383 replies to this topic

[Adaptogen]

that is odd, i always figured there was no downside to ginger

[Galaxyshock]

I've been taking peppermint oil & ginger to treat IBS successfully can't say it would have had negative effect.

I'm getting my packet tomorrow and will be experimenting with Cordyceps to see if it really does help. I will also have some other adaptogens, CDP-choline and the CILTEP-supplements to try or add later. Craze, a potent pre-workout supplement discussed for several pages in other thread "Pre-workout stimulant as nootropic", did definitely have some real effects for anhedonia and significant cognitive boost in my case. But I don't want to rely on stimulants at least not yet.

[Adaptogen]

sometimes at wholefoods i will stuff my pocket with a piece of their overpriced organic ginger. i figure it is okay because it is wholefoods.

i have noticed a stimulating and moodlifting effect from this, as well as from eating the stolen ginger. i shall investigate further

[magniloquentc0unt]

"The secret ingredient is crime" cit. hans from peep show

[magniloquentc0unt]

(this btw)

[kevinseven11]

Did i say ginger sorry i meant ginseng. No one read the study?

[Dissolvedissolve]

Did i say ginger sorry i meant ginseng. No one read the study?

I looked at the article you posted titled "Hypnotic Effects and Binding Affinities..."

It seems ginseng binds to 5-HT2c, although it's not exactly clear to me without further reading whether it's agonistic or antagonistic. If it's 5-HT2c agonism, that would likely be counterproductive. If it's antagonistic, that may be beneficial.

From galaxyshock's studies, it seems that ginseng has dopamine modulatory properties, inhibiting a decrease in receptor density with methamphetamine administration.That's certainly promising, and I'll definitely be try it. Another supposed dopamine modulator, uridine monophosphate, did nothing for me, so I'm not particularly optimistic, but ginseng is readily available and cheap, so it's worth a try.

Also, it seems you also posted about silk tree? But according to that study it's a GABA agonist and hypnotic, increasing length of sleep, which is counterproductive in anhedonia. Anyway, at least in my case, I tend to sleep too much rather than too little, and I would associate insufficient sleep with anxiety disorders rather than anhedonia.

Edited by Dissolvedissolve, 19 December 2012 - 08:04 PM.

[kevinseven11]

Gaba agonists release dopamine, but silk tree also binds to 5ht2c also so hopefully it is antagonistic.

[Dissolvedissolve]

I know GABA-B agonism triggers DA release. I am not sure if that is the case for GABA-A - I do not believe so but am not entirely certain. That's the reason why phenibut, a GABA-B agonist, may be able to temporarily abolish anhedonia via indirect release of dopamine. Phenibut is obviously very habit-forming and I'm not recommending, just saying that there's little utility for GABA-A agonism in treating anhedonia. Anecdotally, I've certainly never heard of benzos (GABA-A positve allosteric modifiers, so essentially agonists) being helpful for anticipatory anhedonia, and I anecdotally don't find alcohol to be helpful (another GABA-A PAM).

5-HT2c antagonism could, perhaps, be beneficial, but that study is unfortunately unclear.

Edited by Dissolvedissolve, 19 December 2012 - 09:04 PM.

[Adaptogen]

http://www.youtube.com/watch?v=_8mFdey7Pbo (this btw)

haha exactly! all im lacking is the accent

[Dissolvedissolve]

Midbrain DA neurons exhibit two distinct modes of firing, referred to as “tonic” and “phasic” (Grace andBunney,1984). Tonic DA activity refers to steady-state firing generated by intrinsic pacemaker-like characteristics of DA neurons. Phasic activity—also known as “burst firing”—involves a rapid series of action potentials that induce a rapid rise in extracellular DA at terminal projection targets. Recent evidence suggests that this intracellular pathway can result in increased responsiveness of MSNs to sustained release of glutamate, generating “up-states” (Surmeier etal.,2007). In contrast, D2-like receptor binding results in decreased AC activity, thereby reducing the responsiveness of MSNs (“downstates”)(Hernandez-Lopez 453 et al.,2000). Of note, due to their higher affinity for DA as well as their more centralized location on the post-synaptic membrane, D2-like receptors are often stimulated by tonic levels of DA release, whereas D1-like receptors are stimulated primarily during phasic DA release (Goto etal.,2007).

→ source (external link)

Thanks to magniloquentcunt for linking to the thread on depressionforums, which I read through and pulled that from.

