View Full Version : Benzodiazipenes, neurotransmitters and their actions
I'm putting this in the panic forum to keep it with the other information threads.
All information travels down neural pathways to the brain and from the brain to muscles and organs. These pathways look like rope, but if you could look close they look like sausage links. Each link has a gap between it and the next. Situated around this gap are crossing points and the chemicals that bridge these points. The chemicals are called neurotransmitters and Serotonin is the most common. The largest number are in clusters in the brain. Each sausage feeds into one point on the next and that one might have a number of sausages feeding into it. It feeds into one point on the next. Hypothalamus directs these neurotransmitters to either carry a neuron across or not. Serotonin usually bridges the gap but can say no. Dopamine can override it because it can say yes or no. Dopamine is affected by mood. Serotonin does it's work through your whole body. Dopamine does it's work in your brain.
Although there are far more synapses in the brain it only has five percent of your Serotonin to work with. The rest is in your body and they are separated by the blood brain barrier that it can not cross. SSRIs don't build Serotonin, they keep you from wasting it. Too much and you get cognitive impairment, way too much and you get physical impairment too as it works on the synapses in your body.
Benzo's work by stopping information from crossing the gap and new ones are neurotransmitter specific. Some work best for things like restless leg because they can block instructions to your legs. Some opiates give you restless leg because they stimulate dopamine and dopamine can over ride Serotonin. Street drugs do the same thing. It isn't the street drug that makes you feel good but the increased dopamine production. Addiction happens because you want the feel good from dopamine that works with mood. Alcohol on the other hand is a depressant.
So why do some people need so much more than others and why do they not stop panic in some people?
Designer benzos work on specific triggers (like restless leg) But your doctor doesn't know which does what. So he/she guesses. Or uses Diazepam that works on everything. But Diazepam has a long half life so you need the smallest dose that works. Fine but there is still a reason why they don't sometimes work and that reason is you. Some pathways have to be open for you to function but anxiety can use these. If you use a benzo to get back to feeling positive that you were feeling before an attack they work, but if you are using them to block negative thoughts, you will have limited success. You will be overloading them. Distractions and coping skills work with them because the focus moves off the negative. So if you take a benzo to get the most out of it you want to think positive so it can do it's job without interference.
Ativan is a dangerous drug because it blocks all the crossing points but one making a priority pathway. Hypothalamus has to use that pathway only. When Ativan wears off all the other crossing points open without Hypothalamus's direction. Massive rebound as information floods across.
Diazepam blocks all crossing but not at all synapses so information is just slowed down as it finds detours. Don't worry, it would take very massive doses to shut down every synapse and kill you. Diazepam is usually used for withdrawal because it has a long half life and a blanket effect on the synapses allowing them to come back on line slowly and equally.
Great post Davit. I'd like to add that 90% of the serotonin is found in the gut and there is a link between the types of gut bacteria and the amount of serotonin produced in the body. For this reason, diet is a huge component in healing and recovery.
Diet is also responsible for how much Tryptophan gets to the brain to make Serotonin since Serotonin in the body can not cross the blood brain barrier
---------- Post added at 15:07 ---------- Previous post was at 15:05 ----------
Low platelets are a sign of low Serotonin.
MyNameIsTerry
25-06-15, 07:06
I know Diazepam works by causing an increase in GABA from the GABAA receptors. GABA is the major inhibitory neurotransmitter in the brain. As far as I know, GABA inserts by to certain receptors to inhibit synapses. This causes it to open a door to allow chloride ions in or potassium ions out. I can't say I've got any further than that with it so far though.
Noradrenaline is the excitory neurotransmitter when it comes to anxiety.
Its interesting that L-Tryptophan, from the precursors 5-HTP & vitamin C have been seen to double Serotonin production in the brain. I do always find myself asking why doctors mess around with SSRI's (switching them) when they don't consider whether the person's diet is playing a role in why they are doing naff all!!!
It is interesting that Pregabalin works with GABA too and that has some good feedback on the Meds board.
I do find myself wondering though whether we are being given something that meerly stops it leeking as fast to find we aren't even putting enough in the tank in the first place!
GABA, for instance, is a banned substance in the UK. Its no biggie, it got banned when all the media furore occurred over GHB being used as a date rape drug and the athletics scandals which also say DHEA get banned too. However, you can take GABA precursors and whilst it would be illegal to combine them and put them in a bottle, its not illegal to put them in your body and use that as the lab!
This is important to me because I find myself going up & down and I wonder why this is? Could it be an adverse thing, could it even be a lack of nutrients issue, etc?
