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The Anticipatory Anhedonia Thread

anhedonia motivation depression adhd

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#1 Dissolvedissolve

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Posted 08 December 2012 - 08:58 PM


In order to help differentiate consummatory and anticipatory anhedonia, let's attempt to localize discussion of anticipatory anhedonia here and allow "The Anhedonia Thread" to focus on consummatory anhedonia.

For reference, here's the TEPS (Temporal Experience of Pleasure Scale):

Anticipatory factor
1. When something exciting is coming up in my life, I really look forward to it
3. When I think about eating my favorite food, I can almost taste how good it is
7. I don’t look forward to things like eating out at restaurants
11. When I’m on my way to an amusement park, I can hardly wait to ride the roller coasters
12. I get so excited the night before a major holiday I can hardly sleep
14. When I think of something tasty, like a chocolate chip cookie, I have to have one
15. Looking forward to a pleasurable experience is in itself pleasurable
16. I look forward to a lot of things in my life
17. When ordering something off the menu, I imagine how good it will taste
18. When I hear about a new movie starring my favorite actor, I can’t wait to see it


Consummatory factor
2. The sound of crackling wood in the fireplace is very relaxing
4. I love the sound of rain on the windows when I’m lying in my warm bed
5. The smell of freshly cut grass is enjoyable to me
6. I enjoy taking a deep breath of fresh air when I walk outside
8. A hot cup of coffee or tea on a cold morning is very satisfying to me
9. I love it when people play with my hair
10. I really enjoy the feeling of a good yawn
13. I appreciate the beauty of a fresh snowfall

→ source (external link)


If you have mostly negative responses to the first set of items, then you may have issues with anticipatory anhedonia.

So let's have some discussion of what methods you've tried and found effective or ineffective.

Some possible routes:

Stimulants - positive experiences have been reported for ampetamine, less so for methylphenidate; Have either of these worked for you? What about tolerance control strategies like NMDA antagonists or potentiation strategies like CILTP?

Low-dose psychedelics - some people have reported remission of symptoms with low-dose psychedelics

Bupropion - often prescribed for anticipatory anhedonia side effects of antidepressants. It's an NDRI, but its affinity for the dopamine transporter is around 25%, and it may need to be more like 50% to be effective if we use SSRIs' binding affinities as a guideline. But high affinities for the DAT (maybe 65% +) as well as rapid onset are risk factors for addictivity.

Traditional antidepressants - SSRIs seem to be a terrible choice since they often create anticipatory anhedonia. SNRIs do not affect dopamine, so they do not seem to be a particularly good option either.

MAOIs and tricyclics - these may let us access dopamine, but they have pretty substantial side-effect profiles. Selegiline looks promising as an MAO-B inhibitor with a small stimulant payload.

Uridine and/or CDP choline - uridine may have effects on the dopamine system. CDP choline is reported to increase DA and ACh receptor density, although it is not apparent whether this is just a side effect of it being a prodrug for uridine. Anecdotally, I've been taking uridine monophosphate at 300 mg/day for the past week with minimal and seemingly anxiolytic but not pro-motivation effects.

TMG/SAMe - SAMe may increase monoamine levels, but it does not seem to be selective for dopamine or catecholamines in general. Anecdotally, TMG is somewhat effective for me, but it is not perfect and does not entirely eliminate the issue.

Adaptogens - what about rhodiola rosea and the like?

And one more bizarre idea. What about St. John's Wort? One of its components - which is not necessarily present in all extracts - is hyperforin, which is a SNDRI, with greatest affinity for NET but also quite high affinity for DAT. It has affinity for SERT, but it's quite a bit lower than for NET or DAT.

Edited by Dissolvedissolve, 08 December 2012 - 09:02 PM.

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#2 Adaptogen

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Posted 11 December 2012 - 06:25 AM

Great post...do people really exist that dislike the consummatory factors? That is like a list of some of the best things in existance
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#3 Dissolvedissolve

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Posted 11 December 2012 - 07:23 AM

Great post...do people really exist that dislike the consummatory factors? That is like a list of some of the best things in existance


It apparently is a possible issue. There's a member in "The Anhedonia Thread" who has consummatory anhedonia.

