58 replies to this topic

[protoject]

Hey folks.

Just wanted to let you know that after many years of trying to treat my severe chronic insomnia, I found something that actually works consistently without causing any significant side effects for me.

It is not a medicine currently offered by doctors.

It is also not available as an over the counter remedy. It must be obtained from a chemical supplier and it has been used as a research drug. You cannot get high off it.

I came to this success only after so much trial and error with other medications and natural "remedies", some doing nothing, others causing much worse effects than they're worth. Most not consistently working for sleep, or, not working for sleep at all and making sleep even worse!

The new discovery I made was one of those "ah, theoretically this might work based on what I know". I knew that 5ht2a agonism increased arousal and could potentially significantly decrease deep sleep. So I searched for a 5ht2a antagonist or inverse agonist that particularly would increase SWS.

First I tried ritanserin. Ritanserin might be good for some people, but, for me it increased anxiety. It has a long half life and instigated some panic attacks in me and mental disorganization THis is probably due to the fact that I already have anxiety , underlying schizo type symptoms , and, happen to be pretty sensitive to dopaminergics. Ritanserin has a dopaminergic component to it- acts as a DARI. For some this could work for dysthymia, perhaps. I wouldn't recommend it based on my experience.

Really, the entire time I wanted to get Nelotanserin (seems to be the best bet based on clinical research), but unfortunately i havent found it easy to procure. My next step on the list was then Eplivanserin. I've been using eplivanserin for about a month and it has significantly helped my sleep. It helps deepen sleep so things don't wake me up. I can also get back into a deep sleep again after I've woken up.

This hasn't fixed my sleep problem 100%, but it is helping a lot. Maybe 60%. That's pretty impressive. There are certain things that are fixed and certain things that aren't. For example I can never sleep more than 4 hrs in one sitting and it still usually takes me some time to fall back asleep. My own insomnia is very persistent but at times it is worse than others. When it is worse, the eplivanserin works a little less, but the fact that it works at all is amazing. It's helping me catch up on the 1000s of hours of sleep I've missed over the years.

My only issue with eplivanserin is 1) I have to order it from an oversease supplier , and I have no idea on the purity nor potency of the product, and 2) in a withdrawal report by this major EU medical committee, it listed that a significant side effect of eplivanserin was DIVERTICULITIS. Though this is a real cause for concern, it occurred in 30 out of 3030 patients (i.e. 1%). Also if I'm understanding the report correctly, it appears that many of these were elderly and that a large percentage of people it occurred in had previous episodes of diverticulitis (before treatment with eplivanserin).

I don't believe I've experienced a single side effect to this day, at least nothing that alarms me. Anyway if you would like more information I am attaching a report. I got it from a specific URL but I think last time I checked it was down, so I'm attaching it. If you'd like to know about possible side effects, check the report (any side effect would occur with much less frequency than hypnotic drugs, and mostly less dangerous, and doesn't effect your cognition the next day. )

I would like anyone with a knowledge of how clinical research works to please comment on this report, and comment on whether you think the diverticulitis concern is a valid concern. To me it seems a valid concern yet at the same time considering the factors I mentioned above maybe it isn't as bad as it seems?? Personally I have not experienced diverticulitis after a month of use, but I always look out for the symptoms, because if a diverticulitis attack does rise, it needs to be treated quickly.

Also for me I'd take that chance considering it's only 1% and I haven't slept for years. :p

Anyway. I haven't seen any evidence that Nelotanserin causes diverticulitis- nor have i seen the same evidence for some other similar 5ht2a antagonists- so at least we're going in the right direction.

Edit: sorry i forgot to add the attachment, now it has been added ..

 EPLIVANSERIN SLIWENS EU EXTENSIVE.htm   279.35KB   17 downloads

Edit #2: forgot to mention that although the diverticulitis concern seemed to be mostly older patients, that this risk did not change across age groups.

Edited by protoject, 21 August 2013 - 05:16 PM.