So apparently it's phasic dopamine that's associated with anticipatory pleasure. This explains why dopamine releasers tend to be more effective than reuptake inhibitors - they cause release of (phasic) dopamine rather than just increasing tonic signalling by preventing reuptake.

It is well established that bupropion has little direct effect on 5HT function (Stahl et al., 2004). Several studies exploring bupropion occupancy of DAT at clinical doses have reported occupancy rates ranging from 14% to 26% in the striatum (Kugaya et al., 2003; Learned-Coughlin et al., 2003; Meyer et al., 2002), which are relatively low as compared to standard SERT occupancy rates of SSRIs (80%) or DAT occupancy of reinforcing psychostimulants (>50%) (Volkow et al., 1995, 1997, 1998). These findings suggest that bupropion’s direct ability to increase synaptic DA levels through blockade of DAT may account for only some of its antidepressant effects. However, more recent work has also shown that bupro-
pion increases the activity of the intracellular vesicular monoamine transporter 2 (VMAT2) protein, which may enhance extracellular DA by increasing available DA in presynaptic pools (Rau et al., 2005). Bupropion may also exert regionally specific influence over DA function through its action as an inhibitor of the norepinephrine transporter (NET), which is the primary transporter of DA in prefrontal regions. Finally, more recent work has suggested that bupropion decreases the activity of nicotinic acetylcholine receptors, which play a role in the effects of bupropion on psychomotor symptoms in MDD (see Dwoskin et al., 2006 for a review).

Preclinical studies have suggested that bupropion may be a superior treatment for symptoms of motivational anhedonia. Rats treated with bupropion demonstrate decreased immobility time during the forced swim test and tail suspension tests (Cryan et al., 2001, 2004) and showed greater willingness to work for food rewards during a progressive ratio task (Bruijnzeel and Markou, 2003). Moreover, the influence of bupropion was blocked via administration of both D1-like and D2-like receptor antagonists, suggesting that effects of bupropion were partially mediated through DAergic mechanisms (Paterson and Markou, 2007). Additionally, rats treated with either chronic or acute doses of bupropion show a reduced threshold for intracranial self-stimulation of the posterior lateral hypothalamus (Paterson, 2009;Paterson et al., 2007). Similarly, bupropion enhanced responding to a conditioned reinforcer (Palmatier et al., 2009), although a separate study reported a bupropion-induced decrease in responding for sucrose (Reichel et al., 2008). The latter result is contrary to what would be expected, given the findings of Bruijnzeel and Markou (2003) and highlights the complex effects of the bupropion on reward processing. Interestingly, bupropion-mediated enhancement of conditioned reinforcers in the study by Palmatier et al. was ameliorated by Prazosin, an 2-NE receptor antagonist, suggesting that bupropion’s effects on reinforcement may also rely on noradrenergic mechanisms.

→ source (external link)

So we know that bupropion is not very effective as a DRI - thanks to medievil for mentioning this a while back - but it has other pro-dopamine mechanisms. It's more significant as a norepinephrine releasing agent, and pro-NE effects should help with lethargy symptoms that often accompany anhedonia.

Overall, head-to-head clinical trials between DA-acting agents and other pharmacotherapies have revealed strikingly similar response rates in the case of bupropion and pramipexole, (Chouinard, 1983; Coleman et al., 1999; Corrigan et al., 2000; Croft et al., 1999; Kavoussi et al., 1997; Mendels et al., 1983; Thase et al., 2005; Weihs et al., 2000; Weisler et al., 1994). For psychostimulants, response rates are usually significantly worse than other alternatives (Candy et al., 2008; Orr and Taylor, 2007). However, the potential role of DA-acting drugs as a superior treatment for anhedonic symptoms has received some empirical support. Bupropion has shown to be more effective at treating symptoms related to motivational and consummatory anhedonia (Bodkin et al., 1997; 1308 Tomarken et al., 2004). In a large-sample review of treatment records of 910 patients receiving outpatient pharmacotherapy for depression, Jamerson et al. (2003) reported that patients receiving bupropion sustained release (SR) showed significant improvement of symptoms related to reduced interest, energy and loss of libido as compared to placebo. Additionally, bupropion is often used to counter-act specific side effects of SSRIs (Nutt et al., 2007), which may include reduced responsiveness to rewards and positive experience (McCabe et al., 2009a,b; Price et al., 2009; Shelton and Tomarken, 2001). A recent meta-analysis of DA-acting antidepressant treatments suggests that they enhance overall quality-of-life in individuals with MDD (IsHak et al., 2009). These findings are not only promising in terms of treatment options; they also further underscore the importance of tailoring DA-acting treatments to specific symptoms.

