217 replies to this topic

[Rational Madman]

I think I'm coming perilously close to concluding that the dosage guideline for Vitamin A is not universally applicable, and that official guidelines are doing a disservice to many disorders where an impairment of retinoic acid synthesis seems to have some pathological involvement. This was part of the impetus behind my order of Acitretin, but I'm wondering how many refractory cases within the patient population are contending with a similar deficit. Assuming that this is the case---and I'll elaborate on the potentially serious implications of an alteration of retinoic acid receptor expression---are there any ideas on an effective dose? I think that I've already arrived at the answer, but I'm interested in user thoughts.

Edited by Rol82, 26 September 2010 - 07:44 AM.

[maxwatt]

I think I'm coming perilously close to concluding that the dosage guideline for Vitamin A is not universally applicable, and that official guidelines are doing a disservice to many disorders where an impairment of retinoic acid synthesis seems to have some pathological involvement. This was part of the impetus behind my order of Acitretin, but I'm wondering how many refractory cases within the patient population are contending with a similar deficit. Assuming that this is the case---and I'll elaborate on the potentially serious implications of an alteration of retinoic acid receptor expression---are there any ideas on an effective dose? I think that I've already arrived at the answer, but I'm interested in user thoughts.

Genetic variation in phenotype -> non-universality for Vit A dosage -> non-univerrsatlty of effective dose.

Vitamin A as retinol and dehydroretinol; the vegetable carotenes: alpha-carotene, beta-carotene, gamma-carotene and crypto-carotene. Difference in absorption, metabolism? Therapeutic applicatons use the retinols rather than carotenes.

Deficiency symptoms: dry eyes, with itching, nasal congestion, frequent colds.

Therpeutic doses can be many times the RDA, (which is a minimum that prevents deficiency in most people .) The RDA is 5,000 IU per day (actually 1,000 µg)in retinoic equivalent. Over 15,000 IU a day medical, supervision is generally advised. Overdose symptoms include: nausea, dizziness, skin dryness, itchiness, irritability, vomiting, headaches. Chronic verdose: hair loss, bone and muscle pain, headache, liver damage, blood lipid changes. With vegetable carotene overdose not possible, though you might turn orange, and I believe some studies found increased cancer rate w high dose beta-carotene.

As you seem a knowledgeable self-experimenter, you probably could titrate the dose to find what's effective.

[aLurker]

While I'm sure you're most interested in discussing the juicier items on your list, I wonder if you'd take a moment to relate your experience with atomoxetine? I'd be interested in any further elucidation of why you consider the mechanisms advantageous, but perhaps more in your subjective description of its effects. It's been much maligned on this forum, and the positive accounts on ADDForums are cursory, to say the least.

I finally got around to cracking open a sample bottle I've had for a few years, and have been very pleasantly surprised at the instant improvement in the social anxiety and motivational domains of my dopaminergic troubles. But I have a partially-irrational bias against medicines which change my subjective experience considerably, that I can't also take "breaks" from if I want (without weeks-long tapers both ways), so I'm trying to get some more informed opinions about what it might entail subjectively.

I believe Atomoxetine has considerable potential for treating mental illnesses marked by fatigue, and is a useful adjunct to amphetamine salts in the treatment of the inattentive subsets of ADHD. With its activation of alpha 1 adrenoreceptor targets, it has been demonstrated to increase cortical volumes acetylcholine, and ameliorate the symptoms of frontal lobe disorders through an unclear mechanistic increase of catechoamines in the prefrontal cortex. Its effects on NMDA receptors, though, are of a yet to be determined therapeutic value, for reasons that I've elucidated in previous entries. But, when combined with an ample amount of psychostimulants, there should be less of an issue, and may create a useful synergy in preventing the onset of tolerance with the latter class of agents. Indeed, since many have used it as a monotherapy, that's probably the reason why it, and many classes of antidepressants, have been unfairly maligned. Luckily, it can also be cheaply attained----if your psychiatrist is not fond of the polypharmaceutical approach that I'm so evidently fond of----in addition to a serotonergic to help guard against catechloamine induced reduction in serotonin volume, or a disturbance of the HPA. Norephinephrine---Atomoxetine's target messenger for selective reuptake inhibition---it should be noted, is especially critical for long term induction and the retrieval of memories, and I believe, overlooked by clinicians in the treatment of memory disturbances. So, go forward, but again, I achieved the best outcome when Atomoxetine was combined with other agents---mainly the psychostimulants and antidepressants that formed the basis of my cocktail.

Very interesting.
How might Atomoxetine prevent the onset of tolerance with stims? I'm guessing through the NMDA receptor blocking effects although this was all I could find regarding those. Anecdotally from your own point of view, does it seem to work or is it too early to tell?

[Rational Madman]

I think I'm coming perilously close to concluding that the dosage guideline for Vitamin A is not universally applicable, and that official guidelines are doing a disservice to many disorders where an impairment of retinoic acid synthesis seems to have some pathological involvement. This was part of the impetus behind my order of Acitretin, but I'm wondering how many refractory cases within the patient population are contending with a similar deficit. Assuming that this is the case---and I'll elaborate on the potentially serious implications of an alteration of retinoic acid receptor expression---are there any ideas on an effective dose? I think that I've already arrived at the answer, but I'm interested in user thoughts.

Genetic variation in phenotype -> non-universality for Vit A dosage -> non-univerrsatlty of effective dose.

