Benzo withdrawal or histamine intolerance and acetylcholine reactions?

[[id...]]

I've been off benzos for almost 7 years.

Since I was thrown into a bad wave a couple of weeks ago I started re-reading my taper and post-taper progress logs and I noticed something.

Right now I believe my wave is caused by stopping doxylamine (old unisom, now unisom has a different ingredient). I'm researching anti-histamine and anti-cholinergic effects of drugs now and realizing that my original benzo withdrawal might have been related to that rather than GABA issues. 

After the acute benzo withdrawal 6 years ago I tested my neurotransmitters and my GABA was normal but histamine was through the roof and it puzzled me then.

Now It makes so much sense.

Originally (over 7 years ago) I got in a bad shape after cold turkey'ing Remeron which has anticholinergic and anti-histamine qualities. However, while I was still on Remeron, I stopped Klonopin cold turkey (8 years ago) for a couple of months without any ill effects. I restarted Klonopin while I was waiting for my test results back (they suspected cancer and it was during the holidays in the US so it took me TWO months to get all the testing and follow up scheduled and during those 2 months I reinstated Klonopin) not because of withdrawal. Later I stopped Remeron while still on Klonopin and the hell broke loose.

However, when I was tapering Klonopin I was taking Benadryl on and off and also some other anti-histamine and anti-cholinergic drugs (Hydroxyzine, Seroquel) and now rereading my log I see that my waves were worsening on the days I wasn't taking those drugs.

Now I'm questioning if I really had a bad Klonopin withdrawal or if it was a mild Klonopin withdrawal with horrendous anti-cholinergic drugs withdrawal?

So I wonder how many of you were prescribed anti-histamine and anti-cholinergic meds (including many anti-depressants, like Remeron) along with benzos? Could it be the difference between the people who, as doctor's claim, stop benzos without any issues and those who have PAWS for years?

While I was searching for more information I came across this video that explains which drugs have anti-histamine and anti-cholinergic effects, how they act in the body and what a withdrawal might look like:

 

I am not posting this in "other meds" board, because it's not about meds, it's my pet theory about complicating factors and outcomes of stopping benzos while on other meds or having histamine intolerance predisposition. 

[[id...]]

If I don't get any response in this forum, I'll repost it in the "Other meds" section but will edit the post to adhere to the rules.

[[Ar...]]

You're right about the acetylcholine, though I haven't yet investigated histamine. Last night I found the following article, from 24 years ago, explaining why I have most of my withdrawal symptoms. I posted the information elsewhere on the site but have just found your thread so am reposting it here.

It details how diazepam (valium) is similar to newer benzodiazepines in inhibiting both acetylcholinesterase and ATPD'ase. https://link.springer.com/article/10.1023/A:1007500424392    As acetylcholinesterase breaks down acetylcholine its inhibition leads to excessive levels of acetylcholine. Too much acetylcholine causes muscle cramps, depression, jitters, restlessness, damage to the immune system, increased stress and anxiety, imbalance, hair loss, disruption of the circadian rhythm and sleep patterns, confusion, respiratory depression, nausea, vomiting, blurry vision, slowed heart rate, increased or decreased sex drive, involuntary muscle movements, increased allergic response, gastrointestinal issues involving constipation and diarrhea, paralysis, muscle weakness. In severe cases it can cause convulsions, depression of respiratory activity, improper processing of information on every level of the body and brain, and decreased behavioural inhibition. Nicotinic/acetylcholine receptors, which are the target of benzodiazepines, regulate aggressive behaviour so dysregulation can lead to increased aggression. After all of this time I feel it necessary to point out that all of these symptoms appear in benzodiazepine withdrawal and that I have experienced them all to some degree or another. I think that it’s also likely that, since acetylcholine signaling underlies dreaming, high levels of it may well induce the depersonalization/derealization which occurs in benzodiazepine withdrawal, like a waking lucid dream state.

ATPD'ase reduces ATP to ADP, releasing a molecule of phosphate for cellular production of energy in aerobic respiration. So inhibition of this process switches cells around the body over to using anaerobic respiration to produce energy; a far less efficient process leaving some of us fatigued during effort.

Disagreement still exists about the role of acetylcholine in tinnitus but hydrolysis of ATP, by ATPD'ase, alleviates tinnitus so the inhibition of the enzyme is likely to be the cause of the exacerbation of tinnitus experienced by us. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235102/

It's possible that the body might release histamine in response to this inhibition in order to increase levels of ATP in order to try to increase the production of cellular energy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779754/