![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 38 to 62 of 201. Go back in thread:
Posted by Phillipa on September 7, 2011, at 20:59:00
In reply to 40% down to 25%, posted by SLS on September 7, 2011, at 13:46:01
Think has anything to do with the daylight hours? Less light? Maybe a light box would help? Phillipa
Posted by Lamdage on September 8, 2011, at 3:06:42
In reply to Re: 40% down to 25% » SLS, posted by Phillipa on September 7, 2011, at 20:59:00
Scott sorry to hear that. Let us know what you and your doc are considering now!
Posted by Solstice on September 8, 2011, at 7:47:58
In reply to 40% down to 25%, posted by SLS on September 7, 2011, at 13:46:01
> 40% was nice for a few days. Unfortunately, it didn't last. I remain at a 25% improvement as of two days ago. After being on Nardil for a whole year, this is wholly inadequate. I don't feel very much different than I did a year ago. I made an appointment to see my doctor tomorrow. I would like to discontinue Nardil and replace it with either Pristiq or Effexor.
>
> I would like to thank everyone for their help and support over the years.
>
> I haven't given up.
Scott -Your courageous and steadfast 'fighting the fight' is an inspiration. During my times in the valley of it, I've often been a big baby and toyed with the idea of giving up.
As I've been reading your threat, I've become increasingly interested in how you go about rating where you are at a given point (0% vs 15%, 25%, 40%). I read where one of these included being able to drive, but unable to work. It makes sense to me that various specific characteristics of functioning would be a great way to assess whether one is at 25%.. vs 50%.. vs 75%.
Have you constructed a list of characteristics of functioning that helps you determine your level of functioning? For example, I guess at the social level, there would be complete withdrawal, vs. being able to tolerate receiving phone calls from certain people, vs. willing & able to place phone calls to certain people, vs. being able to tolerate receiving phone calls from people who are not in the inner circle, vs. being willing to go out and participate in various types of social interaction (i.e. it's one thing to go to Sonic with a trusted friend and eat in the car at the drive-thru, vs. going out with a group for a big meal at Logan's Steakhouse). Anyway, do you have behavioral functioning characteristics categorized in such a way that they end up putting you at a certain percentage of functioning? What it brings to mind for me is the Glascow Coma Scale for assessing level of coma.
Solstice
Posted by Solstice on September 8, 2011, at 8:36:03
In reply to Re: 40% down to 25%, posted by Solstice on September 8, 2011, at 7:47:58
> > 40% was nice for a few days. Unfortunately, it didn't last. I remain at a 25% improvement as of two days ago. After being on Nardil for a whole year, this is wholly inadequate. I don't feel very much different than I did a year ago. I made an appointment to see my doctor tomorrow. I would like to discontinue Nardil and replace it with either Pristiq or Effexor.
> >
> > I would like to thank everyone for their help and support over the years.
> >
> > I haven't given up.
>
>Scott -
Your courageous and steadfast 'fighting the fight' is an inspiration. During my times in the valley of it, I've often been a big baby and toyed with the idea of giving up.
As I've been reading your (s/b *thread*), I've become increasingly interested in how you go about rating where you are at a given point (0% vs 15%, 25%, 40%). I read where one of these included being able to drive, but unable to work. It makes sense to me that various specific characteristics of functioning would be a great way to assess whether one is at 25%.. vs 50%.. vs 75%.
Have you constructed a list of characteristics of functioning that helps you determine your level of functioning? For example, I guess at the social level, there would be complete withdrawal, vs. being able to tolerate receiving phone calls from certain people, vs. willing & able to place phone calls to certain people, vs. being able to tolerate receiving phone calls from people who are not in the inner circle, vs. being willing to go out and participate in various types of social interaction (i.e. it's one thing to go to Sonic with a trusted friend and eat in the car at the drive-thru, vs. going out with a group for a big meal at Logan's Steakhouse). Anyway, do you have behavioral functioning characteristics categorized in such a way that they end up putting you at a certain percentage of functioning? What it brings to mind for me is the Glascow Coma Scale for assessing level of coma.
Solstice
>
Posted by Dinah on September 16, 2011, at 21:16:07
In reply to 40% down to 25%, posted by SLS on September 7, 2011, at 13:46:01
There was a two week difference between your post saying you were at 40% and your post saying you'd gone down to 25%. Is it possible to segregate permanent change from the natural ups and downs of any illness? If you've felt well for a while on this medication, is it possible that this is a dip rather than a decline?
