Can opioids be neurotoxic?

[Ghaenrynquau]

How neurotoxic are opioids? I heard a psychiatrist say that opioids do not harm the brain like other hard drugs do.

 

[nAON]

They don't seem to cause neurone death in the same way as a massive dose of methamphetamine would. However, if you OD and stop breathing you'll certainly suffer brain damage, and one could argue that psychological aspects such as addiction are a form of semipermanent damage too.

 

[Ghaenrynquau]

They don't seem to cause neurone death in the same way as a massive dose of methamphetamine would. However, if you OD and stop breathing you'll certainly suffer brain damage, and one could argue that psychological aspects such as addiction are a form of semipermanent damage too.

That makes them seem much more acceptable than stimulants. So much talk about mdma neurotoxicity as well.

 

[grue]

I would just like to add to the prior comments that this lack of associated neuronal death except from secondary hypoxia is true of mu-opioid agonism as an activity, not true of every opioid molecule. There are of course opioids which have many other affinities. For example, pethidine, also known as meperidine (Demerol), is extraordinarily promiscuous in its receptor interactions, and seems to possess independent monoaminergic affinities, is an NMDA antagonist, interrupts sodium channels a la cocaine, thus acting as a local anesthetic, and is anticholinergic. More to the point, meperidine metabolizes to normeperidine or norpethidine, which is assuredly neurotoxic, producing convulsions. And I'm not sure why this drug is still used in a medical setting.

 

[WSH]

That makes them seem much more acceptable than stimulants.

Whereas the fact that they cause physical addiction, unlike stimulants, makes them much less acceptable than stimulants.

In my personal opinion opioids are much more dangerous than stimulants.

EDIT: the user markosheehan sent me the following PM:

hi

do you know if opiate use is neurotoxic or does any prmanent brain damage in long term use?

thanks

Here is my reply, since I think that he got his question by viewing this thread, and i also want others to read it and maybe reply to it (e.g when you want me to elaborate on things, eewheer I wrote "comment if you want me to elaborate on that".


I don't think that they cause neurotoxity, at least not in the same way that e.g. methamphetamine does, but quitting opioids cold turkey could cause a hyperstimulation of brain functioning (e.g. glutamate) which at least in extreme cases could lead to neurotoxicity.

And also an overdose that causes oxygen deprivation could of course also cause major neurotoxicity and even death!

So, generally I think that the "best" drugs are the ones that are neither directly nor directly neurotoxic , which leaves out opioids, methamphetamine,

and also cocaine (while it doesn't appear to be neurotoxic [source 1] , it certainly can induce lung damage (source 2 ),

and also ketamine, because it can cause bladder problems (source 3), even if it only causes it at higher doses that are consumed most often daily, the addictive porperties makes it so that this pattern of abuse can be achieved with ketamine, and by analogy, also with other nmda channel blockers [they are technically not antagonists, which classically are orthosteric, so ketamine and the others {e.g. mxe, dxm, ...} are all indirect channel blockers rather than direct nmda-antagonists, like CPP or Selfotel], because i think that the effects on the bladder are caused by the nmda channel blockers themselves, e.g. (anecdotal, but in my opinion still empirical evidence [comment if you want me to elaborate on that.])

Methylphenidate is one of the few drugs that actually doesn't cause almost any kind of toxicity, neither acutely (the LD50 in mice is an INTRAPERTIONIAL INJECTION of 32 mg/kg -> similar ~2400mg (!!!) which are INJECTED INTRAMUSCULARLY in humans, and yes I know abot allometric scaling, but for Methylphenidate you have to use linear scaling, just like with cocaine [source 4] [comment if you want me to elaborate on why allometric scaling is in order for cocaine/methlyphenidate/MDMA and not for drugs like ketamine], and also not chronically, except in extremely high doses [source 5]

[we again have to LINEALLY scale between 10mg/kg in mice -> 750mg again injected INTRAMUSCULARLY in humans, so therefore the statement in the study "chronic MPH usage in mice at doses spanning the therapeutic range in human" is ABSOLUTELY INCORRECT), which isn't very surprising, since it's a PLOS one study, and PLOS one has already PROVED it's at least relative lack of peer reviewing with their psychedelic binding study, which contains DEFINITE mistakes (comment if you want me to elaborate on that) .

However, even methlylphenidate (at higher doses than are used for ADD) can cause "neurophysiological and behavioral sensitization which can induce an addiction that could make it so that doses that actually ARE neurotoxic can be reached.

 

[WSH]

I realized that i had to bump in order to make the thread viewable again by pushing it to the front, to indicate that new content has been added.