[nowayout]

Thank you, this is good to know.

Something related: I have had some modest (not great, but okay) success from agomelatine, which is a 5ht-2C (not A though) antagonist. Since melatonin never did anything for me, it must be its inhibitory effect on these serotonin receptors that is doing the trick for me too. I still wake up a lot at night but I fall back asleep much more easily. My initial sleep latency is also much improved.

Have you tried low dose amitriptylene, by the way. It also antagonizes 5ht-2a and 5ht-2c, among other things, and is also used for insomnia (it does several other things also that can be sedative, so I don't know what contributes most to the sedative effect.) (Since it also inhibits serotonin reuptake, I don't know if the net effect on serotonergic neurotransmission is inhibitory, though.) Doses as low as 10-20 mg can be effective for many people for insomnia, and at those doses it is relatively side effect free. It is known to increase time spent in restorative stage 4 sleep.

Edited by nowayout, 22 August 2013 - 06:19 AM.

[lourdaud]

What would be the benefit of taking this instead of, say, cyproheptadine?

[protoject]

Thank you, this is good to know.

Something related: I have had some modest (not great, but okay) success from agomelatine, which is a 5ht-2C (not A though) antagonist. Since melatonin never did anything for me, it must be its inhibitory effect on these serotonin receptors that is doing the trick for me too. I still wake up a lot at night but I fall back asleep much more easily. My initial sleep latency is also much improved.

Have you tried low dose amitriptylene, by the way. It also antagonizes 5ht-2a and 5ht-2c, among other things, and is also used for insomnia (it does several other things also that can be sedative, so I don't know what contributes most to the sedative effect.) (Since it also inhibits serotonin reuptake, I don't know if the net effect on serotonergic neurotransmission is inhibitory, though.) Doses as low as 10-20 mg can be effective for many people for insomnia, and at those doses it is relatively side effect free. It is known to increase time spent in restorative stage 4 sleep.

I think maybe you get a nice effect from 5ht2c antagonism because, like my earlier mentioned Ritanserin, it disinhibits dopamine as far as I know.
For me, trying amitriptyline is a bit of a scary thought because it affects so many receptors and has a lot of side effects and risks. These selective 5ht2a antagonists, however, have a much more selective action and better side effect and risk profile.

You did mention not getting side effects at the low dose though. I guess it's worth trying especially as an antidepressant that doesn't mess up my sleep. I do have a fear about 5ht2c antagonism though since I've had a bad experience with ritanserin. Perhaps its dual action of DARI and 5ht2c antagonist is what caused my reaction. . . but I can't say. Anyway I do realize amityptiline may be good for sleep onset since it's a dopamine antagonist as well, though I do fear anything related to long term dyskinesia, not sure if it's a realistic fear or not in this case..

What would be the benefit of taking this instead of, say, cyproheptadine?

Hits too many receptors and causes too many side effects. With Eplivanserin i get practically no side effects. It's selective to the 5ht2a receptor. Other than that crypto does look like it might help with sleep. . . but at what cost

Edited by protoject, 22 August 2013 - 04:52 PM.

[lourdaud]

Hits too many receptors and causes too many side effects. With Eplivanserin i get practically no side effects. It's selective to the 5ht2a receptor. Other than that crypto does look like it might help with sleep. . . but at what cost

I don't know, personally nothing makes me as dull and depressed as 5ht2a antagonism.
Have you tried diphenhydramine and high dose magnesium btw?

[nowayout]

Amitriptylene's effect on dopamine receptors appears to be negligible (of the order of 1000 times weaker than its effect on serotonin receptors) so I wouldn't worry about that especially at low doses. But I agree it does hit a lot of different receptors one might not necessarily want. It does hit quite a few other receptors that increases its sedative effect; it is antihistaminic, anticholenergic, and antiadrenergic.