Glutamate is the major neurotransmitter and I'm aware there are some studies of it lacking in anxiety disorders as well as other mental health issues and it can be converted into GABA. The trouble is, if you load up on L-Glutamine, which one of the 2 are you going to get? Excitory or Inhibitory? Or maybe you will simply increase both which are lacking and the brain will get rid of what it doesn't need? (but Glutamate toxicity is a real issue so I guess you have to work out just how high that is first)
Is not taking Gaba if you are on an SSRI considered dangerous? If Gaba blocks and Serotonin blocks could you not end up in a coma?
---------- Post added at 01:25 ---------- Previous post was at 01:23 ----------
So is vitamin C the Tryptophan carrier, I thought it might be.
Thanks for this thread. Very interesting.
MyNameIsTerry
25-06-15, 10:09
I would have to check on the vitamin C issue but vitamin B6 tends to be needed for synthesis of certain neurotransmitters so it could be that or a carrier? Since the brain is said to hold 10-50 times the level of vitamin C found in blood plasma, which is seen as the threshold, it would suggest it would be.
Is vitamin B6 the carrier for the others even?
Since GABA is already being synthesised from our diet, I wouldn't have thought so otherwise wouldn't we need to be modifying our diets? But then we still need glutamate so it will convert what it needs. I suppose there could be a level you could go beyond that could be an issue but I have no idea on that one. They are making meds that work with glutamate now and they have expanded out the SSRI's & SNRI's to combine with Dopamine and eventually Glutamine so there should be some research out there somewhere.
Great post... very simple to understand:yesyes:
Insulin strips the carrier off the other seven amino acids so I thought it might be glucose based. Needs more reading.
Gotagetthroughthis
25-06-15, 16:54
Great post Davit. This would explain while at my worst and consumed by negative thoughts no amount of Benzos really help. They make my body feel lathargic and slow/heavy and made me drowsy but they had little to no affect at stopping or reducing my negative depressive/anxious thoughts. Its like the body is slowed down but the but the anxious brain is hardly affected.
Also, is there any way to naturally increase dopamine?
I don't know, maybe Terry does. I will see if I can find out. It does increase with stimulation from opiates. So it increases on it's own with need.
Hi davit
Great post I found it very interesting.
A question I wonder you can help me with?
I take diazepam daily (low dose 2mgs) which I'd like to eventually get off. I understand diazepam stays in the body a long time ( some people say 100 hrs others say 8 days some say even longer).
If I take 2mg today, will that 2mg be added to yesterday's 2mg and the previous day's 2 mg etc.
What I'm trying to ask (not very well) how much will actually be in my system today if I take 2mg daily? Taking into account all the build up from previous days?
Well this is interesting. Dopamine production happens through out the body and brain where ever it is needed as needed. Dopamine can not cross the blood brain barrier but Ldopa can. Parkinson's happens when Dopamine production drops when the gland that produces it in the area that controls it is damaged. Ldopa is in the drugs for Parkinson's.
Reward stimulates dopamine production. (runners high) Dopamine affects few neurons compared to the other neurotransmitters. (400,000 only) Dopamine affects mood and is affected by mood. Happy makes more happy. Positive thought and feeling good about yourself stimulates it to produce. It appears worry doesn't waste it but it does waste Serotonin. So other than Ldopa the only way to increase Dopamine is with medication, tricyclic anti depressant, Trimipramine. Or CBT.
---------- Post added at 12:22 ---------- Previous post was at 11:49 ----------
Michelle1
Dr Google doesn't explain this very well.
Half life of Diazepam is 24 hours. Therapeutic effectiveness could be as little as 8. Metabolites can take a very long time to break down. (metabolites have ver little effect) Traces have been found a year later in some studies. Half life is the same whether you take 2mg or 10. Excretion rate is still the same just more of it. So you don't actually compound. Twice or three times a day bridges the half Therapeutic time span so you have a steady state over the half life keeping it effective. Half life means in 24 hours half is gone but effectiveness goes before then. Withdrawal symptoms show anytime after eight on a single dose. EG: take it at night for sleep and sometime the next morning anxiety starts to creep in. How long it says in your system and it's effectiveness depends on what other Medication is using the P450 enzyme system in your liver to break it down. P450 is the most common enzyme and a lot of meds are broke down by it. I have used Diazepam 2mg PRN with no side effects other than a bit of agitation 8 or more hours later. I have taken Diazepam every day for a year twice with no withdrawal problems. No reduction in affect either. It works best with you rather than for you. Reduction only happens with increased anxiety from increased negativity beyond what the dose handles.
So if you exceed what your liver can process you could possibly get a build up but I think in healthy people this is like 40mg a day.