→ source (external link)

So bupropion and pramipexole are both often effective in treating anticipatory anhedonia. According to these authors, stimulants are actually less useful, although there really isn't much research on them because psychiatrists are very hesitant to prescribe them to anyone who does not exhibit ADHD symptoms.

Edited by Dissolvedissolve, 20 December 2012 - 07:34 AM.

[magniloquentc0unt]

does anyone else have the feeling acetylcholine plays a big role in anticipatory anhedonia?

[nupi]

Also, it seems you also posted about silk tree? But according to that study it's a GABA agonist and hypnotic, increasing length of sleep, which is counterproductive in anhedonia. Anyway, at least in my case, I tend to sleep too much rather than too little, and I would associate insufficient sleep with anxiety disorders rather than anhedonia.

The two are not necessarily mutually exlusive, though. So it might be of use to some.

[Dissolvedissolve]

does anyone else have the feeling acetylcholine plays a big role in anticipatory anhedonia?

I've thought that excess cholinergic activity may be an issue, since choline has a tendency to worsen symptoms. Also, choline tends to be antagonistic to dopamine, so in addition to excess serotonin being able to cause reduced dopaminergic signaling, excess acetylcholine could do the same. I'm actually reading an article that discusses the role of acetylcholine in depression right now, so I'll paste in some material. It isn't specific to anhedonia, so feel free to discuss/elaborate if you have any thoughts.

the muscarinic cholinergic system is overactive or hyper-responsive in depression. Janowsky et al. (1994) reported that increasing cholinergic activity using the acetylcholine–esterase inhibitor physostigmine resulted in the rapid induction of depressive symptoms in currently manic bipolar subjects, and in a worsening of symptoms in unipolar depressed patients. In addition, depressed individuals express exaggerated polysomnographic, neuroendocrine and pupillary responses to cholinergic agonists or muscarinic receptor agonists relative to healthy controls (Dilsaver 1986; Janowsky et al. 1985; Janowsky and Overstreet 1995; Rubin et al. 1999; Riemann et al. 1994), and aspects of sleep abnormalities observed in depression, including decreased REM latency and increased REM density (Gillin et al. 1979), are thought to reflect hypersensitivity of muscarinic cholinergic receptors. Taken together, these data contribute to the hypothesis that a hyper-responsive cholinergic system may contribute to mood symptoms associated with mood disorders (Janowsky et al. 1994).

The preclinical literature also implicates the muscarinic receptor system in mediating the cholinergic effects on emotional behavior. In a line of rats genetically bred for increased sensitivity of muscarinic receptors, the use of cholinergic agonists results in the enhancement of the behavioral analogs of depression, while the use of antimuscarinic drugs results in the improvement in these behaviors (Overstreet 1993). Consistently, the muscarinic cholinergic receptor antagonist, scopolamine, exerts rapid and robust antidepressant effects in depressed MDD and BD patients (Furey and Drevets 2006).

Several studies more specifically implicate the M2-receptor (M2R) in mood-regulation and depression. Multiple M2R gene polymorphisms were associated with increased risk for developing MDE (Comings et al. 2002; Wang et al. 2004). The administration of the M2R antagonist procaine elicits emotional responses in humans ranging from sadness, fear and severe anxiety, to euphoria, and results in increased physiological activity of the cingulate cortex (Ketter et al. 1996; Benson et al. 2004), a region densely innervated by cholinergic projections. Finally, decreased M2R binding has been reported in the cingulate cortex in bipolar depressives (Cannon et al. 2006a), using PET-neuroreceptor imaging (Fig. 4).

[...]

Excessive cortical cholinergic activity in experimental animals results in “hyperattentive impairments” (Sarter et al. 2005), where over activity of the cholinergic system reduces the signal detection threshold and leads to over processing of stimuli. Given the central role of ACh in emotional and sensory processing, the over-activity of the cholinergic system in mood disorders conceivably could alter S/N processing to produce an over-representation of emotionally laden information, creating the emotional processing bias and correlated cognitive deficits (see below).

→ source (external link)

So we have excess muscarinic acetylcholine activity --> overprocessing. So presumably extended overactivation of the muscarinic acetylcholine system could cause downregulation, meaning emotional flatness. So that's one idea, at least.

