Restoring the Balance - (title of an old triple J program)

[Frazz]

wow what a duck hunt !! im surprised you are still flying danoz, youve taken on alot of lead , nevertheless we still have boxes and boxes of cartridges left ...

 

seems to me its a waste of your finely tuned brain to attempt to shove sceintific mumbo jumbo down our throats, after all most of us are mainstream folks who you beleive to be "pretty dumb" ..

 

instead i invite you to research the harmful effects of prohibition upon those whom partake in the use of Cannabis,

it would be groundbreaking as i beleive no such study has ever been taken..

 

cause the direction you are taking now has everybody here crossing you off their xmas list , and that is a fact!

 

[noface]

Yes but frazzle we the government don't consider your shizo son being caught growing a bit of weed, going to prison and copping it up the arse as harmful, no not at all, we are rehabilitating him. Trust us. Now give me your taxes these prisons are expensive to run (and build muahahaha)

 

aaaahhh

shoot me.

[entheofarm]

danoz the troll

 

I to can copy and paste but I can also spell neuro, not bad for someone with no formal education

 

Cannabis:

Old medicine with new promise for neurological disorders

 

Gregory T. Carter1* & Patrick Weydt2

 

Addresses

1Department of Rehabilitation Medicine and

2Department of Neurology

University of Washington School of Medicine

Seattle, WA 98531

 

USA

 

Email: gtcarter@u.washington.edu

 

*To whom correspondence should be addressed

 

Current Opinion in Investigational Drugs 2002 3(3):437-440

 

ã PharmaPress ISSN 1472-4472

 

Marijuana is a complex substance containing over 60 different forms of cannabinoids, the active ingredients. Cannabinoids are now known to have the capacity for neuromodulation, via direct receptor-based mechanisms at numerous levels within the nervous system. These have therapeutic properties that may be applicable to the treatment of neurological disorders; including anti-oxidative, neuroprotective, analgesic and anti-inflammatory actions; immunomodulation, modulation of glial cells and tumor growth regulation. This article reviews the emerging research on the physiological mechanisms of endogenous and exogenous cannabinoids in the context of neurological disease.

 

Introduction

 

Over the past few decades, there has been widening interest in the viable medicinal uses of cannabis. The National Institutes of Health, the Institute of Medicine, and the Food and Drug Administration have all issued statements calling for further investigation. The discovery of an endogenous cannabinoid system with specific receptors and ligands has led the progression of our understanding of the actions of cannabis from folklore to valid science. It now appears that the cannabinoid system evolved with our species and is intricately involved in normal human physiology, specifically in the control of movement, pain, memory and appetite, among others. The detection of widespread cannabinoid receptors in the brain and peripheral tissues suggests that the cannabinoid system represents a previously unrecognized ubiquitous network in the nervous system. Dense receptor concentrations have been found in the cerebellum, basal ganglia and hippocampus, accounting for the effects on motor tome, coordination and mood state. Low concentrations are found in the brainstem, accounting the remarkably low toxicity. Lethal doses in humans has not been described.

 

The Chemistry of Cannabis

 

Marijuana is a complex plant, with several subtypes of cannabis, each containing over 400 chemicals. Approximately 60 are chemically classified as cannabinoids. The cannabinoids are 21 carbon terpenes, biosynthesized predominantly via a recently discovered deoxyxylulose phosphate pathway. The cannabinoids are lipophilic and not soluble in water. Among the most psychoactive is D9-tetrahydrocannabinol (THC), the active ingredient in dronabinol (Unimed Pharmaceuticals Inc). Other major cannabinoids include cannabidiol (CBD) and cannabinol (CBN), both of which may modify the pharmacology of THC or have distinct effects of their own. CBD is not psychoactive but has significant anticonvulsant, sedative and other pharmacological activity likely to interact with THC. In mice, pretreatment with CBD increased brain levels of THC nearly 3-fold and there is strong evidence that cannabinoids can increase the brain concentrations and pharmacological actions of other drugs.

