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Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

arctica

arctica

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Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

There's an interesting new read in Cell about how NSAIDs like ibuprofen can both kill your buzz and decrease memory impairment associated with marijuana use.

ETA: Here is a link to the full paper.
 
I should have added that it will kill your buzz and decrease memory impairment if you're a mouse. The rest is extrapolation, but I would be interested if anyone can back these findings up with anecdotal personal experience, i.e., ibuprofen definitely kills my buzz/definitely improves memory issues. I haven't noticed this effect myself, but I don't consume a lot of ibuprofen or other COX-2 inhibitors.
 
ebola? said:
Heh, the study doesn't indicate anything about the mouse's "buzz". :P

ebola
Click to expand...

True, "buzz" was my wording. They used "cataleptic effect" and "hypomotility." Toh-may-to, toh-mah-to. :P

Now the link that was working for me earlier is redirecting back to their "buy this article for $31.50" page, but if you click on the PDF 2.59 MB link from the Abstract page, it sends you to the full article. This might work better: http://download.cell.com/pdf/PIIS0092867413013603.pdf
 
I'm a chronic migraine and chronic muscle tension (in my neck ) sufferer and over the years I've taken vast ammount of NSAIDs Ibuprofan in particular is my remedy of choice and I also use cannabis on a daily basis to treat chronic :
pain/muscle tension/insomnia. Never, ever have I noticed that any NSAID had any effect on my cannabis buzz. I cannot comment on whether or not it had cognitive protective effect or not. But certainly zero effect on the duration of cannabis' effects.
 
arctica said:
True, "buzz" was my wording. They used "cataleptic effect" and "hypomotility." Toh-may-to, toh-mah-to. :P
Click to expand...

But it's unclear how such cataplexy relates to the mouse's subjective experience (let alone those of humans).

ebola
 
I just tried it when the study came out. No effect on buzz, but 400mg Advil reversed the performance reduction on forward digit span I usually get on weed, same as 4g piracetam does.

I still prefer the piracetam a bit, as it intensifies the high too, but I'd call this practical.
 
tweex said:
I just tried it when the study came out. No effect on buzz, but 400mg Advil reversed the performance reduction on forward digit span I usually get on weed, same as 4g piracetam does.

I still prefer the piracetam a bit, as it intensifies the high too, but I'd call this practical.
Click to expand...

You believe it will improve your performance so it did. Get someone to blind you.
 
Yup. Decent idea of a pilot though, and objective measures about performance in those types of basic tests (did you use something like n-back procedures?), and expectations about performance are unlikely to influence their results.

ebola
 
endotropic said:
You believe it will improve your performance so it did. Get someone to blind you.
Click to expand...
ebola? said:
Yup. Decent idea of a pilot though, and objective measures about performance in those types of basic tests (did you use something like n-back procedures?), and expectations about performance are unlikely to influence their results.

ebola
Click to expand...
endotropic said:
Yea I didn't mean to sound so critical, it's a great first step.
Click to expand...

Haha, I actually did do the trial blinded, should have mentioned that, just didn't bother typing it all out. I could tell I which was which during testing very easily though.

Here was the procedure:
-grind 400mg advil tablets, pack into white 000 capsule, place in a small bag with a folded piece of paper saying "Active"
-pack identical mass of baking soda into identical 000 capsule, place in a small bag with a folded piece of paper saying "Placebo"
-take the two identical bags, toss them both behind my back at once, turn around and pick up the one that landed closer to me and consume
-wait 30 minutes, consume a portion of indica cheeba chew with ~40mg THC
-wait 30 minutes, then measure forward digit span (didn't do dual n-back, because I'd mostly used forward span for short term memory previously), could already tell I'd gotten the advil (digit span at 10, close to my baseline)
-sobered up, then repeated with the second bag and an identical portion of cheeba chew, with a resulting forward span of 6
-read the folded paper slips, confirming my suspicions that the first one was active

