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Treating substance abuse disorder - self destructive behaviour?

JohnBoy2000

Bluelighter
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May 11, 2016
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Not for myself.

I'm just curious.

There was recently a court case held an account of a man accused of attempted murder; name Jon Koppenhaver.
Was a UFC fighter.
His girlfriend was a pornographic actress - Christy Mack - the victim.

He had a long history of impulsive violent outbursts, and a traumatic childhood - his mother a junkie, his father died in his arms whilst he attempted to revive him with CPR.
He said he made it through is childhood by being effectively fostered by a gym owner - then wrestled and lifted weights, almost as an occupation, ultimately becoming a professional fighter.

He had described that, his mother had spent his college fund on drugs - his mother and her boyfriend - so he beat her boyfriend to an inch of his life.

Several other assaults followed - two stints in prison.
He actually beat up an entire room full of pornstars, including his then pornstar girlfriend (different from Christy Mack), for flirting with other male actors at a party for performers.

Ultimately now looking at a life sentence in prison for beating up his following pornstar girlfriend, Christy Mack, and her then boyfriend.


In Stahls book - he emphasizes that, childhood trauma can often give rise to neuronal malfunction.
It can trigger or induce bipolar or schizophrenia.

He also mentions that, a huge percentage of those who suffer neuronal malfunction - due to dopamine imbalances in the reward pathway in the limbic system, can often exhibit substance seeking hahaviour - drugs, binge drinking, nicotine and marijuana etc - as these can secondarily incite DA release in the mesolimbic DA channel - compensating for that neuronal deficiency.


The case described above - I assume could be classified as perhaps the induction of somewhat manic phases brought about by stress or provocation - the guy gets angry basically - and has violent outbursts, even he himself can't control.


A young dude - about 23 years old, recently moved into my shared accommodation.

He exhibits clear and obvious drug seeking behaviour.
He drinks constantly, takes illicit drugs constantly.
When he doesn't drink alcohol - he attempts to pacify his craving by constantly drinking tea.

He has described terrible trauma in his childhood also - like truly crazy.


So - my question.

Pharmacologically - these types of situations - and I can think of many more - how are they treated?

Can that impulse to trigger DA in the reward channel via substance abuse - can it be soothed, via any pharmacological approaches?

The aggressive outbursts and violence - can they be controlled - perhaps if they were likened to manic phases of bi-polar - they would be treated with anti-psychotics as mood stabilizers, and perhaps GABA'ergic type drugs?


Is there a pharmacological type treatment for these conditions?
 
Its probably important to note the role that chronic traumatic encephalopathy (boxer's pugilistica/dementia) can play a major role in violence and erratic behavior seen in former sports people. The orbits of the eye sockets are very effective at impacting the orbitofrontal cortex and doing some serious harm.

The other thing to realize is that chronic stress during a developmental phase is going to impact the development of the PFC, which would normally inhibit erratic/impulsive behavior. If someone has PTSD specifically, some of those symptoms can be treated with b2 antagonists (propranolol) because of the role the amygdala plays and its b2 expression, but exposure therapy and CBT is still kinda the mainstay. Maybe MDMA therapy will be the mainstay someday for PTSD.

I think antipsychotics and mood stabilizers are known to help control violent outbursts. But side effects yada yada.
 
The aggressive outbursts and violence - can they be controlled - perhaps if they were likened to manic phases of bi-polar - they would be treated with anti-psychotics as mood stabilizers, and perhaps GABA'ergic type drugs?

I wouldn't call antipsychotics "mood stabilizers", they only work against mania but not against depression, therefore a true mood stabilizer would be better.

Valproate would be an excellent choice:

To date, there are no definitive methods of treating dopamine dysregulation syndromes in PD patients. We sought to uncover an effective treatment option for future study. We report a series of 3 PD patients with ICDs who were effectively treated with valproate

Valproate for the treatment of medication-induced impulse-control disorders in three patients with Parkinson's disease.

dopamine dysregulation syndrome seems to be a very good model for what you're describing:

Hypomania, manifesting with feelings of euphoria, omnipotence, or grandiosity, are prone to appear in those moments when medication effects are maximum; dysphoria, characterized by sadness, psychomotor slowing, fatigue or apathy are typical with DRT withdrawal.[4] Different impulse control disorders have been described including gambling, compulsive shopping, eating disorders and hypersexuality.[4] Behavioral disturbances, most commonly aggressive tendencies, are the norm. Psychosis is also common.[4]

So if Valproate works for that, then it should also work for the similar case study that you've desribed.
 
So a GABA enhancer.

Downregulation of the activating transmitters?

In terms of substance seeking behavior - downregulation of DA - could that potentially exacerbate the problem?

And one thing I've always wondered.
Dopamine agonists - could they compensate for the impulse to ingest substances that will activate DA release in the limbic system?

Schizophrenic patients are known to seek these substances but, wouldn't them substances exacerbate their positive symptoms and counter the effect of DA blocking anti-psychotics?