Vitamin A as retinol and dehydroretinol; the vegetable carotenes: alpha-carotene, beta-carotene, gamma-carotene and crypto-carotene. Difference in absorption, metabolism? Therapeutic applicatons use the retinols rather than carotenes.

Deficiency symptoms: dry eyes, with itching, nasal congestion, frequent colds.

Therpeutic doses can be many times the RDA, (which is a minimum that prevents deficiency in most people .) The RDA is 5,000 IU per day (actually 1,000 µg)in retinoic equivalent. Over 15,000 IU a day medical, supervision is generally advised. Overdose symptoms include: nausea, dizziness, skin dryness, itchiness, irritability, vomiting, headaches. Chronic verdose: hair loss, bone and muscle pain, headache, liver damage, blood lipid changes. With vegetable carotene overdose not possible, though you might turn orange, and I believe some studies found increased cancer rate w high dose beta-carotene.

As you seem a knowledgeable self-experimenter, you probably could titrate the dose to find what's effective.

For now, I'm starting with 20,000 IU/daily until my Acitretin arrives, which is preferable because it consists of the reduced form, and should present the user with less side effects. There are, however, some potential problems with excess retinoic acid, though, like an uncertain effect on COMT inhibition, an undesired amount of 5ht1A upregulation, and possible depressive symptoms through a reduction in serotonin volumes. But, retinoic acid administration also holds the promise of improved glucose metabolism, heightened LDL metabolism, increased neurotrophic factors (GDNF in particular), improved mitochondrial function, enhanced dendritic spine growth, reduced inflammation, reelin promotion, and many other positive attributes that I'm delightfully discovering. The pathological alteration in synthesis is mind boggling, and appears to be all over the spectrum of pervasive neuropsychiatric disorders. I think it really might be an important missing link, and I regret previously scoffing at the notion of therapeutically using Vitamin A or its derivatives. Additionally, it has been postualted that DHA might convey its cognitive benefits in part through its interaction with liver x receptors.

Edited by Rol82, 27 September 2010 - 06:37 AM.

[Rational Madman]

While I'm sure you're most interested in discussing the juicier items on your list, I wonder if you'd take a moment to relate your experience with atomoxetine? I'd be interested in any further elucidation of why you consider the mechanisms advantageous, but perhaps more in your subjective description of its effects. It's been much maligned on this forum, and the positive accounts on ADDForums are cursory, to say the least.

I finally got around to cracking open a sample bottle I've had for a few years, and have been very pleasantly surprised at the instant improvement in the social anxiety and motivational domains of my dopaminergic troubles. But I have a partially-irrational bias against medicines which change my subjective experience considerably, that I can't also take "breaks" from if I want (without weeks-long tapers both ways), so I'm trying to get some more informed opinions about what it might entail subjectively.

I believe Atomoxetine has considerable potential for treating mental illnesses marked by fatigue, and is a useful adjunct to amphetamine salts in the treatment of the inattentive subsets of ADHD. With its activation of alpha 1 adrenoreceptor targets, it has been demonstrated to increase cortical volumes acetylcholine, and ameliorate the symptoms of frontal lobe disorders through an unclear mechanistic increase of catechoamines in the prefrontal cortex. Its effects on NMDA receptors, though, are of a yet to be determined therapeutic value, for reasons that I've elucidated in previous entries. But, when combined with an ample amount of psychostimulants, there should be less of an issue, and may create a useful synergy in preventing the onset of tolerance with the latter class of agents. Indeed, since many have used it as a monotherapy, that's probably the reason why it, and many classes of antidepressants, have been unfairly maligned. Luckily, it can also be cheaply attained----if your psychiatrist is not fond of the polypharmaceutical approach that I'm so evidently fond of----in addition to a serotonergic to help guard against catechloamine induced reduction in serotonin volume, or a disturbance of the HPA. Norephinephrine---Atomoxetine's target messenger for selective reuptake inhibition---it should be noted, is especially critical for long term induction and the retrieval of memories, and I believe, overlooked by clinicians in the treatment of memory disturbances. So, go forward, but again, I achieved the best outcome when Atomoxetine was combined with other agents---mainly the psychostimulants and antidepressants that formed the basis of my cocktail.

Very interesting.
How might Atomoxetine prevent the onset of tolerance with stims? I'm guessing through the NMDA receptor blocking effects although this was all I could find regarding those. Anecdotally from your own point of view, does it seem to work or is it too early to tell?

Yes, it's antagonist effect on NMDA currents may confer it potential as a therapeutic device for amphetamine desensitization. But, despite my previous entry, I've become somewhat ambivalent, sentiments which are elaborated on in the thread that you posted a link to, but I urge followers not to jump to conclusions on until my ceaseless research and bold self-experimentation reach their zenith----which I imagine is making some of the more religious empiricists on this board foam at the mouth.

Edited by Rol82, 27 September 2010 - 06:12 AM.

[Rational Madman]

I think I've concluded that freeze dried coffee is the most cost effective cognitive enhancer on the market. But when consumed rather than brewed----which may be a bit intense for some. Another few underutilized gems would be the neurotrophic methylfolate and ribose.

Edited by Rol82, 27 September 2010 - 04:57 AM.

