GABA-B agonist abuse and the changes to brain

[Vieno]

1. Yes I have tried a lot of drugs (32 at the moment). Here's a brief summary of the effects. Opioids had zero effects. Phenibut had zero effects up to 4,5g and a slight hypnotic effect at 10g. GHB had zero effects up to 1,3g and a very slight non-euphoric intoxication at 2,7g-3,5g. Adaptogens and other natural products had very neglible effects even at extremely high doses. Hallucinogenic drugs such as LSD and DXM had normal effects except euphoria. Cannabis produced no pleasant of psychedelic effects and instead induced strong tachycardia, hypotension, memory troubles and loss of coordination. Benzos and alcohol produced normal effects except euphoria. Stimulants produced normal effects and at high doses countered the CA slightly. An enormous dose of meth was able to almost restore normal pleasure response, but the dose was so high that my heart rate didn't normalize for a week. MDMA produced an extremely potent antidepressant effect but no pleasure. Diphenhydramine produced normal effects but no pleasure. The atypical antipsychotic perphenazine removed my circadian rhythm issues and provided slight pro-focus effect. I didn't mention all the substances but in terms of the effects you know the essential things now.

2. I never tried an opioid before CA - I didn't do any drugs - but I am absolutely certain opioids would have worked prior to my CA and here's why. Apparently I haven't yet mentioned it in this thread but my brother has CA too and he neither responds to opioids - but he used to. He used opium recreationally but did it only once a week to avoid tolerance. However after some months the effects started to wane off until they almost disappeared. He stopped because he figured it was tolerance, however he never had any withdrawal. After months he tried again and got hardly any effects. The effects never returned, he still gets only extremely diminished effects. I don't get any though so it seems that his case is slightly milder. Anyway, it appears that the lack of response to opioids goes hand in hand with this CA.

Why would the GABA-B be a wrong thing to look at even though this is not drug induced?

Surely there could be a malfunction somehwere else than in the GABA system, but like atrollappears said, GABA is strongly implicated in natural pleasure. In fact, the GABA and the opioid systems are the only known systems to directly mediate natural pleasure, ie. natural stimuli-induced pleasure can be both blocked and enhanced via direct manipulation of the GABA and opioid receptors in certain parts of the brain. So there could be a malfunction somewhere else, but I have no idea where should I look at. I do know where to look at in terms of GABA and opioids.

But yes, this is very bad, and in fact, it is killing me to realize how the dysfunction probably is in a specific small brain location that is extremely hard to manipulate via traditional drug administration. I would take paralysis of my all limbs over this any day.

E: If GABA-B is not considered central to the pathogenesis of this condition, then what explains the lack of response to GABA-B agonists?

 

[Vieno]

I just read an abstract from a study that stated a group of rats were given a pleasure inducer (sucose solution) and when it was established with the group, before each administration, a stressor was added. In this case a restraint for 60mins. Anhedonia was observed with the falling pleasure levels but when naloxone was administered, pleasure levels were normalised.
I dont know how helpful that is as the abstract (and likely, the whole study) was pretty sparse but its where my thinking is added.
Does this train of thought have merit? Or am i on the wrong route?lol.

Post a link to the study. The study is irrelevant if it didn't dissociate reward 'liking' (ie pleasure) from reward 'wanting' (ie motivation). But anyway, the point is that naloxone restored pleasure? That does sound odd, post the link! This train of thought can lead to something, can't tell yet. All paths must be explored.

 

[bunge]

I cant post the link at the moment because im on a mobile and cant use the laptop til tomorrow but i will do it asap.
My thoughts are leaning towards a unexplained down regulation in opioid receptors. Would it be possible through repeated administration of an antagonist (naloxone) to re-sensitize the opioid receptors and.cause them to become responsive again to natural levels of neuro-transmitters?.
I wasnt saying that GABA b is unconnected to the problem, just that the problem could be elsewhere and affecting or blocking the downstream effects of these receptors. After all, you did say that benzos have normal effect except for euphoria, so not all of gabas effects are blocked.
That same study also mentioned amphetamines causing a small pleasure response so maybe some link to yourself there.
Its really interesting bout your bro as well, obviously some genetic angle here as well.
Its a shame we cant get a fMRI done of your brain in response to stimuli (and an expert to read it) as that might at least zero in on areas worth futher investigation.lol

