12 replies to this topic

[Joe Monroe]

A Canadian/U.S. research team has reported a novel approach to stimulating recovery from chronic stress disorders. Details of the therapeutic model, which exploits the natural dynamics of the body's 'fight or flight' system, are published 23 January in the open-access journal PLoS Computational Biology. In contrast to conventional time-invariant therapy, the researchers propose a well-directed therapeutic push delivered according to an optimal treatment schedule.
The hypothalamic, pituitary, adrenal (HPA) axis constitutes one of the body's major control systems, serving to maintain body homeostasis with hormone feedback regulatory loops. If the HPA axis is driven very far from its natural homeostatic rest point, it may be unable to fully recover the healthy physiologic state. Under such conditions, the HPA axis dysfunction may become chronic. HPA axis dysfunction has been characterised in disorders including Chronic Fatigue Syndrome (CFS), depression, post- traumatic stress disorder and Alzheimer disease.
The research team, consisting of Drs. Amos Ben-Zvi, Suzanne D. Vernon, and Gordon Broderick, used a relatively simple mathematical description of the HPA axis to show how the complex dynamical behaviour of this system could accommodate multiple stable resting states; some corresponding to chronic loss of function characterised by low cortisol, a hormone that modulates immune function. A robust treatment strategy was designed to take advantage of the body's existing homeostatic mechanism, using a short-duration intervention to assist the HPA axis in re-asserting homeostasis about a healthy equilibrium. Akin to pulling back a slingshot, temporarily reducing the bioavailability of cortisol pharmacologically causes the HPA axis to overcompensate and launch itself back into a correct regulatory regime
Here's the actual full study published on PLOS: http://www.ploscompb...al.pcbi.1000273
I read one of the leading drugs to do this is mifepristone, in high doses for a short time and this blocks the cortisol receptor, up regulating acth and other hpa hormones.. helping to normalize the stress system. Mifipristone is an abortion pill right now, and is really expensive.. I know I'm going out on a limp here but there was studies done and no negative side effects and people with depression and PTSD both showed improvements..

[t234]

Awesome study. Now these guys are smart. Need to do more research on the dosing and timing. If I had to guess I'd think 2 weeks. Can probably figure out dosing by looking at the ACTH response in abortion studies.

[Joe Monroe]

Awesome study. Now these guys are smart. Need to do more research on the dosing and timing. If I had to guess I'd think 2 weeks. Can probably figure out dosing by looking at the ACTH response in abortion studies.

Thanks for the reply. Well the amount that is given for abortions, it isn't significant enough to have any real effect I suppose. I think for abortions it's just a one time dose of 200mg. The study on veterans with ptsd the amount was 600mg/day for 7 days. Here's the study: http://www.hindawi.c...rt/2012/393251/

 

and the part about dosing and results:

 

Eligible veterans were randomized to receive mifepristone (600 mg/day) or matched placebo for one week (7 days), to be taken at bedtime. Clinical assessments were performed at baseline, treatment endpoint, and four weeks after drug discontinuation. Vital signs, adverse events, and concomitant medications were obtained at every visit to monitor safety.

The primary clinical outcome measures were severity of PTSD symptoms, as measured by the total severity score of the CAPS-2, and dichotomously defined clinical responder status. The liberal responder criterion, defined as a 12-point or greater reduction in total CAPS-2 score, reflects reliable clinical changes in veterans with PTSD. The more conservative criterion, a 30% or greater reduction in total CAPS-2 score, is a frequently used definition in PTSD clinical trials. Secondary clinical outcome measures included self-reported symptoms as measured by the PCL and the BDI, and the three PTSD symptom subscale scores from the CAPS-2 (intrusive symptoms, avoidance symptoms, and hyperarousal symptoms). Dichotomous remitter status, defined as no longer meeting diagnostic criteria for PTSD at four-week follow-up, was also explored.

Morning plasma cortisol and ACTH levels and GR binding per cell were measured as indicators of the magnitude of mifepristone’s effects on negative feedback inhibition. The lysozyme  was used to measure mifepristone’s antagonism of peripheral GR sensitivity [5].