[Rational Madman]

Additionally, I think I've just fully appreciated the pathological importance of mRNA expression, an increase of which should help normalize the signaling of glutamate receptors. Combined with the promotion of reelin glycoproteins and increasing catechloamine volume, the most essential elements of addressing the all too frequent dysexecutive disorder will be addressed. Since these are visual processing disorders, and because such are believed to stem from a dysregulation of glutamate receptors, I think we need to steer clear of antagonism, and focus on the aforementioned pharmacological targets. To facilitate further progress, we should start an executive function thread, where findings and hypotheses can be pooled. Furthermore, I propose the creation of a task force for the purpose of beginning correspondences with researchers/clinicians about our findings, observations, and see if they care to comment---or possibly participate in the forum discussions. This is not to say that our findings are groundbreaking, but since there are several forums that facilitate research collaboration, and none---that I know of---where patients and clinicians/researchers openly interact, we might be able expedite the cessation of the suffering of forum participants. Although there might be some concerns about institutional reputation or a detraction from our organization's mission, I believe we need to finally accept that the majority of visitors/members gravitate here not out of regard for the mission goals, but rather, to become enlightened about viable strategies for self-improvement.

Since I'm more familiar with those with a focus on depression (a disorder with symptoms that a frequently complained about in the forums), I'll begin with a short list of individuals that come immediately to mind. Regardless of what other members decide, though, I'll proceed either unilaterally or multilaterally within a few days, since I've nearly completed my assignments for the week.

Sidney Zisook
Michael Gitlin
John Zajecka
Thomas Wehr
Moussa Youdim
Robert Post
Norman Rosenthal
Andrew Nierenberg
Jerrold Rosenbaum
Michael Thase
Richard Brown (actually uses piracetam, Tianeptine, adenosyl methionine, and rhodiola as adjuncts in clinical practice; and laudably does a lot of pro-bono work for PTSD afflicted military veterans and WTC survivors)

Any of these professionals should also be very amenable---especially to my scandalous polypharmacy approach:
http://www.antiaging...com/authors.htm: I'm not familiar with most of them, so it will take some time to sort through the rotten and fresh apples. But Richard Brown is a respected faculty member of the Department of Psychiatry at Columbia. John Morganthaler, Sandy Shaw, Ward Dean, and Ray Sahelian are contemptible clowns though. So, don't even bother looking into their "published work." Ward Dean especially, and don't get me started on his deeply troubling political views.

Edited by Rol82, 27 September 2010 - 05:07 PM.

[chrono]

It's a good idea, and would be potentially highly valuable. But my thought is that most researchers and clinicians would be concerned (perhaps rightly so) with discussing research in a public venue, where many people self-diagnose and -treat, and are all too willing to employ unproven strategies. Indeed, I would be surprised if they felt they could do so without appearing to dispense medical advice, practically if not technically. It would be great to have more knowledgable participants here (and it might be facilitated with something like an 'advanced' subforum, with less noise)—but if you're suggesting a system whereby 'cessation of suffering' is achieved via advice dispensed from professionals in something like a doctor-patient relationship, I can say with near-certainty that most here (including myself) would think that highly problematic and inappropriate.

And while you and I spend most of our time in this part of the forum because of our research interests, many of the non-supplement membership (i.e. the entire board) are not entirely comfortable with the majority of visitors coming here for solely for this content; urging 'acceptance' of this in the way you suggest will probably be counterproductive.

And while it might not be necessary, I feel I should mention that in such correspondence, there is usually anxiety that it be remembered that even moderators aren't permitted to 'speak' for the site/organization without express permission from the board—so no implication should me made as such.

I have a few research groups I'd like to ask questions of as well, but I feel like they would be more likely to respond to private correspondence, than to overtures from a public forum.

[Rational Madman]

It's a good idea, and would be potentially highly valuable. But my thought is that most researchers and clinicians would be concerned (perhaps rightly so) with discussing research in a public venue, where many people self-diagnose and -treat, and are all too willing to employ unproven strategies. Indeed, I would be surprised if they felt they could do so without appearing to dispense medical advice, practically if not technically. It would be great to have more knowledgable participants here (and it might be facilitated with something like an 'advanced' subforum, with less noise)—but if you're suggesting a system whereby 'cessation of suffering' is achieved via advice dispensed from professionals in something like a doctor-patient relationship, I can say with near-certainty that most here (including myself) would think that highly problematic and inappropriate.

And while you and I spend most of our time in this part of the forum because of our research interests, many of the non-supplement membership (i.e. the entire board) are not entirely comfortable with the majority of visitors coming here for solely for this content; urging 'acceptance' of this in the way you suggest will probably be counterproductive.

And while it might not be necessary, I feel I should mention that in such correspondence, there is usually anxiety that it be remembered that even moderators aren't permitted to 'speak' for the site/organization without express permission from the board—so no implication should me made as such.

I have a few research groups I'd like to ask questions of as well, but I feel like they would be more likely to respond to private correspondence, than to overtures from a public forum.

Sure, very good points. So, perhaps it's best if we proceed as individuals, but as part of a collaborative effort. I've had the pleasure of speaking to Neirenberg personally, and although I didn't become a patient, from what I could tell, he's one hell of a guy----and an exceptional researcher. After searching for the best neuropsychiatric clinicians in the country, I concluded that he's perhaps one of the best out there---simultaneously brilliant, empathetic, open-minded, and gregarious. I'll probably start with him first, and if there are any questions that anyone wants to convey, I'll certainly consider them.

Edited by Rol82, 28 September 2010 - 01:15 AM.

