ps418

The plant is definitely psychoactive prior to curing. There's not the slightest doubt about it. You can prove it to yoruself by making brownies with fresh-cut plant. As to whether new cannabinoids are synthesized after harvest, I have no reason to doubt that that happens, at least until the plants lose most of their water. However, I doubt very much that any new psychoactive cannabinoids are synthesized after the curing process is complete.

No, the vast majority of cannabis in the US is indeed relatively low-grade. This is based on my own experience, as well as potency statistics I've seen based on analyses of DEA seized cannabis (I'll look for a source). I didnt say there was no high-grade. There certainly is. But it comes from indoor grow operations that are of very limited scale and low yield, and sells for more money that most people can spend.

Patrick

sweep

well, the thing is, the first batch of cookies I ever made (over two years ago now) after I stopped smoking, worked really well. I'd fry a bud in butter in a shallow pan on medium heat, then add it to the mixture. The following batches didn't work quite so well, and I couldn't figure out why. The only brand that did work, following several weak batches, was purple haze. Perhaps someone here knows how best to prepare weed for ingestion?

So, In order to save on money, since I'm in no position to start growing my own, I buy hashish, crumble it on melted cheese, and eat. I don't feel satisfied unless the stuff really kicks the shit out of me, but it can be frightening and negative, even though I've learned to accept this as part and parcel.

cheers pat

bACK On TRACK

If anything heavy cannabis use has forced me to deal with aspects of myself that I felt uncomfortable with. I can't hide, because time seems to slow down and even the smallest behaviour becomes perceptible. Normally these behaviours happen subconsciously, such as when people always have to have a drink or a smoke in their hands, during a party. I mean any social constraints suddenly seem absurd and feel uncomfortable.

Problems have surfaced due to impaired memory. This has the effect of removing context; conversation no longer fits together and individual lines are interpreted alone. This leads, in my experience, to self-referencing. It seems as though I am attacking myself with my own thoughts. It becomes very easy to jump to conclusions and more difficult to avoid believing what my mind tells me. This isn't brain damage, more psychological warfare. My mind works differently, and it doesn't function normally most of the time.

ps418

You really should reduce your use or eliminate it altogether. The self-referencing and critical internal commentary are not good signs. If you have a latent mental disorder (and I have no idea one way or the other), you could easily make it much worse or precipitate a prolonged negative reaction by eating large quantities of hash. If nothing else, you should really quit eating hash. Its not my business what you do with your own brain, but I hope that if I described the same thing to you that you would give me the same advice.

Patrick

Nuno Figueira

Oral ingestion is the most potent form of administration of cannabis. Back in the days I was a pot head I used to do it all the time. My favorite way was the Baudelaire receipt, Morrocan hax crumbled in a very strong coffe. Works like a charm. The most pleasnt way would be to melt it some kind of fat, butter or olive oil come to mind and then mix it with something like milk, if you drink that stuff that is, and eat it. I had great fun with eaten haxixe, I'll post something that I find entertaining I wrote a while ago in another forum:

"I took it for the first time right before I was taking a bus in order to leave a friend's house. It was around 2 PM when I took around one gram of regular crap moroccan hash crumbled in a very strong coffee. During the trip the bus broke down and I started hallucinating like I had never did before (still hadn't tried LSD at that time). I had to change bus which was a very complicated thing to do, as I couldn't even talk due to having an extremelly dry mouth. Getting some water didn't even cross my mind. I arrived my parents house around 10 PM and it kept getting worst and worst, some friends of theirs were there and I didn't even saw them or heard them. I went straight to the kitchen and ate a lot of food hopping it would go away (I hated being stoned at my parents house). It got worst. Everyone noticed and my parents even asked what the hell had I done. I didn't answer. I went to bed and put on "guess who's comming to dinner" album by Black Uhuru (Sly and Robbie) playing really loud and lied on the bed for a long time. During this time I had the most weird perception changes, from feeling like I was a part of the bed, feeling percussion sounds jumping around the room and ocasionally hitting me in the stomach and other areas, other times I felt so numb that I was seriously convinced I was missing some bodyparts, particulary on my face. I even got up and went to check on the mirror if everything was there a few times. This part was great and a lot of fun, though scary at times, and for the next 15 days I did this every single day. I could never get such an intense experience after that, because at the time of this first experience my tolerance to THC was really low, and I became a chronic user after that.
"

sweep

It's really very nice of you to offer your support ps418, and, to a degree, you're right about my consumption being too heavy. The self referencing and critique are all normal parts of heavy cannabis use- In other words I feel that I have come to terms with the paranoia, which many users experience. It is also the prime reason why people stop. it scares the shit out of them and they start worrying about going insane. It often makes me feel very sensitive. There was one time on this message board when I reread some of the comments on a thread labelled: 'a eulogy to madmordigan'.