Thinking positive reduces the amount you need. Thinking positive is the best way to get to the point you don't need it.
---------- Post added at 13:01 ---------- Previous post was at 12:22 ----------
Anti psychotic drugs reduce dopamine production.
MyNameIsTerry
25-06-15, 23:03
Hi davit
Great post I found it very interesting.
A question I wonder you can help me with?
I take diazepam daily (low dose 2mgs) which I'd like to eventually get off. I understand diazepam stays in the body a long time ( some people say 100 hrs others say 8 days some say even longer).
If I take 2mg today, will that 2mg be added to yesterday's 2mg and the previous day's 2 mg etc.
What I'm trying to ask (not very well) how much will actually be in my system today if I take 2mg daily? Taking into account all the build up from previous days?
Hi Michelle,
Clear elimination looks like this per half life:
0 100%
1 50%
2 25%
3 12.50%
4 6.25%
5 3.13%
When its under 5% its no longer clinically significant.
Diazepam has a half life of 100 hours.
How it reaches "steady state" which is the point where as much is being taken in as eliminated is different to this. I'll post it on later as it's in another thread.
This will be all blood Plasma based and drugs can be stored otherwise than in the blood. I'm not sure how that affects clear elimination though. This is the extra part you need to know, I'll see if there is some information about it.
---------- Post added at 23:03 ---------- Previous post was at 22:57 ----------
Also, is there any way to naturally increase dopamine?
A quick grab from Wiki:
L-phenylalanine and L-tyrosine are both precursors for dopamine, norepinephrine, and epinephrine. These conversions require vitamin B6, vitamin C, and S-adenosylmethionine.
You would need to understand what influences the Dopamine production over the others though.
I found some pictures, but maybe you have something better, Davit?
I think better when I can visualise.
You guys are on it, Davit and MyNameIsTerry! Wish I had this info sooner!! Thank you!!!!!!!!!!!!!
http://www.yourdiagnosis.com/yourdiagnosis/newsletter/mentalillness.htm
No those are very good pictures, I saved them. Good article too. Glad to see you are expanding your research. Knowledge is power. Yes, I wish I had of known what I know now years ago.
Here are the pics.
:bighug1: for Davit and MyNameIsTerry
MyNameIsTerry
27-06-15, 06:22
Hi Michelle,
Clear elimination looks like this per half life:
0 100%
1 50%
2 25%
3 12.50%
4 6.25%
5 3.13%
When its under 5% its no longer clinically significant.
Diazepam has a half life of 100 hours.
How it reaches "steady state" which is the point where as much is being taken in as eliminated is different to this. I'll post it on later as it's in another thread.
This will be all blood Plasma based and drugs can be stored otherwise than in the blood. I'm not sure how that affects clear elimination though. This is the extra part you need to know, I'll see if there is some information about it.
Michelle,
To reach "steady-state", the point at which as much is going in as out looks like this:
1 50%
2 75%
3 87.5%
4 93.75%
5 96.875%
6 96.4735%
7 99.25%
Day 3 is considered clinically significant.
MoreOrless,
Thank you for your response. I am so sorry you had to go through that!!!! I will definitely not be going cold turkey. I will follow a schedule of gradual reduction. I can't believe I was naive enough to think that this medication would be ok to continue for so long. I'm ready to try getting off it, but I will be doing CBT as well. I'm sure Davit and Terry will know when I've started because I've latched onto their input like a security blanket. LOL!! I apologize in advance if I get too clingy! Haven't started yet. Probably will be in another month or so.
Thanks terry I really appreciate your knowledge and research to help me understand how diazepam works and how long it stays in the body for.
Thanks davit too - I get more valuable advice on here than any doctors office.
So terry, if I take 2 mg daily, by the end of 7 days. How many mg approx would be in my body?
Davit, I read your advice on how to withdraw from diazepam and you seem to have withdrawn easily by extending the length of time between doses?
How would that look
Ie today take dose at 7pm
Tomorrow take dose at 10 pm?
Or longer gaps? Or just go with how your own body responds?
I know I'm on a tiny dose (and some people on the diazepam threads have mocked us struggling to come off). But believe me tiny doses too are hard to get off especially when you have taken them daily for 5/6 years.
MyNameIsTerry
27-06-15, 11:11
I know I'm on a tiny dose (and some people on the diazepam threads have mocked us struggling to come off). But believe me tiny doses too are hard to get off especially when you have taken them daily for 5/6 years.
I will see what I can find out because I'm not too sure on the buildup issue from being on it daily as metabolities can be stored. Some others on here might know this though so maybe they will spot this thread and be able to answer that one. I will see what I can find though as its a question that covers all meds, not just these and I would be interesting in how mine would be working too.
