Can anyone make sense of this to explain to a layperson?

Terry, I too have hip take lisinopril 20 mg.  I started it around the same time as crossover to v so I often wonder if some of my symptoms are from that med.  my pressure still is a little high, just top number.  It’s ok in am but creeps up and at drs it goes up a lot, stress I guess.  So happy for you at least you are off drugs.  I feel so hopeless, such a sad place to be, cry all day and can’t control my emotions anymore.  You add so much to this board also, thank you..

 

Free, I don't know what your symptoms are but thought I'd chime in because someone very close to me was on a BP med from the same family as Lisinopril.  They were feeling terrible for a lonnng time and couldn't figure it out, extreme lethargy and malaise, persistent cough, plus, plus.  They actually CT'd the med and within 24hrs they felt like a new person.  Just a thought for you to ponder.

Thanks, will think about it all.

As it is, every time I go to the nephrologist, he prescribes another drug. He told me himself that if doctors don't know exactly what a person has, they prescribe drugs. Exactly what the psychiatrist does. Now I have 6 different drugs! That's why I want to get to the bottom of what is ailing me with the bp issue.

 

I'm reading an interesting book about drugs called Blue Dreams. The writer thinks that in the future, LSD, MDMA, and psilocybin, used in the presence of therapists, will take the place of a lot of pharma drugs.

 

Bolded above.  That is very true, and when it comes to psychoactive pharmaceuticals it becomes a trial and error kind of thing.  The patient is the modern day lab rat......

dm123, this is modern medicine for you! This is doctors showing that they're doing the "right thing." !!!

Terry, I too have hip take lisinopril 20 mg.  I started it around the same time as crossover to v so I often wonder if some of my symptoms are from that med.  my pressure still is a little high, just top number.  It’s ok in am but creeps up and at drs it goes up a lot, stress I guess.  So happy for you at least you are off drugs.  I feel so hopeless, such a sad place to be, cry all day and can’t control my emotions anymore.  You add so much to this board also, thank you..

 

freeme, I'm so sorry that you cry all day and can't control your emotions. I feel hopeless also. I would like to cry, but I'm still blunted in that area. This is a very difficult road, no doubt about it. My heart goes out to you!

 

I wish I were off drugs. I'm still taking a load. My bp is lower in the morning, and I'm able to go a long while without another pill. Oh, it's terrible in the doctor's office. I have never gotten used to people exclaiming about it, and of course that brings on more PTSD.

 

I have a number of side effects from the pills. One of them is increased anxiety when the pills wear off. I don't get it from the Losartan, though. But it's awful trying to combat anxiety also while getting it from the bp pills.

 

My bp was doing great every day. It was really solid. Suddenly, yesterday it got high (150s-161), and it's carried on to today. I don't know what I did wrong and have been going over the things I ate, etc. Maybe it's due to my kidneys? I've been through this so, so many times while in benzo withdrawal/recovery. I wonder if this is still the benzo or am I going to have to deal with this the rest of my life. And that would be just awful! I actually control my environment so that I don't have any stressors, and that makes it a pretty lonely life. I just got DNRS, Dynamic Neural Retraining System. They talk about how screwed up the limbic system can be, and this package helps you to form new pathways in the brain so that you're not compromised. You have to do the exercises for at least 6 months. I think I've been in this so long that it's caused a deep rut in a worn pathway. I'm hoping it does something!

 

Thank you for the compliment! Actually, I come over here to check out what dm123 has to say because there's always something interesting. And he has been doing the lion's share. So much information and research!!!

 

As for bp being a symptom, I keep thinking it is. I have no answers, though. My nephrologist just said, "Some people just have bad blood pressure," but I keep thinking that it's something else. I feel it in my head when my bp goes up, in the frontal lobe. No one ever talks about that.

 

Good luck to you!!!

Thanks Terry, I hope you can get things to a better place.  I just feel hopeless and see no wat out for me, too old and been on all this crap for yrs, doc insisted.  Who knew what nightmare awaited me.  Thanks again.. 

Just keep going, that's all I can say, freeme. We all get so discouraged, and there have been many times that I just feel as if I can't do this anymore. But going back on benzos would not be the answer for me. I just won't do that again. Going on any other psych drug wouldn't do it for me either.

 

Taking it day by day helps. Nova once said, "There is grace enough for today." That gives me hope. If I start looking beyond, I get really discouraged. I think of all the time I've been in this, all the friendships I've lost, the family that thinks I'm kind of crazy, and it just doesn't seem worth it, especially because there's no time limit on this seemingly. It goes on and on and on.