[Rational Madman]

Three parcels arrived today: Clonidine, Valproic Acid, and Rasagiline. The Rasagiline, which I've been using, will be continued on my titrating schedule. Clonidine and Valproic Acid will be eased into, since I'm still deciding on the doses. But, I'm thinking about 30-60 mg for Valproic Acid, and 50-150 mcg for Clonidine. New additions include Revgenetics' Nitro-Mx, Healthy Origins' ribose, Symbiotics' colostrum, and Life Extension's methylfolate. Removals---which shouldn't be mistaken for distaste---include Oregonol, sceletium tortuousum, and Idebenone. In the place of the sceletium, I decided to simply increase my luteolin dosage, which is another phosphodiesterase 4 inhibitor.

Edited by Rol82, 27 September 2010 - 08:21 PM.

[stillwater]

You've probably heard of and are awaiting Ladostigil's eventual release, a derivative of rasagiline, I've noticed there's a handful of dubious Chinese pharmas already offering it on the net. Sounds like a promising substance and a definite improvement on Selegiline.

My link

[Rational Madman]

You've probably heard of and are awaiting Ladostigil's eventual release, a derivative of rasagiline, I've noticed there's a handful of dubious Chinese pharmas already offering it on the net. Sounds like a promising substance and a definite improvement on Selegiline.

My link

Yes, all hail Moussa Youdim.

[rwac]

Three parcels arrived today: Clonidine, Valproic Acid, and Rasagiline. The Rasagiline, which I've been using, will be continued on my titrating schedule. Clonidine and Valproic Acid will be eased into, since I'm still deciding on the doses.

I'm very interested in your experience with valproic acid.

Do you happen to have references for the negative effects of lithium on the hippocampus ?
I ask because I'm using low dose lithium for depression, and thinking of perhaps switching, one of these days.

[Rational Madman]

Three parcels arrived today: Clonidine, Valproic Acid, and Rasagiline. The Rasagiline, which I've been using, will be continued on my titrating schedule. Clonidine and Valproic Acid will be eased into, since I'm still deciding on the doses.

I'm very interested in your experience with valproic acid.

Do you happen to have references for the negative effects of lithium on the hippocampus ?
I ask because I'm using low dose lithium for depression, and thinking of perhaps switching, one of these days.

The first that comes immediately to mind would be "Driving GDNF Expression: The Green and Red Traffic Lights" by Saavedra, et. al., where I believe that effect is discussed in the mood stabilizer and antipsychotic section. There are a few other studies out there, but I would have to dig for them.

Edited by Rol82, 28 September 2010 - 02:59 AM.

[APBT]

I think I've concluded that freeze dried coffee is the most cost effective cognitive enhancer on the market. But when consumed rather than brewed----which may be a bit intense for some. Another few underutilized gems would be the neurotrophic methylfolate and ribose.

As most of the other posters are focusing on the super-sexy Rx, I'll inquire about the more mundane....

Curious as always, how did you conclude - in a seemingly short period of time, based on when you posted to your regimen - "that freeze dried coffee is the most effective cognitive enhancer on the market?" What is the mechanism; certainly not the caffeine? Why freeze dried? Any magic to your brand of choice?

I've put together some pretty wicked foodstuff concoctions myself, some I actually like, what do you mix the coffee with? Please don't tell me it's down the hatch with a tablespoon of freeze dried coffee. Also, is this consumed in a single dose in the AM?

I tried ribose, in a relatively short three week trial for improvement in athletic performance. For that purpose, I found it utterly useless. I didn't notice any obvious cognitive enhancement either.

[Rational Madman]

For the time being, and due to some new arrivals, I decided to calibrate my medication cocktail a bit. The following will be used for a few weeks, because it constitutes a good base, and because I'm not sure how superfluous or absolutely necessary the other agents are, but if anyone is currently using the medications that I'm temporarily ceasing, please don't interpret my changes as a loss of confidence.

Donepezil: 10 mg
Modafinil: 200 mg
Vyvanse: 30 mg
Valproic Acid: 30 mg
Rasagiline: 2 mg
Clonidine: 75 mcg
Cabergoline: 0.25 mg twice weekly

On Deck
Atomoxetine: Its preference for NMDA receptors is somewhat bothersome, and although its inhibition of the reuptake norephinephrine and frontal cortical effects are attractive properties, Modafinil and Clonidine's relationship with alpha receptors should more than amply compensate, and Modafinil and Vyvanse both have a similar effect on the catechloamine volumes in frontal regions. But, like I said, its combination with psychostimulants may neutralize its effect on NMDA currents, so I'm still open to use.

Amisulpride: Although its effects on the frontal cortical areas enhance greatly enhance its therapeutic value when adminstered at small doses, there is still a risk of decreasing dopamine in other regions, such as the mesolimbic and striatum regions. Furthermore, it has yet to be entirely clear effects on neurotrophic agents, which are highly dependent on the expression of D2 receptors. Further, the valproic acid should substitute as a reelin promoter, but Valproic's reelin property is still a matter of debate. But given the evidence of its effects, which was quantified in one study to be roughly equal to the much celebrated Amineptine, I'm still open to using it as an augmenting agent.

Fluvoxamine: Overall great antidepressant that I highly recommend, but its use may compete with the psychostimulant's effects on frontal regions, and by using Rasagiline at 2 mg, it begins to have an effect on serotonin---but yet to be entirely quantified effect. However, since I'll be without an agent with effects on opioid pathways and oxytocin synthesis, I'm most likely to resume use with this agent. But, the Acitretin may solve these problems, which is unfortunately en route, but I'm wondering if my temporary experimentation with liquid emulsified vitamin A might be somewhat sufficient.

