Benzos Benzo long-term regular/sporaric use - lack of withdrawal?

[Dextro .45]

Check this out….taken from a medical journal on BDZ Treatment & Withdrawal

Front. Psychiatry, 11 January 2023

Sec. Addictive Disorders

Volume 13 - 2022 | https://doi.org/10.3389/fpsyt.2022.1060949

GABA-A receptor subtypes and benzodiazepine use, misuse, and abuse​

In addition to the above complex changes taking place in the GABAARs, BDZ tolerance and withdrawal involve other neurotransmitter systems in the brain. The glutamatergic system and synaptic plasticity involving NMDA and AMPA receptors, for instance, are causally involved in the development of a withdrawal syndrome following the cessation of chronic BDZ treatment (156). When the drug is withdrawn at the end of chronic BDZ treatment, there is often an asymptomatic refractory period of 3 to 5 days before the symptoms begin. Even for longest-acting BDZs, this refractory period is too long to be explained by the gradual clearance of the drug. During this refractory period, glutamatergic synapses go through a number of plastic changes with the insertion of AMPA receptors into the synapse and their subsequent phosphorylation, leading to increased AMPA/NMDA transmission ratio (157–163). Treatment with AMPA (but not NMDA) receptor antagonists during the refractory period abolishes the development of the withdrawal syndrome (164–167), demonstrating the causal involvement of this type of plasticity in excitatory synapses in the development of the withdrawal symptoms. A reduction in NMDA receptor expression and function is observed secondary to this enhancement of AMPA-mediated conductance (167) and the administration of NMDA receptor antagonists during the symptomatic portion of the withdrawal period can ameliorate symptoms (164). Even more strikingly, it was demonstrated that the co-administration of an NMDA receptor antagonist during chronic lorazepam administration can abolish tolerance to the anticonvulsant effects of lorazepam, although an overall reduction of BDZ-binding sites was observed in NMDA antagonist administered animals similar to controls (109), suggesting that glutamatergic mechanisms may be more important for the development of tolerance and dependence than changes in GABAAR expression.


Very important information…..refractory period of 3-5 days before withdrawal symptoms manifest for long acting benzodiazepines.

Treatment with AMPA (but not NMDA) receptor antagonists during the refractory period abolishes the development of the withdrawal syndrome…..Reeeallllyyyy ???? Hmmm

 

[Dr. John Thackery]

Check this out….taken from a medical journal on BDZ Treatment & Withdrawal

Front. Psychiatry, 11 January 2023

Sec. Addictive Disorders

Volume 13 - 2022 | https://doi.org/10.3389/fpsyt.2022.1060949

GABA-A receptor subtypes and benzodiazepine use, misuse, and abuse​

In addition to the above complex changes taking place in the GABAARs, BDZ tolerance and withdrawal involve other neurotransmitter systems in the brain. The glutamatergic system and synaptic plasticity involving NMDA and AMPA receptors, for instance, are causally involved in the development of a withdrawal syndrome following the cessation of chronic BDZ treatment (156). When the drug is withdrawn at the end of chronic BDZ treatment, there is often an asymptomatic refractory period of 3 to 5 days before the symptoms begin. Even for longest-acting BDZs, this refractory period is too long to be explained by the gradual clearance of the drug. During this refractory period, glutamatergic synapses go through a number of plastic changes with the insertion of AMPA receptors into the synapse and their subsequent phosphorylation, leading to increased AMPA/NMDA transmission ratio (157–163). Treatment with AMPA (but not NMDA) receptor antagonists during the refractory period abolishes the development of the withdrawal syndrome (164–167), demonstrating the causal involvement of this type of plasticity in excitatory synapses in the development of the withdrawal symptoms. A reduction in NMDA receptor expression and function is observed secondary to this enhancement of AMPA-mediated conductance (167) and the administration of NMDA receptor antagonists during the symptomatic portion of the withdrawal period can ameliorate symptoms (164). Even more strikingly, it was demonstrated that the co-administration of an NMDA receptor antagonist during chronic lorazepam administration can abolish tolerance to the anticonvulsant effects of lorazepam, although an overall reduction of BDZ-binding sites was observed in NMDA antagonist administered animals similar to controls (109), suggesting that glutamatergic mechanisms may be more important for the development of tolerance and dependence than changes in GABAAR expression.


Very important information…..refractory period of 3-5 days before withdrawal symptoms manifest for long acting benzodiazepines.

Treatment with AMPA (but not NMDA) receptor antagonists during the refractory period abolishes the development of the withdrawal syndrome…..Reeeallllyyyy ???? Hmmm

thanks for finding that. can you cite the paper it’s from?

 

[Dextro .45]

Frontiers

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.1060949/full

 

[Dr. John Thackery]

Frontiers

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.1060949/full

thanks.

