Naloxone, naltrexone and nalmefene instead of hcg on cycle

**stumbras** · 04-01-2007, 04:04 PM

I read this article on **** http://www.****morphosis.com/article...modulation.htm

son why we dont use these anti opioids instead hcg to prevent shutdown

**J*U*icEd** · 04-01-2007, 04:12 PM

naltrexone is an opiate receptor blocker.... its molecules fill the receptors in the brain so that if u do happen to try to get high on opiates while on naltrexone it wont have any effect... what does this have anything to do with HPTA shutdown and testosterone production???

not a good substitue for HCG at all!!

**J*U*icEd** · 04-01-2007, 04:54 PM

seriously stumbras id really like to hear why you feel naltrexone has anything to do with your endocrine system being shut down...

**stumbras** · 04-01-2007, 07:05 PM

Post Cycle Therapy (PCT) is a key component in a steroid cycle, as suppression of the Hypothalamus, Pituitary, Testicular Axis (HPTA) is seemingly unavoidable to a steroid user. What I will be presenting in this article is a new idea to the world of AAS users. This exciting new concept addresses the possibility of limiting and possibly preventing suppression of the (HPTA) during cycle. More specifically, we will learn how we can actively modulate the hypothalamus & pituitary pulse generator during cycle and how this can prime our endocrine system for a quicker, smarter, and healthier recovery from anabolic androgenic steroids (AAS).

For a moment, let’s forget the concept of "post cycle therapy", and embrace the idea of "constant cycle therapy" – active therapy throughout a steroid cycle. The HPTA involves a constant biological interplay of responses and feedback loops that can ultimately become shutdown and degraded during exogenous hormone administration. However, research suggests suppression of the hypothalamus and pituitary may be preventable during steroid use . Before we delve into the details, lets first take a quick recap on the HTPA and how it responses to AAS.

HPTA – The basics

When the hypothalamus senses low hormone levels, it secretes gonandotropin releasing hormone (GnRH). This GnRH then travels a short distance to the nearby pituitary gland to stimulate gonadotrope receptors. These, in turn, secrete the gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). These gonadotrophins travel all the way down to the testis, to activate their respective leydig and seritoli cells. LH initiates testosterone production via the leydig cell receptor (steroidogenesis), while FSH initiates sperm production via the sertoli cell receptor (spermatogenesis).

AAS’s inhibit hormone production just as endogenous hormones do. Testosterone interacts with the androgen receptor (AR) and estrogen interacts with the estrogen receptor (ER). When these hormones are in high concentration, they cause the hypothalamus to decrease its release of GnRH, which decreases LH and FSH production from the pituitary.1 This cuts off the signal to the testis and halts all hormone production. This process is a daily event for the rhythmic endocrine system. Spikes in LH & FSH are followed by spikes in testosterone, and spikes in testosterone result in a reduction of LH & FSH release until testosterone levels decline and LH & FSH is released again. The caveat with most steroids, is that hormone levels remain chronically high (24/7) and do not allow release of LH or FSH, thus leaving the pituitary and testis in a dormant state for as long as the steroids are administered.

While low-dose on-cycle hCG is a good protocol to mimic LH and keep the testis from atrophy, (to be covered in a future article) it does nothing to prevent pituitary atrophy. We forget that the pituitary is susceptible to the same degradation and atrophy as the testis. That is, when the GnRH secretion from the hypothalamus stops (during a steroid cycle), the pituitary reduces its number of GnRH receptors and becomes less and less responsive to GnRH stimulation as weeks pass.11 This is analogous to atrophy of the testis, during absence of an LH or FSH signal. On the same accord, both the pituitary and testis will decrease receptor concentration during over stimulation as well, as its been found from too much hCG use or too much GnRH stimulation.12,13 The point here, is that only minor stimulus is required for preservation of function and sensitivity. Perhaps a completely neglected and suppressed pituitary may explain the lack of full and prompt recovery for many steroid users, despite adherence to a "tried and true" hCG, clomid/nolva regimen. So the question is – How can we prevent suppression of the pituitary, and better yet, how can we prevent suppression of the hypothalamus?