And here's some discussion of the structural causes of anhedonia, mostly focusing on the effects of the limbic system on phasic dopamine, which I've been largely focusing on:

Dysfunction of the MPFC coupled with amygdala hyperactivity also may contribute to the anhedonia, amotivation and inattention manifest in depression. The ACC receives extensive dopaminergic innervation from the VTA, and sends projections to the VTA that regulate phasic DA release. In rats, stimulation of these ventral ACC areas elicits burst firing patterns in the VTA-DA neurons, while inactivation of the ventral ACC converts burst firing patterns to pacemaker-like firing activity (Drevets et al. 1998; Murase et al. 1993; Taber and Fibiger 1993; Gariano and Groves 1988). The burst firing patterns increase DA release in the accumbens, which appears to encode information regarding reward prediction in monkeys (Schultz et al. 1997). If the neuropathological changes extant within the ventral ACC in mood disorders interfere with its drive on VTA-DA neuronal burst firing activity they may impair reward perception, conceivably seen as a loss of the pleasure and behavioral reinforcement derived from normally rewarding activities.
In addition, the cognitive and behavioral response patterns supporting goal- or reward-directed activity are thought to depend upon PFC inputs to the ventral striatum, which are maintained or “gated” by projections from the hippocampal subiculum to the ventral striatum (Goto and Grace 2005). Stimulation of projections from the amygdala to the ventral striatum interrupts the maintenance of these cortically driven response patterns, providing an adaptive, limbic override that interrupts goal-directed thought or behavior in response to unexpected threats or novelty. Nevertheless, in MDE the excessive amygdala activity conceivably could interfere with cognitive performance and goal directed behavior to an extent that is maladaptive.

→ source (external link)

By the way, the article that I'm pulling from in this post, on the causes of major depressive disorder as well as the article in my last post, discussing the biological basis of wanting, liking, and anhedonia, are both worth reading.

Edited by Dissolvedissolve, 20 December 2012 - 05:52 PM.

[magniloquentc0unt]

i would like to report my personal experience:
in the past year, i went on vacation for one month to a very sunny, warm, dry place.
there i had local food, and the only stimulant i had was a daily coke and a coffee.
on my second week i got sick for four or five days, and lost 6kg.
the last week i had very intense muscle cramps and night sweats, i attributed the night sweating as resudues of the fever
when i got back from vacation and started my normal life, i felt literally great, mental clarity 101%, healed.
but i still had the muscle cramps, and the night sweats. mind you, the temperature was something like minus 5 degrees celsius.
i tought it was a lack of magnesium due and took some supplementation for that: the cramps and the sweats slowly went away, personally i cant say it was the magnesium.
i just recently found out that acetylcholine plays a role on both sweat glands and muscle contraction...

two possible answers in my opinion:

1 the acethylcholine has something to do with that
2 being on vacation is great and lifts any unaware depression one might have

somehow id like answer 1 better...

this is interesting, not sure if it has any scientific research to back it up thou...
http://mindrenewal.us/page13.html

Edited by magniloquentcunt, 20 December 2012 - 06:21 PM.

[medievil]

Midbrain DA neurons exhibit two distinct modes of firing, referred to as “tonic” and “phasic” (Grace andBunney,1984). Tonic DA activity refers to steady-state firing generated by intrinsic pacemaker-like characteristics of DA neurons. Phasic activity—also known as “burst firing”—involves a rapid series of action potentials that induce a rapid rise in extracellular DA at terminal projection targets. Recent evidence suggests that this intracellular pathway can result in increased responsiveness of MSNs to sustained release of glutamate, generating “up-states” (Surmeier etal.,2007). In contrast, D2-like receptor binding results in decreased AC activity, thereby reducing the responsiveness of MSNs (“downstates”)(Hernandez-Lopez 453 et al.,2000). Of note, due to their higher affinity for DA as well as their more centralized location on the post-synaptic membrane, D2-like receptors are often stimulated by tonic levels of DA release, whereas D1-like receptors are stimulated primarily during phasic DA release (Goto etal.,2007).

→ source (external link)

Thanks to magniloquentcunt for linking to the thread on depressionforums, which I read through and pulled that from.

So apparently it's phasic dopamine that's associated with anticipatory pleasure. This explains why dopamine releasers tend to be more effective than reuptake inhibitors - they cause release of (phasic) dopamine rather than just increasing tonic signalling by preventing reuptake.