Also, some individuals with depression may display at least some consummatory anhedonia in addition to anticipatory anhedonia, but it's difficult to untangle because anticipatory anhedonia can experientially feel like consummatory anhedonia in some circumstances.

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#4 Galaxyshock

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Posted 11 December 2012 - 03:13 PM

It's wierd, as PAWS symptom from GABAergics I seem to have anticipatory anhedonia yet the consummatory factor is actually pronounced. I do really enjoy the moment but lack real desires and I tend to be unable to feel positively excited about things which lowers my motivation. I also seem to be completely unable to feel addiction to anything or that certain euphoria linked to it. It seems that the anticipatory factors and motivation tend to go hand-in-hand. Lately I've had moments of getting that old feeling of desire and drive back, Forskolin may have contributed to this and it seems to make stimulative substances work more "like they should" (Rhodiola, Muira puama, preworkout supps). I also take magnesium 1000mg/day. I hope things continue to get better.

I had sample of Cordyceps and it seemed to synergize with forskolin even better and give me a lot of drive. There may be something to this traditional, powerful adaptogenic herb: https://www.jstage.j...9_1758/_article

I ordered couple of bottles and should get my packet this week so I can share my experiences if it really does help.


St. John's Wort was no help in my case. Uridine seemed to have a lot of positive effects for a while but it stopped working quite rapidly. Note that my PAWS also consists of some other fluctuating symptoms so I can't give completely accurate "testimonials", but the anticipatory anhedonia seems to be the major issue at this point.

Edited by Galaxyshock, 11 December 2012 - 03:40 PM.

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#5 Vieno

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Posted 11 December 2012 - 05:22 PM

Great post...do people really exist that dislike the consummatory factors? That is like a list of some of the best things in existance


Dislike... what an expression :laugh:

Here's another point of view: wouldn't it be extremely odd, if nobody's pleasure system would be broken? If everybody's pleasure processes would always function perfectly? Doesn't sound plausible. I think it is reasonable to expect some people to have consummatory anhedonia.
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#6 Dissolvedissolve

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Posted 11 December 2012 - 06:10 PM

That's interesting regarding SJW. It's a less common substituent, hyperforin, that has potential, so it may just be dependent on which extract you have, or it may just not work.

I'm planning on trying rhodiola. I guess I'll try CILTP with it. I do find artichoke and forskolin seem to potentiate stimulants. Forskolin on its own "feels" like it enhances norepinephrine. It's a bit edgy without any real motivation, at least for me. Actually, now that I think about it, this makes sense, since it increases cAMP levels. cAMP is the second messenger for NE signalling. I'm just thinking out loud here, so if anyone wants to correct me, go for it.

Cordyceps is an interesting idea. Its pharmacology does not seem to be well understood. The fact that it's been used as an aphrodisiac would suggest that there's something dopaminergic happening.

#7 Adaptogen

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Posted 11 December 2012 - 09:03 PM

Great post...do people really exist that dislike the consummatory factors? That is like a list of some of the best things in existance


Dislike... what an expression :laugh:

Here's another point of view: wouldn't it be extremely odd, if nobody's pleasure system would be broken? If everybody's pleasure processes would always function perfectly? Doesn't sound plausible. I think it is reasonable to expect some people to have consummatory anhedonia.


I agree...but it's not even about raw pleasure, it's about the elements...

Who doesn't like rain, snow, fire, fresh air? Life as we know it would end without these.
These seem like ubiquitous pleasure factors to me.

As for the most effective treatment, my vote goes for low dose psychedelics ;)

Edited by Adaptogen, 11 December 2012 - 09:04 PM.

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#8 kevinseven11

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Posted 11 December 2012 - 09:26 PM

Serotonin antagonists as well as high doses of inositol have been seen as very effective. I believe gaba antagonists should in the long term correct abnormalities.

#9 Dissolvedissolve

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Posted 11 December 2012 - 10:14 PM

As for the most effective treatment, my vote goes for low dose psychedelics ;)


I agree that is a very promising avenue. Unfortunately, given the state of psychedelics in the medical community and especially the consciousness of the public, it's unlikely to be viable for quite a few years, unless one is willing to risk taking research chemicals on a daily basis or acquiring vast amounts of illegal substances.

