New PCT Theory

[xtopherrobbins]

I was a pain management patient for a year and now I have low test levels when they were fine before even with cycle. So I was researching the effects of endogenous peptide hormones on the endocrine system because hypogonadism/low testosterone effects up to 74% of people on pain medications. Anyway, I came across some interesting research that I think could benefit PCT and also explains why HCG is suppressive on its own:

Endogenous opioids like endorphin and enkephalins (also exogenous ones like morphine or oxy) potentiate the negative feedback mechanism testosterone has on the hypothalamic/pituitary/gonadal axis.

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC425183/​

Endogenous Opioids Participate in the Regulation of the Hypothalamic-Pituitary-Luteinizing Hormone Axis and Testosterone's Negative Feedback Control of Luteinizing Hormone
http://press.endocrine.org/doi/abs/10.1210/endo-104-5-1286

Inhibition of Luteinizing Hormone Release by Morphine and Endogenous Opiates in Cultured Pituitary Cells
http://press.endocrine.org/doi/abs/10.1210/endo-118-5-2097
​

Furthermore, studies indicate that HCG causes an increase in testicular interstitial levels of both testosterone and β-endorphin. The increased testicular secretion of β-endorphin serves in a paracrine function and travels to the hypothalamus to contribute to the negative feedback of LH secretion in the presence of testosterone. It's a 1, 2 punch to the hypothalamus to signal it to stop the production of LH and ultimately lower testosterone levels (because the body wants balance).

Proopiomelanocortin-Derived Peptides in Testicular Interstitial Fluid: Characterization and Changes in Secretion after Human Chorionic Gonadotropin or Luteinizing Hormone-Releasing Hormone Analog Treatment
http://press.endocrine.org/doi/abs/10.1210/endo-118-1-32​

Anyway, this is where it gets more interesting - the administration of opioid antagonists like naloxone (or oral naltrexone) causes a significant increase in both the amplitude and the frequency of LH secretion.

Naloxone-induced increases in serum luteinizing hormone in the male: mechanisms of action.
http://jpet.aspetjournals.org/content/212/3/573.short

Effect of Endogenous Opioid Blockade on the Amplitude and Frequency of Pulsatile Luteinizing Hormone Secretion in Normal Men
http://press.endocrine.org/doi/abs/10.1210/jcem-54-4-854

Use of naltrexone as a provocative test for hypothalamic-pituitary hormone function
http://www.sciencedirect.com/science/article/pii/0091305786903564​

I think that adding low-dose naltrexone to our regimens could potentially be used on cycle to lessen the shutdown of the HPG axis or possibly be used during PCT to bring your endogenous testosterone back online faster and therefore keeping more of your gains. Food for thought bros. Anyone have any thoughts on this?

 

[Blue_Shine]

Holy shit man. I don't even know what to say to that. I do wanna say that it's really cool to see someone thinking outside the box, I'm a believer in that and I'm sure many here are as well.
From a purely segmental physiological standpoint I can see how you imagine that blocking this pathway could be beneficial. I simply don't have the time or fortitude to detail a clinical explanation that would properly encapsulate the shit peppered avalanche that is waiting you at the end of this rainbow, but I'll leave you with these points:

1. When looking at a research on animal models you have to look at the dosage regiment with respect to human dose per Kg and animal dose per Kg, the the onset, as well as the steady state serum levels of the agent vs the control group. You have to also look into other confounding factors that I can't get into right now.

2. You have to consider that your endopeptide pathways generate your own opioids that take measure in MANY physiological processes throughout the day. Including appetite, sleep, Gastrointenstinal mobility, gastric emptying, reproduction, reward centres and social behaviour. Shutting down a pathway like this with an agent such as naltrexone could be catastrophic, I suggest you look at the potential side effects this drug carries

3. It's very expensive, and highly regulated. Just a thought.

4. I would be very weary of manipulating any hormonal axis that is hard wired into my central nervous system in a way never before experimented on in cellular or animal models.

5. At the end of the day you can be your own experiment, and just go for it. I'm very sorry I don't have the time to go through the publications and point out the obvious problems, and you do have to pick up a lot of education about opioid neurosignaling for any of it to make sense, but since you've come this far, I'm sure you're no idiot, and would make an educated guess either way.

Wish I could help more.

 

[44YOGearHead]

Opiods for PCT? QP of hashish for everybody... ready go! I didn't understand a lick of that as I made a profession out of shooting people for a living, but it sounded cool and expensive as well as dangerous. I like my idea of the smoking hash however.

 

[RickRock]

I'd like to see a lot more data on this before saying that it's a viable option. I'd also like to know what other things might be negatively affected. I do appreciate you sharing this info. Makes for a decent discussion

(PM me for a price list for Biotech Labs and 10% discount)

 

[xtopherrobbins]

Hey guys,

Thanks for the thoughts! I didn't really mean to say that we should all go jump on these drugs now but more so open up a discussion about these pathways since a lot of guys don't really try to understand how AAS works in the body beyond the basics. Plus, I hate to say it but we're no strangers to using unknown compounds with less than favorable side effect profiles. As far as I know SARMs haven't passed clinical testing or been approved for the treatment of a medical condition by any regulatory agency in the world. In the spirit of continuing the discussion though I think I can address some of the things:

1. I looked at the studies referenced above because they were studied in man rather than animals because dosages and effects don't translate well.

2. Low dose naltrexone has shown to be effective in subtherapeutic doses of 5-15 mg/day whereas the typical dose is 100 mg/day and actually sensitizes the body to its own endogenous peptides over time via receptor site upregulation. It also may have an antiinflammatory effect. One thing not addressed by any of the studies I found was if the effect on the hypothalamus is continued over time. It would be possible for the hypothalamus to upregulate receptor sites too and negate the LH effect.

3. Naltrexone is less regulated than AAS and is in the same regulatory class as clomid, nolva, and adex.

4. I think an important takeaway here is that we manipulate hormonal axes all the time and that has cascading signal effects throughout the entire body including the CNS. Androgen receptor activation enhances dopamine signaling in the brain. There's an obvious interaction between testosterone and the opioid pathways that we didn't consider already or we wouldn't see these effects on LH. Some of us use MT II or HGH. MT II is a form of MSH derived from Preopiomelanocortin (which also creates b-endorphin) and has cascading effects on the CNS as well causing changes in mood and libido. We use HGH primarily for its effect on IGF-1 but it hits a lot of other pathways too and is a "dirty" hormone in that sense.

Anyway, I think we just need to be educated about the intricate effects the compounds we put in our bodies have and obviously be open to discussion about it as well. So, yeah, I'm not advocating going out and jumping on these drugs right away but some people do like to be their own guinea pigs I guess haha

 

[xtopherrobbins]

Opiods for PCT? QP of hashish for everybody... ready go! I didn't understand a lick of that as I made a profession out of shooting people for a living, but it sounded cool and expensive as well as dangerous. I like my idea of the smoking hash however.

The opposite haha opioid antagonists, which are basically the complete opposite of opioids. Opioids during PCT will further suppress your natural test production.