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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by linkadge on June 27, 2021, at 16:20:52
I know I've posted on this topic before, but there is a high occurrence of schizophrenia and psychostimulant abuse (particularly amphetamines).
The actions of amphetamine are complex (I don't understand it myself) but they do activate a receptor called TAAR1. Interestingly, TAAR1 activation can actually reduce hyperdopaminergic function (i.e. reduce dopamine). It is hypothesized that amphetamine may for for ADHD via TAAR1 activation.
https://www.pnas.org/content/108/20/8485
Amphetamine is typically seen to increase dopamine, but it does have this action which does the exact opposite. It is complex but interesting.
I am certainly not recommending the use of amphetamine for people with psychotic disorders, but more a thought experiment on exactly what is going on.
TAAR1 agonists actually have antispychotic effects. I wonder if some schizophrenic patients are actually feeling more of the TAAR1 agonist effect than normal people.
Linkadge
Posted by Christ_empowered on June 27, 2021, at 18:38:57
In reply to Amphetamine for schizohprenia?, posted by linkadge on June 27, 2021, at 16:20:52
Schizophrenia is a surprisingly vague diagnosis, at least here in the modern US where I live. I don't think Schizophrenia is quite so ridiculously vague and broad as it was in the 50s and 60s, but...
to be honest, a lot of times the label says more about race, social class, education level, and level of employment (if any) than it does about the symptoms, per se.
which isn't to say that the people so labeled do not need some sort of treatment and/or the whole thing is pseudoscience. Its just...
I could see lots of Schizophrenics prone to bad depression and probably the ones more inclined to drug-induced dysphoria benefiting from a stimulant of some sort. I think the old school solution was Ritalin, back when uppers for Schizophrenia was an OK practice.
these days...I think the Vyvanse people may have funded a small study on low doses of Vyvanse in carefully selected, stable Schizophrenics, but...
other than that, I think uppers in Schizophrenia is an old practice many now frown upon, unless its Wellbutrin or perhaps Provigil now and then. I could be wrong, of course.
Posted by rjlockhart37 on June 28, 2021, at 0:47:31
In reply to Amphetamine for schizohprenia?, posted by linkadge on June 27, 2021, at 16:20:52
dexedrine used to be combined with antipsyotics in the 60s, they were combinatioons and under patents. Thorazine was one that was combined with dexedrine but i don't think it was used paticulary for pshotisis or schizophenia. d-amphetamine maybe it does hit regins of brain to nromal lize dopamine levls without causing psychosis. You would really think dexedrine would worsen psychosis, it does at higher doses same with methamphetamaine, that be a nightmare if d-amphetamine was used at high doses with schizoophenia. But at low doses, it defeinttly can have benefit, like 5-10mg of dextro-amphetamine
Posted by rjlockhart37 on June 28, 2021, at 0:51:18
In reply to Re: Amphetamine for schizohprenia?, posted by rjlockhart37 on June 28, 2021, at 0:47:31
low doses could be benefit because it increaes locomotor activity and if combined with a antipsyhotic (like it was in the 60s, under name brands) it could be benefit. But usally only 10mg of d-amphetamine would be benefit, higher doses cause alteration in behavior and also psychosis
Posted by rjlockhart37 on June 28, 2021, at 0:54:50
In reply to Amphetamine for schizohprenia?, posted by linkadge on June 27, 2021, at 16:20:52
but nothign i wrote describes the article, 10mg of d-amphetamine tablet may be some benefical in schizophenia cases in helping locomotor activity and alertness
Posted by undopaminergic on June 28, 2021, at 5:31:59
In reply to Amphetamine for schizohprenia?, posted by linkadge on June 27, 2021, at 16:20:52
>
> The actions of amphetamine are complex (I don't understand it myself) but they do activate a receptor called TAAR1. Interestingly, TAAR1 activation can actually reduce hyperdopaminergic function (i.e. reduce dopamine). It is hypothesized that amphetamine may for for ADHD via TAAR1 activation.
>
> https://www.pnas.org/content/108/20/8485
>
> Amphetamine is typically seen to increase dopamine, but it does have this action which does the exact opposite. It is complex but interesting.
>That is roughly my understanding too, which is confirmed by the abstract of the article you link to. More specifically, agonism of trace amine associated receptors (TAARs) seems to reduce spontaneous firing of dopamine neurons, but amphetamine still (at least at higher doses) increases post-synaptic dopamine agonism through its dopamine-releasing action. I have often speculated that this reduction of spontaneous firing may, in some cases, be the underlying mechanism behind the so-called paradoxical calming effect of amphetamines in subjects with ADHD.