[protoject]

Amitriptylene's effect on dopamine receptors appears to be negligible (of the order of 1000 times weaker than its effect on serotonin receptors) so I wouldn't worry about that especially at low doses. But I agree it does hit a lot of different receptors one might not necessarily want. It does hit quite a few other receptors that increases its sedative effect; it is antihistaminic, anticholenergic, and antiadrenergic.

True. I guess for me I've found antihistaminic, anticholenergic, and antiadrenergic types of drugs ones that I don't want to take long term. Usually they end up causing more problems for me, unfortunately. So far with eplivanserin it doesn't appear to be the case.

I don't know, personally nothing makes me as dull and depressed as 5ht2a antagonism.
Have you tried diphenhydramine and high dose magnesium btw?

I'm sad to hear it doesn't work for you. Have you tried selective 5ht2a antagonists? I find that with eplivanserin, it only lasts as long as I'm in bed, and I'm using it for purposes of sleep. It doesn't seem to cause a depressing effect the next day. I am wondering what drug you did try though, because most 5ht2a antagonists I've heard of usually have an array of pharmacological effects that the depressing effect for you could be based on, or perhaps , a combination of more than one effect. Not saying that's definitely the case but something to consider. Also eplivanserin's half life is pretty short... see below to consider. If interested though you might want to do further research because I think I may have seen conflicting studies here and there. In other words if you're worried about adverse effects, you would take it at night time for sleep only, and generally should wake up fine. Lastly eplivanserin has been shown to upregulate 5ht2a receptors. Personally I've stopped taking it a couple times but couldn't comment on any type of effect. I've also taken 5ht2a agonists the day after and wasn't sure I noticed any difference.

Here are some further notes on eplivanserin that I jotted down:


EPLIVANSERIN
up to 10 mg used for sleep......
--10 and 40 mg has a half-life of 3.9 and 10.7 h
--SHouldnt show any psychoactive effect whether taken in morning or night,
other than increasing SWS and improving sleep. (reduces WASO [Wake time after sleep onset] and NASO [number of awakenings after sleep onset])
-- one study said no difference in response from 5 mg to 40 mg (sleep effect
not dose-dependent.) that was in humans;
"In a dose-ranging study 1, 10, or 40 mg eplivanserin in healthy adults increased slow wave sleep time by about 30%,"
from title : Drug-related Sleep Stage Changes: Functional Significance and Clinical Relevance
URL: http://www.ncbi.nlm....les/PMC3041980/

but another said dose response was present in animals... but were talking about much higher dosage..)
--1% chance of diverticulitis was a concern, were very serious cases developed. However the confounding factor is that these people did have episodes of diverticulitis before treatment. Age was not a factor, though many of the patients studied were elderly.
--Does decrease stage 2 sleep which is corresponding with the increase in sws
--SOLUBILITY: Sigma Aldrich site says DMSO: =10 mg/mL ; another link that I lost said in water its solubility is between 18-19 mg per 500ml of water. (dont quote me on that, it might be per L, check google)

-Eplivanserin upregulates 5ht2a receptors.
-No rebound effect, except return to baseline insomnia.

Edited by protoject, 22 August 2013 - 06:21 PM.

[dereknel]

Interesting information. Ive had bad insomnia lately due to worries hopefully this will work.

[meatsauce]

A 5ht2 antagonist will down regulate the receptor. Agonists and antagonists both down regulate the 5ht2a receptor.

[protoject]

A 5ht2 antagonist will down regulate the receptor. Agonists and antagonists both down regulate the 5ht2a receptor.

But some 5ht2a antagonists have shown upregulation of the receptor. 5ht2c antagonism , on the other hand, will cause further downregulation. Eplivanserin has been shown to upregulate the 5ht2a receptor. BTW it is an inverse agonist , not sure if that has anything to do with it. (ive been calling it an antagonist but its likely an inverse agonist)

Have you tried diphenhydramine and high dose magnesium btw?

Yes and both are useless for me, beyond some very short lived help.

[meatsauce]

Huh pretty cool. I would like to try it.