The Future
Rapamycin: Very cool anti-aging agent that should help keep mTOR and excess calcineurin in check, but I'm having trouble finding a precedent for twice weekly use in otherwise healthy subjects. However, I found a good price at my new favorite pharmacy that I'm using for much of everything, and since I'm no longer using Minocycline, I need something else with an effect on calcineurin levels.


Methylphenidate: May be a bit excessive, but since my monthly visit with my psychiatrist is tomorrow, I feel like I might be able to convince him to prescribe it as a substitute for Atomoxetine, since it also acts as a norepinephrine reuptake inhibitor, is exceedingly safe, and has a short half-life. Unfortunately, I wasn't able to convince him to prescribe Guanfacine, which he doesn't seem to be too fond of due to its fatigue promoting properties.

Prescription Supplements: There are some prescription supplements out their that have a neuropsychiatric rationale, and I'm eager to get a prescription for since I have an excellent insurance plan, and because my selective callousness makes me indifferent to the inflation in health care costs, and my symbolic ---but systemically immaterial---role. The first would be Lovaza, a fish oil supplement that I'll probably ask for next month when my bottle of Nordic Natruals is finished. The second would be Deplin, or prescription methylfolate, which would be pretty cool to take at 15 mg, and substantially better than the 5 mg of Life Extension methylfolate that I just started taking. The third would be injectable methylcobalamin, but has anyone heard of its clinical use in neuropsychiatry?

Cerebrolysin: I'm still on the look out for bargain prices on the Internet, but as a matter of principle, I'm unwilling to pay the inflated prices that Internet pharmacies are charging. I have a number of foreign friends from Europe, China, India, etc., and I'm tempted to ask one of them to smuggle some drugs back from their pilgrimages to their home countries. Alternatively, I got an offer from an unnamed government agency to help kill terrorists whilst working comfortably in a cubicle in downtown Islamabad, but for philosophical and personal reasons, I turned down the offer. However, I keep getting less than subtle "feeler" e-mails, so I imagine their offer still stands. But, a re-analysis of the spiral effect that the radical Islam contagion might have on the security dilemma between India and Pakistan is making me reconsider. This employment opportunity is germane because it would provide the additional benefit of putting me in close proximity to a number of cool pharmacies (which would probably be across the border, of course) that cater to individuals like myself, or Indian Institute of Technology students---whom are shockingly brilliant. But, I'll have to convince my consumption companion to join me, but after repeated acts of unfaithfulness (including a close friend...I know, I'm awful), I was forced to cede virtually all relationship decisions to her, which I'm sure she believes includes my future place of employment. What can I say, she can have a Lady Macbeth effect on me, and as long as she's near me, she's the only woman that doesn't leave me bored, and eager to resume my misogynist objectification of the many interesting women that possess abundant physical charms and exhibit exploitable vulnerabilities. I know, I sound like some sort of relic from another decade that is evidently unmoved by normative innovations and the now standardized bombardment with feminist literature. But, I'm at least not loud about my beliefs, which shouldn't be mistaken for subscribing to the notion of there being any innate differences between genders. And, I suppose this loathsome quality can be rationalized as just another manifestation of the tragic and inescapable human condition. But, whatever the reason, I've entered into several relationships purely for sexual gratification, and strangely, am not wracked with guilt. Well, whatever, and I apologize for the deviation, but this thread also serves as a device for recording my thoughts---so readers will have to stomach the good, the bad, and the ugly.

Methylene Blue: I'm waiting for a consumer accessible grade that's comparable to Rember, but unless I commit an act of fraud, I won't find any such compound.

Dimebon: I continue to follow research developments and pharmacy prices, because I think its recent clinical trial failure does not mark its end.

Edited by Rol82, 30 September 2010 - 01:35 AM.

[Rational Madman]

Although it's a bit premature, I'm wondering if there might be something to the low dose Dilantin therapy advocated by Jack Dreyfus, and if low dose Valproic Acid might be a better alternative. Since I allowed my confident understanding of the scientific rationale of each agent overwhelm my usually cautious, and more sound empiric approach, it would be difficult for me to judge the relative contribution of each new addition. But in concert, they're yielding a calm serenity that doesn't diminish the positive cognitive effects of the other agents. So, it appears that I've created a very effective synergy that I'll monitor closely over the next two weeks. What's probably most noteworthy is the combination's influence on impulse control, which would be an immensely encouraging effect if it can be demonstrated to have durability. The synergy with Valproic Acid and Modafinil is probably most important in this regard, because the combination's likely stabilization of Gaba and Glutamate receptor signaling.

Edited by Rol82, 29 September 2010 - 10:05 AM.

[Rational Madman]

I think I've concluded that freeze dried coffee is the most cost effective cognitive enhancer on the market. But when consumed rather than brewed----which may be a bit intense for some. Another few underutilized gems would be the neurotrophic methylfolate and ribose.

As most of the other posters are focusing on the super-sexy Rx, I'll inquire about the more mundane....

Curious as always, how did you conclude - in a seemingly short period of time, based on when you posted to your regimen - "that freeze dried coffee is the most effective cognitive enhancer on the market?" What is the mechanism; certainly not the caffeine? Why freeze dried? Any magic to your brand of choice?

I've put together some pretty wicked foodstuff concoctions myself, some I actually like, what do you mix the coffee with? Please don't tell me it's down the hatch with a tablespoon of freeze dried coffee. Also, is this consumed in a single dose in the AM?

