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5HT2A, Genetics, and Supplements... Advice?

5ht2a genetics supplements nantenine

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#1 gizmobrain

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Posted 18 September 2016 - 10:46 PM


Currently trying to help a female that struggles with low BP, high anxiety, fatigue, etc. We are combating it from multiple angles, but I'd like to throw this out there. The following is her genetic markers for 5ht2a:
 
 Attached File  5ht2a.PNG   19.18KB   3 downloads
 
Given that she would seem to be predisposed to a high amount of 5ht2a activation, it would seem a good pathway to try to treat.
 
Nantenine is an extract that has been shown to antogonize 5ht2a, but I don't see any products on the market, and it would seem that the plant it is sourced from is most likely toxic by itself.[/size][/font][/color]
 
She currently takes:
Feverfew
Gingko
Myo-Inositol (at night)
 
Also, since 5ht2a activates GSK3, we have also added Zinc.
 
Just looking for thoughts/discussion about this certain pathway and how to optimize it when your genetics aren't optimal.

Edited by zrbarnes, 18 September 2016 - 11:30 PM.

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#2 gizmobrain

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Posted 19 September 2016 - 01:33 AM

Patents like these annoy me that they exist, but are informative:

Selective serotonin 2A/2C receptor inverse agonists as therapeutics for neurodegenerative diseases

Other possible naturally sourced compounds:

Also, it looks like mangosteen has interesting properties:

 

In summary, we found that gamma-mangostin is a 5-HT2A/2C receptor antagonist at the transcriptional level. Although many additional pharmacological studies are still required, information from this study provides the opportunity to develop gamma-mangostin from Garcinia mangostana, a plant that is abundantly available in Thailand, as a novel antidepressant and/or drug used to treat neuropsychiatric disorders. Additionally, we found that gamma-mangostin up-regulated M4, H1 and BK2 receptor expression, suggesting the antagonistic effects. These findings support the traditional uses of Garcinia mangostana.

 



Mangosteen as Schizophrenia treatment

 

 


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#3 Flex

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Posted 30 September 2016 - 02:18 PM

I believe to read that cyproheptadine behaves like an antipsychotic at Serotonergic sites. so it supposedly downregulates them.

It was a hard find but look out for those infos on e.g. google scholar, if I dont call You back.



#4 jack black

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Posted 30 September 2016 - 02:52 PM

zrbarnes

thanks for posting the SNPs. there are a few females in my family with anxiety. i'll compare the SNPs.

how is your female doing with the stack?

i experimented with inositol and first time i took it (5g) was like instant SSRI effect. now it doesn't seem to work anymore.



#5 PeaceAndProsperity

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Posted 30 September 2016 - 04:07 PM

I believe to read that cyproheptadine behaves like an antipsychotic at Serotonergic sites. so it supposedly downregulates them.

It was a hard find but look out for those infos on e.g. google scholar, if I dont call You back.

Looks like a very interesting compound. I would actually like to try it. I wonder if it's prescription only. but holy Christ the amount of possible adverse effects.


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#6 Flex

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Posted 30 September 2016 - 06:35 PM

Well yes. the side effects for me were the typical cholinergic ones + a serotonine blocker effect like from mitrazapine and I felt quite robotic and dysphoric.

good news, half life is 8h and You need a relative low dose to occupy a high percentage of the 5-ht2a (80% iirc) but I forgot the dose. I guess it was 10mg. I dont know.

It´s perscription in Germany but not in the UK. and dont take it long-term. theres were some news stating that the usage of anticholinergics over a few months can increase the risk of late-life dementia (via oxidative damage iirc)

 

As usual: Talk to Your Doc. I dont want to be responsible for anything.

 

Edit: I guess You dont need to use it for a long time in order to achieve a down regulation (given my information is right) but better ask somebodyelse about it.


Edited by Flex, 30 September 2016 - 06:39 PM.


#7 jack black

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Posted 30 September 2016 - 06:36 PM

OK, i compared the OP's SNPs and the rs6311/rs6313 status matched one person in my family. the other SNPs didn't. it just happens that the person in question has the most severe social and anxiety issues and is recovering from a major depression (multiple suicide attempts, etc).

before jumping to conclusion, that particular rs6311/rs6313 status is quite common (~20%), so it's not likely the only thing. the research i found on rs6311/rs6313 is not very conclusive.

 

this is the best info i could find on 5HT2AR: https://selfhacked.c...blems-and-cirs/



#8 gamesguru

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Posted 30 September 2016 - 08:50 PM

What are her symptoms?  Someone said anxiety..?  How much ginkgo and feverfew?  Add magnesium[1], perhaps low dose lithium[2] and some of these (the blue guys at least).

