Alrightah, haven’t made any decent, contributes in a while so I’ll give an explanation here. A crucial portion of addiction to opiates lies within the over expression of delta fos B (gene) in a portion of the brain known as the accumbens nucleus as well as dysregulation of dopamine transmission (opiates bind to opiate receptors in of the accumbent nucleus, send signals towards dopamergic pathways to release more dopamine, exact mechanism isn’t entirely known I believe, however this may have been updated). An interesting theory is that opiate receptor binding decreases the release of gaba on a receptor level, gaba inhibits dopamine secretion, this theory is plausible as the accumbens nucleus contains gaba receptors. Furthermore, opiates somehow activate the mesolimbic reward system, of which can signal the VTA (part of the brain) to release dopamine (of which would be released into the accumbens nucleus), this would create a sense/ feeling of pleasure, of which certain parts of the brain (involving conditional memory) would come to quickly associate the taking of X substance with the feeling of pleasure and overwhelming bliss.
Withdrawl symptoms of opiates appear to be caused by over expression and dysregulation of insulin receptor substrates (1 and 2 depending on which literature we look at), a decrease in MTORC2 activity (regulates cellular metabolism via interaction between mtor and rictor) and a few others I can’t really remember and can’t be bothered to look for as I’m currently also studying for exams thus this response is required to be somewhat snappy as I’m going back and fourth between tasks. Opiates (well, morphine at least) also unfortunately reduces the size of neuronal soma while consequently increasing neuronal excitability in VTA. Furthermore it’s hypothesized dysregulation of CREB, CAMP/PKA in the locus caerules (or however you spell it) is also likely a major portion of why opiates induce dependence. Similar up regulation of these pathways is also evident with many other drugs of addiction, however typically the up regulation appears to be in the accumbens nucleus with most drugs, as with opiates (not sure if it’s also in the AN but it def occurs in the LC)
Due to the various inhibitory and dysregulative properties of opiates, when discontinued the inhibitory effects of opiates on various genes is gone, excess CAMP is released into the NA (prior to inhibition of enzyme that converts ATP to CAMP occurs), dopamine production goes through the floor, user feels shit… Prolonged use of opiates cause adaptations on a cellular level that prevent the aforementioned inhibitory changes/dysregulations occurring, thus tolerance develops and the same “high” isn’t present, thus higher doses are needed for increased neuronal excitability, dopamine secretion, the same pleasurable feeling some people get.
This is how I understand it anyhow (and there’s far more complex mechanisms involved too of which I haven’t ever read up on)
Sexual dysfunction… Well firstly opiates decrease sensation (they decrease pain, sensation, create a feeling of numbness), a feeling of stimulation is partially involved in achieving orgasm. Secondly opiates (aside from tapentadol and somewhat buprenorphine but tapentadol is the only opiate shown to have next to no effect at all) decrease GNRH production, thus causing a lack in LH/FSH causing secondary hypogonadism (domino effect), idk about you but when I had hypogonadism reaching orgasm became a chore (if I even wanted to jerk off that is). The increased dopamine secretion may increase libido somewhat (as mesolimbic pathways are pivotal for libido and erectile maintenance/achieving a boner), however the lack of ability to feel stimulation (while some is in the mind, I find that I can’t cum from thinking or watching porn without touching myself lol) may be the cause as to why y’all can’t ejaculate while recreationally (or medicinally using) opiates.
Opiates are fucking evvvvilllll, drugs, they can seriously ruin lives if abused (sometimes), I’ve fucking seen drug addiction turn people into complete hollowed out shells of their former selves. While some of it no doubt genetic presdisposition, there is no denying that opiates such as oxycodone, hydrocodone, morphine, diacetylmorphine and fentanyl are probably the most habit forming and depending causing drugs on the planet… Tread carefully if you’re using this stuff (recreationally or medicinally). While I don’t condone recreational use of pain medication, as a matter of fact I think it’s a really bad idea due to the risk of addiction/development of cravings, people will always do these things, thus the best way to go about it (I believe) is to dispense advice catered towards the minimisation of harm while making sure the other party knows you don’t condone or wish to enforce/support their actions in any way or form.
