70 replies to this topic

[tronatula2]

Sorry for my English.

 

I've spent 1 year to find substances that can enhance my motivation. I cannot buy Amphetamine in my country.

 

I have very low motivation, I usually skip school, do not have ambition. I am a procrastinator.

 

I am confident, I do not have depression.

 

Exercise does not help, I exercise everyday.

 

I am a Piracetam responder (I take 800mg-800mg-400mg everyday).

 

I daydream a lot (especially when riding motorbike).

 

I have good short-term memory (scored 13~15 on Digit span), logical thinking.

 

I react badly to cholinergic substance (fish oil, CDP Choline, DMAE, Nicotine,...), or even weak cholinergic stuff like deer velvet antler (anti-acetylcholinesterase), KSM-66 (Withanolide A appears to directly influence acetylcholinesterase in an inhibitory manner),... They make me duller.

 

Almost every substance I research has cholinergic properties (vitamin D, Forskolin,...)

 

I react badly to L-theanine (makes me sleepy, duller).

 

Almost all the nootropics in the 2016 NOOTROPICS SURVEY do not help (Modafinil, Semax, Pramiracetam, Phenylpiracetam,...). One day I took 200mg modalert and 5mg selegiline, and all they did is keeping me awake to think about how to beat laziness. They did not motivate me an inch.

I had thought modafinil and selegiline would enhance my motivation somehow but I was so disappointed. After thay day, I hate myself a lot, even selegiline and modafinil could not help me.

 

At this time, after spending lots of money, time and effort, I'm so desperate, I think I have to accept my fate.

 

 

[jack black]

Motivation is a tough one. do a search and see yourself.
Any addictions?
Internet, gaming, social media, movies, sex, porn, drugs, alcohol, nicotine, etc?
I'm surprised you find DMAE cholinergic. I though it was anti-cholinergic (based on theory and my experience)?
Have you tried low protein diet and other anti-cholinergic substances?

Edited by jack black, 16 September 2016 - 01:11 PM.

[tronatula2]

Motivation is a tough one. do a search and see yourself.
Any addictions?
Internet, gaming, social media, movies, sex, porn, drugs, alcohol, nicotine, etc?
I'm surprised you find DMAE cholinergic. I though it was anti-cholinergic (based on theory and my experience)?
Have you tried low protein diet and other anti-cholinergic substances?

DMAE can also increase levels of the compound involved with memory, acetylcholine (https://examine.com/supplements/dmae/)

 

No addiction, I have not touched my PS4 for months. 

 

Masturbating like 2 times a week. I have high sex drive. 

[psychejunkie]

looks like low Serotonin; take 5-HTP every morning and see what happens.

 

but just to be sure, Do you get headaches frequently or not? and what level of pain tolerance do you rate yourself?

Edited by psychejunkie, 17 September 2016 - 05:12 AM.

[thedevinroy]

You say you are not depressed, but you may be able to treat standalone apathy with an SNRI or even an NDRI like bupropion. Motivation has a lot to do with the adrenal gland and getting that norepinephrine up is important. The question is whether you'll have to couple it with a CNS dopaminergic or CNS serotonergic (avoiding peripheral types like precursors) keeping it selective to the areas of the brain that are important.

I know that's a loaded response, but you have a lot of question marks about yourself that I can't possibly answer so specifically. I can treat you like I would an indecisive girl and just list off a thousand options until you don't shoot one down...

But... I think you'll be more efficient if you just do it yourself.

Can you list off a couple dozen drugs you'd like to try? Add to that list Zembrin+caffeine, an NRI, an SNRI, and an NDRI.

Edited by devinthayer, 17 September 2016 - 05:42 PM.

[thedevinroy]

I think I remember seeing a thread on this a while back... but this may be of relevance to your situation:

https://examine.com/...ts/hederagenin/

[tronatula2]

looks like low Serotonin; take 5-HTP every morning and see what happens.

 

but just to be sure, Do you get headaches frequently or not? and what level of pain tolerance do you rate yourself?

I don't think I have low Serotonin, I'm confident and optimistic. According to "The mood cure" quiz, I only have low dopamine.

 

You say you are not depressed, but you may be able to treat standalone apathy with an SNRI or even an NDRI like bupropion. Motivation has a lot to do with the adrenal gland and getting that norepinephrine up is important. The question is whether you'll have to couple it with a CNS dopaminergic or CNS serotonergic (avoiding peripheral types like precursors) keeping it selective to the areas of the brain that are important.

I know that's a loaded response, but you have a lot of question marks about yourself that I can't possibly answer so specifically. I can treat you like I would an indecisive girl and just list off a thousand options until you don't shoot one down...

But... I think you'll be more efficient if you just do it yourself.

Can you list off a couple dozen drugs you'd like to try? Add to that list Zembrin+caffeine, an NRI, an SNRI, and an NDRI.

 

I did try Bupropion 2 times, the first time I took 150mg Bupropion + 1.5g tyrosine + piracetam, and I felt lethargy, very sleepy, horrible. I think it was because of the tyrosine the next day I took only bupropion and piracetam and did not notice noticeable effects. I think I'll try it again.

 

Which substance would you recommend for me? I've tried Selegiline, Tianeptine (Stablon), Sulbutiamine, Phenibut yet they do not help.

 

P/s: I also feel uncomfortable when drink coffee, and the crash afterward makes me sleepy, tired.

Edited by tronatula2, 17 September 2016 - 06:53 PM.

[jack black]

DMAE can also increase levels of the compound involved with memory, acetylcholine (https://examine.com/supplements/dmae/)

 

 

 

weird, i got this:

Page Not Found

 

but, according to https://examine.com/supplements/DMAE/

DMAE blocks choline transporter, so it could be anti-ACh in some circumstances. I certainly get that anti-ACh effect and get stimulation and lifting of emotions, unlike things increasing ACh.

[gamesguru]

Euthymic amotivation and motivational anhedonia are almost always dopaminergic in origin.  Not sure where devin is getting this bit about norepinephrine, I'm afraid he's mistaken.. that will just increase anxiety symptoms!!

 

I would recommend copious amounts of japanese tea, red ginseng, and ginkgo.  Ginseng has inhibitory properties on dopamine beta-hydroxylase and stimulatory properties on tyrosine hydroxylase, so it should result in a very favorable balance of DA:NE

"In the last decade and a half, animal models have found that the neurotransmitter dopamine, long known to be involved in reward processing, is involved in craving or motivation, but not necessarily enjoyment," Treadway said. "To date, research into reward processing in individuals with anhedonia has focused on enjoyment of rewards, rather than assessing the drive to work for them. We think this task is one of the first to do that."
Read more at: http://phys.org/news...ressed.html#jCp

 

also check out Relationship between anticipatory, consummatory anhedonia and disorganization in schizotypy and Attention-deficit-hyperactivity disorder and reward deficiency syndrome

 

Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment.
Fehske CJ1, Leuner K, Müller WE. (2009)

In order to explain cognition-enhancing effects of standardized Ginkgo biloba extract (EGb761), an increase of central monoaminergic neurotransmission has been suggested, but the underlying mechanisms have not yet been elucidated. Here, we confirm that the norepinephrine (NET), the serotonin (SERT), the dopamine (DAT) uptake transporters and MAO activity are inhibited by EGb761 in vitro, although rather high concentrations are required for inhibition of MAO-A and MAO-B activity. However, after 14 days of daily oral treatment with 100mg/kg EGb761 only NE uptake is significantly decreased in NMRI mice, while 5-HT uptake and MAO activity are not affected. As synaptic dopamine clearance in the frontal cortex is mediated by NET, not DAT, these findings may give an explanation for the enhancement of dopaminergic neurotransmission by EGb761 seen in animal models, presumably linked to its positive effects on cognition and attention.

Effect of ginseng saponins on enhanced dopaminergic transmission and locomotor hyperactivity induced by nicotine.
Kim SE1, Shim I, Chung JK, Lee MC. (2006)

Several studies have shown that behavioral hyperactivity induced by psychomotor stimulants is prevented by ginseng saponins. In an attempt to investigate whether the effect of ginseng saponins is through their inhibitory action on the enhanced dopaminergic transmission by psychomotor stimulants, we examined the effects of ginseng total saponin (GTS) presynaptically on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using in vivo microdialysis technique and postsynaptically on the in vitro and in vivo binding of [3H]raclopride to DA D2 receptors. Also, we examined the effects of GTS on nicotine-induced locomotor hyperactivity and on nicotine-induced Fos protein expression in the nucleus accumbens and striatum. Systemic pretreatment with GTS (100 and 400 mg/kg, intraperitoneally (i.p.)) resulted in a dose-dependent inhibition of locomotor hyperactivity induced by nicotine. GTS decreased nicotine-induced DA release in the striatum in a dose-dependent manner. However, GTS had no effects on resting levels of locomotor activity and extracellular DA in the striatum. GTS inhibited the in vitro binding of [3H]raclopride to rat striatal membranes with an IC50 of 5.14+/-1.09 microM. High doses of GTS (400 and 800 mg/kg, i.p.) resulted in decreases in the in vivo binding of [3H]raclopride in the striatum. GTS decreased nicotine-induced Fos protein expression in the nucleus accumbens and striatum, reflecting the inhibition by GTS of nicotine-induced enhancement of dopaminergic transmission. The results of the present study suggest that GTS acts not only on dopaminergic neurons directly or indirectly to prevent nicotine-induced DA release but also postsynaptically by binding to DA D2 receptors. This may explain the blocking effect of GTS on behavioral activation induced by nicotine and conceivably by other psychostimulants. Our data raise the possibility that GTS, by attenuating nicotine-induced enhancement of dopaminergic transmission, may prove to be a useful therapeutic agent for nicotine addiction and warrant further investigation on its effect on nicotine's rewarding property.