I tried ribose, in a relatively short three week trial for improvement in athletic performance. For that purpose, I found it utterly useless. I didn't notice any obvious cognitive enhancement either.

My choice of freeze dried coffee was based on my former copious consumption---and unfortunate intermittent intolerance---that has resumed with less intensity, and an enlightenment about its pharmacology. The effects of caffeine have been exhaustively studied, and I don't want to have to explain the rationale for caffeine use when it can be so easily discovered. But, a full appreciation of the ORAC value is another reason for my conclusion, which is secondary, though, to the more important discovery of the substantial amount of pyroglutamic acid that appears to be more ample in freeze dried coffee. So, when you combine an inexpensive and subjectively effective substance containing cognitive enhancing constituents like caffeine, pyroglutamic acid, and abundant antioxidants, and weigh it against my vast experience, I suppose that's how I came to my somewhat unsubstantiated conclusion.

[dilenja]

Rol82, I've noticed reading your regimen you're fond as well of luteolin as a means of PDE4 inhibition. Are there any luteolin supplements in particular which have gained your trust that you'd feel comfortable recommending? I've been looking for a pure luteolin extract for sometime now but have been unable to locate the compound unfortunately outside of olive leaf extract. Is there a particular dosage do you know which would be considered generally effective for achieving PDE4 inhibition?

Fascinating thread I'd like to add as well. I've personally taken a lot from reading your well-considered, intelligent and intriguing perspectives and contributions. I realize it must take a lot of time to maintain this thread and am appreciative of your continued efforts to preserve your experiences and advice here on imminst. Thanks so much, Dilenja

[Recortes]

dilenja,
http://lutimax.com/

[medievil]

Although it's a bit premature, I'm wondering if there might be something to the low dose Dilantin therapy advocated by Jack Dreyfus, and if low dose Valproic Acid might be a better alternative. Since I allowed my confident understanding of the scientific rationale of each agent overwhelm my usually cautious, and more sound empiric approach, it would be difficult for me to judge the relative contribution of each new addition. But in concert, they're yielding a calm serenity that doesn't diminish the positive cognitive effects of the other agents. So, it appears that I've created a very effective synergy that I'll monitor closely over the next two weeks. What's probably most noteworthy is the combination's influence on impulse control, which would be an immensely encouraging effect if it can be demonstrated to have durability. The synergy with Valproic Acid and Modafinil is probably most important in this regard, because the combination's likely stabilization of Gaba and Glutamate receptor signaling.

Ive researched dilantin extensively in the past and the anecdotal reports dont seem to be consistent with the claims on the site jack dreyfus has, in fact it seems to have quite a few detrimental side effects, i was intrigued too at first, but after some research decided to drop the idea.

Also a comment on amphetamine counteract the NMDA antagonism of strattera, i think (not sure will need to further look at the literature) that the spike in glutamate caused by amphetamine only occurs in the nucleus accumbens and not specifically in other brainregio's related to cognition, so it wouldnt effectively counteract the NMDA antagonism.

D cyclosering wich i tought you were using would be an excellent candidate for that tough.

[Rational Madman]

Although it's a bit premature, I'm wondering if there might be something to the low dose Dilantin therapy advocated by Jack Dreyfus, and if low dose Valproic Acid might be a better alternative. Since I allowed my confident understanding of the scientific rationale of each agent overwhelm my usually cautious, and more sound empiric approach, it would be difficult for me to judge the relative contribution of each new addition. But in concert, they're yielding a calm serenity that doesn't diminish the positive cognitive effects of the other agents. So, it appears that I've created a very effective synergy that I'll monitor closely over the next two weeks. What's probably most noteworthy is the combination's influence on impulse control, which would be an immensely encouraging effect if it can be demonstrated to have durability. The synergy with Valproic Acid and Modafinil is probably most important in this regard, because the combination's likely stabilization of Gaba and Glutamate receptor signaling.

Ive researched dilantin extensively in the past and the anecdotal reports dont seem to be consistent with the claims on the site jack dreyfus has, in fact it seems to have quite a few detrimental side effects, i was intrigued too at first, but after some research decided to drop the idea.

Also a comment on amphetamine counteract the NMDA antagonism of strattera, i think (not sure will need to further look at the literature) that the spike in glutamate caused by amphetamine only occurs in the nucleus accumbens and not specifically in other brainregio's related to cognition, so it wouldnt effectively counteract the NMDA antagonism.

D cyclosering wich i tought you were using would be an excellent candidate for that tough.

Dilantin has a pretty nasty side effect profile, and in general, is a pretty antiquated drug, both of which may explain the poor user responses. But the use of Valproic Acid should normalize the electrical activity in the brain in the same way as Dilantin, though, and thus, may confer the same benefits. For the amphetamine, thanks for correcting me, because I was less clear about its effects on glutamate, and will have to reevaluate some false beliefs related to this mechanism. The cycloserine might indeed be a good candidate in this regard, but I'm worried about its uncertain effects on protein synthesis---serine/threonine protein kinase activity in particular---and less than illuminating in-vivo evidence. One prominent enthusiast, Donald Goff, has concluded that once weekly doses are best for providing therapeutic benefits, but I want to wait a bit until more evidence emerges, since I think my former enthusiasm was premature.

[medievil]

Perhaps lisuride (wich i suggested before) may be a good idea, its a extremely strong 5HT2A agonist, with a simular pharmacological profile as LSD, and 5HT2A agonism induces glutamate release.

