Kindling, is there a treatment for it ?

[Kdem]

Especially when the core drug is a benzodiazepine ...

Possibly my reaction to an opiate is a matter of kindling. I'm sensitive all all kinds of substances, it depends on the substance of course.

https://en.wikipedia.org/wiki/Kindling_(sedative–hypnotic_withdrawal)

A brief quote 'Kindling refers to the phenomenon of increasingly severe withdrawal symptoms, including an increased risk of seizures, that occurs as a result of repeated withdrawal from alcohol or other sedative–hypnotics with related modes of action. Ethanol (alcohol) has a very similar mechanism of tolerance and withdrawal to benzodiazepines, involving the GABA_A receptors , NMDA receptors and AMPA receptors, but the majority of research into kindling has primarily focused on alcohol.^[1] An intensification of anxiety and other psychological symptoms of alcohol withdrawal also occurs.^[2]

I know the phrase 'go slow'. But anything else, really ?
It mentions acomprosate, but that's for alcohol withdrawal. I recall that once upon a time there was a thread about NMDA antagonists to prevent the development of benzodiazepine tolerance.

https://en.wikipedia.org/wiki/Kindling_model I'm sorry about the messy font, I can't seem to fix it.

 

[adder]

I doubt NMDA antagonists could be a solution here in any way as they rapidly lead to NMDA receptor upregulation, which is also one of the responses of your body for long-term benzodiazepine intake (i.e. trying to combat depressant effect of increased GABA via increasing glutamatergic neurotransmission). While an NMDA antagonist might provide a short-lasting relief of benzodiazepine withdrawal symptoms, once it wears off, it will make the symptoms much worse. I myself experienced a flashback of some withdrawal symptoms after small doses of DXM taken for a few days many months after quitting benzodiazepines and already feeling relatively stable. Of course many psychoactive substances can induce anxiety and/or paranoia if you had quit benzodiazepines after long-term dependence, but that only shows how important GABAergic and glutamatergic neurotransmission is for many processes in your body and how disruptive benzodiazepine dependence is. I can't say what effect taking an NMDA antagonist would have for a benzodiazepine-naive person before starting a two-week trial of benzodiazepines though, but I also can't picture a protective mechanism against tolerance to benzodiazepines behind this.

 

[sekio]

The only real treatment is prevention, if you've abused BZDs or opioids for many years you're going to suffer through w/ds if you use what you've been addicted to for any continuous amount of time.

So don't get stuck in the trap of daily, high dose banzo/opioid use, and if you can, discontinue with a taper rather than cold-turkey. There is no drug that you can take that will prevent/slow the development of tolerance reliably, and the "allowable" dosage regimens for both BZDs and opioids are really only for acute cases anyway. If you have a doctor prescribing you BZDs for daily use for any longer than ~2 weeks you had better make a decision if you want to be on them for the long-haul or not.

 

[Kdem]

In agreement with Sekio, long term daily benzodiazepine use is a terrible thing.

But doctors can abuse drugs too. I was told to just take it daily, when I first got some problems reactions varied from 'take some more' to 'just stop taking it'. I never knew that 2 (or even 4!) mg clonazepam was that powerful.

The question was about kindling. I think it affects the entire CNS. Possibly also the HPA axis etc.

 

[Cotcha Yankinov]

I suppose an AMPA antagonist (perampanel) may be interesting if a lot of kindling is really compensatory glutamate upregulation, but who knows if there would be compensatory upregulation to AMPA blockade that one would eventually have to deal with.

Antiepileptics have been shown to be helpful for acute GABA drug withdrawals. Lamotrigine has some anti-AMPA effects I believe.

Some of those mood stabilizers may actually help with whatever mental illness people were using drugs to cope with in the first place as well

 

[Kdem]

Not to say it´s a good idea but to bring something up: aside from other issues, physical dependence seems to be related to the muscarinic receptors.

https://www.ncbi.nlm.nih.gov/pubmed/1358120

https://books.google.nl/books?id=f-...epage&q=muscarinic receptors kindling&f=false

complicated ! : https://link.springer.com/chapter/10.1007/978-1-4684-5769-8_50

as in epilepsy : http://www.sciencedirect.com/science/article/pii/0006899378907163

That doesn´t necessarily mean that drugs that are muscarinic antagonists are helpful. I once took two drugs that are in that category, and there both short term and especially long term negative effects. (problems)
Some vague (?) evidence for the role of the HPA axis in kindling.