23 replies to this topic

[synkyr]

So after a couple weeks of reading up on nootropics, I decided to delve into experimenting with what seemed to me to be one of the least harmful of these substances. I decided to try CDP Choline and I tried doses between 200 and 250 mg per day for about a week.

 

At the beginning of the week I alternated days (one day on one day off) but towards the middle / end of the week I took 250 mg every day to see if it had a cumulative effect. I noticed a slight sense of euphoria and mild energy boost and I also noticed that towards the end of the day I felt spaced out. I also began to notice jaw tension and muscle soreness that felt quite unusual so I stopped taking it and later saw these to be possible indicators of choline dominance.

 

About a week after I quit taking CDP Choline, I began to notice memory issues and these accumulated until I experienced a nearly complete loss of my working memory in addition to a crushing depression that left me trapped in suicidal thoughts. I imagine what I felt was similar to what it's like after you have a stroke. My mind hardly functioned and I had no motivation for anything.

 

It has almost about a month since this began and though my mood is slightly elevated, my mind hardly functions at all which is proving to be very problematic in my work and personal life. I feel trapped in this brain fog. I also feel a general sense of numbness to everything but I'm trying to maintain hopefulness and take care of my life the best I can.

 

I have experimented with taking doses of between 100 and 250 mg of Phenylpiracetam and 750 mg of Aniracetam upon recommendation from others who experienced Choline depression / brain fog and it has slightly helped but after taking several doses of each, I am still stuck in this predicament and am hesitant to add more drugs to my brain…

 

One last note is that I have begun to take L-Tyrosine and Tryptophan as I heard that Acetylcholine has an inverse relationship with levels of dopamine and serotonin and this seems to help some too. 

 

Any advice / recommendations and welcome and thank you for reading this...

 

 

Edited by synkyr, 15 September 2015 - 02:17 PM.

[gamesguru]

We (some of us) think acetylcholine and dopamine are antagonists, but we have little proof.^{[1], [courtesy of MrHappy]}

Tyrosine and tryptophan will only help short-term.  Both will eventually lead to desensitization (specifically of receptors and enzymes, eg D2, TH), and tyrosine in particular will, given time, increase dopaminergic oxdiation.

And if tyro/trypto don't help in the short-term (like within hours or days), your issue could be more akin to racetam-induced choline depletion.  Besides...people with depression and ADD don't get much relief from 5-HTP or tyrosine, respectively.  A lot of people think these precursours will resolve imbalances the way adderall or SSRIs do, but experience proves them wrong.

 

Even if they "seem to help some", you can probably get more (sustainable) help from things like, cardio, green tea extract, ginkgo, bacopa, ginseng, saffron, st. johns, magnesium/chromium/lithium, flax/fish, and high ORAC foods

As for the potential choline depletion, I recommend eggs (preferably backyard eggs/vital farms/alfresco/similar pasture-raised), which contain per egg ~100mg choline,  2-3mg phosphatidylcholine (which never hurts)

 

I understand you've had this brain fog for almost a month now, but stop juggling racetams & monoamine precursors, and do something more predictable and sustainable long-term, give that another 2-3 months and see if you don't feel better.  If no improvement by that point, it's probably due to depression, perhaps atypical, dysthmic, or bipolar.

 

Edit:  If you look back in the original 2012 thread, I posted this study. 

Nicotinic acetylcholine receptors as targets for antidepressants

In support of this hypothesis, preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. If this hypothesis is supported by further preclinical and clinical research, nicotinic acetylcholine receptor antagonists may represent a novel class of therapeutic agents for treating mood disorders.

 

Keep in mind 2-AG and anandamide are released during exercise, permeate the BBB, and noncompetitively antagonize and upregulate α7 and α4β2^[2] respectively, which are implicated in mood and cognition:

Exercise also increases the levels of endocannabinoids, the brain's natural cannabis-like molecules, in the bloodstream. Unlike beta-endorphin, which cannot readily pass the blood-brain barrier, endocannabinoids easily move throughout the body. Thus exercise-induced increases in endocannabinoid levels in blood are presumably mirrored in the brain and could also contribute to the euphoria of runner's high.