I have added much new content in my edit, so i hope it isn't against the rules.

 

[Ghaenrynquau]

Whereas the fact that they cause physical addiction, unlike stimulants, makes them much less acceptable than stimulants.

In my personal opinion opioids are much more dangerous than stimulants.

EDIT: the user markosheehan sent me the following PM:



Here is my reply, since I think that he got his question by viewing this thread, and i also want others to read it and maybe reply to it (e.g when you want me to elaborate on things, eewheer I wrote "comment if you want me to elaborate on that".


I don't think that they cause neurotoxity, at least not in the same way that e.g. methamphetamine does, but quitting opioids cold turkey could cause a hyperstimulation of brain functioning (e.g. glutamate) which at least in extreme cases could lead to neurotoxicity.

And also an overdose that causes oxygen deprivation could of course also cause major neurotoxicity and even death!

So, generally I think that the "best" drugs are the ones that are neither directly nor directly neurotoxic , which leaves out opioids, methamphetamine,

and also cocaine (while it doesn't appear to be neurotoxic [source 1] , it certainly can induce lung damage (source 2 ),

and also ketamine, because it can cause bladder problems (source 3), even if it only causes it at higher doses that are consumed most often daily, the addictive porperties makes it so that this pattern of abuse can be achieved with ketamine, and by analogy, also with other nmda channel blockers [they are technically not antagonists, which classically are orthosteric, so ketamine and the others {e.g. mxe, dxm, ...} are all indirect channel blockers rather than direct nmda-antagonists, like CPP or Selfotel], because i think that the effects on the bladder are caused by the nmda channel blockers themselves, e.g. (anecdotal, but in my opinion still empirical evidence [comment if you want me to elaborate on that.])

Methylphenidate is one of the few drugs that actually doesn't cause almost any kind of toxicity, neither acutely (the LD50 in mice is an INTRAPERTIONIAL INJECTION of 32 mg/kg -> similar ~2400mg (!!!) which are INJECTED INTRAMUSCULARLY in humans, and yes I know abot allometric scaling, but for Methylphenidate you have to use linear scaling, just like with cocaine [source 4] [comment if you want me to elaborate on why allometric scaling is in order for cocaine/methlyphenidate/MDMA and not for drugs like ketamine], and also not chronically, except in extremely high doses [source 5]

[we again have to LINEALLY scale between 10mg/kg in mice -> 750mg again injected INTRAMUSCULARLY in humans, so therefore the statement in the study "chronic MPH usage in mice at doses spanning the therapeutic range in human" is ABSOLUTELY INCORRECT), which isn't very surprising, since it's a PLOS one study, and PLOS one has already PROVED it's at least relative lack of peer reviewing with their psychedelic binding study, which contains DEFINITE mistakes (comment if you want me to elaborate on that) .

However, even methlylphenidate (at higher doses than are used for ADD) can cause "neurophysiological and behavioral sensitization which can induce an addiction that could make it so that doses that actually ARE neurotoxic can be reached.

Please elaborate, why allometric scaling for those stimulants. Thank you very much! Very informative post.

 

[AlphaMethylPhenyl]

Simply put: opioids depress breathing, and breathing rate. As a result, the body doesn't get the oxygen it needs to maintain homeostasis. Hypoxia (oxygen deficiency) will reach the brain, and in time will not provide neruons/glia the nutrition they need to exist. So, yes. Of course this effect is lesser if they're taking it by prescription, versus chasing a high.

 

[adder]

There are plenty of scientific articles on changes in the brain long-term opioid use causes, search "morphine neurotoxicity" in Google Scholar if interested in finding out more. Certain side effects of opioids can appear after long-term use, e.g. opioid-induced hyperalgesia which is an increased pain sensitivity (although this effect may also occur as paradoxical side effect during acute use). I don't know the exact mechanism of this, but certainly it is a result of opioids changing the normal activity of the nervous system so it may be considered a neurotoxic effect going by the definition of neurotoxicity, whether it is reversible or not is a another thing. Similarly, other side effects of opioids that appear at some point during opioid addiction, e.g. anhedonia as a result of changes in the brain areas responsible for feeling pleasure, and persist upon discontinuation long after acute withdrawal or persist despite dose increase can be seen as neurotoxicity as well in my opinion.

I suppose one might debate whether it is easier to recover after heavy methamphetamine or heavy heroin addiction, but both can certainly leave you impaired in different ways for the rest of your life even if you stop taking them for good, that doesn't mean you can't still live a fairly normal life.