Author Topic: Role of cAMP in Opioid Tolerance  (Read 344 times)

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Offline Thetakishi

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Role of cAMP in Opioid Tolerance
« on: September 09, 2014, 12:44:30 am »
Originally posted by Psychomanthis aka Iudicium Infernalum.

Foreword

There are several theories about how opioid tolerance develops. The general consensus is that it is a combination of: Mu-downregulation, cAMP pathway upregulation and some CCK counter-regulatory mechanism that isn't fully understood yet.

Of these three types of countermeasures the human body employs to combat the effects of excess amount of opiates within the CNS. I find the role that cAMP plays most interesting. Therefore i have made this thread in hopes of together with you getting to understand more fully the role that cAMP plays in opioid tolerance development.


This is my understanding of how cAMP and opioid tolerance fit together

cAMP or cyclic adenosine monophosphate is used in the body for signal transduction or more specifically to activate the cAMP-dependent pathway to trigger a signaling cascade used in cell communication. Simply put cAMP helps through certain mechanisms govern the rate at which specific neurons communicate. When you know this it seems logical that the body should employ measures such as cAMP pathway upregulation to combat the effects of opiates. Why, you might ask. Well as we all know opiates/opioids are CNS depressants this means that simply put they decrease the rate of neuron communication. Thus to combat this, the body upregulates the cAMP pathway to increase the rate of neuron communication returning it to a more normal state.


Non traditional approach at decreasing opiate/opioid tolerance

If all i said here is right. (I could be wrong, please correct me if that's the case) we can take counter measures against our bodies defenses, effectively decreasing opiate/opioid tolerance in a non traditional way. To do this we must force cAMP downregulation and i have happend to find the perfect substance to be used to that effect. It is called theobromine, now theobromine is a naturally occuring alkaloid in cocoa beans and a metabolite of caffeine. It is a competative non-selective phosphodiesterase inhibitor. Phosphodiesterase enzymes are responsible for breaking down cAMP so when theobromine is taken cAMP isn't broken down as effectively. The result is that higher than usual concentrations of cAMP will be present within the CNS. Ofcourse the body will react to this by downregulating the cAMP pathway and thus our goal is achieved.

This could be a possible new weapon in our arsenal against opiate tolerance. The trick would be ofcourse to balance down versus up regulation of the cAMP pathway accordingly with enough theobromine to take the role of cAMP in the development of tolerance out of the equation.




Thank you for reading! I hope you found my insights interesting. Also if you have anything to add or if you want to correct me on some points please feel free to do so. It was my intent with this thread to increase our understanding of the topic, so that means me as well. So please feel free to do just that!

Offline Iudicium Infernalum

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Re: Role of cAMP in Opioid Tolerance
« Reply #1 on: September 09, 2014, 12:49:03 am »
Now we need to get a moderator in here to sticky some of these or sticky the resoucre thread when all info if copied.


'When choosing between two evils i always like to choose the one i've never tried before.'

The real psychomanthis.