 

[Vieno]

The down regulation of opioid receptors has been a theory I have considered a lot but it has became clear that the problem doesn't lie there. Firstly, opioid tolerance would not explain the lack of response to GABA-B agonists. Secondly, opioid tolerance would be likely to cause withdrawal-like effects (such as those seen in endogenous opioid deficiency). Thirdly, mere opioid dysfunction is unlikely to cause CA as neither opioid blockage with an opioid antagonist nor opioid withdrawal produce CA. Fourthly, I have tried anti-tolerance drugs such as proglumide and NMDA antagonists with no success. ULDN, antioxidants and NO synthase inhibitors would be options to explore but considering how indeed opioid tolerance does not seem to be a reasonable explanation for CA, I have chosen not to pursue these treatments.

However I'm interested in the study, do link it here when you can. As for the naloxone working for opioid tolerance, I'm not so sure about that, the opiod system is a funny one. Unlike with other systems, opioid antagonism itself has very little effects if no exogenous opioid has been administrated.

 

[Jimmy69]

I cannot go deep on scientific talking 'cause don't have a medical formation but i can share my practical experience with Baclofen that maybe can helps you understand better.
I was a daily and heavy drinker from more than 15yrs (alcoholic we can easily say).
I take Baclofen from 15 months and my craving for alcohol is dead from almost a year (3 months to titrate 2 180mg/day and then down to actual 60mg/day).
I don't drink anymore or just small quantity occasionally but when happened that i drank more than normal (on new years eve for example) i was able to feel the full effect of alcohol, similar as before, but did not feel at all any desire of drinking the day after. The opposite i would say! Stayed 2 weeks AF easily, without "forving" myself to don't drink, but naturally.

The way as Baclofen exactly works is still not fully understood, but there are already a lot of studies (and people) that, dose dependently reduce or suppress craving, but seems to works in a totally different (and safer) way than GHB, Phenibut and Gabapentin and, even if withdrawal exists and can be serious, Baclofen does not have all the other characteristics to be considered an addictive drug, while the others are.
There are really a lot of studies about Baclofen and addiction, not only alcohol but cocaine, opioids, marjiuana, GHB addiction, binge-eating.
All receptors involved in addiction are in some way affected by Baclofen in an effective positive way.
Is not a "substitution" theraphy as GHB is and GHB has a big abuse potential because of the recreational effect while Baclofen no.
Baclofen does not cause anhedonia.
Is largely in Multiple Sclerosis from at least 40yrs, so no problems with long-terms effects.

There is a really big medical literature about Baclofen and addictions, not only in animal but in humans too, obviously.
I can post few links on subject if someone interested...

 

[belfort]

well i believe in my case, anhedonia led me to start taking ghb and other gaba B agonists..Ghb is the only constant that relieves my anhedonia..phenibut also to a much lesser degree..has it caused my anhedonia to get worse in the long ru, probably but its a 'damned if you do, damned if you dont' situation..in life, without pleasure things become quite pointless..

 

[Michaelangelo]

I have used the gaba-b agonist phenubit to successfully conquer Crack Addiction. It should not be used everyday although to get through the first three months of abstinence it may be useful. I also must mention that day treatment or a drug rehab is paramount if you have not successfully stopped smoking crack on your own. Crack is a deadly drug and the use of a gaba-b agonist whichever one works is far better long term because your brain will heal from it just like a methamphetamine addicts brain recovers after 14months of abstinence which can be proven by looking at pet scans. Successful recovery from crack or other stimulants requires at least a year of abstinence as well as serious behavioral and environmental changes. I believe the trade off of the temporary compensatory changes in the brain from the gaba-b agonist are well worth the pros of not being a lifelong crack addict! You really need to find out whatever works for your own personal situation. I just know phenubit helped me immensely along with rehab and major changes to myself including increasing my spiritual side.

 

[Albstr1403]

Just want to let anyone know who’s reading this that I was on ghb for 2 years. After I quit I thought I was going to die and very anhedonic. No other drugs worked. It’s been a little over a year and I’m about 50-60% better. Healing from this is a long process