Please don't entertain anyone mocking someones dose. Some people drop from higher doses much easier and struggle on low doses and as seen on NMP so whether they were on high or just stayed on low, the likeihood would be the same.
Besides there's just no place for mockery on here, its born out of ignorance.
MyNameIsTerry
29-06-15, 07:00
Xanax is by far one of the worst drugs ever,some would even consider it worse than heroin. I have been going around spreading awareness of the dangers of taking benzodiazapines and what they can do to your body.Many people do not realize that benzos are one of the only drugs that can actually kill you from withdrawals alone. My doctor did not even know this and had me come off of xanax and valium cold turkey. I ended up in the hospital for 3 days and almost died.
Yes, you do seem to be going around spreading awareness, of a product you are selling for £59.99 via Clickbank that your first username on NMP is attached to! Then you signed up with several different usernames to do the same and you were banned on them all.
Michelle I just went with how my body felt, so some times it would be at night. Eventually it was getting so extended I forgot to take them even though there was some agitation. But remember I was combining it with a lot of positive thought.
Terry I took a lot of flack because I can spot a phoney. I should not have fought back, I knew he would get caught, but he might have sold some books first.
MyNameIsTerry
29-06-15, 08:41
You are without a doubt right to point things out about these affiliate marketers, many of them are complete fakes who make up a blog to appear like sufferers. They can be easy to spot, a blog selling a method with hardly any entries is a good candidate and I've seen quite a few now. I've even seen fake forums themselves set up to promote goods. Vulnerable people get stung by these people.
I don't think people knew about this person hence why I posted that message to all so I think that was out of context. I doubt there is a public forum in existence where everyone gets along, I fall out with the odd person here & there and I do get slightly annoyed at how some of the OCD'ers get treated on a certain board but I try to keep emotion out of it or it can spiral. The issue itself is between the people airing their feelings and I get on with all of you.
It would be a boring world without debate anyway.
Nice Catch! I'm not sure how you did that, but being aware is important! Nice work guys! ;)
Davit and My Name is Terry your knowledge is incredible and I love the explanations. Thank you. BUT for a simpleton like me could you explain things without all the jargon...perhaps as you would explain to a 13 yr old. I sometimes have to give up reading your posts because I don't understand:doh:
Sarah
What would you like explained. You can ask here or on PM.
MyNameIsTerry
05-07-15, 11:34
Thanks Sarah,
Fire away if there is anything unclear, if I wander into jargon land give me bop with your truncheon :D
Listen you both have exceptional knowledge but you lose me in the overly long explanations. I M SURE others understand it but I don't always. I will try to keep up:).
Just a little personal note..and I don't want to interfere with the big argument that is going on..but I find Ricardo is ALSO great on here. PLEASE could you all try to get along. Its really sad to loose anyone from NMP:weep:
Sarah
MyNameIsTerry
07-07-15, 06:51
Listen you both have exceptional knowledge but you lose me in the overly long explanations. I M SURE others understand it but I don't always. I will try to keep up:).
Just a little personal note..and I don't want to interfere with the big argument that is going on..but I find Ricardo is ALSO great on here. PLEASE could you all try to get along. Its really sad to loose anyone from NMP:weep:
Sarah
Just ask if you need any help, Sarah, and I'll try.
I'm afraid I can't help on the last issue, I don't know why Ricardo chose to say certain things to me and since there was no answer before he left, its a dead issue now.
MyNameIsTerry
02-08-15, 09:27
Updating previous Day vs. %:
The plasma levels issue is in relation to "steady-state" which is 4-5 half lives of any drug. It looks like this:
HL.......%
1........50
2........75
3........87.5
4........93.75
5........96.875
6........98.4735
7........99.25
Clear elimination has the following:
HL.......%
0.........100
1.........50
2.........25
3.........12.50
4.........6.25
5.........3.13
When its under 5% its no longer clinically significant. It's more complicated than this when you consider how people taper as it will mean some overlap and then with some meds (e.g. Benzo's) you also have the storage outside of blood plasma which also needs elimination.
Factors involved in speed of distribution (drug starting to work) & elimination (clearance out of blood plasma) can be things like age (children differ, there are specific calculations for age that can be used for older people), speed of metabolism, weight (which will impact on metabolism), renal insufficiency conditions, etc. There are some very complicated guides on the internet for those interested such as some books on pharmacokinetics on Google Books but they are very difficult to understand without a medical background.