It is well established that bupropion has little direct effect on 5HT function (Stahl et al., 2004). Several studies exploring bupropion occupancy of DAT at clinical doses have reported occupancy rates ranging from 14% to 26% in the striatum (Kugaya et al., 2003; Learned-Coughlin et al., 2003; Meyer et al., 2002), which are relatively low as compared to standard SERT occupancy rates of SSRIs (80%) or DAT occupancy of reinforcing psychostimulants (>50%) (Volkow et al., 1995, 1997, 1998). These findings suggest that bupropion’s direct ability to increase synaptic DA levels through blockade of DAT may account for only some of its antidepressant effects. However, more recent work has also shown that bupro-
pion increases the activity of the intracellular vesicular monoamine transporter 2 (VMAT2) protein, which may enhance extracellular DA by increasing available DA in presynaptic pools (Rau et al., 2005). Bupropion may also exert regionally specific influence over DA function through its action as an inhibitor of the norepinephrine transporter (NET), which is the primary transporter of DA in prefrontal regions. Finally, more recent work has suggested that bupropion decreases the activity of nicotinic acetylcholine receptors, which play a role in the effects of bupropion on psychomotor symptoms in MDD (see Dwoskin et al., 2006 for a review).

Preclinical studies have suggested that bupropion may be a superior treatment for symptoms of motivational anhedonia. Rats treated with bupropion demonstrate decreased immobility time during the forced swim test and tail suspension tests (Cryan et al., 2001, 2004) and showed greater willingness to work for food rewards during a progressive ratio task (Bruijnzeel and Markou, 2003). Moreover, the influence of bupropion was blocked via administration of both D1-like and D2-like receptor antagonists, suggesting that effects of bupropion were partially mediated through DAergic mechanisms (Paterson and Markou, 2007). Additionally, rats treated with either chronic or acute doses of bupropion show a reduced threshold for intracranial self-stimulation of the posterior lateral hypothalamus (Paterson, 2009;Paterson et al., 2007). Similarly, bupropion enhanced responding to a conditioned reinforcer (Palmatier et al., 2009), although a separate study reported a bupropion-induced decrease in responding for sucrose (Reichel et al., 2008). The latter result is contrary to what would be expected, given the findings of Bruijnzeel and Markou (2003) and highlights the complex effects of the bupropion on reward processing. Interestingly, bupropion-mediated enhancement of conditioned reinforcers in the study by Palmatier et al. was ameliorated by Prazosin, an 2-NE receptor antagonist, suggesting that bupropion’s effects on reinforcement may also rely on noradrenergic mechanisms.

→ source (external link)

So we know that bupropion is not very effective as a DRI - thanks to medievil for mentioning this a while back - but it has other pro-dopamine mechanisms. It's more significant as a norepinephrine releasing agent, and pro-NE effects should help with lethargy symptoms that often accompany anhedonia.

Overall, head-to-head clinical trials between DA-acting agents and other pharmacotherapies have revealed strikingly similar response rates in the case of bupropion and pramipexole, (Chouinard, 1983; Coleman et al., 1999; Corrigan et al., 2000; Croft et al., 1999; Kavoussi et al., 1997; Mendels et al., 1983; Thase et al., 2005; Weihs et al., 2000; Weisler et al., 1994). For psychostimulants, response rates are usually significantly worse than other alternatives (Candy et al., 2008; Orr and Taylor, 2007). However, the potential role of DA-acting drugs as a superior treatment for anhedonic symptoms has received some empirical support. Bupropion has shown to be more effective at treating symptoms related to motivational and consummatory anhedonia (Bodkin et al., 1997; 1308 Tomarken et al., 2004). In a large-sample review of treatment records of 910 patients receiving outpatient pharmacotherapy for depression, Jamerson et al. (2003) reported that patients receiving bupropion sustained release (SR) showed significant improvement of symptoms related to reduced interest, energy and loss of libido as compared to placebo. Additionally, bupropion is often used to counter-act specific side effects of SSRIs (Nutt et al., 2007), which may include reduced responsiveness to rewards and positive experience (McCabe et al., 2009a,b; Price et al., 2009; Shelton and Tomarken, 2001). A recent meta-analysis of DA-acting antidepressant treatments suggests that they enhance overall quality-of-life in individuals with MDD (IsHak et al., 2009). These findings are not only promising in terms of treatment options; they also further underscore the importance of tailoring DA-acting treatments to specific symptoms.

→ source (external link)

So bupropion and pramipexole are both often effective in treating anticipatory anhedonia. According to these authors, stimulants are actually less useful, although there really isn't much research on them because psychiatrists are very hesitant to prescribe them to anyone who does not exhibit ADHD symptoms.

Its probably far more complex then concluding phasic da plays the biggest role, as an example we now know that consumatory reward is actually caused by the opiate receptors (can be indirectly activated by other neurotransmitters etc).

