cannabis and Apoptosis

[bartman]

 

[Cursed]

On 6/24/2019 at 3:56 PM, bazil brush said:

love u man!

hey man, ive just watched bartmans video a couple of posts below the one ive just quoted. It explains everything in layman's terms. I'm happy to go a bit more in depth if you want but that video kind of covers lots.

[Cursed]

@bazil brush

 

Ok i've pulled out some of the more interesting stuff specifically about apoptosis. It involves lots of cellular pathways that are pretty boring and long winded but essentially cannabinoids cause different cellular pathways to be activated or change the levels of certain cellular molecules that keep cells alive by altering certain components. Its cellular biochemistry and gets proper confusing

 

Apoptosis:

 

Cell cycle, cancer is basically breakdown in the mechanisms that prevent cells just replicating themselves endlessly. Cells can be arrested in cell cycle phases to stop this so cells can repair the DNA damage they have or go down pathway to apoptosis.

AEA (very structurally similar to thc and apparently has similar effects in high enough doses, now thought to be responsible for runners high) found to arrest breast cancer cell proliferation in the s phase, does this by activating alternate pathways at a cellular level. Doesn’t necessarily lead to apoptosis but likely in some cells. Basically, anandamide stops the cancer cells from growing and dividing.

 

THC blocks breast cancer cell proliferatin by blocking cell cycle in the G2/m phase. Similar thing, binding of THC to cb2 receptors on tumour cells. Buth they found when they blocked the CB2 receptor there was still a mechanism of action, meaning some of the effects of THC are receptor independent. (as an aside here there is work looking for another receptor or other receptors that bind cannabinoids).

 

THC has been shown to induce apoptosis in cancer cells through pathways activated by CB1 binding. Does this by various cellular mechanisms but really interesting is it causes a downregulation of a cellular factor known as survivin. When cells have lots of survivin, they survive (its anti-apoptotic), so reduced tumour apoptosis. THC reduces the levels of survivin and encourages apoptosis. But the paper also reports that the same effects can be gained from certain other CB1 antagonists. So is related to CB1 activation rather than THC itself but THC binds more effectively so it induces a larger effect.

Activation of CB1 and CB2 receptors has shown to increase synthesis and therefore levels of ceramide in some human tumours. Ceramide is proapoptotic and stimulates other cellular pathways that increase the chances of apoptosis.

Also in there it talks about cytotoxic T-cells. These are part of your immune system (type of white blood cell) and clear dead and damaged cells. These have been found to have CB receptors on these cells. Binding of cb2 on these cells causes them to express more CB1 receptors. I'm not 100% sure why ( i havent read up on it and its a bit of a rabbit hole i don't have time to go down right now), but is related to immunological function and their role in clearing dead cells. From another paper on it

  In summary, up-regulation of CB1 in T lymphocytes in response to CBs themselves may facilitate or enhance the various immunomodulatory effects related to CBs.

 

 

I hope some of that answers any questions. if you want more info or a greater detail let me know.

 

Edited June 26, 2019 by Cursed

[JimmyPage]

So how does this impact on glaucoma, which is apoptosis of the optic nerve ?

 

All very well reducing intra ocular pressure with cannabis, but if it's just speeding up the process of going blind, I may have been taking the wrong medicine.

[Cursed]

33 minutes ago, JimmyPage said:

So how does this impact on glaucoma, which is apoptosis of the optic nerve ?

 

All very well reducing intra ocular pressure with cannabis, but if it's just speeding up the process of going blind, I may have been taking the wrong medicine.

 

Not necessarily. They seem to have a modulatory role, so may increase in cancer but decrease in glaucoma

 

receptors and signalling is very complex and intertwined.

 

cannabinoids may increase apoptosis in cancer cells because they are showing other signs of damage i.e. it will increase apoptosis in damaged cells that would either be cleaned anyway or are hiding because of cellular trickery from the tumour.

 

It may be that other signals and receptors In your ocular cells are preventing the increased apoptosis. 

 

Ill have a read up, see what I can find

 

Edited June 26, 2019 by Cursed

[Cursed]

@JimmyPage

 

Quote

 

 

In glaucoma, the final pathway leading to visual loss is the selective death of retinal ganglion cells through apoptosis. Apoptosis is initiated by axonal injury at the optic disc, either by compression and/or by ischaemia. In ischaemia, glutamate is released and activates NMDA receptors. NMDA receptor activation appears to be one of several pathways that result in apoptotic cell death. After activation of NMDA receptors there is an influx of calcium into the cells and free radicals are generated. Substances that prevent this cascade of events and inhibit the retinal ganglion cell death are currently under investigation.

 

Recent studies have documented the neuroprotective properties of cannabinoids. There is evidence that Δ9-THC can inhibit glutamic acid release by increasing K+ and decreasing Ca2+ permeability and that the synthetic cannabinoid HU-211 can block glutamate (NMDA) receptors. These actions are mediated by presynaptic CB1 receptors. Yoles et al, using a calibrated crush injury to adult rat optic nerve (optic nerve axotomy), showed a beneficial effect of HU-211 on injury induced metabolic and electrophysiological deficits. However, the optic nerve crush model may not resemble the mechanisms responsible for glaucomatous nerve damage.

 

Classic cannabinoids such as Δ9-THC, HU-211, and CBD have antioxidant properties that are not mediated by the CB1 receptor. As a result, they can prevent neuronal death by scavenging toxic reactive oxygen species (i.e. free radicals) produced by overstimulation of receptors for the excitatory neurotransmitter, glutamic acid.

 

Cannabinoids have vasorelaxant properties and so might be able to increase the ocular blood flow. The mediator endothelin-1, produced by vascular endothelial cells, has a significant role in the regulation of local circulation, producing vasoconstriction and being involved in the pathophysiological processes of ischaemic and haemorrhagic stroke, Raynaud’s phenomenon, ischaemic heart disease and pulmonary arterial hypertension, among others.65 The possible role of endothelin-1 in the pathogenesis of glaucoma has been suggested. For example, patients with open angle glaucoma may have an abnormal increase in plasma endothelin-1 in response to vasospastic stimuli.66,67 Mechoulam et al61 could demonstrate that 2-arachidonoylglycerol, an endogenous cannabinoid, was able to reduce endothelin induced Ca2+mobilisation, inhibiting vasoconstriction. Thus, cannabinoids may have beneficial properties in ischaemia induced optic nerve damage.

 

 

2 mins of searching and a quick scan found this, i've highlighted the relevant bits (its all interesting so i thought i'd stick it up ) From 2004 so things might have moved on but what they are saying makes sense.

Edited June 26, 2019 by Cursed

[JimmyPage]

@cursed Thanks for that. I'll be honest, I can't read too much about glaucoma - it's a bad headspace and leads to very dark thoughts. Anything else (like MrsJPs MS) no problem.

[Cursed]

no worries man, this is what (roughly) my dissertation was about so i find it really interesting. i don't feel like that's a totally satisfactory answer so i'll do some more searching and see what else i can find.

[Bustin Jieber]

8 hours ago, Cursed said:

no worries man, this is what (roughly) my dissertation was about so i find it really interesting. i don't feel like that's a totally satisfactory answer so i'll do some more searching and see what else i can find.

i hope you grade well, thats jedi level. i bow to you. fremen.