• N&PD Moderators: Skorpio | thegreenhand

Perplexed by the relationship of Stimulant Psychosis to Neurotoxicity.

BathedinMercury

Greenlighter
Joined
Jun 14, 2015
Messages
3
I experience amphetamine psychosis at comparatively low doses/ levels of sleep and nutrient deprivation.
I also experience toxic psychosis on methylphenidate. Possibly at even lower doses/ stressors.

I am healthy to my knowledge except for standard issue hand of mental illnesses that are of course always diagnosed as this that and the other (at this point I am not wasting money/time on treatment, with the exception of prescribed stimulants because I "enjoy" abusing drugs, though I do believe a diagnosis of ADHD and Impulse Control Disorder is correct to some extent.) I did lie to this doctor about history of substance use, as well as Bipolar symptoms.

I am an amateur when it comes to neurology and pharmacology but it fascinates me.

If methylphenidate is really Neuroprotectant, than what could this have to do with the mechanism by which stimulant psychosis occurs? Is it less to do with glutamate?

Just curious really.
 
i don't think neurotoxicity has much to do with stimulant induced psychosis

that idea that MPH is neuroprotectant i guess is based on that idea that phosphorylation of monoamine transporters by monoamine releasers such as amphetamine is neurotoxicity, and in a setting where MPH was administered together with amphetamine, MPH would bind to some transporters and prevent them from being phosphorylated, therefore protect agains amphetamine's neurotoxicity. someone correct me if i'm wrong

now, methylphenidate doing this doesn't have anything to do with how likely or not it is to induce psychosis. i believe we don't often see cases of MPH-induced psychosis because it is not very common and a very short-lasting stimulant when compared to, for example, methamphetamine, which is the first drug that comes to my mind when you say 'stimulant psychosis', and i believe it is due to its long duration leading to long binges and lots of sleep and nutrient deprivation.

if it was all about dopamine, we'd see people going psychotic from a very high dose of stimulants alone, but these things tend to happen more like on the 3rd day consecutively awake or so.

i don't know what could be the conclusion from the fact that you went psychotic with low doses of stimulants, other than that you probably should avoid them.

take this with a grain of salt, i'm not formally educated on the subject...
 
i don't think neurotoxicity has much to do with stimulant induced psychosis

Ditto on that. Psychosis is a tangible phenotypical expression, e.g. if you don't see it yourself being the observer from which you as a subject undergoes mental divergent challenges, others *can* see it. Neurotoxicity is something that others can't even see/observe unless it is empirically observed on the level of the brain as the minds object. (Getting rather Cartesian there, speaking more like a philosopher than a molecular biologist, but that suits my mood as late.)
 
Was there not an experiment done where people were injected with high doses of methamphetamine to determine if psychosis was caused more by high dosage than by sleep deprivation and other stress on the system? I think a few of the subjects experienced induced psychosis immediately after being injected.
 
Interestingly enough, towards the end of a 2-3 day binge the other day I was psychotic (visual, auditory true hallucinations) but lucid enough to test the hollow mask optical illusion. I did not fail to detect the illusion as it is said that schizophrenics are unable to do. A friend of mine is diagnosed with schizophrenia/schizoaffective disorder and does not fail to detect the illusion either. I wonder why that is?
Just a musing.
 
Was there not an experiment done where people were injected with high doses of methamphetamine to determine if psychosis was caused more by high dosage than by sleep deprivation and other stress on the system? I think a few of the subjects experienced induced psychosis immediately after being injected.

i'd like to read about this... i was under the impression that stimulant psychosis had much more to do with sleep dep./other stress combined with the heightened levels of dopamine and paranoia/alertness induced from stims rather than very high levels of dopamine alone. i have no experience with stimulant psychosis but i have done obscene shots of cocaine and methylphenidate and i don't think i got not even a bit more psychotic, just high a f

Interestingly enough, towards the end of a 2-3 day binge the other day I was psychotic (visual, auditory true hallucinations) but lucid enough to test the hollow mask optical illusion. I did not fail to detect the illusion as it is said that schizophrenics are unable to do. A friend of mine is diagnosed with schizophrenia/schizoaffective disorder and does not fail to detect the illusion either. I wonder why that is?
Just a musing.

