Effects of opioids and dissociative use, tolerance, withdrawal on sex hormones and relation to depression, fitness

[plumbus-nine]

It's generally known and accepted that opioids suppress testosterone in male rats and men, not or less so in women (jealous of that indeed), thus leading to hypogonadism; buprenorphine less so than morphine and methadone, and not just testosterone but general adrenergic insufficiency, that it's directly related to tolerance and that testosterone replacement improves some specific symptoms like weakness, fatigue, loss of libido, anemia, guess muscle wasting and obesity and this is inversed by naltrexone, even low doses appear to help. That a single dose of morphine is enough to cause long lasting suppression, and hyperalgesia, intolerance to coldness. Yet I've never heard of levels being checked in chronic pain or opioid maintenance people, let alone them being offered replacement therapy.

Now a pretty theoretical theory of mine is that NMDA antagonists might actually cause the opposite (I've seen conflicting data, possibly structure and/or dosage related as we have mostly data about anesthesic dosages, also there're differences between the sexes) which I've seen a speculation about here on BL some years ago - it was about arylcyclohexylamines possibly being steroid mimetics - but then still would cause suppression in the long run when the body reacts to stimulation with downregulation.

Do you guys think this might be the explanation for why long term opioid use is depression inducing and which are the mechanisms behind, peripherally or centrally mediated, indirect stimulation or direct agonism etc?

 

[sekio]

Do you guys think this might be the explanation for why long term opioid use is depression inducing

It probably contributes but there is no single explanation. In fact some people on long term methadone therapy tend to be less depressed because it provides stability to your life.

I think a big factor in opioid (ab)use is not the drug itself - generally addicts given free supplies of opioids report less depression and not more - but instead the whole "scene" that comes with it. Having to spend money every day to avoid becoming crippled with withdrawals, dealing with drug dealers (waiting for them, getting ripped off, unreliable quality/quantities, potentially lethal cuts, having to find new suppliers, going to bad parts of the city to cop, etc), hiding use from family/friends, seeing no way out of addiction, spending more time copping/high/sick and less time doing recreational activities, and so on.

Plus even if you do have low testosterone levels, it is easily treatable with medication these days, there is even an oral tablet formulation now.

Yet I've never heard of levels being checked in chronic pain or opioid maintenance people, let alone them being offered replacement therapy.

It does happen (case in point, myself) but generally only if the patient specifically asks for it or if symptoms dictate a test might help. For instance I could regularly sleep 23 hours a day (without any drugs in me) for whole weeks on end - turns out I had the testosterone level of a prepubescent girl. Was it the opioids (I'm on methadone) or was it genetic (father has low T as well)? Maybe both.

I've seen a speculation about here on BL some years ago - it was about arylcyclohexylamines possibly being steroid mimetics

Was it a mention of some of the arylcyclohexylamines being estrogen agonists? I think that was just a SwissTargetPrediction thing. And (despite what some people on this board seem to think) that service just compares homology between known active drugs based on 2d structures. Doesn't do any 3d docking or anything. Basically speaking it's a novelty at best, relying on its "predictions" as the gospel truth is dumb.

The unfortunate reality is arylcyclohexylamines have been highly restricted from medical use thanks to their scheduling as illegal drugs. As a result there is a paucity of studies on their effects in humans. Ketamine is just now becoming available for use outside emergency medicine though so that may change.

I think that if any of the arylcyclohexylamines were active as steroids their activity would have been realized earlier. They did have some use in both veterinary and human medicine after all.

 

[plumbus-nine]

Yeah I know about methadone stabilizing people and find it strange too that in the substitution center where I used to pick my pills up every week, the other folks were all normal weight or even slightly anorexic but nobody was fat like expected from low testosterone - and of these who have some pounds too much, it was tendentially more the women. Never really talked much about others about this stuff or with specially many other substituted people in general though. One woman told me not to get her period anymore since upping the morphine dose. I put on like 10-15kg while on morphine without eating more, before I was slightly underweight and now slightly over but it's all fat while before was all muscle so even more like 15-20kg, and I didn't really eat more than before or more than other people who aren't fat. But have to admit that I was drinking quite heavily during some shorter (2-3 weeks x2-3) periods of time, managed to down a bottle of vodka during 24-36h. But did that before while also using deschloroketamine with much less impact, also that one countered the hangover/withdrawal pretty nicely.

At some point early into substitution, first they tried buprenorphine and was on that for maybe 2 months, together with DCK, I got heavy pain/spasms in my balls. Visited an acute care doc who couldn't find any cause and later another one who prescribed me some antibiotic because he thought I had a sexually transmittable disease even when I didn't have much sex at all or with changing partners so I don't think that was really the cause. Read that people using steroids which suppress the gonads can cause such pain too but it's described as minor. Also lost a good part of my hear, it regrew eventually but read that's a symptom of hormonal changes too. Was in the same time that I was prescribed sodium valproate 900mg/d for what I'm not sure if it really was a manic episode cause I never had such before or after, it was caused by a weird reaction to a weird chemical sold as 3-MeO-PCP (had that before & was pretty different). Unfortunately my ex destroyed it so no analysis.

Plus even if you do have low testosterone levels, it is easily treatable with medication these days, there is even an oral tablet formulation now.

Interesting, there is an orally bioavailable form of testosterone? Or some new medication which improves it?

I needa get my T level checked, have many of the symptoms, specially physical weakness/fatigue, oversleeping without feeling rested, insomnia, no libido, depression/anxiety, low willpower, low self esteem and I don't react to antidepressants anymore.

Agree that much of the stuff around opioid addiction comes from the environment but not all, as I never was in a scene and avoided contact to suspicious individuals, only used meds, RCs, and off the internet. But then again I have been and am in a very depressing social/financial situation and maybe opioid use just increases the vulnerability or decreases the resilience, so that people can be stabilized but need a stable life for that..
Also maybe methadone is different from morphine in that its dextro isomer is a weak NMDA antagonist. Strange that methadone is said to have worse withdrawal than morphine. I found the latter to give me REM sleep movement disorder while methadone didn't and adding memantine to morphine also suppressed it.

The unfortunate reality is arylcyclohexylamines have been highly restricted from medical use

That's a pity yeah. In Europe they had theoretically more freedom because no group scheduling yet but some countries like Germany are catching up & cracking down on RCs now.

I think that if any of the arylcyclohexylamines were active as steroids their activity would have been realized earlier.

We had the rumors about DCK being an antibiotic, or some, or any being such, based on an old patent for DCK but afaik it has never really been proven and people including me abuse the hell out of these derivates but they feel, besides some heavily toxically impure batches, pretty benign physically.

Was it a mention of some of the arylcyclohexylamines being estrogen agonists? I

Not sure, it was here on BL but I don't find the thread anymore. It was about people having superhuman strength on PCP, dunno whether about estrogen agonism too.