Serotonin antagonists as well as high doses of inositol have been seen as very effective. I believe gaba antagonists should in the long term correct abnormalities.


SSREs are indeed promising. Strangely, I've heard tianeptine, the only SSRE I know of, is anxiolytic. Does anyone have any experience with tianpetine with regard to anhedonia?

I've heard of inositol being used for anxiety, OCD, and so on - things that typically respond to increases in serotonin levels. So that's surprising. Any experience or pharmacology to back up this idea?

And GABA agonists also seem viable, although I do not know of any safe, readily available ones. Any suggestions?

Edited by Dissolvedissolve, 11 December 2012 - 10:15 PM.


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#10 Vieno

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Posted 11 December 2012 - 10:47 PM

I agree...but it's not even about raw pleasure, it's about the elements...

Who doesn't like rain, snow, fire, fresh air? Life as we know it would end without these.
These seem like ubiquitous pleasure factors to me.


That pleasure scale is not the most advanced. For example, in consummatory anhedonia one doesn't lack "appreciation", as suggested by the scale.

As for the most effective treatment, my vote goes for low dose psychedelics ;)


Funnily, along with glutamatergic stimulants, this has been suggested for consummatory anhedonia too.


SSREs are indeed promising. Strangely, I've heard tianeptine, the only SSRE I know of, is anxiolytic. Does anyone have any experience with tianpetine with regard to anhedonia?


Actually, serotonin releasers could possibly be beneficial. It's been said that SSRIs inhibit phasic serotonin, whilst the releasers inhibit tonic. Both increase the overall levels I suppose, but it's not so essential.
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#11 Dissolvedissolve

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Posted 11 December 2012 - 10:59 PM

Actually, serotonin releasers could possibly be beneficial. It's been said that SSRIs inhibit phasic serotonin, whilst the releasers inhibit tonic. Both increase the overall levels I suppose, but it's not so essential.


In that case, either an SSRE (like tianeptine) or a releaser (like MDAI) could be useful. But it seems that finding pure MDAI is difficult, and it is not prescribed or approved for anything. I guess one could order a custom synthesis and then check purity, but that would be extremely expensive and time-consuming.

The goal would be increasing the ratio of phasic to tonic serotonin to eliminate mood blunting.

#12 Vieno

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Posted 11 December 2012 - 11:02 PM

Actually, serotonin releasers could possibly be beneficial. It's been said that SSRIs inhibit phasic serotonin, whilst the releasers inhibit tonic. Both increase the overall levels I suppose, but it's not so essential.


In that case, either an SSRE (like tianeptine) or a releaser (like MDAI) could be useful. But it seems that finding pure MDAI is difficult, and it is not prescribed or approved for anything. I guess one could order a custom synthesis and then check purity, but that would be extremely expensive and time-consuming.

The goal would be increasing the ratio of phasic to tonic serotonin to eliminate mood blunting.


Yea, I have no idea whether some particular research chemicals sold online are pure or not... some companies may be innocent, but I suppose that majority of them are more or less scams.

E: Btw, since low-dose psychedelics are recommended for anticipatory anhedonia, I wonder what would happen when combining them with MDAI or SSRE... both are serotonergic...

Edited by Vieno, 11 December 2012 - 11:03 PM.


#13 Adaptogen

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Posted 11 December 2012 - 11:51 PM

which research chemicals in particular do you think would be most effective? 4-aco-dmt is the only one i've tried before but it has tremendous therapeutic potential

#14 Dissolvedissolve

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Posted 12 December 2012 - 12:18 AM

which research chemicals in particular do you think would be most effective? 4-aco-dmt is the only one i've tried before but it has tremendous therapeutic potential


You'd want a chemical with 5-HT2a agonist activity but no activity as a releasing agent. I'm simplifying a whole lot, but releasing agents have a higher risk of neurotoxicity. As far as I know of, all pure, classical psychedelics (and by this I mean 5-ht2a agonists without any releasing agent or reuptake inhibition activity) are non-neurotoxic. Although it is not a concern for occasional dosing, the risk of heart valve problems could be problematic if one administers a psychedelic daily. I can't recall which specific types of 5-HT receptors are responsible for the heart problems, but it could be that a sufficiently selective psychedelic could avoid heart complications.