that's interesting. i did not think stimulant psychosis had anything in common with chronic psychotic illnesses other than paranoid delusions and the like. that is, we know that schizos are able to tell the hollow mask and have higher semantic priming and these things (and so do people on psychedelics!) but i didn't think people on the third day of a meth binge would have these charachteristics too.

if that is the case, then stimulant psychosis is more similar to schizophrenia than i had thought. your report is only anedoctal though... i'd like to see other people's thoughts on this...

EDIT: wait a minute OP you and your schizophrenic friend WERE able to tell the illusion? well that's what in fact happens, average people get fooled by the illusion and schizos don't. perhaps you are a little bit on the schizo edge OP lol stay away from the stimulants man...
 
Last edited:
This is a couple years old --- > Potential adverse effects of amphetamine treatment on brain ...

For me there were times upon inducement of drug, but more so with sleep deprivation. I would see shadow people, images etc out of corners of my eyes, electric… dark and moving flashes, then they would disappear.

Of course it also depends on AXIS I disorders and trauma involved prior to use, and I would say environment used in.
 
Last edited:
Psychoses disorders and schizophrenia-like disorders are truly the two most perplexing (neuro)psychiatric abnormalities I know.

Nobody knows shit about their etiology or even if they're part of a spectrum of disorders or individual conditions.

Moreover, such numerous and disparate stimuli can mimic these disorders, which greatly complicates any attempt to attribute them to this or that area of the brain or this or that neurotransmitter. For example, psychotics or schizophrenics can be indistinguishable from mentally healthy people affected by any one of the following:

Sleep deprivation
NMDAR antagonists
κOR agonists
acute stress
major depression
bipolar disorder
5HT2A receptor agonists
Deliriants
alcohol withdrawal
excessive use of psyhostimulants
dementia
borderline personality disorder
various neurodegenerative disorders and diseases
pervasive developmental disorders
schizoaffective disorder
certain kinds of brain damage

And the list goes on and on. So many drugs that are vastly pharmacologically different—PCP, cannabis, alcohol, methamphetamine, nicotine, atropine, LSD, Salvinorin A, butorphanol, and so on—all effect the brain in different ways, yet are nonetheless classified as 'psychotomimetic' or 'psychotogenic', in sufficient quantities.

Nobody knows jack shit about psychosis and its related disorders. They may not even exist, like dozens of mental 'disorders' since time immemorial of which we now know had no basis in reality, which is precisely why the erstwhile psychiatrists tried so damned hard to understand them but failing all the way—the very thing they'd wished to find never existed to be found.
 
So many drugs that are vastly pharmacologically different—PCP, cannabis, alcohol, methamphetamine, nicotine, atropine, LSD, Salvinorin A, butorphanol, and so on—all effect the brain in different ways, yet are nonetheless classified as 'psychotomimetic' or 'psychotogenic', in sufficient quantities.

Almost none of the drugs you listed of are actually classified as being psychotomimetic. The exceptions are LSD and PCP. Chronic use of methamphetamine can cause symptoms that overlap with paranoid schizophrenia, but acute methamphetamine use is not psychotomimetic. Salvinorin and butorphanol may be listed as psychotomimetics by some authors, but that is really because "psychotomimetic" is sometimes used as a synonym for "hallucinogenic".

Nobody knows jack shit about psychosis and its related disorders. They may not even exist, like dozens of mental 'disorders' since time immemorial of which we now know had no basis in reality, which is precisely why the erstwhile psychiatrists tried so damned hard to understand them but failing all the way—the very thing they'd wished to find never existed to be found.

You are entitled to your opinion but almost everyone else in the word, including many schizophrenia patients, believes that it is a real disorder. Psychiatrists certainly haven't made as much progress as they would like in understanding schizophrenia but you are wrong if you think the disorder doesn't exist.
 
