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inthecloset

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About inthecloset

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  1. OK so lets see the molecular players in cannabis... Attached are images of the various cannabinoid componds isolated so to date (well mostly to date). There are a few things to keep in mind when looking at what compounds are present in any plant (or anything really): 1. Relative abundance. The less there is of something the harder it is to find. This does not mean the lower abundance compounds are not pharmacologically significant. 2. The method of isolation. Isolation procedures can cause modifications to the compounds, therefore just because you have found it doesn't always mean it is in the plant (or whatever). 3. Method of detection. Same as 2. Mass spectometry (MS) based methods while super-sensitive can aso cause modifications to detected compounds. This is especially relavent to MS methods since in order to detect a compound it must carry a charge (MS doesn't measures mass, it measures mass:charge ratio), so by definition these methods cause chemical modifications (which impart charge) which have to be taken into account. 4. Structural determination. Nucelar magnetic resonance (NMR), the most powerful methods for determining structures are notoriously insensitive. Meaning you need a lot of the compound in the first place, and if it's not pure, the major constituent can mask minor ones (this is especially relevant to structurally related compounds, which will generate very similar NMR spectra. The upside is that there are also sorts of variants on NMR experiments that can be used in combination with MS methods to determine structures 5. Natural products (organic compounds found in living organisms) are the results of multi-step (often), enzyme mediated, biosynthetic pathways. Therefore you may also find intermediates to the final compound (depending on their "steady-state" concentrations, again they too can be pharmacologically relevant, but are often low abundance. There are also example of enzymes that may not be a "part of the pathway" but can cause minor (often) modifcations to the end-product (or indeed any intermediate compounds). Right having said all of that, here are (at least some, probably not all) of the cannabinoids isolated and identified to date: These were taken from the reference posted in the medicinal section by Running Water, (https://www.opengrow...icancer-agents/) Next up we'll get into some of the proposed targets mentioned in that paper, and again there are a few things to keep in mind... (disclaimer: If I've missed something yell out, I always miss something...)
  2. inthecloset

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  3. Hey fellas, I've been thinking about starting this topic for a while, my primary research focus is drug mode-of-action and drug target identification, and I smoke cannabis so it's natural for me think about how the various physiological effects of cannabis are generated at the molecular level. What I want to do here is mention some of the intricacies of drug action using cannabinoids present in cannabis as example compounds, where possible I will add peer reviewed primary research articles for reference but I also want to explain some of the possibilities, not necessarily the facts. So to start with I will define some of terms I will use, and some I already have: 1. Molecular pharmacology: easiest to define this in contrast to "traditional" pharmacology. Traditional pharmacology is concerned with how drugs affect a entire organism, and what the organism does to the drugs. Here we would mention bodily distribution of the drug (where it goes/accumulates in the body, where is doesn't go - typically known as pharmacodynamics), also drug metabolism (how the body modifies the drug, usually in order to excrete it - typically known as pharmacokinetics). While I'm not a traditional pharmacologist we have to keep these things in the background when we talk about the effects of cannabis. In terms of bodily distribution we know cannabinoids cross the blood-brain-barrier, and hence get into the brain. But keep in mind the possibility of the brain having "compartments", cannabinoids could distribute unevenly in the brain. Also metabolism is one way the body tries to clear a drug. Generally most metabolism works to makes compounds more water soluble so they can be excreted through the kidneys, and while some of these modifications may inactivate the compound, they can also generate new compounds with different activities (a great example of this is glucuronidation of morphine, which generates a conjugate with even greater analgesic properties). Generally molecular pharmacology looks at what targets a drug interacts with and how. Most drugs interact with proteins and perturb their function. In the case of cannabinoids, as you will be aware, the "major" receptors are the cannabinoid receptors (CB1 and CB2 subtypes). These are proteins the sit in the cell membrane with which cannabinoids physically interact with. But as you will see there are a number of other proteins for which we have evidence of an interaction with, some membrane bound (like the CB receptors), some inside the cell (such as PPARg). Cell surface receptors relay signals into the cells, to elicit a response. Other cell membrane proteins act as channels, allowing the influx of things (nutrients and ions for instance) which can’t cross the membrane directly. Any ion (a molecule/atom that carries a charge, tetrahydrocannabinolic acid for instance) has to enter the cell via a channel of some description, the force required to push a charged compound through the lipid (fatty) portion of the cell membrane is so great that only uncharged compounds (such as tetrahydrocannabinol) are able to enter the cell by crossing the membrane directly) To understand the action of just a single drug, you must have an appreciation of the array of targets it interacts with, the relative affinities for those interactions (ie how strongly they bind to the protein), and the plasma/local concentration of that drug. So what I will mention here is really a fusion of molecular and traditional pharmacology, which is what you need if you want to explain the array of physiological effects of any drug. 2. Exogenous cannabinoids These are cannabinoids that originate outside the body. In contrast to endogenous, which are produced inside the body, such as anandamide. So in the simplest case, of a single exogenous cannabinoid that interacts with just one CB receptor we have to think about whether that compound activates (acts as a agonist) the receptor, or competes with the endogenous ligand for the receptor (acts as an antagonist). Bear in mind even in the case of an agonist, there may well be competition with the endogenous ligand, so the overall “receptor output” is a combination of the agonising effect of exogenous ligand, and the effects of competing off the endogenous ligand. So, I think that will do for now. I will leave you with this: There have been isolated at least 10 different cannabinoids from cannabis, and there is “evidence” for the possibility of 20-30 separate protein targets of these cannabinoids (including the CB receptors). Different cell types in the body express different proteins and we all know cannabis has a wide variety of different physiological effects, and that different types of cannabis elicit different (sometimes wildly different) response in different individuals... Just in case anyone though this shit is easy to understand, and I’m really only going to focus on psychoactive effects let alone the possibility that non-target mediated effects (such as the potent antioxidant activity of most cannabinoids) could also contribute to their physiological effects... Ugh what am I getting myself into... (disclaimer: my typing sucks, if I haven't made sense, ask me a question)
  4. Good to have another Southerner here, welcome!
  5. Those are some awesome looking strawberries, never heard of them before. We've (me and the little girly) have just planted out our winter garden (southern hemisphere), hopefully in 2 weeks of so we'll have sugar snap peas, broad beans, forkhead silverbeet, spinach, onions, spring onions, purple savoy cabbage, purple brocolli and normal brocolli sprouting... fingers crossed! Does anyone have anymore suggestions for good winter crops? We've also planted out some marigolds, foxglove and camomile to help everything along. I never cared much for growing veges until I started growing canna, plants are cool! Sun = free food!
  6. SG: Yeah I know, I'm going to read the review in Trends in Pharmacological Sciences posted on the other thread and comment further there. It was an interesting read, just a little unsatisfying for me. Cheers for understanding
  7. I would have to say that the anti-cancer portion of this review is poorly written and without any stated concentrations for the cell culture experiments mentioned it is difficult to assess whether CBD would be of use clinically. I will have to look into the primary articles the author cites to get past the hand-waving arguments he makes in this section. Not being a dick, but in all honesty this is not a very informative review...
  8. I've got this article, if anyone wants yell out and I'll send it to you. Or I can upload it somewhere, just not sure where Edit: what a dick... sorry Running Water, it seems you are more onto it than me...
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