A closer look –

In should be mentioned that another mechanism in which AAS inhibit LH and FSH release from the pituitary is by direct suppression upon the pituitary GnRH receptors and consequent quenching of LH & FSH secretion.35,38 However its appears that AAS which bind strictly to the AR, do not exert a direct negative effect on pituitary function or sensitivity.34,37,39 This agrees with the theory that non-aromatizing steroids such as Primobolan , Proviron or Masteron are not nearly as suppressive as an aromatizing AAS’s such as testosterone or Dianabol . Evidence suggests that estradiol is about 200x more suppressive than testosterone on a molar basis37, and that administration of arimidex can greatly reduce testosterones suppression on GnRH and LH release.42 So, we know anti-estrogens can limit suppression of AAS, but this only solves half the problem.

When it comes to suppression of the hypothalamus, and what seems to be basic endocrinology, we find it is not so simple upon closer examination. There is more than a simple on-off switch for the hypothalamus control center, a lot more. Evidence suggests that there isn’t even a direct AR or ER action upon GnRH release.2-6 That is, steroid hormones do not directly influence GnRH release from the GnRH neurons.7

It was well summarized here by A.J Tilbrook et al,

"It follows, that the actions of testicular steroids on GnRH neurons must be mediated via neuronal systems that are responsive to steroids and influence the activity of GnRH neurons."

And again here by FJ Hayes et al

"It was thus postulated that estrogen-receptive neurons were acting as intermediaries in the non-genomic regulation of GnRH by estrogen"

There is a network of neurogenic intermediaries in the hypothalamus for GnRH release that communicate the inhibitory effects of steroid hormones. More specifically, it is the combined efforts of neuro-active peptides and catecholamines which send the message of "suppression" to the GnRH neurons once activated by steroid hormones.16 These primary messengers are known as a group of neuro-active peptides called endogenous opioid peptides (EOP’s).7,16 The EOP’s consist of the three main peptides -- b-endorphin, dynorphin, and enkephalins, which act upon their respective u-opioid, k-opioid, and s-opioid receptors. It appears that the most influential EOP in GnRH modulation is b-endorphin, acting upon the u-opioid receptor. 8-10 For this reason, b-endorphin will be the main focus of the article, although there are other intermediates involved.

When steroid hormones reach the hypophysial portal, they activate the EOP’s, which suppress GnRH. We know that steroid hormones must communicate with these opioid receptors in order for them to inhibit the release of GnRH from the GnRH neurons, since the GnRH neurons do not have AR or ER receptors. What’s most interesting here is that the suppression on GnRH neurons can actually be intercepted by a u-opioid receptor antagonist – such as naloxone, and the orally active congers naltrexone, and nalmefene.

This is accomplished by blocking the u-opioid receptor and preventing the inhibitory effects of b-endorphin upon the GnRH releasing neuron. It should be noted that this "antagonism" of suppression is not due to antagonism of the AR or ER itself, since u-opioid antagonists to not bind to these hormone receptors.15,32

The effect of a u-opioid receptor antagonist on the HPTA can be seen here --

Essentially, a u-opioid antagonist such as naloxone takes the brakes off of GnRH release and allows pulses of GnRH to occur as if no steroid hormones are present.17 Naloxone, and related u-opioid antagonists have consistently proven to block the suppressive effects of testosterone , DHT, and estrogen administration in both animals and humans.18-25 It also appears that these drugs have the ability to increase pituitary sensitivity to GnRH.26,27

U-opioid antagonists have long been used for treatment of opioid dependence; not only to control cravings of narcotics, but to restore a suppressed endocrine system.28,29 It’s well known that strong opioid based drugs such as methadone, cocaine, heroin and alcohol can suppress GnRH and therefore suppress LH & FSH. It seems that this decease of GnRH is due to the same EOP mechanisms seen with AAS induced suppression.33 In alcoholics, cocaine and heroin users, naltrexone and naloxone have been used to restore LH and testosterone levels.28,29 Naltrexone has even been proposed as a treatment for male impotence and erectile dysfunction.30,31

