9 replies to this topic

[fall]

So I've always had a hard time falling asleep. I remember it started in primary school at around ~10 years old. I would sometimes go to school having not slept at all. The main issue is falling asleep aka sleep onset. My 20s was quite party-filled and I enjoyed stimulants and alcohol a bit too much, which only made matters worse, I went through prolonged periods with barely any sleep. During more crazy times, total sleep time for a week could very well be 8-16 hours, even then I sometimes doubted if I actually slept or if I was just so far gone that I thought I was sleeping, lol, since getting any sleep during this time usually meant dropping several benzos at once combined with either booze or quetiapine or a Z-drug. Even 4-5 of a given benzo would not get me to sleep, I simply had to combine atleast two depressants to get some shuteye. Dangerous... Anyway, nowadays I lead a healthy active life and still find it very hard to fall asleep. I will list a selection of medicines I have used and would appreciate suggestions of alternatives.

 

Although I have found a number of effective medicines, it appears all the ones that work for me come with serious side-effects, are not suitable for long-term use, or simply not appropriate for other reasons. I shall list them in terms of effectiveness:

 

After using zolpidem (5-10 mg) for years it is becoming apparent that it has negatively impacted my memory (very considerably) both short-term and long-term recall, also some next day grogginess although lesser so than the medicines that follows.

Quetiapine I would say works second best. Too many serious side-effects (mechanism of action too broad to justify use as only a sleep-aid), next day grogginess, appears to counteract my anti-depressant medicine (MAOI). 

Benzos work third best, same issues as quetiapine AND zolpidem e.g., grogginess, memory issues, obvious slurring of words if dose too high or combined with certain other medicines.

Alcohol, works quite well if I drink ~50 cl booze. For obvious reasons long list of issues with this including addiction, harm, lack of healthy sleep etc.

Cannabis works quite well, especially combining smoked plant with oral THC. Similar issues, memory problems, next day grogginess. Another issue is legal access, I travel regularly and have easy access in some places and extremely difficult and illegal access in others. It also does not work as effective or consistent as say zolpidem or quetiapine.

Strong antihistamines, they work at times, but comes with next day grogginess, often times drying of sinus and mouth, causes cognitive deficits and increases risk of alzheimer and dementia.

 

I have searched for alternatives and as you can clearly tell, tried a lot. I did not mention some herbal remedies, minerals, etc as these simply does not even come close to aforementioned pharmaceuticals in terms of effectiveness. I guess a lot of people who suggest herbs or minerals either does not have as severe insomnia, or simply never tried stronger medicines.

 

I would appreciate some suggestions. And perhaps some thoughts on the following medicines I found in my research:

Lemborexant, brand name Dayvigo, (or other orexin antagonists). Are these effective and without any of the sides I have mentioned?

Clonidine?

Trazodone, reports on cognitive impact seems mixed here, any thoughts? Also read about potential next day grogginess.

Perhaps a combination of herbs+minerals+melatonin? Would something like lemon balm or glycine+magnesium+melatonin be effective while devoid of serious side effects? One of concern with a cocktail like this is that it might irritate the digestive system, while perhaps not helping sleep onset considerably.

Currently trying agomelatine, only one day in but so far has only made insomnia worse.

[Galaxyshock]

Quetiapine at doses around the 25 mg usually prescribed for sleep ain't too bad - it's mostly a central antihistamine at that dose. Histamine is pretty unique as neurotransmitter as histaminergic signaling completely stops during sleep and only starts firing again shortly before waking up. Which is the reason histamine antagonists work well for sleep. But if there's next day grogginess it might not be ideal - or perhaps with a lower dose you could avoid that. Quetiapine also has active metabolite, Norquetiapine, which might interfere with day-time functioning.

 

Not a fan of Melatonin, it seems to guarantee headache next day for me for some reason. Melatonin also lowers the levels of all hormones except growth hormone.

 

If you can find source for nobel Kava Kava, that might do the trick similar to benzos but without side effects I'm thinking. 

[fall]

Quetiapine at doses around the 25 mg usually prescribed for sleep ain't too bad - it's mostly a central antihistamine at that dose. Histamine is pretty unique as neurotransmitter as histaminergic signaling completely stops during sleep and only starts firing again shortly before waking up. Which is the reason histamine antagonists work well for sleep. But if there's next day grogginess it might not be ideal - or perhaps with a lower dose you could avoid that. Quetiapine also has active metabolite, Norquetiapine, which might interfere with day-time functioning.

 

Not a fan of Melatonin, it seems to guarantee headache next day for me for some reason. Melatonin also lowers the levels of all hormones except growth hormone.

 

If you can find source for nobel Kava Kava, that might do the trick similar to benzos but without side effects I'm thinking. 

 

Thanks for responding.

 

Quetiapine at 25mg works OK, at 50mg works extremely well. I am saddened by the fact that upon further researching into low-dose Quetiapine finding credible studies pointing to significant risks and adverse effects. Among the more alarming studies is a Danish one with a large data pool which specifically discussed low doses intended for sleep. There are other studies pointing to long-term low-dose Quetiapine leading to weight gain in almost every single user(!) including other metabolic disorders, increased risk of cardiovascular events, etc.

