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The Anhedonia Thread

anhedonia depression attention l-dopa ssre adaptogen quetiapine consummatory anhedonia

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#331 Vieno

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Posted 01 July 2013 - 08:12 AM

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.

Edited by Vieno, 01 July 2013 - 08:12 AM.


#332 nowayout

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Posted 01 July 2013 - 02:39 PM

Has hyperthyroidism been mentioned in the thread yet?

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#333 Vieno

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Posted 01 July 2013 - 06:37 PM

Probably not but my thyroid values are normal and surely hyperthyroidism doesn't cause consummatory anhedonia and lack of response to opioids huh?

#334 3AlarmLampscooter

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Posted 01 July 2013 - 06:44 PM

Nicotine apparently helps: http://jop.sagepub.c...391831.abstract

And apparently administering nicotine without an MAO-I is not as addictive: http://www.sciencedi...091305703002235

#335 Vieno

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Posted 01 July 2013 - 06:56 PM

Again, depressive anhedonia has nothing to do with my condition.

#336 airplanepeanuts

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Posted 01 July 2013 - 07:47 PM

Again, depressive anhedonia has nothing to do with my condition.


You seem to take some pleasure in protecting this thread at least :)

In other words: Even though you started a thread, it's never only about yourself.
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#337 Vieno

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Posted 01 July 2013 - 08:04 PM

Haha, true, but it gets confusing if people discuss treatment options for different conditions here. I believe it's for everyone's benefit if this thread focuses on CA and my condition - this way other people with these issues will find ideas here. There are threads for the more normal types of anhedonia, like Dissolvedissolve's "The Anticipatory Anhedonia Thread". I guess the name and first post of this thread should be changed. I will consider that and possibly tell some moderator to take care of it.

#338 nowayout

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Posted 02 July 2013 - 07:31 AM

Prior opioid use or prior recreational drug use could cause lack of response to opioids or benzos. It is quite common.

#339 Vieno

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Posted 02 July 2013 - 08:21 AM

I have zero history of drug use. Also it's not benzos that I don't respond to, it's GABA-Bergics (phenibut and GHB).

#340 nowayout

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Posted 02 July 2013 - 09:27 AM

Maybe your dealer sells you fake pills. :)

#341 Vieno

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Posted 02 July 2013 - 11:18 AM

I don't use crappy sources :) Seriously, that's not a possibility. People get high from the very stuff that I use.

#342 Vieno

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Posted 02 July 2013 - 12:41 PM

I have been reading a bit on cholecystokinin (CCK) and despite my initial enthusiasm, it seems now that it might not be the culprit here. Increased CCK levels are seen in opioid tolerance yet opioid withdrawal does not cause CA despite all the dysphoria. Hyperactive CCK or CCK receptors could explain stimulatory issues via orxeinergic modulation and also the gastrointestinal things, but the link to CA is still completely speculative. There's not really any evidence suggesting a link between CCK and CA: instead, there's a lot of evidence showing elevated CCK levels NOT causing CA (as in opioid tolerance/withdrawal).

This doesn't mean that high doses of herbs won't work as they have tons of functions, but I'm doubtful regarding the role of CKK.

#343 Vieno

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Posted 14 July 2013 - 09:30 AM

So I and Galaxyshock have been discussing the different possible pathologies and treatment strategies regarding my CA over private messages and here are some of our conclusions.

Firstly, my CA seems highly similar to GABA-Bergic (phenibut/GHB) abuse induced post-acute withdrawal syndroms. We have three sources for this claim:

First, Galaxyshock himself used too much phenibut and months after stopping cold turkey and experiencing a short lived acute withdrawal he experienced so strong CA that he finds it likely that not even an opioid would have worked. When he later tried phenibut again, it didn't work nearly as strongly as before indicating a similarity to my lack of response to GABA-Bergics. He also experienced other symptoms similar to mine such as feelings of hotness, disturbed circadian rhythm and excess stimulation. The herbs St. John's Wort and Ginseng corrected most of his symptoms and the herb Gotu Kola was particularly helpful for the CA.

