The Anticipatory Anhedonia Thread
#301
Posted 09 June 2013 - 01:50 PM
SAM-e is one of the things I desperately want to try, because of from what I can tell from anecdotes, whether it works for me or not could help me determine where my actual problem or the cause of my anhedonia lies.
I'm not certain what to think about the whole over- or under methylator theory, it's more about finding out if my problem is solely of dopaminergic nature (add-pi diagnosis),
or if low serotonine actually plays a part too. (I might has well have too much Serotonine going on, for all that I know)
I would of course also be hesitant to start with SAM-e before I've given the adaptogen-combo itself enough time to show it's efficiancy. But once a few weeks in, I would really like to try SAM-e as well (unless of course, my problems should totally diminsh by then). So is it generally safe to take it in addition?
(also finally getting motivated enough to read and learn more about the various receptors, Transporters and working-mechanisms in general, so that in a few weeks/months time from now, I won't have to ask stupid standard questions like the one above I guess the stuff is slowly starting to show effects allready...)
#302
Posted 09 June 2013 - 05:11 PM
Does anyone know if it's safe to combine SAM-e with the adaptogen combo (SJW, Panax Ginseng, Jiaogulan, Bacopa and eventually Rhodiola) mentioned above?
First of all, SJW does not mix well with very much. If you treat it as an MAOI, that means you can't mix it with adrenergics (risk of hypertensive crisis) or serotonergics (risk of serotonin syndrome). Now realistically, it's not a very intense MAOI, so those risks are pretty low, but they do theoretically exist.
Now let's treat it as a reuptake inhibitor, which it definitely is, with notable affinities for NE, DA, GABA, and 5-HT (it also inhibits glutamate reuptake, but the IC50 is so low as to probably not be relevant). So you can't mix it with serotonin releasers (ie MDMA would be a very bad idea). You probably shouldn't mix it with catecholamine releasers (ie amphetamine is functionally a releaser by reversing DAT flow).
It also induces certain liver enzymes which can affect bloodstream concentrations of other drugs.
Now SAMe is not very well understood, unfortunately. I've read a good number of articles on it, and there was speculation that it causes NT release of a variety of kinds. Now in that case, you definitely do not want to mix it with SJW. You could probably mix it with ginseng and jiaogulan. I can't speak to the safety of rhodiola and bacopa with it. I'd encourage caution with bacopa since it often causes sedation. For me, personally, the sedation never went away, and it worsened my anticipatory anhedonia in the ~3-4 months I used it.
I'd encourage you to try one supplement at a time. Don't start with a bunch because you'll have no idea what's working and what isn't.
#303
Posted 09 June 2013 - 05:42 PM
Well, I guess I'll try Jiaogulan instead of Bacopa with SJW and Panx Ginseng for the time being, then. Seemed to work well for Galaxyshock, too. Will save the Bacop as a last resort, should the rest get too stimulating (which I highly doubt ATM).
Regarding SAM-e - I guess I'll give it a try some time soon and start with really low doses. It's just such a pain in the ass having to whait several weeks to determine wether a single compound is usefull or not... -_-'
#304
Posted 10 June 2013 - 09:49 AM
Bacopa goes fine with SJW, I really like the serotonergic effects of both. Make me very sociable - and I have asocial tendencies, even felt misanthropic at times. I can really see good in people, feel connection and genuine interest. Bacopa is not usually sedative or dulling to me (calming and anxiolytic yes) as long as there is something like Ginseng in my stack. Alone these serotonergics can start to make me feel like bit of a wussy and passive though.
The induction of P450 enzymes by SJW should be noted though if one uses drugs metabolized by them.
Edited by Galaxyshock, 10 June 2013 - 09:51 AM.
#305
Posted 10 June 2013 - 09:56 AM
#306
Posted 10 June 2013 - 10:21 AM
I think the add-on of Jiaogulan and my preworkout supp made me very stimulated or a bit hypomanic even, especially without Bacopa balancing things a out. Looks like both Ginseng and Jiaogulan increase cyclic AMP acitivity, which perhaps explains the high stimulation. I've reacted quite strongly to things that affect cAMP (Forskolin had especially strong response). Bacopa decreases it which is good for balance to me. I got some more Bacopa now + Schisandra and Ashwagandha extracts too, I'll see where things go from here.