 

Two endogenous lipids, anandamide (AEA) and 2-aracidonylglycerol (2-AG), have been identified as cannabinoids, although there are likely to be more. The physiological roles of these endocannabinoids have been only partially clarified but available evidence suggests they function as diffusible and short-lived intercellular messengers that modulate synaptic transmission. Recent studies have provided strong experimental evidence that endogenous cannabinoids mediate signals retrogradely from depolarized post synaptic neurons to presynaptic terminals to suppress subsequent neurotransmitter release, driving the synapse into an altered state. In hippocampal neurons, depolarization of postsynaptic neurons and the resultant elevation of calcium lead to transient suppression of inhibitory transmitter release. Depolarized hippocampal neurons rapidly release both AEA and 2-AG in a calcium-dependent manner. In the hippocampus, cannabinoid receptors are expressed mainly by GABA-mediated inhibitory interneurons. Synthetic cannabinoid agonists depress GABAA release from hippocampal slices. However, in cerebellar Purkinje cells, depolarization-induced elevation of calcium causes transient suppression of excitatory transmitter release. Thus endogenous cannabinoids released by depolarized hippocampal neurons may function to downregulate GABA release. Further, signaling by the endocannabinoid system appears to represent a mechanism enabling neurons to communicate backwards across synapses in order to modulate their inputs.

 

There are two known cannabinoid receptor subtypes; subtype 1 (CB1) is expressed primarily in the brain, whereas subtype 2 (CB2) is expressed primarily in the periphery. Cannabinoid receptors constitute a major family of G protein-coupled, 7-helix transmembrane nucleotides, similar to the receptors of other neurotransmitters such as dopamine, serotonin and norepinephrine. Activation of protein kinases may be responsible for some of the cellular responses elicited by the CB1 receptor.

 

Neuromodulation and neuroprotection

 

As we are developing an increased cognizance of the physiological function of endogenous and exogenous cannabinoids it is becoming evident that they may be involved in the pathology of certain diseases, particularly neurological disorders. Cannabinoids may induce proliferation, growth arrest or apoptosis in a number of cells, including neurons, lymphocytes and various transformed neural and non-neural cells. In the CNS, most of the experimental evidence indicates that cannabinoids may protect neurons from toxic insults such as glutamatergic overstimulation, ischemia and oxidative damage. The neuroprotective effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson.s disease, cerebrovascular ischemia and stroke. Both endogenous and exogenous cannabinoids apear to have neuroprotective and antioxidant effects. Recent studies have demonstrated the neuroprotective effects of synthetic, non-psychotropic cannabinoids, which appear to protect neurons from chemically-induced excitotoxicity. Direct measurement of oxidative stress reveals that cannabinoids prevent cell death by antioxidation. The antioxidative property of cannabinoids is confirmed by their ability to antagonize oxidative stress and consequent cell death induced by the powerful oxidant, retinoid anhydroretinol. Cannabinoids also modulate cell survival and the growth of B-lymphocytes and fibroblasts.

 

The neuroprotective actions of cannabidiol and other cannabinoids have been examined in rat cortical neuron cultures exposed to toxic levels of the exitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both CBD (non-psychoactive) and THC. The neuroprotection observed with CBD and THC was unaffected by a cannabinoid receptor antagonist, indicating it to be cannabinoid receptor-independent. CBD was more protective against glutamate neurotoxicity than either ascorbate (vitamin C) or a-tocopherol (vitamin E).

 

Cannabinoids have demonstrated efficacy as immune modulators in animal models of neurological conditions such as MS and neuritis. Current data suggests that the naturally occurring, non-psychotropic cannabinoid, CBD, may have a potential role as a therapeutic agent for neurodegenerative disorders produced by excessive cellular oxidation, such as ALS, a disease characterized by excess glutamate activity in the spinal cord.