I'm also wondering if you have felt good on a medication for an extended length of time, or if you only felt like it was really working for the first little while you were on it? Is it possible that it's the shock of a change in brain chemistry that makes you feel good for a while? I think on any medication there's a drift back to setpoint. I definitely find this with Provigil. Now I have to take my morning Provigil to avoid sleeping all day. It doesn't feel like it initially did.
Posted by Dinah on September 16, 2011, at 21:31:34
In reply to Re: 40% down to 25% » SLS, posted by Dinah on September 16, 2011, at 21:16:07
I was musing that it may be that it's less a medication or cocktail you need, but to keep your brain chemicals in a desirable state of flux? A pattern of shifting medications?
I have no idea what I'm talking about here, as my brain craves stability and flux makes me nuts. But I think I remember you describing a pattern of feeling good on medications for only a little while. And since, again if I understand correctly, melancholia rather than agitation and anxiety is the problem it might be healthy for you to seek that state that no matter how pleasant I find it is very risky and unhealthy for me.
Posted by zonked on September 16, 2011, at 22:29:37
In reply to Re: 40% down to 25% » SLS, posted by Dinah on September 16, 2011, at 21:16:07
>Is it possible that it's the shock of a change in brain chemistry that makes you feel good for a while? I think on any medication there's a drift back to setpoint. I definitely find this with Provigil. Now I have to take my morning Provigil to avoid sleeping all day. It doesn't feel like it initially did.
Homeostasis is a bitch. I think an under-researched (or at least under-acknowledged) problem in psychiatry is tolerance/adaptation and how the body seems to try it's DAMNDEST to get people back to their set points.
Posted by SLS on September 17, 2011, at 9:11:37
In reply to Re: 40% down to 25% » SLS, posted by Dinah on September 16, 2011, at 21:16:07
Hi Dinah.
> There was a two week difference between your post saying you were at 40% and your post saying you'd gone down to 25%. Is it possible to segregate permanent change from the natural ups and downs of any illness?
I think I understand what you are saying. Were I to keep a daily mood chart, it is possible that any differences between your two scenarios would be revealed. That I still experience a depression that is considered to be severe (although less severe than in the past) is unacceptable when alternate treatments exist.
> If you've felt well for a while on this medication, is it possible that this is a dip rather than a decline?
It really doesn't matter to me which of the two it is. I rate myself now as being only slightly better than a year ago. Of course, this is better than nothing. If Nardil had not been a MAOI, I could simply add other drugs to it, and have a reduced risk of relapsing. Unfortunately, this is not the case, as the two medications I am to try are serotonin reuptake inhibitors, which if they were to be mixed with Nardil would most certainly provoke serotonin syndrome.
> I'm also wondering if you have felt good on a medication for an extended length of time,
Yes. 100% for 6 months in 1987 on a treatment regime of Parnate and desipramine.
> ...or if you only felt like it was really working for the first little while you were on it?
Yeah, I got that more robust improvement during the first few weeks of Nardil treatment.
> Is it possible that it's the shock of a change in brain chemistry that makes you feel good for a while?
I guess there must be some degree of disruption of homeostasis forced by the drug being used in order to provoke an antidepressant response.
> I think on any medication there's a drift back to setpoint. I definitely find this with Provigil. Now I have to take my morning Provigil to avoid sleeping all day. It doesn't feel like it initially did.
That stinks. Have you already been through the stimulants? I suppose there is a chance that Nuvigil could effectively replace Provigil. Knowing that Risperdal functions as a 5-HT2a receptor antagonist leads me to wonder if using nortriptyline might provide you with similar benefit and with less daytime sedation or sleepiness. Perhaps you don't need any dopamine receptor antagonists at all. Just a thought or two...
Have you ever tried Geodon? It is the most antidepressant-like of the APs. It can be stimulating. Unfortunately, it is a very unpredictable drug that is hard to categorize. You need to start at 40mg per day as a minimum dosage to avoid the emergence of anxiety. If it produces somnolence, profound brain-fog, and cognitive blunting early in treatment, it probably will not be of any use, and you could discontinue it immediately should these things appear and persist for a few days.
I don't see any reason why you would have to discontinue Riserdal to perform any of these trials.
Getting back to me, I can remember where I was and what I was doing when I experienced robust improvements in my depressive condition. This includes periods of time lasting but for a few hours; so profound is the difference in experience. I guess it's like someone who is blind from birth suddenly gaining sight for a few minutes. The experience is unmistakeable as a change in his perception of the universe, and will never be forgotten.