Its also a potent neuroprotectant and according to a patent acted as a psychostimulant with minimal side effects after the adjustment period.

[Rational Madman]

Perhaps lisuride (wich i suggested before) may be a good idea, its a extremely strong 5HT2A agonist, with a simular pharmacological profile as LSD, and 5HT2A agonism induces glutamate release.

Its also a potent neuroprotectant and according to a patent acted as a psychostimulant with minimal side effects after the adjustment period.

I'm assuming its affinity for 5ht1a is your rationale for its use for amphetamine desensitization? Right? To be honest, I've given it a look, but how often is it used clinically? Is there any reason for its marginalization? There is some pretty impressive evidence, but I think its important not to judge these findings at face value, because there might be some yet to be known effect that has led to a dampening of research interest. However, I'll shoot an e-mail to a few professors that I'm acquainted with, and make some inquiries, because you seem to be quite interested, and based on its pharmacology and your symptom presentation, it might have some therapeutic value for your case. But personally, it just seems like too much of a trip into the wilderness.

On a separate note, I urge you to start a regimen thread here, since there are a lot of Medieval's wandering through these threads that are in desperate need of your insights. Sooner or later, we'll get to the bottom of all of your problems!

[Rational Madman]

Rol82, I've noticed reading your regimen you're fond as well of luteolin as a means of PDE4 inhibition. Are there any luteolin supplements in particular which have gained your trust that you'd feel comfortable recommending? I've been looking for a pure luteolin extract for sometime now but have been unable to locate the compound unfortunately outside of olive leaf extract. Is there a particular dosage do you know which would be considered generally effective for achieving PDE4 inhibition?

Fascinating thread I'd like to add as well. I've personally taken a lot from reading your well-considered, intelligent and intriguing perspectives and contributions. I realize it must take a lot of time to maintain this thread and am appreciative of your continued efforts to preserve your experiences and advice here on imminst. Thanks so much, Dilenja

The inhibition of phosphodiesterase 4 is great target for increasing CREB, and when combined with the widely studied properties of the flavonoid, there should be statically significant effect on long term induction. My current dosage is 800 mg/day, which has been working great, but I haven't arrived at the optimal dose as of yet. When it comes to luteolin, and resveratrol, I'm less well versed, so perhaps you should shoot a message to someone like Maxwatt.

And I appreciate your sentiments, as I try to do my best in spite of my limited academic exposure to the sciences. Moreover, although others are loath to speak candidly about their experiences, I endeavor to be open as possible about the taboo illnesses that are criminally undertreated. This forum has been a valuable tool for my research efforts over the last two years, and I imagine others feel the same way. But I've witnessed far too many participants visit with the dim hope of relief, and leave disillusioned, which is a common outcome that has left me immensely dismayed, and is a pattern that I hope I can make somewhat of a humble contribution in altering. So I'm more than happy to sacrifice potentially pleasurable portions of my personal life for the sake of altruism---which is still a higher form of pleasure that can be rationalized by utilitarianism. And I suppose is healthier than sadistically manipulating and disheartening vulnerable women on Match.com---where you'll never find a more depressing population of easily seducible romantic idealists. But fortunately, I think I've permanently suppressed this more wicked side---which I sincerely hope others won't succumb to due to self-loathing or shallowness.

Anyway, based on your posting in the thread of the exceedingly embittered StrangeAeons----whom I suspect is perilously, and perhaps irretrievably close to suicide----I was somewhat shocked by your endorsement of the orthomolecular approach to psychiatry, which might be understandable under the conditions of desperation, but should be deemed ultimately futile. And given this dalliance, I'm curious about your current status? Have the amphetamine salts ceased to work? Are you facing an intransigent psychiatrist? Has something else gone awry?

Edited by Rol82, 30 September 2010 - 11:58 PM.

[medievil]

Perhaps lisuride (wich i suggested before) may be a good idea, its a extremely strong 5HT2A agonist, with a simular pharmacological profile as LSD, and 5HT2A agonism induces glutamate release.

Its also a potent neuroprotectant and according to a patent acted as a psychostimulant with minimal side effects after the adjustment period.

I'm assuming its affinity for 5ht1a is your rationale for its use for amphetamine desensitization? Right? To be honest, I've given it a look, but how often is it used clinically? Is there any reason for its marginalization? There is some pretty impressive evidence, but I think its important not to judge these findings at face value, because there might be some yet to be known effect that has led to a dampening of research interest. However, I'll shoot an e-mail to a few professors that I'm acquainted with, and make some inquiries, because you seem to be quite interested, and based on its pharmacology and your symptom presentation, it might have some therapeutic value for your case. But personally, it just seems like too much of a trip into the wilderness.

On a separate note, I urge you to start a regimen thread here, since there are a lot of Medieval's wandering through these threads that are in desperate need of your insights. Sooner or later, we'll get to the bottom of all of your problems!

?
No i'm not interested in lisuride for its potential effects on amp desensitization at all, besides that, LSD is a very strong 5HT1A agonist too yet it induces glutamate release wich i assume is simular to lisuride.

Have to go to work now, will write more later.

[Rational Madman]

Perhaps lisuride (wich i suggested before) may be a good idea, its a extremely strong 5HT2A agonist, with a simular pharmacological profile as LSD, and 5HT2A agonism induces glutamate release.

Its also a potent neuroprotectant and according to a patent acted as a psychostimulant with minimal side effects after the adjustment period.

