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TREATING ANXIETY SAFELY & EFFECTIVELY


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#61 ScienceGuy

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Posted 05 February 2012 - 02:33 PM

Regarding, Afobazol. If you look at the details it looks more like a semi-antipsychotic than something for anxiety... thouhts?

Mild tranquilizer afobazol is a selective anxiolytic, not related to the class of receptor agonists benzodiazepin. Prevents the development of membranozavisimyh changes in GABA-receptor.


You could be right in that AFOBAZOLE might indeed have effects akin to semi-antipsychotic ;) ; however, that does not necessarily mean that it might not also be highly effective in treating ANXIETY. Note that many drugs have multiple applications. :)

There does exist an amount of substantiated evidence to support AFOBAZOLE's ANXIOLYTIC effects; and hence it may indeed be of use in TREATING ANXIETY SAFELY & EFFECTIVELY.

However, AFOBAZOLE is a relatively new drug, and such studies are somewhat limited, which I why I have put it on the 'POSSIBLY' list ;)

This study for example does seem to lend substantiation to its ANXIOLYTIC effects:

Bulletin of Experimental Biology and Medicine, Vol. 151, No. 5, September, 2011 PHARMACOLOGY AND TOXICOLOGY

Effects of Afobazole on the Content of Neurotransmitter Amino Acids in the Striatum in Global Transient Ischemia

V. S. Baykova, I. A. Kadnikov, M. V. Voronin, T. S. Ganshina, A. V. Gnezdilova, A. A. Gorbunov, P. C. Mirzoyan, and S. B. Seredenin

EDITED FROM FULL TEXT:

The objective of this study was to investigate delayed effects of afobazole on the levels of neurotransmitter amino acids in brain structures…

GABA level was significantly decreased in the striatum of ischemic rats. After afobazole administration, GABA level improved and reached the control values recorded in intact animals…

Afobazole administration resulted in restitution of striatal GABA content, which approached the control values; this should promote recovery of neuroprotective systems related to inhibitory influences…

Afobazole administration to ischemic animals resulted in more substantial increase in taurine level in the striatum. Agonistic interaction between afobazole and σ1-receptors, possibly underlies this phenomenon…

Thus, the increase in taurine level alongside with GABA can be regarded as components of recovery therapy…

Our findings led us to a conclusion that afobazole administered in a dose of 10 mg/kg to the animals 40 min after modeling of global ischemia restored the impaired balance of excitatory and inhibitory amino acids in the striatum, normalized their content to control values, and activates endogenous taurine-dependent neuroprotection system…

Anxiolytic agent afobazole (10 mg/kg intraperitoneally) 24 h after ischemia restores impaired balance of excitatory and inhibitory amino acids in the striatum of mongrel rats, normalizes their content to control levels, and activates endogenous taurine-dependent system of neuroprotection.

Edited by ScienceGuy, 05 February 2012 - 02:35 PM.


#62 Introspecta

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Posted 05 February 2012 - 02:44 PM

Hm this stuff sounds interesting. I may have to try sometime in the future

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#63 Ampa-omega

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Posted 05 February 2012 - 05:34 PM

i found this thread very interesting, at least to bring up some out of the box perspective on anti anxiety, it is kind of disheartening though that so many anti anxiety aids are not recommended, many that are very popular and have been used by many people, im a bit wary of the exotic recommendations though but i appreciate this thread.

i want to mention that maybe cortisol inhibition/lowering could be another option for anti anxiety, at least something to look into.

#64 ScienceGuy

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Posted 05 February 2012 - 06:00 PM

i want to mention that maybe cortisol inhibition/lowering could be another option for anti anxiety, at least something to look into.


YES, absolutely! :)

That is in fact one of RHOLIOLA ROSEA's ANXIOLYTIC mechanism's of action ;)

The problem with other CORTISOL REDUCING substances, is their other physiological effects... take PHOSPHATIDYLSERINE (PS) for example, wherein you need to take 600+mg PS to experience CORTISOL REDUCING effects; the problem being that at that dosage many individuals will experience intolerable SIDE EFFECTS such as NAUSEA, STOMACH UPSET and INSOMNIA...

However, I am open to suggestions! :)

#65 ScienceGuy

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Posted 05 February 2012 - 06:08 PM

i found this thread very interesting, at least to bring up some out of the box perspective on anti anxiety, it is kind of disheartening though that so many anti anxiety aids are not recommended, many that are very popular and have been used by many people, im a bit wary of the exotic recommendations though but i appreciate this thread.


Thank you for the feedback. That is partly my reason for posting the thread. :)

I have treated many people for ANXIETY for many years; and it is a key area regarding which the information on how best to safely and effectively treat it is sadly lacking and/or poorly understood.

The MISUSE / ABUSE of GABA RECEPTOR AGONISTS (and I am not just referring to BENZODIAZEPINES) is an EPIDEMIC that causes millions to suffer unecessarily :sad:

N.B. They DO have their uses; but should be treated with exactly the same respect as OPIOID RECEPTOR AGONISTS, and taken appropriately (i.e. restricted to short-term use (only) and CYCLED ON / OFF if wishing to use for the longer-term).