 

We have to have great resilience and courage to go through this. I keep wanting to know what's on the "other side." I keep wanting to see what I would feel like well. I don't get windows at all, so I have to keep hoping for that.

 

I hope that we can both experience freedom from this!!

dm123, I have a question. Yesterday my bp was in the 150s-161 area. I didn't understand this at all. I feel pressure in my frontal lobe when my bp goes up. This morning my bp was back to 116/64. I knew it was down because I feel a "cushion-y" effect on my frontal lobe, like there's a cushion protecting it. I've always been curious about this and don't know if others feel the same thing. Is it because of the benzo effect or something else? I always feel it in my head when the blood pressure goes up. This yanking of my bp has gone on far too long.

 

If you can help me figure this out, I would be very thankful!!

Just to update- I listened to the YouTube presentation by Dr Martin Pall - very good , and very clarifying on this NO/ONOO thing .

I like his summary of supplemental protocols at the end , what to use , why and how .

I'm adding vitamin C to my regimen along with a little more Methyl folate today to see how I do .

 

With the genetic polymorphisms I have , it seems obvious that my body would need some hope with anti oxidizing . The especially with very little activity of the SOD enzyme

 

Thanks for everything. DM .

I will update if I feel improvements. I've already been taking ALCAR for a while , it's always felt really good for me , I see he has a caviat for it though which I have to revisit .

 

Hang in there everyone , make the most of today in whatever way you can ,

MiYu

 

THank you DM for both your responses to mine.

I do think that antioxidants are really important for me at this time. SInce I've been experimenting with more B's (not all methyl) , and adding some C and ALCAR, I feel more energy.

 

If CLonazepam does indeed deplete dopamine, (which  with my genetic COMT variants I should be high in) , it might make sense why my restless legs are so much worse these days. I take a little Mucuna pruriens extract if they get bad and that always calms them down ( natural source of L-dopa, velvet bean)

 

on we go ... thanks for everything .

We will heal heal from this won;t we????it's a bit scary reading this thread to me , but I also find the information so helpful too thank you.

 

MiYu

 

Hi MiYu,

 

We do know that when things are working, benzdiazaphines tend to increase extracellular levels of DA, at least in the VTA region of the brain.  This is because benzdiazaphines are able to inhibit GABAERGIC interneurons (since the GABAaRs are still functioning properly), so less GABA is released from their axon terminals that project to DA interneurons.  So the VTA DA interneurons get overly excited and their projections out to the mPFC and NAcc regions of the brain release more DA out to these areas of the brain.  They think that this creates the reinforcement of benzdiazaphine drug use (even though I don’t believe it creates classical addiction , but rather dependency)

 

 

When we go into tolerance or wd, assuming the GABAaRs are insufficient and dysfunctional just the opposite can occur.  Less inhibition of GABAERGIC interneurons, so they release more GABA out their axon terminal projections to the DA interneurons.    The VTA DA interneurons become overly inhibited and release less DA out their projections.

 

I take antioxidants as well.

 

Yes we heal from it.  The body is amazing when it comes to adaptation.

 

Now applying this to a cortical motor circuit (restless legs) is much more complex, but my point is that in tolerance and wd, benzdiazaphines do have very opposite effects in neurotransmitter levels like DA, etc.

 

thank you for explaining this DM ,a nd for your reassurance that we do heal!

I will just trust my body's response to the mucuna for now , it definitely helps the restless legs, and mucuna  is known for it's L-dopa content.

 

I don;t take it nightly as one can become tolerant to that too.

 

Anti-oxidants seem very important for me at the moment ,

 

miYu

I'm not sure if I got this right:

 

https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor

 

https://en.wikipedia.org/wiki/Somatic_nervous_system

 

'Thus somatic nervous system consists of two parts:

 

    Spinal nerves: They are peripheral nerves that carry sensory information into and motor commands out of the spinal cord.

    Cranial nerves: They are the nerve fibers that carry information into and out of the brain stem. They include smell, vision, eye, eye muscles, mouth, taste, ear, neck, shoulders, and tongue.'

 

´he somatic nervous system controls all voluntary muscular systems within the body, and the process of voluntary reflex arcs.

 

The basic route of nerve signals within the efferent somatic nervous system involves a sequence that begins in the upper cell bodies of motor neurons (upper motor neurons) within the precentral gyrus (which approximates the primary motor cortex). Stimuli from the precentral gyrus are transmitted from upper motor neurons and down the corticospinal tract, via axons to control skeletal (voluntary) muscles. These stimuli are conveyed from upper motor neurons through the ventral horn of the spinal cord, and across synapses to be received by the sensory receptors of alpha motor neurons (large lower motor neurons) of the brainstem and spinal cord.

