Abolisng the reward of abusable drugs while retaining their therapeutic potential

[MeDieViL]

From my experience; the addition of ginseng; minocycline and nac (wich all blunt amp euphoria) completely eliminate he high of amp no matter how much i dose; yet i have anhedonia and it does still counteract wich seems to indicate that the brain somehow knows what a normal level of reward is (just an idea).

I use amphetamine for social anxiety so i need memantine with it to prevent tolerance; all the therapeutic effects remained completely and yet despite megadosing no euphoria would appear.

This supports my hypothesis that dopamine is involved in social behavor and that amphetamine doesnt help it because it makes you high; also the things i added to it deplete glutamate; the addition of GHB wich induces glutamate release allowed the euphoria to kick in wich also supports the hypothesis that glutamate is responsible for euphoria and not dopamine.

It does look like da plays a permissive role on euphoria; so with enough glutamate release more da would induce more euphoria because it permits glutamate to do so.

This only refers to amphetamine; most drugs induce euphoria trough MU; however VTA glutamate must be there before MU can be euphoric.

Seperating therapeutic from euphoric effects is an interesting avenue to make abusable drugs as possible options for the treatment of many disorders; but lets not forget about the reinforcing issue wich is disconnected from the euphoria.

 

[atrollappears]

Epsilon Alpha posted this in the amph neurotoxicity thread a while back and it's very relevant to this.
http://www.springerlink.com/content/y13g4j7287330848/
MGlu5R also increases NMDA activity, indicating that at least those two glutamate receptors need not be activated for DA-mediated conditioned place preference. However, blocking the receptor does actually decrease cocaine self-administration (KO mice actually do not self-administer cocaine at all regardless of dose). Now, when you talking about euphoria, are you talking about environment or drug-associated reward? Maybe CPP is the therapeutic part xD

On a side note, I wonder whether a MGlu5 knockout human would also not self-administer cocaine. My guess is that he actually would, and that humans are capable of cognitively linking drug administration with whatever experience leads to CPP, meaning that they can understand taking a drug as a means to get to that preferred place, while mice/rats cannot. Humans do self-administer drugs which mice don't but which do produce CPP in mice, e.g. LSD.

 

[MeDieViL]

Self administration has nothing to do with euphoria; on some combo i was extremely mentally addicted to benzo's wich im completely immume for and lost intrest in that time my beloved GBL.

Wich makes the issue more complex; we can block the drugs from being rewarding but its likely ppl keep taking as much as when they were rewarding.

The wanting just relates to dopamine; my currect sups potentiate glut a ton but inhibit rewarding drugs da release and i much less want my drugs.

This is gonna take some time but i will analise the effects of the metabolite of ibogaine; it works as well in blocking craving as ibogaine; yet wellbutrin wich blocks the same receptor doesnt; also you can still get high on ibogaine wich is what we need; being addicted sucks but not being able to get high sucks too tbh; so this is even better then blocking the euphoria.

I like to be high but when i was high too much all i saw were drugs in the sky.

 

[Deleted member 137730]

Epsilon Alpha posted this in the amph neurotoxicity thread a while back and it's very relevant to this.
http://www.springerlink.com/content/y13g4j7287330848/
MGlu5R also increases NMDA activity, indicating that at least those two glutamate receptors need not be activated for DA-mediated conditioned place preference. However, blocking the receptor does actually decrease cocaine self-administration (KO mice actually do not self-administer cocaine at all regardless of dose). Now, when you talking about euphoria, are you talking about environment or drug-associated reward? Maybe CPP is the therapeutic part xD

On a side note, I wonder whether a MGlu5 knockout human would also not self-administer cocaine. My guess is that he actually would, and that humans are capable of cognitively linking drug administration with whatever experience leads to CPP, meaning that they can understand taking a drug as a means to get to that preferred place, while mice/rats cannot. Humans do self-administer drugs which mice don't but which do produce CPP in mice, e.g. LSD.

I have schizophrenia with predominate negative symptoms and cocaine is not rewarding to me at any dose. My brain also cannot crave anything and in my opinion cannot establish CPP. I can however feel mild euphoria from amp (but i never crave or want it) and become very mildly dependent on drugs such as benzos/opiates even while they totally lack all reward. Opiates totally lack reward and analgesia in me. Also nicotine is placebo for me. I feel like im on an nmda antagonist all the time.

 

[atrollappears]

I have schizophrenia with predominate negative symptoms and cocaine is not rewarding to me at any dose. My brain also cannot crave anything and in my opinion cannot establish CPP. I can however feel mild euphoria from amp (but i never crave or want it) and become very mildly dependent on drugs such as benzos/opiates even while they totally lack all reward. Opiates totally lack reward and analgesia in me. Also nicotine is placebo for me. I feel like im on an nmda antagonist all the time.

Hmm well there are many other glutamate receptors than just NMDA and MGlu5R, maybe the establishment of CPP has to do with one of those? Also, what kind of euphoria do you experience from amp? Maybe the fact that you can talk about experiencing a "euphoria" indicates a type of CPP?

This is extremely interesting though... I've often wondered if that is what schizophrenia would feel like, but I didn't think it would because of the other glutamate receptors at play.

 

[endotropic]

As far as I know there is no evidence of cpp in humans (although I suppose you could test for it in the same way as with animals). In either case cpp would probably occur at an unconscious level, so even if it does occur you might not know its happening.

Cpp is really just an indirect measure of "liking" or "wanting" for a drug, since we can't interview the rats and ask them what they felt. So really whether you think a drug causes "euphoria/reward" or not, the fact that you continue taking it suggests you still "like" or "want" its effects, and thats all cpp is claiming to measure.

 

[Epsilon Alpha]

Interesting concept, but for the love of your god this is a bad idea.
Seriously its like giving a bag of meth to a speed addict and saying "be sure to take these pills with it so you don't get high!"

 

[Aetherius Rimor]

I have schizophrenia with predominate negative symptoms and cocaine is not rewarding to me at any dose. My brain also cannot crave anything and in my opinion cannot establish CPP. I can however feel mild euphoria from amp (but i never crave or want it) and become very mildly dependent on drugs such as benzos/opiates even while they totally lack all reward. Opiates totally lack reward and analgesia in me. Also nicotine is placebo for me. I feel like im on an nmda antagonist all the time.

Can you point me in some direction that I can find more information about this effect of schizophrenia?

One thing that has been really strongly provoking my curiosity is my complete lack of cravings/addictive symptoms for any drug I'm tried (other than nicotine). I also know I usually experience far less euphoria than most people (except on psychedelics where I feel much more).

I would like to just say I have self-discipline and practice moderation and claim my lack of addictions as the result of virtue... but I really am beginning to suspect it's attributable to something else.

I was diagnosed with bi-polar, social anxiety, and am OCD, and I've read online about how similar bi-polar and schizophrenia are.

The only "craving" I ever get is the desire to redose when doing dissociatives, cocaine or amphetamines... but if I resist for a few hours it goes away completely no matter how much or how long I'd been on it.

 

[MeDieViL]

Interesting concept, but for the love of your god this is a bad idea.
Seriously its like giving a bag of meth to a speed addict and saying "be sure to take these pills with it so you don't get high!"

Well they prob would take them as the lack of mania causes drastic improvement in quality of life and dramatic reduction of the severe "side effects" of addiction; as the dosed drug still abolishes craving (liking is disconnected from addiction and remains simular) i wouldnt see much reason to return to the previous state as i like my drugs as much.