In particular, the physicians who hand out BENZODIAZEPINES like sweets / candy should be lined up in front of a firing squad and shot... :ph34r:

Edited by ScienceGuy, 05 February 2012 - 06:11 PM.

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#66 Ampa-omega

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Posted 05 February 2012 - 06:21 PM

i must say you do put alot of detail in your writing, lots of attention to the font,
in regards to cortisol i dont know much but i have heard of relora, gingko, grapeseed, icariin, colostrum, being shown to reduce cortisol, there could be more substances that could also though.
http://www.ergo-log.com/cortisol.html

#67 ScienceGuy

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Posted 05 February 2012 - 07:18 PM

i must say you do put alot of detail in your writing, lots of attention to the font,
in regards to cortisol i dont know much but i have heard of relora, gingko, grapeseed, icariin, colostrum, being shown to reduce cortisol, there could be more substances that could also though.
http://www.ergo-log.com/cortisol.html


Very interesting the CORTISOL LOWERING topic, and thank you for the suggestions! :)

I am very familar with all those that you have suggested and for the sake of clarity I think it best that I address each individually / grouped as follows:

RELORA (MAGNOLIA OFFICINALIS and PHELLODENDRON AMURENSE)

Yes, brilliant! This one is definitely going on the list... nice one! ;)

I should mention that in my clinical practice, despite the brand's marketing spiel regarding RELORA, it does cause sedation in some (but not all) people which can be a 'deal-breaker' regards taking it; however, there are many people who can take it without any side effects whatsoever, whom find it a helpful adjunct in treating ANXIETY :)

GINKGO BILOBA and HORNY GOAT WEED (ICARIIN) gotta love that name! Never gets old! :laugh:

Both these can in fact cause ANXIETY in some (but not all) people.

GRAPE SEED EXTRACT

The problem with GRAPE SEED EXTRACT in relation to CORTISOL REDUCTION is akin to PHOSPHATIDYLSERINE (PS) in that, like PS, the dosage that effectively impacts CORTISOL levels also has the potential to induce intolerable SIDE EFFECTS in many people, including but not limited to: HEADACHE, INSOMNIA, NAUSEA and STOMACH UPSET.

COLOSTRUM

Unfortunately, there does not exist conclusive substantiated evidence regards COLOSTRUM being effective in reducing CORTISOL levels.

There is only a single study that indicates a reduction in CORTISOL, but from the FULL TEXT it is clear that is limited, and furthermore there was NO SIGNIFICANT DIFFERENCES in either HS [High Stress] subjects or LS [Low Stress] subjects with regards to TENSION, DEPRESSION, ANGER, VIGOR or FATIGUE

Furthermore, there is another study reporting COLOSTRUM have no effect in reducing CORTISOL LEVELS.

See the following:

Am J Clin Nutr. 2000 Jun;71(6):1536-44.

The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress.

Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE.

Source

TNO Nutrition and Food Research Institute, Zeist, The Netherlands. markus@voeding.tno.nl

Abstract

BACKGROUND:
Increased brain serotonin may improve the ability to cope with stress, whereas a decline in serotonin activity is involved in depressive mood. The uptake of the serotonin precursor, tryptophan, into the brain is dependent on nutrients that influence the cerebral availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp-LNAA ratio). Therefore, a diet-induced increase in tryptophan availability may increase brain serotonin synthesis and improve coping and mood, particularly in stress-vulnerable subjects.

OBJECTIVE:
We tested whether alpha-lactalbumin, a whey protein with a high tryptophan content, may increase the plasma Trp-LNAA ratio and reduce depressive mood and cortisol concentrations in stress-vulnerable subjects under acute stress.

DESIGN:
Twenty-nine highly stress-vulnerable subjects and 29 relatively stress-invulnerable subjects participated in a double-blind, placebo-controlled study. Subjects were exposed to experimental stress after the intake of a diet enriched with either alpha-lactalbumin or sodium-caseinate. Diet-induced changes in the plasma Trp-LNAA ratio and prolactin were measured. Changes in mood, pulse rate, skin conductance, and cortisol concentrations were assessed before and after the stressor.

RESULTS:
The plasma Trp-LNAA ratio was 48% higher after the alpha-lactalbumin diet than after the casein diet (P = 0.0001). In stress-vulnerable subjects this was accompanied by higher prolactin concentrations (P = 0.001), a decrease in cortisol (P = 0.036), and reduced depressive feelings (P = 0.007) under stress.

CONCLUSIONS:
Consumption of a dietary protein enriched in tryptophan increased the plasma Trp-LNAA ratio and, in stress-vulnerable subjects, improved coping ability, probably through alterations in brain serotonin.

PMID: 10837296

FROM FULL TEXT:

“A cortisol stress response was prevented in HS [High Stress] subjects but not in LS [Low Stress] subjects…”

Furthermore there was NO SIGNIFICANT DIFFERENCES in either HS [High Stress] subjects or LS [Low Stress] subjects with regards to TENSION, DEPRESSION, ANGER, VIGOR or FATIGUE.