Edited by Galaxyshock, 10 June 2013 - 10:40 AM.
#307
Posted 11 June 2013 - 06:03 AM
I'm thinking about adding either Cordyceps or Panax Ginseng to my existing regime of just Rhodiola. Any thoughts on this? Does Rhodiola affect 5-HT2A?
On another note, it seems SJW upregulates both 5-HT1A and 5-HT2A when taken for a chronic period:
#308
Posted 11 June 2013 - 01:17 PM
I tried tried combining SJW, Panax, Rhodiola and a (for me) small dose of 37,5mg Armodafinil at 8pm - and Holy shit!
Best state of mind I've been in for months! Felt motivated, optimistic, and calm - without the nasty overtimulated feeling that stimulants gave me, and also minus the jitters or muscle cramps. Also no siginficant comedown thereafter. (not too much sleep naturally, since taken so late in the evening, but then again yesterday was E3 night anyways, so yeah )
Guess I'll go with that combo for the next few days. Of course it might also just be that SJW and Panax slowly start working after a few days of Onset...
That being said, Wikipedia tells me that (Ar)modafinil does infact induce a few cytochrome p450 enzymes. My pharmacologicla knowledge isn't nearly good enough to have the slightest clue what that means though...
Is (Ar)modafinil a dangerous gamble with SJW in the long term? If so, I'm gonna completely eliminate it from my stack. But for now, it seems like low doses don't hurt the mix...
Also I've got DHEA and Tongkat Ali 200:1 extract coming soon. Like with Sam-e, I'll only start finicking around with those, once I can fully determine how SJW and Panax affect me, though.
Naturally, I'm then gonna gow start low with the DHEA ( basically want to determine if my problem is also testosteronergic in nature, and don't have money/time to beg for a test at my doc right now)
Tongkat Ali should be interesting, too. Since neither of those are really "stimulants" though, I guess adding them to SJW and Panax can't hurt?
#309
Posted 11 June 2013 - 01:22 PM
I'm thinking about adding either Cordyceps or Panax Ginseng to my existing regime of just Rhodiola. Any thoughts on this? Does Rhodiola affect 5-HT2A?
From personal experience (Cordyceps didn't do much for me even after longer use) and evidence based on human studies I'd clearly suggest Panax Ginseng! Cordyceps also has quite a few positive anecdotal reports, but unlike Panax, there isn't really any scientific prove for most of it's effects at this point.. Of course that doesn't mean they aren't there, but Panax seems like the safer bet, I guess.
Well at least according to this site: search for both compounds and comnpare to form your own opinion!
www.examine.com
#310
Posted 12 June 2013 - 12:36 AM
Also I've got DHEA and Tongkat Ali 200:1 extract coming soon. Like with Sam-e, I'll only start finicking around with those, once I can fully determine how SJW and Panax affect me, though.
Naturally, I'm then gonna gow start low with the DHEA ( basically want to determine if my problem is also testosteronergic in nature, and don't have money/time to beg for a test at my doc right now)
Tongkat Ali should be interesting, too. Since neither of those are really "stimulants" though, I guess adding them to SJW and Panax can't hurt?
Taking DHEA isn't going to tell you whether you have a problem with test or not. If solving low test problems was as simple as that people wouldn't be taking pharmaceuticals and going on hormone replacement therapy at great cost and bother. I wouldn't waste my time with DHEA. Here is one of the first studies that came up on dhea and test:
http://jap.physiolog.../87/6/2274.full
SJW is well studied. If you are going to give it a try why not give it enough time for an effective trial?