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

findings suggest that an impairment of the cholinergic α4β2 nicotinic acetylcholine receptor system with the greater amount of amyloid deposition in the system plays an important role in the pathophysiology of Alzheimer's disease.

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

Nicotinic α7 receptors have been shown in a variety of studies with animal models to play important roles in diverse components of cognitive function, including learning, memory and attention. Mice with α7 receptor knockouts show impairments in memory. Selective α7 agonists significantly improve learning, memory and attention. α7 receptors in limbic structures such as the hippocampus and amygdala have been demonstrated to play critical roles in memory. Blockade of α7 receptors in these areas cause memory impairments. In the brains of people with schizophrenia α7 receptors are impaired. This may be related to pronounced cognitive impairments seen with schizophrenia. There has been a major effort to develop α7 nicotinic agonists for helping to reverse cognitive impairment. These receptors are a promising target for development of therapeutic treatments for a variety of diseases of cognitive impairment including Alzheimer's disease, attention deficit hyperactivity disorder (ADHD) and schizophrenia.

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

[α7] binding was significantly increased in the CA1 and perirhinal cortex of patients with bipolar disorder compared to control subjects, whereas in patients with schizophrenia or major depressive disorder the level of binding did not significantly differ from control subjects in any region measured.
These data are consistent with the reported genetic associations linking the α7 nAChR to the pathology of bipolar disorder, and may suggest a dysfunction of α7 nAChR-dependent signalling in bipolar disorder. We could not reproduce the previously reported decrease in hippocampal bungarotoxin binding in schizophrenia.

Edited by gamesguru, 15 September 2015 - 02:59 PM.

[Baten]

Tyrosine and tryptophan will only help short-term.  Both will eventually lead to desensitization (specifically of receptors and enzymes, eg D2, TH), and tyrosine in particular will, given time, increase dopaminergic oxdiation.

 

I've been wondering about this, but isn't there plenty of tyrosine in food as well? I had ordered a thyroid supplement (Now's) with 1000mg tyrosine, and since reading that it could lead to desensitization/downregulation I've been wary of actually taking it. I was thinking that perhaps half the recommended dose (containing 500mg of tyrosine) would perhaps be okay? Taking it only once or twice a week? Or I could just thrash the supplement because of the tyrosine... what do you think gamesguru? Thanks for your many detailed posts btw.

[gamesguru]

Americans average 2.5g tyrosine daily.  I suppose 500-1000mg could be supplemented (espcially just 1-2x weekly) to no noticeable detriment, but it may also not produce much desired effect at that dose.  Most people take 2-6g daily, some more.   So it's like doubling or tripling dietary intake.

 

Not sure the oxidation is even a big concern at 6gs^{[1], [2], [3], [4], [5]}, but I would err on the side of caution, and certainly at that daily dosage, tolerance will occur.  Dopamine adjusts itself to everything by changing nothing.

let's just say if i someone was forcing me to take 10g tyrosine, I would want to take it alongside high ORAC things, specifically ones with efficacy in dopaminergic pathways., like selenium^[6], blueberries, green tea extract.

 

There are other (perhaps more sustainable) ways to increase DA activity, taken from the thread "raise dopamine without increasing adrenergic":

• noradrenaline is anxiogenic, not always cognitive as dopamine
• problem is dopamine is convereted to noradrenaline by dopamine-Beta-hydroxylase esp in mPFC, and this has undesirable effects.
• in that thread Area-1255 explains an inhibitor of dopamine-Beta-hydroxylase (he mentions st. johns, I add ginseng^[7]) may be useful
• he also gives reasons why D1 activation would raise noradrenaline, and D2 would lower it (w/o affecting DA)
• as if that's not overwhelming enough, he also recommends H1 regulators and 5-HT7 antagonists

Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms

• 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.

Mucuna^[1]

Rhodiola (MAO-B)

 

Inducers of PH (phenylalanine hydroxylase):

Lamiaceae^[1]

Simple diet^[2]

Exercise^[3]

Iron^[4]

High ORAC foods^[5]

 

Inducers of TH (tyrosine hydroxylase):

Horny goat weed^[1]

Lithium

Ginkgo

Bacopa^[2]

Green tea^[3]

 

Upregulators of receptors (dopamine):

Caffeine^[1]

Bacopa^[2]

Exercise^[3]

 

Edited by gamesguru, 16 September 2015 - 02:42 PM.