Not stoned I simply noticed all the smileys and wondered whether the posters were there to play billiards rather than to create an actual eulogy. A little later I looked again and saw some of the more sensitive responses, particularly by some of the girls here, and I began to feel the loss. It hit me and made me feel physically sick. I'm sure when I stop taking it, the differential will disappear, then there'll be no change between feeling numb and charged. But that's one of the reasons why I do; to experience that change that isn't perceptible to one who functions normally most of the time.

too true. It really does force people to face fear and paranoia. one of the problems of cannabis use is that it makes thinkers think more. Extroverted types don't seem to be so bothered. On a major trip the worst thing to do is nothing, because the user stops looking at things and starts thinking. that's when all the wierd stuff starts to happen. Sure, it can be so heavy that its impossible to communicate, or for anyone to understand that your memory is temporarily disabled. But as soon as that mundane environment hits you, the mind starts to wander and the next thing you know the dog is picking up your vibes, and everything your sister says is directly connected with your psyche:

my friend would barely trust me when it came to cannabis. the first time he tried it I fed him a gram. After an hour he was high but not high enough and naively, I thought that it had stopped working; so I fed him another gram. Two hours later he was feeling really funny and I told him the best thing to do would be to lay down in darkness while listening to 'chill out' by KLF. I checked on him occassionaly to hear his reports of trains running straight throught the living space, and fed him some pop and chocolate to keep him quiet.

A few months later, he reluctantly accepted my offer of a big pipe hit. I put a marble sized ball of super skunk on the pipe and he had a couple of big tokes. Two minutes later he shot out of the chair grabbed his personal stereo and bolted out the door. Good choice!

ps418

I found my source for this. The Potency Monitoring Project at the University of Mississippi has been measuring the potency (% THC by weight) of law-enforcement seized cannabis for over 20 years. For the years 1983 and 1993, the mean potency of siezed cannabis was between 1.96% (1992) and 3.96% (1984). These firgures are adjusted for weight, and are based on between 1119 and 3354 seizures per year. From 1993 to 1998, the average rose a bit, to about 4.3%. Though there has been roughly a doubling of average potency over the past 20 years, these numbers support what I said about the vast majority of the US cannabis market is low-potency cannabis. By comparison, most of the typical indoor, high-grade is about 10-30% THC, and 1% is barey distinguishable from placebo.

Quaterly Report, Potency Monitoring Project, Report #60, University of Mississippi: Research Institute of Pharmaceutical Sciences.

Patrick

PS- I found a few more interesting things (dexanabinol and HU-210) I want to talk about, but I'm in the middle of a bad allergic reaction, and my hands are so swollen its makes typing difficult, plus I'm taking massive dose of benadryl that is making it hard to stay awake. Be back tomorrow.

ps418

Over the weekend I spent some time catching up on cannabinoid research. I'm pretty impressed with how far this research has progressed in the past 4 years since the release of the IOM report on Medical Marijuana, and with the diversity of therapeutically-interesting effects demonstrated for natural and synthetic cannabinoids. These include neuroprotective effects, possible cardioprotective effects, anti-spastic effects, intraoccular pressure reducing effects, anti-nausea and anti-emesis (vomiting) effects, and analgesic or antinociceptive effects, particularly with respect to neuropathic pain. In each of these domains, cannabinoids are at least competitive with existing pharmacological therapies, and may prove useful as either alternatives or compliments to existing therapies which by themselves are less than completely effective. The following is a short and nonsystematic overview of some of the latest research in these areas, with an emphasis on recent research on the highly potent synthetic cannabinoids HU-211 (Dexanabinol) and HU-210.