(-)-Epigallocatechin gallate regulates dopamine transporter internalization via protein kinase C-dependent pathway.
Li R1, Peng N, Li XP, Le WD. (2006)

Dopamine transporter (DAT) provides not only an integral component of dopaminergic neurotransmission but also a molecular gateway for the accumulation of some neurotoxins such as 1-methyl-4-phenylpyridinium (MPP(+)), a metabolite of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Previous study reported that the neuroprotective effects of green tea polyphenols against MPP(+)-induced neurotoxicity were related to its inhibitory effect on MPP(+) uptake via DAT in dopaminergic cells. To extend the study, we investigated (-)-epigallocatechin gallate (EGCG), a monomer of green tea polyphenols, on DAT internalization in DAT-overexpressed PC12 cells. We found that EGCG (1-100 microM) can induce a dose-dependent inhibition of dopamine uptake in DAT-PC12 cells. In parallel, treatment of EGCG decreased membrane-bound DAT by 15% to 60%. Furthermore, protein kinase C (PKC) inhibitor GF109203X at 2 microM can markedly diminish the inhibitory effects of EGCG on dopamine uptake and reverse the EGCG-induced internalization of DAT. In addition, semiquantitative RT-PCR analysis indicated that EGCG did not affect DAT mRNA expression in the PC12 cells. These data suggest that EGCG exerts its inhibitory effect on DAT by modulating DAT internalization, in which PKC activation may be involved.

Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies.
Chen D1, Wang CY, Lambert JD, Ai N, Welsh WJ, Yang CS. (2005)

(-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenol present in green tea. We previously demonstrated that EGCG was both a substrate and potent inhibitor of human liver cytosolic catechol-O-methyltransferease (COMT). We now report the structure-activity relationship for the inhibition of COMT-catalyzed O-methylation of catecholestrogens in human liver cytosol by tea catechins and some of their metabolites. The most potent inhibitors were catechins with a galloyl-type D-ring, including EGCG (IC(50)=0.07 microM), 4''-O-methyl-EGCG (IC(50)=0.10 microM), 4',4''-di-O-methyl-EGCG (4',4''-DiMeEGCG) (IC(50)=0.15 microM), and (-)-epicatechin-3-gallate (ECG) (IC(50)=0.20 microM). Catechins without the D-ring showed two to three orders of magnitude less inhibitory potency. Enzyme kinetic analyses revealed that EGCG behaved as a mixed inhibitor, whereas 4',4''-di-O-methyl-EGCG exhibited competitive kinetics for the S-adenosylmethionine (SAM), and noncompetitive kinetics for the catechol binding site. These compounds may represent a new type of COMT inhibitor. In silico molecular-modeling studies using a homology model of human COMT were conducted to aid in the understanding the catalytic and inhibitory mechanisms. Either D-ring or B-ring of EGCG could be accommodated to the substrate binding pocket of human COMT. However, the close proximity (2.6A) of 4''-OH to the critical residue Lys144, the higher acidity of the hydroxyl groups of the D-ring, and the hydrophobic interactions between the D-ring and residues in the binding pocket greatly facilitated the interaction of the D-ring with the enzyme, and resulted in increased inhibitory potency. These results provide mechanistic insight into the inhibition of COMT by commonly consumed tea catechins.

Caffeine Induces Dopamine and Glutamate Release in the Shell of the Nucleus Accumbens
Marcello Solinas1, Sergi Ferré1, Zhi-Bing You2, Marzena Karcz-Kubicha1, Patrizia Popoli3, and Steven R. Goldberg1 (2002)

An increase in the extracellular concentration of dopamine in the nucleus accumbens (NAc) is believed to be one of the main mechanisms involved in the rewarding and motor-activating properties of psychostimulants such as amphetamines and cocaine. Using in vivo microdialysis in freely moving rats, we demonstrate that systemic administration of behaviorally relevant doses of caffeine can preferentially increase extracellular levels of dopamine and glutamate in the shell of the NAc. These effects could be reproduced by the administration of a selective adenosine A1 receptor antagonist but not by a selective adenosine A2A receptor antagonist. This suggests that caffeine, because of its ability to block adenosine A1 receptors, shares neurochemical properties with other psychostimulants, which could contribute to the widespread consumption of caffeine-containing beverages.

Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats.
Yokogoshi H1, Kobayashi M, Mochizuki M, Terashima T. (1998)

Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (+/-)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.

[tronatula2]

 

DMAE can also increase levels of the compound involved with memory, acetylcholine (https://examine.com/supplements/dmae/)

 

 

 

weird, i got this:

Page Not Found

 

but, according to https://examine.com/supplements/DMAE/

DMAE blocks choline transporter, so it could be anti-ACh in some circumstances. I certainly get that anti-ACh effect and get stimulation and lifting of emotions, unlike things increasing ACh.

 

 

DMAE is obivously cholinergic, from examine: 

 

Things to Note

Via increasing acetylcholine levels, DMAE is slightly stimulatory.

 

 

 

Euthymic amotivation and motivational anhedonia are almost always dopaminergic in origin.  Not sure where devin is getting this bit about norepinephrine, I'm afraid he's mistaken.. that will just increase anxiety symptoms!!

 

I would recommend copious amounts of japanese tea, red ginseng, and ginkgo.  Ginseng has inhibitory properties on dopamine beta-hydroxylase and stimulatory properties on tyrosine hydroxylase, so it should result in a very favorable balance of DA:NE

"In the last decade and a half, animal models have found that the neurotransmitter dopamine, long known to be involved in reward processing, is involved in craving or motivation, but not necessarily enjoyment," Treadway said. "To date, research into reward processing in individuals with anhedonia has focused on enjoyment of rewards, rather than assessing the drive to work for them. We think this task is one of the first to do that."
Read more at: http://phys.org/news...ressed.html#jCp

 

also check out Relationship between anticipatory, consummatory anhedonia and disorganization in schizotypy and Attention-deficit-hyperactivity disorder and reward deficiency syndrome

 

Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment.
Fehske CJ1, Leuner K, Müller WE. (2009)

In order to explain cognition-enhancing effects of standardized Ginkgo biloba extract (EGb761), an increase of central monoaminergic neurotransmission has been suggested, but the underlying mechanisms have not yet been elucidated. Here, we confirm that the norepinephrine (NET), the serotonin (SERT), the dopamine (DAT) uptake transporters and MAO activity are inhibited by EGb761 in vitro, although rather high concentrations are required for inhibition of MAO-A and MAO-B activity. However, after 14 days of daily oral treatment with 100mg/kg EGb761 only NE uptake is significantly decreased in NMRI mice, while 5-HT uptake and MAO activity are not affected. As synaptic dopamine clearance in the frontal cortex is mediated by NET, not DAT, these findings may give an explanation for the enhancement of dopaminergic neurotransmission by EGb761 seen in animal models, presumably linked to its positive effects on cognition and attention.

Effect of ginseng saponins on enhanced dopaminergic transmission and locomotor hyperactivity induced by nicotine.
Kim SE1, Shim I, Chung JK, Lee MC. (2006)

Several studies have shown that behavioral hyperactivity induced by psychomotor stimulants is prevented by ginseng saponins. In an attempt to investigate whether the effect of ginseng saponins is through their inhibitory action on the enhanced dopaminergic transmission by psychomotor stimulants, we examined the effects of ginseng total saponin (GTS) presynaptically on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using in vivo microdialysis technique and postsynaptically on the in vitro and in vivo binding of [3H]raclopride to DA D2 receptors. Also, we examined the effects of GTS on nicotine-induced locomotor hyperactivity and on nicotine-induced Fos protein expression in the nucleus accumbens and striatum. Systemic pretreatment with GTS (100 and 400 mg/kg, intraperitoneally (i.p.)) resulted in a dose-dependent inhibition of locomotor hyperactivity induced by nicotine. GTS decreased nicotine-induced DA release in the striatum in a dose-dependent manner. However, GTS had no effects on resting levels of locomotor activity and extracellular DA in the striatum. GTS inhibited the in vitro binding of [3H]raclopride to rat striatal membranes with an IC50 of 5.14+/-1.09 microM. High doses of GTS (400 and 800 mg/kg, i.p.) resulted in decreases in the in vivo binding of [3H]raclopride in the striatum. GTS decreased nicotine-induced Fos protein expression in the nucleus accumbens and striatum, reflecting the inhibition by GTS of nicotine-induced enhancement of dopaminergic transmission. The results of the present study suggest that GTS acts not only on dopaminergic neurons directly or indirectly to prevent nicotine-induced DA release but also postsynaptically by binding to DA D2 receptors. This may explain the blocking effect of GTS on behavioral activation induced by nicotine and conceivably by other psychostimulants. Our data raise the possibility that GTS, by attenuating nicotine-induced enhancement of dopaminergic transmission, may prove to be a useful therapeutic agent for nicotine addiction and warrant further investigation on its effect on nicotine's rewarding property.