---

So they have already done trials on the drug, I read one for depression too that they did. THey were saying that the results might have been better if the drug was administered in higher amounts for shorter time frame. I guess 7 days is a little long. I'm guessing maybe 3 days at 900mg or something? I dunno. There aren't much studies on it yet, but from what I read there were no significant negative side effects and makes a lot of sense for stress disorders... 

Because a lot of times they say to get back to a state of normalcy you must reduce all stressors, which is basically saying reduce cortisol as much as possible, so the body can become sensitized to the hormone, to help bring the body back to homeostasis. When the body goes through repeated stress through a long period of time, the body downregulates and the effects of cortisol become blunted. 

I wish the drug wasn't so much, and was more available. I have extreme hyperarousal, super jumpy all the time, effects my sleep and makes me feel very wired but tired. 

[YimYam]

 

Awesome study. Now these guys are smart. Need to do more research on the dosing and timing. If I had to guess I'd think 2 weeks. Can probably figure out dosing by looking at the ACTH response in abortion studies.

Thanks for the reply. Well the amount that is given for abortions, it isn't significant enough to have any real effect I suppose. I think for abortions it's just a one time dose of 200mg. The study on veterans with ptsd the amount was 600mg/day for 7 days. Here's the study: http://www.hindawi.c...rt/2012/393251/

 

and the part about dosing and results:

 

Eligible veterans were randomized to receive mifepristone (600 mg/day) or matched placebo for one week (7 days), to be taken at bedtime. Clinical assessments were performed at baseline, treatment endpoint, and four weeks after drug discontinuation. Vital signs, adverse events, and concomitant medications were obtained at every visit to monitor safety.

The primary clinical outcome measures were severity of PTSD symptoms, as measured by the total severity score of the CAPS-2, and dichotomously defined clinical responder status. The liberal responder criterion, defined as a 12-point or greater reduction in total CAPS-2 score, reflects reliable clinical changes in veterans with PTSD. The more conservative criterion, a 30% or greater reduction in total CAPS-2 score, is a frequently used definition in PTSD clinical trials. Secondary clinical outcome measures included self-reported symptoms as measured by the PCL and the BDI, and the three PTSD symptom subscale scores from the CAPS-2 (intrusive symptoms, avoidance symptoms, and hyperarousal symptoms). Dichotomous remitter status, defined as no longer meeting diagnostic criteria for PTSD at four-week follow-up, was also explored.

Morning plasma cortisol and ACTH levels and GR binding per cell were measured as indicators of the magnitude of mifepristone’s effects on negative feedback inhibition. The lysozyme  was used to measure mifepristone’s antagonism of peripheral GR sensitivity [5].

---

So they have already done trials on the drug, I read one for depression too that they did. THey were saying that the results might have been better if the drug was administered in higher amounts for shorter time frame. I guess 7 days is a little long. I'm guessing maybe 3 days at 900mg or something? I dunno. There aren't much studies on it yet, but from what I read there were no significant negative side effects and makes a lot of sense for stress disorders... 

Because a lot of times they say to get back to a state of normalcy you must reduce all stressors, which is basically saying reduce cortisol as much as possible, so the body can become sensitized to the hormone, to help bring the body back to homeostasis. When the body goes through repeated stress through a long period of time, the body downregulates and the effects of cortisol become blunted. 

I wish the drug wasn't so much, and was more available. """I have extreme hyperarousal, super jumpy all the time, effects my sleep and makes me feel very wired but tired. """

 

 

 

Thanks for that incredibly interesting study, hope is a great thing.

 

My main symptom is cognitive dysfunction and this constant fluctuating wired symptom which gets better or worse depending on various factors.

 

Hypersensitive stress response, even very small stressors set it off, very jumpy, sound sensitivity and constant 24/7 nervous system activity. Increased nervous system activity upon waking and from ingesting ANYTHING. The more quick release glucose, caffeine, cigarettes ingested the worse the wired feeling gets.

