Can glutamate inhibitors alters cocaine effects?

[twoface]

Hello all

Can glutamate inhibitors like Topiramate and Lyrica alter cocaine effects?

I'm wondering if they can null the rewarding effects of cocaine

Thanks!!!

 

[eldub v7.0]

i have no clue on the mechanisms of action for topiramte but i don't think there are any contraindications with taking lyrica and cocaine (tri - triple reuptake inhibitor) - this interaction checker says there are no risks between the 3.

there's always a risk of overdose of cocaine especially when combined with depressants such as lyrica. the sedative/anti-convulsant effects will mask stimulation from the cocaine tricking you into thinking you're not as high as you might be.

 

[Zarathustra1313]

Please correct me if I'm wrong but glutamate is what the brain produces In concert with dopamine. The glutamate is the actual chemical that causes addiction as it (in lay terms) cause the brain to remember the reward the drug provided.

So I would think that taking glutamate inhibiting drugs along with your DOC would perhaps lead to decreased addiction risk.

 

[eldub v7.0]

is there such thing as a glutamate re-uptake inhibitor?

i don't think it would necessarily help deter addiction/tolerance under certain circumstances as it's a little more complicated than that, but black and white in others.

addiction and tolerance progress through actions on the DA pathways normally associated with learning.
Activation of these DA-ergic pathways has 2 physiological functions (from Kalivas 200:
1. to facilitate initial learning of adaptive responding to important stimuli
2. to cue the retrieval of the information needed to execute the adaptive behavioral response when environmental circumstances predict that food is imminent

from djsim

Addiction progresses because of the acton of drugs on dopaminergic neural pathways which are normally associated with learning. Activation of these DA-ergic pathways has 2 physiological functions (from Kalivas 200:
1. to facilitate initial learning of adaptive responding to important stimuli
2. to cue the retrieval of the information needed to execute the adaptive behavioral response when environmental circumstances predict that food is imminent

What this means is DA is released only when a behavior is being learned, or a learned behaviour needs to be 'cued' from environmental triggers. Think of it this way; we all eat pretty much at the same time every day out of habit (a cue by the time of day). But now think of when you're really hungry... eating feels great because DA has been released to reinforce the fact that we must eat to live. In other words, DA is not often released under everyday conditions.

But because drugs of addiction activate DA pathways every time, and do so very efficiently, use of these drugs essentially hijacks the learning systems we have to its own ends so that now the brain has learned that boiling water in a spoon then filtering and injecting is a very important stimuli; why? Because copious amounts of DA were released.

So how does this all fit in I'm sure you're wondering...?
My point is that repeated dosing is the problem for addiction, NOT physical addiction to a substance. If it were about the physical WDs then people would easily be able to detox from H w/ an ultra-rapid naltrexone detox, not would coke/amphetamine/etc be addictive. So clearly the issue is your brain learning to like the act of getting high.

Whilst time off for a few weeks won't be able to disrupt this learning process there is a way which should work... make your drug use so unpredictable and widely spaced that your brain can make no predictions. So if you always dose every third weekend, change that so your brain doesn't start learning to associate weekends with good feelings, b/c from there it's not much of a stretch for your brain to justify more frequent use.

IX. DOPAMINE

The primary monoamine neurotransmitters are dopamine, norepinephrine and serotonin. Dopamine and norepinephrine are catecholeamines, whereas serotonin is an indolamine.

The amino acid tyrosine is not an essential amino acid because it can be synthesized in the liver from phenylalanine by the enzyme phenylalanine hydroxylase. But it cannot be synthesized in the brain, and therefore must enter the brain by the large neutral amino acid transporter, which also transports phenylalanine, tryptophan, methionine and the branch-chained amino acids. These amino acids all compete for the transporter, so a large quantity of one of the other amino acids in the blood stream could greatly limit the amount of tyrosine entering the brain. One case in which this occurs is when there is a liver deficiency of phenylalanine hydroxylase. In that case, Phenylalanine reaches high concentrations in the blood and monopolizes the large neutral amino acid transporter, producing the mental retardation of phenylketonuria.

Dopamine synthesis [Dopamine synthesis]

Once in the brain, tyrosine can be converted to DihydrOxyPhenylAlanine (DOPA) by the tyrosine hydroxylase enzyme using oxygen, iron and TetraHydroBiopterin (THB) as co-factors. High concentrations of dopamine inhibit tyrosine hydroxylase activity through an influence on the THB co-factor. DOPA is converted to dopamine by Aromatic Amino Acid Decarboxylase (which is fairly nonspecific insofar as it will decarboxylate any aromatic amino acid) using PyridoxaL Phosphate (PLP) as a co-factor. This reaction is virtually instantaneous unless there is a Vitamin B6 deficiency.

Dopamine & epinephrine are primarily inhibitory neurotransmitters that produce arousal. This may sound paradoxical, but the most likely explanation for this effect is that the postsynaptic cells for catecholamines themselves are inhibitory. There are 3-4 times more dopaminergic cells in the CNS than adrenergic cells. Dopamine in the caudate nucleus facilitates posture, whereas dopamine in the nucleus accumbens is associated with an animal's speed (and pleasure).
[dopamine receptors]

There are two primary dopamine receptor-types: D1 (stimulatory) and D2 (inhibitory), both of which act through G-proteins. D2 receptors often occur on the dopaminergic neurons, partially for the purpose of providing negative feedback. These so-called autoreceptors can inhibit both dopamine synthesis and release.

 

[Zarathustra1313]

Thanks for that info.

Perhaps I need to read it three more times or maybe it's just late but heres what I'm thinking after my one read of it.

Taking a glutamate inhibiting bruh could reduce the addiction factor of your DOC. If you were new to that drug and the pathways hadn't already been cut in the brain.

I'll also dissagree with the person saying that addiction isn't really your physical dependency on your DOC but rather the act of doing it.

I have been addicted to opiates/heroin for roughly 8 years and only recently after countless bouts of WD trying to kick at home/no medical help I finally decided to do a proper medically overseen inpatient detox. That was about 21-22 days ago and as of midnight, I have been 26 days clean. I'm not saying I'm anywhere close to being through the woods but still, prior to going through detox I had spent at most 3 days clean in utter agony before I just couldn't stand it anymore and I knew I would have to go to work the next day. I just made that call, made my run and I was sick no longer.

Now that I don't NEED H to function I see no reason to ever use it again.

 

[twoface]

Im am considering doing it for that purpose indeed. But I still have my doubts as if it will work as a comedown aid.

 

[pasha]

Moving this to OD.

BDD -> OD