ps418

State-dependence is something of a misnomer, since there is AFAIK no drug in which recall is truly state-dependent. It is true however that information learned under one mental state is recalled a bit better under the same mental state; this includes not only cannabis but also caffeine and other stimulants, tobacco, alcohol, scopolomine, and other drugs. 'State-dependent' recall has also been demonstrated for non-drug-induced states. For instance, words learned while riding an exercise bike are better recalled while on the bike than at rest, and vice versa (Miles and Hardman, 1998).


Kelemen and Creeley, 2003. State-dependent memory effects using caffeine and placebo do not extend to metamemory. Gen Psychol. 130(1):70-86.

Miles and Hardman, 1998. State-dependent memory produced by aerobic exercise. Ergonomics 41(1):20-8.

Peters and McGee, 1982. Cigarette smoking and state-dependent memory. Psychopharmacology 76(3):232-5.


Given that marijuana was once thought to cause psychosis, blindness, homocidal rage, brain damage, genetic mutations, and impotence, I'd have to disagree.


Uggh! This brings up a bad memory for me. I used to work with a 40-something nurse. She was a great nurse, very compassionate. One day a patient crashed into her ankle with their wheelchair, fracturing it. She declined to have it x-rayed or seek medical care. That night, it began to hurt worse and worse. She took a prescription pain pill from a year-old prescription. The next day, she couldn't walk at all, and went to the hospital for x-ray. Sure enough, it was fractured. Blood or urinalysis (I dont know which) indicated the presence of the opioid pain pill, as well as THC metabolites. I don't recall how her situatuation turned out in the end, as we lost contact about this time, but she lost her job, was reported to the state board of nursing, and there was some kind of attempt (unsuccessful I think) to hold this woman financially liable for her own medical treatment. Of course, she never smoked pot on the job, never came to work high, and the opioids were from an old but legitimate prescription. This is the same thing that pisses me off about job-related urinalysis, particularly for THC metabolites -- you can't determine from their mere presence whether someone was smoking an hour ago or two weeks ago, yet employers and insurance companies often seem to make such assumptions.

Patrick

ps418

There is a good review of research on the endogenous cannabinoids and cannabinoid receptors. Currently the 2 cannabinoid receptor subtypes, CB1 and CB2, and the endocannabinoids that activate them, are the focus of a lot of research, as targets for various therapeutic applications.
An Overview of the Endogenous Cannabinoid System

For instance, there was an article in Nature Medicine last year that demonstrated that when you inhibit the enzyme that normally breaks down anandamide (an endocannabinoid that activates CB1), this has an anti-anxiety effect in a rodent model. There is also research on cannabinoids looking at how they affect appetite and nausea -- which is good, since there are not many medicines that increase appetite, and many existing anti-nausea medicines are pretty toxic.

Yet other research and development--quite interesting in light of the topic of this thread -- seeks to exploit the neuroprotective qualities of cannabinoids: contrary to past reports that pot kills brain cells, it is now known that both THC and cannabidiol are potent protectors against glumate excito-toxicity, which causes massive brain cell death during ischaemic stroke (Hampson et al, 1998). This effect is not mediated by CB receptors, because the neuroprotective benefits are still seen when the cells have been pretreated with CB receptor antagonists. So, theoretically, a patient beginning a stroke or at high risk for one could be administered THC and/or cannabidiol, plus as CB receptor antagonist, and thus get a neuroprotective effect without actually getting any of the typical psychoactive effects of THC (which are mediated by the CB receptors). Actually, the study in PNAS suggests that cannabidiol may turn out to be much better than anything currently used for this purpose, such as butylhydroxytoluene (BHT), which has tumor-promoting qualities, or NMDA antagonists, which have their own side-effects. Cannnabidiol, in contrast, is quite benign, and not toxic at high doses.

It would not surpise me in the least if in the near future you see a new class of pharms based on endocannabinoid system interactions, much as you se so many new drugs now based on serotonin and dopamine systems.


Hampson et al, 1998. Cannabidiol and D-9 tetrahydrocannabinol are neuroprotective antioxidants. PNAS 95, pp. 8268–8273.

Kathuria et al, 2003. Modulation of anxiety through blockade of anandamide hydrolysis. Nature Medicine 9, pp 76 - 81.

Patrick

Gurdur

Once again I thank blind fate that I do not live in the USA.