[synkyr]

Thanks for the informative replies gamesguru. Does anyone else have any helpful information? I'm having a really difficult time with this situation and would appreciate if anyone else had any advice or had gone through something similar. 

 

Thank you.

[Area-1255]

 

 

• noradrenaline is anxiogenic, not always cognitive as dopamine
• problem is dopamine is convereted to noradrenaline by dopamine-Beta-hydroxylase esp in mPFC, and this has undesirable effects.
• in that thread Area-1255 explains an inhibitor of dopamine-Beta-hydroxylase (he mentions st. johns, I add ginseng^[7]) may be useful
• he also gives reasons why D1 activation would raise noradrenaline, and D2 would lower it (w/o affecting DA)
• as if that's not overwhelming enough, he also recommends H1 reglators and 5-HT7 antagonists

 

 

Yeah, btw GG; don't think that I am intentionally trying to pick on you or correct you for anything; you've done a really good job and in many instances; you have pointed out things that I should have outlined or have permitted me to enthuse the rest of the synopsis.

One more thing, D1 activation certainly can raise neural norepinephrine but it also can increase GABA in some brain regions..so perhaps it can have it's benefits in coordination with other GABAergic activators but depending on NET (Norepinephrine Transporter Activity), among other factors.

 

Effects of AMPA and D1 receptor activation on striatal and nigral GABA efflux.
Byrnes EM1, Reilly A, Bruno JP.

Author information

 

Abstract

The ability of locally-administered AMPA and D1 receptor ligands to modulate in vivo striatal and nigral GABA efflux was determined in awake, intact male rats using a dual-probe microdialysis technique. Intrastriatal perfusion of AMPA (100 microM) produced a 50-100% increase in striatal GABA efflux that was totally blocked by co-perfusion with TTX (10.0 microM). This AMPA-stimulated, TTX-sensitive GABA efflux was similar across repeated dialsysis perfusions. The effects of intrastriatal perfusion of the full D1-like agonist SKF 81297 were complex. Perfusion of the higher dose (100 microM) of SKF 81297 enhanced GABA efflux, whereas perfusion of the lower dose (10 microM) decreased GABA efflux. Both of these effects were blocked by co-perfusion with the D1-like antagonist SCH 23390 (10 microM). Intrastriatal perfusion of AMPA (100 microM), SKF 81297 (100 microM), or AMPA + SKF 81297 did not stimulate GABA efflux in the substantia nigra. These bidirectional effects of D1 agonists and the apparent dissociation, under certain conditions, between striatal and nigral GABA efflux highlight the complexities of DA- and Glu-modulated striatonigral activity in situ.

 

 

 

  [PubMed - indexed for MEDLINE]

 

 

 

Neuroscience. 2002;115(3):743-51.

Adenosine A1 receptors control dopamine D1-dependent [(3)H]GABA release in slices of substantia nigra pars reticulata and motor behavior in the rat.

Florán B1, Barajas C, Florán L, Erlij D, Aceves J.

Author information

 

Abstract

Abnormalities in dopaminergic control of basal ganglia function play a key role in Parkinson's disease. Adenosine appears to modulate the dopaminergic control in striatum, where an inhibitory interaction between adenosine and dopamine receptors has been demonstrated. However the interaction has not been established in substantia nigra pars reticulata (SNr) where density of both receptors is high. Here we have explored the interaction between A1/D1 receptors in SNr. In SNr slices, SKF 38393, a selective D1 receptor agonist, produced a stimulation of depolarization-induced Ca(2+)-dependent [(3)H]GABA release that was inhibited by adenosine. The adenosine inhibition was abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist. DPCPX per se enhanced GABA release, indicating inhibition of the release by endogenous adenosine. When D1 receptors were blocked with SCH 23390 or the slices were depleted of dopamine, the effect of DPCPX was suppressed, showing that activation of dopamine receptors was necessary for the adenosine inhibition. In normal slices, 2-chloro-n(6)-cyclopentyladenosine (CCPA), a selective A1 agonist, inhibited GABA release, but the inhibition was prevented by the blockade of D1 receptors with SCH 23390. Superperfusion with 8-bromo-cAMP produced a stimulation of GABA release that was not blocked by CCPA: this finding indicates that the blockade of D1 effects caused by activation of A1 receptors is specific. To see if these actions on GABA release were correlated with changes in motor behavior we studied the effect of unilateral intranigral injections of modifiers of adenosine A1 and dopamine D1 receptors in rats challenged with systemic methamphetamine. Both the A1 agonist CCPA and the D1 antagonist SCH 23390 produced ipsilateral turning whereas the A1 antagonist DPCPX caused contralateral turning. These motor effects are consistent with the findings on GABA release. The results indicate the presence of an inhibitory A1/D1 receptor interaction in SNr. The inhibition exerted by A1 adenosine receptors on GABAergic striatonigral transmission would be due exclusively to blockade of the facilitation resulting from activation of D1 dopamine receptors. The data permit to better understand the action of adenosine antagonists in the treatment of Parkinson's disease.

