Kindling

[[Si...]]

Just saw this post on reddit which explains a lot..

 

 

Long story short: Every withdrawal will be harder than the last, primarily in relation to sedative-hypnotics.

Longer version: The GABA system is very sensitive and easily reprogrammed by everything from thoughts, behaviours and of course substances that act on the wide range of binding sites for GABA. Each time you overinduldge, be it a short term but highly destructive binge, or a long-term regimine of ritualistic use, there are a number of things happening within the system.

Most notably are two instances of receptor binding-efficiacy being impacted. The first instance is the outright destruction of receptors. This generally does not contribute to long-term kindling, as much of the time, repair of these systems is suspected to be possible. The second phenomenon is receptors protecting themselves from the aforementioned damage, as every system in our mind and body is somewhat intelligent. Receptors either retract into the neuron, retaining their sensitivity, or some other, currently unknown mechanism is activated that otherwise protects these receptors from being bound by monoamine transmitters or the antagonism of foreign compounds.

This mechanism is partially responsible for withdrawal symptoms. As GABA becomes less available in the synapse during cessation, so does the number of available receptors to be bound too, ultimately creating withdrawal. Everytime you reintroduce a sedative-hypnotic into your system post-withdrawal, this mechanism appears to activate faster and more effectivly in your brain's attempt to protect itself using the knowledge from the use of the compound in the past. In the end, when it comes time to get off the drug, you are left with even fewer sites for binding than last time. Yes, these receptors become available again eventually, but not immediately. For whatever reason, it takes some time for them to come back out.

This is one mechanism that contributes to kindling, and is speculated to be the most impactful. Other issues that contribute are long-term tolerence, the repeated destruction of receptors before they could fully heal from the prior rounds of substance use/abuse, impeded development of the corresponding monoamine transmitter(s) (in this case, GABA) as another protective measure set out by homeostasis, and countless other, fairly insignificant factors.

Theoretically it is possible that any substance can cause kindling in their respective systems, but because GABA is one of the most "sensitive" classes of primary binding sites, it is much more likely too happen. Kindling of the serotonin system comes as a close second in terms of practical cases, but we understand so little of what's happening with how our bodies prioritize the production and binding of 5HT, that it would be irresponsible to fully recognize this phenomenon in clinical practice. And so, gabaergic agonists such as benzodiazpenes, barbituates, alcohol, GABA-analogues and so on, are currently the only substances observed as kindling agents in modern medicine.

 

[Guest [...]]

"The GABA system is very sensitive and easily reprogrammed by everything from thoughts, behaviours ........"

interesting isn't it, its not just the drug involved here. Its the way we think and what we do. When I look back to what I was going through when I was first given a prescription I was all over the place, terrible stress in all directions.  The drug never helped me for very long but for some stupid reason I kept getting more prescriptions, never really addressing the real problem, ie that I was just bloody miserable and have had a rotten time over the years with one thing and another.  Meanwhile without knowing it the so called medical profession has helped to make things much worse for us!  What a crazy world we live in!

BTW does it give the source for who wrote the reddit piece?

[[Li...]]

Hello @[Si...].  Thank you for sharing the above Reddit post with us. 

Did the author of the post include citations (references) to support the claims made?  If so, would you be so kind as to share these with us so we can evaluate the veracity of the claims?  

 

 

[[Si...]]

@[Li...] no, no citations, it could all be nonsense... I was wondering if anyone knew if the idea that the receptors might retract into the neuron had any basis

[[Li...]]

Tip of the hat for recognizing the need to be cautious about unsubstantiated claims on the internet, @[Si...].  

Re: your question about receptors … The short answer is ‘We don’t know.’  But here’s a more complete answer from a trusted source - the Benzodiazepine Information Coalition.  The entire clip is worth a watch, but your specific question is addressed at the 5:33m mark.