Pramipexole will supress phasic da and shift it to tonic da with chronic treatment, it also increases sero firing if im correct, i think the pfc is mostly implicated in anticipatory anhedonia, bupropion is a da and ne releaser there (ne pump reuptakes da in the pfc).

[Dissolvedissolve]

Its probably far more complex then concluding phasic da plays the biggest role, as an example we now know that consumatory reward is actually caused by the opiate receptors (can be indirectly activated by other neurotransmitters etc).

Pramipexole will supress phasic da and shift it to tonic da with chronic treatment, it also increases sero firing if im correct, i think the pfc is mostly implicated in anticipatory anhedonia, bupropion is a da and ne releaser there (ne pump reuptakes da in the pfc).

I agree things are very complex - I'm simplifying to try to find therapeutic routes.

I do not have consummatory issues - and most people with anhedonia of some brand or another have mostly or exclusively anticipatory issues - so I'm focusing on anticipatory anhedonia. Someone with consummatory issues likely needs something that targets the opioid and/or glutamate systems. Interestingly, it seems that amphetamine would work for mostly everyone since it causes glutamate and opioid activation, but I think pramipexole, wellbutrin, and perhaps selegiline are probably more sustainable for someone with just anticipatory issues.

Regarding pramipexole - agreed, making it a pretty ideal treatment. From what I've read, it does ultimately increase serotonin. I don't like the idea of an adjustment period or that some have reported becoming totally dependent on it, but others have said they tapered off without issue.

And as far as wellbutrin, it's strange that it works as well as it does in studies given that its main action is as a norepinephrine releaser. I guess NET inhibition in the PFC and the other mechanisms mentioned in that paper make it dopaminergic enough to work.

As far as the brain regions implicated in anhedonia, it seems the VMPFC is central. The hypothesis is that increased VMPFC activation indicates a cognitive effort to notice positive stimuli. It seems that the nACC and VTA may also be implicated, although those findings seem to be more confusing.

[nupi]

And as far as wellbutrin, it's strange that it works as well as it does in studies given that its main action is as a norepinephrine releaser. I guess NET inhibition in the PFC and the other mechanisms mentioned in that paper make it dopaminergic enough to work.

Working well? Not so sure there - In my experience, it gave energy (very much like SNRI give me energy so I conclude it's primarily NE) for a while (2-3 months), did little for anhedonia and then pooped out making me more anxious and more obsessive... Heck, even pure SSRIs like Escitalopram work better for my type of anhedonia than Bupropion ever did.

But then again I believe I am more on the consummatory then anticipatory side (I can fantasize about some things juuuuust fine - much too well, in fact), they just usually turn out to be rather underwhelming in the end which kind of took away motivation to even pursue them. Plus my anxiety ridden mind has great skills in making me fear things that ought to be positive experiences and thus I shy away from them (pun intended)

Edited by nupi, 22 December 2012 - 04:06 PM.

[kevinseven11]

Been watching yourbrainonporn.com It is possible you guys could have addictions and your brain is "rewired". Perhaps if its not from porn its from other dopamine releasing activities. What do you think?

[nupi]

That page is religiously-driven garbage (there used to be some background on it on Wikipedia, seems to have been removed in the meanwhile). See http://www.longecity...-porn-dopamine/

The religious right (together with the feminists) hates porn because it significantly weakens one of the few powerful sticks they still have at their disposal. And while we are at it, despite legal prostitution for like, forever, the world has still not ended in most of the world (ex-US/Arabia, obviously)

Edited by nupi, 22 December 2012 - 04:42 PM.

[Dissolvedissolve]

As far as bupropion, I definitely agree that it doesn't have as much pharmacological support as, say, pramipexole, but it does have clinical studies to support it. So it does seem like it may work for some people. I honestly think I have plenty of NE as well since I have above average blood pressure and heart rate, and I have physical energy, just not as much mental energy.

And as far as that anti-porn campaign - beyond the fact that it's bad science, I don't have that sort of issue.

[kevinseven11]

Nupi, have you even looked the website or videos?

[nupi]

some time ago yes, I really it doubt it has changed


frankly don't even consider it to be bad science, it's really just propaganda

Edited by nupi, 22 December 2012 - 09:26 PM.

[medievil]

That page is religiously-driven garbage (there used to be some background on it on Wikipedia, seems to have been removed in the meanwhile). See http://www.longecity...-porn-dopamine/

The religious right (together with the feminists) hates porn because it significantly weakens one of the few powerful sticks they still have at their disposal. And while we are at it, despite legal prostitution for like, forever, the world has still not ended in most of the world (ex-US/Arabia, obviously)

Putting that stick in a hooker prevents it from getting weaker.