Have you tried using Ipamorelin with modified grf (1-29)? It increases deep sleep in me and most users. I bet if you combine this combo with the Eplivanserin it would be pretty good.

[nowayout]

I actually tried ipamorelin + grf. It made me lie wide awake all night. I have seen several other users report this effect. As far as I could determine, the speculation is that in some people GHRPs tend to release lots of cortisol, causing insomnia. The same thing happened to me also with ghrp6 instead of ipamorelin.

I actually tried ipamorelin + grf. It made me lie wide awake all night. I have seen several other users report this effect. As far as I could determine, the speculation is that in some people GHRPs tend to release lots of cortisol, causing insomnia. The same thing happened to me also with ghrp6 instead of ipamorelin.

I actually tried ipamorelin + grf. It made me lie wide awake all night. I have seen several other users report this effect. As far as I could determine, the speculation is that in some people GHRPs tend to release lots of cortisol, causing insomnia. The same thing happened to me also with ghrp6 instead of ipamorelin.

[protoject]

A 5ht2 antagonist will down regulate the receptor. Agonists and antagonists both down regulate the 5ht2a receptor.

Sorry I'm not sure if it's you who downvoted my original answer or someone else, but eplivanserin is actually one of the rare molecules that can in fact upregulate 5ht2a receptors with chronic administration, both in vitro and in vivo, if you've having trouble finding the studies in your search, then use the chemical name SR 46349B rather than eplivanserin, as they do show up under that chemical name. Also at this point as far as Im understanding it does not always upregulate but sometimes does nothing. Also the studies I saw were done in rats. The research continues...

Edited by protoject, 23 August 2013 - 10:39 AM.

[3AlarmLampscooter]

FYI Trazodone is a somewhat weak 5-HT2A antagonist, but an excellent sleep aid. I'm prescribed it, and find it work wonders as long as I'm within a couple hours of wanting sleep naturall (I'm at about a 26 hour circadian rhythm on freerunning sleep).

I've also used the antipsychotic Lurasidone, a very powerful 5-HT2A antagonist, and find it to have absolutely no effect on my sleep patterns. Seroquel on the other hand... 14 hours of very non-restful sleep. I hated that stuff.

The moral of the story? Probably more at play than *just* 5-HT2A antagonism here.

[nowayout]

My experience with Trazodone - works about as well as a sugar pill for me.

Seroquel: I was prescribed a very low dose, which I only took once. It cause a nightmarish 36 hours of central apnea even when I was awake, but especially as soon as I would fall asleep I would stop breathing completely. I actually sat up two nights drinking coffee so as not to fall asleep and die. Nightmare on Elm Street indeed. It also gave me mild but scary myoclonal seizures (involuntary contractions of the hands and feet). It did make me very horny though and gave me very strong erections. But overall this drug is the devil.

Edited by nowayout, 24 August 2013 - 06:50 AM.

[protoject]

FYI Trazodone is a somewhat weak 5-HT2A antagonist, but an excellent sleep aid. I'm prescribed it, and find it work wonders as long as I'm within a couple hours of wanting sleep naturall (I'm at about a 26 hour circadian rhythm on freerunning sleep).

I've also used the antipsychotic Lurasidone, a very powerful 5-HT2A antagonist, and find it to have absolutely no effect on my sleep patterns. Seroquel on the other hand... 14 hours of very non-restful sleep. I hated that stuff.

The moral of the story? Probably more at play than *just* 5-HT2A antagonism here.

Are you sure about that? I mean, yes you're right in a sense, about it possibly being more than one thing working in trazadone. However it appears lurasidone isn't indicated for insomnia in any regard... (I only did a brief search.. does it even increase sws?) Additionally lurasidone is potent on more than just the 5ht2a receptor... perhaps it is the molecule's particular effect.

It appears that many highly selective 5ht2a antagonists & drugs w/ 5ht2a antagonism as a prominent effect, increase slow wave sleep, and even perhaps other sleep parameters depending on which molecule it is and the dose, but, lurasidone does not. (at least according to my quick search I couldn't find any study saying lurasidone helps with sleep). (also eplivanserin and nelotanserin are both inverse agonists and not just antagonists...)