(-)-Epigallocatechin gallate regulates dopamine transporter internalization via protein kinase C-dependent pathway.
Li R1, Peng N, Li XP, Le WD. (2006)

Dopamine transporter (DAT) provides not only an integral component of dopaminergic neurotransmission but also a molecular gateway for the accumulation of some neurotoxins such as 1-methyl-4-phenylpyridinium (MPP(+)), a metabolite of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Previous study reported that the neuroprotective effects of green tea polyphenols against MPP(+)-induced neurotoxicity were related to its inhibitory effect on MPP(+) uptake via DAT in dopaminergic cells. To extend the study, we investigated (-)-epigallocatechin gallate (EGCG), a monomer of green tea polyphenols, on DAT internalization in DAT-overexpressed PC12 cells. We found that EGCG (1-100 microM) can induce a dose-dependent inhibition of dopamine uptake in DAT-PC12 cells. In parallel, treatment of EGCG decreased membrane-bound DAT by 15% to 60%. Furthermore, protein kinase C (PKC) inhibitor GF109203X at 2 microM can markedly diminish the inhibitory effects of EGCG on dopamine uptake and reverse the EGCG-induced internalization of DAT. In addition, semiquantitative RT-PCR analysis indicated that EGCG did not affect DAT mRNA expression in the PC12 cells. These data suggest that EGCG exerts its inhibitory effect on DAT by modulating DAT internalization, in which PKC activation may be involved.

Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies.
Chen D1, Wang CY, Lambert JD, Ai N, Welsh WJ, Yang CS. (2005)

(-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenol present in green tea. We previously demonstrated that EGCG was both a substrate and potent inhibitor of human liver cytosolic catechol-O-methyltransferease (COMT). We now report the structure-activity relationship for the inhibition of COMT-catalyzed O-methylation of catecholestrogens in human liver cytosol by tea catechins and some of their metabolites. The most potent inhibitors were catechins with a galloyl-type D-ring, including EGCG (IC(50)=0.07 microM), 4''-O-methyl-EGCG (IC(50)=0.10 microM), 4',4''-di-O-methyl-EGCG (4',4''-DiMeEGCG) (IC(50)=0.15 microM), and (-)-epicatechin-3-gallate (ECG) (IC(50)=0.20 microM). Catechins without the D-ring showed two to three orders of magnitude less inhibitory potency. Enzyme kinetic analyses revealed that EGCG behaved as a mixed inhibitor, whereas 4',4''-di-O-methyl-EGCG exhibited competitive kinetics for the S-adenosylmethionine (SAM), and noncompetitive kinetics for the catechol binding site. These compounds may represent a new type of COMT inhibitor. In silico molecular-modeling studies using a homology model of human COMT were conducted to aid in the understanding the catalytic and inhibitory mechanisms. Either D-ring or B-ring of EGCG could be accommodated to the substrate binding pocket of human COMT. However, the close proximity (2.6A) of 4''-OH to the critical residue Lys144, the higher acidity of the hydroxyl groups of the D-ring, and the hydrophobic interactions between the D-ring and residues in the binding pocket greatly facilitated the interaction of the D-ring with the enzyme, and resulted in increased inhibitory potency. These results provide mechanistic insight into the inhibition of COMT by commonly consumed tea catechins.

Caffeine Induces Dopamine and Glutamate Release in the Shell of the Nucleus Accumbens
Marcello Solinas1, Sergi Ferré1, Zhi-Bing You2, Marzena Karcz-Kubicha1, Patrizia Popoli3, and Steven R. Goldberg1 (2002)

An increase in the extracellular concentration of dopamine in the nucleus accumbens (NAc) is believed to be one of the main mechanisms involved in the rewarding and motor-activating properties of psychostimulants such as amphetamines and cocaine. Using in vivo microdialysis in freely moving rats, we demonstrate that systemic administration of behaviorally relevant doses of caffeine can preferentially increase extracellular levels of dopamine and glutamate in the shell of the NAc. These effects could be reproduced by the administration of a selective adenosine A1 receptor antagonist but not by a selective adenosine A2A receptor antagonist. This suggests that caffeine, because of its ability to block adenosine A1 receptors, shares neurochemical properties with other psychostimulants, which could contribute to the widespread consumption of caffeine-containing beverages.

Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats.
Yokogoshi H1, Kobayashi M, Mochizuki M, Terashima T. (1998)

Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (+/-)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.

 

 

I did say in my first post: I react badly to L-theanine, green tea, EGCG,... all things related to green tea.

 

I also feel uncomfortable when drink coffee, and the crash afterward makes me sleepy, tired.

 

Ginkgo biloba and ginseng have cholinergic properties. I react badly to cholinergic stuff.

[gamesguru]

I mean bacopa also induces TH and D2, but is much more cholinergic than ginseng. Did you tried ginseng?

Try mucuna, mu gua, shilajit, catuaba, rhodiola, vinpocetin, rosmarinic acid, forskolin, iron, and lithium.

[thedevinroy]

I still think the adrenal response is involved, just maybe not in a straight ADHD type way where the NET is the target. He doesn't respond well to tyrosine, caffeine, and has no response to typical ADHD medicine or even exercise. Sounds like burnout and a lot of bad habits. I don't see anything clinically wrong with that... sounds normal, just needs a better self image, maybe new people, too. I know that is mean, but whatever, it's the truth - believing is half the battle, and we are social beings that need reinforcement in our beliefs.

What's not normal is the bad response to everything nootropic. That's messed up. Maybe it is just the pessimism screwing with the effects. I know pessimism negates the placebo effect, but maybe it can tip the scales the other way, too.

And what the hell helps? There has to be something. Let's find the bright spots. Everyone has an elixir to some degree. Not everything can be a poison or a dud.

[thedevinroy]

Granted, yes, norepinephrine alone and not coupled with another mechanism would increase anxiety in a nervous type way, but that is not always bad. Some people like me do not have a productive anxiety without boosting norepinephrine levels, so in my case, I feel motivated when I'm anxious and thus can stay in a more anxious state for longer to get something done and can even have the ability to shut that whole thought process off when required because norepinephrine also enhances will power as it is a mental resource. Sort of like carbing up before hitting the gym. That's why it is thought to be involved in depression and ADHD - both have high mental fatigue or even working mental capacity issues.

Not all anxiety is bad anxiety. The kind he has right now is more of a frustration than nervousness. If he could trade that lethargy into controlled excitement, don't you think he would?

And yeah everyone who takes a noradrernergic who needs one feels like poopoo because their new brain isn't a better version of their old one - it is the same one with more fuel. The brain can do more tricks, but not without practice. It takes time to learn how to put those new feelings (like nervousness) to use in your life.
Cheese and rice. You do want me to list off a thousand things to try?

[psychejunkie]

 

looks like low Serotonin; take 5-HTP every morning and see what happens.

 

but just to be sure, Do you get headaches frequently or not? and what level of pain tolerance do you rate yourself?

I don't think I have low Serotonin, I'm confident and optimistic. According to "The mood cure" quiz, I only have low dopamine.

 

You say you are not depressed, but you may be able to treat standalone apathy with an SNRI or even an NDRI like bupropion. Motivation has a lot to do with the adrenal gland and getting that norepinephrine up is important. The question is whether you'll have to couple it with a CNS dopaminergic or CNS serotonergic (avoiding peripheral types like precursors) keeping it selective to the areas of the brain that are important.

I know that's a loaded response, but you have a lot of question marks about yourself that I can't possibly answer so specifically. I can treat you like I would an indecisive girl and just list off a thousand options until you don't shoot one down...

But... I think you'll be more efficient if you just do it yourself.

Can you list off a couple dozen drugs you'd like to try? Add to that list Zembrin+caffeine, an NRI, an SNRI, and an NDRI.

 

I did try Bupropion 2 times, the first time I took 150mg Bupropion + 1.5g tyrosine + piracetam, and I felt lethargy, very sleepy, horrible. I think it was because of the tyrosine the next day I took only bupropion and piracetam and did not notice noticeable effects. I think I'll try it again.