Suppressive effect of mitragynine {Kratom, see other study on NTs and anxiety} on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice.
Matsumoto K1, Mizowaki M, Takayama H, Sakai S, Aimi N, Watanabe H. (1997)

We investigated the effects of mitragynine, a major alkaloid isolated from the leaves of Mitragyna speciosa Korth (Rubiaceae), on the 5-HT2A receptor-mediated head-twitch response in mice. Intraperitoneal injection of mitragynine (5-30 mg/kg), as well as intraperitoneal injection of 5-HT2A receptor antagonist ritanserin, inhibited the 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT: 16 mg/kg, IP)-induced head-twitch response in a dose-dependent manner. In contrast, mitragynine affected neither head-weaving caused by 5-MeO-DMT, nor drug-free spontaneous motor activity. Pretreatment of mice with reserpine (5 mg/kg, IP), p-chlorophenylalanine (p-CPA, 300 mg/kg x 3 times, IP), or 6-hydroxydopamine (6-OHDA, 50 micrograms/mouse, ICV) plus nomifensine (5 mg/kg, IP) did not change the suppressant effect of mitragynine on the head-twitch response caused by 5-MeO-DMT. On the other hand, the alpha 2-adrenoceptor antagonists yohimbine (0.5 mg/kg, IP), and idazoxan (0.2 mg/kg, IP), significantly attenuated the suppressant effect of mitragynine. Lesion of central noradrenergic systems by 6-OHDA plus nomifensine did not alter the effect of idazoxan (0.2 mg/kg) on mitragynine-induced suppression of the head-twitch response. These results indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5-HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated head-twitch response by mitragynine.

Identification of antidepressant-like ingredients in ginseng root (Panax ginseng C.A. Meyer) using a menopausal depressive-like state in female mice: participation of 5-HT2A receptors.
Yamada N1, Araki H, Yoshimura H. (2011)

RATIONALE: After reports of adverse effects with hormone replacement therapy, such as reproductive and breast cancer and coronary heart disease, much attention has been given to the development of new remedies to alleviate menopausal depression in women, but methods for their preclinical evaluation have not been clarified. We previously developed a procedure to predict the drug effect on the menopausal depressive-like state in female mice.
OBJECTIVES: We attempted to identify psychoactive components from ginseng root, one of the earliest known materials for menopausal disorder, and to clarify the possible mechanism involved.
METHODS: As an index of a depressive-like state, we used the prolongation of immobility time induced by an ovariectomy during the forced swimming test. Chronic treatment with the candidate substance began the day after ovariectomy and continued for 14 days. To examine whether the 5-HT(2A) receptor antagonist ritanserin antagonized the antidepressant-like effect of ginsenoside Rb(1), ritanserin was given as pretreatment 15 min before the daily administration of ginsenoside Rb(1) and the antagonistic effect was compared with ginsenoside Rb(1) alone.
RESULTS: Ginsenoside Rb(1) and compound K were active ingredients that dose-dependently prevented the prolongation of immobility time induced by ovariectomy. Co-administration of ritanserin, a 5-HT(2A)-receptor antagonist, antagonized the effect of ginsenoside Rb(1).
CONCLUSIONS: We suggest that ginsenoside Rb(1) and its metabolite, compound K, are antidepressant-like components of the ginseng root, and that 5-HT(2A) receptors may play an important role in mediating the antidepressant-like effect of ginsenoside Rb(1).

 

Antidepressant-like activity of dehydrozingerone: involvement of the serotonergic and noradrenergic systems.
Martinez DM1, Barcellos A2, Casaril AM3, Savegnago L4, Lernardão EJ2. (2014)

Dehydrozingerone (DHZ) is a phenolic compound isolated from ginger rhizomes (Zingiber officinale). It is known for its diverse spectrum of biological activities as an antioxidant, anti-inflammatory and antitumor compound. The present study was designed to assess the antidepressant effect of DHZ and the involvement of the monoaminergic system and to evaluate its in vitro antioxidant activity in the hippocampus, cortex and cerebellum of mice. For this study, the tail suspension test (TST), forced swim test (FST) and yohimbine lethality test were performed. DHZ administered orally 30min prior to testing reduced the immobility time in the TST (1-40mg/kg) and the FST (10-40mg/kg), with no change in locomotor activity in the open field test. The antidepressant-like effect of DHZ (1mg/kg) was prevented by ketanserin (1mg/kg, i.p.; a 5-HT2A/2C receptor antagonist), ondansetron (1mg/kg, i.p.; a 5-HT3 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist) and yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist) pretreatments. Furthermore, DHZ administered at doses of 10 and 20mg/kg increased the lethality of yohimbine (35mg/kg, i.p.). DHZ had antioxidant activity on in vitro lipid peroxidation induced by sodium nitroprusside in all brain regions tested. The results revealed that DHZ has a potent antidepressant effect, which seems to involve the serotonergic and noradrenergic systems.

