Comment · Sat, December 27, 2014 · Ceretropic
Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans (2014)
What they were answering
Ballaticianaire · 3 points
I'm not saying what you're proposing is wrong, I guess I just think it plays less of a role. From what I've seen & read, I feel many people who complain of long-term deficits are just experiencing the attention deficits that are caused, essentially making them more impulsive and less attentive and their working memory is pretty much shit lol.
Eh, it may just be a combination of all these things acting congruently though, there's really no definite answer now. You may be right about the IEG downregulation though.. I mean, the CB receptors are Gi coupled, which would decrease CREB concentrations so that would make complete sense.
I guess I'm also dubious as to deficits too.. this is probably a bit cynical of me, but I think a lot of it is a placebo induced deficit due to the stigma associated with cannabis. I've smoked just about every day (1-2 bowls most days) for over a year and I've noted literally no problem or really much difference than before.
In fact, if anything I think my long-term memory is MAYBE better for the nuances of biology, though I have noted my memory of random day to day events or someone's name (basically non-salient stimuli) has pretty much went to shit. That would make sense with an LTD/pruning hypothesis as well.
PS: semax has been pretty good so far. The attention boost from it is insane. That's the main thing I've noticed, it's seemed to last fo…
u/MisterYouAreSoDumb · Ceretropic
Yeah, there is nothing certain yet. Just be careful basing your assumptions off your individual case. Some people build tolerance to stims much slower than others. That does not mean that long term stimulant tolerance is not a big factor for some. The same goes for marijuana. I have spoken to a lot of people that do have long lasting memory issues with cannabis use. It seems to be a real issue for a subset of people, and probably at least a small issue for most.
http://examine.com/supplements/Marijuana/
Look at section 4.8
The impact on working memory seems to rely mostly on the effects of Δ9THC on astrocytes, as abolishing the CB1 receptor on these cells, but not on glutamatergic or GABAergic neurons, abolishes its negative effects on spatial memory and long term depression (LTD) of synaptic strength between hippocampal synapses.[183] CB1 activation on astrocytes increases their release of ambient glutamate, which activates a particular subset of glutamate receptor on neurons known as the NMDA receptor (NR2B subunit);[183] This activation of NMDA receptors lead to internalization of another type of glutamate receptor on neurons, the AMPA receptor, which leads to synaptic LTD and working memory impairment.[183]
Subchronically (one week of THC infusion at 5-10mg/kg in rodents), it appears that Δ9THC causes a downregulation in NMDA receptor expression (specifically the GluR1, NR2A and NR2B subunits[184][185]). The downregulation is dose- and time-dependent, and is mediated through the upregulation of COX2.[186] The glutaminergic target CREB, whose activation downstream of both NMDA and AMPA receptor activation is pivotal for memory formation[187], has its activation reduced relative to baseline, which may in turn lead to decreased NMDA receptor expression.[184]
This results in a reduction in hippocampal plasticity, which is noted in vitro and seen in vivo with subchronic Δ9THC administration, and is thought to underlie its impairment of memory.[188][184][183]
I was speaking to /u/Silverhydra about it, which is what got me to thinking about the parallels to other tolerances, and IEG expression.
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Glad you are liking the Semax! You need to try N-Acetyl Semax, and see how much it increases the stimulation. Then you will have to try my even newer version. It's not here yet, but I am super excited about it. I only have a small amount coming, just to see if it works. However, I think it will give a similar style increase to the nootropic effect, on top of the stimulation from the acetyl group.