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Cannabis biochemistry

BullDogUK

Member
Hey GMT, I'm going to be covering a lot of that in the next post. As I've not had nearly as much time as I'd originally planned I've only really had time to write up the brief introduction you see above but to answer your questions:

- Yes, each cannabinoid has a different affinity for each receptor but I haven't seen anything suggesting that one may activate CB1 without being able to activate CB2. As to the precise affinity, this can vary from individual to individual due to single nucleotide polymorphisms (SNPs) in the genome of each individual. I've not had time to look into SNPs in cannabinoid receptors but presumably there is a fair bit of variation there.

- The functions can vary so much that I'm not even going to try and answer it fully here but suffice to say the effects range from immune cell activation to the regulation of short term plasticity in neurons and from promoting cell replication to encouraging apoptosis...

I'll add a bit more about SNPs because they're actually pretty important to understand:

Evolution is driven by evolutionary pressures, generally affecting those that allow an organism to mature and reproduce successfully and not a whole lot else. When people think of mutations they generally either think of tentacles or turtles however most are far more subtle than this. A mutation is generally a change in a single base in the entirety of the genome and, if this occurs in a germ-line cell (eggs/sperm/pollen), can be passed on to offspring. Provided this mutation does not result in a non-sense protein (Remember DNA -> mRNA -> Protein) or some other catastrophic mishap, there is no pressure to remove the mutation from the genepool. The result of this is a huge variation between the various proteins expressed by individuals which, whilst they affect the ability to, say, process various foods or get over a bad mood/habit or how quickly you can learn something, do not affect the overall ability of the individual to survive and reproduce in a natural setting.

As you can imagine, most of the enzymes (proteins!) involved drug-activated pathways or what have you, are not very sensitive to evolutionary pressures at all. Whilst a completely failure of the cannabinoid system in your body may be pretty catastrophic (i.e. fatal - http://www.pnas.org/content/96/10/5780.full), the ability of your body to be influenced by a foreign psychoactive substance is not really going to stop you breeding.
 

BullDogUK

Member
Also just generally, as Dawkins very eloquently explains in The Selfish Gene, evolution happens at the genetic level, not the individual level as per the common conception.
 

BullDogUK

Member
if the the alcohol is strong enough it might open up the mucus membranes allowing for more absorption leading to getting higher per hit?

or oxygen deprivation?

Oh man I don't even want to think about someone doing that :yoinks: I don't think you'd take another hit/breath again

Having done a bit of thinking I can picture a scenario of someone inhaling microscopic vodka droplets in this vodka-bong hit which may aid in dissolving cannabinoids in alveolar surfactant but still... Defiantly not something I'd encourage haha
 

BullDogUK

Member
http://sensiseeds.com/en/blog/cannabinoid-science-101-what-is-anandamide/

A great little introduction to the role of Anandamide, of which THC is an ortholog.



This is a nice little summary of the article - a signal causes the synthesis of endocannabinoids from omega-6 essential fatty acids in the cell membrane (ever wonder why omega-6 FA's were so good for you? :p) and release of the endocannabinoid from the cell membrane into the extracellular matrix. As you can see from the generalized 'effects', it's really not fully understood precisely what is happening.
 

SacredBreh

Member
Excellent in-depth information.

Slightly off subject but you seem to have the knowledge base. I am a healthcare professional and know another that also has a Masters in Molecular Biology...... We have debated about the beneficial attributes as far as medicinal effects of Cannabis many time.... the problem is there are so few actual legitimate trials or studies beyond anecdotal and testimonial. Do you know of any direction I may look to find scholarly papers or research to bolster my position and educate myself. I have searched far and wide but most that are cited have such small sample sizes or poor controls that they simply invalid to a person who has anything more than a basic education. Even good science research would help. Thanks if you have any ideas or references that may help.

Peace
 

BullDogUK

Member
I have searched far and wide but most that are cited have such small sample sizes or poor controls that they simply invalid to a person who has anything more than a basic education. Even good science research would help. Thanks if you have any ideas or references that may help.

Peace

Yes this is a huge problem and largely a product of cannabis being a schedule 1 drug under American and international law, meaning that it officially has no medicinal value and has made getting grants to perform research into the effects of cannabis rather difficult. As we come closer to the end of prohibition this does seem to be changing though god help us if we end up with 'Big Cannabis' to go along with out Big Tobacco, oil and alcohol haha. Again slightly off topic!

Anyways as for some research - As cannabis was fairly ubiquitous in 19th and early 20th century medicine, I've heard of (though not read myself) numerous papers from this period in journals such as the BMJ, Lancet and others. I can't really vouch for the quality of these articles as I've no idea what the peer review system was like at that time but I'm sure they'd have a lot of good information sans propaganda.

