[smart (OP)]

how can Caffeine modulate cannabinoid-induced emotional response to stress?

[chris]

I wasn't aware that caffeine did this? Have you got some references on this?

[smart (OP)]

www.sciencedirect.com/science/article/pii/S0028390808005030

[chris]

That's interesting; I'd not come across that line of work before. They're taking the stance that caffeine helps overcome stress by reversibly manipulating the sensitivity of parts of the endocannabinoid system in the brain to certain neurotransmitters.

However, it's an electrophysiological study, which is something of a leap from what happens when you are dealing with networks containing millions of neurones in real life.

[smart (OP)]

Adenosine is an important neurotransmitter of intrinsic brain activity; Cannabinoid CB1 receptor activation by endocannabinoids modulate emotional response to stress via Adenosine receptors.

Furthermore, caffeine and THC potentiate acetylcholine levels in the hippocampus:

www.ncbi.nlm.nih.gov/pubmed/7752065
 

[smart (OP)]

Adenosine receptor antagonism impair mobilization of intracellular Ca2+ influx induced by anandamide: Caffeine potentiate THC/anandamide effects on stress response.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115444/

[smart (OP)]

Caffeine potentiate CB1 affinity!

[evan_au]

It is interesting that the sciencedirect article suggests that both caffeine & cannabinoids reduce stress.
- But caffeine is a stimulant and cannabis is a depressant.
- So they must have different actions in some other respects.
- I think that having too much coffee can overstimulate people (racing heartbeat, etc) - and withdrawing it after heavy use increases stress.
- Similarly, I suspect that withdrawing cannabis after heavy use would also be stressful
- In many cases, the body attempts to adapt to an external pharmacological disturbance by modifying the production of neurotransmitters or reducing the sensitivity of receptors to return the body to a semblance of "normal". 
- Suddenly removing the external analogue throws the system out of balance (withdrawal symptoms)

I think that sometimes people confuse "coffee withdrawal symptoms" with "the stress of life"; they then wrongly attribute coffee with "relieving stress" when it is actually relieving "coffee withdrawal symptoms". This is a marketing dream - a product which defers the symptoms which it causes!

I imagine that the withdrawal pathways for multiple drugs could have components in common.

[smart (OP)]

It is interesting that the sciencedirect article suggests that both caffeine & cannabinoids reduce stress.
- But caffeine is a stimulant and cannabis is a depressant.
- So they must have different actions in some other respects.
- I think that having too much coffee can overstimulate people (racing heartbeat, etc) - and withdrawing it after heavy use increases stress.
- Similarly, I suspect that withdrawing cannabis after heavy use would also be stressful
- In many cases, the body attempts to adapt to an external pharmacological disturbance by modifying the production of neurotransmitters or reducing the sensitivity of receptors to return the body to a semblance of "normal". 
- Suddenly removing the external analogue throws the system out of balance (withdrawal symptoms)

I think that sometimes people confuse "coffee withdrawal symptoms" with "the stress of life"; they then wrongly attribute coffee with "relieving stress" when it is actually relieving "coffee withdrawal symptoms". This is a marketing dream - a product which relieves the symptoms which it causes!

I imagine that the withdrawal pathways for multiple drugs could have components in common.

Thanks for this info. Yes caffeine intake is a stimulant and using it with cannabinoids (THC) potentiate intracellular cannabinoid receptor 1 (CB1) affinity. Adenosine-CB1 transactivation reduce stress and selectively induce BDNF/TrkB expression. Stress reduction depends heavily on positive adenosine-BDNF feedback loop.

[smart (OP)]

- But caffeine is a stimulant and cannabis is a depressant.

This is incorrect, THC is a antidepressant.

See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866040/