PMID:   12435413  

 

 

 

 

Neuroscience. 1997 Sep;80(1):241-9.

Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata.

Garcia M1, Floran B, Arias-Montaño JA, Young JM, Aceves J.

Author information

 

Abstract

The release of [3H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K+ from 6 to 15 mM in the presence of 10 microM sulpiride was inhibited by 73 +/- 3% by 1 microM SCH 23390, consistent with a large component of release dependent upon D1 receptor activation. The histamine H3 receptor-selective agonist immepip (1 microM) and the non-selective agonist histamine (100 microM) inhibited [3H]GABA release by 78 +/- 2 and 80 +/- 2%, respectively. The inhibition by both agonists was reversed by the H3 receptor antagonist thioperamide (1 microM). However, in the presence of 1 microM SCH 23390 depolarization-induced release of [3H]GABA was not significantly decreased by 1 microM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [3H]GABA, but in the presence of 1 microM SKF 38393, which produced a 7 +/- 1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 microM) also inhibited the depolarization-induced release of [3H]dopamine from substantia nigra pars reticulata slices, by 38 +/- 3%. The evidence is consistent with the proposition that activation of histamine H3 receptors leads to the selective inhibition of the component of depolarization-induced [3H]GABA release in substantia nigra pars reticulata slices which is dependent upon D1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [3H]dopamine release.

PMID:   9252235   [PubMed - indexed for MEDLINE]

 

Edited by Area-1255, 19 September 2015 - 04:08 AM.

[Area-1255]

My overall feeling of acetylcholine is that you want a good amount of it to feel balanced, but excessive amounts seem to have two main issues.

 

1.) Can release too much ACTH.

2.) Can distort, over-inhibit or otherwise mess with sympathetic nervous system activity...

 

OP - my guess is you probably have too much M1 activation. Read the LAST link carefully. 

 

Stimulation of nicotinic acetylcholine receptors seems to be involved with the anxiety-provoking effects of acetylcholine; this is consistent with the nicotine research and on the anti-depressants and novel anti-anxiety agents that are specific nicotinic antagonists...but also, overstimulation of nicotinic receptors seems to lead to serotonin accumulation which subsequently creates a lessening of dopaminergic impulses...so my feeling is that if you are feeling ANXIOUS from acetylcholine boosting it is most likely coming from nicotinic activation...in which case you could look into nicotinic antagonists if you feel you HAVE to raise your acetylcholine levels...muscarinic receptors on the other hand are opposite (in most cases) to nicotinic receptors and tend to be ANTI-SYMPATHETIC aka lowering heart rate and adrenaline release..however, on average, muscarinic receptors are the ones we want to core intellectual and creative function as well as maintaining normal blood pressure and such...lack of muscarinic activity typically leads to very high heart rate, oxygen delivery issues and high blood pressure, among other things including psychological issues that may manifest. 

 

Activation of the α7 nicotinic ACh receptor induces anxiogenic effects in rats which is blocked by a 5-HT1a receptor antagonist

M₂ and M₄ Receptor Knockout Mice: Muscarinic Receptor Function in Cardiac and Smooth Muscle In Vitro

 

Selectivity of muscarinic antagonists in radioligand and in vivo experiments for the putative M1, M2 and M3 receptors.

Nucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local M1 antagonist in the Porsolt swim test.

Edited by Area-1255, 19 September 2015 - 04:21 AM.

[gamesguru]

don't think that I am intentionally trying to pick on you or correct you for anything; you've done a really good job and in many instances; you have pointed out things that I should have outlined or have permitted me to enthuse the rest of the synopsis.

One more thing...

 

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[Area-1255]

Nice swords, if I didn't know any better  I'd say this is renaissance imagery.   

 

don't think that I am intentionally trying to pick on you or correct you for anything; you've done a really good job and in many instances; you have pointed out things that I should have outlined or have permitted me to enthuse the rest of the synopsis.

One more thing...

 

 

 

[gamesguru]

Nice swords, if I didn't know any better  I'd say this is renaissance imagery.   

 

I'll stick a sword in you, Socrates.  jk, jk!!

[Area-1255]

 

Nice swords, if I didn't know any better  I'd say this is renaissance imagery.   

 

I'll stick a sword in you, Socrates.  jk, jk!!

 

You can't impale the King of Roman's my friend. 

[gamesguru]

I'll stick a sword in you, Socrates.  jk, jk!!

You can't impale the King of Romans my friend. 

 

we'll see about that, you manlet

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Edited by gamesguru, 02 October 2015 - 09:19 PM.

[Area-1255]

What's wrong with you today bro, you need a hug or something? 

 

I'll stick a sword in you, Socrates.  jk, jk!!

You can't impale the King of Romans my friend. 

 

we'll see about that, you manlet

 

 

[gamesguru]

What's wrong with you today bro, you need a hug or something? 

 

Only if it leads to something more...

[Area-1255]

 

What's wrong with you today bro, you need a hug or something? 

 

Only if it leads to something more...

 

Something more? Like free meth crystals? Or do you want me to put a hoe in a helicopter and drop her down into your chimney wrapped in plastic!? lol  

[gamesguru]

Both plz free, and make it a virgin hoe... also smart, sexy, nice, funny, and without relatives or friends who could notice her disappearance.

[Area-1255]

Both plz free, and make it a virgin hoe... also smart, sexy, nice, funny, and without relatives or friends who could notice her disappearance.

A Virgin hoe? Now that's a new one. 

Maybe flying to Alaska to find a half-eaten Penguin would be easier. 

As far as the other stuff...I'm pretty sure you could find an escort who would meet those requirements. 

[synkyr]

hey all. I appreciate a good humorous exchange like most other people, but I was hoping to use this thread to help alleviate my symptoms and help make my life one that is well worth living once again. so on that note, I am going to hijack this thread with a question specifically for area (though all answers are welcome).

 

Area: you said in another thread in which the OP claimed Alpha GPC gave him hypothyroidism that: 

 

"Excess acetylcholine would be very noticeable...you would feel lethargic, have restless legs type symptoms - dysphoric/anhedonic, and you would probably be terrible pessismistic and have some social anxiety."

 

I was curious if you had any studies that mention these symptoms as they seem to perfectly describe my state of being especially the anhedonia, lethargy, and most recently the restless legs (and arms / head / face). Or if not how you arrived at the correlation between excess acetylcholine and these symptoms.

[Area-1255]

hey all. I appreciate a good humorous exchange like most other people, but I was hoping to use this thread to help alleviate my symptoms and help make my life one that is well worth living once again. so on that note, I am going to hijack this thread with a question specifically for area (though all answers are welcome).

 

Area: you said in another thread in which the OP claimed Alpha GPC gave him hypothyroidism that: 

 

"Excess acetylcholine would be very noticeable...you would feel lethargic, have restless legs type symptoms - dysphoric/anhedonic, and you would probably be terrible pessismistic and have some social anxiety."

 

I was curious if you had any studies that mention these symptoms as they seem to perfectly describe my state of being especially the anhedonia, lethargy, and most recently the restless legs (and arms / head / face). Or if not how you arrived at the correlation between excess acetylcholine and these symptoms.

Another big symptom of high acetylcholine would be persistent nausea. (as further reinforced by the AD drug Donepezil and it's frequent side-effect of nausea) http://www.drugs.com.../donepezil.html

But yes... I have studies...always!   