 

Antidiabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats

Sanjay P. Akhani, Santosh L. Vishwakarma and Ramesh K. Goyal (2014)

 

Z. officinale per-se did not produce any significant alteration in glucose and insulin levels; however, it inhibited 5-HT-induced hyperglycaemia and hypoinsulinaemia.  Lumb (1993) reported the involvement of 5-HT3 receptors in the anti-emetic action of Z. officinale.  Earlier studies from our laboratory have reported that 5-HT-inducedhyperglycaemia was inhibited by the 5-HT2A antagonists arpogrelate and the 5-HT3 antagonist ondansetron(Goyal etal 2003).  The inhibition of 5-HT-induced hyperglycaemia by Z.officinale suggests the presence of a 5-HT2A or 5-HT3 receptor antagonist in Z.officinale.  Chronic treatment with arpogrelate and ondansetron is reported to decrease blood glucose and to have beneficial effects on lipid profile in STZ-diabetic rats (Goyal etal 2003).

The flavonoid quercetin reverses pulmonary hypertension in rats.
Morales-Cano D1, Menendez C2, Moreno E1, Moral-Sanz J1, Barreira B1 (2014)

Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os) or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH.

Stimulation of spinal 5-HT(2A/2C) receptors potentiates the capsaicin-induced in vivo release of substance P-like immunoreactivity in the rat dorsal horn.
Kjørsvik Bertelsen A1, Warsame Afrah A, Gustafsson H, Tjølsen A, Hole K, Stiller CO. (2003)

Stimulation of spinal serotonin (5-HT)(2A/2C) receptors has previously been reported to lead to either a pro-nociceptive or an anti-nociceptive response. Behavioral data have indicated that the pro-nociceptive effect is related to the release of substance P (SP). The aim of this in vivo microdialysis study was to investigate if stimulation of spinal 5-HT(2A/2C) receptors by the selective agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) induces spontaneous or capsaicin-evoked increase in the release of SP-like immunoreactivity (SP-LI) in the rat dorsal horn. A dose of capsaicin (25 microM in the perfusion medium administered for 30 min), which did not lead to a significant release of SP-LI on its own, induced a significant increase of greater than 4-fold of the SP-LI level following spinal application of 50 nmol DOI. Higher (500 nmol) or lower (5 nmol) doses of DOI failed to induce a similar effect. In rats with a peripheral inflammation, induced by carrageenan, capsaicin (25 microM) induced a non-significant increase of SP-LI. A significant 8-fold increase of the SP-LI level was detected following administration of 50 nmol DOI in combination with capsaicin. The effect of DOI, which was completely prevented by co-administration of the 5-HT(2A) receptor antagonist ketanserin in control animals without peripheral inflammation, was only partly blocked in animals with carrageenan induced peripheral inflammation. In conclusion, stimulation of 5-HT(2A/2C) receptors facilitates the capsaicin-evoked release of SP-LI in the dorsal horn in both animals with and without carrageenan-induced unilateral inflammation. The observation that the highest dose of DOI failed to induce SP-LI release may be due to an inhibitory postsynaptic action at this dose.

Psychopharmacological profile of the alkaloid psychollatine as a 5HT2A/C serotonin modulator.
Both FL1, Meneghini L, Kerber VA   , Henriques AT, Elisabetsky E. (2005)

Behavioral effects of psychollatine, a new glycoside indole monoterpene alkaloid isolated from Psychotria umbellata, was investigated in models of anxiety, depression, memory, tremor, and sedation related to 5-HT and/or GABA neurotransmission. The GABA antagonist picrotoxin and the 5-HT2 antagonist ritanserin were used to examine the role of GABA and 5-HT2 receptors in psychollatine-induced effects. In the light/dark and hole-board models of anxiety, diazepam (0.75 mg/kg) and psychollatine (7.5 and 15 mg/kg) showed anxiolytic-like effect at doses that do not increase sleeping time nor alter spontaneous locomotor activity. The anxiolytic effect of psychollatine was prevented by prior administration of ritanserin, but not of picrotoxin, indicating that 5-HT2 but not GABA receptors are implicated. In the forced swimming model of depression, psychollatine (3 and 7.5 mg/kg) effects were comparable to the antidepressants imipramine (15 mg/kg) and fluoxetine (20 mg/kg). Psychollatine suppressed oxotremorine-induced tremors in all doses. In the step-down learning paradigm, diazepam (0.85 mg/kg), MK-801 (0.15 mg/kg), and psychollatine 100 mg/kg impaired the acquisition of learning and memory consolidation, without interfering with retrieval. It is concluded that the effects of psychollatine at the central nervous system involve serotonergic 5HT2(A/C) receptors.


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#9 kurdishfella

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Posted 24 January 2018 - 12:09 PM

mianserin and mirtazapine block 5ht2

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#10 DeGenisis

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Posted 21 February 2018 - 05:11 PM


Very low dose risperidone (0.25 mg) should block 5-HT2a and not much else.
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