One thing that has become clear is that many of the therapeutic effects of cannabinoids are receptor-independent, or are dependent upon activation of CB2 but not CB1. This means that it should be possible to get many of these benefits without also getting the psychoactive or potentially unpleasant CNS effects. The synthetic cannabinoid Dexanabinol is very similar to THC, except that it does not bind CB receptors, and thus is not psychoactive and does not affect heart rate and blood pressure as THC does. Therefore it can be used to produce most of the receptor-independent effects of THC.

Dexanabinol, for example, has been investigated extensively using animal and in vitro neural models of stroke and brain injury, and the results are pretty impressive. Dexanabinol has been shown to reduce the volume of cerebral infarct (i.e. the infarct is the area of tissue destroyed by lack of oxygen) and motor disability in a rat model of ischemic stroke produced by experimentally blocking the middle cerebral artery (Lavie et al, 2001), so the molecule may be an effective at limiting stroke-related brain damage in humans. Filbert et al (1999) showed that brain damage due to Soman neurotoxin-induced seizures in rats is significantly reduced with administration of Dexanabinol. The result was very significant. In fact, "when administered 40 min post-onset, the reduction in necrosis was 81.5% despite the presence of continuous seizures for 4-5 hr." Gallily et al (1997) showed that toxic shock mortality in rats and mice following injection of the potent bacterial endotoxin lipopolysaccharide was greatly reduced (up to 90% reduction) by Dexanabinol injections. These and other studies suggest that Dexanabinol would be useful as a defense against nerve gas type agents, such as Soman. Further, Zalish and Lavie (2003) showed that Dexanabinol resulted in axon regrowth in the optic nerves or rats that were crushed. "Viable axons were found 0.5 mm distal to the site of injury in 6 of 8 dexanabinol treated rats, but in only 1 of 10 rats in the control groups. These results have clinical implications for the prevention of secondary degeneration and promotion of regeneration after injuries to the central nervous system."

Dexanabinol is now in advanced Phase III trials for treatment of traumatic brain injury (TBI), and promises to be one of the most signficant pharmacological developments in neurological critical care medicine in the near future. Much of the brain damage that occurs with strokes, closed head injuries, and other brain injuries is due to the secondary effects of inflammation and swelling of the brain, which increases intracranial pressure and expands ischemia, and by glutamate excito-toxicity. Glutamate excitotoxicity is caused when injured neurons suddenly release the excitatory neurotransmitter glutamate into the extracellular space. This glutamate binds NMDA receptors on nearby neurons, opening sodium channels and allowing a influx of calcium ions, which causes the neuron to swell and possibly burst, releasing more glutamate into the extracellular environment. Dexanabinol is neuroprotective in several different ways: it inhibits the release of tumor necrosis factor alpha and other factors which lead to an inflammatory response that raises intracranial pressure, it acts as a potent antioxidant, and it is also a NMDA receptor antagonist (protecting against ischemia-induced glutamate excito-toxicity). Data from ongoing double-blind, placebo-controlled, mutli-center trials (Knoller et al, 2002) indicates that Dexanabinol is safe (no adverse reaction so far), and that when given within 6 hours of closed head injury results in much lower levels of intracranial pressure (reducing the probability that a pressure-reducing craniectomy will be needed), and better neurological outcomes as measured by the Glascow Outcome Scale. When Dexanabinol is approved, it will be the first effective pharmacological therapy for traumatic brain injury. Given that roughly 375,000 Americans suffer a serious head injury each year, this single compound could result in significantly better outcomes in millions of traumatic brain injury patients over time on a worldwide basis.

Other cannabinoids are being investigated as neuroprotective agents. HU-210 is a CB1 agonist, like THC, but is 100-800 times more potent than THC (Ottani and Giuliani, 2001). Pretreatment with CB1 antagonist reduces the neuroprotective effect, indicating perhaps that not all of the neuprotective effects of cannibinoids are receptor-independent. Leker et al (2003) showed that injection of HU-210 in rats 1 hour after middle cerebral artery occlusion resulted in reduced motor disability and up to 77% smaller infarct volumes as compated to control rats. Significantly, the protective effects were partially reversed by pretreatment with the CB1 antagonist SR-141716.

There is emerging evidence that cannabinoids possess some cardioprotective prperties as well. Krylatov et al (2002) reported that in rats HU-210 increased cardiac resistance to the arrhythmogenic effect of epinephrine, aconitine, coronary artery occlusion and reperfusion. The effect was abolished by the CB2 receptor antagonist SR144528, but not affected by treatment with the CB1 antagonist SR141716A, indicating that the effect is mediated by activation of the CB2 receptor (see also Ugdyzhekova et al, 2000).

