420 replies to this topic

[nefarious one]

I thought about posting in this thread.

but I really just don't give a f*ck.

[lourdaud]

Have you tried GHB? Amphetamine with an opiate? If you're still anhedonic after that then I don't know what..

[FeelsNumbMan]

FeelsNumbMan, I'm sorry for your condition. I recommend you to check out "The Anticipatory Anhedonia Thread", your anhedonia clearly extends to block actual pleasure too but the pathogenesis might be the same as with AA, you're just a severe case. Also check out itstrevor's thread about anhedonia on Depressionforums, a lot of rambling there but some useful info too. This thread isn't gonna help you at all, maybe it's finally time for me to ask a mod change the title... lol

SlimNm, why are you interested in constipation specifically? Because it's caused by peripheral mu receptors? Perhaps a huge dose indeed might be worth testing to see if peripheral effects like constipation and itching would occur. My records indicate that whilst opium clearly had absolutely zero CNS effects, I did experience slight constipation - not sure if it was just a coincidence or actually caused by the opium. My brother gets hardly any CNS effects from opioids these days but he still gets the itch. Thanks for the idea, I'll take a huge dose when I'll have an opportunity. Btw, everything's illegal in Finland including loperamide, I just checked :P

Thanks, I've seen that thread before and it's huge. Really huge, haha. I don't know if anyone actually found a solution to their numbness, though. I really do appreciate these kind of threads... they're helpful... And hopefully, one person can chime in saying that their poblem has been solved, and solved for good... and tell us what they did.

It's crazy because everyone's different... Everyone's who's "anhedonic" is anhedonic in a different way but at the same time, similar.

I thought about posting in this thread.

but I really just don't give a f*ck.

Meh. Apathy and anhedonia aren't the exact same. If I was just apathetic, I couldn't care less about not being able to care about anything. But when I'm anhedonic, I care about not being able to feel anything. Emotions, etc. At least people who are apathetic can still feel their emotions, right? Somewhat?

[Vieno]

Aw, maybe you could order some online from the U.S.A.?

I thought it might be useful to find out if you have constipation, because if you don't, that might mean that your body is metabolizing opioids into an inactive substances really quickly. Unlikely, I know, but it's just a theory

I'm sure my metabolia's functional. The opiod dysfunction is clearly directly related to the CA itself, I mean, the opioid system is central to pleasure generation. But I still want to try a huge dose because it would be interesting to see if the peripheral mu receptors are functional. I can see how that could theoretically be possible.

Have you tried GHB? Amphetamine with an opiate? If you're still anhedonic after that then I don't know what..

A hallmark feature of my condition is that I barely respond to GABA-B agonists. My thershold for GHB is around 2,5g and even 3,5g produces absolutely zero pleasure, just a very short lived non-sedating intoxication. Phenibut doesn't work at all, I took 10g of it and MAYBE experienced a slight hypnotic effect - not sure.

I did a poor man's speedball combining methiopropamine with codeine, didn't get any pleasure. Stimulants, opioids, they do not help me.

Edited by Vieno, 11 September 2013 - 11:45 AM.

[Vieno]

Gotta take my words back, loperamide seems to be prescription free here. Might try it some day then.

[SlimNm]

Gotta take my words back, loperamide seems to be prescription free here. Might try it some day then.

Nice.

You know, if loperamide DOES cause symptoms of peripheral opiate receptor activation, then that may mean either:

Your brain metabolizes opioids into an inactive substance (highly unlikely, since you seem to be immune to the pleasant effects of other classes of drugs too)

OR

Your opioid receptors in your brain actually ARE being activated, but one of the FOLLOWING steps is mal functioning in the pleasure process. Maybe the opioid receptors are being activated, but they aren't causing the same metabolic changes in brain cells that should happen. In which case, maybe we should do research into what happens in brain cells when opioid receptors are activated. Maybe it would be helpful to take on a different perspective other than "what neurotransmitters are released in what locations" and look more from a point of view of "what happens INSIDE cells when the receptors sticking out of them attach to a ligand."