- Scott
Posted by FrustratedMama on September 17, 2011, at 9:51:09
In reply to Re: 40% down to 25% » Dinah, posted by SLS on September 17, 2011, at 9:11:37
Getting back to me, I can remember where I was and what I was doing when I experienced robust improvements in my depressive condition. This includes periods of time lasting but for a few hours; so profound is the difference in experience. I guess it's like someone who is blind from birth suddenly gaining sight for a few minutes. The experience is unmistakeable as a change in his perception of the universe, and will never be forgotten.
I COMPLETELY AGREE SCOTT! I am thinking of you and really hope you see these days again soon and that they outlast the days that aren't so bright.
Posted by SLS on September 17, 2011, at 10:08:52
In reply to Re: 40% down to 25% » SLS, posted by FrustratedMama on September 17, 2011, at 9:51:09
> Getting back to me, I can remember where I was and what I was doing when I experienced robust improvements in my depressive condition. This includes periods of time lasting but for a few hours; so profound is the difference in experience. I guess it's like someone who is blind from birth suddenly gaining sight for a few minutes. The experience is unmistakeable as a change in his perception of the universe, and will never be forgotten.
>
> I COMPLETELY AGREE SCOTT! I am thinking of you and really hope you see these days again soon and that they outlast the days that aren't so bright.That was worth a tear or two. Thank you.
I haven't seen you in a long while. How have you been?
- Scot
Posted by Dinah on September 17, 2011, at 13:12:33
In reply to Re: 40% down to 25% » Dinah, posted by SLS on September 17, 2011, at 9:11:37
For me, my problems generally stem from agitation and anxiety - perhaps some bipolarish tendencies. While Provigil may not cause wakefulness like it used to, it has the huge advantage of not causing anxiety or agitation in me.
Nortryptiline was as very bad for me as Effexor and Wellbutrin. I have concluded that norepinephrine is something that doesn't agree with me.
I'm happy enough with my current mix, although I think I'd like to take a holiday from Provigil and then go back to it. If I ever have the leisure to sleep all day for a few weeks. I'd love for it to work like it used to.
I wonder if those experiences you perceive as normal are something that can realistically be expected for a long period of time, since the longest period you've experienced them is six months. It occurs to me it might be something akin to the mild hypomania I often get with medications. For me, it's not a good thing because my set point has so much anxiety and agitation. I'm better off avoiding it, even if it feels good. But if your set point is the flat melancholic type of depression it might be what makes you feel so good. The problem is, I've never found it possible to maintain that state over time. For me, that's a good thing, for you perhaps not. Is there any way nonmedication way to improve a life with a lower set point? Maybe one of the treatments that provide disruption to the brain, perhaps not ECT but that trms is it? - the one that Twinleaf successfully used?
Posted by Phillipa on September 17, 2011, at 19:36:02
In reply to Re: 40% down to 25% » SLS, posted by Dinah on September 17, 2011, at 13:12:33
The three day blip. Where the meds seem to work well for three days and then switch back. Maybe the "normal" of yesterday isn't the normal of today? But Scott wasn't it the doc that said he wasn't satisfied with your progress? If you were he can't feel how you feel. Just wondering Phillipa
Posted by SLS on September 17, 2011, at 23:02:33
In reply to Re: 40% down to 25%, posted by Phillipa on September 17, 2011, at 19:36:02
> The three day blip. Where the meds seem to work well for three days and then switch back. Maybe the "normal" of yesterday isn't the normal of today? But Scott wasn't it the doc that said he wasn't satisfied with your progress? If you were he can't feel how you feel. Just wondering Phillipa
Yeah. My doctor wanted to jump in several months ago and make treatment changes. He wasn't at all happy with the degree of improvement I was reporting. My silly little optimistic brain decided that if I were to just wait long enough - perhaps another year - I would feel at least 50% better. I think I could return to work at that level of improvement. The 40% blip was nice for a few days. However, as I dropped to 25% and settled back to 35% again, I could not justify leaving my treatment regime unchanged.
It took me 7 days to taper and discontinue Nardil. I experience substantial variations in my depression throughout the day. There were a few hours today when I felt as if I fully relapsed. I'm not doing too bad now, but I expect to deteriorate as time passes and MAO activity recovers. With a little luck, I won't relapse completely by the time Viibryd starts to work.
I can start Viibryd 9 days from now. However, my prescription plan has denied coverage. So the game begins.
- Scott
Posted by floatingbridge on September 17, 2011, at 23:12:13
In reply to Re: 40% down to 25% » Phillipa, posted by SLS on September 17, 2011, at 23:02:33
Not a fun game, the insurance game. Why deny that particular medicine? It is not in generic nor is it prescribed off label, is it?
