vary greatly between strains of cannabis.

Medical regulatory authorities require a very high threshold of proof of safety and effectiveness before a therapeutic drug is approved.
This means that a therapeutic drug vendor must outlay a considerable amount of money to have just one compound approved. It is only in the case of lethal and resistant diseases like TB will multiple compounds be approved.

The costs are so high that a pharmaceutical company won't even bother unless they have patent protection, which won't be possible on a natural chemical soup like cannabis.



Thanks,   I'll look through the links provided.

It seems like most of the references to the entourage effect cite the improved performance of THC vrs Marinol.

Is there anywhere direct comparisons of these have been studied and published? 
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: chiralSPO on 01/10/2018 23:07:39
The entourage effect seems to be more "magical incantation" rather than  "scientific evidence".

I haven't yet looked in detail at the links you have provided, but I wouldn't be so quick to write off the "entourage effect."

Pharmacology is very complex stuff. There are seeveral actual mechanisms of action that a biologically active molecule can have (mostly limited to: binding to endogenous receptors, allostery, interference with endogenous reuptake or metabolism of endogenous neurotrasmitters, interacting with intracellular signaling or DNA/RNA transcription), and one must also consider ADME of the compound (absorption, distribution, metabolism and excretion).

Many of the "hundreds" of compounds found in cannabis are going to be easily absorbed and distributed. The primary wildcard is metabolism--and it turns out that there are multiple pathways that apply, some of which produce more active metabolites, and some of which deactivate and lead to faster excretion. The presence of multiple (non-psychoactive) terpene-derived products could change the extent to which different metabolic pathways act on the active components.

There is also plenty of evidence (at least for THC and CBD) that there is competition for the same receptors (THC being a partial agonist, and CBD acting as an antagonist). It is quite likely that other closely related compounds have some degree of activity, and could produce mildly different effects.

Of course there is a fair bit of "stoner lore" that science will never back up, and anecdotal evidence for the "entourage effect" is likely biased by "set and setting." But my understanding of the pharmacology involved suggests that it wouldn't be unreasonable for there to be some significant qualitative (and possibly quantifiable) differences based on the makeup of non-psychoactive components....
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: deanb on 02/10/2018 00:47:17
The entourage effect seems to be more "magical incantation" rather than  "scientific evidence".

I haven't yet looked in detail at the links you have provided, but I wouldn't be so quick to write off the "entourage effect."

Pharmacology is very complex stuff. There are seeveral actual mechanisms of action that a biologically active molecule can have (mostly limited to: binding to endogenous receptors, allostery, interference with endogenous reuptake or metabolism of endogenous neurotrasmitters, interacting with intracellular signaling or DNA/RNA transcription), and one must also consider ADME of the compound (absorption, distribution, metabolism and excretion).

Many of the "hundreds" of compounds found in cannabis are going to be easily absorbed and distributed. The primary wildcard is metabolism--and it turns out that there are multiple pathways that apply, some of which produce more active metabolites, and some of which deactivate and lead to faster excretion. The presence of multiple (non-psychoactive) terpene-derived products could change the extent to which different metabolic pathways act on the active components.

There is also plenty of evidence (at least for THC and CBD) that there is competition for the same receptors (THC being a partial agonist, and CBD acting as an antagonist). It is quite likely that other closely related compounds have some degree of activity, and could produce mildly different effects.

Of course there is a fair bit of "stoner lore" that science will never back up, and anecdotal evidence for the "entourage effect" is likely biased by "set and setting." But my understanding of the pharmacology involved suggests that it wouldn't be unreasonable for there to be some significant qualitative (and possibly quantifiable) differences based on the makeup of non-psychoactive components....

This seems interesting. I've read it multiple times without fully understand it, though. Would you please be able to point me in the right direction to learn more about the pathways and how these are important?
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: chris on 02/10/2018 08:14:53
A recent edition of the Naked Scientists Podcast (https://www.thenakedscientists.com/podcasts) was about medicinal uses of cannabis (https://www.thenakedscientists.com/podcasts/naked-scientists-podcast/medicinal-cannabis-weeding-out-hype) and includes information on the questions you raise, @deanb
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: deanb on 02/10/2018 13:20:44
A recent edition of the  was about medicinal uses of cannabis[/url] and includes information on the questions you raise, @deanb
[/quote

Thanks Chris, I will check this out now.
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: chiralSPO on 02/10/2018 15:17:20
This seems interesting. I've read it multiple times without fully understand it, though. Would you please be able to point me in the right direction to learn more about the pathways and how these are important?

Honestly, there isn't much I can recommend that you wouldn't just find on google or wikipedia (as a starting point, you can look up terms that I used that you want to know more about--I was writing fairly generally, so much of it isn't specifically related to cannabis). You might find a textbook on pharmacology useful if you really want to hunker down and learn this stuff (I have my favorites, but there isn't much substantive difference between them, so really, whatever you can get your hands on would be best).

As far as cannabinoids go specifically, I would recommend looking up "cannabinoid receptors" "cannabinoid metabolism" and "terpene metabolism"

Good luck!
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: tkadm30 on 02/10/2018 20:16:59
am i still forbidden to talk here?  ???

tk
Title: Re: Other than THC and CBD, how much is known about cannabinoid treatments?
Post by: deanb on 04/10/2018 15:47:45
chiralSPO

Thanks again, Chris. I will look into these