Almost none of the drugs you listed of are actually classified as being psychotomimetic. The exceptions are LSD and PCP. Chronic use of methamphetamine can cause symptoms that overlap with paranoid schizophrenia, but acute methamphetamine use is not psychotomimetic. Salvinorin and butorphanol may be listed as psychotomimetics by some authors, but that is really because "psychotomimetic" is sometimes used as a synonym for "hallucinogenic".

Psychotomimetic drugs are drugs that have a potential to cause psychotomimesis (psychosis mimicking effects). It is not synonymous with hallucinogen, rather hallucinogens are a subset of drugs within the super set of psychotomimetics. Hence, all hallucinogens—including psychedelics, dissociatives, deliriants, and some obscure others—are psychotomimetic as far as the bailiwicks of medicine, psychiatry, psychology, and the demesne of behavioral health, etc., maintain.

1.) Cannabis, especially infused into foodstuffs, is as psychotomimetic as one wants; simply eat enough of the laced edibles and you'll produce bona fide psychotomimesis.

2.) Alcohol in large quantities is patently psychotomimetic. I'm an inveterate souse; I know from experience. When one gets into liberally quaffing libations as if lemonade—you take a drink, then the drink takes a drink, then the drink takes you, as some author someplace once indited—the product is tantamount to a brief psychotic episode.

3.) Methamphetamine: stimulant psychosis tout court.

4.) Nicotine is a psychotomimetic, but not in cigarette-sized quantities. Have you never smoked uncured tobacco?

5.) Atropine goes without saying.

6.) κOR agonists, such as Salvinorin A and butorphanol, are psychotomimetic.

But, you're entitled to your opinion...

You are entitled to your opinion but almost everyone else in the word, including many schizophrenia patients, believes that it is a real disorder. Psychiatrists certainly haven't made as much progress as they would like in understanding schizophrenia but you are wrong if you think the disorder doesn't exist.

I didn't say no disorder existed. Rather, I said schizophrenia and psychoses may not exist.

Your argument is equivalent to the following:
Person A has epilepsy. Person B is convinced person A is possessed by some evil spirit and tries to cure Person A by ridding him of the supposed spirit. Person C says that there is no evil spirit and therefore the therapy is all wrong for person A. Person B then argues for the existence of the evil spirit by pointing to Person A's obviously poor condition.

But person C never said nothing was wrong with person A ; rather he doesn't believe person B's assertion that person A is possessed.

I am to person C, as you are to B, and the psychotic is to A.

My belief is that the reason the accessible pharmacotherapies only treat some but not all symptoms of schizophrenia (only the positive symptoms respond to contemporary pharmacotherapies, whilst the negative symptoms are unaffected) is because the drugs were created and employed on erroneous notions and unrealistic hypotheses about what schizophrenia is and what abnormal neural, cognitive, structural, physiological, or chemical mechanisms are at play in the schizophrenic's brain that causes and maintains schizophrenia in the individual? We know it's genetic and epigenetic in origin. But we don't know what these genetic and epigenetic anomalies do, other than cause schizophrenia.

Until then, schizophrenia will be treated experimentally as it always has been, with no one knowing what the fuck they're supposed to do other than dole out the most expensive pharmaceuticals from the companies that pay the largest kickbacks.
 
Last edited:
Was there not an experiment done where people were injected with high doses of methamphetamine to determine if psychosis was caused more by high dosage than by sleep deprivation and other stress on the system? I think a few of the subjects experienced induced psychosis immediately after being injected.

(And I'm one of them. No I wasn't in said study, but I can vouch for this occurring to me.)
 
Psychotomimetic drugs are drugs that have a potential to cause psychotomimesis (psychosis mimicking effects). It is not synonymous with hallucinogen, rather hallucinogens are a subset of drugs within the super set of psychotomimetics. Hence, all hallucinogens—including psychedelics, dissociatives, deliriants, and some obscure others—are psychotomimetic as far as the bailiwicks of medicine, psychiatry, psychology, and the demesne of behavioral health, etc., maintain.

1.) Cannabis, especially infused into foodstuffs, is as psychotomimetic as one wants; simply eat enough of the laced edibles and you'll produce bona fide psychotomimesis.