MyNameIsTerry
12-10-15, 06:43
Posting in a very useful thread about future types of meds by NoPoet as it shows the range of neurotransmitters that pharmaceutical companies are looking to exploit in meds that could be useful in the future:
http://www.nomorepanic.co.uk/showthread.php?t=54701
It will be interesting to see how dopamine, glutamate and GABA all fit together in future meds on top of the current types e.g. SNRI's and the later variants that added a 3rd & 4th neurotransmitter system to them.
chickenhawk
08-11-15, 22:30
I have depended on Ativan for the past 4 years as a safety net for occasional panic, and to get an occasional good nights sleep. I have used it at the rate of 1/2mg per week, (ie once a week, sometimes twice a week, sometimes none). Because I keep a meds diary, I know I have taken between 20 and 30 mgs a year. This year so far I am up to 25mg. Now I am too scared to take it anymore because I have read articles that say that benzos, along with tri-cyclics and sedating antihistamines, ie anticholinergics, are linked to brain damage and 'frontal temporal dementia'. As if I dont have enough to panic about already! I have long-standing GAD and agaraphobia, and am facing a home move in the next couple of weeks and not coping well. Doc prescribed some valium to help me over the worst of it, but again, too scared to take this stuff anymore, as I am in the older age group and feel like a sitting duck for dementia as it is! Now I feel I have nothing to fall back on and don;t know what to do. I am not on any other meds, but at this rate will end up on something, if I have a complete breakdown over this move (which is huge for me). Anyone else worried about this? I'm really sorry to bring up a stressful subject.
MyNameIsTerry
09-11-15, 05:29
I have depended on Ativan for the past 4 years as a safety net for occasional panic, and to get an occasional good nights sleep. I have used it at the rate of 1/2mg per week, (ie once a week, sometimes twice a week, sometimes none). Because I keep a meds diary, I know I have taken between 20 and 30 mgs a year. This year so far I am up to 25mg. Now I am too scared to take it anymore because I have read articles that say that benzos, along with tri-cyclics and sedating antihistamines, ie anticholinergics, are linked to brain damage and 'frontal temporal dementia'. As if I dont have enough to panic about already! I have long-standing GAD and agaraphobia, and am facing a home move in the next couple of weeks and not coping well. Doc prescribed some valium to help me over the worst of it, but again, too scared to take this stuff anymore, as I am in the older age group and feel like a sitting duck for dementia as it is! Now I feel I have nothing to fall back on and don;t know what to do. I am not on any other meds, but at this rate will end up on something, if I have a complete breakdown over this move (which is huge for me). Anyone else worried about this? I'm really sorry to bring up a stressful subject.
Have you got an article we can look at?
The last one I saw was in the British Medical Journal (BMJ) and it made NO connection between Benzo's and Dementia. It only established that there were older people on Benzo's that had dementia but it was completely unknown whether their symptoms of anxiety leading to treatment with Benzo's was actually Dementia's early symptoms.
I have depended on Ativan for the past 4 years as a safety net for occasional panic, and to get an occasional good nights sleep. I have used it at the rate of 1/2mg per week, (ie once a week, sometimes twice a week, sometimes none). Because I keep a meds diary, I know I have taken between 20 and 30 mgs a year. This year so far I am up to 25mg. Now I am too scared to take it anymore because I have read articles that say that benzos, along with tri-cyclics and sedating antihistamines, ie anticholinergics, are linked to brain damage and 'frontal temporal dementia'. As if I dont have enough to panic about already! I have long-standing GAD and agaraphobia, and am facing a home move in the next couple of weeks and not coping well. Doc prescribed some valium to help me over the worst of it, but again, too scared to take this stuff anymore, as I am in the older age group and feel like a sitting duck for dementia as it is! Now I feel I have nothing to fall back on and don;t know what to do. I am not on any other meds, but at this rate will end up on something, if I have a complete breakdown over this move (which is huge for me). Anyone else worried about this? I'm really sorry to bring up a stressful subject.
Chicken hawk
I had been taking Valium 4 mg once/twice weekly to help me through exposure therapy for agoraphobia.
Eventually, I realised I was building a tolerance/additiction to the drug when my panic was increasing/becoming more severe, and frequent. yet vanishing on taking the drug!! Duh.
Ironically it did help me to attempt my exposure therapy tasks, which did improve overall!
Moving home will be so stressfull, and I do believe taking a SHORT course will be beneficial to you. But I would def try to find other ways of dealing with long-term anxiety after that.
There is the danger of turning everything into a major stressful event that ONLY a benzo can fix.
I haven't taken any vakium since Feb 2015. I had just over a month of withdrawal symptoms, which SHOCKED me because, I thought I was taking so little and so infrequently!!!
I do worry now because I don't have anything (meds) to turn to 'if' I am in a desperate state
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