 

Which substance would you recommend for me? I've tried Selegiline, Tianeptine (Stablon), Sulbutiamine, Phenibut yet they do not help.

 

P/s: I also feel uncomfortable when drink coffee, and the crash afterward makes me sleepy, tired.

 

 

Confident & Optimistic? it isn't that simple!

Also, if you have low Dopamine you'd not have strong sexual drive.

 

Usually low Serotonin circulation causes: High Acetylcholine, Constipation, Strong sexual drive, High risk taking, Insomnia and Low motivation.

and high Acetylcholine symptoms are usually: Muscle weakness, Tiredness, Agitation associated with Dysphoria, Intelligent but Poor Common sense, Anhedonia or Blunt emotions, Itching and Low Heart-rate.

Low Serotonin (Low Inhibitory) and High Acetylcholine (High Inhibitory) might cause intolerance for Stimulants and Cholinergics (I am not 100% sure about this, personal assumption!)

 

anyway, I still suggesting 5-HTP at least for 4 weeks and see what happens.

Edited by psychejunkie, 18 September 2016 - 04:13 AM.

[tronatula2]

I mean bacopa also induces TH and D2, but is much more cholinergic than ginseng. Did you tried ginseng?

Try mucuna, mu gua, shilajit, catuaba, rhodiola, vinpocetin, rosmarinic acid, forskolin, iron, and lithium.

I've tried No Life deer Velvet, Planetary Cordyceps CS-4. They have cholinergic property and they make me duller. Ginseng has even stronger cholinergic effect so I will never try it. I react poorly to cholinergic stuff.

 

Tried Himalaya Herbal Healthcare Mucuna many times and noticed nothing, moreover mucuna has cholinergic property (increased  phosphatidyl choline, lyso phosphatidyl choline), rhodiola, Vinpocetine ( Studies have demonstrated that vinpocetine increases the levels of neurotransmitters involved in memory functions, namely noradrenaline, dopamine and acetylcholine), forskolin ( This inhibitory effect could be partly prevented by simultaneous addition of 10 microM forskolin) all have cholinergic properties, and I didn't notice enhanced motivation when on them. Why do you keep suggest cholinergic stuff to me while I did say that I react poorly to them?

 

The rest of your list I've never heard of them improve motivation? Do you have any scientific researchs, or even anecdotal report to back up your claim?

 

 

I still think the adrenal response is involved, just maybe not in a straight ADHD type way where the NET is the target. He doesn't respond well to tyrosine, caffeine, and has no response to typical ADHD medicine or even exercise. Sounds like burnout and a lot of bad habits. I don't see anything clinically wrong with that... sounds normal, just needs a better self image, maybe new people, too. I know that is mean, but whatever, it's the truth - believing is half the battle, and we are social beings that need reinforcement in our beliefs.

What's not normal is the bad response to everything nootropic. That's messed up. Maybe it is just the pessimism screwing with the effects. I know pessimism negates the placebo effect, but maybe it can tip the scales the other way, too.

And what the hell helps? There has to be something. Let's find the bright spots. Everyone has an elixir to some degree. Not everything can be a poison or a dud.

 

I reacted poorly to bupropion AND tyrosine (some people report the same), but I react well to Tyrosine alone.

 

 

 

Confident & Optimistic? it isn't that simple!

Also, if you have low Dopamine you'd not have strong sexual drive.

 

Usually low Serotonin circulation causes: High Acetylcholine, Constipation, Strong sexual drive, High risk taking, Insomnia and Low motivation.

and high Acetylcholine symptoms are usually: Muscle weakness, Tiredness, Agitation associated with Dysphoria, Intelligent but Poor Common sense, Anhedonia or Blunt emotions, Itching and Low Heart-rate.

Low Serotonin (Low Inhibitory) and High Acetylcholine (High Inhibitory) might cause intolerance for Stimulants and Cholinergics (I am not 100% sure about this, personal assumption!)

 

anyway, I still suggesting 5-HTP at least for 4 weeks and see what happens.

 

 

THE MOOD TYPE QUESTIONNAIRE is a reliable quiz to find out which neurotransmitters you lack, and I scored very low on serotonin quiz.

 

I do not have Constipation and I am a Low risk taking, Also never heard of low motivation related to serotonin, usually it's dopamine. Do you have any sources?

 

Low serotonin is ofter related to pessimistic (I'm optimistic), low self-esteem (I'm confident), insomnia (I've never woken up in the middle of the night in my life), I've never had depression, panic attack, carbohydrate craving or suicidal thoughts (there are many beautiful things I've not tried, why I have to die?).

 

I just have low motivation, daydreams a lot and tinnitus, that's all. I just want to eat and play everyday, I Do not want a lot of money (of course, more is better but just adequate is ok for me). I usually choose low effort activities rather than high effort activities.

Edited by tronatula2, 18 September 2016 - 05:59 AM.

[psychejunkie]

 

THE MOOD TYPE QUESTIONNAIRE is a reliable quiz to find out which neurotransmitters you lack, and I scored very low on serotonin quiz.

 

I do not have Constipation and I am a Low risk taking, Also never heard of low motivation related to serotonin, usually it's dopamine. Do you have any sources?

 

Low serotonin is ofter related to pessimistic (I'm optimistic), low self-esteem (I'm confident), insomnia (I've never woken up in the middle of the night in my life), I've never had depression, panic attack, carbohydrate craving or suicidal thoughts (there are many beautiful things I've not tried, why I have to die?).

 

I just have low motivation, daydreams a lot and tinnitus, that's all. I just want to eat and play everyday, I Do not want a lot of money (of course, more is better but just adequate is ok for me). I usually choose low effort activities rather than high effort activities.

 

 

Actually Serotonin IS related to motivation.

here are some sources backing this:

http://www.jneurosci...2/17/5833.short

http://www.sciencedi...028390811004060

http://europepmc.org...act/med/1752861

... etc

 

you need to be more open minded

as a matter of fact, mostly, all of neurotransmitters have overlaps in their effects on mood regulation and emotions.

you just cant determine deficiencies through some internet questionnaires! if that was possible, no doctor would ask for experiments or blood/urine work!

 

excess Day Dreaming means DMN (Default Mode Network) over-activity, this network mostly is consists of Serotonergic and Dopaminergic circuits; this might sound high levels of both Dopamine and Serotonin at first, but you should keep in mind that most of bodily and brain functions involve the law of Negative-Feedback. So, your DMN is overly active because Serotonin or Dopamine or BOTH are low and your brain is trying to activate more related neurons.

But, low Dopamine and High Serotonin results in Blunt Sexual Desire or Sexual Anhedonia, which you're experiencing quite the opposite: Strong Sexual Desire, Which is a symptom of High/Normal Dopamine and Low Serotonin. 

Low Serotonin disrupts Mood Regulations, Motivated Behaviors and (along with normal/high Dopamine) cause excess sexual drive.

 

Though, lets not judge too soon.

you mentioned of strong intolerance to Cholinergics (both agonists and antagonists I guess) but a reponder to Piracetam. Also it might be good to know that people often get satisfying results when they take Choline and Piracetam as combination.

this single symptom is straight forward. Acetylcholine isnt like other neurotransmitters. High Acetylcholine acts inhibitory but low levels of it have Stimulation on neurons. you are experiencing intolerance (sleepy, drowsy, dull, fatigue, etc << all excess inhibitory side-effects) to cholinergics because you have High Acetylcholine levels (too much inhibition) in Cholinergic Circuits; and that's why Piracetam response in good results as it depletes neurons' Acetylcholine storage and increases Choline supplies.

Also, as you know, High Acetylcholine levels cause low heart-rate and low blood pressure, which might result in headaches or tinnitus; and 

 

Serotonergic supplements like 5-HTP, both increase your Serotonin Levels and decrease excess Acetylcholine secretion.

 

Good luck!

[gamesguru]

Choline makes everyone "duller".  So why make a mountain out of a molehill.  Don't be a baby.  Just pick something weakly cholinergic, and be thankful you have something!!

 

You're hastily dismissive of things you've never tried, a classic characteristic of close-mindedness.  All those substances were dopaminergic.  Maybe instead of downvoting everyone and dismissing everything as "potently cholingeric", Mr. perfectionist... you should give them a try, and also give a try to noFap.. dude.  You might be surprised to discover the world is not in perfect accord with your ideas.  Good luck, Mr. Disagreeable.  Good luck ;P

 

Dopamine itself has inhibitory effects on acetylcholine, much like 5-HT2C does on dopamine.