2.) Alcohol in large quantities is patently psychotomimetic. I'm an inveterate souse; I know from experience. When one gets into liberally quaffing libations as if lemonade—you take a drink, then the drink takes a drink, then the drink takes you, as some author someplace once indited—the product is tantamount to a brief psychotic episode.

3.) Methamphetamine: stimulant psychosis tout court.

4.) Nicotine is a psychotomimetic, but not in cigarette-sized quantities. Have you never smoked uncured tobacco?

5.) Atropine goes without saying.

6.) κOR agonists, such as Salvinorin A and butorphanol, are psychotomimetic.

But, you're entitled to your opinion...



I didn't say no disorder existed. Rather, I said schizophrenia and psychoses may not exist.

Your argument is equivalent to the following:
Person A has epilepsy. Person B is convinced person A is possessed by some evil spirit and tries to cure Person A by ridding him of the supposed spirit. Person C says that there is no evil spirit and therefore the therapy is all wrong for person A. Person B then argues for the existence of the evil spirit by pointing to Person A's obviously poor condition.

But person C never said nothing was wrong with person A ; rather he doesn't believe person B's assertion that person A is possessed.

I am to person C, as you are to B, and the psychotic is to A.

My belief is that the reason the accessible pharmacotherapies only treat some but not all symptoms of schizophrenia (only the positive symptoms respond to contemporary pharmacotherapies, whilst the negative symptoms are unaffected) is because the drugs were created and employed on erroneous notions and unrealistic hypotheses about what schizophrenia is and what abnormal neural, cognitive, structural, physiological, or chemical mechanisms are at play in the schizophrenic's brain that causes and maintains schizophrenia in the individual? We know it's genetic and epigenetic in origin. But we don't know what these genetic and epigenetic anomalies do, other than cause schizophrenia.

Until then, schizophrenia will be treated experimentally as it always has been, with no one knowing what the fuck they're supposed to do other than dole out the most expensive pharmaceuticals from the companies that pay the largest kickbacks.

I am sorry, but your facts are incorrect.

1. Cannabinoids do not mimic the symptoms of psychosis. Clinicians can easily differentiate between the symptoms of THC intoxication and those of schizophrenia. The term "psychotomimetic" was thrown around a lot in the 1950s and 1960s and is no longer a preferred term. At the time, it was another name for "hallucinogen", but it fell out of use because it has a negative connotation, and focuses only on one aspect of the drug experience. The term does still see some use, primarily in cases where a drug is used to model the symptoms of schizophrenia. Serotonergic hallucinogens mimic some of the positive symptoms of schizophrenia, and NMDA antagonists mimic some of the negative symptoms and cognitive deficits. This is determined using objective criterea, primarily rating scales used to measure symptom severity on schizophrenia. In those studies, DMT and ketamine produce schizophrenia-like symptoms, but cannabinoids do not.

2. What you wrote about alcohol is complete nonsense. Schizophrenia is associated with specific positive and negative symptoms, none of which are induced by alcohol. The state that you described occuring with alcohol has nothing in common with either the positive or negative symptoms of schizophrenia. Alcohol can produce excitement, relaxation, reductions in reaction time, sedation, minor euphoria, cognitive impairment, progressing to anesthesia -- none of which is a specific symptom of schizophrenia.

3. Stimulant psychosis is not an acute effect of methamphetamine. It is a product of neurochemical changes that occur in response to continued use of the drug, combined with exhaustion.

4. I have used high doses of nicotine, and it is certainly very psychoactive, but not in a way that specifically mimics the symptoms of schizophrenia. There is actually evidence that nicotine reduces the symptoms of schizophrenia.

5. Atropine does not mimic the symptoms of schizophrenia. It is a delerient, and it mimics the symptoms of confusional delirium, which is not the same as schizophrenia. No psychiatrist would mistake a scopolamine overdose for schizophrenia.