Naloxone, naltrexone and nalmefene seem progressively more powerful in their potency to dis-inhibit LH release, respectively14,18 Naloxone lacks oral bioavailability therefore injection is required. An injectable preparation could easily be made with BA water due to the water solubility of the compound. A 40mg subcutaneous injection would be a typical dose of naloxone. Naltrexone is orally active, with a safe and effective oral dose being about 100mg for a 220lb male.18 While a lower dose of about 25-50mg of nalmefene would seemingly have the same benefit.20,24 Increasing the dose with either of these drugs will surely increase the likelihood of side-effects without notably increasing the benefit. An every 3rd day protocol would seem appropriate with these drugs, as only to increase GnRH and LH release enough to prevent pituitary and testicular shrinkage – Just enough to keep them in the "ball game". Also, a twice a week dosing protocol would most likely limit the increased opioid sensitivity induced by the long-term use of the drugs.

A word of caution: The opioids antagonists mentioned in this article are recognized as safe and non-toxic at the given dosages, however they can cause severe withdrawal symptoms in opiate users (methadone, morphine, cocaine, and heroin addicts.) Caution is also advised when using opioid antagonists prior to sedation or surgery as they can reduce effectiveness of anesthetics. Temporary nausea, headache or fatigue, are occasional side-effects associated with the use of these drugs. Naltrexone has been reported to heighten liver enzymes, while naloxone and nalmefene do not appear to have this issue. At any rate, a twice a week protocol for 4-16 weeks is unlikely to cause any liver issues that may be associated with naltrexone.

A few point to consider -

For those who choose to embark on a every 3rd day protocol of an opioid antagonist several things should be considered. First, total prevention of HPTA suppression is unlikely in a cycle of 1gm or more per week of AAS. However, by following smart cycling guidelines, suppression will at least be minimized to the point where normal HPTA function could be regained within days of AAS clearance, rather than months. The protocol suggested in this article would at least allow steroid users to limit the usage of classic SERM’s for PCT, as these drugs can have obvious undesired effects. Several things shall be considered when planning an AAS protocol designed to limit suppression.

It appears that progestin based AAS such as trenbolone and nandrolone which bind not only to the AR, but also to the progesterone receptor (PR) also have a directly suppressive effect on pituitary sensitivity36 (similar to estrogens). It also appears that no opioid receptor antagonist or anti-aromatase can prevent suppression via the PR. Therefore, a multiple gram stack of testosterones and nandrolones is no doubtingly going to completely suppress HTPA function by causing suppression via the ER, AR and PR.40,41 If one hopes for a prompt and full recovery post cycle, perhaps nandrolones are better avoided, or at least not stacked with heavily aromatizing AAS without the concurrent use of a strong AI.

As it was pointed out earlier in this article, estrogen has a markedly stronger effect on suppression of LH release compared to androgens since estrogens suppresses the hypothalamus and pituitary. Usage of an AI such as anastrozole, letrozole , or exemestane (Aromasin ) can reduce estrogen and greatly reduce suppression on GnRH, LH and FSH release by preventing excessive ER activation in the hypothalamus and desensitization of the pituitary gonadotropes. 35,37,38 Anastrozole has ~50% maximal total estrogen suppression at 1mg/day. Exemestane has ~50% maximal total estrogen suppression at 25mg/day. While letrozole has ~60% at 1mg/day. These are averages based on compiled data from several studies. Similar estrogen suppression can also been seen from only twice a week administration of these AI’s.43-47

**stumbras** · 04-01-2007, 07:07 PM

This is shorter version:
http://www.****morphosis.com/article...modulation.htm

U-opioid antagonists have long been used for treatment of opioid dependence; not only to control cravings of narcotics, but to restore a suppressed endocrine system.28,29 It’s well known that strong opioid based drugs such as methadone, cocaine, heroin and alcohol can suppress GnRH and therefore suppress LH & FSH. It seems that this decease of GnRH is due to the same EOP mechanisms seen with AAS induced suppression.33 In alcoholics, cocaine and heroin users, naltrexone and naloxone have been used to restore LH and testosterone levels .28,29 Naltrexone has even been proposed as a treatment for male impotence and erectile dysfunction.30,31