I'm assuming its affinity for 5ht1a is your rationale for its use for amphetamine desensitization? Right? To be honest, I've given it a look, but how often is it used clinically? Is there any reason for its marginalization? There is some pretty impressive evidence, but I think its important not to judge these findings at face value, because there might be some yet to be known effect that has led to a dampening of research interest. However, I'll shoot an e-mail to a few professors that I'm acquainted with, and make some inquiries, because you seem to be quite interested, and based on its pharmacology and your symptom presentation, it might have some therapeutic value for your case. But personally, it just seems like too much of a trip into the wilderness.

On a separate note, I urge you to start a regimen thread here, since there are a lot of Medieval's wandering through these threads that are in desperate need of your insights. Sooner or later, we'll get to the bottom of all of your problems!

?
No i'm not interested in lisuride for its potential effects on amp desensitization at all, besides that, LSD is a very strong 5HT1A agonist too yet it induces glutamate release wich i assume is simular to lisuride.

Have to go to work now, will write more later.

That might indeed be the case, but the increase in glutamate is probably not caused by an activation of 5ht1a receptors, which rather, has a largely inhibitory effect on the release of glutamate. And since you suggested this agent while we were discussing the subject of amphetamine desensitization, I only assumed that you were privy to information about its mechanism that I was unaware of, and was at odds with my somewhat tentative understanding of its pharmacology. From my previous understanding, the application of Lisuride leads to an increase in glutamate primarily in the prefrontal cortex via 5ht2a/5ht1a activation. And through its more Parkinsinion affinities, a dose dependent decrease in glutatmate release in certain regions like the striatum, which is coupled by a reduction in the concentrations of co-agonists glycine and glutamic acid through a mechanistically influenced increase in glutathione synthesis.

In any case, my previously reluctant endorsement shouldn't be confused with a research borne interest in its potential as an adjunct for amphetamine desensitization.

Edited by Rol82, 30 September 2010 - 05:28 AM.

[medievil]

Yes im aware that 5HT1A agonism has a supressive effect on glutamate, but lisuride share the same intrinsic activity on 5HT1A and 5HT2A as LSD if i'm correct and LSD induces glutamate release.

I wasnt aware that 5HT2A agonism only increases glutamate in the frontal cortex? I tought it caused a glutamate spike in the whole striatum.

I'm also unaware of D2, D3 and D4 agonism causing a decrease in glutaminergic firing (except D4 agonism, but lets look at the full picture.

Personally i dont think lisuride can be of any benefit for amphetamine desentisation actually and i'm happy with the results im getting from memantine atm.

Memantine also is the reason i probably wont try lisuride any time soon as it also keeps the presynaptic receptors sensitive, leaving me into the adaptation phase where i would feel worse.

Lisuride appears to be a:
5HT1A agonist
5HT1B agonist
5HT2A agonist
5HT2C agonist (neglible in human cells)
5HT6 agonist
5HT7 antagonist
5HT5A didnt find yet
D2 agonist
D3 agonist (also neglible in human cells)
D4 agonist
ALPHA 2 antagonist
And a few other adrogenic receptors.

Binding to D3 is negliable.

t is also useful to present the npKi data of Fig. S2 in numerical format. In the listing below, the npKi values for each drug are arranged in decreasing order. A value of 0.00 means that the Ki value was measured as >10,000 nm. “ND” indicates that the data is not available. The 5-HT2A and 5-HT2C receptors are also highlighted in bold font for easier location. npKi values below about 2.0 should be imperceptible, while values above about 2.0 should be perceptible, and the higher the npKi value, the more perceptible a receptor should be.
So basicly, this is what counts:
lisuride: 4.00 5ht1a, 3.88 Alpha2C, 3.78 Alpha2B, 3.22 Alpha2A, 3.01 5ht2b, 2.99 5ht5a, 2.90 D4, 2.74 5ht2a, 2.65 D2, 2.64 5ht7, 2.61 5ht6, 2.56 Beta1, 2.27 5ht1b, 2.09 Alpha1A,

Edited by medievil, 30 September 2010 - 01:39 PM.

[medievil]

Rol, i have a few questions for you since you have a extensive knowledge on a variaty of things.

As you may know i'm ignoring supplements (and not intrested) in supplements that slow down my aging, but rather things that reduce my chances of getting cancer and stuff (like curcumin and resveratrol).

I'm also interested in supplements that promote my chances of recovery in a deadly accident (i know pretty vague) something that increases tissue regeneration, slows the dying proces?, improve survival of my organs, and for example like to avoid things that thin my blood that reduce the chances of bleeding to death that sort of stuff.

Dunno wheter its even possible, just asking as you know your stuff. I'm mostly interested in increases chances of survival in my current lifespan, rather then focussing on increasing it.

My regime is very experimental, i'l make a thread about it on here soon, but have differend goals then most people here.

Edited by medievil, 30 September 2010 - 06:36 PM.

[e Volution]

I'm mostly interested in increases chances of survival in my current lifespan, rather then focussing on increasing it.

I think this is misguided by focusing on life span and ignoring health span. As a male and living in Belgium your life expectancy is 76.5. The oldest man in the world lived to 120. That's an extra 43 years. And slowing down aging is really just focusing on those latter years. Squaring the curve is essentially life extension viewed this way.

To get back on-topic: I'm just an observer in this thread, but it is truly fascinating! My mind boggles at the thought of this regimen in 20+ years when we really start getting a more complex understanding of the brain!