----------------------------------------------------------------------------------------------------------------------------------------------

Int J Sport Nutr Exerc Metab. 2011 Apr;21(2):135-45.

Bovine colostrum supplementation's lack of effect on immune variables during short-term intense exercise in well-trained athletes.

Carol A, Witkamp RF, Wichers HJ, Mensink M.

Source

Div. of Human Nutrition, Wageningen University and Research Center, Wageningen, The Netherlands.

Abstract

The purpose of this study was to investigate the potential of bovine colostrum to attenuate postexercise decline in immune function. The authors evaluated the time course of a number of immune variables after short-term intense exercise in 9 male athletes after 10 d of supplementation with either colostrum or skim-milk powder. To increase the stress on the immune system subjects performed a glycogen-depletion trial the evening before the endurance trial (90 min at 50% Wmax). Blood samples were taken before the glycogen-depletion trial, before and after the endurance trial, and the next morning, ~22 hr after cessation of the exercise. Plasma cortisol levels increased over time, reaching the highest level directly after exercise, and were still elevated ~22 hr after exercise compared with baseline values (p < .001). Neutrophil cell count was increased after exercise and dropped below starting values 22 hr after exercise (time effect p < .001). Circulating immunoglobulins did not change over time. A significant time effect was seen for interleukin (IL)-6, IL-10, IL-1-receptor agonist, and C-reactive protein, with levels being higher directly after exercise (p < .05). Other cytokines (interferon-γ, IL-1a, IL-8, tumor necrosis factor-a) did not show a time effect. No differences were seen between colostrum and skim-milk powder in any of the investigated variables. Our results are consistent with the hypothesis that intense exercise affects several variables of the immune system. Colostrum did not alter any of the postexercise immune variables compared with skim-milk powder, suggesting no role for bovine colostrum supplementation in preventing postexercise immune suppression after short-term intense exercise.

PMID: 21558575
----------------------------------------------------------------------------------------------------------------------------------------------


I should add that there is another 'supplement' which effectively reduces CORTISOL and is a safe and effective ANXIOLYTIC, which is GEROVITAL H3; however, it requires administration via INTRAMUSCULAR INJECTION, which (for obvious reasons) is why I have not included it on the list.

Edited by ScienceGuy, 05 February 2012 - 08:23 PM.


#68 Ampa-omega

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Posted 05 February 2012 - 08:49 PM

well im glad your willing to look into these things for the rest of us, thanks ;) and for all the effort

#69 ScienceGuy

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Posted 05 February 2012 - 09:00 PM

well im glad your willing to look into these things for the rest of us, thanks ;) and for all the effort


Thank YOU for suggesting the RELORA :)

P.S. Nutraceuticals happens to be a specialist field of mine, so there wasn't much looking into required as I'm very familiar with all them already, so I shouldn't take credit for effort really ;)

Edited by ScienceGuy, 05 February 2012 - 09:03 PM.


#70 Ampa-omega

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Posted 05 February 2012 - 09:07 PM

well im glad your willing to look into these things for the rest of us, thanks ;) and for all the effort


Thank YOU for suggesting the RELORA :)

P.S. Nutraceuticals happens to be a specialist field of mine, so there wasn't much looking into required as I'm very familiar with all them already, so I shouldn't take credit for effort really ;)


no, thank you for this thread, and all your detail, truly i would be more willing to contribute but I'm a bit fatigued lately so i apologize for that, i suspect there is likely more to the topic of cortical reduction though.

#71 health_nutty

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Posted 12 February 2012 - 01:27 AM

What about low dose lithium? 5mg of lithium was more noticeable than magnesium for me.

#72 manic_racetam

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Posted 12 February 2012 - 11:18 AM

i found this thread very interesting, at least to bring up some out of the box perspective on anti anxiety, it is kind of disheartening though that so many anti anxiety aids are not recommended, many that are very popular and have been used by many people, im a bit wary of the exotic recommendations though but i appreciate this thread.

i want to mention that maybe cortisol inhibition/lowering could be another option for anti anxiety, at least something to look into.


Interestingly enough I recently started taking 11-oxo (adrenosterone) which is a cortisol blocker. I wasn't sure if I was experiencing this stress blocking effect or if it was placebo but it must be blocking stress. I recently drove about 1,000 miles in a day and had a couple close calls on the freeway. The strange part about it was that I didn't seem to have any physical reaction to the near accidents. I was startled and reacted quickly but my heart didn't start pounding and I didn't feel any sort of peripheral changes in mood.... I just started driving again as if nothing had happened.

A very strange sensation indeed. Also, my very stressful current work situation seemed to be less of an emotional burden as well. I actually envisioned myself possibly abusing these things as a long-term solution, similar to performers with stage fright coming to rely on beta-blockers to perform but I'm sure the long term safety of taking adrenosterone is ill advised.