Haha or having a girlfriend, the proper way those sites are stupid, ppl use porn and go to prostitutes if they have no other options or cant be bothered going out. The urge is nature. Paid sex is fake and pretty stupid dont know how that ends the world haha.

Edited by medievil, 22 December 2012 - 10:31 PM.

[medievil]

i would like to report my personal experience:
in the past year, i went on vacation for one month to a very sunny, warm, dry place.
there i had local food, and the only stimulant i had was a daily coke and a coffee.
on my second week i got sick for four or five days, and lost 6kg.
the last week i had very intense muscle cramps and night sweats, i attributed the night sweating as resudues of the fever
when i got back from vacation and started my normal life, i felt literally great, mental clarity 101%, healed.
but i still had the muscle cramps, and the night sweats. mind you, the temperature was something like minus 5 degrees celsius.
i tought it was a lack of magnesium due and took some supplementation for that: the cramps and the sweats slowly went away, personally i cant say it was the magnesium.
i just recently found out that acetylcholine plays a role on both sweat glands and muscle contraction...

two possible answers in my opinion:

1 the acethylcholine has something to do with that
2 being on vacation is great and lifts any unaware depression one might have

somehow id like answer 1 better...

this is interesting, not sure if it has any scientific research to back it up thou...
http://mindrenewal.us/page13.html

About a 100 differened conditions can cause those symptions, you cant conclude anything from it, i used to conclude shit based on symptions too and mostly i was you guessed it right... wrong.

[kevinseven11]

The guy at that website first said he doesn't care what people do with their selves but if they need help listen to his advice. They have alot of poeple who have fixed their addiction.

[Galaxyshock]

I had total abolishment of anhedonia yesterday. Not only that but I felt great clarity and motivation.

I took 25mg Forskolin, 2x450mg Artichoke, 4x750mg Cordyceps extract, 250mg CDP-Choline and some caffeine.

This morning I cut out the Forskolin and seems that it's indeed the compound that makes the real difference.

Problem is that Forskolin feels very unpredictable and tends to make me very edgy. I feel like it increases stress hormones too much. Artichoke balances it somewhat and increases the clarity. But when it wears off I may start feeling very bad and stressed and like a part of my brain shuts down. I'll take couple days break and start experimenting with small amount of forskolin like 5mg or even less.

I wonder how the acetylcholine plays a part here and if I should stop taking CDP-choline. I have some wierd symptoms from my PAWS like barely able to sweat even when exercising, vasoconstriction and a lot of those in the "mindrenewal" list. Is there something to counteract excess acetylcholine?

Edited by Galaxyshock, 23 December 2012 - 09:58 AM.

[Galaxyshock]

Gotu Kola:

It was observed that alcoholic extract decreased the acetylcholine and histamine content of the whole brain homogenate of albino rats. Inhibition of the increase in acetylcholine in the brain in stressed rats was observed. (Singh RH et al., J. Res. Ind. Med. Homeo, 14:3 (1979))

I wonder if this is part of the reason why Gotu Kola always makes me feel better. It's not very "prohedonic" but does give this profound positivity and calm energy.

[Dissolvedissolve]

I had total abolishment of anhedonia yesterday. Not only that but I felt great clarity and motivation.

I took 25mg Forskolin, 2x450mg Artichoke, 4x750mg Cordyceps extract, 250mg CDP-Choline and some caffeine.

This morning I cut out the Forskolin and seems that it's indeed the compound that makes the real difference.

Problem is that Forskolin feels very unpredictable and tends to make me very edgy. I feel like it increases stress hormones too much. Artichoke balances it somewhat and increases the clarity. But when it wears off I may start feeling very bad and stressed and like a part of my brain shuts down. I'll take couple days break and start experimenting with small amount of forskolin like 5mg or even less.

I wonder how the acetylcholine plays a part here and if I should stop taking CDP-choline. I have some wierd symptoms from my PAWS like barely able to sweat even when exercising, vasoconstriction and a lot of those in the "mindrenewal" list. Is there something to counteract excess acetylcholine?

Interesting. I have noticed that forskholii tends to feel "edgy." When I take foskholii with caffeine, it exaggerates the "jitteriness" of caffeine. It feels like it's increasing the NE-centric effect of caffeine. Do you notice any improvement from caffeine by itself? I personally find caffeine helpful, although I need to do more trials since I'm not entirely sure to what extent it's caffeine itself and to what extent it's assisted by MAO inhibition of coffee. There's tolerance obviously, so it's not a long-term solution, but coffee, for instance, makes me feel pretty normal for a few hours.