Posted by SLS on September 17, 2011, at 23:29:58
In reply to Re: 40% down to 25% » SLS, posted by Dinah on September 17, 2011, at 13:12:33
> For me, my problems generally stem from agitation and anxiety - perhaps some bipolarish tendencies. While Provigil may not cause wakefulness like it used to, it has the huge advantage of not causing anxiety or agitation in me.
>
> Nortryptiline was as very bad for me as Effexor and Wellbutrin. I have concluded that norepinephrine is something that doesn't agree with me.That is very possible. Have you ever thought to take guanfacine? It is a NE alpha-2 agonist that suppresses NE, and is often used for ADD. The net effect is to improve function in the prefrontal cortex. This might explain why guanfacine is seen to reduce anxiety and improve attention. The thought just crossed my mind as I read your above post. Now that I have checked Google, I am very happy to report to you that my musings were accurate. Perhaps you can research it further.
> I wonder if those experiences you perceive as normal are something that can realistically be expected for a long period of time,
I don't see why not. Most people spend their whole lives feeling that way.
> since the longest period you've experienced them is six months.
I did more living in a day during those six months than I do in a year while ill.
> It occurs to me it might be something akin to the mild hypomania I often get with medications.
Actually, for me, my infrequent manic reactions to medication launches me into BP I type psychotic mania. I do not spend weeks in hypomania. It is an all-or-nothing severe mania. Thus, the six months I spent in a state devoid of psychotic mania represents a euthymic remission. Compared to severe depression, euthymia is nirvana.
There is a doctor near me who administers rTMS. I will consider paying him a visit if I do not respond to the next two antidepressant trials. Of course, I can't afford the treatments, so I might not have the luxury of choice.
Dinah, I appreciate your devoting some portion of your formidable brain-power pondering my plight.
:-)
- Scott
Posted by SLS on September 17, 2011, at 23:38:19
In reply to Re: 40% down to 25% » SLS, posted by floatingbridge on September 17, 2011, at 23:12:13
> Not a fun game, the insurance game. Why deny that particular medicine? It is not in generic nor is it prescribed off label, is it?
Viibryd is a brand-new antidepressant, and is probably expensive.
My doctor enjoys threatening insurance companies with law suits for their pretentiousness in playing doctor with his patients. I feel as if I am being taken advantage of by the pharmaceutical companies and insurance companies both. Bullies.
- Scott
Posted by floatingbridge on September 18, 2011, at 0:01:08
In reply to Re: 40% down to 25% » floatingbridge, posted by SLS on September 17, 2011, at 23:38:19
Well, I am glad he's going to bat for you.
Posted by Phillipa on September 18, 2011, at 19:40:40
In reply to Re: 40% down to 25% » floatingbridge, posted by SLS on September 17, 2011, at 23:38:19
No more free samples? I'd think they would hand them out like candy. When on cymbalta never bought it the doc supplied me for three months? And since new must have been expensive? Phillipa
Posted by SLS on September 18, 2011, at 19:49:10
In reply to Re: 40% down to 25% » SLS, posted by Phillipa on September 18, 2011, at 19:40:40
> No more free samples? I'd think they would hand them out like candy. When on cymbalta never bought it the doc supplied me for three months? And since new must have been expensive? Phillipa
They are starter packs. I guess I'll need my calculator. :-)
- Scott
Posted by Dinah on September 19, 2011, at 7:59:45
In reply to Re: 40% down to 25% » Dinah, posted by SLS on September 17, 2011, at 23:29:58
> That is very possible. Have you ever thought to take guanfacine? It is a NE alpha-2 agonist that suppresses NE, and is often used for ADD. The net effect is to improve function in the prefrontal cortex. This might explain why guanfacine is seen to reduce anxiety and improve attention. The thought just crossed my mind as I read your above post. Now that I have checked Google, I am very happy to report to you that my musings were accurate. Perhaps you can research it further.
I'll look into that!
> > I wonder if those experiences you perceive as normal are something that can realistically be expected for a long period of time,
>
> I don't see why not. Most people spend their whole lives feeling that way.Life can be grossly unfair. I suppose that I'm thinking in Linehan's dialectical terms of continuing to hope for it while also practicing radical acceptance of the now.
> Actually, for me, my infrequent manic reactions to medication launches me into BP I type psychotic mania. I do not spend weeks in hypomania. It is an all-or-nothing severe mania. Thus, the six months I spent in a state devoid of psychotic mania represents a euthymic remission. Compared to severe depression, euthymia is nirvana.
I had forgotten that, Scott. That's far more serious, and definitely something to avoid. Which medications caused that?