Just brainstorming.

[Vieno]

Hmm perhaps you're right. For some time already I've believed that systemically administrating different drugs isn't going to do anything as the dysfunction seems to be about something else than mere neurotransmitter/receptor hypofunction or something like that. The culprit could be some extremely local issues, or perhaps something like what you just described. Either way, the treatment will be not be anythin orthodoxic. I've got ideas, I'll post about them a bit later.

Brainstorming's very valuable at this point

[zephyrprime]

I think it might be useful for you to get to know all the possibly related symptoms I'm experiencing so here goes a list:

Subjective
Consummatory anhedonia
Occasionally occurring feelings of excess stimulation
Depressive feelings timed to a specific period of a day (around 3PM-9PM)

Bodily
Excessive body heat during nights
Inability to sleep before morning
Skin becoming loose and coming off (as a consequence of hot nights)
Excessive gastronitestinal function (excessive stomach motility and gas build-up)
High appetite and calorie intake without weight gain
Substantial difficulty building muscle mass and improving aerobic performance

Pharmacological
No euphoria from any recreational drug
Zero reaction to opioids (moderately high doses tested)
Very little reaction to GABA-Bergics (high doses tested)
Correction of circadian rhythm and no adverse effects from an antipsychotic



During this month I will get to test most of the recommended herbs as well as diphenhydramine, and next month probably piracetam and proglumide too. I will keep you updated.

This is so interesting to me because I also do not receive much euphoria from recreational drugs. Even when they work, I build up a strong tolerance after only 1 usage! You might want to get your dhea and cortisol levels checked because some of your symptoms are indicative of high cortisol. I have a weird problem when my dhea is low which causes my cortisol to be overly expressed.

[medievil]

Inflammation linked to weakened reward circuits in depression

https://www.scienced...51120182942.htm

 

 

Can’t Experience Pleasure? Blame Inflammation

http://www.brainprot...n-inflammation/

 

 

 

Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward

Naomi I. Eisenberger, Elliot T. Berkman, Tristen K. Inagaki, Lian T. Rameson, Nehjla M. Mashal, and Michael R. Irwin

Author information ► Copyright and License information ►

 

The publisher's final edited version of this article is available at Biol Psychiatry

See other articles in PMC that cite the published article.

 

Go to:

Abstract

Background

Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia—namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood.

Methods

Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards.

Results

Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward.

Conclusions

 

Too lazy to post more.

 

[medievil]

A combination of a treshold dose of 1p lsd, 3fpm, 4 fluoroethylphenidate, cannabinoid, phenibut and codeine doesnt even reverse the olanzapine anhedonia, cant beleive it screwed up my reward system after taking it a few days with nefiracetam.

 

Its not unheared off that aps, especially olanzapine cause severe anhedonia for god knows how long after stopping the drug.

 

What is the mechanism behind this?

[machete234]

"What is the mechanism behind this?"

 

Obviously its supposed to lower neurotransmitters especially dopamine because they believe or believed that psychosis is too much dopamine.

What the hell were you trying to do with that combination of 5 drugs?

 

Im microdosing ald-52 or 1p-lsd currently which always ends up as more of a recreational, enjoying myself thing, doesnt get me off my ass that much.

I also got my hands on something that I believe is dexedrine which has very little kick compared to some street amps which are racemic and have caffeine+ lots of filler material.

Its dopaminergic because I chain vape on it and porn is more of a stimulus, so it does work but "clean" dopaminergic stimulants are not necessarily the answer.

 

I keep hearing a lot about this "rat park" study: In short rats who have a stimulating environment dont get addicted to drugs.

The old conditions for this type of experiment was a rat alone in a cage with nothing but drugs, guess what it does then.

