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cannabis and neurotoxicity

N

nevada

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Joined
Mar 21, 2010
Messages
38
the documentation about this topic is often confusing and contraddictory:
i hear of thc(or cbd) protecting from mdma neurotoxicity(this finding is very recent btw) and from gluthammate neurotoxicity, inducing neuroregeneration,reducing neurodegeneration in dementia,beeing antioxidants,but i also hear the generation of free radicals, thinning of perfrontal cortex and neuronal apoptosis, and some other things that now i cant recall

every 1 week or 2 there is a new research paper claiming some finding either pro or agains cannabis neurotoxicity

i would like to hear some opinions from the bluelight users here in advanced drug discussion that understand biochemistry and physiology very well, what they think may be the real threat to neurons associated with cannabis(lets suppose eaten or vaporized,excluding toxic smokes) according with the latest findings in scientific research

im sorry if this topic is already covered somewhere else; just made a search and only found a 6 year old topic entirely about this, so decided to start a new one

(PS sorry if the grammar is bad, im not english speaking!!)
 
Ive been smoking marijuana for almost 10 years and im still going. My doctor actually recommends i keep smoking as it helps me with anxiety and my muscle spasm pain. If Cheech and Chong are still going then i think your good. They been smoking since hell knows when lol.
 
nevada said:
i hear of thc(or cbd) protecting from mdma neurotoxicity(this finding is very recent btw)
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That's not all that recent. Conflicting reports on the supposed neuroprotective effects cannabis has on MDMA neurotoxicity, via MDMA induced hyperthermia. There's these:
THC coadministration did not prevent MDMA-induced temperature increase, but it delayed the onset and prolonged the duration of temperature elevation
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http://www.ncbi.nlm.nih.gov/pubmed/19440186
These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.
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http://www.ncbi.nlm.nih.gov/pubmed/20307280

But then there's these:
These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors.
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http://www.ncbi.nlm.nih.gov/pubmed/15081792?dopt=Abstract

THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1) receptor antagonist AM251, neither in CB(1) and CB(1)/CB(2) knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2) cannabinoid antagonist and in CB(2) knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1) receptor, although CB(2) receptors may also contribute to attenuate neuroinflammation in this process.
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http://www.ncbi.nlm.nih.gov/pubmed/20174577

So they haven't really gotten further than this:
The two ecstasy user groups did not differ significantly from each other on any of the measures. Both user groups were significantly worse than non-ecstasy users on measures of associative learning, verbal and visuo-spatial working memory and reasoning. The results suggest that consuming cannabis at the same time as ecstasy does not reduce the likelihood of cognitive impairment.
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http://onlinelibrary.wiley.com/doi/10.1002/hup.777/abstract

the documentation about this topic is often confusing and contraddictory
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It is. But something can be neuroprotective in one place and neurotoxic in the other. Considering cannabinoids have a very complicated pharmacology which is not well understood, you will often see conflicting reports with different outcomes; especially when it concerns cannabis products, which have a bit more than just THC in them. You will also have people saying that it's governments trying to debunk positive results by setting up fraudulent research with negative outcomes, but I think that's silly. Some of the research is bogus (on either "side"), a lot of it isn't.

That it's protective against glutamate excitoxicity is new to me, I haven't read that before. Assumed it was the other way around seeing as GABA-A agonists inhibit glutamate release and cannabis is GABA-A inhibitory, releasing more glutamate. Seems it's a little more complex upon reading that paper. Oh well.