Naloxone, naltrexone and nalmefene seem progressively more powerful in their potency to dis-inhibit LH release, respectively14,18 Naloxone lacks oral bioavailability therefore injection is required. An injectable preparation could easily be made with BA water due to the water solubility of the compound. A 40mg subcutaneous injection would be a typical dose of naloxone. Naltrexone is orally active, with a safe and effective oral dose being about 100mg for a 220lb male.18 While a lower dose of about 25-50mg of nalmefene would seemingly have the same benefit.20,24 Increasing the dose with either of these drugs will surely increase the likelihood of side-effects without notably increasing the benefit. An every 3rd day protocol would seem appropriate with these drugs, as only to increase GnRH and LH release enough to prevent pituitary and testicular shrinkage – Just enough to keep them in the "ball game". Also, a twice a week dosing protocol would most likely limit the increased opioid sensitivity induced by the long-term use of the drugs.

**stumbras** · 04-01-2007, 07:20 PM

I think it is worth trying, cuz it is very important issue

**stumbras** · 04-01-2007, 08:23 PM

bump

**stumbras** · 04-02-2007, 08:46 PM

anybody

**Property of Steroid.com** · 04-03-2007, 12:39 PM

Eric (the author of the article) sent me this before it was published on ****. He's a good guy with a good product (he produces Dermacrine, which has been very worthwhile for several people on PCT).

That being said, I don't see this working...I told him that once I read the article...I can see where he's going with it, and it looks alright on paper, in some respects...I guess we'll see if people try it, and we get their results back. Another unfortunate truth is that...well...I don't even know who's going to try sourcing the stuff to give it a go on the word of someone they have never heard of before.

I told him that (industry-wise) it wasn't a great idea to come out with an article like that for his first piece (and certainly not an exclusive piece on a site where he pays to advertise...IMHO, you need to be paid for your time, not the other way around, if you're writing a piece that involved). I'd have liked it more if he was a writer first, got a bunch of industry credibility as such, then came out with his supplement line...you know? I don't know if it will work in reverse, and not sure if it poisons the well to write exclusively for a site that you pay to advertise on...

That being said, I DO think that he cares quite a bit about the consumer/reader, and he has total faith that his idea for opiod antagonists for PCT should work...and I know he produces a worthwhile PCT product also...so...What I'm saying is that the article, at very least, was written in good faith, and HE believes it will work. Regardless of whether this PCT is good or not, Dermacrine (*his nutritional product) works well (from what I've read of the user feedback)....

Who knows? Maybe this method will pan out and I'm wrong. I've been wrong before...

If anyone does happen to try it, drop me an e-mail and let me know how it goes.

**J*U*icEd** · 04-03-2007, 08:19 PM

i tried posting from my internet enabled phone the other day and haven't gotten back to this thread since... i was also going to say that while this looks great on paper i don't see any experimental evidence to support this mans theory... and in reality i don't see this working b/c the mechanisms while in place on paper don't work the way things are stated in that article, im not going to go into the way it wouldn't work right now cause i have to get to work right now and don't have the time or energy to type all that... and if something does arise in somebody trying this out, i don't see people sourcing this sort of drug in the first place.... IMO not a good PCT drug!

**nl5xbb** · 04-04-2007, 04:11 PM

One thing you guys are forgetting is that if you are to take any of those drugs even if you are not opiate dependent you will feel like crap. I mean serious depression and a general feeling of malaise. I have had a room mate accidentally experiment with naloxone injections thinking they were an abusable drug. He ended up feeling quite bad for about an hour and was not an opiate addict. I personally would not trade an easier PCT for feeling that bad for any period of time.

**thebrakes** · 04-04-2007, 05:02 PM

Originally Posted by Anthony Roberts

Eric (the author of the article) sent me this before it was published on ****. He's a good guy with a good product (he produces Dermacrine, which has been very worthwhile for several people on PCT).