 

Acetylcholine-dopamine balance hypothesis in the striatum: an update.
Aosaki T1, Miura M, Suzuki T, Nishimura K, Masuda M. (2010)

The imbalance between cholinergic activity and dopaminergic activity in the striatum causes a variety of neurological disorders, such as Parkinson's disease. During sensorimotor learning, the arrival of a conditioned stimulus reporting a reward evokes a pause response in the firing of the tonically active cholinergic interneurons in targeted areas of the striatum, whereas the same stimulus triggers an increase in the firing frequency of the dopaminergic neurons in the substantia nigra pars compacta. The pause response of the cholinergic interneurons begins with an initial depolarizing phase followed by a pause in spike firing and ensuing rebound excitation. The timing of the pause phase coincides well with the surge in dopaminergic firing, indicating that a dramatic rise in dopamine (DA) release occurs while nicotinic receptors remain unbound by acetylcholine. The pause response begins with dopamine D5 receptor-dependent synaptic plasticity in the cholinergic neurons and an increased GABAergic IPSP, which is followed by a long pause in firing through D2 and D5 receptor-dependent modulation of ion channels. Inactivation of muscarinic receptors on the projection neurons eventually yields endocannabinoid-mediated, dopamine-dependent long-term depression in the medium spiny projection neurons. Breakdown of acetylcholine-dopamine balance hampers proper functioning of the cortico-basal ganglia-thalamocortical loop circuits. In Parkinson's disease, dopamine depletion blocks autoinhibition of acetylcholine release through muscarinic autoreceptors, leading to excessive acetylcholine release which eventually prunes spines of the indirect-pathway projection neurons of the striatum and thus interrupts information transfer from motor command centers in the cerebral cortex.

Inhibitory effect of dopamine on acetylcholine release from caudate nucleus.
Vizi SE, Rónai A, Hársing L Jr, Knoll J. (1977)

It has been shown that dopamine inhibits the release of acetylcholine (ACh) from nerve terminals of caudate cholinergic interneurons, and the imbalance between dopaminergic and cholinergic system by 6-hydroxydopamine pretreatment leads to an increased ACh release. The Parkinson-syndrome induced by drugs which depress dopaminergic function either by reducing the output of dopamine, such as reserpine, or by antagonizing its action on DA receptors, as for instance haloperidol or chlorpromazine, can be attributed to the augmented release of ACh from caudate cholinergic nerve terminals and a consequent increase of cholinergic outflow from caudate nucleus. However, athetoid and choreiform hyperkinesis in patients and hypermotility in animals might result from increased dopaminergic outflow of nigro-striatal pathway and a consequent reduction in cholinergic neurosecretion of caudate nucleus.

 

Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms.
Campos MM1, Fernandes ES, Ferreira J, Santos AR, Calixto JB. (2005)

RATIONALE:
Currently available therapy for depression treatment is often associated with several undesirable side effects, and it is effective only in a certain portion of the population. Therefore, the identification of alternative therapeutic tools for the treatment of depression is still needed.

OBJECTIVE:
The present study analyzed the possible antidepressant-like effects of the Brazilian medicinal plant, Trichilia catigua, in rodents. Attempts were also made to investigate some of the possible mechanisms implicated in its actions.

METHODS:
The antidepressant-like effects of T. catigua extract were assessed in two species of rodents (mice and rats) by means of in vivo (forced swimming test) and in vitro (monoamine reuptake and release in synaptosomal preparations) approaches.

RESULTS:
Acute oral treatment with the extract of T. catigua produced antidepressant-like effects in the forced swimming model in both mice and rats. Anti-immobility actions of T. catigua extract in mice were significantly reversed by haloperidol or by chlorpromazine, but not by pimozide, ketanserin, spiroxatrine or p-chlorophenylalanine. In vitro, T. catigua extract concentration-dependently inhibited the uptake and increased the release of serotonin, and especially of dopamine, from rat brain synaptosomal preparations.

CONCLUSIONS:
The present study provides convincing evidence for a dopamine-mediated antidepressant-like effect of the active principle(s) present in the hydroalcoholic extract of T. catigua in mice and rats when in vivo and in vitro strategies were employed. Therefore, a standardized T. catigua extract or its purified constituents could be of potential interest for the treatment of depressive disorders.

Mechanisms of tryptophan and tyrosine hydroxylase.
Roberts KM1, Fitzpatrick PF. (2013)

The aromatic amino acid hydroxylases tryptophan hydroxylase and tyrosine hydroxylase are responsible for the initial steps in the formation of serotonin and the catecholamine neurotransmitters, respectively. Both enzymes are nonheme iron-dependent monooxygenases that catalyze the insertion of one atom of molecular oxygen onto the aromatic ring of their amino acid substrates, using a tetrahydropterin as a two electron donor to reduce the second oxygen atom to water. This review discusses the current understanding of the catalytic mechanism of these two enzymes. The reaction occurs as two sequential half reactions: a reaction between the active site iron, oxygen, and the tetrahydropterin to form a reactive Fe(IV) O intermediate and hydroxylation of the amino acid by the Fe(IV) O. The mechanism of formation of the Fe(IV) O is unclear; however, considerable evidence suggests the formation of an Fe(II) -peroxypterin intermediate. The amino acid is hydroxylated by the Fe(IV) O intermediate in an electrophilic aromatic substitution mechanism.

 

Dopamine-β-Hydroxylase (DBH), Its Cofactors and Other Biochemical Parameters in the Serum of Neurological Patients in Bangladesh
Md. Khalilur Rahman,1 Farhana Rahman,1 Tania Rahman,1 and Takeshi Kato (2009)

Dopamine-β-hydroxylase (DBH) is a neurotransmitter synthesizing enzyme which catalyzes the formation of norepinephrine from dopamine. In this study, we measured the level of DBH activity in the serum of patients of three different age groups (8–14 yrs, 20–40 yrs and 45–60 yrs) suffering from neurological diseases. Serum DBH activity was measured in 38 neurological patients and 38 normal individuals in order to determine significant variables for its potential use to diagnose the neurological patients. It was found that the DBH activity decreased in the patients of all age groups. A considerable decrease in activity was observed in the patients of 8–14 yrs age group (14.2 nmoles/min/ml in patients compared to the normal value of 22.6). A significant decrease in activity was found in the 20–40 yrs age group (23.4 nmoles/min/ml in patients compared to the normal value of 33.0). The decrease in DBH activity was also found in the patients of 45–60 yrs age group but to a lesser extent (26.4 nmoles/min/ml in the patients compared to the normal value of 30.2). The kinetic studies of DBH exhibited an increase of Km value and a decrease in Vmax in the neurological patients. Serum copper and ascorbic acid levels (cofactors of DBH) were found to be decreased in neurological patients and hence are in agreement with the decrease in DBH activity in these patients. Other parameters such as glucose and cholesterol levels increased, protein and zinc levels decreased and ALT, AST, creatinine and urea content remained nearly unchanged in the patients’ serum.

 

sometimes a push in the other direction may be what is needed...

Neurorescue effect of rosmarinic acid on 6-hydroxydopamine-lesioned nigral dopamine neurons in rat model of Parkinson's disease.
Wang J1, Xu H, Jiang H, Du X, Sun P, Xie J. (2012)

Rosmarinic acid (RA) is a naturally occurring polyphenolic compound. It has been reported that RA possessed antioxidant and anti-inflammatory properties. Our previous study showed that RA could protect MES23.5 dopaminergic cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. The purpose of this study was to explore the neuroreparative (neurorescue) effect of RA on 6-OHDA-lesioned rat model of Parkinson's disease (PD) in vivo. In this study, the rats were given RA orally after intrastriatal 6-OHDA lesion. Results showed that the dopamine content in the striatum decreased and the numbers of tyrosine hydroxylase-immunoreactive neurons reduced after 6-OHDA treatment. RA treatment after 6-OHDA administration could restore these changes. Further studies demonstrated that 6-OHDA treatment increased the iron-staining positive cells, which were markedly decreased by RA treatment. Moreover, RA suppressed the increased ratio of Bax/Bcl-2 at gene level induced by 6-OHDA. This indicates that the neurorescue effects of RA against 6-ODHA-induced degeneration of the nigrostriatal dopaminergic system were achieved by decreasing nigral iron levels and regulating the ratio of Bcl-2/Bax gene expression.

Effect of chronic lithium and withdrawal from chronic lithium on presynaptic dopamine function in the rat.
Ferrie L1, Young AH, McQuade R. (2005)

Bipolar affective disorders can be successfully treated with long-term use of the mood stabilizer lithium. However, discontinuation of lithium treatment is followed by a high incidence of manic episodes. In the present study, we attempted to identify neurobiological changes that might mediate this rebound mania. In vivo microdialysis in the anaesthetized rat and in situ hybridization histochemistry were used to study the effect of chronic lithium treatment and withdrawal from chronic lithium treatment on presynaptic dopamine (DA) function. Rats were maintained for 28 days on a lithium diet or control diet. The lithium-withdrawn treatment group had their lithium diet substituted for control diet from day 25 of the treatment period. Microdialysis probes were implanted in the shell of the nucleus accumbens and both basal extracellular DA levels and DA levels in the presence of the DA uptake inhibitor bupropion (1 microM) were collected. Basal DA levels did not differ between any of the treatment groups. However, during local perfusion of bupropion, the increase in DA was significantly attenuated in the lithium-treated animals compared to controls or lithium-withdrawn animals. In situ hybridization of DA transporter mRNA in the ventral tegmental area revealed no difference in the abundance of this mRNA in any of the groups. These data suggest that there is impaired DA release in rats during chronic lithium treatment, but DA release returns to normal levels on withdrawal from lithium treatment, and is therefore unlikely to underlie the rebound mania associated with lithium withdrawal.