 

So if your life is objectively shit, not enough friends to talk to, no rewards, no perspective, you just cannot win then anhedonia might be the natural reaction to that. Thats putting your reward system to sleep.

The problem is getting out of that situation with no drive is very hard.

Edited by machete234, 25 February 2016 - 10:00 AM.

[medievil]

I ment that the anhedonia doesnt go away while before 3 days after olanzapine i would get anhedonia relief from stims again, now i am still asocial and anhedonic on stms like im on that damn ap.

 

I looked op withdrawals even tough i never took it more then a few days and ppl report that it takes months to recover from this anhedonia.

 

Well in shizophrenia there seems to be complete dysregulation of the reward system, and targetting every pathway in balanced doses so you dont get skyhigh i notice remission of anhedonia in all its diff forms... hard to explain, every reward pathway is unique, also for me stimulants are the foundation for tonic reward, without them nothing else works and i remain in torture no matter what recreational substance i try.

Edited by medievil, 25 February 2016 - 09:57 AM.

[medievil]

I took low doses of MXP yesterday, ketamine infusions cure bipolars of anhedonia which other antidepressants dont do by resetting the reward system or something, dunno wheter a few treshold doses did much tough, im still quite the same but waiting for phenibut atm.

[medievil]

With regards to the evidence linking inflammation to anhedonia, theres 2 treatment options that immediatly come to mind:

 

Candesartan which abolishes brain inflammation trough ARB1 blockade.

Meriva long acting curcumin, altough its been said its half life in the brain is 24 hours, im not sure about that so i would go for a long acting formulation,

[medievil]

MXP wasnt really my thing, but then again i took it during benzo withdrawal as ketamine has been studied for alcohol withdrawal for some succes and i know that glutamate is implicated, but besides feeling weird and thinking i was in the syrian war one time and other confusion i dont think it did much but no clue how i would have felt without it.

 

I liked treshold mxe doses, never been fond of ketamine.

 

Nah the pro glutaminergic racetams are all for me, except memantine, one of my most favored meds.

 

Phenibut arrived and i think olanzapine is leaving my system more, im starting to feel enjoyment in ways again, stims are still extremely blunted.

[medievil]

 

I keep hearing a lot about this "rat park" study: In short rats who have a stimulating environment dont get addicted to drugs.

The old conditions for this type of experiment was a rat alone in a cage with nothing but drugs, guess what it does then.

 

So if your life is objectively shit, not enough friends to talk to, no rewards, no perspective, you just cannot win then anhedonia might be the natural reaction to that. Thats putting your reward system to sleep.

The problem is getting out of that situation with no drive is very hard.

This is absolutely correct and i should have been posting this before, you can only enjoy life when you have a enjoyable life, this is unrelated to anhedonia, and more to boredom, if you are living a good life, but find hanging out with friends torture, listening to music painfull, waiting every second for a pleasurable (a situation you like when anhedonia is treated) for it to end, then we are talking about anhedonia.

 

Too many ppl claim to be anhedonic when they are in fact bored, get a life folks.

[airplanepeanuts]

Man, this is like the good old days when medievil was always about to find the cure...

[gamesguru]

olanzapine cause severe anhedonia for god knows how long after stopping the drug.

What is the mechanism behind this?

 

 

dopaminergic oxidation?

Dopamine Oxidation and Autophagy

Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum.

short of experimental brain grafts or implants, STAY OPEN to herbal options...
Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse.

 

maybe the "inflammation" you talk of is stress-induced?

Chronic mild stress-induced anhedonia: A realistic animal model of depression

Chinese herbs found to enhance resistance to all causes of stress

ok these are jokes
Methods for promoting nerve regeneration and neuronal growth and elongation

Identification of oxidative degradation impurities of Olanzapine drug substance as well as drug product

[medievil]

Why do you emphatise on staying open for herbal options? im a big supplement freak, also take essential oils orally, beleive in acupuncture etc, only with being open to the whole gamma of treatments like sups, aromatherapy, chinese medicine, research chemicals, color therapy etc i beleive we can find solutions for many problems, im far from a a all meds guy.

