420 replies to this topic

[chris106]

Antihistamine like Diphenhydramine is worth a try to see what happens

I will go check out all the mentioned substances: DPH, Gingseng and St. John's.

Could anyone tell me a source for DPH (Diphenhydramine)? I 've searched the web high and low and checked all my trusted online pharamcies / generic-shops.

I usually find at least one source for even the most exotic compounds I read up on here, but no results this time :(

[Dissolvedissolve]

Could anyone tell me a source for DPH (Diphenhydramine)? I 've searched the web high and low and checked all my trusted online pharamcies / generic-shops.

I usually find at least one source for even the most exotic compounds I read up on here, but no results this time :(

In the US, it's sold as Benadryl, an over-the-counter allergy medication. It should be readily available in any drug store as the active ingredient of a first-generation antihistamine.

[Vieno]

Regarding adenosine: I recently have noticed caffeine to produce unpleasant effects in me and therefore have reduced its intake. I don't like coffee so I get all my caffeine from (black) tea, which I have restricted to a max of four cups a day. I don't seem to be particularly sensitive to caffeine, but if I do feel the effects, they are unpleasant. I once drank two liters of coffee just to see how it works and I got quite the crappy stimulation - didn't last for long though. I don't think these experiences speak for hyperactivity of adenosine as the culprit, but neither do they explicitly rule it out. I did some reading and the torpour-inducing effects seem interesting as indeed I seem to have trouble entering a torpourish state at nighttime.

On the other hand, according to wikipedia: "Consumption of caffeine antagonizes adenosine and increases activity in neurotransmission including acetylcholine, epinephrine,dopamine, serotonin, glutamate, norepinephrine, cortisol, and in higher doses, endorphins which explains the analgesic effect to some users"

Indeed extra adenosine doesn't very much seem to cause mu-dysfunction. But this is all very speculative. How could I test it? All adenosine receptor agonists seem research substances, I have no access to them. There are many reuptake inhibitors though. I've felt that alcohol momentarily sort of helped my circadian and sleep problems but it didn't improve CA. No doubt benzos would do the same. Is it due to GABA-B or adenosine modulating actions? Could very well be just the former, but if it's the latter, then pro-adenosinergia doesn't seem to improve my CA. If hypoactive adenosinergia is responsible (in part) for my stimulatory issues, perhaps the underlying cause - whatever it is - is causing hypoactive adenosine in addition to hyperactive dopamine (which seems indisputable due to the positive effects of perphenazine) and whatever mechanism it is that is blocking pleasure and mu. This is getting far out there... gotta try stuff.

Recommendations on what adenosinergics to try?

Edited by Vieno, 17 June 2013 - 07:25 AM.

[Galaxyshock]

St. John's Wort seems to have effects at adenosine too.
http://www.ncbi.nlm....pubmed/12775192

The compounds in it also bind to delta opioid receptor and do a whole lot of NT modulation:
http://link.springer...-0440-8/001.png

SJW is definitely something to try because wide range of mechanisms.

For more selectively targeting adenosine you could take Reishi in high dose.

Ginseng works very well as a mood boost, thanks Galaxyshock! I feel I get pretty tired around 5 PM if I take it in the morning, does this ever happen to you? I'm going to keep testing this gem.

The anti-depressive effect is through 5-HT2A agonism, stimulative effects through cAMP. Calming/antipsychotic-like effects through binding to NMDA, GABA, serotonin and dopamine receptors. Does a whole bunch of other things too. I have noticed that when it wears off at some point I may feel tired, dosing two or three times a day works well. Sometimes I've taken it at night when feeling restless and it helped calm down to sleep. It's very good adaptogen if one responds to it.

But how about those H3 agonists, are there any easily accessible ones? It is my understanding that H3 agonism, not antagonism, is the desired function.

There are some H3 receptor agonists listed in the wikipedia page: http://en.wikipedia....ine_H3_receptor
I'm not sure about accesibility though.

Edited by Galaxyshock, 17 June 2013 - 09:09 AM.

[stablemind]

Ginseng works very well as a mood boost, thanks Galaxyshock! I feel I get pretty tired around 5 PM if I take it in the morning, does this ever happen to you? I'm going to keep testing this gem.

The anti-depressive effect is through 5-HT2A agonism, stimulative effects through cAMP. Calming/antipsychotic-like effects through binding to NMDA, GABA, serotonin and dopamine receptors. Does a whole bunch of other things too. I have noticed that when it wears off at some point I may feel tired, dosing two or three times a day works well. Sometimes I've taken it at night when feeling restless and it helped calm down to sleep. It's very good adaptogen if one responds to it.