Can dopamine agonists induce psychosis, like prolonger AMP use??
 
PS - the dude in my house took MDMA last night, and he was still drinking like a fish today - so whilst it may be effective for PTSD, substance seeking behaviour?
Not so much, I don't think.

He got up this morning and told me he was gonna start drinking again.
I gave him a couple Solpidine - marketed here as analgesics, with a small opioid action, codeine.
He said it eased his hangover, but he still felt like drinking.
 
I wouldn't call antipsychotics "mood stabilizers", they only work against mania but not against depression, therefore a true mood stabilizer would be better.

Valproate would be an excellent choice:



Valproate for the treatment of medication-induced impulse-control disorders in three patients with Parkinson's disease.

dopamine dysregulation syndrome seems to be a very good model for what you're describing:



So if Valproate works for that, then it should also work for the similar case study that you've desribed.

Is
it possible that, for that initial case of violence I described that, sertonergic enhancing agents, could exacerbate the violent impulses?
 
Something I just wrote elsewhere that I shall paste here "In some sense dopamine gives one the energy and motivation to act on something. So if you put an animal in a cage and give it a lever that it has to press 20 times in order to get a treat after a light comes on, eventually it will learn that the light means that the lever is about to get activated and they will start to get a dopamine surge as the light comes on, not just when they actually get the treat. But apparently if you block the rise in dopamine that occurs with the light coming on, the animal doesn't go after the lever very much."

Dopamine antagonists can cause anhendonia so there are issues with side effects and patient compliance but they can sometimes reduce compulsions. Schizophrenics often abuse some drugs because of the side effects of antipsychotics, although nicotine is a different matter. Amphetamine is known to worsen and speed along the development of schizophrenia.

Re: dopamine agonists - compulsive disorders often develop with dopamine agonists, they will probably just worsen compulsions. Blocking DA in the cortex can reduce executive function and hence control over impulses but blocking the DA in the midbrain that can lead to those compulsions in the first place may outweigh that.

RE: GABA enhancer; In Huntington's disease, dopamine antagonists are used to increase net GABAergic output because dopamine often inhibits GABAergic interneurons.
 
PS - the dude in my house took MDMA last night, and he was still drinking like a fish today - so whilst it may be effective for PTSD, substance seeking behaviour?
Not so much, I don't think.

He got up this morning and told me he was gonna start drinking again.
I gave him a couple Solpidine - marketed here as analgesics, with a small opioid action, codeine.
He said it eased his hangover, but he still felt like drinking.

Yeah I think MDMA and other substituted amphetamines are still going to be pretty reinforcing and in animals still cause similar changes in neurons/behavior related to addiction.

Something like ibogaine may be more helpful for addiction.
 
Yeah I think MDMA and other substituted amphetamines are still going to be pretty reinforcing and in animals still cause similar changes in neurons/behavior related to addiction.

Something like ibogaine may be more helpful for addiction.

Regarding
dopamine agonists versus reuptake blockers, and what the dude was saying in the other thread...

If a dopamine agonist can stimulate impulsive behaviours - but he mention bupropion as a potential treatment to impulsiveness, like excessive eating....

Both increase DA neurotransmission - though I'm still a little ill-informed - as agonists induce lethargy, yet buproprion or amphetamine analogues, known as stimulants, obvious do not.
Yet ultimately, I'm assuming, the end product is the agonist or endogenous transmitter stimulating a receptor and inciting a biological cascade.

Yet - sedating, vs stimulating...?
 
Dopamine antagonists can cause anhendonia so there are issues with side effects and patient compliance but they can sometimes reduce compulsions. Schizophrenics often abuse some drugs because of the side effects of antipsychotics, although nicotine is a different matter. Amphetamine is known to worsen and speed along the development of schizophrenia.

Re: dopamine agonists - compulsive disorders often develop with dopamine agonists, they will probably just worsen compulsions. Blocking DA in the cortex can reduce executive function and hence control over impulses but blocking the DA in the midbrain that can lead to those compulsions in the first place may outweigh that.

RE: GABA enhancer; In Huntington's disease, dopamine antagonists are used to increase net GABAergic output because dopamine often inhibits GABAergic interneurons.

Is
that the primary reason for substance abuse among schizophrenics?

Cause I've read a huge percentage of them abuse substances.
It's a product of the treatment, not the condition and underlying neuronal malfunction itself?

GABA enhancers downregulate dopamine - but, they don't really lead to substance abuse - right?
In fact, isn't the FDA now issuing a control license on several GABA'ergics like lyrica?
i.e. it itself has abuse potential.
I'm going to blindly assume that situation is due to the DA downregulation occurring in a brain area that's not the limbic system?
 
Regarding
dopamine agonists versus reuptake blockers, and what the dude was saying in the other thread...

If a dopamine agonist can stimulate impulsive behaviours - but he mention bupropion as a potential treatment to impulsiveness, like excessive eating....