I think 4-aco-dmt is a good candidate. It's unlikely to be neurotoxic. In fact, I am not familiar with any tryptamines with neurotoxicity issues, since they do not have releasing agent properties. Most RC psychedelics are phenethylamines, which are far more varied in effects, and it's safe to say plenty of phenethylamines are neurotoxic while others aren't.

#15 Adaptogen

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Posted 12 December 2012 - 01:28 AM

I have seen some interesting information about ketamine/mxe, I wonder what effect it might have on anhedonia. I don't know much about it, really.

Do dissociatives have any nootropic potential?

#16 FunkOdyssey

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Posted 12 December 2012 - 01:43 AM

You guys aren't going to look at causes? That's where it really gets interesting -- all the interactions between the immune system and the brain, the gut microbiota and the brain, inflammation & oxidative stress & sickness behavior. Almost forgot chronic stress(ors) of all types.

You should also consider that millions of people have probably suffered this, and many recovered, although you won't necessarily find it labelled "anticipatory anhedonia". What has worked for others, sustainably, for years? I don't think you'll find medievil'esque stacks on the list.

Edited by FunkOdyssey, 12 December 2012 - 01:56 AM.

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#17 Dissolvedissolve

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Posted 12 December 2012 - 01:50 AM

I am not very optimistic about dissociatives. Dissociatives are typically NMDA antagonists, and NMDA antagonism is useful for preventing or reducing stimulant tolerance, but reduced NMDA function may also be associated with schizophrenia, especially negative symptoms, which are very similar to anhedonia.

Interest has also focused on the neurotransmitter glutamate and the reduced function of the NMDA glutamate receptor in schizophrenia, largely because of the abnormally low levels of glutamate receptors found in the postmortem brains of those diagnosed with schizophrenia,[59] and the discovery that glutamate-blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with the condition.[60] Reduced glutamate function is linked to poor performance on tests requiring frontal lobe and hippocampal function, and glutamate can affect dopamine function, both of which have been implicated in schizophrenia, have suggested an important mediating (and possibly causal) role of glutamate pathways in the condition.[61] But positive symptoms fail to respond to glutamatergic medication.[62]

→ source (external link)


For this reason, I have experimented with glycine receptor agonists. I haven't tried glycine enough times to judge it, but it wasn't particularly useful. I found sarcosine to be interesting. It seemed to briefly and mildly improve cognition, in my subjective, placebo-vulnerable judgment. I've used it perhaps 6-12 times. It seems to increase my irritability noticeably - things that normally bother me begin to, which is a bit obnoxious.

You guys aren't going to look at causes? That's where it really gets interesting -- all the interactions between the immune system and the brain, the gut microbiota and the brain, inflammation & oxidative stress & sickness behavior.

You should also consider that millions of people have probably suffered this, and many recovered, although you won't necessarily find it labelled "anticipatory anhedonia". What has worked for others, sustainably, for years? I don't think you'll find medievil'esque stacks on the list.


I am definitely not recommending "medievil'eque" stacks. I think that any therapy should either use OTC substances or be conducted under the supervision of a psychiatrist, preferably both. As far as stimulants or other bold or atypical therapies, I think zrbarnes' use of 5 mg dextroamphetamine with tolerance breaks is an interesting example.

If you have any suggestions of causes or any behavioral interventions, I would love to hear them. As far as behavior, I eat a "healthy" diet with 6+ servings of vegetables daily, plenty of protein, healthy fats, and so on. I exercise four times weekly. I meditate around 4-5 times per week. I don't find that any of these particularly help with anhedonia, although they do make me generally more content, energetic, relaxed, and so on.

Edited by Dissolvedissolve, 12 December 2012 - 01:51 AM.


#18 Vieno

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Posted 12 December 2012 - 02:45 AM

You guys aren't going to look at causes? That's where it really gets interesting -- all the interactions between the immune system and the brain, the gut microbiota and the brain, inflammation & oxidative stress & sickness behavior. Almost forgot chronic stress(ors) of all types.