I also take Seroquel at night, which antagonizes the 5HT2A receptors which still caused an antidepressive effect for me when taken alone, which I find strange since 5HT2A agonism/antagonism both work for me. However, I take it at night so do you think it's possible that the antagonism at night causes receptor sensitivity/upregulation in the morning, and when combined with 5HT2A agonism, causes an even greater antidepressive effect rather than either alone?

Edited by stablemind, 17 June 2013 - 11:31 AM.

[Galaxyshock]

Actually it seems that the receptor works differently and that a 5-HT2A antagonist decreases 5-HT2A signalling both for its duration of effect and afterwards. It may be that Ginseng competitively neutralizes the effect of Quetiapine on 5-HT2A, or the mood boost you experience is from Ginseng's antipsychotic or stimulative effects.

[Vieno]

I'm working on getting the mentioned substances, it's gonna take time but I'll update on instant when I get to try something. In the meantime I'll study basic biology to get some foundation for my investigations.

I'm not certain that there's a link between my circadian/stimulatory issues and CA, however I do see the possibility as they seem to have developed rather simultaneously. Recreational substances have anyway been ruled out as therapeutic agents and stimulants in particular have been proven unpleasant for me, so I suppose depressant/sedative non-recreational drugs, such as the mentioned antihistamines and adenosinergics, are my best bet at the moment. However I believe I should not rule out anything I haven't tried as all our theories are extremely speculative. So in addition to going for the mentioned drugs, I'll do pretty much anything I can get my hands on. I will report.

Perphenazine continues to effectively normalize my circadian rhythm and prevent depressive feelings.

6mg perphenazine + 36 methylphenidate combo resulted in rather severe tachycardia (resting BPM 120-150 for three hours), didn't see that coming.

The next product I'm most likely to test is St. John's wort.

Edited by Vieno, 19 June 2013 - 05:43 PM.

[Vieno]

By the way, regarding the possible link between stimulatory issues and CA: my brother seems to have the latter to an extent as evidenced by diminished response to opioids, yet does not seem to have the former. This indicates that the two conditions are not necessarily linked, and therefore I should also continue to seek for drugs that do not possess anti-stimulation/pro-torpor effects.

It is also entirely possible that there is a link as my stimulatory issues are far less pronounced than the obvious CA, so if my brother has both to a lower extent, maybe the stimulatory issue just is not big enough to be noted. I just think it's good for you all to know how my brother's condition relates to mine.

[Vieno]

Another hypothesis could be some metabolic disorder affecting neuropeptides. Hyperexpression of cholecystokinin or overactivation of cholecystokinin -A receptor, leading to both high endogenous opiate tolerance and hyperactivity of Orexin / Hypocretin (http://www.jneurosci...tent/25/32/7459). Hypocretin is another wakefulness modulator (low in narcolepsy for example) and central administration of orexin-A strongly promotes wakefulness, increases body temperature, locomotion and elicits a strong increase in energy expenditure (you mention body temperature issues and excitability strong enough to be unable to stand still). It's also linked to mood and social interaction (http://www.nature.co...ncomms2461.html), you mentioned sudden lift from anhedonia when talking to a friend and the connections to music. Cholecystokinin A also regulates the release of dopamine and beta-endorphin (http://www.ncbi.nlm....ermToSearch=886). This is again wild guessing I'm doing based on some connections I picked up but some very novel approach I'm pretty sure is needed. There are at least some cholecystokinin A antagonist drugs, and the herbs Gotu Kola and Neem have CCK modulative effects too. I'm thinking high CCK-blocking to see if any relief or effect, and perhaps then try an opiate if the tolerance would have reversed.

Has your appetite/satiety been affected or any gastrointestinal symptoms? Could give some indications about neuropeptide activity.

Neuropeptides are worth investigating in the sense that neurotransmitter modulation doesn't seem to work for my CA. Obviously not all NTs have been tried yet but I must prepare myself for none of them having effect on CA.

I have had significant problems with appetite and satiety for the past years, but I attribute them more to lifestyle and personality than to physical abnormalities. Can't be sure though. I have had issues such as feeling hungry excessively often and not being able to increase bodyweight by eating more, but indeed I feel these have mostly been due to the type of diet etc.

My gastrointestinal system on the other hand has expressed some dysfunction, such as excessive gas build up, slight occasional stomach pain, digestion issues, hypersensitivity to fiber. As I don't (yet) know almost anything about neuropeptides, could you clarify what symptoms are we looking for? I could then focus my thinking to specific issues to see if I indeed have some neuropeptide-linked dysfunction.

These gastrointestinal issues, just like my stimulatory and circadian issues, are nothing compared to CA, but they most certainly have puzzled me for a long time and therefore they do exist and are clearly noticeable.

Edited by Vieno, 22 June 2013 - 12:19 PM.