Smoked cannabis has long been known to be effective in reducing intraoccular pressure (Jarvinen et al, 2002), by an average of about 25%, indicating that cannabinoids may be an effective treatment for glaucoma, which, after cataracts, is the leading cause of blindness in humans. Beilin et al (2000) have shown that IV Dexanabinol significantly reduces intraoccular pressure in rabbits. Naveh et al (2000) showed that topical Dexanabinol reduces IOP in rabbitts as well. Topical doses of the synthetic cannabinoid WIN55212-2, a CB1 agonist, also reduces IOP in some treatment-resistant human glaucomas (Porcella et al, 2001). The IOP-reducing effects of WIN55212-2 are reduced signicantly by pretreatment with the CB1 receptor antagonist SR141716A (Song and Slowey, 2000), which indicates that there are both CB receptor dependent and CB receptor independent effects on IOP. Because the CNS effects of THC will be undesirable for most glaucoma patients, and because of the short time range of IOP reduction with THC, synthetic cannabinoids will probably be of more value in treating glaucoma than plant cannabinoids.

Of course, there are also many therapeutic effects that are dependent upon activation of CB1 receptors, and hence are probably not seperable from the psychoactive effects. A well-known example is the anti-nausea, anti-emesis properties of cannabinoids. Cannabinoids are modestly effective anti-nausea, anti-vomiting drugs, though many patients do not like the side effects (e.g. dizzyness, anxiety, paranoia, orthostatic hypotension) (Levitt et al. 1984; Tramer et al, 2001), and much more effective antiemetic drugs are now available. Research on animal models suggest that the anti-emetic effect is mediated by activation of CB1 receptors in the brainstem (Darmani, 2002; Van Sickle et al, 2001, 2003).

Cannabinoids have proven moderately effective in controlling muscle spasticity and other symptoms of mutiple sclerosis in both human patients and in animal models of MS, such as allergic encephalomyelitits (Consroe et al, 1997; Pertwee, 2002; Smith, 2002; Baker et al, 2000).Wade et al (2003) showed that cannabis plant extracts signficantly improved intractable neurological symptoms including spasticity and neuorgenic pain in a group of patients suffering from multiple sclerosis, spinal cord or brachial plexus injury, and amputation. Cannabinoids may also prove useful in controlling tremors or dyskinesia associated with Parkinson's Disease and other movement disorders (Sevcik, 2000), as has been shown in a marmoset model of Parkinson's Disease (Fox et al, 2002), though it is likely that existing medications will prove to be superior and better-tolerated by most patients. THC has proven effective for reducing tics and other symptoms associated with Tourrette's Syndrome (Muller-Vahl et al, 2002;2003a), without diminishing cognitive performance (Muller-Vahl et al, 2003b).

Refs

Baker et al., 2000. Cannabinoids control spasticity and tremor in a multiple sclerosis model, Nature 404, 84-87.

Beilin et al, 2000. Pharmacology of the intraocular pressure (IOP) lowering effect of systemic dexanabinol (HU-211), a non-psychotropic cannabinoid. Journal of Ocular Pharmacology and Therapeutics 16(3), 217-30.

Consroe et al., 1997. The Perceived Effects of Smoked Cannabis on Patients with Multiple Sclerosis. European Neurology 38, 44-48.

Darmani, 2002. The potent emetogenic effects of the endocannabinoid, 2-AG (2-arachidonoylglycerol) are blocked by delta(9)-tetrahydrocannabinol and other cannnabinoids. Journal of Pharmacology and Experimental Therapeutics 300(1), 34-42.

Facchinetti et al, 2003. Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide. Glia 41, 161-168.

Filbert et al, 1999. Neuroprotective effects of HU-211 on brain damage resulting from soman-induced seizures. Annals of the New York Academy of Sciences 890, 505-514.

Fox et al, 2002. Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease. Movement Disorders 17(6), 1180-1187.

Gallily et al, 1997. Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid. Journal of Pharmacology and Experimental Therapeutics 283(2), 918-924.

Jarvinen et al, 2002. Cannabinoids in the treatment of glaucoma. Pharmacology and Therapeutics 95(2), 203-220.