Weird that it seemed to block fight or flight reaction though... Does that make sense at all or is it just my imagination?

i found this thread very interesting, at least to bring up some out of the box perspective on anti anxiety, it is kind of disheartening though that so many anti anxiety aids are not recommended, many that are very popular and have been used by many people, im a bit wary of the exotic recommendations though but i appreciate this thread.


Thank you for the feedback. That is partly my reason for posting the thread. :)

I have treated many people for ANXIETY for many years; and it is a key area regarding which the information on how best to safely and effectively treat it is sadly lacking and/or poorly understood.

The MISUSE / ABUSE of GABA RECEPTOR AGONISTS (and I am not just referring to BENZODIAZEPINES) is an EPIDEMIC that causes millions to suffer unecessarily :sad:

N.B. They DO have their uses; but should be treated with exactly the same respect as OPIOID RECEPTOR AGONISTS, and taken appropriately (i.e. restricted to short-term use (only) and CYCLED ON / OFF if wishing to use for the longer-term).

In particular, the physicians who hand out BENZODIAZEPINES like sweets / candy should be lined up in front of a firing squad and shot... :ph34r:



#73 ScienceGuy

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Posted 12 February 2012 - 02:52 PM

What about low dose lithium? 5mg of lithium was more noticeable than magnesium for me.


Thank you for the suggestion.

I am glad to hear that LITHIUM works for you. I am assuming that you take the OROTATE form? :)

I did consider LITHIUM when compiling the list, and thought about adding it to the 'POSSIBLY' list; however, after much consideration I ultimately decided to omit it from the list, primarily due to its ANTI-NOOTROPIC effects and TOXICITY ;)

#74 health_nutty

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Posted 12 February 2012 - 06:44 PM

What about low dose lithium? 5mg of lithium was more noticeable than magnesium for me.


Thank you for the suggestion.

I am glad to hear that LITHIUM works for you. I am assuming that you take the OROTATE form? :)

I did consider LITHIUM when compiling the list, and thought about adding it to the 'POSSIBLY' list; however, after much consideration I ultimately decided to omit it from the list, primarily due to its ANTI-NOOTROPIC effects and TOXICITY ;)


I do take the orotate form that contains 5mg of elemental lithium. I'm very curious about the anti-nootropic effects. I do know lithium has potential toxicity issues at high clinical doses 120mg of elemental lithium or more per day. I thought lithium would have nootropic effects long term because it promotes neurogenesis. I woud love to get your opinion on this:

http://www.ncbi.nlm....pubmed/10987856
Enhancement of hippocampal neurogenesis by lithium.

Increasing evidence suggests that mood disorders are associated with a reduction in regional CNS volume and neuronal and glial cell atrophy or loss. Lithium, a mainstay in the treatment of mood disorders, has recently been demonstrated to robustly increase the levels of the cytoprotective B-cell lymphoma protein-2 (bcl-2) in areas of rodent brain and in cultured cells. In view of bcl-2's antiapoptotic and neurotrophic effects, the present study was undertaken to determine if lithium affects neurogenesis in the adult rodent hippocampus. Mice were chronically treated with lithium, and 5-bromo-2-deoxyuridine (BrdU) labeling of dividing cells was conducted over 12 days. Immunohistochemical analysis was undertaken 1 day after the last injection, and three-dimensional stereological cell counting revealed that lithium produced a significant 25% increase in the BrdU-labeled cells in the dentate gyrus. Double-labeling immunofluorescence studies were undertaken to co-localize BrdU-positive cells with neuron-specific nuclear protein and showed that approximately 65% of the cells were double-labeled. These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders.

Edited by health_nutty, 12 February 2012 - 06:45 PM.


#75 Ampa-omega

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Posted 13 February 2012 - 03:32 PM

i found this thread very interesting, at least to bring up some out of the box perspective on anti anxiety, it is kind of disheartening though that so many anti anxiety aids are not recommended, many that are very popular and have been used by many people, im a bit wary of the exotic recommendations though but i appreciate this thread.

i want to mention that maybe cortisol inhibition/lowering could be another option for anti anxiety, at least something to look into.


Interestingly enough I recently started taking 11-oxo (adrenosterone) which is a cortisol blocker. I wasn't sure if I was experiencing this stress blocking effect or if it was placebo but it must be blocking stress. I recently drove about 1,000 miles in a day and had a couple close calls on the freeway. The strange part about it was that I didn't seem to have any physical reaction to the near accidents. I was startled and reacted quickly but my heart didn't start pounding and I didn't feel any sort of peripheral changes in mood.... I just started driving again as if nothing had happened.

A very strange sensation indeed. Also, my very stressful current work situation seemed to be less of an emotional burden as well. I actually envisioned myself possibly abusing these things as a long-term solution, similar to performers with stage fright coming to rely on beta-blockers to perform but I'm sure the long term safety of taking adrenosterone is ill advised.