I found trazadone was pretty good for sleep initiation, but continuing sleep beyond very few hours was not possible, and, it caused bad tachycardia , 160-180 bpm in this individual. It was one of the first drugs i tried due to it being a drug that increases SWS. It also caused a dysphoric feeling upon taking it, though I'm not sure that was all that bad.

Edited by protoject, 24 August 2013 - 11:11 AM.

[3AlarmLampscooter]

Preciesly my point about Lurasidone being more powerful than Trazodone in 5-HT2A antagonism, yet not functioning as a sleep aid! Thus my skepticism about 5-HT2A antagonism alone being the cause, and not that combined with some other factor.

[protoject]

Preciesly my point about Lurasidone being more powerful than Trazodone in 5-HT2A antagonism, yet not functioning as a sleep aid! Thus my skepticism about 5-HT2A antagonism alone being the cause, and not that combined with some other factor.

I know, but what I am saying is, some 5ht2a antagonists won't make insomnia better, and some will. In this case it's been pointed out that Eplivanserin is not just an antagonist but actually an inverse agonist. It appears that other drugs in the same class have the same effect. For example, Nelotanserin. Also, nelotanserin and eplivanserin are both selectively acting on 5ht2a receptors and only has negligible affinity for other receptor sites.

So the question is rather something like is it inverse agonism that causes an increase in deep sleep and some improvement in other parameters? Or can an antagonist also do that> .. .and as far as I am understanding , sometimes these drugs are first said to be antagonists, then later found to possibly be inverse agonists.

Lurasidone is not an inverse agonist.... as far as I understand.

One more thing: it appears that although both molecules that are selective inverse agonists are both causing similar effects on sleep, there are small differences in how well they do this, which parameters they effect, and also, dosage and whether there's a dose response relationship. I'll talk about this more later when I have some time to compile the evidence.. I'd like to be the expert

But would just like to reiterate I'd like to compare the differences between selective inverse agonists of the 5ht2a receptor. That way we can see it's generally a similar effect but that it does depend on that molecule and what it does...without confounding the evidence by asking whether selective 5ht2a inverse agonists do improve sleep on any level ( they definitely do, and due to that property. ) . or if it were due to activity on another receptor site (it's not in the case of these drugs as far as I can tell)

Edited by protoject, 31 August 2013 - 08:16 PM.

[celebes]

This has been a very interesting read. I've been coming around to the idea that a lot of trauma (and iboga) symptoms are due to 5-HT2a downregulation or unresponsiveness for a while now. Inverse agonists are about the the only route for correcting that apart from SJW, and the dose used to achieve it with SJW was something like 21g a day. Plenty of slow wave sleep and waking up to a more responsive dopamine system is just about an ideal combo. Was the Eplivanserin from a Chinese chemical suppler or is there some other source?

Tangentially, I think the association between elevated 5-HT2a expression and depression might develop from high-2a individuals being more sensitive/responsive to negative events, which are in turn more deleterious to mental health. Just a theory, but I doubt any study would have controlled for it.

Edited by celebes, 20 February 2014 - 02:00 AM.

[nowayout]

Anyone have any success from buspirone? It also supposedly downregulates the 2HT-2a response with chronic use.

[celebes]

Anyone have any success from buspirone? It also supposedly downregulates the 2HT-2a response with chronic use.

Buspirone upregulates 5-HT2a, I've personally had great results with it (for trauma). SSRIs downregulate and it's quite possible that's what mediates SSRI 'zombification' (at least partly).