#311
Posted 12 June 2013 - 10:45 AM
I'm not trying to be right here, I know there's a high possibility that the whole DHEA craze of the last years is just a big marketing scam and that it doesn't do anything, unless you're a sixty year old men with proven low DHEA levels. But if scientific evidence from human trials is inconclusive and there are positive anecdotal reports, I'm willing to take a shot in the dark and at least try it for myself once.
Regarding SJW, you're absolutely right - I'm gonna try this at least 4 weeks before adding DHEA.
#312
Posted 14 June 2013 - 09:15 AM
How exactly does 5-HT2A agonism affect anhedonia? I haven't been able to find any information on it with regards to anhedonia. Though, I did find a couple of conflicting studies: some found Ginseng's 5-HT2A agonism to have antidepressant effects, as evidenced by a blockage in its antidepressant effect when a 5-HT2A antagonist is introduced, and some found 5-HT2A antagonism to produce antidepressant effects and to enhance SSRI's existing antidepressant effect.
I'm thinking about adding either Cordyceps or Panax Ginseng to my existing regime of just Rhodiola. Any thoughts on this? Does Rhodiola affect 5-HT2A?
About 5-HT2A at least few things are known
- Is the main excitatory 5-HT receptor subtype
- Threshold psychedelics (5-HT2A agonists) have positive anecdotes for treating anhedonia
- The intensity of negative symptoms (incl. anhedonia) of Schizophrenia are significantly associated polymorphism of the 5-HT2A receptor gene
I read hypothesis that 5-HT2A could mediate the differences between depression types, and this anhedonia and emotional bluntness could be seen as one type IMO. High 5-HT2A activity is seen in depressed suicide victims, which seemingly lead to belief of downregulating the receptor as therapeutic treatment for depression (which sure can help in those cases). To me it seems like that receptor is the key that opens up the perception to sensing or reacting on emotions, highs and lows, pains and pleasures of life, and anticipating these. During the time I have had anhedonia and bluntness, I've never felt anything overwhelming (sadness, fear .. joy), never felt suicidal (at least like taking action) or had really trouble taking care of myself (as if anhedonia could be some evolutionary adaptation where basic survival is ensured with the cost of not truely experiencing life). It wasn't until 5-HT2A activation (I believe) that I could really start recognizing and remember something like those are even possible for some.
Altough one receptor is probably not such all-explainatory. I think acetylcholine can significantly worsen things. Past few days I've tried combinations of strong Ashwagandha extract (AChEI), Bacopa ext. (AChEI), Schisandra ext. (AChEI, altough weak), Rhodiola ext. (AChEI), Caffeine (AChEI), and felt awfully similar to back in fall when using huperzine A and anhedonia was bad - quite zombified and anhedonic but also anxious, tense and depressed, but it subsided in some hours. High dose magnesium helped a bit, it decreases acetylcholine release. I'm starting to think that at least the huperzine lead to worsening of my anhedonia, little did I know back then.. It seems that I'm vulnerable to acetylcholine increases, altough slight elevation doesn't hurt. 5-HT2A activation increases acetylcholine release though (in certain parts of the brain), so things are complicated. The other anti-anhedonic - GABA-B, agonism inhibits acetylcholine release. Something like an anti-muscarinic could be worth a try if one feels stuck..
Just some thoughts and suspicions, I could be wrong, and these things may sure not apply for every case..
Edited by Galaxyshock, 14 June 2013 - 10:11 AM.
#313
Posted 20 June 2013 - 10:04 AM
I've been doing fairly better lately on the cognitive and even emotive spheres.
my regimen has been:
Tianeptine 3x12.5mg
Omega 3 DHA and EPA, 2 grams a day
Uridine UMP, 500mg a day
Choline 500mg a day
Inositol 500mg a day
NAC 600mg a day
s
#314
Posted 03 July 2013 - 01:09 AM
They still carry the standardized American Ginseng extract. What do you think about using American Ginseng? I'm guessing that the type of ginseng does not matter as long as it has ginsenosides. Though, do you know if American Ginseng has a different spectrum of ginsenosides vs panax, korean, or chinese?
On another note, how long did it take before you felt the effects of ginseng?