 

Upper motor neurons release a neurotransmitter, acetylcholine, from their axon terminal knobs, which are received by nicotinic receptors of the alpha motor neurons. In turn, alpha motor neurons relay the stimulus.

 

From there, acetylcholine is released from the axon terminal knobs of alpha motor neurons and received by postsynaptic receptors (Nicotinic acetylcholine receptors) of muscles, thereby relaying the stimulus to contract muscle fibers. ´

 

Achetylcholine in the spinal cord and brain stem, where clonazepam has a strong effect compared to other benzodiazepines. Okay, I´m not having my day and wrapping it up ...

 

Does it seem reasonable that lowered GABA (my case: switching to lorazepam, building tolerance/dependence and switching back thus ´clipping´ GABA receptors) causes hyperexcitability by altering the balance  of dopamine-acetylcholine in favor of elevated achetylcholine ?

 

And I know this is not a proper source: http://thebrain.mcgill.ca/flash/i/i_06/i_06_m/i_06_m_mou/i_06_m_mou.html ´When an action potential reaches a neuromuscular junction, it causes acetylcholine to be released into this synapse. The acetylcholine binds to the nicotinic receptors concentrated on the motor end plate, a specialized area of the muscle fibre's post-synaptic membrane. This binding causes the nicotinic receptor channels to open and let sodium ions enter the muscle fibre. ´ I´m not sure if that somehow pertains to the alleged effect of clonazepam on sodium channels, since that´s outside the CNS.

I'm not sure if I got this right:

 

https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor

 

https://en.wikipedia.org/wiki/Somatic_nervous_system

 

'Thus somatic nervous system consists of two parts:

 

    Spinal nerves: They are peripheral nerves that carry sensory information into and motor commands out of the spinal cord.

    Cranial nerves: They are the nerve fibers that carry information into and out of the brain stem. They include smell, vision, eye, eye muscles, mouth, taste, ear, neck, shoulders, and tongue.'

 

´he somatic nervous system controls all voluntary muscular systems within the body, and the process of voluntary reflex arcs.

 

The basic route of nerve signals within the efferent somatic nervous system involves a sequence that begins in the upper cell bodies of motor neurons (upper motor neurons) within the precentral gyrus (which approximates the primary motor cortex). Stimuli from the precentral gyrus are transmitted from upper motor neurons and down the corticospinal tract, via axons to control skeletal (voluntary) muscles. These stimuli are conveyed from upper motor neurons through the ventral horn of the spinal cord, and across synapses to be received by the sensory receptors of alpha motor neurons (large lower motor neurons) of the brainstem and spinal cord.

 

Upper motor neurons release a neurotransmitter, acetylcholine, from their axon terminal knobs, which are received by nicotinic receptors of the alpha motor neurons. In turn, alpha motor neurons relay the stimulus.

 

From there, acetylcholine is released from the axon terminal knobs of alpha motor neurons and received by postsynaptic receptors (Nicotinic acetylcholine receptors) of muscles, thereby relaying the stimulus to contract muscle fibers. ´

 

Achetylcholine in the spinal cord and brain stem, where clonazepam has a strong effect compared to other benzodiazepines. Okay, I´m not having my day and wrapping it up ...

 

Does it seem reasonable that lowered GABA (my case: switching to lorazepam, building tolerance/dependence and switching back thus ´clipping´ GABA receptors) causes hyperexcitability by altering the balance  of dopamine-acetylcholine in favor of elevated achetylcholine ?

 

And I know this is not a proper source: http://thebrain.mcgill.ca/flash/i/i_06/i_06_m/i_06_m_mou/i_06_m_mou.html ´When an action potential reaches a neuromuscular junction, it causes acetylcholine to be released into this synapse. The acetylcholine binds to the nicotinic receptors concentrated on the motor end plate, a specialized area of the muscle fibre's post-synaptic membrane. This binding causes the nicotinic receptor channels to open and let sodium ions enter the muscle fibre. ´ I´m not sure if that somehow pertains to the alleged effect of clonazepam on sodium channels, since that´s outside the CNS.

 

 

Hi liberty let me take a closer look when I have more time.