 

Can you relate to this?

 

Thanks

 

 

Edited by jdmc123, 01 May 2014 - 09:11 AM.

[Joe Monroe]

Yes, hope is a great thing Without it, where would .. anyone be really? I remember in the hunger games when katnis won and the people in charge or whatever were saying they needed to kill her, because while the people were afraid, they now had hope, which was the only thing stronger than fear.. or it went something like that, haha. I love those movies. 

 

Anyway yes, for sure all those things you mentioned. I am constantly in this weird wired state. Like if someone just touches me and I am not aware that they are going to touch me or my arm accidently brushes up against something my body will instantly react as if someone has just came up behind me and grabbed me and yelled boo.. 

 

My sleep is pretty bad, I used to sleep like a baby never had any problems, now if someone comes to wake me up or even small noises I'll wake up, but when I do wake up I feel like I wasn't even sleeping... Like I was just layind down with my eyes closed. Definitely feel very exhausted all the time, very emotionally blunted and decreased pleasure in life also. 

have you done anything that has helped with this feeling? 

I know for me, of course eliminating any forms of stress and drugs, eating well also helps. What sucks is many times if I take something that is supposed to help and be calming or just like vitamins they make the feeling worse, it's qutie frustrating. 

 

 

Awesome study. Now these guys are smart. Need to do more research on the dosing and timing. If I had to guess I'd think 2 weeks. Can probably figure out dosing by looking at the ACTH response in abortion studies.

Thanks for the reply. Well the amount that is given for abortions, it isn't significant enough to have any real effect I suppose. I think for abortions it's just a one time dose of 200mg. The study on veterans with ptsd the amount was 600mg/day for 7 days. Here's the study: http://www.hindawi.c...rt/2012/393251/

 

and the part about dosing and results:

 

Eligible veterans were randomized to receive mifepristone (600 mg/day) or matched placebo for one week (7 days), to be taken at bedtime. Clinical assessments were performed at baseline, treatment endpoint, and four weeks after drug discontinuation. Vital signs, adverse events, and concomitant medications were obtained at every visit to monitor safety.

The primary clinical outcome measures were severity of PTSD symptoms, as measured by the total severity score of the CAPS-2, and dichotomously defined clinical responder status. The liberal responder criterion, defined as a 12-point or greater reduction in total CAPS-2 score, reflects reliable clinical changes in veterans with PTSD. The more conservative criterion, a 30% or greater reduction in total CAPS-2 score, is a frequently used definition in PTSD clinical trials. Secondary clinical outcome measures included self-reported symptoms as measured by the PCL and the BDI, and the three PTSD symptom subscale scores from the CAPS-2 (intrusive symptoms, avoidance symptoms, and hyperarousal symptoms). Dichotomous remitter status, defined as no longer meeting diagnostic criteria for PTSD at four-week follow-up, was also explored.

Morning plasma cortisol and ACTH levels and GR binding per cell were measured as indicators of the magnitude of mifepristone’s effects on negative feedback inhibition. The lysozyme  was used to measure mifepristone’s antagonism of peripheral GR sensitivity [5].

---

So they have already done trials on the drug, I read one for depression too that they did. THey were saying that the results might have been better if the drug was administered in higher amounts for shorter time frame. I guess 7 days is a little long. I'm guessing maybe 3 days at 900mg or something? I dunno. There aren't much studies on it yet, but from what I read there were no significant negative side effects and makes a lot of sense for stress disorders... 

Because a lot of times they say to get back to a state of normalcy you must reduce all stressors, which is basically saying reduce cortisol as much as possible, so the body can become sensitized to the hormone, to help bring the body back to homeostasis. When the body goes through repeated stress through a long period of time, the body downregulates and the effects of cortisol become blunted. 

I wish the drug wasn't so much, and was more available. """I have extreme hyperarousal, super jumpy all the time, effects my sleep and makes me feel very wired but tired. """

 

 

 

Thanks for that incredibly interesting study, hope is a great thing.