Second, a thread at Bluelight (http://www.bluelight...g-D2-antagonism) describes strong CA as a result of at least GHB/GBL abuse, possibly benzo too. The OP describes both opioids and speedball lacking euphoric properties and the user yaesutom reports hydrocodone working in an extremely diminished manner (to me this sounds similar to my brother's experience with opium). It is not clear if this symptom occurred in acute or post-acute withdrawal but I doubt it was right after discontinuation as not many in that horrible acute GHB withdrawal would try to get high on opioids or a speedball.

Three, in this thread (https://groups.googl...2I/eBOHpcaUVSkJ) disappearance of GHB's euphoric effects is described (I do get high with high doses of GHB but it's not euphoric). The OP's idea of acidosis is highly questionable IMO but his symptoms are nevertheless obviously real.

The conclusion that can be drawn from here is that a GABA-B related disturbance in brain function causes CA and lack of response to opioids. It's not GABA-B downregulation as the CA can persist and/or come in to being after acute withdrawal. I lack response to both opioids and GABA-Bergics.

As for what exactly is this GABA-B related disturbance causing CA, we don't know. It may have to do with sleep and circadian rhythms and thus may involve histamine or orexin, which suggests a possible role of cholecystokinin (CCK) as suggested by Galaxyshock (as CCK regulates orexin release).


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


Since posting here last time I have thoroughly tested St. John's wort (standardized to hypericin content) and Panax Ginseng. I did SJW with doses of 0,6g-4,2g and Ginseng with doses of 1g-6g. Both induced some hypnotic effects but nothing else. Next in line are Gotu Kola and diphenhydramine which I have acquired both. I am working on obtaining Proglumide (a CCK antagonist).

SJW made me considerably tired at evening and allowed me to get to sleep at normal hours. After I discontinued it I continued to get to sleep early. However there has been a lot of fluctuation in my levels of tiredness and at some nights I have been able to sleep better than others. Ginseng amplified general tiredness. In general, for the past couple of weeks I have been sleeping at nights like normal people but my general levels of tiredness have been abnormally fluctuating, for example I have sometimes been so tired at daytime that I have absolutely had to take a nap which is abnormal for me. I haven't been using perphenazine for weeks. Unlike these herbs, it gave a very steady and stabile correction of the circadian rhythm. I can conclude that my weird circadian rhythm is not unyielding as these herbs easily mould it even after discontinuation but nevertheless there is constantly something wrong with my sleep-wakefulness system.


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Some related articles that may shed light on CA in general (unfortunately, only abstracts are available for the first tree for free):


http://www.ncbi.nlm....pubmed/17031710
http://www.ncbi.nlm....pubmed/16099508
http://www.ncbi.nlm....pubmed/15961147
http://www.jneurosci.../27/7/1594.long

Edited by Vieno, 14 July 2013 - 09:43 AM.

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#344 airplanepeanuts

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Posted 24 July 2013 - 08:54 PM

I have zero history of drug use.

Then finally when I overdosed on methamphetamine


So..

#345 Vieno

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Posted 24 July 2013 - 09:43 PM

I have zero history of drug use.

Then finally when I overdosed on methamphetamine


So..


Let me clarify: before late 2012 when I began the attempts of self-medicating CA my all drug experiences constituted of neglible alcohol and cannabis use - so neglible that it really does not count in any measure. The meth overdose occurred on spring. I was very inexperienced with drugs and practiced some bad judgement. That's the only time I've had any problems with drugs.

A little update regarding my situation: Gotu Kola with doses of 0,9-9g failed to produce any effect. Diphenhydramine with doses of 50-285mg produced typical antihistaminic and antimuscarinic effects excluding euphoria and had no positive effect on CA.

Galaxyshock and I are constantly figuring out this stuff, I'll soon post about our ideas and plans. Hopefully some of you can chime in too :)

Edited by Vieno, 24 July 2013 - 09:45 PM.


#346 SlimNm

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Posted 14 August 2013 - 11:33 PM

Hey, I responded to you on the mindandmuscle.net thread, I hope you get back to me either here or there.

#347 SlimNm

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Posted 18 August 2013 - 01:06 AM

Maybe it's time to think outside of the box (even moreso than you already are).

