Awesome compilation. I see a lot of info I had already heard/read of.. A few I had not.. And some new (to me) data on others I found rather fascinating, in particular regarding the up-regulation of GABA receptors with Bacopa & the up-regulation of 5-HT receptors with Inositol. . I had known for some time Inositol was serotonergic, but was unsure via what mechanism exactly. This makes sense as it does not appear to be an agonist nor re-uptake inhibitor.
There's another novel pharmaceutical antidepressant & anxiolytic you may want to add to your list..
Mirtazapine.
I've found Mirtazapine to be one of the most effective prescription anxiolytics thus far, benzodiazapines aside. The addition of the SNRI Venlafaxine (Effexor) has proven even more useful, or vice versa as I began taking Effexor prior, after trying three SSRI's with minimal benefit/efficacy. While the SNRI was moderately more effective, as an anxiolytic, as well as coping with chronic fatigue due to its noradranergic effects. Mirtazapine & Venlafaxine have an interesting synergy, to say the least.. I've noticed the two tend to counteract the side-effects of one another while maximizing efficacy.
Mirtazapine can increase CNS levels of serotonin & epinephrine to a modest extent via pre-synaptic alpha2-adrenergic receptor antagonism (that receptor normally inhibiting the release of 5-HT & NOR, hence causing an 'indirect agonist' or rather modest disinhibition of noradranergic & serotonergic transmission, respectively). This was at first, thought to be responsible for its antidepressant & anxiolytic effects. It is now known that in addition to the aforementioned mechanism of action, it functions as an antagonist/inverse agonist at various 5-HT receptors, notably 5-HT2A, 5-HT2B, 5-HT2C & 5-HT3, all of which can produce a mild to moderate anxiolytic effect when blocked.. Mirtazapine is also a fairly potent H1 receptor agonist, causing sedation, so it best to dose at night. The drowsiness likely contributes to anxiolytic effects. I have personally noticed an often profound anxiolytic (both for panic & generalized in particular) effect, as well as a fairly potent anti-depressant/mildly mood elevating effect upon dosing, even with only 1 dose and having not taken it prior.. It does however, cause one to have an often voracious appetite ~1 hour after dosing, and hence, cause weight gain. I would not recommend this for anyone who is overweight or hypoglycemic. Venlafaxine, on the other hand, tends to cause a sharp decrease in appetite. I've found the Mirtazapine's increase in appetite slightly stronger than Venlafaxine's decrease, either of which being much more potent if taken alone however.
You may also want to look into L-Lysine. It has another novel mechanism of action: a
5-HT4 antagonist, in particular in the
Amygdala. It has also been found to interact with GABA receptors, possibly via up-regulation:
"Fortification of grains with lysine was shown to reduce markers of anxiety, including Cortisol levels, and also led to potentiation of benzodiazepine receptors (common targets of anxiolytic drugs such as Xanax and Ativan
)."Source:
Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria
→ source (external link)
Additional resources:
L-lysine And AmygdalaL-Lysine and AnxietyL-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptorL-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in ratsThanks for the thread
I stopped taking benzos 1 week ago and the last thing I want to do is to mess with my GABA receptors.
I've just bought a bottle of Relora and another of L-Theanine.
(Now Foods and Source Naturals)
As mentioned above, Bacopa has the ability to up-regulate GABA receptors, mitigating memory-related side effects of GABAergics, benzodiazapines to be speific..
Adding Bacopa to your stack may prove beneficial, perhaps extremely beneficial, due to this novel mechanism of action. It should not cause any additional down-regulation as most GABAergic, and will, in fact, have the opposite effect. As an anxiolytic, it may prove useful for coping with benzodiazepine withdrawal, or when tapering off one gradually, or in countering anxiety in general.
I recently picked up a bottle of Bacopa to try for myself.. I've found a mild-to-modest anxiolytic effect and rather mild effect on memory and cognition (so far). This is after about a week of administration, gradually increasing my dosage for this initial period. I began with 500mg twice a day, now up about 1.5g per day divided into three doses.. I may keep this as my target dosage and monitor any futher progress or lack thereof from here. If I don't find any additional benefit after a week or two, I may increase the dosage by another 1/3q or 500mg to 2g daily and see what happens from there..
You can read more about Bacopa starting with
OP's analysis, as well as here:
http://examine.com/s...acopa Monnieri/http://altmedicine.a...fits_bacopa.htmhttp://www.bacopin.c...lyticeffect.htmhttp://www.raysahelian.com/bacopa.html
Edited by quantumcipher, 02 April 2013 - 12:26 AM.