 

My main symptom is cognitive dysfunction and this constant fluctuating wired symptom which gets better or worse depending on various factors.

 

Hypersensitive stress response, even very small stressors set it off, very jumpy, sound sensitivity and constant 24/7 nervous system activity. Increased nervous system activity upon waking and from ingesting ANYTHING. The more quick release glucose, caffeine, cigarettes ingested the worse the wired feeling gets.

 

Can you relate to this?

 

Thanks

 

 

 

 

[AlexCanada]

Wow. Some remarkable research here. Makes a lot of sense.  They also mention oral estrogen as a method in the study.  Which is something I am looking to try anyway.

 

Transdermal pregnenolone might be very useful. Some of the lowest stress response I've had was on preg but the oral form gave bad inconsistencies and skin problems. Oral form can potentially shut down ACTH to my understanding where as transdermal can be very stable. 

Edited by AlexCanada, 22 June 2015 - 01:13 PM.

[Irishdude]

Any updates gentlemen?

[YimYam]

Hello mate. What I've learnt is Escitalopram and Fluoxetine are the best ssri's for normalising a hyperactive HPA axis. I've been on fluoxetine for about 2 and a half months now and it has significantly improved my very overactive HPA and my vast array of symptoms from it. As a result of this it has massively improved my functionality, ability to communicate and general ability to socialise and process information. 

[Irishdude]

Hello mate. What I've learnt is Escitalopram and Fluoxetine are the best ssri's for normalising a hyperactive HPA axis. I've been on fluoxetine for about 2 and a half months now and it has significantly improved my very overactive HPA and my vast array of symptoms from it. As a result of this it has massively improved my functionality, ability to communicate and general ability to socialise and process information. 

Interesting you say that. I have been on Effexor (venlafaxine) for two and a half months now and it seems subjectively to have killed my adrenal response to stressful things. Its like it has switched off my fight or flight response. It has also killed my libido though, and my penis has very little sensitivity to it (where as opposite before lol) I used to get hot worry flashes in the mornings but now I dont get anything. My sleep has also improved and I am almost over sleeping. Now, all that worries me is getting a job again and being productive and feeling good about myself. I still have cognitive problems from my mental breakdown three years ago.

I am working every day to get my testosterone up naturally too from a low of 350. I think one handles stress better with a higher test level.

 

What symptoms did you get from your overactive hpa? Did you get severe cognitive problems like me? Severe Memory, working memory, concentration, personality changes, tinnitus, severe depression and also depersonalisation at the worst times? I thought I was getting psychosis without any hallucinations. I am 28 by the way.

Edited by Irishdude, 14 September 2015 - 10:20 PM.

[Junk Master]

Great thread, I'd like to see this one continue.

 

What about a combination of CBT, Mifepristone, and NSI-189?

 

I also wonder if many steroid users who do not complete proper ancillary treatment develop PTSD symptoms?

[Irishdude]

Great thread, I'd like to see this one continue.

 

What about a combination of CBT, Mifepristone, and NSI-189?

 

I also wonder if many steroid users who do not complete proper ancillary treatment develop PTSD symptoms?

I like this combination. No proof it would work though. I know cortisol is proven to negatively affect neurons in the hippocampus, and that is why if I am ever really stressed I will drink glucose straight away as its shown to protect the neurons from cortisol. I think cortisol affects them by draining their energy away and they die.

 

I would try NSI 189 however I don't have anywhere to send it at the moment. That could change. Thank you ever so much for informing me that mifepristone exists. I would love to trial it, however coming off the SNRI (effexor acts as an SSRI at my dose) is not easy. I like how it has made me less prone to stress but I still feel my mind is impaired. I don't think my pdoc would prescribe mifepristone easily to me either. I have only been diagnosed with MDD, not psychotic MDD. Mifepreistone is currently being trialed to treat PMDD.

Edited by Irishdude, 17 September 2015 - 04:27 PM.