You've probably read this thread as well, but that wasn't really what you were looking for I guess.
 
thanks for replies

the protection from glutamate excitotoxicity is in this paper
http://neuro.cjb.net/cgi/content/full/21/17/6475

and this

http://medicalcbd.wordpress.com/category/glutamate/

here is CBD neuroregenerating nerves
http://www.neuropathie.nu/research-development/cannabinoids-and-nerve-regeneration-or-neuroge.html

but the things that worry me more(because often used by anti drug propaganda)
are thinning of perfrontal cortex
btw after a rapid search i could only find papers about cannabis schizofrenic population and cigarette smoking population: thus if you smoke just cigarettes you may have cortex thinning(just like aging). so cannabis->thinning seems to be not associated with normal population

and hippocampal cells neurotoxicity.in this case i found an article in which is said that the binding by thc to CB receptors induces cell death:

http://www.druglibrary.org/crl/neurological/Chan et.al 98 Neurotoxity_ JNeurosci.pdf

where its also said
"neuron death induced by THC was inhibited by nonsteroidal anti-inflammatory drugs, including indomethacin and aspirin, as well as vitamin E and other antioxidants." so they are antioxidants, but producing oxidants

but even CBD binds to cb1 receptor and the other paper above says it promotes nerve regeneration(without cell proliferation)

so, if you search "CB1 receptor cell death" the first findings are
Cannabinoid Receptor Agonists Protect Cultured Rat Hippocampal Neurons from Excitotoxicity
http://molpharm.aspetjournals.org/content/54/3/459.full
and
CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes.
http://www.ncbi.nlm.nih.gov/pubmed/19942623


here is an article(unfortunately its not free) that says more or less the thruth(in my opinion, after reading all the other things)
Cannabinoids: Between Neuroprotection and Neurotoxicity
http://www.ingentaconnect.com/content/ben/cdtcnsnd/2005/00000004/00000006/art00008

one the thing that i hate, is how anti drug propaganda is manipulating things like the prefrontal cortex thinning(seen even in cigarette smokers) to do this witch-hunt against cannabis

so: eating well or taking anioxidants supplements would block any induced hippocampal cell death
perfrontal cortex thinning,(and lung toxicity) may be avoided just using a non smkeing route of administration(oral, vaporized)
 
To my knowledge, the cannabinoids which have been identified as antioxidants(electron donors) are HU-211, Δ9-THC(specifically the (+) isomer), CBD, CBN, nabilone, and L-nantradol.

Experiments with cultures of rat cerebrocortical neurons have shown CBD to protect against glutamate-induced neurotoxicity, and neurotoxicity mediated by NMDA, AMPA and kainate receptors. Δ9-THC was also effective against AMPA/kainate receptor-mediated toxicity and neither it nor CBD was antagonized by SR141716A. CBD was found to be more neuroprotective than 2 endogenous antioxidants, α-tocopherol(Vitamin E) & ascorbic acid(Vitamin C). Evidence exists also that CBD ad Δ9-THC can protect serum-deprived human B lymphoblastoid cells or mouse NIH 3T3 fibroblasts from oxidative cell death.

A current theory as to why certain cannabinoids such as CBD possess antioxidant activity is because like the established antioxidant tocopherol, they contain a pheonlic OH group and a hydrophobic alkyl side chain. This may explain why cannabinoids such as anandamide and WIN55212-2 lack detectable antioxidant activity, as they also lack those structural features.

Edit - This is just a quick copy/paste from a thread of mine from some time ago. Sorry for being lazy guys :|

Also if you'd like sources just ask I do have them it's just a matter of me finding them.

Edit2.0 - OMG Blowmonkey I have been looking for Bilz0r's paper thank you so much I had it saved on my last hard drive but something happened to it. You're the man. Makes me miss Bilz0r even more now :(
 
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As for cannabis causing neurotoxicity I say no way, no way at all. From personal experience it must help prevent neurotoxicity if anything.
 
Given that cannabis has been used by many millions of people over thousands of years, I really really doubt any surprising new side effects are just suddenly going to be discovered...
 
Dash Riprock said:
Given that cannabis has been used by many millions of people over thousands of years, I really really doubt any surprising new side effects are just suddenly going to be discovered...
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this doesn't make any sense as we now have ways to measure things we didn't before, hence new effects will be discovered.
 
I think I somewhat agree with what I read that magnesium depletion causes neurotoxicity with cannabis or somewhat with it smoked.
Think about the mg depletion thing, if some one is starving to death if they have the hunger increasing thc theyd be just driven more mad, before death by starvation.
 