6. Kappa agonists cause hallucinations, but that does not necessarily mean they psychotomimetic. The experiences people have with salvinorin don't seem to closely track with the experience of schizophrenia patients. You can't treat all hallucinations equally. No one has specifically examined how closely kappa effects match up with the symptoms of schizophrenia. Until someone tests that there is no way to say for sure.

Regarding your comment about schizophrenia, we may not fully understand why the illness occurs, and current treatments may not be fully effective, but that has no bearing on whether or not schizophrenia is an illness. The illness either exists or it doesn't. The fact that we do not understand everything about the illness is due to our rudimentary understanding of the brain and the fact that there are probably numerous minor factors that contribute to the development. But that has no bearing on whether it is a reall illness. The same could be said in the past about the flu or AIDS, but they are still real diseases. You could even make the argument that because schizophrenia is probably a developmental illness, with very disturbed cell functioning and/or connectivity, it is not suprising that medications only have limited efficacy. If the brain is not wired correctly, then just tweaking some neuromodulatory receptors is not going to fix everything.
 
Last edited:
I was under the impression the best drugs for modelling schizophrenia are PCP and the other dissociatives.
 
^ NMDA antagonists certainly are the best approximation, but they primarily model the negative symptoms. On the other hand, serotonergic hallucinogens can more effectively mimic the positive symptoms, but that ends up being more of a model of the acute psychotic state (which occurs early in the disease progression). This makes sense, because the acute psychotic state is primarily when visual hallucinations occur.
 
I was under the impression the best drugs for modelling schizophrenia are PCP and the other dissociatives.

Hmm id have to say the pseudo hallucinations i have gotten from sub anesthetic or anesthetic doses of IV Ketamine where really so absurd that i could tell they where not real. The longest i ever used Ketamine for was about a week and although i felt abit weird after i ran out i was hardly anything near psychotic. I have only taken PCP once and id have to say it was far more like DXM then ket. Though as i was paralyzed from it after smoking way too much i couldn't really do anything about the slightly paranoid hallucinations i was having.

I have gotten psychosis from IV coke/Crack after only maybe a day of use where as with Dextroamphetamine it took a good 3 days of very heavy use to induce a near psychotic breakdown. After 3 months of IV Coke use my personality had changed to the point where my friends where noticing it and it took months to recover from that.
 
All of the stimuli Nom listed model some aspects of psychotic disorders. No pharmacological model replicates endogenous psychosis accurately enough that a trained psychiatrist couldn't distinguish the two.

I'll just leave this here (they address pretty much every point of contention in this thread): Drug models of schizophrenia.

tl;dr
Drug models of schizophrenia said:
Dopaminergic psychostimulants provide a good
model of the paranoid psychosis of schizophrenia
but do not accurately mimic the cognitive or negative
symptom domains [Pratt et al. 2012]. Use of
dopaminergic models to predict the efficacy of
novel therapeutics is likely to select only the medications
that primarily act on dopamine transmission.
In contrast, NMDA receptor antagonists
and THC both generate a more complete model
of schizophrenia, including aspects of the positive,
negative and frontal cognitive symptoms [Krystal
et al. 1994; Morrison et al. 2009; Morrison and
Stone, 2011; D’Souza et al. 2004].
 
All of the stimuli Nom listed model some aspects of psychotic disorders. No pharmacological model replicates endogenous psychosis accurately enough that a trained psychiatrist couldn't distinguish the two.

I'll just leave this here (they address pretty much every point of contention in this thread): Drug models of schizophrenia.

tl;dr

There HAVE been cases where PCP intoxication has been diagnosed as schizophrenia. I don't have the actual case reports handy, but this quote is pretty clear: "...noncompetitive antagonists of the NMDA subtype of glutamate receptors, including PCP and ketamine, produce a behavioral syndrome in healthy humans that closely resembles symptoms of schizophrenia and is frequently misdiagnosed as acute schizophrenia." (REF 1).