As to some more recent studies, there are quite a few that I've found personally quite interesting:

http://www.ukcia.org/research/keele_study/Assessing-the-impact-of-cannabis.pdf - A fairly well known article covering some 700,000 members of the public

http://www.pnas.org/content/109/40/E2657.full.pdf+html - The NZ study showing a decrease in IQ of immature cannabis users. The main thing to note in this study was that the onset of cannabis use beyond the age of 17-21 showed no alterations to IQ or mental faculties at all.

http://www.youtube.com/watch?v=R2lYshR2H1E - A nice lecture at the British Pharmacological Society concerning cannabis medicines.
 

SacredBreh

Member
Thanks BullD...
I will take a read. Your information about the Cannabinoids is very interesting. I have done quite a bit of reading of peer reviewed literature about both endogenous and exogenous cannabinoids. Over time I have come to the belief that even though Cannabis is a scheduled 1 there has been much study in clandestine research by Big Pharm. ( in the area of application of the known research) They would be idiots if they did not do this. One thing is very clear, they are NOT idiots when it comes to making money! I have a suspicion that many medications such as Lyrica for example actually are close cousins in actions to Cannabinoids. I am not saying for sure but there has been enormous amounts of research related to them and these guys do not throw that kind of money around for nothing.

Do you have any thoughts on that?

Peace
 

BullDogUK

Member
I have a suspicion that many medications such as Lyrica for example actually are close cousins in actions to Cannabinoids. I am not saying for sure but there has been enormous amounts of research related to them and these guys do not throw that kind of money around for nothing.

Do you have any thoughts on that?

Peace

As far as I can work out from a quick browse of the web, Lyrica acts to inhibit the activation of Calcium (Ca2+) pumps in the CNS.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654629/ - A Pfizer study on Lyrica's mechanism of action.

Besides that, you're absolutely right that many of the big pharma companies have attempted to use cannabinoids in mainstream pharmacology despite the schedule 1 rating. Perhaps the most well known synthetic cannabinoid is Marinol or Dronabinol, which is pure, synthetic delta-9-THC used in the treatment of chemotherapy/AIDS related eating disorders/nausea. Why this synthetic THC is considered a schedule III drug whilst natural THC remains schedule I is probably one of the best examples of government bias.

Besides Marinol, there's a fairly wide range of synthetic CB receptor agonists that have been developed: Nabilone, another THC mimic, is used in the treatment of neuropathic pain, anorexia, MS, fibromyalgia and a whole host of other conditions.

Some of these synthetics are simply used in the legal cannabis replacements found in head shops, such as spice or Black Mamba, however others, such as the memorably named JWH-133, HU-210 or WIN 55,212-2 are currently being investigated for their potential in reducing inflammation caused by the development of amyloid plaques in Alzheimer's and to prevent neurotoxicity by deactivation of microglia in many animal models.
 

BullDogUK

Member
The problem that cannabis presents to classical drug manufacturers is that, in its natural form, bud contains somewhere in the region of 300 biologically active chemicals, including many non-cannabinoids which may play further roles in modulating the effects in various tissues.

I've not had much time to look into this myself but I'm sure many of you have heard of terpenes, which are responsible for some of the fantastic smells that this plant produces, may have many medically useful properties and may also affect CB receptors to some degree.
 

BullDogUK

Member
http://hightimes.com/lounge/ht_admin/8275 - Talking Terpenes by Martin Lee in High Times Magazine.

Definately worth reading through to get a basic idea of what terpenes are and which specific molecules lend themselves to certain smells. As there are numerous strains out there with very similar/exactly the same cannabinoid profiles, terpenes can be used as an olfactory stamp to differentiate between strains. For those looking to breed the most fantastic smelling plants in the world, this is what you want to concentrate on!
 

OLDproLg

Active member
Veteran
YOU SIR' HAVE HIT IT ON THE NAIL ABOUT TERPENES!!!!!

YOU SIR' HAVE HIT IT ON THE NAIL ABOUT TERPENES!!!!!

LOVE YOUR LAST WORD BRO!!!!

You can and SHOULD BREED CANNABIS FOR THIS TRAIT PERIOD.
FOr cannabis is capable of giving humans thousands of flavors!!!!!!!!!
LOVE it again Bulldog UK!

super duper thinking my good man,one of the better personalities here!
i can tell...

Continue sir'
 

BullDogUK

Member
Howdy everyone :tiphat:

Sorry for the recent silence; I'm free following next Thursday so will begin drafting/researching for the next post after then :dance013:

Anyway I thought it may be an idea to make this whole thing a bit more interactive so with that in mind, what sort of topics are people interested in learning more about?

I'm happy to continue looking at the Biochemistry of cannabinoids within the body however, as this is a grower's forum, I'd love to start looking at some botanical biochemistry and cannabinoid synthesis.
 
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