Potential Root Cause of Depression Discovered by NARSAD Grantee

Neuronal nicotinic acetylcholine receptor α4 subunit (CHRNA4) and panic disorder: An association study

 

Treatment of Social Phobia With Gabapentin: A Placebo-Controlled Study

 

 Another thing , and perhaps more importantly than the above..is that Acetylcholine (ACh) is only going to cause issues in VERY HIGH amounts; which differs for everyone and since these  NT thresholds are partially genetic..it's difficult to say FOR SURE whether your issue is high ACh; a lot things can mimic high ACh ; and it could be just a general deficiency in dopamine and / or other hormones/NTs like NORADRENALINE.

 

Finally  Acetylcholine in normal, moderate amounts can actually decrease anxiety and helps curb excessive adrenaline activity .

 

However, it depends on whether your nicotinic receptors or muscarinics are more activated.

Endogenous Acetylcholine in the Dorsal Hippocampus Reduces Anxiety Through Actions on Nicotinic and Muscarinic i Receptors

Edited by Area-1255, 03 October 2015 - 11:41 PM.

[gamesguru]

"Excess acetylcholine would be very noticeable...you would feel lethargic, have restless legs type symptoms - dysphoric/anhedonic, and you would probably be terrible pessismistic and have some social anxiety."

 

I was curious if you had any studies that mention these symptoms as they seem to perfectly describe my state of being especially the anhedonia, lethargy, and most recently the restless legs (and arms / head / face). Or if not how you arrived at the correlation between excess acetylcholine and these symptoms.

 

One way would be to take galantamine or huperzine and see whether symptoms worsen.  Bacopa is cholinergic and causes me subclincal RLS, but I'm thinking this is a T4 issue^{[1], [2]}. 

It sometimes negatively affects sleep quality, but never improves or worsens nightly bruxism or hyperactivity.

Rivastigmine-Induced REM Sleep Behavior Disorder (RBD) in a 88-Year-Old Man with Alzheimer's Disease

We report the case of an 88-year-old man with Alzheimer's disease (AD) of 8 years duration (emerging shortly after the de novo onset of sleeptalking) who developed REM sleep behavior disorder (RBD) after increasing the nightly dose of rivastigmine, an acetylcholinesterase inhibitor, from 1.5 mg to 3 mg (total daily dose, 4.5 mg), as therapy for his dementia. His family then became aware of recurrent nocturnal episodes arising from sleep of his leaving bed, and he sustained multiple abrasion injuries from falling down. Polysomnography (PSG), utilizing a seizure montage with fast paper speed, conducted with the patient taking rivastigmine 3 mg at bedtime, documented 3 abrupt episodes of bilateral arm-waving with moaning and shouting that emerged exclusively during each of the 3 REM sleep periods, with the duration of the episodes lasting 8 to 25 seconds. No epileptiform discharge appeared with the onset of these REM sleep behaviors. Therapy with clonazepam, 0.5 mg at bedtime (with ongoing 3 mg bedtime and 4.5 mg total daily rivastigmine therapy), fully suppressed the sleep-related events, with prompt relapse whenever clonazepam was not taken. This is the second reported case (both males with AD) of rivastigmine-induced RBD, and the oldest reported case of RBD; and it represents reversible, medication-induced, acute RBD.

of  ^[2]:        77. Carlander B, Touchon J, Ondze B, Billiard M. REM sleep behavior disorder induced by cholinergic treatment in Alzheimer's disease. J Sleep Res. 1996;5(Supplement 1):28.

 

 

Vivid dreams, and more.  But bacopa affects other neurotransmitter systems, and this list is very like an umbrella or blanket... so who's to say these are cholinergic side effects?