 

The above is a motor neural circuit.  I haven’t presented that stuff yet, but the short answer to your question is yes.  In tolerance ( your state) the circuit is under stress and neurotransmitter homeostasis is dysfunctional and action potientials across neurons don’t quite fire off in the precise phasic fashion that they do in the healthy state.  But the circuit can hold up quite well, and there are only severe issues when it can no longer accommodate the dysfunctional inhibitory GABAERGIC signaling.  At this point the circuit crashes and one becomes increasingly symptomatic.

 

By lclipping” I assume you mean those subunit populations are lacking vs. a normal pre benzdiazaphine state, correct?  I ask because it’s an unusual term....

Hi all, there’s a good discussion in the Lapis dizziness support group thread.  Also I introduced a VOR neural circuit.

 

Thanks to Lapis for running that thread 

 

http://www.benzobuddies.org/forum/index.php?topic=128947.6240#lastPost

'clipping' Lorazepam has a higher affinity for alpha 1 than clonazepam (most likely), thus downregulating the GABAA receptors. By whatever mechanism.

Trying to visualize that part of the process ... As in, with scissors ...

 

So in short, the answer is 'yes' I guess. Of course, there is alpha 5,2,3 but I was trying to keep it simple. I never figured out if lorazepam did anything to alpha 5.

 

Note: very hard to find anything about lorazepam and binding to alpha subunits. I´m sure it must affect alpha 2 and 3.

 

My primary source: https://www.ncbi.nlm.nih.gov/pubmed/1653067

 

´we treated mice with lorazepam, 2 mg kg-1 daily for 1-28 days and evaluated mRNAs for the alpha 1 and gamma 2 subunits by Northern hybridization. In cerebral cortex, concentrations of mRNA for the alpha 1 and gamma 2 subunits were unchanged from vehicle or control after 1-10 days of lorazepam. However, after 14 days of treatment mRNA concentrations for both subunits decreased to approximately 50% of control values and remained decreased at 28 days. In contrast, no significant alterations were observed for either subunit mRNA in hippocampus or cerebellum over the same time course. Alterations in mRNAs in cortex occur after the development of tolerance and receptor downregulation in this model.´

 

Mice are small, but that doesn´t necessarily transalate to equivalent doses based on body weight. This points very strongly to alpha 1. note the comments about the hippocampus and cerebellum.

 

Soemtimes hard to retrieve the location of a PDF that has a google reference, but I think this is it see PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917851/

´Binding was decreased in the hippocampus after lorazepam but not

alprazolam, as previously found.´ a bit different. ´hippocampus after lorazepam but not alprazolam, as previously found. For both drugs decreases in binding in the hypothalamus did not achieve significance, in contrast to previous findings´ Side note: I wonder to what extent the effects of hypnotics depend on the (hypo) thalamus. There is a bit more.

 

https://www.nature.com/articles/1380246

´Depression of Thalamic Metabolism by Lorazepam Is Associated with Sleepiness´ It was sedating and a bit hypnotic at first, the full 4 mg a day ... Downregulation of the receptors in the thalamus must not be a good thing.

Just keep going, that's all I can say, freeme. We all get so discouraged, and there have been many times that I just feel as if I can't do this anymore. But going back on benzos would not be the answer for me. I just won't do that again. Going on any other psych drug wouldn't do it for me either.

 

Taking it day by day helps. Nova once said, "There is grace enough for today." That gives me hope. If I start looking beyond, I get really discouraged. I think of all the time I've been in this, all the friendships I've lost, the family that thinks I'm kind of crazy, and it just doesn't seem worth it, especially because there's no time limit on this seemingly. It goes on and on and on.

 

We have to have great resilience and courage to go through this. I keep wanting to know what's on the "other side." I keep wanting to see what I would feel like well. I don't get windows at all, so I have to keep hoping for that.

 

I hope that we can both experience freedom from this!!

 

 

Hi Terry,

Going back on Benzodiazaphines  won’t help.  It will make things worse.  Benzodiazaphines emphatically do more harm than good.  I’ve thought about this long and hard. 

 

The psychiatrist will say “but this class of drugs do help some people”.    I would argue with that.  The problem is, although some people can tolerate chronic benzdiazaphine use better than others , what life do they actually have?.  The psychiatrist will state “ they are working and functioning “.    While this may be true,  I would then ask, “what is their quality of life”.    This gets to the heart of the discussion.

 

While some can tolerate chronic benzdiazaphine use quite well, i would then ask the psychiatrist “how happy is that person, does that person have mysterious aches and pains, is the person depressed, is the person free from anxiety, how many doctors are working with this patient?”

 

The psychiatrist will attribute the aches and pains to aging, the depression to an organic clinical mental disorder, the anxiety to a preexisiting clinical disorder, etc.....