 

About the inflammation, i dont think so, ssris reverse stress induced damage but do not reverse anhedonia in depression in many cases which according to some papers is linked to anhedonia.

 

I know that olanzapine increases da but who gives a fuck if it also blocks the beneficial receptors for that individual? that said i didnt take it for a week and im slowly getting anti anhedonia benefits from stims again.

 

Also what relevance has that cocaine study? addaptive changes with drug addiction are an entirely differened topic.

[medievil]

Man, this is like the good old days when medievil was always about to find the cure...

I dont have a clue what the cure is, stims allways reversed my anhedonia but this is more tonic related reward and i never managed to reverse my symptions well enough to before i triggered shizophrenia, that said i entirely forgot how i used to feel, for example adding differened rewarding substances makes me experience types of reward i completely forgot about.

 

I dont know what times you talk about but i suspect it was when i was badly cognitively impaired because of shizophrenia and had a daily new regime?

[gamesguru]

i think the nucleus accumbens has a lot to do with anhedonic depression.  also can't be bothered atm to dredge them up, but Flex posted a bit about chinese supps on this subject.

 

Anti-inflammatory drugs reduce effectiveness of SSRI antidepressants, study shows
Why Antidepressants Cause Brain Damage, Breast Cancer, and Early Mortality

 

and you said you took olazapine for a while, and i'm just saying dopaminergic oxidation tends to be permanent, and on a brain region where neurogenesis does not occur is unfortunate.  if that's the problem, it'll be hard to solve.

[medievil]

No i only took it for a few days, but the last time with nefiracetam and oxiracetam and i was thinking the drugs programmed themselves into the brain, like how you prevent drugs from doing that with memantine, making it simular to having taking them a long time.

 

I dont think its braindamage, alot of meds can permanently make you more anhedonic, i beleive because the brain gets used to that status and adapts to it.

 

That said i do THINK im going back to normal but its too early to say really, definatly not normal yet.

 

The last you mentioned could have happened as i did overdose on 4 fluoroethylphenidate that time with olanzapine perhaps causing synergetic damage, in that case that dopaminergic restorative rc tlrc has could be the solution but dont have the funds atm.

[medievil]

Also id like to add that maybe it seemed like i was allways looking for the "cure" in the past while also claiming i knew what worked, i mostly was looking for complete remission, im not gonna give up searching with a partional cure, ive come a very far way so thank god for that.

[gamesguru]

especially dopamine system has more sticking points.  less plastic than the others.  best not to fuck around with it too much.

[medievil]

I allways got away with stim abuse lol, wish i had my dex script and could lead a more normal life, 10mg dex 3 times a day is all i need but the uk docters are full of bullshit, offcourse id still abuse drugs in the weekend thats just me lol.

 

I just was experimenting with aps as they can have interesting effects, for example olanzapine gave sports a entertaining effect and i couldnt get enough of top gear while im normally not interested in cars, you can be anhedonic in a 1000 differened ways.

[medievil]

i think the nucleus accumbens has a lot to do with anhedonic depression.  also can't be bothered atm to dredge them up, but Flex posted a bit about chinese supps on this subject.

 

Anti-inflammatory drugs reduce effectiveness of SSRI antidepressants, study shows
Why Antidepressants Cause Brain Damage, Breast Cancer, and Early Mortality

 

and you said you took olazapine for a while, and i'm just saying dopaminergic oxidation tends to be permanent, and on a brain region where neurogenesis does not occur is unfortunate.  if that's the problem, it'll be hard to solve.

 

Trends Neurosci. 2012 Jan;35(1):68-77. doi: 10.1016/j.tins.2011.11.005. Epub 2011 Dec 15.

The neurobiology of anhedonia and other reward-related deficits.