Symptoms of High Acetylcholine

 

Subdued or depressed mood

Anhedonia (inability to experience pleasure)

Difficulty concentrating

Difficulty with higher-order or complex thought processes

Mental fatigue

Mental confusion

Memory problems

Decreased motivation

Feeling overly sleepy or tired (particularly in the evening), despite adequate sleep and rest

Difficulty understanding or performing tasks

Pessimistic, negative ideation or rumination

Feelings of helplessnes and hopelessness

Fretfulness

Irritability or anger

Emotional heightening and lability

Sadness, tearfulness

Blurred vision

Headache

Dry mouth

Altered sense of smell; heighted sensitivity to odors; olfactory delusions

Stomach pain or discomfort

Intestinal gas or bloating

Diarrhea or constipation

Nausea, dizziness, and vomiting

Muscle pain or discomfort

Joint pain, discomfort, or swelling

Tooth or jaw pain or discomfort

Tingling or numbness in arms or legs

Muscle weakness

Increased urinary frequency or problems with bladder control

Flu or cold-like symptoms

Weakening of immune system and increased susceptibility to illness

Cough

Nasal discharge

Chills or sensation of cold

Cold feet, hands

Sleep disturbance

Introversion

Anxiety

More and vivid dreaming, and higher incidence of nightmares

Decreased levels in the brain of the neurotransmitters, serotonin, norepinephrine,  and dopamine

Interference with the release of the above brain transmitters, because of higher inhibition

Note: There is an inverse, antagonistic relationship between acetycholine (ACh) and serotonin (SE) in the brain. In other words as the quantity of one increases, the quantity of the other decreases. A certain amount of ACh is necessary for normal, optimal brain function. Memory, motivation, higher-order thought processes, sexual desire and activity, and sleep (among other things) depend on ACh. In lower amounts, ACh can act like a stimulant by releasing norepinephrine (NE) and dopamine (DA).  However, those brain chemicals are used up (depleted) in the process; and a deficiency can occur. Too much ACh relative to other brain chemicals such as SE, NE, and DA has an adverse effect on brain function. This is because in larger quantities ACh acts like an inhibitory neurotransmitter, causing increased nervous system inhibition (depression). Important to remember is that, in general, as ACh levels go up in the brain, the levels of the other brain transmitters go down.

In terms of mood, the combination of higher ACh and NE, together with lower SE, produces anxiety, emotional lability, irritability, anger, aggressiveness, negative rumination, impatience, and impulsiveness (among other things). When NE, DA, and SE are low and acetylcholine is high, the result is simply depression. SSRI antidepressants, by increasing serotonin, are able to lower acetylcholine levels, thereby lessening or eliminating the symptoms associated with high acetylcholine. However, the major drawback is that increasing serotonin also leads to a reduction of norepinephrine and dopamine in the brain. Therefore, long-term use of SSRI antidepressants will result in a high serotonin condition, which is actually another type of depression (see separate article on this site about serotonin). So, in spite of all of the publicity and common usage, SSRI antidepressants are really not the best choice (at least, not in the long run) for treating depression. Unless the problem of low NE and DA is also addressed, a high acetylcholine depression, in time, will merely be replaced by a high serotonin depression. This explains why SSRI antidepressants do not help everyone, lose their effectiveness over time, make some people more depressed, or cause intolerable side effects.

Generally, ACh levels in the brain will increase proportionately to the amount of choline in the diet. However, ACh levels will also become higher for other reasons. Whenever there is interference with the release of the other neurotransmitters, or their levels have fallen, ACh levels will automatically increase. This is due to the balancing effect between all of the brain transmitters, whereby a decrease in one resuts in a relative increase in the other.

Foods that significantly increase ACh: eggs, fish, soybean products, foods (wide variety) containing lecithin, wheat germ.
Supplements that significantly increase ACh: choline, lecithin, fish oil, flaxseed oil, other.
Other things that increase acetylcholine: MSG (monosodium glutamate), medications, chemicals, physical activity (exercise, work).

Note that some people are more sensitive to choline and, therefore, will experience greater problems than usual with the consumption of the above foods and supplements.  Also, reaction to choline may be age-dependent, with older people generally experiencing more sensitivity.