[YimYam]

 

Hello mate. What I've learnt is Escitalopram and Fluoxetine are the best ssri's for normalising a hyperactive HPA axis. I've been on fluoxetine for about 2 and a half months now and it has significantly improved my very overactive HPA and my vast array of symptoms from it. As a result of this it has massively improved my functionality, ability to communicate and general ability to socialise and process information. 

Interesting you say that. I have been on Effexor (venlafaxine) for two and a half months now and it seems subjectively to have killed my adrenal response to stressful things. Its like it has switched off my fight or flight response. It has also killed my libido though, and my penis has very little sensitivity to it (where as opposite before lol) I used to get hot worry flashes in the mornings but now I dont get anything. My sleep has also improved and I am almost over sleeping. Now, all that worries me is getting a job again and being productive and feeling good about myself. I still have cognitive problems from my mental breakdown three years ago.

I am working every day to get my testosterone up naturally too from a low of 350. I think one handles stress better with a higher test level.

 

What symptoms did you get from your overactive hpa? Did you get severe cognitive problems like me? Severe Memory, working memory, concentration, personality changes, tinnitus, severe depression and also depersonalisation at the worst times? I thought I was getting psychosis without any hallucinations. I am 28 by the way.

 

 

I would get very strong stress responses (in varying degrees) to all for forms of eating/drinking, basically i "reacted" to all food and drink, I couldn't handle more than 5 grams of quick release sugars without getting a fairly strong stress response which would hugely affect my functionality, sleep and ability to socialise. The list is endless of what I couldn't tolerate. What i mean by stress response, is my nervous system would wildly go into fight or flight.

 

This also happened with exercise of any form. If i was to walk up the stairs, walk along a pavement too long, do intensive exercise it would affect functionality, by activating my stress pathway (as well as symptoms..) put me in fight or flight. I got these symptoms from anything which activates a natural stress response in the body. So exercise, eating, drinking etc all activates our stress response naturally, but mine was hugely exaggerated. To simplify the more stress I would put on my body, the more my symptoms would play up. So for example if I went walking my SR symptoms would be fairly manageable. If i did weight training it would wipe me up and make me feel awful.

 

When my stress pathway was activated and depending how strongly it was activated by what I had done, it would induce chronic sinusitis, head pressure, tightness of chest, irritability, low mood, blocked ears, SEVERE cognitive issues and so many more symptoms; same issues as you above apart from severe depression and tinnitus. Although of course i was very depressed at times due to being in such a dysfunctional state for such a long period of time.

 

I'm still at about 70% as cognition is still not there, I still can't think in my mind, don't have a minds eye. But because my SR symptoms are muted it has allowed me to be able to handle getting a simple low pay job and live an ok life and come across as pretty normal in everyday interaction with others. I still can't properly enjoy basic things like reading, doing music prod or anything which requires a significant amount of cognitive skills. 

 

Inbox me your skype details if you'd like to keep this chat going over a more instant message kind of thing, as it seems we've been on a fairly similar journey.

 

all the best

 

 

[YimYam]

 

Great thread, I'd like to see this one continue.

 

What about a combination of CBT, Mifepristone, and NSI-189?

 

I also wonder if many steroid users who do not complete proper ancillary treatment develop PTSD symptoms?

I like this combination. No proof it would work though. I know cortisol is proven to negatively affect neurons in the hippocampus, and that is why if I am ever really stressed I will drink glucose straight away as its shown to protect the neurons from cortisol. I think cortisol affects them by draining their energy away and they die.

 

I would try NSI 189 however I don't have anywhere to send it at the moment. That could change. Thank you ever so much for informing me that mifepristone exists. I would love to trial it, however coming off the SNRI (effexor acts as an SSRI at my dose) is not easy. I like how it has made me less prone to stress but I still feel my mind is impaired. I don't think my pdoc would prescribe mifepristone easily to me either. I have only been diagnosed with MDD, not psychotic MDD. Mifepreistone is currently being trialed to treat PMDD.

 

I've got some NSI-189 available if you want to purchase some