Der-Avakian A1, Markou A.

Author information

 

Abstract

Anhedonia, or markedly diminished interest or pleasure, is a hallmark symptom of major depression, schizophrenia and other neuropsychiatric disorders. Over the past three decades, the clinical definition of anhedonia has remained relatively unchanged, although cognitive psychology and behavioral neuroscience have expanded our understanding of other reward-related processes. Here, we review the neural bases of the construct of anhedonia that reflects deficits in hedonic capacity and also closely linked to the constructs of reward valuation, decision-making, anticipation and motivation. The neural circuits subserving these reward-related processes include the ventral striatum, prefrontal cortical regions, and afferent and efferent projections. An understanding of anhedonia and other reward-related constructs will facilitate the diagnosis and treatment of disorders that include reward deficits as key symptoms.

Copyright © 2011 Elsevier Ltd. All rights reserved.

http://www.ncbi.nlm....pubmed/22177980

 

J Affect Disord. 2013 Nov;151(2):418-22. doi: 10.1016/j.jad.2013.06.045. Epub 2013 Jul 29.

Gray colored glasses: is major depression partially a sensory perceptual disorder?

Fitzgerald PJ1.

Author information

 

Abstract

BACKGROUND:

Major depression is a neuropsychiatric disorder that can involve profound dysregulation of mood. While depression is associated with additional abnormalities besides reduced mood, such as cognitive dysfunction, it is not well established that sensory perception is also altered in this disorder (aside from in psychotic depression). Recent studies have shown that visual processing, in as early a stage as the retina, is impaired in depression. This paper examines the hypothesis that major depression can involve alterations in sensory perception.

METHODS:

A Pubmed literature search investigated several lines of evidence: innervation of sensory cortex by serotonin and norepinephrine; antidepressant drugs and depression itself affecting processing of facial expressions of emotion; electroencephalography (EEG) studies of depressed persons and antidepressant drugs; involvement of the serotonergic 5HT2A receptor in both depression and hallucinogenic drug action; psychotic depression involving sensory distortions; dopamine possibly playing a role in depression; and the antidepressant effect of blocking the NMDA receptor with ketamine.

RESULTS:

Data from each of these lines of evidence support the hypothesis that major depression can involve sensory perceptual alterations.

CONCLUSIONS:

Loss of interest in one's daily activities and inability to experience pleasure, also known as anhedonia, in major depression may in part be mediated by sensory abnormalities, whereby normal sensory perceptions are no longer present to activate reward circuitry.

LIMITATIONS:

The data supporting the hypothesis tend to be associative, so further confirmation of the hypothesis awaits additional controlled experiments.

© 2013 Elsevier B.V. All rights reserved.

 

 

Neuropsychopharmacology. 2015 Dec 14. doi: 10.1038/npp.2015.357. [Epub ahead of print]

High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation.

Dutheil S1, Ota KT1, Wohleb ES1, Rasmussen K2, Duman RS1.

Author information

 

Abstract

Depression and type 2 diabetes (T2D) are highly comorbid disorders that carry a large public health burden. However, there is a clear lack of knowledge of the neural pathological pathways underlying these illnesses. The present study aims to elucidate the molecular mechanisms by which a diet rich in fat can cause multiple complications in the brain, thereby affecting intracellular signaling and gene expression that underlie anxiety and depressive behaviors. The results show that a high-fat diet (HFD; ~16 weeks) causes anxiety and anhedonic behaviors. Importantly, the results also show that 4 months of HFD causes disruption of intracellular cascades involved in synaptic plasticity and insulin signaling/glucose homeostasis (ie, Akt, extracellular signal-regulated kinase (ERK), P70S6K), as well as increased corticosterone levels and activation of the innate immune system, including elevation of inflammatory cytokines (ie, IL-6, IL-1β, TNFα). Interestingly, the rapid acting antidepressant ketamine reverses the behavioral deficits caused by HFD and activates ERK and P70S6 kinase signaling in the prefrontal cortex. In addition, we found that pharmacological blockade of the innate immune inflammasome system by repeated administration of an inhibitor of the purinergic P2X7 receptor blocks the anxiety caused by HFD. Together these studies further elucidate the signaling pathways that underlie chronic HFD exposure on anxiety and depressive behaviors, and identify novel therapeutic targets for patients with metabolic disorder or T2D who suffer from anxiety and depression.Neuropsychopharmacology advance online publication, 13 January 2016; doi:10.1038/npp.2015.357.