 

It is not yet known how glutamatergic insults affect in vivo endocannabinoid homeostasis, including AEA, 2-AG, as well as other constituents of their lipid families, N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs). Hansen et al used three in vivo neonatal rat models characterized by widespread neurodegeneration as a consequence of altered glutamatergic neurotransmission and assessed changes in endocannabinoid homeostasis. A 46-fold increase in cortical NAE concentration and a 13-fold increase in AEA was noted 24 h after intracerebral NMDA injection, while less severe insults triggered by mild concussive head trauma or NDMA receptor blockade produced a less pronounced NAE accumulation. In contrast, levels of 2-AG and other 2-MAGs were unaffected by the insults employed, rendering it likely that key enzymes in biosynthetic pathways of the two different endocannabinoid structures are not equally associated with intracellular events that cause neuronal damage in vivo. Analysis of cannabinoid CB1 receptor mRNA expression and binding capacity revealed that cortical subfields exhibited an upregulation of these parameters following mild concussive head trauma and exposure to NMDA receptor blockade. This suggests that mild-to-moderate brain activity via concomitant increase of anandamide levels, but not 2-AG, and CB1 receptor density. Panikashvili et al demonstrated that 2-AG has an important neuroprotective role. After closed head injury (CHI) in mice, the level of endogenous 2-AG was significantly elevated. After administering synthetic 2-AG to mice following CHI, a significant reduction of brain edema, better clinical recovery, reduced infarct volume and reduced hippocampal cell death compared with controls occurred. When 2-AG was administered together with additional inactive 2-acyl-glycerols that are normally present in the brain, functional recovery was significantly enhanced. The beneficial effect of 2-AG was dose-dependently attenuated by SR-141716A (Sanofi-Synthélabo), an antagonist of the CB1 receptor [30]. Ferraro et al looked at the effects of the cannabinoid receptor agonist WIN-55212-2 (Sanofi Winthrop Inc) on endogenous extracellular GABA levels in the cerebral cortex of the awake rat using microdialysis. Win-55212-2 was associated with a concentration-dependent decrease in dialysate GABA levels. Win-55212-2 induces inhibition was counteracted by the CB1 receptor antagonist SR-141716A, which by itself was without effect on cortical GABA levels. These findings suggest that cannabinoids decrease cortical GABA levels in vivo.

 

Sinor has shown that AEA and 2-AG increase cell viability in cerebral cortical neuron cultures subjected to 8 h of hypoxia and glucose deprivation. This effect was observed at nanomolar concentrations, was reproduced by a non-hydrolyzable analog of anandamide, and was unaltered by CB1 or CB2 receptor antagonists. In the immune system, low doses of cannabinoids may enhance cell proliferation, whereas high doses of cannabinoids usually induce growth arrests or apoptosis.

 

In addition, cannabinoids produce analgesia by modulating rostral ventromedial medulla neuronal activity in a manner similar to, but pharmacologically distinct from, that of morphine. Cannabinoids have been shown to produce an anti-inflammatory effect by inhibiting the production and action of tumor necrosis factor (TNF) and other acute phase cytokines. These areas are discussed in great detail in a recent paper by Rice.

 

Glia as the cellular targets of cannabinoids

 

There is now accumulating in vitro evidence that glia (astrocytes and microglia in particular) have cannabinoid signaling systems. This provides further insight into the understanding of the therapeutic effects of cannabinoid compounds. Glial cells are the non-neuronal cells of the CNS. In humans they outnumber neurons by a factor of about 10:1. Because of their smaller average size they make up about 50% of the cellular volume of the brain. Glial cells of the CNS fall into three general categories: astrocytes, oligodendrocytes and microglia. Schwann cells and the less well-recognized enteric glia are their counterparts in the peripheral nervous system. Glia are ubiquitous in the nervous system and are critical in maintaining the extracellular environment, supporting neurons, myelinating axons and immune surveillance of the brain. Glia are involved, actively or passively, in virtually all disorders or insults involving the brain. This makes them logical targets for therapeutic pharmacological interventions in the CNS. Astrocytes are the most abundant cell type of the CNS. They express CB1 receptors, and take up and degrade the endogenous cannabinoid anandamide. The expression of CB2 receptors in this population appears to be limited to gliomas and may be an indicator of tumor malignancy. Two recent studies suggest that some of the anti-inflammatory effects of cannabinoids, such as the inhibition of nitric oxide (NO) and TNF release are mediated by CB1 receptors on astrocytes.

 

The most recent therapeutic role for cannabinoids in the CNS evolved from the discovery that cannabinoids selectively induce apoptosis in glioma cells in vitro and that THC and other cannabinoids lead to a spectacular regression of malignant gliomas in immune-compromised rats in vivo. The mechanism underlying this is not yet clear but it appears to involve both CB1 and CB2 receptor activation. A recent study comparing the antiproliferative effects of cannabinoids on C6 glioma cells suggests the involvement of vanilloid receptors.