That being said, I don't see this working...I told him that once I read the article...I can see where he's going with it, and it looks alright on paper, in some respects...I guess we'll see if people try it, and we get their results back. Another unfortunate truth is that...well...I don't even know who's going to try sourcing the stuff to give it a go on the word of someone they have never heard of before.

do you have any conjecture, clinical data or user feedback to back that up? any whatsoever? what about you, Juiced?

there are clinical trials that do show it works. some lively discussion on some other "smarter" boards (no offense guys, this is just a more traditional board)

**J*U*icEd** · 04-04-2007, 11:21 PM

Originally Posted by nl5xbb

One thing you guys are forgetting is that if you are to take any of those drugs even if you are not opiate dependent you will feel like crap. I mean serious depression and a general feeling of malaise. I have had a room mate accidentally experiment with naloxone injections thinking they were an abusable drug. He ended up feeling quite bad for about an hour and was not an opiate addict. I personally would not trade an easier PCT for feeling that bad for any period of time.

that is totally untrue.... you DO NOT take naltrexone if you are on opiates... you take naltrexone when not opiate dependent... it acts as an opiate blocker... once clean from opiates naltrexone helps keep an addict clean by blocking opiate receptors in the brain from uptaking any opiates into the receptors.... it's kind of like a place holder... if you do happen to take naltrexone while on opiates you WILL GET VERY VERY SICK.... i mean close to death sick... this happens by the following... if you are on opiates and they are flooding the receptors in the brain with opioids and you introduce naltrexone it will push the exogenous opiates out of the receptors putting your body into complete withdrawl.... very very bad...

you should really watch what you post on here... make sure you know what your talking about before posting harmful information to others on this board... you could really cause harm to somebody here with incorrect and unresearched information....

**J*U*icEd** · 04-04-2007, 11:26 PM

Originally Posted by thebrakes

do you have any conjecture, clinical data or user feedback to back that up? any whatsoever? what about you, Juiced?

there are clinical trials that do show it works. some lively discussion on some other "smarter" boards (no offense guys, this is just a more traditional board)

i have very extensive knowledge in the internal medicine field... i was a med student at stony brook university.... the mechanisms may be in place on paper but ive seen the effects of naltrexone and such drugs from a personal view and naltrexone is not a viable PCT drug....

**J*U*icEd** · 04-04-2007, 11:36 PM

i have access to these types of drugs, so just for the hell of it i will use naltrexone the beginning of next cycle (as i will be using HCG the second half)... just to prove firsthand to everybody that this will not do the same job as HCG nor minic the effects of HCG... i will post my firsthand experience with naltrexone... and i can postively guarrentee that naltrexone will not have the same effects....

***perfectbeast2001*** · 04-05-2007, 12:18 AM

Originally Posted by J*U*icEd

i have access to these types of drugs, so just for the hell of it i will use naltrexone the beginning of next cycle (as i will be using HCG the second half)... just to prove firsthand to everybody that this will not do the same job as HCG nor minic the effects of HCG... i will post my firsthand experience with naltrexone... and i can postively guarrentee that naltrexone will not have the same effects....

does this stuff also have the brand name subutex?

**Drummerboy** · 04-05-2007, 12:42 AM

i would like to know more about this....

~DB~

**J*U*icEd** · 04-05-2007, 01:21 AM

Originally Posted by perfectbeast2001

does this stuff also have the brand name subutex?

no subutex is a different type of drug.... subutex is also known as suboxone... whose active ingredient(drug) is called buprenepherin... this is used to help ween opiate dependents off of their opiate of choice...

*please forgive my spelling*

**stumbras** · 04-06-2007, 12:21 AM

Originally Posted by J*U*icEd

i have access to these types of drugs, so just for the hell of it i will use naltrexone the beginning of next cycle (as i will be using HCG the second half)... just to prove firsthand to everybody that this will not do the same job as HCG nor minic the effects of HCG... i will post my firsthand experience with naltrexone... and i can postively guarrentee that naltrexone will not have the same effects....

yep keep us posted, would be great to have real life results

I would try this too, but it is kind a hard to get these meds