Weird that it seemed to block fight or flight reaction though... Does that make sense at all or is it just my imagination


sorry for the late reply,
thanks for bringing 11-oxo up its actually a supplement i knew about but must of forgot, i may actually consider trying since it seems to be more potent for cortisol reduction than some herbal remedies, thanks for sharing your thoughts, i would think stress is very implicated in flight and fight responces, so reducing cortisol could effect how you respond to emergencies very differently possibly for better and worse, be careful driving! I'd personally rather have my stress responce with me on the road just to be safe, and i'd rather take oxo when off the road, it seems kinda nootropic.

Edited by Ampa-omega, 13 February 2012 - 03:35 PM.


#76 ScienceGuy

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Posted 13 February 2012 - 06:10 PM

I do take the orotate form that contains 5mg of elemental lithium. I'm very curious about the anti-nootropic effects.


There is substantiated scientific evidence both from medical studies and clinical practice that demonstrates LITHIUM to posses ANTI-NOOTROPIC effects; this is further supported by anecdotal reports from many users who have experienced COGNITIVE IMPAIRMENT, including MEMORY LOSS, when taking LITHIUM, including the OROTATE form; and whilst this does appear to be somewhat dosage dependent it does appear to still occur to an extent at low doses (e.g. 5mg LITHIUM).

See the following:

J Clin Psychiatry. 2009 Nov;70(11):1588-97. Epub 2009 Aug 11.

Effects of lithium on cognitive performance: a meta-analysis

Wingo AP, Wingo TS, Harvey PD, Baldessarini RJ.

Source

Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA. aliza.wingo@emory.edu

Abstract

BACKGROUND:
Cognitive impairment is underrecognized among patients with bipolar disorder and may represent not only effects of the illness but also adverse effects of its treatments. Among these, lithium is the best-studied mood stabilizer. As its cognitive effects are mixed and not well-known, we assessed reported effects of lithium on cognitive performance.

DATA SOURCES:
MEDLINE, PsycINFO, and EMBASE databases (1950 to December 2008) were queried with the keywords lithium, cognit*, neurocognit*, neuropsych*, psycholog*, attention, concentration, processing speed, memory, executive, and learning. Database searches were supplemented with bibliographic cross-referencing by hand. The literature search was conducted independently by 2 authors (A.P.W. and T.S.W.) during August and September 2008, and questions about appropriate inclusion or exclusion were resolved between them by consensus.

STUDY SELECTION:
Of 586 reports initially identified as being of potential interest, 12, involving 539 subjects, met our inclusion criteria: (1) cognitive performance compared between subjects taking lithium and comparable subjects not taking lithium; comparability was assured by: (2) patients with the same affective disorder diagnoses in euthymic or remitted status or healthy volunteers; (3) groups of similar age and sex; (4) similar intelligence, education, or occupation; (5) similar distribution of other concurrent psychotropic drugs; and (6) cognitive abilities (outcomes) assessed with performance-based measures.

DATA EXTRACTION:
Standardized mean-difference effect size (ES), corrected for small-sample bias (Hedges' g), was computed for cognitive tasks in each study. ES estimates were transformed so that positive values indicate poorer performance by lithium-treated subjects. Infrequently, when means and standard deviations were not provided, ES was estimated from reported values of t, F, or z tests. For analysis, similar neurocognitive tests were grouped a priori based on the cognitive domains they aimed to assess.

DATA SYNTHESIS:
We identified 12 studies involving 276 lithium-treated and 263 similar or the same subjects, lithium-free. Lithium was taken for a mean duration of 3.9 years by affective disorder patients and 2.5 weeks by healthy volunteers, yielding a mean daily trough serum concentration of 0.80 mEq/L. Overall, lithium treatment was associated with small but significant impairment in immediate verbal learning and memory (ES = 0.24; 95% CI, 0.05-0.43) and creativity (ES = 0.33; 95% CI, 0.02-0.64), whereas delayed verbal memory, visual memory, attention, executive function, processing speed, and psychomotor performance were not significantly affected. Selectively, among the 326 affective-disorder patients, in addition to these overall impairments, long-term lithium treatment also was associated with even greater impairment in psychomotor performance (ES = 0.62; 95% CI, 0.27-0.97), with no evidence of cognitive improvements.

CONCLUSIONS:
Lithium treatment appears to have only few and minor negative effects on cognition.

PMID: 19689922

N.B. Whilst the author of this report has concluded that LITHIUM's negative effects on cognition are "few" and "minor" the data in fact indicates otherwise, wherein there is demonstrable "significant impairment in immedate and verbal learning and memory"

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

lithium has potential toxicity issues at high clinical doses 120mg of elemental lithium or more per day.


There has in fact been poisoning at doses much lower than that, which is demonstrable that the stuff is in fact pretty toxic; see the following for example:

J Med Toxicol. 2007 Jun;3(2):61-2.

Lithium toxicity from an Internet dietary supplement.