You should also consider that millions of people have probably suffered this, and many recovered, although you won't necessarily find it labelled "anticipatory anhedonia". What has worked for others, sustainably, for years? I don't think you'll find medievil'esque stacks on the list.


I believe that the ones looking for help here are those who have failed to identify a cause for their anticipatory anhedonia. Those who suffer from it as a result of a psychological problem or an identifiable physiological problem are probably not looking for help here. If they are, then for sure your advice applies, but I doubt they are.
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#19 kevinseven11

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Posted 12 December 2012 - 03:17 AM

Some people can surely be cured without intervention and just purely fixing the cause but alot of peoples issues are beyond easy repair, especially if theyre here. 5ht2c receptor antagonists are beneficial while another sub type is beneficial when an agonist. So Bacopa monnieri will be beneficial! Possibly yohombine(5ht2a) is also another canadite for treatment. Natural cures are often the only possiblity of treatment because many substances legality.

Edited by kevinseven11, 12 December 2012 - 03:19 AM.


#20 Dissolvedissolve

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Posted 12 December 2012 - 04:40 AM

Some people can surely be cured without intervention and just purely fixing the cause but alot of peoples issues are beyond easy repair, especially if theyre here. 5ht2c receptor antagonists are beneficial while another sub type is beneficial when an agonist. So Bacopa monnieri will be beneficial! Possibly yohombine(5ht2a) is also another canadite for treatment. Natural cures are often the only possiblity of treatment because many substances legality.



I must report the exact opposite with regard to Bacopa. It made my anhedonia much worse. Sure, my mood was good and I was content, but I was without any drive or desire. Negative things did not bother me, and positive things did not please me. My sex drive dropped dramatically, likely due to its serotonergic properties, although there is a study in rats showing inhibition of leydig cells, meaning reduced testosterone levels. The increased serotonin would also explain the anhedonia.

I don't notice much other than stimulation with Yohimbine, but I can do more trials. Also, it's not terribly effective when not fasted, which limits its utility.

#21 Galaxyshock

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Posted 12 December 2012 - 04:43 PM

Any ideas how GABA and GLUTAMATE are involved in the reward-pathway?

Edited by Galaxyshock, 12 December 2012 - 04:43 PM.

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#22 Dissolvedissolve

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Posted 12 December 2012 - 11:39 PM

As far as GABA, all I can say is that excessive GABA activity may dull necessary dopamine activity. So there may be excessive GABAergic signaling in people with anticipatory anhedonia (or perhaps even consummatory anhedonia). Note that if anticipatory anhedonia is a symptom of a broader depressive disorder, then there may be anxiety involved, in which case reducing GABAergic signaling would be unwise.

I've taken an excerpt from a conversation below on glutamate:

Here's a study showing decreases in glutamate in certain brain regions in rats with chronic d-amp administration:
http://www.ncbi.nlm....les/PMC1571853/

And here's a study showing acute increases in glutamate with d-amp administration:
http://www.ncbi.nlm....pubmed/10987845


"]http://www.ncbi.nlm....C3202508/'][/url]Thus, when dopamine is released into the prefrontal cortex or amygdala by a drug-associated cue or stressor, this is thought to stimulate glutamatergic projections between the prefrontal cortex and amygdala, as well as glutamatergic outputs to the accumbens and ventral tegmental area.34
→ source (external link)



So we have DA release --> Glutamate --> downregulation of glutamate.

These sources suggest that any change in dopamine release, which is triggered by amphetamine and amphetamine derivatives, would cause any glutamatergic effects. So methylphenidate is not helpful since it just inhibits DAT, but both d-amp and m-amp act as releasing agents, meaning either should work. For that matter, there are any number of research chemical amphetamine derivatives that could potentially work, but obviously with unknown side effects and neurotoxicty.