> There is a doctor near me who administers rTMS. I will consider paying him a visit if I do not respond to the next two antidepressant trials. Of course, I can't afford the treatments, so I might not have the luxury of choice.
It's not a covered treatment?
> Dinah, I appreciate your devoting some portion of your formidable brain-power pondering my plight.I would say precisely the same to you. I've always been struck by the breadth of your knowledge in this area. I think I'm speaking from total ignorance, and a sense of curiosity on the topic. My knowledge in medications is limited to my own situation.
Posted by SLS on September 19, 2011, at 12:41:58
In reply to Re: 40% down to 25% » SLS, posted by Dinah on September 19, 2011, at 7:59:45
> > That is very possible. Have you ever thought to take guanfacine? It is a NE alpha-2 agonist that suppresses NE, and is often used for ADD. The net effect is to improve function in the prefrontal cortex. This might explain why guanfacine is seen to reduce anxiety and improve attention. The thought just crossed my mind as I read your above post. Now that I have checked Google, I am very happy to report to you that my musings were accurate. Perhaps you can research it further.
> I'll look into that!
> > > I wonder if those experiences you perceive as normal are something that can realistically be expected for a long period of time,
> > I don't see why not. Most people spend their whole lives feeling that way.
> Life can be grossly unfair.I cry about that sometimes - not that often, though. I accept the unfairness most of the time. It is really an exercise in spirituality for me. In God's perfect creation, someone had to be Scott.
> I suppose that I'm thinking in Linehan's dialectical terms of continuing to hope for it while also practicing radical acceptance of the now.
I wouldn't have known how to describe that. Thanks.
I have been doing this for over 30 years. It has kept me alive when I had surely come to the end. My spiritual and philosophical constitutions give me hope in the face of hopelessness. I have dealt with the fairness issue throughout my illness. I made my peace with God long ago that I should have been chosen to be chained to the bottom of a mirky ocean while others play effortlessly in the sun of the pristine shore above.
> > Actually, for me, my infrequent manic reactions to medication launches me into BP I type psychotic mania. I do not spend weeks in hypomania. It is an all-or-nothing severe mania. Thus, the six months I spent in a state devoid of psychotic mania represents a euthymic remission. Compared to severe depression, euthymia is nirvana.> I had forgotten that, Scott. That's far more serious, and definitely something to avoid. Which medications caused that?
Every episode of mania that I have experienced was associated with either Nardil or Parnate treatment. On one occassion it was actually the discontinuation of Nardil that triggered a psychotic mania.
> > There is a doctor near me who administers rTMS. I will consider paying him a visit if I do not respond to the next two antidepressant trials. Of course, I can't afford the treatments, so I might not have the luxury of choice.
> It's not a covered treatment?
The last time I looked into it, a rTMS facility told me that Medicare was not covering it. Maybe things have changed.
> > Dinah, I appreciate your devoting some portion of your formidable brain-power pondering my plight.
> I would say precisely the same to you. I've always been struck by the breadth of your knowledge in this area. I think I'm speaking from total ignorance, and a sense of curiosity on the topic. My knowledge in medications is limited to my own situation.
Your recent writings on Medication expose a great deal of your intelligence, insight and understanding. I bet that we would both see ourselves as unworthy of such accolades. I know enough to know how much I don't know.
- Scott
Posted by morgan miller on September 19, 2011, at 15:07:32
In reply to Re: 40% » hyperfocus, posted by SLS on August 31, 2011, at 8:01:48
Scott, have you considered trying Methylene Blue? If not, I think you should. A low dose of this stuff is far less potentially harmful than some of the drugs you are currently on. I think it would be ashame for you to not give MB a shot.
Morgan
Posted by morgan miller on September 19, 2011, at 15:12:17
In reply to Re: 40% down to 25% » Phillipa, posted by SLS on September 17, 2011, at 23:02:33
Scott, is Viibryd available online from Canadian or European pharmacies? If so, you could just get it this way right?
I guess you would not want to try even a very very low dose of methylene blue until after being on Viibryd for a while. I do think at some point you should try it. I will be taking it very very soon.
M-
Posted by SLS on September 19, 2011, at 15:40:08
In reply to Re: 40% down to 25%, posted by morgan miller on September 19, 2011, at 15:12:17
> Scott, is Viibryd available online from Canadian or European pharmacies? If so, you could just get it this way right?
>
> I guess you would not want to try even a very very low dose of methylene blue until after being on Viibryd for a while. I do think at some point you should try it. I will be taking it very very soon.Can you direct me to some of the literature you read regarding methylene blue? It is an interesting substance that the NIH has become interested in. What are those things about methylene blue that you find appealing? Is there any conjecture as to how it works?