-undopaminergic
Posted by linkadge on June 28, 2021, at 14:42:10
In reply to Re: Amphetamine for schizohprenia?, posted by undopaminergic on June 28, 2021, at 5:31:59
>be the underlying mechanism behind the so-called >paradoxical calming effect of amphetamines in >subjects with ADHD.
Exactly. Interestingly, mice lacking the TAAR1 receptor, become significantly more stimulated by amphetamine than normal mice. This indicates that activating TAAR1 by amphetamine offsets some of the 'stimulant' effects of amphetamines.
TAAR1 agonists seem like a very interesting target. In mice, they have antidepressant and antipsychotic effects. However, the antidopamingic effects are very region specific. (i.e. the don't induce cataplexy).
In animal models of ADHD, there is actually dopamine overactivity. In those responding to amphetamine, the TAAR1 system may be intact (and perhaps upregulated) and, like you say, the brain is responding with more of an antidopaminergic effect. Of note, antipsychotics are also occasionally used for ADHD, and they apparently work too (although less so for cognition). If ADHD was low dopamine, then they should make things worse.
This may be true too for schizophrenics. Perhaps, in a certain dose range, amphetamines may actually be doing something positive. I remember reading reports of 'bipolar' patients having clear 'antimanic' effects from stimulants.
Perhaps there is a deficiency of endogenous TAAR1 agonists in ADHD (PEA, tryptamine, octopamine, tyramine, thyroid metabolites etc).
Linkadge
Posted by undopaminergic on July 1, 2021, at 7:25:48
In reply to Re: Amphetamine for schizohprenia? » undopaminergic, posted by linkadge on June 28, 2021, at 14:42:10
>
> Exactly. Interestingly, mice lacking the TAAR1 receptor, become significantly more stimulated by amphetamine than normal mice. This indicates that activating TAAR1 by amphetamine offsets some of the 'stimulant' effects of amphetamines.
>I've read that amphetamines reverse the direction of the dopamine transporter, and, as far as I understand it, also the vesicular monoamine transporter. Do you know if these actions have anything to do with agonism at the TAAR1?
> TAAR1 agonists seem like a very interesting target. In mice, they have antidepressant and antipsychotic effects. However, the antidopamingic effects are very region specific. (i.e. the don't induce cataplexy).
>Incidentally, the so-called typical antipsychotics do cause cataplexy, or is it catalepsy? Clozapine does not, even at very high doses, but is considered the gold standard for this class of drugs.
I think a possible explanation as to why TAAR1 agonist do not cause these psychomotor reactions, is that there is a ceiling to their effect, or in other words, their dose-response curve flattens with higher doses.
> In animal models of ADHD, there is actually dopamine overactivity. In those responding to amphetamine, the TAAR1 system may be intact (and perhaps upregulated) and, like you say, the brain is responding with more of an antidopaminergic effect. Of note, antipsychotics are also occasionally used for ADHD, and they apparently work too (although less so for cognition). If ADHD was low dopamine, then they should make things worse.
>Yes, but methylphenidate (and cocaine) help too (of course not in all subjects), and it is not a TAAR1 agonist.
You also need to consider the possible involvement of dopamine autoreceptors.
> This may be true too for schizophrenics. Perhaps, in a certain dose range, amphetamines may actually be doing something positive. I remember reading reports of 'bipolar' patients having clear 'antimanic' effects from stimulants.
>I find that although methylphenidate (and ethylphenidate) stimulates me more than it calms me, it improves my self-control.
> Perhaps there is a deficiency of endogenous TAAR1 agonists in ADHD (PEA, tryptamine, octopamine, tyramine, thyroid metabolites etc).
>Incidentally, selegiline helps in a substantial percent of cases, and one of its primary effects is to increase PEA through inhibition of the metabolism thereof.
Also, I think in addition to reducing the rate of spontaneous firing of dopamine neurons, TAAR1 agonists also increase the amount of dopamine released per firing. Thus each "pulse" is more powerful than in the absence of the TAAR1 agonism. This could be a partial explanation of why these agents help in ADHD. In other words, they may increase the signal to noise ratio.
-undopaminergic
Posted by jay2112 on July 1, 2021, at 12:40:30
In reply to Amphetamine for schizohprenia?, posted by linkadge on June 27, 2021, at 16:20:52
Hi Linkadge:
I don't have schizophrenia, but BP2 with major anxiety. Bipolar is, I think, still a bit of a fully uncharted illness..as is schizophrenia, and with the failure rates of most medications (pdocs,Rx's) who I think, just throw any medication, at high doses, at what they were taught in med school.