Edited by gamesguru, 18 September 2016 - 01:06 PM.

[gamesguru]

Maybe just look for something nicotinic specific?

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation
Anne L Collins1, Tara J Aitken1, Venuz Y Greenfield1, Sean B Ostlund2 and Kate M Wassum (2016)

Environmental reward-predictive cues can motivate reward-seeking behaviors. Although this influence is normally adaptive, it can become maladaptive in disordered states, such as addiction. Dopamine release in the nucleus accumbens core (NAc) is known to mediate the motivational impact of reward-predictive cues, but little is known about how other neuromodulatory systems contribute to cue-motivated behavior. Here, we examined the role of the NAc cholinergic receptor system in cue-motivated behavior using a Pavlovian-to-instrumental transfer task designed to assess the motivating influence of a reward-predictive cue over an independently-trained instrumental action. Disruption of NAc muscarinic acetylcholine receptor activity attenuated, whereas blockade of nicotinic receptors augmented cue-induced invigoration of reward seeking. We next examined a potential dopaminergic mechanism for this behavioral effect by combining fast-scan cyclic voltammetry with local pharmacological acetylcholine receptor manipulation. The data show evidence of opposing modulation of cue-evoked dopamine release, with muscarinic and nicotinic receptor antagonists causing suppression and augmentation, respectively, consistent with the behavioral effects of these manipulations. In addition to demonstrating cholinergic modulation of naturally-evoked and behaviorally-relevant dopamine signaling, these data suggest that NAc cholinergic receptors may gate the expression of cue-motivated behavior through modulation of phasic dopamine release.

 

Increase of acetylcholine release by Panax ginseng root enhances insulin secretion in Wistar rats
Chih-Fen Sua, Juei-Tang Chengb, I-Min Liuc (2006)

The present study was designed to ascertain the effect of Panax ginseng root on plasma glucose and investigate the possible mechanisms for the effect. Ninety minutes after the oral administration of P. ginseng root to fasting Wistar rats, plasma glucose decreased in a dose-dependent manner. Simultaneous with the reduction in plasma glucose, an increase in the plasma level of insulin and C-peptide was also observed. Moreover, disruption of the available synaptic acetylcholine (ACh), using the inhibitor for choline uptake (hemicholinium-3), or the inhibitor for vesicular choline transport (vesamicol), abolished the metabolic actions of P. ginseng root. Conversely, physostigmine, at a concentration sufficient to inhibit acetylcholinesterase, enhanced the metabolic effect of P. ginseng root. It is possible that P. ginseng root mediates the release of ACh from nerve terminals to enhance insulin secretion. Blockade of the actions of P. ginseng root by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP) suggested that the site of action is the muscarinic M3 receptor. Taken together, the results suggest that P. ginseng root has the ability to increase the release of ACh from nerve terminals in rats so as to stimulate muscarinic M3 receptors activity located in the pancreatic cells for the secretion of insulin, which in turn lower plasma glucose.

[tronatula2]

 

Maybe just look for something nicotinic specific?

 

 

 

 You mean I should increase muscarinic acetylcholine receptor? Not nicotinic receptor right?

 

 

Disruption of NAc muscarinic acetylcholine receptor activity attenuated, whereas blockade of nicotinic receptors augmented cue-induced invigoration of reward seeking. We next examined a potential dopaminergic mechanism for this behavioral effect by combining fast-scan cyclic voltammetry with local pharmacological acetylcholine receptor manipulation. The data show evidence of opposing modulation of cue-evoked dopamine release, with muscarinic and nicotinic receptor antagonists causing suppression and augmentation, respectively, consistent with the behavioral effects of these manipulations.

 

 

It means REDUCING muscarinic acetylcholine receptor will REDUCE invigoration of reward seeking, while REDUCING nicotinic receptors will Improve invigoration of reward seeking. So to increase motivation, we should increase muscarinic acetylcholine receptors, right?

[thedevinroy]

So your cholinergic system is hyperactive, your serotonergic system is fine-ish (that may change as you fix the root cause), and your endorphins seem to be better than average at baseline. You have a pretty good idea that it is dopaminergic yet you respond poorly to several dopaminergics... which I'm not sure what that means in each case. If you can break down into a paragraph each drug/supplement and how it affected you, that would help us find any bright spots. Sometimes the reasons we avoid drugs are for the side effects, and not only might there be alternatives with less side effects, sometimes that sacrifice is the one we need to make because there are other ways of managing side effects whether mentally, lifestyle adjustments, or just by taking an adjunct therapy.

You say you are not pessimistic, so I'll take your word for it. Your lifestyle is not what you'd like it to be, playing and eating in your free time. So you would like something to make you more serious, right? More motivated to do things that matter?

Drug List to Try:
1. An SSRI or Zembrin. This will help you cope with the side effects from caffeine. Dopamine can be enhanced once the hippocampus is able to perform its duties correctly. Alternatively, meditative or holotropic breathing has a similar effect on grey matter.
2. An SNRI. The serotonin will take the edge of the norepinephrine bump. Trade names like Cymbalta and Effexor fall into this category.
3. An NDRI with an NDRA. Dopamine and norepinephrine enhance the properties of one another. You have already tried bupropion to no avail but have no combined it with a release agent and amphetamines are not allowed. Methylphenidate is both an NDRI and NDRA like amphetamines. Releasing the catecholamines and preventing their uptake has a combined effect greater than the sum of the parts. Release agents like amphetamines and methylphenidate should be slow released throughout the day because the crash is intense when your body goes to start storing the catecholamines in vesicles again.
4. An NRI. You may just need an NRI, as is the case with me. I am on atomoxetine. It raises dopamine levels by raising norepinephrine levels primarily. The NET also has an effect on dopamine transport. Norepinephrine also has affinity for some dopamine receptors.
5. Magnesium water. Use at night for sleep.
6. Partial NMDA antagonist like Memantine. Use in conjunction with another dopaminergic for a combined benefit.
7. & 8. Pramiracetam & Aniracetam. You respond well to Piracetam. Might as well try another analogue and go that route.
9. Tumeric plus an adaptogen. A lot of people notice this has a motivating effect.
10. Methylene Blue. 5-15mg 2x a day. Makes my thoughts more fluid, also can give me a boost. Long term high doses not recommended, but a once in a while burst for focus is fine, given a recovery period. Has a hormetic response curve.
11. Maritime Pinebark Extract. It's no body high or what not, but it does have an ability to stabilize your energy levels. Since you are sensitive to tea, you may be a high responder, since it has similar compounds in more complex forms.
12. Check for vitamin B deficiencies. High levels of Vitamin B6 and B1 can be quite motivating.
13. Check your blood sugar. You may be suffering from mental fatigue and just need a little picker upper. Test by eating a pickle or something with vinegar. Acetic acid (vinegar) is one of the compounds sugar is made into to become energy. This may mean you have to change your diet if this is the case.
14. Check your potassium levels. Low potassium can cause all sorts of problems.
15. Check for allergies. Gluten is big globby mess
of molecules and oligimers. Milk has a bunch of allergens too.
16. Check your social connections. You sound like you have low internal supervision, so maybe you need an accountability partner or group. I joined a business Meetup once, and that really helped. You can start by telling us what you'd actually like to do in your free time.

It's not a thousand things, but it is a start.

Edited by devinthayer, 18 September 2016 - 04:59 PM.

[gamesguru]

In regards muscarinic vs nicotinic, how does tobacco affect you?  One has to be extremely careful when talking in terms of receptor dynamics.  More receptors comes with antagonist treatment.  Less comes with agonists, e.g. smoking tobacoo.  But in the long-term, less receptors means lower activity... which is exactly what you expect in the short-term antagonist treatment.  So smokingi tobacco in the short-term has a similar effect as to taking antagonists long-term, and it's very confusing.  Besides, most herbal supplements are muscarinic-specific agonists, which will (long-term) lower muscarinic receptor levels (down-regulate) which is precisely the conclusion you wished to avoid!

 

FLOWERING QUINCE^[1], also the only NCBI query involving "flowering quince" or "" and "acetylcholine" is this result, which takes note of opposing properties(?)... leading one to believe this plant is thoroughly non-cholinergic.  Similarly good luck pinning down a reference as to catuaba's cholinergic action.  I don't think there is one^{[2], [3]}.  For a pharmaceutical option, wellbutrin is a dopamine reuptake inhibitor with anticholingergic properties.