I'd like to add that NMDA antagonists such as DXM or N20 do offer protection against MDMA induced neurotoxicity.
 
Most of what I've seen thats legit states neuroprotective properties in stroke victims, but then again so are some benzo's. Think "drug induced coma" and you'll get my drift.
 
DJHENRU said:
I think I somewhat agree with what I read that magnesium depletion causes neurotoxicity with cannabis or somewhat with it smoked.
Think about the mg depletion thing, if some one is starving to death if they have the hunger increasing thc theyd be just driven more mad, before death by starvation.
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That makes some sense to me. I've heard that about magnesium too, but supplementing should insure against problems.
 
If cannabis is GABA inhibitory, how does it make people sleepy and relaxed? I have heard that cannabis also affects the interplay between glutamate and gaba, but I'm not really set on the idea that it is gaba affecting. So far that has been a difficult one for me to find a lot of info on. I've also heard cannabis stimulates melatonin release and that makes more sense to me in some ways and also it dopaminergic properties seem to hold up through my experiences, but the gaba thing makes no sense to me.
 
Regenesis2 said:
If cannabis is GABA inhibitory, how does it make people sleepy and relaxed? I have heard that cannabis also affects the interplay between glutamate and gaba, but I'm not really set on the idea that it is gaba affecting. So far that has been a difficult one for me to find a lot of info on. I've also heard cannabis stimulates melatonin release and that makes more sense to me in some ways and also it dopaminergic properties seem to hold up through my experiences, but the gaba thing makes no sense to me.
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i was searching about the GABA - cannabis connection and found this explaination

"While having THC on board and acting in the brain does reduce GABA release from the subset of pre-synaptic terminals that do contain CB1 receptors, this is not nearly as universal of an effect as something that targets GABA receptors. To make this more clear, yes, there are a LOT of CB1 receptors, and they are spread around many parts of the brain. But not all GABA terminals contain CB1 receptors, and not every instance of GABA release is suppressed by THC. This is in contrast to the situation with sleep drugs that target GABA(A) receptors, which are pretty much universally present at GABA synapses."

in second place i think that the sleepiness may be just because of the lowered blood pressure
 
If cannabis is GABA inhibitory, how does it make people sleepy and relaxed?
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This is just something anecdotal but some of the claims for commercial gaba sold as a suppliment is that it can releive depression.

I find this to be actually true; if I eat GABA heavy food or suppliments(we know its reported to not be psychologicly active/ as a depressant*)and I get to sleep but wake up refreshed and definitly not in a depressive mood. I think i find this less so in suppliments becuase food I have is a source of glutamine as well(where the depression thing makes sense.)


Back to cannabis neurotoxicity. I seriously want to know if anyone seems to claim that it can prevent oxygen deprived brain damage through smoke inhilation, or if this itself is maybe the most major reason for conjecture on if it is damamging or not.

Remember, smoke inhilation causes sleepyness.
BUT, I myself have fallen asleep farely quickley after vaporing, and with enough effect to cause my heartrate to increase and see kelidoscopic explosions and the like
(Sobering up, or loosing cognitive "fog" much quicker then I expected!)

*or more so ingested through the stomach
 
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pofacedhoe said:
this doesn't make any sense as we now have ways to measure things we didn't before, hence new effects will be discovered.
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Many things may be changing especially since mj will probably be legal fairly soon. What ever makes more money...pharmaceuticals WILL BE ON TOP probably, unfortunately. We have genetically modified food etc. we have 2 pay a fortune to get organic, I wonder what can,will happen to MJ down the road. One thing for sure high taxes, without benefits, as non pesticides?
 
Well seeing as people are smoking weed more potent than virtually anything before and stupidly large amounts of it, cannabis neurotoxicity or reductions in cognition will be a real concern in the near future.

A quick search on pub med shows that heavy use in adolescents can produce long lasting deficits
 
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