 

Microglia are the tissue macrophages of the brain. In variance from other immune tissue but in accordance with their place in the CNS microglia appear to lack CB2 receptors on protein and RNA levels. Similar to their effect on peripheral macrophages, cannabinoids inhibit the release of NO and the production of various inflammatory cytokines in microglia. Interestingly, the inhibition of NO release seems to be CB1 receptor- mediated, whereas the differential inhibition of cytokines is not mediated by either CB1 or CB2 receptors, suggesting as yet unidentified receptors or a receptor independent mechanism. Irrespective, the potential of cannabinoids on inflammatory processes such as a mouse model of MS or future experiments on brain tumors in immunocompetent animal.

 

Nothing is known of the effects of cannabinoids on oligodendroglia. In the light of the clinical and experimental evidence suggesting the beneficial effects of cannabinoids in MS, investigations in this direction appear promising.

 

Future trends

 

A growing number of strategies for separating the sought-after therapeutic effects of cannabinoid receptor agonists from the unwanted consequences of CB1 receptor activation are now emerging. However, further improvements in the development of selective agonists and antagonists for CB1 and CB2 receptors are needed. This would allow for the refinement of cannabinoids with good therapeutic potential and would facilitate the design of effective therapeutic drugs from the cannabinoid family. Customized delivery systems are also needed; as the cannabinoids are volatile, they will vaporize at a temperature much lower than actual combustion. Thus heated air can be drawn through marijuana and the active compounds will vaporize and can easily be inhaled. Theoretically this removes most of the wealth hazards of smoking, although this has not been well studied. Recently, pharmacologically active, aerosolized forms of THC have been developed. This form of administration is achieved via a small particle nebulizer that generates an aerosol which penetrates deeply into the lungs.

 

From a regulatory perspective, the scientific process should be allowed to evaluate the potential therapeutic effects of cannabis, dissociated from the societal debate over the potentially harmful effects of non-medical marijuana use. This class of compounds not only holds tremendous therapeutic potential for neurological disease but is also confirmed as having remarkably low toxicity.

 

 

YAWN!

Edited October 30, 2008 by entheofarm

[danoz]

For starters the reason why im bothering. Is because i felt like the general culture of this site had mis led me.

However it was pointed out that there are threads which offer these opinions im stating already.

 

 

Secondly the spelling remark was DUMB - i already pointed out myself "fuck i cant spell" in my own post so why bother its beside the point?

 

 

THIRDLY -- ENTHeFARM " i too can copy and paste" DUDE AGAIN I ALREADY SAID IN MY OWN POST at the end of the post i said " ok so i can copy and paste not very scientific........" Again so why bother adding it

 

 

Thirdly ITS NOT ABOUT PROHIBITION!!!!!! .. i even said mmmm could be swayed on the prohibition thing infact iam i conceed that prohibition is more harmfull than legalising its just something i typed out quick

 

ITS ABOUT the neUro effects of weed

 

You guys are like broken records making sly remarks about my age, education, or assistence from someone who understands the scientific literature. OR EVEn spelling haha why bother its a fucken thread. NEEWWWWROOO neUro.

 

Honestly there is so much out there about the neg effects of weed on your brain biochem and anatomy that its not even an argument. However alot of research shows that in moderation its ok or that even chronic use may only cause tempory effects.

 

So anyone wanna talk cannibus biochem with me ??? or shall we swap shit stirring??

 

Another concession i would like to make is that "mainstream people are dumb" was a bad thing to say i would like to retract it. I wasnt claiming im smart merely that im not mainstream being against commercialism, and never watching TV

i was refering to mainstream people engaged and obsessed with consumerism that watches commercial TV and reads the herald sun for their info. I shouldnt have used the word dumb. PLEASE DONT REPLY TO THIS SECTION ITS OFF TOPIC

[danoz]

Enthoenfarm What you copied and pasted didnt really say alot

 

For starters it wasnt research, it was expert opinion. Expert opinion scientifically has value, but is ranked much lower than actual data from an experiment. The guy wasnt even referencing which i found odd given what it was published in doesnt matter though.