This may sounds stupid, but it seems like it can only help:

Go to Wal-Mart in the supplement section, and buy one bottle of EVERYTHING they have there, be it for Women, Men, muscle building, anxiety, cardio health, etc.

Everyday, take the recommended serving of a different bottle.

See if anything helps in the least.

Just trying to help... I know how frustrating this can be, even though I'm not sure if I've ever felt your exact type of anhedonia or whatever... also, good job not getting all rude when so many people chime in on this thread with off-topic stuff xD
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#348 Vieno

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Posted 18 August 2013 - 12:40 PM

Heh mate, the small pieces of off-topic here are nothing compared to the shit I get in real world. People here have at least some background in neurobiology and understand something of this stuff, but IRL, man, it's like talking to walls, no-one understands anything. Think about how off-topicy their talk gets. I appreciate everything that people say in this thread even though it's sometimes indeed quite far from what is relevant to my fight against CA.

My next move is to extend the discussion outside my private discussions with guys like Galaxyshock. I'm trying to get as many people as possible involved in the ponderings, recruiting minds at different forums (hint, please spread the word!). Another thing that I'm doing is that I'm contacting researchers directly. I've recently found some really good research on the topic and I believe the researchers might be interested in my case. It could turn into reciprocal interaction, them learning about the mechanisms of pleasure generation and me getting some sound treatment ideas from the experts.

I appreciate you trying to help me, but I'm afraid that trying drugs mindlessly is not a good idea at this point. I've basically been there, done that. Evidence is pointing at a highly localized dysfunction as the culprit to my CA, and systemic administrations of drugs just won't do anything about such. There are still some drugs that I want to try, but it won't be so much to counter the CA as to check my reactions and thus possibly understand something more about the disease. Even though all my drug experiments have failed to help, they've been of priceless value in terms of revealing the details of the pathogenesis.

In my last post to this thread I said I would soon share our newest ideas and I never did that, I guess I should do it today then. A big update.

#349 SlimNm

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Posted 18 August 2013 - 02:19 PM

I have to say, you're probably the most functional person I've ever read about for having anhedonia (or whatever it is called). Good luck!
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#350 Vieno

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Posted 18 August 2013 - 03:13 PM

That's because I don't have "anhedonia". There is NOTHING wrong with my emotions. It's just the pleasure that doesn't occur. You must make the distinction between emotions and pleasure in order to understand this. I do get very dysfunctional when the thought of never getting rid of this takes over, but then I shake it off and get back to figuring this out. Not having pleasure is torturous in the long term but it doesn't directly affect one's functionality at all.
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#351 SlimNm

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Posted 18 August 2013 - 04:53 PM

That's because I don't have "anhedonia". There is NOTHING wrong with my emotions. It's just the pleasure that doesn't occur. You must make the distinction between emotions and pleasure in order to understand this. I do get very dysfunctional when the thought of never getting rid of this takes over, but then I shake it off and get back to figuring this out. Not having pleasure is torturous in the long term but it doesn't directly affect one's functionality at all.


I still don't understand.

If all your emotions are intact, like excitement, than how does excitement not give you pleasure? I thought excitement and pleasure were inseparable.

Is it because you feel disconnected from you emotions, as if you are watching them instead of experiencing them?

I just don't understand, sorry.

EDIT: To clarify, I thought that all the positive emotions were just variations of pleasure.

Edited by SlimNm, 18 August 2013 - 04:54 PM.


#352 Vieno

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Posted 18 August 2013 - 05:03 PM

Depending on the terminology used, I'm sure in some contexts positive emotions do refer to pleasure and vice versa, but in the context of drugs and neurobiology, they most certainly are not the same. Emotions, like I said at mind and muscle, have a cognitive component. As much as they are feelings they are also thoughts. Pleasure, on the other hand, is like pain, it can exist regardless of the thoughts one is having. Surely these two normally induce certain types of thoughts, but the correlation is not perfect.

