Once I had a really terrific experience from naloxone exposure while I neither had an opioid in my body, nor a tolerance to them. I had crushed a tilidine 100mg / naloxone 8mg pill, knowing that the naloxone is in there to avoid abuse, but thinking it would only be active when injected. And assuming that, should some of it reach the receptors nevertheless, then it would just block the tilidine.
So I snorted maybe 25mg/2mg (very probably less than that) and after less a minute a surge of strong restlessness, anxiety and dysphoria hit me, senseless tears ran down my face without end. This lasted for 30-45 min. It also 'associated' me with the environment, diminishing the usual distance.
Now, it appears to me that we have little data about the reactions of opioid-naives to naloxone (in contrast to naltrexone which is used for alcoholism too - here I've already wondered about how complete endorphin blockade influences emotions and general mood).
I've found this yesterday (Endogenous and Exogenous Opiate Agonists and Antagonists, Proceedings of the International Narcotic Research Club Conference, 1979):
(Holy shit, they make newborn chicks crying!)
But this clearly states that naloxone has, or can have, strong emotional effects in individuals that never saw any opioid before. Okay, we're not guinea pigs or chicks, but I assume it's not that much different in humans.
Doesn't this implicate that naloxone as a tool to measure opioid receptor mediated effects isn't reliable (like when venlafaxine/mirtazapine were tested for opioid involvement)?
Also I think naloxone has been proven to be an inverse agonist and not a plain antagonist - now it would be interesting to compare naloxone and buprenorphine/samidorphine. Even the latter should render the opioid system inactive, blocking endorphins/enkephalins/dynorphins, but without the effects from inverse agonism- or am I wrong?
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In the time of my naloxone contact I have been on 30mg per day of memantine for impulsivity and ADD, and 150mcg of clonidine at bedtime. Neither of them has any direct opioid receptor involvement but both are effective against opioid W/D. The clonidine should just decrease norepinephrine, so the memantine remains.
I've read repeatedly now that the pharmacokinetics of memantine are in a way that it doesn't act like most NMDA antagonists but specifically against over-active currents (or something like that). Might its NMDA effects, or some other target, lead to increased endorphin activity - making it an indirect opioid agonist and explaining my adverse reaction to naloxone?
This would explain its efficacy in opioid W/D - something I can prove because I've used it at a later time for this and it worked really well. If you ask me, it is maybe the most under-used aid for opioid tapering.
Or am I just overly sensitive to naloxone (how can anyone who ceased drinking and is already tensed and maybe depressive, only stand huge 50mg of naltrexone!?)
So I snorted maybe 25mg/2mg (very probably less than that) and after less a minute a surge of strong restlessness, anxiety and dysphoria hit me, senseless tears ran down my face without end. This lasted for 30-45 min. It also 'associated' me with the environment, diminishing the usual distance.
Now, it appears to me that we have little data about the reactions of opioid-naives to naloxone (in contrast to naltrexone which is used for alcoholism too - here I've already wondered about how complete endorphin blockade influences emotions and general mood).
I've found this yesterday (Endogenous and Exogenous Opiate Agonists and Antagonists, Proceedings of the International Narcotic Research Club Conference, 1979):
(Holy shit, they make newborn chicks crying!)
But this clearly states that naloxone has, or can have, strong emotional effects in individuals that never saw any opioid before. Okay, we're not guinea pigs or chicks, but I assume it's not that much different in humans.
Doesn't this implicate that naloxone as a tool to measure opioid receptor mediated effects isn't reliable (like when venlafaxine/mirtazapine were tested for opioid involvement)?
Also I think naloxone has been proven to be an inverse agonist and not a plain antagonist - now it would be interesting to compare naloxone and buprenorphine/samidorphine. Even the latter should render the opioid system inactive, blocking endorphins/enkephalins/dynorphins, but without the effects from inverse agonism- or am I wrong?
---
In the time of my naloxone contact I have been on 30mg per day of memantine for impulsivity and ADD, and 150mcg of clonidine at bedtime. Neither of them has any direct opioid receptor involvement but both are effective against opioid W/D. The clonidine should just decrease norepinephrine, so the memantine remains.
I've read repeatedly now that the pharmacokinetics of memantine are in a way that it doesn't act like most NMDA antagonists but specifically against over-active currents (or something like that). Might its NMDA effects, or some other target, lead to increased endorphin activity - making it an indirect opioid agonist and explaining my adverse reaction to naloxone?
This would explain its efficacy in opioid W/D - something I can prove because I've used it at a later time for this and it worked really well. If you ask me, it is maybe the most under-used aid for opioid tapering.
Or am I just overly sensitive to naloxone (how can anyone who ceased drinking and is already tensed and maybe depressive, only stand huge 50mg of naltrexone!?)