 

Lots of use of the word "promising" "NOT known yet" Also it was in context to medical use, here potential benefits may out weight the negetive ones im talking about. Therefore it still may be harmful to people without a disorder.

 

So where is your actual data? ive copied and pasted mine

 

or shall we all just resort back to name calling. Why doesnt someone post actual data saying weed is fine for your brain chemistry ????

 

spose its easier just to call me a troll - this demonstrates your argument well perhaps point out a gramatical error next time.

[entheofarm]

No need to get upset danoz, I wasn't taking the piss (much) pointing out that I am a dumb mainstream stoner with no education who does not need egotistical phd friends to explain the context of psycho-babble, and my spelling sucks too but I don't claim to be researching something I can't spell and any researcher still at uni would have thier balls scalped for such a thing, you of all people should know that.

 

Your not the first to be wrong and you won't be the last

 

and do some more research, BROAD RESEARCH

 

THiRdly fuck off don't call me DUDE, your attitude is starting to affect any credibiity you may have had, if your going to get upset fuck off and don't post rubbish, if you have your own research (factual) than post it, I will wait a week to get the chance to prove to you that you have indeed made ill-informed, poorly educated and dangerous assumptions.

 

You are a troll and a very good one at that

[MongyMan]

I merged the 2 threads Danoz. No need having 2 threads for people to try and follow about the same thing.

 

Having read it from start to finish my understanding is that you are saying cannabis can have negative effects for some people so the current laws should not only stand but be embraced by the members here.

 

On the first point, Danoz. Almost anything can have a negative effect for some people. Peanuts kills more a year than cannabis ever has for eg. jumping into cold water can trigger a heart attack in some people. By your reasoning we should add them to the list of things prohibited too.

 

As far as supporting the current laws, no one with any indepth understanding on the true cost of cannabis prohibition is going to side with you mate. In fact the very dangers you refer to are often a direct result of prohibition or at minimum greatly aggravated by it due to the social stigma attached to people because of their cannabis use. If someone eats a peanut and needs hospital there is no stigma, why should there be for cannabis? It is criminal imo to have a situation where someone doesn't seek medical advice when needed out of fear of persecution. And that is just the tip of the iceburg of the costs prohibition has on our society.

 

Under prohibition drug education is a joke. Most kids work out pretty quickly that on the whole it's just emotional fear mongering based on very little facts and as a result the few important points that are made are not believed. In fact none of it is believed then which often leads to bigger problems than were trying to be avoided in the first place.

 

Prohibition means that more often than not cannabis is supplied by organized crime. These are the same people who also sell speed, heroin, extacy, cocaine, meth and the list goes on. I've lost count of the times I've been told "nah mate, got no buds atm, but you can buy "(insert truly dangerous dug name here)" if you want or "here's the buds...would you like some meth with that order" just like a macca's drive through but with drugs. That's never happened to me when I went to buy ciggies or a beer under a licenced system of sale.

 

I could go on Danoz but with all due respect mate I think you need to do a bit more research and talk to more people outside your normal social circle on the impact prohibition has on individuals and families and therefor society as a whole. Other than those that blindly say cannabis is 100% safe hoping this will help it's leagal status you will find that most agree it can have risks for some but on the scale of things this risk is tiny compared to most things in our society but the cost of prohibition far outweighs these costs to the point it's the prohibition that is now the major issue. Not the plant it prohibits.

 

Peace MongyMan

[danoz]

thanks for the post mongyman but u must of been writing it while i posted the ones just above it.

 

You make incredibly compelling arguments for legalisation that i greatly appreciate.

 

As i said above my support of its current legal status was ill - informed and thanks for the people who calmly spelled out some excellent arguments.

 

I have shifted my focus to the neural effects cause this is an argumentative island i can safely hang onto and was actually the main focus of the origanal post, maybe i didnt make that clear. the legal bit i finished with in hindsight i should of left out it was acutally a brief after thought

 

Also the point you made about the fear based education, i agree, i think also fear is an over used tool not just for weed. amd like u said the message is lost because eventually they see it as dishonest

 

For me personally the neUro stuff stands. chatting on this site recently had sort of skewed me to think that weed was like a completely consequence-less drug. Maybe this was my poor interpretation of the general culture of the site. None the less the post is intented to point out that there is some sound data which was new to me that weed can be pretty harmful to your neUral health. I thought this was worth sharing.