 

I would then ask the psychiatrist about any other “adjunctive” medications that the patient was on.  Usually as the years pass by the “adjunctive” meds build up over time.  That, or benzdiazaphine dosage increases, or in the worst of cases, tolerance slowly builds up as the patient resists increasing the dose.  One has to ask: what value does such a drug have?

 

My question to the psychiatrist would then be “ how many of these secondary disorders would you attribute to the benzdiazaphine? “ , to which he or she would confidently, firmly, and emphatically reply ::

 

“NONE!”

 

Stevie Nicks talks about this  lot. She became the person she least liked, the longer she continued to use Benzodiazaphines.    If benzdiazaphines helped in any way, shape or form, even with all of their shortcomings, I would be ok with their therapeutic use.  The fact is, beyond 2 weeks (clinically the time is even shorter) physiological changes in the body start to take place, that makes them a completely useless therapeutic compound.  It creates the exact same issues that it was intended to address, and it makes them all far worse..  What kind of drug is that?

 

I’ve never been to a psychiatrist before, but I’ve been on Benzodiazaphines and I know what they do.  I’ve read enough signatures on B.B. to discern the truth about what’s really going on.

 

For the outpatient there’s  absolutely  nothing of value  in the benzdiazaphine.

dm123, I have a question. Yesterday my bp was in the 150s-161 area. I didn't understand this at all. I feel pressure in my frontal lobe when my bp goes up. This morning my bp was back to 116/64. I knew it was down because I feel a "cushion-y" effect on my frontal lobe, like there's a cushion protecting it. I've always been curious about this and don't know if others feel the same thing. Is it because of the benzo effect or something else? I always feel it in my head when the blood pressure goes up. This yanking of my bp has gone on far too long.

 

If you can help me figure this out, I would be very thankful!!

 

Hi Terry, yes i remember that question well.

 

I can only tell you from experience, a long time back, I had very high BP, and I would get intense pressure in the head when it spiked.  I can only attribute this feeling to literal high vascular pressure of the normal blood flow to the brain (arteries) pushing out the vessel walls, ever so slightly, giving us the full head-pressure exploding feeling.  I would get it really bad when going from sitting to standing which makes sense.

 

Ive long since “cured” my HBP through diet alone.  I was allergic to gluten.  Once I quit gluten, vascular inflammation decreased and my BP dramatically dropped.  My BP went from 180/100 to 115/65 over the course of several months.  This was many years ago and I’ve never had an issue again with BP. 

Note: very hard to find anything about lorazepam and binding to alpha subunits. I´m sure it must affect alpha 2 and 3.

 

My primary source: https://www.ncbi.nlm.nih.gov/pubmed/1653067

 

´we treated mice with lorazepam, 2 mg kg-1 daily for 1-28 days and evaluated mRNAs for the alpha 1 and gamma 2 subunits by Northern hybridization. In cerebral cortex, concentrations of mRNA for the alpha 1 and gamma 2 subunits were unchanged from vehicle or control after 1-10 days of lorazepam. However, after 14 days of treatment mRNA concentrations for both subunits decreased to approximately 50% of control values and remained decreased at 28 days. In contrast, no significant alterations were observed for either subunit mRNA in hippocampus or cerebellum over the same time course. Alterations in mRNAs in cortex occur after the development of tolerance and receptor downregulation in this model.´

 

Mice are small, but that doesn´t necessarily transalate to equivalent doses based on body weight. This points very strongly to alpha 1. note the comments about the hippocampus and cerebellum.

 

Soemtimes hard to retrieve the location of a PDF that has a google reference, but I think this is it see PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917851/

´Binding was decreased in the hippocampus after lorazepam but not

alprazolam, as previously found.´ a bit different. ´hippocampus after lorazepam but not alprazolam, as previously found. For both drugs decreases in binding in the hypothalamus did not achieve significance, in contrast to previous findings´ Side note: I wonder to what extent the effects of hypnotics depend on the (hypo) thalamus. There is a bit more.

 

https://www.nature.com/articles/1380246

´Depression of Thalamic Metabolism by Lorazepam Is Associated with Sleepiness´ It was sedating and a bit hypnotic at first, the full 4 mg a day ... Downregulation of the receptors in the thalamus must not be a good thing.

 

Hi liberty, yes.  Unfortunately it is true.  And unfortunately the hippocampus is hit hard by benzdiazaphine induced subunit downregulation and other conformational changes.  And given it is highly plastic, the hippocampus undergoes several morphological changes that take time to revert.