#315
Posted 04 July 2013 - 04:36 PM
#316
Posted 07 July 2013 - 06:46 PM
I went on it for ~3 weeks, noticed changes, tapered off, and then went back on it. This second time, I've been on it for just under three weeks. I've only been using 600 mg daily as to avoid serotonergic side effects, but I might try 900 mg in the future. These effects have been quite consistent between trials.
Positives -
Increased energy & motivation
Reduced need for sleep (from ~9.5-->~8.5)
Higher average mood
Perhaps mild anxiolysis (in any case, not anxiogenic)
Mildly increased libido
Negatives -
Somewhat increased mood lability
Caffeine's effect may be somewhat lessened - or it could just be tolerance
It also seems like there might be some withdrawal type issues if I miss a few doses.
I'll update as I stay on it. I just bought a number of bottles, so I'll be taking it for a while. I'll also experiment with adding ginseng, which I quite like but haven't combined with SJW as of yet.
Edited by Dissolvedissolve, 07 July 2013 - 06:47 PM.
#317
Posted 07 July 2013 - 08:12 PM
I had to prepare for an audition on short notice. Since I had no other choice than to pull allnighters, I used quite the moderate amount of modalert, up to 450mg/day. This would usually end up in a zombie-like state after a few days. But this time, to avoid emotional dulling and getting jittery, I tried adding L-Theanine and Ashwagandha.
100mg or 200mg of Modalert (plus 50mg Caffeine occasionally), with 400mg L-Theanine and 200mg Ashwagandha worked amazingly well for me! I was focussed and awake, yet had the complete range of emotions at my disposal. I also had complete control over my movements, and didn't feel "stiff" or sour, like I normally would on a stimulant. Plus I was hardly nervous at all, and had a really good time talking to the director and his assistant - I felt like I was easily gaining instant sympathy.
I also had no problem letting them finish their sentences and to whait my turn to talk - something that is usually very hard for me when on moda!
All in all - I pretty much nailed it, and I sure as hell wasn't expecting that given the circumstances!
And all that after literally not sleeping at all the night before (except a light one hour nap in the morning)!
Now I don't know if this upper/downer combination is a great idea in the long run. Actually I don't even think chronic long term modafinil use itself is a great idea.
But I still think this discovery was worth sharing.- for me it was the single best experience since I started finicking around with nootropics, period!
Edited by chris106, 07 July 2013 - 08:41 PM.
#318
Posted 08 July 2013 - 11:03 AM
hi guys, just updating with my situation.
I've been doing fairly better lately on the cognitive and even emotive spheres.
my regimen has been:
Tianeptine 3x12.5mg
Omega 3 DHA and EPA, 2 grams a day
Uridine UMP, 500mg a day
Choline 500mg a day
Inositol 500mg a day
NAC 600mg a day
s
How does Uridine work for you? I've been thinking about giving it a go for dopamine function, cognition and productivity etc. I liked Triacetyluridine a lot when I tried it last year but it stopped working within a week if I remember correctly. Quite expensive stuff though so I wonder if it or UMP is worth a try again.
I'd like to update regarding my experience with SJW, Perika brand, standardized for hyperforin.
Good to hear similar positive effects that I've experienced. It may indeed be that SJW lessens caffeine effect, I've read it has demonstrated adenosinergic activity. I noticed that too.
But this time, to avoid emotional dulling and getting jittery, I tried adding L-Theanine and Ashwagandha.
Ashwagandha is very nice for balancing stimulants. The potent AChEI sometimes makes me kinda depressed though.
#319
Posted 08 July 2013 - 11:50 AM
hi guys, just updating with my situation.
I've been doing fairly better lately on the cognitive and even emotive spheres.
my regimen has been:
Tianeptine 3x12.5mg
Omega 3 DHA and EPA, 2 grams a day
Uridine UMP, 500mg a day
Choline 500mg a day
Inositol 500mg a day
NAC 600mg a day
s
How does Uridine work for you? I've been thinking about giving it a go for dopamine function, cognition and productivity etc. I liked Triacetyluridine a lot when I tried it last year but it stopped working within a week if I remember correctly. Quite expensive stuff though so I wonder if it or UMP is worth a try again.