 

 

Please can someone post an abstract of an article from a reputible database suggesting that weed is fine for your neUral health?

 

 

Again Enthefarm you presented an expert opinion to repeat - expert opinions scietifically are worth squat. Where is your data. again and again you resort to personal attacks (not that i give a shit). These do not support your arguments that weed is harmless to your brain chemistry or anatomy. Secondly your expert opinion was full of "not known yet" and "potentially". also it was in the context of mental disorders.

Edited October 30, 2008 by danoz

[Dragonfan]

Mmm, walk outside and inhale . . . now you probably just sucked in more harmful chemicals than you would like to have which may or may not directly or indirectly affect your neural health . . . depending on where you are geographically speaking so, go figure?

 

Should we prohibit breathing too because it MAY be harmful to our neural health?

 

I think the point you're missing [from my perspective] is that marijuana IS efficacious medicinally and should NOT be denied to those who CAN and DO benefit from its use . . . [and who don't want to be pumped full of pharmachemicals which are DEFINATELY harmful to our bloody neural health!]

 

There are oodles of reports, expert opinions, research papers etc available online that support both pro and anti marijuana . . . reading between the lines to see the hidden agenda's in most anti marijuana 'research' is easy . . . the pharmachemical companies and the petrochemical industry are behind a LOT of the nay saying there . . . [and yeah, that's only my opinion too, but, even though Noface will argue the point, last time I looked I was still allowed an opinion]

 

What irks me the most is that you see fit to just slam someone's personal 'life' experience garnered from years of dealing with a substance as next to nothing because it's NOT 'research' . . . well, what's the definition of 'research' . . . diligent and systematic inquiry or investigation into a subject in order to discover or revise facts, theories, applications . . . and I think most 'stoners' would have spent years revising facts, coming up with theories and developing applications for their fave herb!

 

I don't think you have the right to denigrate ANYONE who feels the need [or want, as the case may be, and adults I'm talking about here, not children] to partake of a substance that has never killed anyone [in its natural form]. I for one LOVE the neural affects cannabis has on my pain receptors . . . and if my brain shrinks and I forget what I was . . .

 

Oh, sorry . . . and if my brain shrinks and I forget what I was saying less than a minute ago and I DON'T get cancer and I DON'T get Alzheimers . . . good for me . . . as long as I'm not hurting ANYONE why should I be punished, prosecuted or persecuted?

 

The stress alone from being prosecuted/persecuted has killed more stoners than Cannabis ever will, oh, that's right, Cannabis has NEVER killed anyone . . . in its natural form

 

Lots of referenced reading here --> Cannabis and the Brain

[danoz]

To Dragonfan, thanks for your reply

 

Its getting hard not to keep repeating myself in answers to these posts.

 

Firstly - i conceeded that the remark about its current legal status was ill-informed. i actually have changed my mind about this due to some great replies. Im focussing on what was supposed to be my main contention is the first place see- Posts page 5+6. So your reply about the legal status is great i appreciate it but u may of missed the boat.

 

As to your point about the experience of people on this site - I agree

I was arrogant in some of my replies, this was intentional, a conscience shit stirring mechanism, because i was being stirred myself - god dam did it work.

Im actually a very respectful person but i quickly digress if its not reciprocated.

 

However, my opinion strongy differs from yours regarding anti marijuana research. (again im repeating something i said earlier here ) human behavior studies of weed are easy to distort and are therefore prone to proganda. However, how many of them have been squewed by organisations such as you claim? - there is no way i can know this. Personally, i dont feel it would be as prevalent as some may believe from my experience with sci publications.

 

This statement in particular i disagree with "the pharmachemical companies and the petrochemical industry are behind a LOT of the nay saying there"

 

 

In contrast, the neuro science is much less easy to generate propoganda from. A very large majority of these studies are very anti weed.

 

Its not damming enough to stop me smoking weed in moderation, im just more aware of the risks I felt maybe people on this site would interested in it too.