For more information, see:

http://www.acnp.org/...1000095/CH.html

http://www.yalescien...-of-depression/

[synkyr]

cool. and gamesguru, I have seen that list before and identified with most of the symptoms on it but I was not sure where that list had been compiled from as the accompanying links did not seem to comprehensively cover these symptoms. I believe that I had low dopamine to start with, which was part of the reason I foolishly took CDP Choline since it is supposed to raise D2 receptor density. However, I believe I further skewed this imbalance and was probably high in ACH to begin with (based on tests such as Braverman's, etc). So if this is the case I figure I should try to raise depleted dopamine levels in a sustainable fashion and/or lower acetylcholine. I would be interested what your suggestions would be to achieve this task. Area, I had seen you recommend mucuna before, which was somewhat surprising to me as many on here do not condone that herb due to fear of downregulation. What do you think of using mucuna pruriens to restore depleted dopamine in regards to possible downregulation, cycling, etc.? 

 

thanks again for taking time to answer my posts everyone.

[gamesguru]

CDP-choline is decomposed in the brain to choline + cytidine.  The cytidine is then metabolized to uridine, which itself induces a dopamine release^[1] (hyperdopaminergic) and a downregulation of D2/D3.

If CDP made you worse, and this worsening was due to dopamine alteration, then precisely what is wanted is a reduction of dopamine release to baseline, with an accompanying upregulation of D2/D3 to baseline. 

 

Dopaminergic effects of caffeine in the human striatum and thalamus.
Epidemiological studies have provided evidence that caffeine, an adenosine receptor antagonist, reduces the risk for Parkinson's disease. There are indications of specific interactions between striatal adenosine A(2A) and dopamine D(2) receptors, but the in vivo effects of caffeine on human dopamine system have not been investigated. In the present study, the dopaminergic effects of caffeine were examined with [(11)C]raclopride positron emission tomography (PET) in eight healthy habitual coffee drinkers after 24 h caffeine abstinence. Compared to oral placebo, 200 mg oral caffeine induced a 12% decrease in midline thalamic binding potential (p < 0.001). A trend-level increase in ventral striatal [(11)C]raclopride binding potential was seen with a correlation between caffeine-related arousal and putaminal dopamine D(2) receptor binding (r = -0.81, p = 0.03). The findings indicate that caffeine has effects on dopaminergic neurotransmission in the human brain, which may be differential in the striatum and the thalamus.

 

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A_2A receptors (A_2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [¹¹C]raclopride (DA D₂/D₃ receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D₂/D₃ receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D₂/D₃ receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D₂/D₃ receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D₂/D₃ receptor availability. Instead, we interpret our findings to reflect an increase in D₂/D₃ receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D₂/D₃ receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D₂/D₃ receptors.

 

 

 

as for the list, I'm also not sure of its authenticity or its sources, am putting lots of trust in the author... like i said it looks like a blanket or umbrella list.

 

i would recommend tea over coffee, on account of its theanine and polyphenols, see my profile for links to some sublime Japanese cultivars

 

 

Attached Files

•  theanine.jpg   39.82KB   3 downloads

Edited by gamesguru, 07 October 2015 - 03:22 AM.

[synkyr]

Interesting. I have also read that AcH and Dopamine inhibit one another in the nigrostriatal pathway, hence why anticholinergics are given to some patients who take drugs that block D2 receptors. I know that some contend this science as is mentioned up above but I was curious if you would entertain the alternative hypothesis that my dopaminergic troubles are due to excess AcH activity and a deficiency of Dopamine. More recently I have developed muscle fasiculation and tingling especially in my feet but also in other parts of my body and I was wondering if these could be correlated with improper AcH levels. Especially the muscle twitching.

[Area-1255]

Interesting. I have also read that AcH and Dopamine inhibit one another in the nigrostriatal pathway, hence why anticholinergics are given to some patients who take drugs that block D2 receptors. I know that some contend this science as is mentioned up above but I was curious if you would entertain the alternative hypothesis that my dopaminergic troubles are due to excess AcH activity and a deficiency of Dopamine. More recently I have developed muscle fasiculation and tingling especially in my feet but also in other parts of my body and I was wondering if these could be correlated with improper AcH levels. Especially the muscle twitching.

It's pathway dependent; but generally the above is true. Dopamine increases paraventrical/hypothalamic ACh levels by D2S/D2L activation; but may decrease ACh in the striatum to an extent...the Ventral Tegmental Area has some interactions and co-lozalizations between dopamine D1 and muscarinic receptors as well histamine H1/H3R.

 

http://onlinelibrary...200202/abstract

http://www.ncbi.nlm....pubmed/15289006