Thanks for everything.
- Scott
Posted by morgan miller on September 19, 2011, at 19:15:33
In reply to Re: 40% down to 25% » morgan miller, posted by SLS on September 19, 2011, at 15:40:08
Hey Scott, Methylene Blue basically enhances mitochondrial function, and is a fairly potent MAOI at higher doses.
Here are some quotes/abstracts from studies on MB:
"Neuroprotective strategies, including free radical scavengers, ion channel modulators, and anti-inflammatory agents, have been extensively explored in the last 2 decades for the treatment of neurological diseases. Unfortunately, none of the neuroprotectants has been proved effective in clinical trails. In the current study, we demonstrated that methylene blue (MB) functions as an alternative electron carrier, which accepts electrons from NADH and transfers them to cytochrome c and bypasses complex I/III blockage. A de novo synthesized MB derivative, with the redox center disabled by N-acetylation, had no effect on mitochondrial complex activities. MB increases cellular oxygen consumption rates and reduces anaerobic glycolysis in cultured neuronal cells. MB is protective against various insults in vitro at low nanomolar concentrations. Our data indicate that MB has a unique mechanism and is fundamentally different from traditional antioxidants. We examined the effects of MB in two animal models of neurological diseases. MB dramatically attenuates behavioral, neurochemical, and neuropathological impairment in a Parkinson disease model. Rotenone caused severe do... [...]"
"Posterior cingulate/retrosplenial cortex (PCC) hypometabolism is a common feature in amnestic mild cognitive impairment and Alzheimer's disease. In rats, PCC hypometabolism induced by mitochondrial dysfunction induces oxidative damage, neurodegeneration and memory deficits. USP methylene blue (MB) is a diaminophenothiazine drug with antioxidant and metabolic-enhancing properties. In rats, MB facilitates memory and prevents neurodegeneration induced by mitochondrial dysfunction. This study tested the memory-enhancing properties of systemic MB in rats that received an infusion of sodium azide, a cytochrome oxidase inhibitor, directly into the PCC. Lesion volumes were estimated with unbiased stereology. MB's network-level mechanism of action was analyzed using graph theory and structural equation modeling based on cytochrome oxidase histochemistry-derived metabolic mapping data. Sodium azide infusions induced PCC hypometabolism and impaired visuospatial memory in a holeboard food-search task. Isolated PCC cytochrome oxidase inhibition disrupted the cingulothalamohippocampal effective connectivity, decreased the PCC functional networks and created functional redundancy within the thalamus. An intraperitoneal dose of 4 mg/kg MB prevented the memory impairment, reduced the PCC metabolic lesion volume and partially restored the cingulothalamohippocampal network effects. The effects of MB were dependent upon the local sub-network necessary for memory retrieval. The data support that MB's metabolic-enhancing effects are contingent upon the neural context, and that MB is able to boost coherent and orchestrated adaptations in response to physical alterations to the network involved in visuospatial memory. These results implicate MB as a candidate intervention to improve memory. Because of its neuroprotective properties, MB may have disease-modifying effects in amnestic conditions associated with hypometabolism."
http://www.alzforum.org/new/detail.asp?id=2203
"Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.
Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN.
SourceNutrition & Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA. hatamna@chori.orgAbstract
Methylene blue (MB) has been used clinically for about a century to treat numerous ailments. We show that MB and other diaminophenothiazines extend the life span of human IMR90 fibroblasts in tissue culture by >20 population doubling (PDLs). MB delays senescence at nM levels in IMR90 by enhancing mitochondrial function. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37-70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium. MB also induces phase-2 antioxidant enzymes in hepG2 cells. Flavin-dependent enzymes are known to use NAD(P)H to reduce MB to leucomethylene blue (MBH2), whereas cytochrome c reoxidizes MBH2 to MB. Experiments on lysates from rat liver mitochondria suggest the ratio MB/cytochrome c is important for the protective actions of MB. We propose that the cellular senescence delay caused by MB is due to cycling between MB and MBH2 in mitochondria, which may partly explain the increase in specific mitochondrial activities. Cycling of MB between oxidized and reduced forms may block oxidant production by mitochondria. Mitochondrial dysfunction and oxidative stress are thought to be key aberrations that lead to cellular senescence and aging. MB may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer disease.""Inhibition of hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation.
Wang AM, Morishima Y, Clapp KM, Peng HM, Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP.