Pauzé DK, Brooks DE.
Source

Department of Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. pauzedk@upmc.edu
Abstract

INTRODUCTION:

The widespread availability of medications and herbal products on the Internet has increased the potential for poisonings. We are reporting a case of mild, acute lithium toxicity occurring after the intentional misuse of a lithium-containing "dietary supplement" (Find Serenity Now) obtained over the Internet.
CASE REPORT:

An 18-year-old woman presented to our emergency department (ED) after ingesting 18 tablets of Find Serenity Now; each tablet contained, according to the listing, 120 mg of lithium orotate [3.83 mg of elemental lithium per 100 mg of (organic) lithium orotate compared to 18.8 mg of elemental lithium per 100 mg of (inorganic) lithium carbonate]. The patient complained of nausea and reported one episode of emesis. Her examination revealed normal vital signs. The only finding was a mild tremor without rigidity. Almost 90 minutes after the ingestion, her serum lithium level was 0.31 mEq/L, a urine drug screen was negative, and an electrocardiogram (ECG) showed a normal sinus rhythm. The patient received intravenous fluids and an anti-emetic; one hour later, her repeat serum lithium level was 0.40 mEq/L. After 3 hours of observation, nausea and tremor were resolved, and she was subsequently transferred to a psychiatric hospital for further care. Prior human and animal data have shown similar pharmacokinetics and shared clinical effects of these lithium salts.
DISCUSSION:

Over-the-Internet dietary supplements may contain ingredients capable of causing toxicity in overdose. Chronic lithium toxicity from ingestion of this product is also of theoretical concern.

PMID: 18072162

Edited by ScienceGuy, 13 February 2012 - 06:14 PM.


#77 ta5

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Posted 13 February 2012 - 11:41 PM

Great thread. And timely for me.

I'm curious if these will down-regulate GABA receptors too?:

Holy Basil
Passion Flower
California Poppy
Skullcap

Gabapentin
Pregabalin

#78 ScienceGuy

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Posted 14 February 2012 - 08:46 PM

I'm curious if these will down-regulate GABA receptors too?:

Holy Basil
Passion Flower
California Poppy
Skullcap

Gabapentin
Pregabalin


My comments regarding these are as follows:

HOLY BASIL (Ocimum Sanctum) - HOLY BASIL is a potent ANTI-ANDROGENIC; and as such I wouldn't go near it with a 50-foot barge pole, not unless you particularly want to screw up your ENDOCRINE SYSTEM function ;)

PASSION FLOWER (Passiflora Incarnata) - PASSION FLOWER's mechanism of action appears to be that of a GABA REUPTAKE INHIBITOR as opposed to GABA RECEPTOR AGONIST; however, this will still induce DOWN-REGULATION of the GABA RECEPTORS with prolonged usage, and hence I would advise against prolonged usage for the medium or long-term. Therefore, I have added PASSION FLOWER to the 'AVOID' list, and added some relevant STUDIES.

CALIFORNIA POPPY (Eschscholzia Californica) - CALIFORNIA POPPY is indeed a GABA RECEPTOR AGONIST and hence I would advise against prolonged usage for the medium or long-term. I have added this to the 'AVOID' list, and added a relevant STUDY.

SKULLCAP (Scutellaria lateriflora) - SKULLCAP is indeed also a GABA RECEPTOR AGONIST and hence I would advise against prolonged usage for the medium or long-term. I have added this to the 'AVOID' list, and added a relevant STUDY.

GABAPENTIN and PREGABALIN - BOTH of these drugs significantly INHIBIT IMMUNE SYSTEM FUNCTION, which includes REDUCING WHITE BLOOD CELL COUNT, so I would advise against prolonged usage for the medium or long-term for this reason alone :)

#79 ta5

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Posted 15 February 2012 - 01:41 AM

Thanks ScienceGuy.

I still wonder about tiagabine and passion flower. Is there evidence that gaba reuptake inhibitors produce significant tolerance with long term use?

I also wonder about these:

Hops
Chamomile
Lemon Balm

Edited by ta5, 15 February 2012 - 02:33 AM.


#80 noos

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Posted 15 February 2012 - 05:19 PM

I can´t download the attachments in the first post:

[#10171] You do not have permission to view this attachment.

I read the post again and honestly, maybe the suggested products work for common everyday anxiety but I doubt they will have an effect on anxiety disorders.
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#81 ScienceGuy

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Posted 15 February 2012 - 05:49 PM

I read the post again and honestly, maybe the suggested products work for common everyday anxiety but I doubt they will have an effect on anxiety disorders.


Pfahahaha... Seriously?!!! You ARE joking, right? :laugh:

Did you in fact read the whole post, including all the relevant clinical studies? :wacko:

Or are you seriously stating that NONE of the following "will have an effect on anxiety disorders"?!:

1) GARUM ARMORICUM (brands: STABILIUM; ADAPTON)

2) MAGNESIUM

3) BACOPA MONNIERI


4) RHODIOLA ROSEA

5) RELORA (MAGNOLIA OFFICINALIS and PHELLODENDRON AMURENSE)

6) THEANINE

7) LOW DOSE NALTREXONE (LDN)


8) AFOBAZOLE

9) TIANEPTINE

10) ESCITALOPRAM

11) ANIRACETAM / PIRACETAM / NEFIRACETAM

12) PROPRANOLOL

13) CLONIDINE

So which is it? Are you JOKING or are you SERIOUS? :)
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#82 ScienceGuy

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Posted 15 February 2012 - 06:14 PM

Thanks ScienceGuy.

