A meth user with a neuro question

[Dcole461]

So, I know that meth has a very high addiction potential and has completely destroyed many lives. I am also famiiar with the many damaging effects on the body. About me, I am bipolar (type 1) and have been using daily for several months (smoking only). Although I use daily, I do not use meth to get high. I use for the purposes of self medicating (taking away suicidal thoughts that were constant BEFORE my meth usage and having tried unsuccesfully twice, I would prefer meth than putting my parents through that again). Being bipolar, and relatively smart (I'm trying for med school), I thought of how meth is perceived and the research behind it. I won't cite as most of this is considered common knowledge, my question I hope just provokes thought.

Mood disorders are characterized by chemical imbalances (like dopamine) especially in schizophrenia and bipolar mania. Many of the worst side effects of meth (paranoia, delusions, halucinations) are caused by the lack of sleep and would happen to anyone who stayed up for 6 nights in a row. However, I know they can also be caused by high levels of dopamine in the brain as is the case for the aforementioned mood disorders. This is what confuses me.

I know there is research that shows brain scans of meth users are different than normal scans and studies have been done on rats and that meth has been shown to cause possibly irreparable damage to dopamine receptors. However, having bipolar 1 myself, and having seen many psychologists and psychiatrists, not one of them has said anything about damage to dopamine receptors for people with mood disorders (N.B. I am talking about non-substance users with mood disorders). Therefore, I am wondering, if a person is using meth, but not showing signs of psychosis and sleeping nightly, wouldn't that imply that their dopamine levels are below those of someone with schizophrenia or in a manic episode? Hypomania (as in bipolar 2) can cause euphoria without the psychosis of full blown mania so it can't be said that meth still causes damaging increases in dopamine levels as evidenced by the euphoria without saying people with bipolar 2 would have similar brain damage.

I'm not saying meth can't cause brain damage, the neurotoxicity is well established. But I find it odd (on the level of marijuana propaganda from the 50s and 60s) that it is a blanket statement that meth causes brain damage. If you're a heavy user going on week long binges (no judgements here), I can see that level of usage having a very negative effect on the brain Not just from the dopamine, but also increased body temperature, lack of sleep, and probable dehydration (if you've been up for a week, I doubt you've had enough water). If you're a daily user on a maintenance dose, I can't see the anecdotal evidence and personal experience of mood disorders, matching up with what everyone says about the neurotoxicity (again, yes it's been researched, but I feel like they've researched the worst case scenario only and applied it to everyone).

Anyway, does anyone have any thoughts on this? Only on the brain please, no matter what I know stimulants can be hard on the heart and other organs.

 

[kleinerkiffer]

I think this is more suited for Neuroscience and Pharmacology Discussion, so I'm go to move it
OD - > NPD

 

[Cotcha Yankinov]

First for the sake of clarity, meth doesn't actually damage dopamine receptors (they are recycled and replaced all the time) but rather it can damage dopamine nerve terminals with extended use. Also, sleep deprivation itself can cause the brain to flood with dopamine.

Now that being said I think there is a whole lot more to mood disorders than excess dopamine etc. especially concerning schizophrenia where we see all sorts of abnormalities such as brain cells pointing the wrong direction, or decreased volume of overall brain size and prefrontal cortex, and concerning bipolar I believe we see differences in amygdala volumes, anyways my point is essentially there is a lot of thought that was floated around a while ago that depression is due to chemical imbalances and hence boosting serotonin will cure depression and all that jazz, but I think it skips some of the underlying pathology. SSRIs function as antidepressants regardless of whether or not there is a serotonin deficit. And just because excess dopamine causes meth users issues similar to that of issues seen during mania I don't think that necessarily implies there is excess dopamine as the underlying pathology of bipolar patients (though it might be observed).

Meth's neurotoxicity is not mediated through dopamine but rather meth uptake into nerve terminals, so I wouldn't expect to see meth-like neurotoxicity with excess dopamine from mood disorders.

Any questions are welcome, I hope this cleared things up a bit.

 

[Rossak]

First for the sake of clarity, meth doesn't actually damage dopamine receptors (they are recycled and replaced all the time) but rather it can damage dopamine nerve terminals with extended use. Also, sleep deprivation itself can cause the brain to flood with dopamine.

Now that being said I think there is a whole lot more to mood disorders than excess dopamine etc. especially concerning schizophrenia where we see all sorts of abnormalities such as brain cells pointing the wrong direction, or decreased volume of overall brain size and prefrontal cortex, and concerning bipolar I believe we see differences in amygdala volumes, anyways my point is essentially there is a lot of thought that was floated around a while ago that depression is due to chemical imbalances and hence boosting serotonin will cure depression and all that jazz, but I think it skips some of the underlying pathology. SSRIs function as antidepressants regardless of whether or not there is a serotonin deficit. And just because excess dopamine causes meth users issues similar to that of issues seen during mania I don't think that necessarily implies there is excess dopamine as the underlying pathology of bipolar patients (though it might be observed).

Meth's neurotoxicity is not mediated through dopamine but rather meth uptake into nerve terminals, so I wouldn't expect to see meth-like neurotoxicity with excess dopamine from mood disorders.