But, research is showing that traditional Rx is much a failure. So, after looking at research with microdoses of magic mushrooms (sorry, I don't know the chemical names) Extacy/Molly, and so on, I have been taking two microdoses of Risperdal and Nozinan (a typical antipsychotic) for about a month, along with my regular dose of Effexor (225 mg), and 5mg of amytriptaline, and lamictal for mood stabalization. Plus, 30 mg of Vyvanse, and the result has been, just barely short of amazing.
Ok, yes, it is a lot of meds, but not much more than most I see with bipolar. The thing that sticks out is, the antipsychotics. Doctors plaster their patients with the so-called 'average' dose of Rx's. Those ALWAYS left me with major side effects, in particular, DULL flatness, and ALWAYS, major akathasia. And the thing is, the larger doses, even is Schizophrenia, make patients, usually, have to constantly increase the dose, and constantly change medications because often, of poop out. For me, regular doses also suck me into huge anxiety attacks, panic, and feeling scared. The microdoses have a 'slight' effect of bedtime lite sedation, and a much, much more handle on my anxiety and depression. The Nozinan is about 1 mg *regular 25 and 10mg, and the Risperdal .25mg. (Regular dose... 2-3mg. It's not placebo, because I get a bit of dry mouth after taking them, and I have a tiny bit of shaking in my hands (only lasts for a few seconds).
And, back when I first started psych meds, I had a very good effect on my depression and anxiety with
about 1mg of Nortryptaline, and about same dose of Zoloft. I had forgotten about those.Regarding Stims for Schizophrenia, on the Schiz website discussion boards, I saw MANY people also taking stims, without psychotic episodes. Same on Bipolar boards. Also, there was discussion on here about the microdosing of asenapine (Saphris) benefits, with very consistent positive reviews.
The drug companies seem really lame to this, with really only one example. That was with the tricyclic antidepressant doxepin. Many years recently, they went from 50-200mg as the 'effective' dose. Then, they came out with a new patented dose of 5-10mg's, backed by research. (Silenor).
Seriously, with all of the failures many people with drugs and mental illness, I think this may be a good alternative. We should be researching this more...much more!
Jay
Posted by linkadge on July 1, 2021, at 13:37:38
In reply to Re: Amphetamine for schizohprenia? » linkadge, posted by undopaminergic on July 1, 2021, at 7:25:48
>I've read that amphetamines reverse the >direction of the dopamine transporter, and, as >far as I understand it, also the vesicular >monoamine transporter. Do you know if these >actions have anything to do with agonism at the >TAAR1?
Good question. I don't think the two effects are directly connected. I.e. they have found TAAR1 agonists which do not affect monoamine transporters like amphetamine. However, there seems to be some cross talk between the two mechanisms. Whatever I read is totally above my head. Interestingly, the reverse transport effect though can be blocked by DAT inhibitors (like ritalin) or by PKC inhibitors (like lithium).
>Yes, but methylphenidate (and cocaine) help too >(of course not in all subjects), and it is not >a TAAR1 agonist.
That is true, although some studies link methylphenidate response to an increase in PEA (which is a TAAR1 agonist). Also, some people respond to amphetamine but not ritalin (or vice versa).
Posted by linkadge on July 1, 2021, at 13:41:47
In reply to Re: Amphetamine for schizohprenia? microdoses? » linkadge, posted by jay2112 on July 1, 2021, at 12:40:30
T>hen, they came out with a new patented dose of >5-10mg's, backed by research. (Silenor).
I think Silenor is only approved for insomnia (not depression like doxapin is). But, I totally get your point. There were some studies that showed that 10mg of prozac was as good as 20mg, but with fewer side effects.
I take microdoses of ritalin and effexor. Lately however, I've found that the effexor makes me feel worse and the small amounts of ritalin seem to work well.
Linkadge
Posted by Christ_empowered on July 13, 2021, at 17:15:51
In reply to Re: Amphetamine for schizohprenia? microdoses?, posted by linkadge on July 1, 2021, at 13:41:47
I could see 10-15mgs dexedrine or vyvanse being helpful for some people with some forms of schizophrenia. having said that...
I think it also depends on the tranquilizer. an acquaintance has taken seroquel and adderall for a while now. covers lots of bases, she seems happy-ish. I did better with ritalin while on abilify, to a point (when the ritalin wore off I got all twitchy and said...stopped the ritalin..).
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