[Vieno]

^^ Sry, this thread isn't about anhedonia :D

Did 50mg of tramadol today. I'm not sure but it possibly induced unpleasant stimulation. I had a worse day than usually. I was unable to perform attention-requiring tasks that I normally get done easily. I got sweaty and anxious. Later I had to walk for a long time as I felt an unpleasant urge to move. Felt like a very small dose of methylphenidate, maybe 15mg. Is this NE reuptake inhibition? What's puzzling is that the effects were extremely long lasting, they're now finally wearing off after 12 hours of administration. Maybe the perphenazine somehow contributed, at least methylphenidate + perphenazine combo was very bad. I have some MDMA here and I'm curious about the SE release - my brother loved MDMA when he recently tried it - but I'm hesitant to try even a small dose due to bad experiences with DA/NE transmission enhancement.

Edited by Vieno, 22 June 2013 - 07:35 PM.

[chris106]

Did 50mg of tramadol today.

I tried around with Tramadol because of my PE various times in doses up to 150mg. It seems extemely weird to me that it would be stimulating for anyone, but then again everyones brain chemistry is different etc...

However I find it even more odd that it had any profound effects at such a low dose. I don't even know what perphenazine is, but I'm still pretty sure it must have been the interaction between the two. Cause Tramadol does not like being mixed with A LOT of substances at all, it's quite drug-interaction crazy. I would only take it isolated - stuff can get ugly, believe me...

Edited by chris106, 22 June 2013 - 09:55 PM.

[Vieno]

What's PE?

I don't know if tramadol caused those effects or not. Perphenazine is a typical antipsychotic and I can't see much interaction between the two, but weirder things have happened like my methylphenidate + perphenazine combo. I don't know perphenazine's binding affinities so maybe it works at some same sites as tramadol. I would like to try more tramadol but I'm unwilling to ruin a day once again, that has happened too many times recently. Maybe I'll just go for the St. John's wort next.

Edited by Vieno, 23 June 2013 - 08:03 AM.

[chris106]

What's PE?

I'd rather if you don't ask - it's an annoying but not lethal condition, let me just put it that way... ^_^'

[Vieno]

Yea ok I know it now, good that tramadol is working for you.

[John Schlongfellow]

I'm gonna be a newb here....

cannibinoid agonists were mentioned on the first page

I've had wonderful luck shaking CA with canibinoids, unfortunately the most available kind don't come with a COA and dosing is problematic, non to mention health repercussions and maaking you dumb and or lazy.

are there any cleaner canibinoid agonists?
the JWH-XXX series comes to mind

ok I'll go back and read the whole thread now.....


IIRC tramadol is a MAOI
DXM might also work for your PE.
careful as large doses can cause anorgasmia, wouldn't that be ironic?

Edited by John Schlongfellow, 27 June 2013 - 12:21 AM.

[magniloquentc0unt]

I found out that Tianeptine helps a lot for anticipatory anhedonia: i find myself slightly excited at the tought of doing something.
example: even only printing out a document and store it somewhere to create a sort of library seems a good idea now, whereas 3months ago i wouldve tought it was pointless.
there is some slight, inicial excitement, but i lack the energy/motivation to act out on that. (besides, i rarely feel rewarded or satisfied)
the problem is the asthenia that still remains, i have apparently very little energy to act on this excitement. even if i start, i get bored immediately as there is no reward feeling, im never satisfied and never feel accomplishment: anyone found a substance that helps in that sense?

[magniloquentc0unt]

Imipramine (a TCA antidepressant).

could you describe what imipramine is doing for you? Im looking for some kind of augmentation on the tianeptine

[noos]

Thanks, will read upon that stuff too but I'll comment only antihistamines now. There's a whole plethora of H1 antagonists known and I'm sure I can access some of them. DPH will be an excellent testing tool as it possesses two potentially therapeutic functions, antihistaminic and antimuscarinic. Also it's great how many antipsychotics are also antihistamines, they may have many therapeutic functions combined. If anyone knows of any particularly promising compounds, let me know.

But how about those H3 agonists, are there any easily accessible ones? It is my understanding that H3 agonism, not antagonism, is the desired function.

Why will DPH help anhedonia? Please explain.

Edited by noos, 27 June 2013 - 12:47 PM.

[Vieno]

@John,

Thanks for your input. Could you describe your CA in greater detail? It is so rare of a condition that I want to be sure you do really have it and not somethibg else like AA. Do you have any baseline AA, depression or anxiety? If you let yourself relax and don't think too much (ie let yourself enjoy stuff), how much pleasure/euphoria do you experience when listening to music, eating sugar foods, getting an orgasm or doing recreational drugs?