I still wonder about tiagabine and passion flower. Is there evidence that gaba reuptake inhibitors produce significant tolerance with long term use?


YES, there is, specifically through down-regulation of the GABA RECEPTORS :)

However, to get things in perspective please kindly note that PASSION FLOWER is a relative weak GABA REUPTAKE INHIBITOR as compared with TIAGABINE, and hence present much less of a problem in this regard than the TIAGABINE ;)
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#83 noos

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Posted 15 February 2012 - 06:14 PM

Most I can´t obtain. I was thinking in the supplements, sorry if I generalized. 9 (not sure if it will work for panic),10 (obvious, it´s an SSRI),12 (for adrenaline like anxiety, not all) I know and can work, the rest I don´t know, can´t obtain or what I read posted is not enough. Do you know people taking them with success?
2 nice, but expecting to cut a panic attack with a dose of Mg? Who is joking? :)
What are you talking here when you use the word anxiety (stress, social phobia, simple phobias, panic, psychotic anxiety, paranoia)? The study on garum is on stressed students, is that an anxiety disorder clinical test? Will it work for exam phobia? BTW add fish oil, there is a similar study on fish oil helping stressed students:

http://www.ncbi.nlm.nih.gov/pubmed/21784145
The reduction in anxiety symptoms associated with n-3 supplementation provides the first evidence that n-3 may have potential anxiolytic benefits for individuals without an anxiety disorder diagnosis.



#84 ScienceGuy

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Posted 15 February 2012 - 07:45 PM

I also wonder about... Lemon Balm


LEMON BALM (MELISSA OFFICINALIS)

LEMON BALM’s primary mechanism of action in relation to its ANXIOLYTIC effects appears (somewhat uniquely) to be that of a GABA TRANSAMINASE INHIBITOR.

GABA TRANSAMINASE is an enzyme which breaks down GABA within the brain, and hence inhibition of this enzyme induces an INCREASE in GABA LEVELS, which with prolonged usage theoretically will induce a down-regulation of the GABA RECEPTORS.

Therefore, it could be considered that if one wanted to be ‘absolutely safe’, prolonged usage of LEMON BALM for the medium to long-term should be avoided for exactly the same reasons as GABA RECEPTOR AGONISTS and GABA REUPTAKE INHIBITORS; and hence usage should be restricted to short-term usage only and/or CYCLING ON/OFF.

However, to put things into perspective, LEMON BALM’S GABA TRANSAMINASE INHIBITION effects are relatively weak. Furthermore, it is by no means LEMON BALM’s only mechanism of action. As such, LEMON BALM’s physiological effects are somewhat complex.

Consequently, after weighing up all the evidence I have placed LEMON BALM onto the ‘POSSIBLY TO AVOID’ list; and I feel the need to repeat that if one wanted to be ‘absolutely safe’ one can take LEMON BALM completely safely by CYCLING it ON and OFF. :)

Phytother Res. 2009 Aug;23(8):1075-81.

Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity.

Awad R, Muhammad A, Durst T, Trudeau VL, Arnason JT.

Source
Centre for Advanced Research in Environmental Genomics (CAREG), Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

A novel pharmacological mechanism of action for the anxiolytic botanical Melissa officinalis L. (lemon balm) is reported. The methanol extract was identified as a potent in vitro inhibitor of rat brain GABA transaminase (GABA-T), an enzyme target in the therapy of anxiety, epilepsy and related neurological disorders. Bioassay-guided fractionation led to the identification and isolation of rosmarinic acid (RA) and the triterpenoids, ursolic acid (UA) and oleanolic acid (OA) as active principles. Phytochemical characterization of the crude extract determined RA as the major compound responsible for activity (40% inhibition at 100 microg/mL) since it represented approximately 1.5% of the dry mass of the leaves. Synergistic effects may also play a role.
PMID: 19165747
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Canadian Journal of Physiology and Pharmacology, Volume 85, Number 9, September 2007 , pp. 933-942(10)

Effects of traditionally used anxiolytic botanicals on enzymes of the γ-aminobutyric acid (GABA) system

Awad, R.; Levac, D.; Cybulska, P.; Merali, Z.; Trudeau, V.L.; Arnason, J.T.

Source

NRC Research Press.