Only confounding factor is selegiline, which doesn't seem to modulate weed's effects on short term any alone (but does increase the euphoria and dissociation a lot). My baseline forward span is 10-11 ("The magic number seven, plus or minus two" my ass. I'm a freak on the tweak, I guess?) =D
 
Removing hypomotility is evidence that some of the mouse's behaviour was modified. But in order to determine if the mouse liked it we would probably look at effects on self-administration. Self-administration of drugs by rodents is a decent predictor (though not a great one) of subjective experience in humans, but it's not the whole story either: if it really "killed" the buzz we would expect it to remove all or most behavioral effects of THC!

Unfortunately most, if not all, COX-2 inhibitors have worse side-effects than marijuana itself, albeit side-effects which do not include this synaptic depletion: nonselective NSAIDs such as ibuprofen, acetylsalicylate, and naproxen have potentially fatal gastric complications and kill some thousands annually, while currently available COX-2 selective agents, including celecoxib used in the study and rofecoxib (Vioxx®) increase the risk of vascular diseases, including heart attacks. Paracetamol is only weakly anti-inflammatory and may in fact exert its effects via CB1 or some other unknown mechanism. Cannabis is still the safest pharmaceutical analgesic known to humans.

Despite the risk, of course, some people might like this. We could perhaps formalize tweex's protocol and collate results from people who are willing to try it.
 
atara said:
At the appropriate dose, if it is absorbed properly, if it reaches the target in the CNS. These are not trivial considerations: quercetin for example is not absorbed at all, even when massive quantities are consumed.
Click to expand...

I have this extract that is called bcm-95 extract that consists of 95% curcuminoids, supposedly boasting a very high absorption rate. From what Ive read, adding black pepper should increase absorption as well. I know it at least inhibits cox-2 because there is a significant reduction is joint pain when I take it
 
How did you perform the forward-digit span test? Can anyone recommend a good website that does free digit span tests?

tweex said:
Haha, I actually did do the trial blinded, should have mentioned that, just didn't bother typing it all out. I could tell I which was which during testing very easily though.

Here was the procedure:
-grind 400mg advil tablets, pack into white 000 capsule, place in a small bag with a folded piece of paper saying "Active"
-pack identical mass of baking soda into identical 000 capsule, place in a small bag with a folded piece of paper saying "Placebo"
-take the two identical bags, toss them both behind my back at once, turn around and pick up the one that landed closer to me and consume
-wait 30 minutes, consume a portion of indica cheeba chew with ~40mg THC
-wait 30 minutes, then measure forward digit span (didn't do dual n-back, because I'd mostly used forward span for short term memory previously), could already tell I'd gotten the advil (digit span at 10, close to my baseline)
-sobered up, then repeated with the second bag and an identical portion of cheeba chew, with a resulting forward span of 6
-read the folded paper slips, confirming my suspicions that the first one was active

Only confounding factor is selegiline, which doesn't seem to modulate weed's effects on short term any alone (but does increase the euphoria and dissociation a lot). My baseline forward span is 10-11 ("The magic number seven, plus or minus two" my ass. I'm a freak on the tweak, I guess?) =D
Click to expand...

ETA: This could be interesting/entertaining, if we could find a site, come up with a protocol, and have a mod put a poll in the thread...
 
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I have sometimes wondered if marijuana-induced memory impairment produces a short-term antidepressant effect through "enforced mindfulness." It's hard to ruminate about all the bad things in your life while smoking weed because....oh! shiny!
 
I used cambridgebrainsciences.com for the digit span test

arctica said:
I have sometimes wondered if marijuana-induced memory impairment produces a short-term antidepressant effect through "enforced mindfulness." It's hard to ruminate about all the bad things in your life while smoking weed because....oh! shiny!
Click to expand...

This may be a bit of it actually. I think this is most of the therapeutic action of GABA-A agonists for anxiety. I was really just focused on the euphoric/giddy effects, not any "enforced mindfulness".
 
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