Both increase DA neurotransmission - though I'm still a little ill-informed - as agonists induce lethargy, yet buproprion or amphetamine analogues, known as stimulants, obvious do not.
Yet ultimately, I'm assuming, the end product is the agonist or endogenous transmitter stimulating a receptor and inciting a biological cascade.

Yet - sedating, vs stimulating...?

Reuptake inhibitors will only magnify whatever NTs are "naturally released" by action potentials, action potentials cause vesicles to fuse with the presynaptic cellular membrane and release the stored NTs into the synapse. Presynaltic autoreceptors can prevent vesicle fusion and presynaptic release though.

Releasing agents like amphetamine on the other hand essentially force neurotransmitters out of the presynaptic neuron irrespective of autoreceptors, so they differ very much in that regard. Agonists are more akin to releasing agents in that they once again bypass autoreceptors by binding postsynaptically, independent of vesicle fusion and natural presynaptic release. Although agonists can also stimulate autoreceptors.
 
Is
that the primary reason for substance abuse among schizophrenics?

Cause I've read a huge percentage of them abuse substances.
It's a product of the treatment, not the condition and underlying neuronal malfunction itself?

GABA enhancers downregulate dopamine - but, they don't really lead to substance abuse - right?
In fact, isn't the FDA now issuing a control license on several GABA'ergics like lyrica?
i.e. it itself has abuse potential.
I'm going to blindly assume that situation is due to the DA downregulation occurring in a brain area that's not the limbic system?

I'm sure schizophrenics abuse various drugs to help with their unmedicated schizophrenia, I believe this was shown with opioids for example. A classic one is that schizophrenics smoke a lot of cigarettes because nicotine helps with some of their dopamine regulation issues (they used to instead think that cigarettes caused schizophrenia)

Benzos are weird because many find them reinforcing and abuseable, although this is different from benzo to benzo because GABA-A receptors can vary with different subunit compositions and different benzos have affinity for different GABA-A receptors. Why exactly there are abuseable it's mysterious to me. They are certainly relaxing and that is easy enough to understand but they can also cause euphoria. Whereas opioids and NMDA antagonists sort of work by turning off GABA interneurons, and they can also be euphoric.

There might be a baseline with euphoria to the left and euphoria to the right, in terms of increasing GABA with a benzo and decreasing GABA with an NMDA antagonist/opioid, but this is probably going to depend upon specific populations of receptors.

In other words, a benzo is going to be affecting GABA receptors everywhere, but NMDA antagonists might just be addicting because they inhibit the interneurons that target the nucleus accumbens (normally NMDA receptors activate those interneurons)

Also I thought I'd mention I personally think Lyrica/Gabapentin don't have much GABA action to them. They tend to be anti glutamate and excitation though. Supposedly perampanel is intoxicating and abuseable as well and got scheduled a bit higher in the US, and it's just an AMPA antagonist (although less AMPA means less NMDA so maybe it's sort of an indirect NMDA antagonist)
 
That guy I described in the opening post:

He was yesterday, sentenced to 36 years in prison.

http://www.mmafighting.com/2017/6/5...s-to-life-in-christy-mack-sexual-assault-case

He described in his closing statement that, since he can remember, he suffered internal turmoil.
As therapy, to avoid suicidality - he was look in the mirror, and punch his own face. Indeed I recall interviews over the years where his face appeared swollen.

He described acute anxiety, depressive phases, spanning his entire life - inexplicable violent tendencies, that resulted in time after time of charges for violent conduct, going right back to his school days.

Again - his childhood was highly traumatic.

The judge imposed a lengthy sentence, as she felt he could not be allowed to re-offend.


Most recently - he seems to have, "found God" - which I would assume is a self imposed delusion, as a means to psychologically deal with the gravity of his situation - the fact that he remains to have untreated neurologic dysfunction, and will be in a small cell for the next 36 years, at a minimum.

Does the justice system not factor neurologic explanations for behaviour in otherwise productive positive individuals?
If he was outright psychotic - I'm sure he was be treated in some capacity.
Just because it's something lesser, but equally self destructive - is treatment overlooked?
 
There have been some cases where medical causes of aggression were considered and the punishment was adjusted, but it's still a mystery to me why we treat something like a brain tumor (see Charles Whitman) or orbitofrontal cortex damage from MMA fighting any different from aggression caused by more subtle pathology.

If we say "Oh look here on this MRI, there is a chunk missing out of the OFC because the hits to the head caused the brain to ricochet off the orbits of the eyes, and oh look people with damage to the OFC can't control themselves" - this shouldn't be any more exculpatory than pathology that isn't readily identifiable with current imaging.

But jail can still be a means of deterring crime and segregating criminals from society I suppose.

When you begin to view addiction as a disease and illness rather than a moral failure that needs punishing, that can change the legal system's game a lot too.
 
Is
it possible that, for that initial case of violence I described that, sertonergic enhancing agents, could exacerbate the violent impulses?

serotonin enhancing agents like the selective serotonin releasing agent MMAI are actually sedating so they actually inhibit violent impulses!

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