Abstract

In Canada, the use of botanical natural health products (NHPs) for anxiety disorders is on the rise, and a critical evaluation of their safety and efficacy is required. The purpose of this study was to determine whether commercially available botanicals directly affect the primary brain enzymes responsible for γ-aminobutyric acid (GABA) metabolism. Anxiolytic plants may interact with either glutamic acid decarboxylase (GAD) or GABA transaminase (GABA-T) and ultimately influence brain GABA levels and neurotransmission. Two in vitro rat brain homogenate assays were developed to determine the inhibitory concentrations (IC50) of aqueous and ethanolic plant extracts. Approximately 70% of all extracts that were tested showed little or no inhibitory effect (IC50 values greater than 1mg/mL) and are therefore unlikely to affect GABA metabolism as tested. The aqueous extract of Melissa officinalis (lemon balm) exhibited the greatest inhibition of GABA-T activity (IC50 = 0.35mg/mL). Extracts from Centella asiatica (gotu kola) and Valeriana officinalis (valerian) stimulated GAD activity by over 40% at a dose of 1mg/mL. On the other hand, both Matricaria recutita (German chamomile) and Humulus lupulus (hops) showed significant inhibition of GAD activity (0.11-0.65mg/mL). Several of these species may therefore warrant further pharmacological investigation. The relation between enzyme activity and possible in vivo mode of action is discussed.
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#85 ScienceGuy

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Posted 15 February 2012 - 08:01 PM

Most I can´t obtain. I was thinking in the supplements, sorry if I generalized. 9 (not sure if it will work for panic),10 (obvious, it´s an SSRI),12 (for adrenaline like anxiety, not all) I know and can work, the rest I don´t know, can´t obtain or what I read posted is not enough. Do you know people taking them with success?
2 nice, but expecting to cut a panic attack with a dose of Mg? Who is joking? :)
What are you talking here when you use the word anxiety (stress, social phobia, simple phobias, panic, psychotic anxiety, paranoia)? The study on garum is on stressed students, is that an anxiety disorder clinical test? Will it work for exam phobia? BTW add fish oil, there is a similar study on fish oil helping stressed students:


http://www.ncbi.nlm....pubmed/21784145
The reduction in anxiety symptoms associated with n-3 supplementation provides the first evidence that n-3 may have potential anxiolytic benefits for individuals without an anxiety disorder diagnosis.


OK firstly it is very clear that you haven't bothered to take the time to read the post properly... For example, you state: "2 nice, but expecting to cut a panic attack with a dose of Mg? Who is joking?" when I have clearly stated: "MAGNESIUM is unlikely be a 'magic bullet' regards treating ANXIETY but can most certainly be a highly useful adjunct, through its mechanism of action as an NMDA RECEPTOR ANTAGONIST"

So, with the utmost respect, I will be spending as much time composing this reply as you have yours ;)

In short, you are wrong about a great many things and there is a very good reason why FISH OIL is not on the list (which I will let you work out for yourself) :)

#86 Ampa-omega

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Posted 16 February 2012 - 12:27 AM

scienceguy, i have a question for you, do you know of any good natural mood stabilizers since you do not recommend lithium?

#87 hippocampus

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Posted 16 February 2012 - 11:36 AM

Fish oil is a mood stabilizator for me. :)

#88 ScienceGuy

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Posted 16 February 2012 - 12:40 PM

scienceguy, i have a question for you, do you know of any good natural mood stabilizers since you do not recommend lithium?


Please kindly note that whilst I do not specifically recommend using LITHIUM, I do not as such specifically recommend against using it either; this is why LITHIUM is not on either list; furthermore, my primary reason for mot including it on the positive list is due to its ANTI-NOOTROPIC effects, since COGNITIVE ENHANCEMENT is a primary goal of the majority of individuals within this forum :)

However, that is not to say that for some individuals, who are not concerned about its ANTI-NOOTROPIC effects, should not take LITHIUM to benefit from its MOOD STABILIZATION effects ;)

With regards to what other items I recommend for MOOD STABILIZATION, that would include (but is not limited to) the following (in no particular order) :) :

1) ESCITALOPRAM (at 5mg DOSAGE)

2) GARUM ARMORICUM (brands: STABILIUM; ADAPTON)

3) LOW DOSE NALTREXONE (LDN)

4) PIRACETAM


5) GEROVITAL H3

6) RHODIOLA ROSEA

N.B. Please note that the above list does include both 'natural' and 'synthetic' compounds; however, this is deliberate, since NATURAL does NOT always = SAFE; and as such, I do not personally agree with the philosophy of considering only taking substances that technically are classified as 'natural'; take ASPIRIN versus WHITE WILLOW BARK for example (I can elaborate if you wish) ;)

As such substances should be considered individually with respect to their own merit irrespective of whether they are technically classified as 'natural' or 'synthetic' :)

Edited by ScienceGuy, 16 February 2012 - 12:50 PM.


#89 ScienceGuy

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Posted 16 February 2012 - 12:42 PM

Fish oil is a mood stabilizator for me. :)


However, FISH OIL (EPA / DHA) causes and/or exacerbates DEPRESSION and/or ANXIETY for many individuals... ;)

Edited by ScienceGuy, 16 February 2012 - 12:43 PM.

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#90 bkmk

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Posted 16 February 2012 - 12:59 PM

scienceguy what is rhodiola rosea mechanism of action.is it MAOi? rhodiola rosea ( only salidroside ) stimulates me to much and gives insomnia.




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