If you're having issues with anhedonia, I really don't know why you'd take CDP-choline. I get worsened lack of drive and increased lethargy with excessively high doses of choline citrate, which has caused me to not bother with more exotic forms of choline. I do not know of any ways to decrease ACh other than getting rid of pro-choline supplements. You can always add back CDP-choline if you notice any damage from removing it.

Edited by Dissolvedissolve, 25 December 2012 - 12:23 AM.

[brainslugged]

Hi, everyone, thanks for the advice. LDN looks promising, and I plan on trying it soon.

However, I don't think that there is a pure split against dopamine and opioid function.

I would like to point out that many low-dopamine related illnesses such as ADHD and (According to the other thread) AvPD do not include anticipatory anhedonia as depicted by the OP.

In fact, it seems to me like there are several stages, more than just Anticipation and Consummation.

Upon reconsidering, there are 3 stages to me.
1.Planning/fantasy - Imagining potential outcomes. Thinking of how pleasurable it would be. Perhaps daydreaming - This seems to be intact in ADHD, and is very intact in AvPD. This is what causes ADHD people to take on more projects than they can handle and what causes the actual problems of AvPD. This is a major difference between AvPD and schizoid personality. Schizoids have dysfunction at this stage, but avoidants do not. It also may be the stage of disruption in depression.
2.Acting/short term anticipation - Motivation. The act of taking your wants and organizing them into immediate action and sustaining the short term anticipation that makes you keep acting - I think this is where ADHD and AVPD primarily have difficulties. ADHD people tent to have problems with finishing what they start, which is this phase. Similarly, AvPD people tend to have trouble actually acting on their fantasies. The problem is that, in theory, the idea is fantastic, but they lack the motivation reward that is constantly telling them it is worth it to keep on going. So, ADHD people switch tasks because doing something gets boring not because they can't imagine it being pleasurable, but because they don't have the psychological "energy"; they become fatigued. This is also what happens when avoidants exaggerate difficulties. It is not that they don't imagine social interactions as being pleasurable, but that they lack the "push" that gets them started or keeps them going short term and thus they come up with excuses to back out. This isn't a pleasure stage in itself, more of an intermediate, energy-related stage. This stage would allow for the activation of the 3rd stage.
3.Consummary pleasure - This would be the actual enjoyment of the activity as it is happening. If any other stage doesn't happen, this one cannot happen. By keeping the "push", the person is able enjoy a continuous stream of this activity, but this stage does not actually provide motivation. This would be a zen type of feeling. - Honestly, I think this is the most common among the general population. This is where the problem is for the kind of person who isn't happy no matter what they accomplish or accumulate. If it was purely on this stage, the person would have no problem actually preforming actions. I would imagine that that kind of person would be the type who is very high in society, like CEOs. I have several family members who are like this, a lot of drive and everything always looks good to them in the first few stages, but when they are finished, they are always disappointed because it doesn't make them as happy as they hoped it would, even though the end product is good.


The second, I think is mostly caused by dopamine.
The third, I agree is probably an opioid problem.

The first is more complicated, and I don't really know what causes it. It does seem to be overactive in ADHD and AvPD, though. This, in combination with the fact that piractam(which upregulates NMDA receptors) helps me with it, and that glutamate sensitivity is inverse to dopamine makes me think that maybe it is at least partially caused by low glutamate sensitivity. This would compound on why adderall is helpful to ADD-PI patients. Not only does it increase motivation through the dopamine, but it draws them out of daydreaming by desensitizing their NMDAs, making them more "in the now" because it reduces the likelihood that they will fantasize.

It seems to me like the first stage is where most of you are having trouble, and I don't think that is primarily a dopamine problem. Either that, or I am misunderstanding the usage of anticipatory.

I think that Medievil said this in another post, but I don't think dopamine has much to do with pleasure directly. It is more of a mediator between fantasy and pleasure. So, more dopamine results in more pleasure, but only because it allows change of panning to consummation.

It is difficult to tell where my problem is, but I plan on experimenting with both dopamine and opioid functions. I think my problem is somewhere between the 2nd and 3rd. My first stage is normally okay, but fluctuates every now and then. This is the stage that seems to have improved since taking noots.

Just my 2 cents.

Edited by brainslug, 25 December 2012 - 02:51 AM.