 

Since you were on 4mg at one time, and are currently at 2 mg, as you know you are probably in tolerance at your current dose.  As you know, the only way you can effectively start healing the receptors is to get off the benzdiazaphine.    I wish there was an easier way, but those receptors need the time and freedom to heal. 

 

Best,

Dm123

Just to update- I listened to the YouTube presentation by Dr Martin Pall - very good , and very clarifying on this NO/ONOO thing .

I like his summary of supplemental protocols at the end , what to use , why and how .

I'm adding vitamin C to my regimen along with a little more Methyl folate today to see how I do .

 

With the genetic polymorphisms I have , it seems obvious that my body would need some hope with anti oxidizing . The especially with very little activity of the SOD enzyme

 

Thanks for everything. DM .

I will update if I feel improvements. I've already been taking ALCAR for a while , it's always felt really good for me , I see he has a caviat for it though which I have to revisit .

 

Hang in there everyone , make the most of today in whatever way you can ,

MiYu

 

THank you DM for both your responses to mine.

I do think that antioxidants are really important for me at this time. SInce I've been experimenting with more B's (not all methyl) , and adding some C and ALCAR, I feel more energy.

 

If CLonazepam does indeed deplete dopamine, (which  with my genetic COMT variants I should be high in) , it might make sense why my restless legs are so much worse these days. I take a little Mucuna pruriens extract if they get bad and that always calms them down ( natural source of L-dopa, velvet bean)

 

on we go ... thanks for everything .

We will heal heal from this won;t we????it's a bit scary reading this thread to me , but I also find the information so helpful too thank you.

 

MiYu

 

Hi MiYu,

 

We do know that when things are working, benzdiazaphines tend to increase extracellular levels of DA, at least in the VTA region of the brain.  This is because benzdiazaphines are able to inhibit GABAERGIC interneurons (since the GABAaRs are still functioning properly), so less GABA is released from their axon terminals that project to DA interneurons.  So the VTA DA interneurons get overly excited and their projections out to the mPFC and NAcc regions of the brain release more DA out to these areas of the brain.  They think that this creates the reinforcement of benzdiazaphine drug use (even though I don’t believe it creates classical addiction , but rather dependency)

 

 

When we go into tolerance or wd, assuming the GABAaRs are insufficient and dysfunctional just the opposite can occur.  Less inhibition of GABAERGIC interneurons, so they release more GABA out their axon terminal projections to the DA interneurons.    The VTA DA interneurons become overly inhibited and release less DA out their projections.

 

I take antioxidants as well.

 

Yes we heal from it.  The body is amazing when it comes to adaptation.

 

Now applying this to a cortical motor circuit (restless legs) is much more complex, but my point is that in tolerance and wd, benzdiazaphines do have very opposite effects in neurotransmitter levels like DA, etc.

 

thank you for explaining this DM ,a nd for your reassurance that we do heal!

I will just trust my body's response to the mucuna for now , it definitely helps the restless legs, and mucuna  is known for it's L-dopa content.

 

I don;t take it nightly as one can become tolerant to that too.

 

Anti-oxidants seem very important for me at the moment ,

 

miYu

 

Hi MiYu

 

Yes we do heal.  I’m not just being a cheerleader.  I believe it.  But it can be terribly slow.  It is for me.  We lose a lot during the journey, but we also gain a lot of wisdom and fortitude and strength.

dm123, I have a question. Yesterday my bp was in the 150s-161 area. I didn't understand this at all. I feel pressure in my frontal lobe when my bp goes up. This morning my bp was back to 116/64. I knew it was down because I feel a "cushion-y" effect on my frontal lobe, like there's a cushion protecting it. I've always been curious about this and don't know if others feel the same thing. Is it because of the benzo effect or something else? I always feel it in my head when the blood pressure goes up. This yanking of my bp has gone on far too long.

 

If you can help me figure this out, I would be very thankful!!

 

Hi Terry, yes i remember that question well.

 

I can only tell you from experience, a long time back, I had very high BP, and I would get intense pressure in the head when it spiked.  I can only attribute this feeling to literal high vascular pressure of the normal blood flow to the brain (arteries) pushing out the vessel walls, ever so slightly, giving us the full head-pressure exploding feeling.  I would get it really bad when going from sitting to standing which makes sense.

 

Ive long since “cured” my HBP through diet alone.  I was allergic to gluten.  Once I quit gluten, vascular inflammation decreased and my BP dramatically dropped.  My BP went from 180/100 to 115/65 over the course of several months.  This was many years ago and I’ve never had an issue again with BP.