AMPA antagonists sound great in general. i’d love to hear from ppl that have been on them. all my downer loving homies hate glutamate.

might be good for a new thread to ask who has taken these drugs

 

[Dextro .45]

Even way back when I was a rookie…..all my knowledge & information comes strictly from medical journal studies. Medical literature of all kinds, often 3-7 papers/studies on a specific topic or subject….that way I can read if any discrepancies between studies surface, or all information is identical with same result

Never is anecdotal b.s. from some guy, oh I heard that…… No, no.

Even Wikipedia is Awesome…..I’d never go to the manufacturer website. It’s for the layman. Some senior citizen who just got prescribed Lyrica and needs to know about it….all that info would just scare the shit outta them and they won’t really understand truly how the drug works

I have binders full of pharmacology related medical studies on specific compounds I’m interested in, and am prescribed long term….mostly CII controlled substances, opioids, benzodiazepine, gabapentinoids, dopaminergic stimulants, various research chemicals like Diclazepam, Ethylphenidate, Phenibut, Phenylpiracetam, etc. littered with hand drawn molecules ha ha I laugh when I browse through it ….even Vendor inventory lists of their RC products and prices dating back 20 years ago….compoumds you can’t even find anymore and one’s Health Canada banned and were removed by vendor…like Isopropylphenidate IPH which was being considered a safer, longer lasting analog to Ritalin (Methylphenidate) and I acquired 10 grams before vendor removed. Health Canada has it still classified as a compound of great interest as its longer lasting and only 1/3 Norepinephrine activity than Ritalin.

In-vitro research & studies & in-vivo self administration ha ha ….for research purposes lol

 

[Syntherize]

Yes, I know….that’s why I wrote this thread.

Ethanol & benzodiazepine withdrawal are the most serious and can be fatal.

Even during COVID….Health Canada made a statement regarding the LCBO staying open. “We would like to address that all LCBO stores will remain open, and are considered essential business. Whether we like to admire it or not, there is a segment of the population that are dependent and rely on alcohol, and can be very serious if they go without”.

They actual said that

Opioid withdrawal/dependency while severe is not life threatening. You’re just sick for weeks. Benzodiazepine withdrawal if severe causes seizures, heart arrhythmia, rapid respiratory system, etc and could be fatal

I’m just pleased with my extensive long term use, of sporadic therapeutic dosing of long acting compounds, I was able to taper off dosing and be without for 2-3 weeks…..even a month here and there without any concerning symptoms or discomfort. The most I’ve ever experienced was 2-3 days of poor sleeping patterns, mild day time cognitive impairment for 2-3 days and that’s about it.

Having on hand certain medications to modulate any mild discomfort is essential….my fav are:

Clonidine 0.1mg - extremely effective anxiolytic & sedative, lowering BP & HR, eliminating RLS, hot/cold flashes, etc
Pregabalin & Gabapentin - Anticonvulsant with robust anxiolytic properties, can help reduce doses of opioid/benzo
Trazadone 50mg - Night time sleep disturbances, very effective hypnotic & sedative
Zopliclone 7.5mg - Hypnotic (half tablet usually) same subunit at benzo site a1 a5 hypnotic & sedative

I’ve take these 3-7 days after ramping down benzodiazepine use, tapering off doses, then using the above meds for about a week, and after I’m perfectly fine.

I hate Trazadone and much prefer Seroquel in doses above 100mg for that use. Also, I seriously dislike Ambien, but Lunesta works great for me instead. “To each their own”.

 

[DeathIndustrial88]

clon has a super long half life so skipping a few days you’re still under the influence of the drug and nowhere near withdrawl.

True. I'm only prescribed 1.5mg a day though. And some times I'll just take .5mg a day if my anxiety isn't terrible. And then I can go like 5 days without any & not really notice much. I dunno if .5mg or even 1.5mg would keep me WD free for 5 days or more.

Ironically, my klonopin never shows up in my urine either for some reason. Including the lab ones where they test for everything.

At my last piss test, I took 1.5mg the night before I went in & then another .25mg the next morning & it still didn't show up on my drug screen for some reason. Neither did my buproprion, which I also took 75mg XL the night before. So who knows. I made a whole post about it on here a little while back because it makes no sense to me.

 

[Dr. John Thackery]

True. I'm only prescribed 1.5mg a day though. And some times I'll just take .5mg a day if my anxiety isn't terrible. And then I can go like 5 days without any & not really notice much. I dunno if .5mg or even 1.5mg would keep me WD free for 5 days or more.

Ironically, my klonopin never shows up in my urine either for some reason. Including the lab ones where they test for everything.

At my last piss test, I took 1.5mg the night before I went in & then another .25mg the next morning & it still didn't show up on my drug screen for some reason. Neither did my buproprion, which I also took 75mg XL the night before. So who knows. I made a whole post about it on here a little while back because it makes no sense to me.

if it’s a low dose and the LOQ of the analysis method is high, it won’t show.

it’s absolutely in there though if you use a sensitive enough method which clinical labs generally don’t. a toxicoligy lab would though