I am not entirely certain on the specifics, but we definitely know that dopamine releasers but not reuptake inhibitors increase glutamate. And response rates for anhedonia seem to be higher with DA releasers than reuptake inhibitors. So it seems that increasing glutamate is helpful for anticipatory anhedonia. Although it may also be helpful for consummatory anhedonia. Again, I am not sure on the specifics, and this is very complicated since glutamate is the most common excitatory neurotransmitter and is intricately connected with pretty much every other neurotransmitter.

One other thought: anticonvulsants are often glutamate antagonists. Anticonvulsants are very useful for treating bipolar disorder, acting as mood stabilizers and being especially helpful in treating mania. So this would suggest that, perhaps, mood flattening - which is largely synonymous with anticipatory anhedonia in my mind - may involve insufficient glutamate signaling, or at least glutamate signaling that is in some way flawed.

I had previously tried sarcosine, anywhere from 600 to 1800 mg (NMDA glycine receptor agonist and reuptake inhibitor) with not much effect other than perhaps mild focus enhancement and irritability. I tried 1200 mg sarcosine today but with 3000 mg D-Aspartic Acid, and it seemed to be substantially more potent with quite a bit of focus enhancement. Placebo could be an issue, as could the fact that I used to administer sarcosine at night. Also, no real effect on motivation or interest per-se, so it doesn't really help anhedonic symptoms, but it may be useful to minimize one part of anhedonia - difficulty staying on task. I'll report in this thread if the combo continues to be useful.
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#23 medievil

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Posted 13 December 2012 - 01:27 AM

" I don't think you'll find medievil'esque stacks on the list."

I can provide some long term anecdotes soon, you are purely skeptical based on my regimes wich have nothing to do with individual suggestion for a particular issue.

I must report the exact opposite with regard to Bacopa. It made my anhedonia much worse.

I often see completely useless suggestions for issues like this, my suggestions are based on anecdotes showing succes, as an example amisulpiride and zyprexa where included, and in contrast to what funk says they also have a ton of long term anecdotes behind them.

#24 kevinseven11

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Posted 14 December 2012 - 01:52 AM

Bacopa is used to induce premature ejaculation. I figured it could be related. Hmm does anyone know anti serotonin chems? Dopamine so uridine? Also ive heard cbd haseffects on serotonin.

#25 Dissolvedissolve

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Posted 14 December 2012 - 02:35 AM

As far as premature ejaculation, I didn't notice any effect on that domain.

I don't know of any anti-serotonin agents other than tianeptine, which may be useful but is not approved in the US.

CBD is a 5-HT1a agonist. I'm not sure if that has any utility. I'm inclined to think 5-HT2a agonism would be desirable due to the efficacy of psychedelics in treating anhedonia.

I did list uridine in the original post, but I haven't noticed much of any effect from 300 mg daily, original sublingual, but now often oral. I think zrbarnes may have had better results with it. More opinions would be great.



Also, medievil, I think the idea of amisulpride is interesting. I've seen some anecdotes in support of it, although the fact that it's not available in the US is bothersome. There's also some anecdotal support for olanzapine. I personally have no interest in either due to the horrible side effect profile of antipsychotics, but they may be options.

And one final note: the items listed for the TEPS above actually aren't the final TEPS, which is apparently 18 items and is slightly different. Regardless, the list should be adequate since we aren't focusing on diagnosis but on treatment and causes.

#26 Animal

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Posted 14 December 2012 - 05:34 AM

" I don't think you'll find medievil'esque stacks on the list."

I can provide some long term anecdotes soon, you are purely skeptical based on my regimes wich have nothing to do with individual suggestion for a particular issue.

I must report the exact opposite with regard to Bacopa. It made my anhedonia much worse.

I often see completely useless suggestions for issues like this, my suggestions are based on anecdotes showing succes, as an example amisulpiride and zyprexa where included, and in contrast to what funk says they also have a ton of long term anecdotes behind them.


Amisulpride is a good suggestion; but I hope you're not going to recommend some illegal research chemical like MDPV, or 'psychosis powder' as it is otherwise known. :blink:

Personally the most effective pharmaceutical I have trialled for both subtypes of anhedonia has been Pramipexole. I know it's not very popular because of the adaptation phase, and it's complete lack of recreational value, but it is the closest thing to a cure I've ever experienced. It's also had some negative exposure relatively recently because a few loud idiots took it in combination with memantine. Which subsequently resulted in dysfunctional adaptation and an overall unpleasant experience. Of course they typically fail to mention this combination when posting about how pramipexole is the product of the devil.