Any questions are welcome, I hope this cleared things up a bit.

excellent post.... +1 learned from it.

 

[Raysu]

I second that excellent post! I'm curious what the correlation is between the disorders where a speed drug has a calming effect like adderall for people with ADD for example. Could meth in low doses also apply? I can't say I've ever seen anyone calm on meth personally but it seems plausible.

 

[Cotcha Yankinov]

In general processes in the prefrontal cortex function on a non linear curve (upside down U shaped) concerning concentrations of dopamine/norepinephrine, so if you boost dopamine there you'll see an increase in functions like working memory to a point, and then as dopamine concentrations increase further the working memory etc. will get worse. Some people have genes that cause them to express lower levels of dopamine receptors or have too much of an enzyme that breaks down dopamine, so for those people a little extra dopamine might not push them into the dopamine concentration range where working memory etc starts to decay, whereas normal people (without ADHD etc.) will be pushed into the dopamine concentration range where working memory decays much sooner.

How this applies to something like bipolar I have no idea on but I think the prefrontal cortex is very important in regulating the brain so maybe it does have something to do with upside down U shaped curves and such. As I recall meth has relevant serotonin activity so that opens up a lot of possibility although normally SSRIs trigger manic switches for some, but then again reuptake inhibitors and releasing agents like meth can be very different. Wish I knew more about bipolar to be of more service concerning specifically meth and bipolar. Last thing I'll say is that there are situations where dopamine and norepinephrine are inhibitory, and if those inhibitory instances happen to be in important brain areas that are dysfunctional in bipolar but normal in average people then maybe that could explain why something would be normalizing for one with bipolar and stimulating/psychosis inducing for another person.

Any questions are welcome I hope this was helpful

 

[Raysu]

You are awesome at explaining!! Thank you for sharing your wealth of knowledge!

 

[Burnt Offerings]

The exact neurotransmitters responsible for various mood disorders/illnesses (depression, bipolar disorder, schizophrenia etc) have been subject to much discussion...i.e. the varying roles of dopamine, serotonin, GABA, glutamate/NMDA receptors etc etc. Wasn't there even a theory that schizophrenic behaviors were brought upon by an excess of dimethyltryptamine (DMT) in the bloodstream?

Excess dopamine being associated with psychosis is definitely the dominant theory today, I would think. "Amphetamine induced psychosis" is one model for psychosis generally-speaking, and that does involve excess dopamine, but researchers have also made models of psychosis based on other substances, like PCP-induced psychosis (NMDA receptor activity) and LSD/psychedelic-induced psychosis (serotonin receptor activity). Or so I remember reading in an old pharmacology book I had at one point.

 

[aced126]

The idea about PFC processes being related in a non linear upside down U curve fashion is called the Yerkes-Dodson law I believe, if anyone wants to find out more.

 

[serotonin2A]

The idea about PFC processes being related in a non linear upside down U curve fashion is called the Yerkes-Dodson law I believe, if anyone wants to find out more.

The Yerkes-Dodson law shows that arousal and performance have an inverted U-shaped relationship. The finding that D1 receptor activation influences PFC working memory processing with an inverted U-shaped function is not necessarily related to what Yerkes and Dodson observed. There was no reason to believe, when the studies of working memory were performed, that they would find an inverted U-shaped relationship at the single-cell level.

 

[aced126]

The Yerkes-Dodson law shows that arousal and performance have an inverted U-shaped relationship. The finding that D1 receptor activation influences PFC working memory processing with an inverted U-shaped function is not necessarily related to what Yerkes and Dodson observed. There was no reason to believe, when the studies of working memory were performed, that they would find an inverted U-shaped relationship at the single-cell level.

It is not necessarily related, OK, but is it likely related in some way, or is there a link between the 2 observations?

 

[serotonin2A]

Just seeing that two different phenomena have inverted U-shaped dose-responses does not mean they are related. As an example, you can read this on wikipedia:

"A 2007 review of the effects of stress hormones (glucocorticoids, GC) and human cognition revealed that memory performance vs. circulating levels of glucocorticoids does manifest an upside down U shaped curve and the authors noted the resemblance to the Yerkes–Dodson curve. For example, long-term potentiation (the process of forming long-term memories) is optimal when glucocorticoid levels are mildly elevated whereas significant decreases of LTP are observed after adrenalectomy (low GC state) or after exogenous glucocorticoid administration (high GC state)."

So we've been talking about dopamine causing the inverted U-shaped curve. In the review article quoted above, someone else was saying glucocorticocoids are responsible. There are many other effects that are bell-shaped and potentially relevant. So guessing about which neurochemical effect(s) cause Yerkes-Dobson ends up being a catch-all for every bell-shaped effect that is potentially relevant.

So to answer your question, they may or may not be linked. No one knows yet.

 

[Jabberwocky]

If a dopamine releasing agent is helping, you may want to investigate the multitude of legal dopamine releasing agents that are now available, but seem to have a better adverse effect profile.

Regardless of whether you get high or not, smoking meth daily will rot your teeth out of your mouth given enough time (the hydrochloride salt is deposited on your tooth enamel and becomes hydrochloric acid when moistened)