The more I read the more it appears both over and under expression are disease states. The difference between active, excitable misery and flat, dull depression? Expression is positively associated with 'neuroticism', but couldn't neuroticism be characterised foremost as sensitivity? Being more emotionally reactive would naturally make negative events harsher. And oestradiol just happens to increase 5-HT2a levels and response. Conversely, schizophrenics have lower levels; this could be the cause for much of the negative/flat affect and possibly the sensory gating deficits too. Iboga's effect on addiction probably has a lot to do with making overly sensitive people numb via downregulation. All this is without getting into its intimate linkage with 5-HT1a and 2c function.

Altogether, crucial. As are the -anserin drugs. SJW is shown to be active down to 10g, possibly lower. Still unrealistic, I fear.

[nowayout]

Anyone have any success from buspirone? It also supposedly downregulates the 2HT-2a response with chronic use.

Correction - I meant 5HT-1a.

Anyone have any success from buspirone? It also supposedly downregulates the 2HT-2a response with chronic use.

Buspirone upregulates 5-HT2a, I've personally had great results with it (for trauma). SSRIs downregulate and it's quite possible that's what mediates SSRI 'zombification' (at least partly).

See above.

Are you saying it does something to 5HT-2a as well?

[celebes]

Chronic buspirone treatment decreases 5-HT1B receptor densities and the serotonin transporter but increases the density of 5-HT2A receptors in the bulbectomized rat model of depression

Sato H1, Skelin I, Diksic M.

Buspirone at a high enough dose essentially normalizes 5-HT1a levels in the depressed: lowering receptors in the raphe nuclei and amygdala, raising postsynaptic receptors in the cortex, hippocampus and striatum.

Chronic buspirone treatment normalizes open field behavior in olfactory bulbectomized rats: assessment with a quantitative autoradiographic evaluation of the 5-HT1A binding sites.

Sato H1, Skelin I, Debonnel G, Diksic M.

The comparison between the OBX-B20 and control (SHX-B20) rats suggests that the buspirone treatment resulted in a regional balance in the 5-HT(1A) sites. A dose dependent reduction in the density of 5-HT(1A) sites was observed in the sham rats, but the buspirone treatment had very little effect on the density of the 5-HT(1A) receptors in the OBX rats. From these observations, we conclude that the antidepressant effects of buspirone in the OBX rat model of depression are likely mediated through the fine tuning of the regional imbalance of 5-HT(1A) receptors with even increases of about 20% in some limbic regions.

[penisbreath]

For those wanting a simple way to test the 5-HT2A theory, the herb Feverfew is a selective antagonist. I personally found it helped sleep induction. Mangosteen also has some effect on 5-HT2A.

[Brett Black]

The tricyclic antidepressants have 5ht2a antagonism, some more selective and with high affinity than others.

Doxepin, an old tricyclic antidepressant, has recently been approved in low-dose (3mg and 6mg) form as a sleep aid under the name "Silenor." It's expensive and many people believe the much cheaper, but slightly higher dose generic doxepin is potentially as good. It hits histamine and 5ht2A receptors amongst others. It is indicated for sleep maintenance, rather than sleep initiation and does, I believe, increase slow wave/deep sleep.

Amitryptiline is another tricyclic antidepressant that is used for insomnia and hits ht2A. My concern with this is that a human study has shown the major metabolite, nortriptiline, may be carcinogenic, so I would avoid it.

Mirtazipine has, from memory, high affinity selectivity for mainly just the histamine and 5ht2A receptors, as an antagnoist. However, my understanding is that it has tested positive as a carcinogen in both mice and rats, so my personal opinion is to avoid it.

Cyclobenzaprine, a muscle relaxant / antispasmodic also hits 5HT2A. It is being prepared for "repurposing"(ie seeking regulatory approval for a new indication) as a fibromyalgia treatment (some evidence suggests fibromyalgia may be causatively linked to issue with slow wave sleep, and alpha wave intrusions.)

Cyproheptadine has high affinity for histamine and 5ht2A, is extremely cheap and available over the counter in many countries. It is classed as an antihistamine that it shares a lot of similarity with the tricyclic antidepressants. Its so old that it was not subject to rodent carcinogenisis bioassays, as is the norm since the 70's, so its rodent carcinogenic potential is unknown(in so far as I know, though I think it is not genotoxic at least.)