SourceDepartment of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.Abstract
The Hsp90/Hsp70-based chaperone machinery regulates the activity and degradation of many signaling proteins. Cycling with Hsp90 stabilizes client proteins, whereas Hsp70 interacts with chaperone-dependent E3 ubiquitin ligases to promote protein degradation. To probe these actions, small molecule inhibitors of Hsp70 would be extremely useful; however, few have been identified. Here we test the effects of methylene blue, a recently described inhibitor of Hsp70 ATPase activity, in three well established systems of increasing complexity. First, we demonstrate that methylene blue inhibits the ability of the purified Hsp90/Hsp70-based chaperone machinery to enable ligand binding by the glucocorticoid receptor and show that this effect is due to specific inhibition of Hsp70. Next, we establish that ubiquitination of neuronal nitric-oxide synthase by the native ubiquitinating system of reticulocyte lysate is dependent upon both Hsp70 and the E3 ubiquitin ligase CHIP and is blocked by methylene blue. Finally, we demonstrate that methylene blue impairs degradation of the polyglutamine expanded androgen receptor, an Hsp90 client mutated in spinal and bulbar muscular atrophy. In contrast, degradation of an amino-terminal fragment of the receptor, which lacks the ligand binding domain and, therefore, is not a client of the Hsp90/Hsp70-based chaperone machinery, is enhanced through homeostatic induction of autophagy that occurs when Hsp70-dependent proteasomal degradation is inhibited by methylene blue. Our data demonstrate the utility of methylene blue in defining Hsp70-dependent functions and reveal divergent effects on polyglutamine protein degradation depending on whether the substrate is an Hsp90 client."http://www.sciencedaily.com/releases/2009/09/090929181808.htm
"Methylene blue administered post-training improves memory retention in avoidance and appetitive tasks, and restores spatial memory impaired by an inhibitor of cytochrome oxidase. Methylene blue may improve memory retention by increasing brain oxygen utilization. We investigated which doses improve memory without nonspecific behavioral effects, and whether methylene blue enhances brain oxygen consumption. Different doses were evaluated 24 h after administration in wheel running, feeding, open field habituation and object recognition tests. The 110 mg/kg methylene blue-treated rats were not different from saline-treated rats in locomotion or feeding behavior. The 50100 mg/kg doses decreased running wheel behavior. The 4 mg/kg dose improved behavioral habituation and object memory recognition. Dose-dependent effects of methylene blue on brain oxygen consumption revealed that low concentrations increased brain oxygen consumption in vitro and 24 h after in vivo administration. Therefore, methylene blue doses that increase brain oxygen consumption also facilitate memory retention."
One of many reports on MB experiences:
"Brainfogged, on 21 June 2011 - 03:57 PM, said:
Does the drug alter DNA?
Im sorry, I responded to the wrong quote on my response to brainfogged. The answer is no, this is from pg 2 of the link I provided. It can alter DNA given circumstances, but these are usually extreme cirumstances and unlikely.
"This photosensitization thing seems quite absurd, to me anyways. MB isn't something brand new. It's been around for ages, used at concentrations way beyond 100nM (~1mg!) in humans and no ill "photosensitization" effects have been reported to my knowledge. Considering ~200mg of MB is used routinely for methylhemoglobinemia, and anywhere from ~733mg (12mg/kg/day) to ~1,500mg (24mg/kg/day) in humans is used to treat malaria with few ill effects (the minimal dosage needed to see any toxic effect what so ever from MB is estimated around 600mg from the rat toxicological studies)... Yeah, I'm sorry, but these studies with crayfish neurons (sunlight is actually 137 mW/cm2 at nigh noon, staring directly into the sun; so the crayfish study used three times the amount of energy that sunlight has, and you already can't stare directly into the sun, MB notwithstanding) and fungi (which used mM amounts of MB in their study) just don't cut it for me. Also, do we even know what doses were used in PMID: 6603875? They did say that vitamin E completely stopped any photosensitization by MB, and considering the issue is singlet oxygen production, which is made constantly all the time in our bodies, including our eyes, I really don't worry - the human body is quite apt at not only dealing with but actually using super oxide for a variety of signals.
I have no doubt, and this is only my opinion, that you have nothing to worry about with your retina and MB at these doses, what so ever. Not to mention humans have a better antioxidant system than most creatures on this planet, and even many mammals, our retinas are not prone to failure by any direct "sensitization" effect, and retinas can heal quite well. It's only if you lose the optic nerve or degenerate the retina faster than it can heal (usually this is genetic) that you run into trouble; and I'm afraid MB at these dosages just isn't going to be able to do that. You'll lose your lens long before retina trouble, more likely than not, since the lens is one of the very rare things that aren't turned over."