Honestly the first time i tried the fishoil/uridine/choline combo i was kind of skeptic... but when i came off of it, after a week or two, i noticed everything costed me more energy.. like a sort of heaviness added to my body. So i ordered some more and went back on, and i believe it is really doing something for my memory too, together with tianeptine. I believe it is one of the few things that has a vague effect on me.. bacopa too, but makes me tired (i take it in the evening and i notice i have way more difficulty waking up in the mornings, and i dream less: guess it makes my already deep sleep even deeper). Anyhow, uridine, imo its a good candidate for a long term stack, been on it for about 3 months in the past 6, and am awaiting the next shipment, this time with proper citicoline instead of cheap choline.
as a quick update, I also dropped the NAC and will drop the inositol too.. just trying to figure out the essentials.
I will experiment with huperzine: im already quite happy with the memory improvement i did over the past half year, but id like to see if AchE inhibition proves helpful. I still have a weird feeling i am slightly disconnected from myself and how i experience reality, kind of dissociaton... no idea how to try to fix that, but im sure its the final layer for my recovery between my coscience and reality
#320
Posted 13 July 2013 - 02:25 AM
#321
Posted 13 July 2013 - 05:36 AM
Galaxyshock, you never updated us on Catuaba, how did that turn out for you?
It felt somewhat pleasantly stimulative, quite weak overall though. I tried big doses like 7 grams even but did only seem to increase stimulativeness, not pleasurability. For specifically sexual anhedonia I'd say it can be useful as it's noticeable aphrodisiac.
#322
Posted 13 July 2013 - 09:28 AM
On another note, it's almost been 2 weeks since i started taking Ginseng alongside Rhodiola and I've noticed my mood has been depressed and that I'm a lot more irritable than usual. I haven't noticed any benefits in the anhedonia area either. Should I give up on Ginseng or give it some more time?
I'm also thinking of adding in some Schizandra. Are you still taking it? What are the effects you've noticed? How long does it take to start working?
#323
Posted 14 July 2013 - 03:12 PM
With Catuaba I needed 4 caps to feel any effects and 6 caps was quite good dose as noticeably stimulative.
#324
Posted 26 July 2013 - 10:52 AM
#325
Posted 27 July 2013 - 12:36 AM
I have some schisandra and jiaogulan coming in. I'll try combining Rhodiola with those herbs separately and see what happens. I'm not sure if taking all 3 would be safe.
#326
Posted 30 July 2013 - 07:54 AM
Edited by Galaxyshock, 30 July 2013 - 07:56 AM.
#327
Posted 31 July 2013 - 05:07 AM
I'll try Jiaogulan tomorrow. I think I'll take Jiaogulan for about 4 weeks before concluding its effects on me. The only reason I bought it is because of this article you linked to, Galaxyshock:
The human equivalent dose of 30 mg/kg should be 4.84 mg/kg, which is feasible. The brand I'm using is Paradise Herbs. I'm not sure if it's an ethanol extract though or if it even matters.
#328
Posted 31 July 2013 - 05:43 AM
#329
Posted 31 July 2013 - 06:21 AM
It's worth a try. I have an appointment with my psychiatrist in September. I'll ask him about memantine and if he prescribes it then I'll post updates of its effects here.
#330
Posted 31 July 2013 - 06:51 AM
Compared to control treatment, administartion of Rhodiola rosea extract increased leu-enkephalin (endogenous opioid peptide) concentration in blood plasma, suprarenal glands and myocardium of rats exposed to stress.
http://novagenex.com...-rosea-Copy.pdf
If one is not exposed to stress, then perhaps the opioidergic effect disappears? heh. NMDA-antagonism could work, Cholecystokinin-B antagonism too, but it's usually better to just cycle adaptogens. I'm sure memantine can be very useful with various things though.
Edited by Galaxyshock, 31 July 2013 - 07:22 AM.
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