Total flavonoids from C. speciosa were shown to relax gastrointestinal smooth muscles, through exerting an inhibitory effect on the contraction of the isolated rabbit gastric fundus and ileum induced by acetylcholine and CaCl₂ in a dose-dependent manner and suppressing the contraction of the isolated rabbit taenia coli elicited by high K⁺ depolarization. These relaxant effects may be associated with the voltage-dependent Ca²⁺ channel blockade by total flavonoids (40,41).

 

Thunbergia Laurifolia appears to have a protective effect on acetycholinerase[!] (but I found one conflicting study), while inhibiting dopamine uptake.  Salvia Miltiorrhiza is another candidate for dopamine uptake, but it clearly has strong cholinergic properties[!].  Both these substances were brought to my attention by 'agwoodliffe', thread.

Effect of Thunbergia laurifolia extract on extracellular dopamine level in rat nucleus accumbens.
Thongsaard W1, Marsden C. (2013)

BACKGROUND:
Thunbergia laurifolia Linn. (TL) is a herbal medicine used as an antidote for several poisonous agents in Thai traditional medicine. TL were reported not only to significantly increase potassium-stimulated dopamine release from rat striatal slices but also potentiated the effect of amphetamine on potassium-stimulated dopamine release.
OBJECTIVE:
The present study aim to investigate the effect of TL on extracellular dopamine levels in rat nucleus accumbens in vivo in comparison to cocaine.
MATERIAL AND METHOD:
Single injections of methanol extract of TL (200 mg/kg, ip) and cocaine (10 mg/kg, ip) were performed to determine the levels of extracellular dopamine in vivo in the living brain using the microdialysis technique (collecting time = 20 minutes).
RESULTS:
Cocaine and TL significantly (p < 0.05) increased extracellular dopamine levels in the rat nucleus accumbens in a similar manner, but the effect of cocaine had a faster onset than that of TL.
CONCLUSION:
The results are in agreement with a previous in vitro study. It can be summarized that TL stimulated rat dopamine release from the nucleus accumbens both in vitro and in vivo. This brain area is responsible for the reward mechanism of addiction. The clinical significance for the use of TL in humans and the effect of long term treatment with TL on addiction requires further investigation.

Salviae miltiorrhizae radix increases dopamine release of rat and pheochromocytoma PC12 cells.
Kim CH1, Koo BS, Kim KO, Kim JK, Chang YC, Lee IS. (2006)

The Radix of Salvia miltiorrhiza Bunge (Labiatae) (SMR), an eminent herb, is often included as an ingredient in various herbal remedies recommended for vascular circulation therapies. The present study investigated the effect of SMR on dopaminergic neurotransmission. Various extracts prepared from the stems of SMR were tested for cytotoxic activity on pheochromocytoma PC12 cells using the XTT assay method. The ethanol extract (IC50 > 100 microg/mL), water extract (IC50 > 100 microg/mL) and chloroform (IC50 = 90 microg/mL) fraction exhibited weak cytotoxic activity. However, the butanol (IC50 = 80 microg/mL) and ethyl acetate (EtOAc; IC50 = 70 microg/mL) fractions exhibited strong cytotoxic activity. Also, the extracts and fractions were investigated for dopamine release effects. The EtOAc fraction showed a stronger stimulatory effect on dopamine release activity than the other fractions. The effect of the crude EtOAc fraction (50 microg/mL) of SMR on K+ (20 mm)-stimulated dopamine (DA) release from rat striatal slices was compared with amphetamine (10(-4) m) using high-performance liquid chromatography with electrochemical detection to measure endogenous DA. The EtOAc fraction significantly increased K+ -stimulated DA release (p < 0.001) from rat striatal slices when compared with K+ -stimulated alone. The EtOAc fraction potentiated the effect of amphetamine on K+ -stimulated DA release (p < 0.001) when compared with amphetamine alone. To examine whether in vitro the EtOAc fraction treatment induces DA release in PC12 cells, the role of protein kinases was investigated in the induction of the EtOAc fraction-mediated events by using inhibitors of protein kinase C (PKC), mitogen activated protein kinase (MAP kinase) or protein kinase A (PKA). The PKC inhibitors chelerythrine (50 nm and 100 nm) and Ro31-8220 (100 nm) and the MAP kinase kinase inhibitor, PD98059 (20 microm), inhibited the ability of the EtOAc fraction of SMR to elicit the EtOAc fraction-stimulated DA release. The PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA, 100 nm) mimicked the ability of the EtOAc fraction of SMR to elicit DA release. In contrast, a selective PKA inhibitor, 50 microm Rp-8-Br-cAMP, blocked the development of EtOAc fraction-stimulated DA release. It was demonstrated that the EtOAc fraction of SMR stimulated DA release. Therefore the mechanism by which the EtOAc fraction of SMR induced the enhancement in EtOAc fraction-stimulated DA release is apparent.

 

As per the shilajit:

Effects of Shilajit on memory, anxiety and brain monoamines in rats
AK Jaiswal, SK Bhattacharya (1992)

The effect of Shilajit was investigated for putative nootropic and anxiolytic activity, and its effect on rat brain monoamines using Charles Foster strain albino rats. Nootropic activity was assessed by passive avoidance learning and active avoidance learning acquisition and retention. Anxiolytic activity was evaluated by the elevated plus-maze technique. Rat brain monoamines and monoamine metaboliteswere estimated by a HPLC technique. The results indicated that Shilajit had significant nootropic and anxiolytic activity. The biochemical studies indicated that acute treatment with Shilajit had insignificant effects on rat brain monoamine and monoamine metabolite levels. However, following subacute (5days) treatment, there was decrease in 5-hydroxytryptamine and 5-hydroxyindole acetic acid concentrations and an increase in the levels of dopamine, homovanillic acid and 3.4-dihydroxyphenyl-acetic acid concentrations, with insignificant effects on noradrenaline and 3-methoxy-4- hydroxyphenylethylene glycol levels. The observed neurochemical effects induced by Shilajit, indicating a decrease in rat brain 5-hydroxytryptamine turnover, associated with an increase in dopaminergic activity, helps to explain the observed nootropic and anxiolytic effects of the drug.

 

but it also appears off limits for the highly sensitive OP

Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain.
Schliebs R1, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V. (1997)

Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei including medial septum and the vertical limb of the diagonal band. Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A. These changes were accompanied by enhanced M1-muscarinic cholinergic receptor binding in lateral and medial septum as well as in frontal cortices, whereas the M2-muscarinic receptor binding sites were increased in a number of cortical regions including cingulate, frontal, piriform, parietal and retrosplenial cortex. Treatment with Shilajit or the defined extract from Withania somnifera affected neither GABAA and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor subtypes in any of the cortical or subcortical regions studied. The data suggest that Shilajit and the defined extract from Withania somnifera affect preferentially events in the cortical and basal forebrain cholinergic signal transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of extracts from Withania somnifera observed in animals and humans.

Edited by gamesguru, 18 September 2016 - 05:02 PM.

[psychejunkie]

I don't know why some people still think Serotonin has something to do with Depression and bad-weather-like mood hence its been a while that anti-depressant effects of Serotonergics are associated with glucocorticoid receptors and related to BDNF/Neurogenesis at certain regions of hippocampus. 

when I suggest someone to try 5-HTP, quickly he/she becomes reactive like "why!? im not depressed! i dont want to kill myself"...

 

this behavior of close-mindedness and illusion of knowing everything after reading some random internet articles is pretty boring.

 

Op has came here to get some opinions and answers to his problems hence he tries to reject everyone and push his own thoughts in our mouth as an answer.

he obviously hasnt responded to anything Dopaminergic, but he still rejects anything unrelated.

is this your optimistic behavior? really?

Edited by psychejunkie, 19 September 2016 - 03:42 AM.

[tronatula2]

Hey, just want to let you guys know that I will try Bupropion today, it's difficult and expensive to buy substances here. And I've wasted a lot of money on other stuff so I have to be cautious. I am not rich, I am just a student, please understand.

 

Moreover, I did react well to Tyrosine alone (improved mood, more talkative). Bupropion + tyrosine is overkill, that's why I'll try Bupropion alone + piracetam today. (Piracetam is constant in my stack).

 

However, Himalaya Mucuna did nothing for me.

 

Interestingly, Planetary Herbals Cordyceps power CS-4 (3 tablets) increased my digit span score (from 16 to 18). It contains:

Cordyceps sinensis Mycelia CS-4 (0.1% adenosine) (which promotes M1 muscarinic acetylcholine receptor), Astragalus Root, Codonopsis Root, Adenophora Root, Eucommia Bark, Eleuthero Root, Bai-Zhu Atractylodes Rhizome and Ginger Root.

Which ingredient do you think made me better if I react poorly to cholinergics?

 

One more thing: I've tried the protocol: 250mcg hydoxocobalamin B12 once time a day + 400mcg Swanson Methylflotae every 6 hours (up to 3 times a day). While it improved my cognition (tested by cambridgebrainsciene), it did not increase my motivation.