My Experience with Methylene BlueMy first day: I bought Methylene blue from the aquarium last night. Prepared it, a 60 microgram solution, its very easy thing to do , you just need a eye dropper, a few cups and a measuring glass.
When I took it I felt great energy. My thoughts were easily facilitated, it was as if I got the stereotypical "this is how I am usually supposed to feel" feeling. Which this could actually be the case because its increasing metabolism in the places of your brain that need it.
This nootropic has a different feel to it. I can say it definitely takes away social anxiety no problem, because it feels like your young again, where your whole world is focused on what's in front of you. That was the biggest effect I noticed. The second biggest thing I noticed, is the learning after the fact process. I could say that MB does help with thinking while doing a task due to the relaxed nature of how you feel which I just described as reduced social anxiety, but I would say that the biggest nootropic effect is after the fact learning. I felt when I would read or do something, after I am done, I feel like I fully understand the subject thoroughly and can implement it from there on out, whether it is a life lesson or an academic lesson or even a logical lesson. I would say that methylene blue facilitates the idea "fool me once shame on you, fool me twice shame on me" but without the fool me twice, because the MB facilitated the full understanding of the subject after the first try. Sort of..kind of..like selectively putting what is in your long term memory. Ask me more questions, if you ask me a question Ill be able to answer it instead of me just rambling. MB also definetly increases the energy department, I have in the past always felt tired when I knew I shouldn't or I would get tired much faster than other people, and I feel like MB kicks that completely out the door. Not only do you get the energy from optimal mitochondrial processing, but I feel like most people get tired quickly due to stress, and it seems as if it eliminates stress (or makes stress not seem as monumental as people can make it) thus facilitating more energy with a relaxed state of mind.
There are more effects I will continue to right about when I come across them again. Im taking 60 micrograms right now each dosing, and I dose periodically, mostly 4 hours apart, we'll see what happens.
Smoking marijuana and Methylene Blue - Very Nice, I guess you can describe it as how people would idealize the typical marijuana experience: (no nervousness, boosted creativity, mood increase, and talkative)
I would also be interested if I could see the difference in ratio of compound to side effects of methylene blue compared to an adderall or even an SSRI that people are likely to be prescribed"
Here's an explanation of how to get and use a low dose of MB from a product like Kordon's. For you and I, I think staying at between 60 and 100 mcg is a safe dose, considering we are going to be on drugs that inhibit serotonin reuptake. Viibryd inhibits serotonin reuptake right? Anyway, higher doses of MB would likely inhibibit MAO A too much for it to be safe for those of use taking certain antidepressants.
" Dosing Explained:
Quotefish methylene blue
is 2.303% w/v so that is 2.303 grams in 100cc of distilled purified
water. Take a ml or 1/100th = 23 mg / ml (1ml = 1 dropperful) .. Take
2 ml or 2 dropperfuls = 46mg , place it in 30ml water and you get a
dilution of 1.53 mg /ml. There 20 drops to a ml in a medicine
dropper, so 1.53 mg divided by 20 = .075 mg which is 75 microgram- we
only want 60mcg, so let's go back to the 2 dropperfuls X 60mcg/75mcg =
1.6 dropperful in 30 ml medicinal dropper bottle and qs to 30ml which
now gives the 60mcg per DROP!
In short, 1.6 ml of fish-store MB in 28.4 ml of distilled water, at 20 drops to the ml, one drop gives a 60 mcg dose. Or use Perrier. Whatever floats your boat.
To be precise one can buy measuring equipment, including tenths-of-a-milliliter accurate pipettes in a drug store, the section with medicine dispensers.
Explained More: Get a eye dropper from CVS like they are like 2 dollars. Fill up 30 ml of water which is about 1/8 of a cup and keep it to the side. With a ~2% concentration MB, (1 eye dropper full is about 20 drops...there is 20 drops to a mL in standard eye droppers). Put 2 dropperfuls (which is 2 mL...which is 40 drops) of 2% MB into the 30mL of water already prepared in a cup. Create another 1/8 cup (30mL) of water without MB and put it to the side. Take ~36 drops from the previous mixture of MB and water, and then transfer that to the new 30mL of water. Then you have about 60 micrograms per drop when taken from the new mixture."The appeal of MB for me is that it appears to be very safe at very low doses, it's effective for many that have given anecdotal reports, it has some good research coming out, it may increase physical energy along with mental energy(for me they always go hand in hand), and I desperately need a boost in cognitive function.
Morgan
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