CB2 mediated apoptosis of immune cells

[Sturnam]

Recently, I've been talking with someone who has told me that CB2 agonists induce apoptosis of immune cells, specifically T-cells, and that since the thymus is basically done producing T cells at age 14 (IIRC), this can mess with your immune system later in life.

Marijuana has a partial CB2 component, but obviously there isn't any notable immunosuppression, because even heavy users do not develop opportunistic infections. Therefore, any suppression of the immune system is likely 'superficial' and not detrimental to long term health.

My question is regarding the immunosuppressive effects of the 'new' cannabinoids (JWH-018, 073, 250, etc). These compounds are largely full agonists, which means that they will most likely have a greater effect on CB2 mediated apoptosis of T-cells. The person I talked to about this was very insistent that use of these compounds would severely fuck you up, for lack of a better term.

However, some research has determined that these drugs would be beneficial for pain, as well as fighting cancer.
http://www.ncbi.nlm.nih.gov/pubmed/17185040

I personally know of several different trials that are utilizing CB2-selective agonists for a variety of ailments, which to me, hints that these compounds are not as immunosupressive as my friend led me to believe.

Does anyone here have any insight to how detrimental these potent CB agonist could be for the immune system? Is it likely that use of these compounds could produce permanent immune system dysfunction through destruction of T-cells? I understand that I will most likely not get a definitive answer, I'm just looking for someone who has a better understanding of CB2 receptors and the immune system, as well as how 'delicate' the population of T-cells is (i.e. how much destruction of T-cells before noticeable impairments in immune function. For example, Parkinson's symptoms aren't exhibited until >70% neuron loss in the substantia nigra.)

Edit: I realize my example of Parkinson's is not exactly analogous, however, it highlights the issue of distinction between destruction of cells and measurable impairment.

 

[melange]

but would their benefits overshadow their possibly carcinogenic metabolite producing abilities is the question

 

[atara]

It doesn't matter: any such effect is temporary. Increasing the rate of apoptosis of t-cells is easily reversed by not administering a CB2 agonist any more.

Same goes for nicotine inhibiting the apoptosis of lung cells, except, unsurprisingly, if you get cancer before you stop smoking.

 

[Sturnam]

It would matter, assuming it reaches a critical threshold.

T-cells are unique, and each one is capable of binding only one antigen. And after the thymus is done producing T-cells, if you wipe out a T-cell for a certain antigen, you won't be able to mount a proper defense against that antigen because you don't have any T-cell that recognize it. Therefore, although the increase in apoptosis in temporary, the damage is permanent.

Some people will abuse these new cannabinoid agonist like they would marijuana, which means that it could potentially wreck their immune system. And even if they stop, they could have destroyed enough T-cells to be slightly immunocompromised.

The nicotine example doesn't apply because lung cells are non-specific.

 

[Sturnam]

Anyone have any thoughts? I have a feeling that this might actually become an issue, as the new cannabinoid agonists are extremely potent, and seem like they have potential to be more psychologically/physically addictive than marijuana.

There's already one report of an addiction on erowid here, and I feel that more will arise as time goes on.

 

[33Hz]

but would their benefits overshadow their possibly carcinogenic metabolite producing abilities is the question

CB-13 contains 2 naphthalene rings yet it passed animal studies and went on to be tested in human trials. Nowhere is there any mention of it being carcinogenic in mice. I'm assuming if it gave rise to cancers in mice it would have been shelved like pronethalol was, never making it to the human trials stage.

 

[Sturnam]

I appreciate the carcinogenic talk, however that's not what I was asking about...

Any comments on the possible immune system dysfunction induced by these compounds?