Knoller et al, 2002. Dexanabinol (HU-211) in the treatment of severe closed head injury: A randomized, placebo-controlled, phase II clinical trial. Critical Care Medicine 30, 548-554.

Krylatov et al, 2002. Increase of the heart arrhythmogenic resistance and decrease of the myocardial necrosis zone during activation of cannabinoid receptors. Ross Fiziol Zh Im I M Sechenova 88(5):560-567.

Krylatov et al, 2002. Endogenous cannabinoids improve myocardial resistance to arrhythmogenic effects of coronary occlusion and reperfusion: a possible mechanism. Bulletin of Experimental Biology and Medicine 133(2), 122-124.

Lavie et al, 2001. Long term cerebroprotective effects of dexanabinol in a model of focal cerebral ischemia. Brain Research 901(1-2), 195-201.

Leker et al, 2003. Drug-Induced Hypothermia Reduces Ischemic Damage. Effects of the Cannabinoid HU-210. Stroke. 2003 Jun 26 [Epub ahead of print].

Levitt et al., 1984. Randomized double-blind comparison of delta-9-THC and marijuana as chemotherapy antiemetics. Proceedings of the American Society for Clinical Oncology 3:91.

Muller-Vahl et al, 2002. Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry 35(2), 57-61.

Muller-Vahl et al, 2003a. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. Journal of Clinical Psychiatry 64(4), 459-465.

Muller-Vahl et al, 2003b. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. Neuropsychopharmacology 28(2), 384-388.

Naveh et al, 2000. A submicron emulsion of HU-211, a synthetic cannabinoid, reduces intraocular pressure in rabbits. Graefe's Archive for Clinical and Experimental Ophthalmology 238:334–338.

Ottani and Giuliani, 2001. Hu 210: a potent tool for investigations of the cannabinoid system. CNS Drug Review 7(2), 131-145.

Parker et al, 2003. Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea. Psychopharmacology (Berl) 166(2):156-162.

Pertwee, 2002. Cannabinoids and multiple sclerosis. Pharmacology and Therapeutics 95(2):165-174.

Porcella et al, 2001. The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. European Journal of Neuroscience 13(2), 409-412.

Sevcik, 2000. Potential role of cannabinoids in Parkinson's disease. Drugs and Aging 16(6):391-395.

Smith, 2002. Cannabinoids in the treatment of pain and spasticity in multiple sclerosis. Current Opinion in Investigational Drugs 3(6):859-864.

Song and Slowey, 2000. Involvement of cannabinoid receptors in the intraocular pressure-lowering effects of WIN55212-2. J Journal of Pharmacology and Experimental Therapeutics 292(1):136-9.

Tramer et al, 2001. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. British Medical Journal 323(7303), 16-21.

Ugdyzhekova et al, 2000. Involvement of central and peripheral cannabinoid receptors in the regulation of heart resistance to arrhythmogenic effects of epinephrine. Bulletin of Experimental Biology and Medicine 130(11):1087-1089.

Van Sickle et al, 2001. Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret. Gastroenterology 121(4):767-74.

Van Sickle et al, 2003. Delta-9-tetrahydrocannabinol selectively acts on cannabinoid (CB1) receptors in specific regions of the dorsal vagal complex to inhibit emesis in the ferret. American Journal of Physioogy, Gastrointestinal and Liver Physiology, Jun 4 [Epub ahead of print].

Wade et al, 2003. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clinical Rehabilitation 17(1), 21-29.

Zalish and Lavie, 2003. Dexanabinol (HU-211) has a beneficial effect on axonal sprouting and survival after rat optic nerve crush injury. Vision Research 43(3), 237-242.

Patrick

ComestibleVenom

""Drug Czar" John Walters — said in December that Canada is "a dangerous staging area for some of the most potent and dangerous marijuana" and that people with no sense of how strong modern marijuana is "seem to be living with the view of the 'reefer-madness' seventies.""
:banghead:

The dangerous thing about marijuana is that it's illegal, it produces black-market money, it exposes youngsters to other drugs and there is a lack of responsible examples for using it. Thanks Mr. Walters for making our fine Canadian pot that much more deadly. (Thanks for all you american boys sending us coke and heroin and guns.)

ComestibleVenom

Dude, where are you getting your information? I want proof of neurotoxicity.

ComestibleVenom

I have a very important question. How much should you use to get a substential oral dose?