Nom didn't say the drugs model schizophrenia, he said they mimic schizophrenia. Modeling schizophrenia, vs. actually mimicking the symptoms of the disorder, are very different things. There are several criteria for determining the validity of models of a psychiatric illness (REF 2). For the purposes of this discussion - -what most people think "psychotomimetic" means -- the only type of validity that matters is face validity. As an example, amphetamine-induced hyperactivity has been used as a model of schizophrenia because the effect can be blocked by haloperidol, but no one would argue that the fact that amphetamine induces hyperactivity means that it should be classified as a psychotomimetic drug. Hyperactivity is not a symptom of schizophrenia. Schizophrenia models can be heuristic even if they lack face validity.



The review you posted is relevant to models of schizophrenia, but again, a drug can be a good model without actually being psychotomimetic. To quote directly from the review:

p. 50: "the effects of salvia divinorum may not be particularly representative of schizophrenic psychosis, since participants describe entering other realms and meeting entities or beings [MacLean et al. 2013] and this is rarely reported in schizophrenia." Given that statement, would you really argue that Salvia can accurately be called a psychotomimetic drug?

p. 51: "drugs affecting GABAergic and cholinergic receptors are less likely to directly induce psychosis-like effects in healthy volunteers"

The situation with alcohol and nicotine is pretty clear. They simply do not mimic the symptoms of schizophrenia. With THC, there is some evidence of psychotomimetic effects. But does that actually warrant classifying it as a psychotomimetic drug? The answer to that question is still up for debate. Although there are some similarities, there are also significant differences. It has also been argued that THC-induced sedation may be producing false-positive results in some tests designed to measure negative symptoms.


Ref 1 = "Neuropsychopharmacology: The 5th Generation of Progress" p. 695.
Ref 2 = http://www.acnp.org/G4/GN401000076/CH.html
 
Last edited:
3. Stimulant psychosis is not an acute effect of methamphetamine. It is a product of neurochemical changes that occur in response to continued use of the drug, combined with exhaustion.

This is not entirely true. I have experienced acute stimulant psychosis from a massive meth overdose and it manifested within a few hours of taking about 500mg dextromethamphetamine in the span of 3 hours, with very little tolerance. Also very very pure pseudo-made crystal.

It messed me up....I mean full blown psychosis and paranoid hallucinations and real shadow people. Not the shadow shadow but actual hallucinations that looked real and interacted with me and freaked me the fuck out and it lasted almost 4 days. So it was before any sleep deprivation or lack of food or anything. But generally it does take some time to get that bad of stim psychosis and it does not model all or even perfectly model some of the sympts of schizophrenia.
 
This is not entirely true. I have experienced acute stimulant psychosis from a massive meth overdose and it manifested within a few hours of taking about 500mg dextromethamphetamine in the span of 3 hours, with very little tolerance. Also very very pure pseudo-made crystal.

It messed me up....I mean full blown psychosis and paranoid hallucinations and real shadow people. Not the shadow shadow but actual hallucinations that looked real and interacted with me and freaked me the fuck out and it lasted almost 4 days. So it was before any sleep deprivation or lack of food or anything. But generally it does take some time to get that bad of stim psychosis and it does not model all or even perfectly model some of the sympts of schizophrenia.

If you took a massive overdose of methamphetamine then your experience has little relevance to understanding the acute effects of meth. Overdoses of a variety of substances can produce delirium and symptoms of toxic psychosis. If present at high enough concentrations, methamphetamine probably binds promiscuously to many receptors that it would not normally interact with. The other thing to consider is that you may actually have been experiencing a psychotic break, rather than methamphetamine inducing psychotic-like symptoms. The fact that your symptoms lasted for 4 days suggests that you may have been experiencing endogenous psychosis.

When I am saying that methamphetamine is not a psychotomimetic drug, I am specifically referring to the acute effects of the drug, given at normal doses. I would think the distinction between methamphetamine, and drugs like PCP and LSD, would be fairly obvious here. Methamphetamine doesn't reliably induce psychosis-like symptoms, and so classifying it as a psychotomimetic drug doesn't accurately describe its effects.

Second, in some ways it seems more like methamphetamine is inducing a particular type of psychosis. That is very different than producing an acute pharmacological effect that mimics the symptoms of schozophrenia.
 
Last edited:
Top