Positive emotions, like happiness, are thoughts about things being good. A happy person is thinking about how his/her life is good, how other people's lives are good, how the sun is shining and the rain is far away, how the future will be good - and these thoughts make the person experience the happines, ie feel the happiness. I'm not sure if positive emotions itself also induce pleasure, maybe they do, but they're not the same thing nevertheless. Pleasure is something that can be induced regardless of the thoughts. Also, unlike emotions, that have endless variations - there is an infinite amount of different emotions - pleasure is always the sime. The easiest way to induce pleasure is to activate the mu receptors. With the exception of some extremely rare cases like mine and yours* for that one month, people feel strong pleasure when thir mu receptors are activated. Strong pleasure = euphoria.

When I recently took MDMA I experienced many positive emotions, I was very content. My mind was bright and I was thinking about good things, I felt good, I felt positive emotions. But I didn't experience pleasure.

When I listen to a sad song, I get sad, but the song fails to induce any pleasure. Music doesn't lift me up, it doesn't take me to "another place". Emotions are there but pleasure isn't.

* For the information of others, SlimNm does not and never had my condition, his SSRI withdrawal temporarily made him so anhedonic that he couldn't even feel the pleasure of opioids, however opioids did induce their other effects so the pathogenesis was clearly completely different.

Edited by Vieno, 18 August 2013 - 05:05 PM.

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#353 SlimNm

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Posted 19 August 2013 - 07:42 AM

Wow, that was very informative! I think I understand now.

#354 Vieno

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Posted 19 August 2013 - 12:03 PM

I'm glad I could help. Now it's time for my update.

Every theory presented in this thread has now been tested and ruled out. There is no reason to test drugs endlessly as the chances for some random choice to help are minimal, and recently we've encountered some research that is pointing to a cause that is anyway inaccessible with systemic drug administrations: highly localized dysfunctions. These two articles have given us a lot of insight into the mechanisms that generate pleasure in the brain:

Hedonic Hotspots: Generating Sensory Pleasure in the Brain
http://www.smith-lab...es-of-Brain.pdf

Ventral Pallidum Roles in Reward and Motivation
http://www.ncbi.nlm....les/PMC2606924/

Even though it's not clear where and how exactly my pleasure pathways have become dysfunctional, it appears that the pleasure generation is a highly localized process, and that the only way to block pleasure from occurring (like in CA) is to disturb the function of certain very specific and small sites inside the basal ganglia. Indeed, even very widespread lesions have not been able to induce CA, so for CA to occur some very specific and unique dysfunction is required.

What puzzles me though is how my mu-opiod as well as GABA-B receptors seem to be extremely non-responsive. How can a local issue prevent the function of mu-receptors that are distributed all the way down in the intestines? Also, it is puzzling how the only clear symptom I have is CA (and possibly some less severe sleep and stimulatory issues) and yet my drug reactions are much more extensively disturbed. For example, I would assume that the kind of total mu-opioid dysfunction I have would also cause pain hypersensitivity, but no, all I have is CA and some small sleep and stimulatory issues.

Figuring out the exact pathogenesis by ourselves has proven to be quite the challenge, and thus I'm instead trying to look at the big picture now and to sum up the essentials of the condition to make it easier for others to chime in. So the essential features of my condition are:

Consummatory anhedonia
This is the symptom that I'm trying to treat. It is complete lack of pleasure as a response to pleasurable stimuli such as sex, sugar and music. It has pretty much nothing to do with the normal anhedonia seen in psychiatric disorders and in several neurotransmitter, hormone or even dietary deficiencies.

Rewarding drugs fail to induce pleasure
I also lack pleasure as a response to drugs. Stimulants are capable of inducing some pleasure, but even very big doses induce only very little pleasure. I suspect that other rewarding drugs might have the same effect at high doses, but I have mostly stuck to low to moderate dosages.

Opioids have zero effect
Opioids do not induce any effect in me. At this point it is unclear whether huge doses could induce some effects.

GABA-B agonists have extremely diminished effects
Phenibut induced some hypnotic effect at 10g but nothing else. GHB threshold is around 2,5g, 3,5g produces a short lived and non-euphoric intoxication.