 

Interesting, dm123! I'm on gluten, so maybe I ought to really cut it down. Don't know if I can eliminate it entirely, though, but it's worth thinking about! Thank you!!

Note: very hard to find anything about lorazepam and binding to alpha subunits. I´m sure it must affect alpha 2 and 3.

 

My primary source: https://www.ncbi.nlm.nih.gov/pubmed/1653067

 

´we treated mice with lorazepam, 2 mg kg-1 daily for 1-28 days and evaluated mRNAs for the alpha 1 and gamma 2 subunits by Northern hybridization. In cerebral cortex, concentrations of mRNA for the alpha 1 and gamma 2 subunits were unchanged from vehicle or control after 1-10 days of lorazepam. However, after 14 days of treatment mRNA concentrations for both subunits decreased to approximately 50% of control values and remained decreased at 28 days. In contrast, no significant alterations were observed for either subunit mRNA in hippocampus or cerebellum over the same time course. Alterations in mRNAs in cortex occur after the development of tolerance and receptor downregulation in this model.´

 

Mice are small, but that doesn´t necessarily transalate to equivalent doses based on body weight. This points very strongly to alpha 1. note the comments about the hippocampus and cerebellum.

 

Soemtimes hard to retrieve the location of a PDF that has a google reference, but I think this is it see PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917851/

´Binding was decreased in the hippocampus after lorazepam but not

alprazolam, as previously found.´ a bit different. ´hippocampus after lorazepam but not alprazolam, as previously found. For both drugs decreases in binding in the hypothalamus did not achieve significance, in contrast to previous findings´ Side note: I wonder to what extent the effects of hypnotics depend on the (hypo) thalamus. There is a bit more.

 

https://www.nature.com/articles/1380246

´Depression of Thalamic Metabolism by Lorazepam Is Associated with Sleepiness´ It was sedating and a bit hypnotic at first, the full 4 mg a day ... Downregulation of the receptors in the thalamus must not be a good thing.

 

Hi liberty, yes.  Unfortunately it is true.  And unfortunately the hippocampus is hit hard by benzdiazaphine induced subunit downregulation and other conformational changes.  And given it is highly plastic, the hippocampus undergoes several morphological changes that take time to revert.

 

Since you were on 4mg at one time, and are currently at 2 mg, as you know you are probably in tolerance at your current dose.  As you know, the only way you can effectively start healing the receptors is to get off the benzdiazaphine.    I wish there was an easier way, but those receptors need the time and freedom to heal. 

 

Best,

Dm123

 

Minor error: while I was on 4 mg clonazepam once upon a time, that was long ago.

That foolish switch to lorazepam was to a dose of 4 mg lorazepam and a taper that lasted 2.5 to 3 months.

So, after having spent quite some time trying to get access to a 3-nitrotyrosine test, or any reliable test in respect of the NO-ONOO- cycle biomarkers I have come up with a goose egg..... a phat zero.  I am still waiting to hear back from the naturopath as my last possibility of a test source.

 

Had a first visit to neurologist yesterday.  He was funny.  He said "just cut down the gabapentin and then go off it, it might make you uncomfortable for 5 or 6 days".  I had to set him straight about withdrawal without being a 'problem patient'.  He prescribed a lot of blood tests and seems pretty confident I also suffer from "small fiber neuralgia".  This is often seen in patients who are diabetics.  I hope I'm not becoming diabetic too!!!  In any case, the neuralgia diagnosis is interesting in that it may somewhat explain why my burning pain is so chronic and enhanced by withdrawal.

 

Anyway, not much new to report.  I'm still holding and semi-stable.  I think it's fair to say I must be in tolerance now because the pattern has settled into one of a few tolerable days sprinkled amongst a larger number of crappy days. 

 

I'm looking at the Ketogenic diet and selecting something from the Pall protocol.  I have to plan it strategically, especially if I'm becoming diabetic.  Still dealing with insurance issues on the mold cleanup at work and my home.....  sigh!

 

Anyway, onward we will go. 

 

Keep your chins up, everyone.

 

-RST

As in post #584:

 

In 2013 I took a muscarinic antagonist, technically off label. solifenacin.

 

Last year I took another dose for a different issue. Aside from anything else, that time I also got extreme muscle rigidity. Or possibly if that's a misinterpretation, the subjective perception of muscle rigidity.

In a PM we discussed the possible use of a dopamine agonist. I think that in a way a muscarinic antagonist is like a dopamine agonist ?