.

Mcdonalds, im not loving it is the new slogan with the anhedonia induced by eating too many big macs.

 

 

Theres soo much literature to go trough, sigh

Edited by medievil, 26 February 2016 - 03:57 AM.

[MichaelTheAnhedonic]

Any update in this thread? I'm waiting for my SPECT scan. Latest MRI showed changes in fronto-temporal region and atrophy at the cerebellum... 

 

Methylphenidate worked for me, now I need to take a break from it (nutritional deficiencies, hypothyroidism, anxiety/panic attacks and lessened effectiveness).

[Hip]

I posted a list of supplements here that I find help my anhedonia. The two most effective are:

 

Colostrum powder 8 grams (= 2 heaped teaspoons) twice daily on an empty stomach

Hydrogen rich water drinking several glasses throughout the day (HRW boosts ghrelin, which in turn has mood boosting effects)

 

These make some improvements to my anhedonia, but the certainly do not eliminate the anhedonia. 

 

My anhedonia was caused by a chronic viral infection with coxsackievirus B4 (still ongoing after 14 years), which also called emotional flatness (blunted affect), and nasty generalized anxiety disorder symptoms. My website about my virus is here.

Edited by Hip, 27 May 2017 - 03:33 AM.

[PeaceAndProsperity]

 

I posted a list of supplements here that I find help my anhedonia. The two most effective are:

 

Colostrum powder 8 grams (= 2 heaped teaspoons) twice daily on an empty stomach

Hydrogen rich water drinking several glasses throughout the day (HRW boosts ghrelin, which in turn has mood boosting effects)

 

These make some improvements to my anhedonia, but the certainly do not eliminate the anhedonia. 

 

My anhedonia was caused by a chronic viral infection with coxsackievirus B4 (still ongoing after 14 years), which also called emotional flatness (blunted affect), and nasty generalized anxiety disorder symptoms. My website about my virus is here.

 

Fatigue, anxiety and flattened affect can be caused by the 5ht2a receptor. Did you try a 5ht2a antagonist?

[Hip]

Fatigue, anxiety and flattened affect can be caused by the 5ht2a receptor. Did you try a 5ht2a antagonist?

 

That's very interesting, thanks. I don't think I have ever tried a 5HT2A antagonist, but I will certain do so if it can help remedy flattened affect, which I have found is very difficult to treat. 

 

Looking at this list of 5HT2A antagonists, the antihistamine hydroxyzine is on the list, and this is a drug that I have on my shelf, but have not tried yet, so I will try that immediately — in fact I have just put a hydroxyzine tablet in my mouth as I am writing this!

 

The antidepressants mirtazapine and trazodone on that list also look like options worth trying.

 

Would you have any links to studies or articles about 5HT2A and flattened affect?

 

 

 

The virus I caught really screwed up my brain: it caused severe generalized anxiety disorder, some mild psychosis, severe anhedonia, blunted affect, as well as triggering chronic fatigue syndrome (myalgic encephalomyelitis).

 

I eventually managed to find some good treatments for the anxiety and psychosis (detailed in this post), but the anhedonia  and blunted affect are still problems for me, although they have improved a bit over the years. And the CFS is ongoing, but that's a hard disease to treat.

Edited by Hip, 29 May 2017 - 12:47 AM.