I don't know that 5HT2A antagonism(or reverse agonism?) is suitable for sleep initiation, but it does seem to induce slow wave, stage 3 and 4, delta wave and generally "deep" and "restorative" sleep. Many of these medications have not been promoted/indicated as sleep aids and there may be some particular caveats to their use in this role.

For instance, doxepin and cyproheptadine take an average of 3 to 4 hours to reach maximum plasma concentrations, and doxepin(and maybe cyproheptadine too) peak concentration can be delayed by a further 3 hours if it is taken too close to a meal(Silenor instructs not to eat for 3 hours before taking it.) It may be that Silenor is indicated for sleep "maintenance"(preventing early waking) because it takes so long to reach maximum plasma concentrations, and hence only begin to have effect on sleep half-way through the night.

However, sleep is tied closely to circadian rhythm and the bulk of slow wave/stage 3 & 4/delta wave sleep occurs in the first half of sleep. In particular, the surge of growth hormone that occurs concurrently with the onset of slow wave sleep, generally occurs within about the first hour of sleep. Thus, the most effective outcome may be to try to get plasma levels of these 5HT2A antagonists close to peak at around the onset of sleep.

The trials with cyclobenzaprine in fibromyalgia patients has had them dosing around 2 to 3 hours before sleep. When you add in the fact that a meal may delay peak concentrations, that may mean not eating for 6 hours before bedtime, dosing at about 3 hours before bedtime and then going to sleep at the target time consistently - this may be too onerous for some(hence the cyclobenzaprine development for fibromyalgia apparently attempting to create a more quickly absorbed product).

So my suggestion is to experiment with dose timing and meal timing, as these may have a substantial impact on the outcome of these drugs.

Gabapentin and pregabalin are believed to increase slow wave sleep - I'm not aware of these having any affinity for 5HT2A.

Sodium oxybate (the legal version of GHB) is known to increase slow wave sleep. Some people claim this is an excellent medication for restorative sleep, but it is very expensive, and the illicit use of GHB means it is under tight control and may be difficult and problematic to get a hold of.

Edited by Brett Black, 23 March 2014 - 04:16 AM.

[Brett Black]

Some good articles on drugs that induce induce slow wave sleep, with an emphasis of 5HT2A:

"Enhancement of Slow Wave Sleep: Implications for Insomnia"
(tiagabine, gaboxadol, gabapentin, pregabalin, eplivanserin, ritanserin, mirtazapine, trazodone, and olanzapine)
http://www.ncbi.nlm....les/PMC2824211/

"Selective Histamine H1 Antagonism: Novel Hypnotic and Pharmacologic Actions Challenge Classical Notions of Antihistamines"
http://www.cnsspectr...?articleid=1916

Edited by Brett Black, 23 March 2014 - 05:17 AM.

[Brett Black]

"Drug-related Sleep Stage Changes: Functional Significance and Clinical Relevance"
http://www.ncbi.nlm....les/PMC3041980/

[protoject]

[..]nothing makes me as dull and depressed as 5ht2a antagonism

May I ask what you've taken that is a 5ht2a antagonist that makes you depressed?

[lourdaud]

[..]nothing makes me as dull and depressed as 5ht2a antagonism

May I ask what you've taken that is a 5ht2a antagonist that makes you depressed?

Cyproheptadine and melatonin in particular. Also promethazine and a bunch of AP's and other dirty drugs (mirtazapin, mianserin etc).. And yes I know these drugs have affinities for other receptors bla bla but the fact remains: 5HT2a antagonism is probably a very bad idea for anyone suffering from atypical depression or schizo related problems.

[lourdaud]

But of course it's great if it works for your insomnia though!
Speaking of which, have you tried alimemazine? I get groggy for 10 - 12 h after taking it but it's a very potent antihistamine and has less side-effects than most of the other antihistamines I've tried.