I will probably elaborate on my extensive experience with the substance in a dedicated thread. I'm about to start taking it again, after a 9 month hiatus for various reasons, so I may even post a log. I just wanted to make people aware of it as a potential option. At least it has some clinical evidence for it's effectiveness in this regard.

#27 nupi

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Posted 14 December 2012 - 09:23 AM

Bacopa is used to induce premature ejaculation. I figured it could be related. Hmm does anyone know anti serotonin chems? Dopamine so uridine? Also ive heard cbd haseffects on serotonin.


Induce? If anything serotonergics (bacopa definitely has some serotonergic properties but not to the level of an SSRI) would delay ejaculation. The SSRIs are notorious for that and in fact sometimes used to treat premature ejaculation off-label....

#28 Galaxyshock

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Posted 14 December 2012 - 02:32 PM

As far as GABA, all I can say is that excessive GABA activity may dull necessary dopamine activity. So there may be excessive GABAergic signaling in people with anticipatory anhedonia (or perhaps even consummatory anhedonia). Note that if anticipatory anhedonia is a symptom of a broader depressive disorder, then there may be anxiety involved, in which case reducing GABAergic signaling would be unwise.


The dulling effect does seem to be there especially with GABA-A agonists - whereas Muira Puama that is supposably GABA-A antagonist is nicely stimulative though it also has some other activity. But phenibut is a GABA-B agonist (altough in higher doses agonizes GABA-A too) and tends to be quite pleasant and even benificial for anhedonia. The GABA-B receptors may be more involved with the reward-pathway. Interestingly phenylethylamine (PEA) is GABA-B antagonist but can be euphoric.

#29 AwesomeName

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Posted 14 December 2012 - 05:11 PM

I got massive anhedonia(as well as memory and sleep problems) from taking benzos for 3 months, it pretty much damaged my brain.

Maybe a benzo/gaba method would work for fixing it.

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#30 Dissolvedissolve

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Posted 14 December 2012 - 07:14 PM

Personally the most effective pharmaceutical I have trialled for both subtypes of anhedonia has been Pramipexole. I know it's not very popular because of the adaptation phase, and it's complete lack of recreational value, but it is the closest thing to a cure I've ever experienced. It's also had some negative exposure relatively recently because a few loud idiots took it in combination with memantine. Which subsequently resulted in dysfunctional adaptation and an overall unpleasant experience. Of course they typically fail to mention this combination when posting about how pramipexole is the product of the devil.

I will probably elaborate on my extensive experience with the substance in a dedicated thread. I'm about to start taking it again, after a 9 month hiatus for various reasons, so I may even post a log. I just wanted to make people aware of it as a potential option. At least it has some clinical evidence for it's effectiveness in this regard.


Although I forgot to list in the first post, I'm interested in pramipexole (and to some extent ropinirole, although I believe pramipexole is thought to be more effective since it's a full agonist). It's one of the few medications that seem to develop little tolerance (although selegiline looks promising in that regard, albeit slightly less so).

Here's an interesting thread on prampexole, although it seems no one was able to deal with the adaptation. Nonetheless, it has studies showing it to be effective for both unipolar and bipolar depression: http://www.longecity...50-pramipexole/
More studies / really long thread: http://www.mindandmu...ipexole-mirapex

In the long-term, pramipexole seems to work through desensitizing 5-HT and DA autoreceptors, leading to increased 5-HT and DA levels.

And it's wise to mention a few cautions. There are some compulsive behaviors occasionally caused as side effects, so people with a tendency for addiction or OCD are probably better off avoiding pramipexole. Also, it seems like the withdrawal is pretty long-lasting and unpleasant, so it's probably a long-term commitment. There was initially concern of cardiac fibrosis, but that now seems to be unfounded.

Edited by Dissolvedissolve, 14 December 2012 - 07:15 PM.






Also tagged with one or more of these keywords: anhedonia, motivation, depression, adhd

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