As for reading the whole thread, bear in mind that the terminology was not that well established at the beginning of the thread and the CA/AA distinction was not made clear until Dissolvedissolve pointed it out (thanks!).

For me cannabis is bad. It induces tachycardia, hypotension, loss of coordination, trouble recalling and anxiety. Zero pleasure. Haven't done other cannabinoids. Medievil mentione that cannabis on its own is bad for him but with a serotonergic like a releaser it works for his CA. Appears though that despite the same symptom, my and medievil's patjologies are entirely different.

@noos,

What I have is complete lack of pleasure in response to pleasurabsle stimuli or even recreational drugs. It is no anhedonia, I had understood anhedonia wrongly when I created this thread. The potential of DPH is based on a) histamine's action on the mu-receptor and b) on antimuscarinics' lpeasurable and opioid-enhancng effects.

[Vieno]

^^ Sry for the typing mistakes, was using an iPad.

Anyway. I have looked into cholecystokinin (CCK) based on Galaxysshock's ideas and it seems like a highly potential candidate. First, CCK has effects on mu-function: CCK antagonist proglumide enhances opioid effects and prevents tolerance from building up. Second, CCK enhances gastrointestinal motility which I have abnormally much. CCK antagonist would suppress this. Third, CCK enhances orexin transmission. The orexing-induced arousal and stimulation are exactly like my symptoms, more so than the effects of any other neurochemical.

Edited by Vieno, 27 June 2013 - 02:33 PM.

[chris106]

DXM might also work for your PE.

It sure might, but it seems way too risky to me to even conscider it Thanks for the suggestion, though.

On a site note, regarding PE I'm having quite good results with 50mg of Anafranil, which is a tricyclic AD. It works better and causes less side-effetcts for me than Tramadol.
But let's not derail this thread - should I (hopefully) soon find a somewhat safe treatment option for PE, I'm gonna start a new thread about the topic.

[Vieno]

How is DXM risky? Answer that and then we'll stop offtopicing :D

[chris106]

Well, to be fair - I haven't really looked further into it, because thread titles like the following instantly made it seem like the worst thing ever:

http://www.longecity...oxicity-of-dxm/

http://www.longecity...g-dissociation/

http://www.longecity...uced-psychosis/

While I have no time to dig deeper into the subject right now, I guess those horror stories are more related to long term abusive use? Like taking it recreationally to get high?
I suppose if taken occasionally in the right doses just to treat PE you would conscider it safe then? After all Tramadol isn't an exactly "safe" compound either if taken over longer periods of time...

As I said I don't know the first thing about DXM as of now, guess I'll have to do some research. That being said, do you know of anyone who has taken it occasionally to treat PE?

Edited by chris106, 27 June 2013 - 08:51 PM.

[Vieno]

Pretty much every recreational drug does shit like that but it's always about long-term abuse. Not sure how it should be used for PE though. If it's simply about NMDA antagonism, then memantine would be a safer option. DXM itself isn't anything particularly dangerous, far safer than say stimulants or benzos. But yeah go make your own thread, it's for everyone's benefit

Edited by Vieno, 27 June 2013 - 08:53 PM.

[chris106]

Not sure how it should be used for PE though.

I remember stumbling across claims like that before regarding DXM when doing intensive PE research - so there's definetely something to this. I just vaguely remember some annecdotal reports claiming it's the best thing ever against PE for some people - don't ask me about the mechanisms behind it though. The other thing I remember are horror-stories like those in my previous post, which made me instantly drop the idea of using DXM.

Like I said - pretty short on time right now, but I guess I'll do some extensive research about it next week.
I'm searching for something with imediate onset of effects with few or no side effects, which I would only use occasionally. (2 times a week max, since not in a relationship right now :3 )
So I pretty much wouldn't care for negative consequences of long term chronic use of the compound, as long as it works well regarding the two criteria mentioned above...

[Vieno]

Lol man, a low dose of DXM once to see how it works is as far from dangerous as anything can be. But well, go to your own thread now!! :D

[nowayout]

A cognitive trick I read about recently that I am trying: simply try to notice whenever anything in your day makes you feel even slightly good or, if not good, better than otherwise. The idea is to slowly reprogram yourself.

I don't really believe in self-talk and all that pop psychology, but this is something really simple that seems eorth a try.

Edited by nowayout, 28 June 2013 - 07:47 PM.

[Vieno]

That often works for anhedonia indeed Anhedonia seems to be often curable or at least significantly alleviated by CBT (well, BT is enough). Doesn't work for me however, I tried to notice the effects of opium very carefully but they just weren't there

[nowayout]

I don't think it is good to continually self-monitor. That is counterproductive. It is better to monitor after than during.

[Vieno]

It's not the typical anhedonia that I'm dealing with. Monitoring is not an issue here.