 

dm123,

 

Anything obvious insights ? I know these things can be terribly complicated.

dm123, I have a question. Yesterday my bp was in the 150s-161 area. I didn't understand this at all. I feel pressure in my frontal lobe when my bp goes up. This morning my bp was back to 116/64. I knew it was down because I feel a "cushion-y" effect on my frontal lobe, like there's a cushion protecting it. I've always been curious about this and don't know if others feel the same thing. Is it because of the benzo effect or something else? I always feel it in my head when the blood pressure goes up. This yanking of my bp has gone on far too long.

 

If you can help me figure this out, I would be very thankful!!

 

Hi Terry, yes i remember that question well.

 

I can only tell you from experience, a long time back, I had very high BP, and I would get intense pressure in the head when it spiked.  I can only attribute this feeling to literal high vascular pressure of the normal blood flow to the brain (arteries) pushing out the vessel walls, ever so slightly, giving us the full head-pressure exploding feeling.  I would get it really bad when going from sitting to standing which makes sense.

 

Ive long since “cured” my HBP through diet alone.  I was allergic to gluten.  Once I quit gluten, vascular inflammation decreased and my BP dramatically dropped.  My BP went from 180/100 to 115/65 over the course of several months.  This was many years ago and I’ve never had an issue again with BP.

 

Interesting, dm123! I'm on gluten, so maybe I ought to really cut it down. Don't know if I can eliminate it entirely, though, but it's worth thinking about! Thank you!!

 

Hi Terry

 

It would initiallly need to be a complete 100% elimination of gluten.  Then after around 6 weeks of complete abstinence you could gradually add in some non processed gluten products.  However, it’s unfortunate because for me, at least, I have to remain 100% gluten free.  The one good thing is that now there are gluten free alternatives.  15 years ago there was none of that and restaurants did not have any gluten free alternatives on their menu.

 

Best wishes,

Dm123

So, after having spent quite some time trying to get access to a 3-nitrotyrosine test, or any reliable test in respect of the NO-ONOO- cycle biomarkers I have come up with a goose egg..... a phat zero.  I am still waiting to hear back from the naturopath as my last possibility of a test source.

 

Had a first visit to neurologist yesterday.  He was funny.  He said "just cut down the gabapentin and then go off it, it might make you uncomfortable for 5 or 6 days".  I had to set him straight about withdrawal without being a 'problem patient'.  He prescribed a lot of blood tests and seems pretty confident I also suffer from "small fiber neuralgia".  This is often seen in patients who are diabetics.  I hope I'm not becoming diabetic too!!!  In any case, the neuralgia diagnosis is interesting in that it may somewhat explain why my burning pain is so chronic and enhanced by withdrawal.

 

Anyway, not much new to report.  I'm still holding and semi-stable.  I think it's fair to say I must be in tolerance now because the pattern has settled into one of a few tolerable days sprinkled amongst a larger number of crappy days. 

 

I'm looking at the Ketogenic diet and selecting something from the Pall protocol.  I have to plan it strategically, especially if I'm becoming diabetic.  Still dealing with insurance issues on the mold cleanup at work and my home.....  sigh!

 

Anyway, onward we will go. 

 

Keep your chins up, everyone.

 

-RST

 

Hi RST, you are making forward progress.  I assume he is running all the standard tests for diabetes.    I hope you don’t have it as well.  The mold remediation is expensive and time consuming but well with it for SB mold. 

 

Prayers out to you

Dm123

As in post #584:

 

In 2013 I took a muscarinic antagonist, technically off label. solifenacin.

 

Last year I took another dose for a different issue. Aside from anything else, that time I also got extreme muscle rigidity. Or possibly if that's a misinterpretation, the subjective perception of muscle rigidity.

In a PM we discussed the possible use of a dopamine agonist. I think that in a way a muscarinic antagonist is like a dopamine agonist ?

 

dm123,

 

Anything obvious insights ? I know these things can be terribly complicated.

 

Hi liberty,

 

I am coming up blank insofar as the muscarinic antagonist, especially since you did not use it much.  Are you still experiencing muscle rigidity? 

 

Yes, I remember the dopamine agonist.  I think the side effects from taking a dopamine agonist would make it very risky.  Some of the side effects like psychosis are quite serious.  Also long term treatment often results in protracted wd when one withdraws from these types of drugs.

 

I do think muscle tension occurs during benzdiazaphine tolerance.  I had it during the acute stages.  Very stiff.  I’m getting sporadic short lived cramping of certain muscles during the taper.

 

Best,

Dm123