On/off nature
The consummatory anhedonia has on occasion switched off and I have felt all the pleasures to the fullest extent for anything from one hour to two days. It is unclear whether opioids and GABA-B agonists would have worked normally during these "windows", I suspect at least opioids would have as they appear to be of such critical importance for pleasure. It is noteworthy that even though systemic opioid antagonism does not induce CA, opioid antagonism at certain "hedonic hotspots" ie small specific sites implicated in pleasure generation does indeed cause CA. Coupled with this lack of opioid response of mine, it is clear that opioids and the mu receptor play a central role in natural pleasure.

Some have suggested that my condition could be due to lesions, organic brain damage or neurodegeneration of specific sites and/or mechanisms pertaining to pleasure generation. I think that the on/off nature of my condition proves that this is not the case: a damaged brain is not capable of switching back to healthy function for a while just to go back to dysfunction soon again.

Genetic causes
My brother also has this condition. He has severe consummatory anhedonia and like me, has diminished response to opioids. He does have some response however so it appears that his CA is slightly less severe. As we were already living separately when the CA started to occur (it came first for me, then later for him), it appears that environmental factors do not play critical role.

Other symptoms
In addition to CA, I do suffer from certain circadian rhythm and stimulation related issues too. I generally feel hot and alert during night time and find it difficult to fall asleep before morning. This does severely impair my everyday functioning. Sometimes I also get over excited about something and find myself behaving and feeling like I would be on stimulants. This is a minor trouble. Interestingly, the typical antipsychotic perphenazine corrected both my sleep/circadian and stimulatory symptoms. I haven't tried other antipsychotics.

I do not have any other symptoms that could in any way be related to the CA (ie be related to brain function) which makes my condition seem to be extremely specific instead of being a widespread dysfunction.

GABA-B agonist use causes the same condition
Apparently, in some rare cases the excess use of the GABA-B agonists phenibut and GHB has induced the same condition. Consummatory anhedonia, lack of opioid response, lack of drug pleasure and high tolerance to GABA-B agonists have all been present for anything from one month to one year following the cessation of GABA-B agonist use.


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To sum up all of the above, it seems to me that it is certain that there is no damage in my brain but a mere signalling mistake. The role of genetics is pretty obvious. Even though viewing the endorphins as the pleasure generators is simplistic, it is clear that the opioid system is involved in the pleasure generation and therefore modulating it is a good strategy. GABA-B probably plays some central role in this.
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#355 FeelsNumbMan

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Posted 09 September 2013 - 11:34 PM

Honestly, I feel anhedonic all day everyday and I don't know what can I even do.

I don't even get windows of pleasure. Especially not with music.

#356 SlimNm

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Posted 10 September 2013 - 01:09 AM

Vieno, have you tried high dose opioids and noticed whether or not they cause constipation? If even massive doses of opioids do not cause constipation, that would be VERY weird. On top of the other weird things, of course.

Does staying up for 36 hours cause any relief? I don't remember if you said anything about this yet.

P.S. To test the opioid thing, you don't need to go out of your way to get anything illegal. Just get the legal version at Wal-Mart.

Edited by SlimNm, 10 September 2013 - 01:10 AM.


#357 FeelsNumbMan

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Posted 10 September 2013 - 01:37 AM

Vieno, have you tried high dose opioids and noticed whether or not they cause constipation? If even massive doses of opioids do not cause constipation, that would be VERY weird. On top of the other weird things, of course.

Does staying up for 36 hours cause any relief? I don't remember if you said anything about this yet.

P.S. To test the opioid thing, you don't need to go out of your way to get anything illegal. Just get the legal version at Wal-Mart.

I'm curious. What's a legal opioid thing that you can buy at Wal-Mart?

#358 SlimNm

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Posted 10 September 2013 - 01:58 AM

Loperamide.

#359 Vieno

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Posted 10 September 2013 - 06:40 PM

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

Edited by Vieno, 10 September 2013 - 06:45 PM.


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#360 SlimNm

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Posted 10 September 2013 - 07:30 PM

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


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 :)





Also tagged with one or more of these keywords: anhedonia, depression, attention, l-dopa, ssre, adaptogen, quetiapine, consummatory anhedonia

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