 

 

 

 

Edited by tronatula2, 19 September 2016 - 05:12 AM.

[tronatula2]

Took 150mg Bupropion today with 800mg piracetam, did nothing for motivation, in fact, I felt somehow sad and small. So no bupropion.

 

 

 

I don't know why some people still think Serotonin has something to do with Depression and bad-weather-like mood hence its been a while that anti-depressant effects of Serotonergics are associated with glucocorticoid receptors and related to BDNF/Neurogenesis at certain regions of hippocampus. 

when I suggest someone to try 5-HTP, quickly he/she becomes reactive like "why!? im not depressed! i dont want to kill myself"...

 

this behavior of close-mindedness and illusion of knowing everything after reading some random internet articles is pretty boring.

 

Op has came here to get some opinions and answers to his problems hence he tries to reject everyone and push his own thoughts in our mouth as an answer.

he obviously hasnt responded to anything Dopaminergic, but he still rejects anything unrelated.

is this your optimistic behavior? really?

 

May you ELI5 (English is not my first language) why all the websites I visit say that, low Serotonin is related to pessimism, low self-esteem, constipation,... and I have the totally opposite symptoms (optimism, confident, today I already had 2 bowels) , but you keep telling me I have low Serotonin?

 

Does this mean all those websites are wrong?

 

Edit: Tyrosine (1 or 2g) gave me noticeable effects only the first few times. After that, I didn't notice much effect.

Edited by tronatula2, 19 September 2016 - 09:08 AM.

[thedevinroy]

Bupropion took almost a month to kick in for me. I was also taking Modafinil which negates it's effects by interfering with metabolism. The very next day, I was pissed off and plotting to end a toxic 3 year friendship. It wasn't a nice drug, but that was the most productive thing I did in a while for myself. I do wonder if it was a combination of it building up effects in my system and the stopping of modafinil. I guess we will never know...

I wasn't suggesting you have low serotonin per say, only that you could benefit from adding a serotonergic to enhance dopamine signaling from a different angle. As previously mentioned, it increases BDNF in the hippocampus, which then increases Tyrosine Hydroxylase, the enzyme for creating more dopamine. Not to mention, Piracetam's primary method of action is thought to be on the mineralcorticoid system, which may be on the same lines of the glucocorticoid system being enhanced by serotonergics. There could be some synergy there, but I would not use that as my first line of defense. Rather, it is something you can come back to to manage side effects or enhance the effects of something else you are taking.

Also, when I mentioned Bupropion last, I recommended you take it with a release agent (NDRA). It won't have the same effect on motivation without it. The whole is greater than the sum of the parts. Here is the Wiki article:

https://en.m.wikiped...releasing_agent

The most easily available is phenethylamine, found in chocolate. This is often taken with Hordenine, to enhance its metabolism. This will cause euphoria, as this combo is the staple of the legal party drugs, so it is not a recommended approach (as mentioned previously, Methylphenidate, as this is usually first line of defense for your situation). As an alternative to a release agent, I find caffeine also has an enhanced effect on NDRI's but also increases the side effects of each other including scatter brain from caffeine. That's why I would stick to a release agent. Tyramine is also readily available, but it does not cross the BBB. A more gentle alternative is L-Phenylalanine. It is a precursor to phenethylamine and tyrosine. Unfortunately, like tyrosine, you have to take a lot and at an increasing scale. For more consistent results, people take both tyrosine and phenylalanine sublingually.

If you do find an NDRI/NDRA combo that works, the next thing is to add in a serotonergic to enhance those effects or reduce side effects. I recommend Zembrin, an herbal alternative. I feel like I could chug an entire pot of coffee and still be entirely stable, just more creative and motivated.

Edited by devinthayer, 19 September 2016 - 11:14 AM.

[tronatula2]

Confident & Optimistic? it isn't that simple!

 

 

Also, if you have low Dopamine you'd not have strong sexual drive.

 

Usually low Serotonin circulation causes: High Acetylcholine, Constipation, Strong sexual drive, High risk taking, Insomnia and Low motivation.

and high Acetylcholine symptoms are usually: Muscle weakness, Tiredness, Agitation associated with Dysphoria, Intelligent but Poor Common sense, Anhedonia or Blunt emotions, Itching and Low Heart-rate.

Low Serotonin (Low Inhibitory) and High Acetylcholine (High Inhibitory) might cause intolerance for Stimulants and Cholinergics (I am not 100% sure about this, personal assumption!)

 

anyway, I still suggesting 5-HTP at least for 4 weeks and see what happens.

 

 

Today afternoon, I took 100mg 5-HTP, 1 and a half hour after that I had goosebumps to almost every song I listened too. I usually do not have goosebumps easily like that. What does this mean?

[thedevinroy]

Confident & Optimistic? it isn't that simple!


Also, if you have low Dopamine you'd not have strong sexual drive.

Usually low Serotonin circulation causes: High Acetylcholine, Constipation, Strong sexual drive, High risk taking, Insomnia and Low motivation.
and high Acetylcholine symptoms are usually: Muscle weakness, Tiredness, Agitation associated with Dysphoria, Intelligent but Poor Common sense, Anhedonia or Blunt emotions, Itching and Low Heart-rate.
Low Serotonin (Low Inhibitory) and High Acetylcholine (High Inhibitory) might cause intolerance for Stimulants and Cholinergics (I am not 100% sure about this, personal assumption!)

anyway, I still suggesting 5-HTP at least for 4 weeks and see what happens.

Today afternoon, I took 100mg 5-HTP, 1 and a half hour after that I had goosebumps to almost every song I listened too. I usually do not have goosebumps easily like that. What does this mean?

Sounds like it reversed a long standing anhedonia.

[Junk Master]

I think I'd try a different strategy entirely.  How much exercise do you get a day?  Have you ever tried at least 3 high intensity exercise sessions per week for 8 weeks?

 

I'd rotate Azure B, COQ10, or Ubiquitol, and since I still have confidence in one seller C60/OO.

 

If you are a piracetam responder I can almost guarantee you will respond to 100-300 mg of Phenylpiracetam, which I find is great for motivation.  But is definitely not an everyday "cure."

 

I'd need a lot more of a psychological history, but 2x a week masturbation doesn't sound like "high sex drive" for anyone under 45.  More like 2x per day.  4x per day gets into the sexual addiction range, again IMO.

 

By the way, got to give DT props for making me laugh with his mack daddy strategy for dealing with indecisive women.

[tronatula2]

I don't know why some people still think Serotonin has something to do with Depression and bad-weather-like mood hence its been a while that anti-depressant effects of Serotonergics are associated with glucocorticoid receptors and related to BDNF/Neurogenesis at certain regions of hippocampus. 

when I suggest someone to try 5-HTP, quickly he/she becomes reactive like "why!? im not depressed! i dont want to kill myself"...

 

this behavior of close-mindedness and illusion of knowing everything after reading some random internet articles is pretty boring.

 

Op has came here to get some opinions and answers to his problems hence he tries to reject everyone and push his own thoughts in our mouth as an answer.

he obviously hasnt responded to anything Dopaminergic, but he still rejects anything unrelated.

is this your optimistic behavior? really?

 

 

 

 

Confident & Optimistic? it isn't that simple!


Also, if you have low Dopamine you'd not have strong sexual drive.

Usually low Serotonin circulation causes: High Acetylcholine, Constipation, Strong sexual drive, High risk taking, Insomnia and Low motivation.
and high Acetylcholine symptoms are usually: Muscle weakness, Tiredness, Agitation associated with Dysphoria, Intelligent but Poor Common sense, Anhedonia or Blunt emotions, Itching and Low Heart-rate.
Low Serotonin (Low Inhibitory) and High Acetylcholine (High Inhibitory) might cause intolerance for Stimulants and Cholinergics (I am not 100% sure about this, personal assumption!)

anyway, I still suggesting 5-HTP at least for 4 weeks and see what happens.

Today afternoon, I took 100mg 5-HTP, 1 and a half hour after that I had goosebumps to almost every song I listened too. I usually do not have goosebumps easily like that. What does this mean?

Sounds like it reversed a long standing anhedonia.

 

 

I don't think so. 3 hours after taking 100mg 5-HTP, my mood went down, I felt sad, I talked to my girlfriend and cried without clear reasons, I just felt sad.

 

12h07 pm: 150mg Bupropion

5h13 pm: 100mg 5-htp

7h: have goosebumps easily when listening to music

9h mood went down dramatically, felt sad for no reasons, cried easily. It was definitely because of the 5-htp.

 

Individuals with social phobia have too much serotonin -- not too little

Edited by tronatula2, 19 September 2016 - 04:29 PM.

[gamesguru]

Try it with no 5htp. Stay away from serotonergics and cholinergics. Try one of the DRIs above, and something as simple as wheat can inhibit the conversion to NE. Watch out for symptoms of high dopamine tho