Godless Dave

I'm assuming you're referring to your laws on marijuana. What are the laws and enforcement like in Germany? Or are you speculating that new drugs based on cannabinoids will be delayed because of our American anti-pot hysteria?

ps418

Regarding the possibility of an association of cannabis smoking with lung cancer, I learned the following interesting bits of information last night that may explain how cannabis smoke may be much less carcinogenic than tobacco smoke, even on a per-voume basis, despite their overall chemical simularity.

The first bit is that nicotine-- a major component of tobacco smoke that is not in cannabis smoke-- actually inhibits apotosis. This is significant, because tobacco smoke clearly has "genotoxic" properties. So, with tobacco but not cannabis, you get both an increase in mutations in airway epithelial cells, AND an inhibition of cell death, which dramatically increases the probability that some of these cells will incur a set of mutations leading to cancerous cell growth! From West et al (2003):


The second observation, even more interesting, is that, strange as it may seem, cannabinoids have actually been demonstrated to have tumor-supressor properties in vitro, on a variety of cancer types! For instance, Casanova et al (2003) demonstrated that CB1 and CB2 agonists inhibited growth of skin cancers in vitro:

Another study by McKallip et al (2002) showed the same thing for both mouse and human lymphoblastic tumor cells in vitro, using both THC and other CB2 agonists.

Melck et al (2000) showed that the endogenous cannabinoids anandamide and 2-arachidonoylglycerol inhibit growth in vitro of both human breast cancer cells and prostate cancer cells. This affect is mediated by the CB1 receptor, as demonstrated by the use of a CB1 antagonist. The authors did not use THC, but given that THC is known to be a CB1 agonist, it may well have those properties as well.

Refs

Casanova et al, 2003. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest. 111:43-50.

McKallip et al, 2002. Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood 100:627-634.

Melck et al, 2000. Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation. Endocrinology 141:118-126.

West et al, 2003. Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. J Clin Invest. 111(1):81-90.

Patrick

sweep

I'm going to look like a total moron but, with all due respect to mr scientist (ps418) how the hell do you expect me or dozens of other posters to work out where you're at. Talk about assuming knowledge on the readers behalf!



no fair. Call me mr thicko but Western Immunoblotting is about as familiar to lil' ol' me as dog biscuits are to sea urchins. Please, please please, cater for the wider audience and help the laypeople to understand, or perhaps Its time to spend ten grand on a phD.

!QUESTION TIME!>>> dear ps418, I would like to know why it is that my nerves feel as though they're on fire after ingesting lots of hashish? It feels as though all the gates in my brain are open and if I don't relax, I'll pass out. Its really quite scary?????

ps418

The abstracts are included for those want to read them, but I always include a brief synopsis that can be understood by anyone with a basic understanding of neurology and pharmacology: receptors, agonists/antagonists, and so on. If you'd like clarification on something, feel free to ask. But I won't apologize for including detail.


Given the frequency with which you describe adverse reactions, I hope that you will consider ceasing or at least reducing your use of cannabis, particularly if you are "ingesting lots of hashish" as you say. As to your question, I'm not sure what the answer is. Among other possible factors, eating cannabis results in the production of psychoactive metabolites that are not present in the same amounts with smoked cannabis. The prime example is 11-hydroxy-THC, the blood level of which is much higher with oral cannabis than with smoked cannabis.

Patrick

ps418

I'm assuming that this would be a neuron running to my feet along the spinal cord. Assuming that there are axons that reach all the way from my brain to my toes with no synapses, I'd say 6 feet in the longest nerve in my body. If there are synapses along the way, then I have no idea.

Patrick

Koyaanisqatsi

Thanks everyone for all the info!

Does anyone know if "state-dependant" learning was factored in (or factored out) of any of the studies done on memory in regard to pot?

And another "final" question ( ): I've heard it told that THC triggers dormant THC (i.e., that regular users have "stored" THC or "residual" THC from past uses and when that user fires up, they don't need too much--one or two hits--to trigger the THC that is already in their systems).

True or false (old stoner's tale)?

Fascinating stuff, by the way!

ps418

I'm pretty certain that is a myth. THC is metabolized pretty quickly (the blood THC level drops to well-below psychoactive range within a couple of hours), and I don't see how it could be stored in any kind of dormant or reusable state. After all, if you take a chunk of cannabis that is already cured and let it sit out for a few days, it will lose most of its potency due to oxidation. I don't see either how THC could be stored without being broken down, or how it could be remobilized by taking in more THC. If there were such an effect, it should be easy to demonstrate in mice. You could give one group of mice regular, controlled doses, then stop the doses, then give them another, test dose. You could then compare the blood THC levels for the former-stoner mice to the never-stoned control mice, and see if the stoner-mice achieve higher blood THC levels.


Patrick