 

The Danish study:

 

We aimed to assess the risk of major adverse cardiovascular events with use of low‐dose quetiapine compared to use of Z‐drug hypnotics in a nationwide, active comparator‐controlled cohort study. The cohort included new users of either drugs in Denmark from 2003 to 2017, aged 18‐85 years, without history of ischemic stroke, myocardial infarction, cancer, and severe mental illness. The main outcome was the occurrence of major adverse cardiovascular events, defined as non‐fatal myocardial infarction or ischemic stroke, or death from cardiovascular causes. Selective serotonin reuptake inhibitors (SSRIs) were used as an alternative comparator in sensitivity analyses. Altogether, we compared 60,566 low‐dose quetiapine users with 454,567 Z‐drug users, followed for 890,198 person‐years in intent‐to‐treat analysis, and 330,334 person‐years in as‐treated analysis. In intention‐to‐treat analysis, low‐dose quetiapine was associated with an increased risk of major adverse cardiovascular events (adjusted hazard ratio, aHR=1.13, 95% CI: 1.02‐1.24, p=0.014) and cardiovascular death (aHR=1.26, 95% CI: 1.11‐1.43, p<0.001). In as‐treated analysis, continuous low‐dose quetiapine use was associated with increased risk of major adverse cardiovascular events (aHR=1.52, 95% CI: 1.35‐1.70, p<0.001), non‐fatal ischemic stroke (aHR=1.37, 95% CI: 1.13‐1.68, p=0.002) and cardiovascular death (aHR=1.90, 95% CI: 1.64‐2.19, p<0.001). The risk of major adverse cardiovascular events was greater in women (aHR=1.28, p=0.02) and those aged ≥65 years at initiation (aHR=1.24, p<0.001). Compared to SSRIs, low‐dose quetiapine use was associated with an increased risk of major adverse cardiovascular events (aHR=1.42, p<0.001), non‐fatal ischemic stroke (aHR=1.27, p=0.0028) and cardiovascular death (aHR=1.72, p<0.001). So, we conclude that the use of low‐dose quetiapine is associated with an increased risk of major adverse cardiovascular events, especially in women and the elderly. On the basis of these findings, we suggest that use of off‐label low‐dose quetiapine for sedative or hypnotic purposes should be discouraged.

 

From a Norwegian paper:

 

There is considerable risk of side effects when quetiapine is used even in low doses. Weight gain and metabolic disorders, including an increase in triglycerides, have been reported for low doses of quetiapine (15–17). Daytime sedation (‘hangover’) is frequently reported (7–9), (15–17). Among other observed side effects of low-dose quetiapine are restless legs, akathisia, dry mouth and impaired attention (9, 15).

 

https://tidsskriftet...t-sleeping-pill

 

I will definitely look into Kava Kava. Thanks again!

[Mind]

Here is an interesting read on getting good sleep.

[fall]

Here is an interesting read on getting good sleep.

Thanks for this. Great read with some interesting and rather rare points about the benefits of good sleep, especially enjoyed the part about the sleep process wherein memories are either stored safely or 'discarded' essentially the brain tries to prioritize important and positive memories and get rid of bad and hurtful memories. This in part explains why lack of sleep worsens depression, PTSD etc.
The author appears to praise GHB for sleep. I never took GHB seriously in terms of therapeutic use. Is it reasonable easy to source nowadays? I know it can be synthesized with precursor GBL. I rather not manufacture my sleep meds though. Might as well cook speed while I am at it lol.
One of my issues with GHB also - since it is a natural endogenous process in human, long-term use has shown a rebound effect since long-term use decreases concentration of GHB and in return primarily work on other receptors. GHB is well known for this characteristic i.e., having both stimulating and depressant qualities. Perhaps useful for sleep if not used daily. That is if GHB and GBL can be sourced without going through hoops(?).
BTW I recently watched a private video of someone under the influence of GHB and boy did this guy seem to have a wonderful time, dancing and talking for a good while. Supposedly this person was naturally introvert but became addicted to GHB for a period of time because it made him euphoric and extrovert.

Edited by fall, 29 January 2025 - 02:31 PM.

[fall]

I welcome more suggestions for effective sleep onset aids without next day grogginess and cognitive retardation/harm.

I will continue to post progress.

Day 1 I mentioned I started agomelatine. I barely slept that night, I was sweating a lot and very uncomfortable.
Day 2. Had a feeling agomelatine was not going to cut it and added 40mg liquid Alimemazine (just the kind of medicine I want to avoid). First night in a while where I fell asleep within short time and slept through a full 8hr. I might have slept a full night without awakening about a month ago (also with Alimemazine), other than those two times one hand is not enough to count the years it's been since I slept more than 5hr without waking up at least once. Problem is with Alimemazine, don't want to use it for many reasons (sides) including prominent next day tiredness, esp. slowing of thought and body feeling heavier.
Despite of this, I welcome a good night sleep so much that tonight (day 3) will run with agomelatine and alimemazine again until I can replace it with something else, might consider using quetiapine again until I get my hands on something else.

[gamesguru]

Getting supplementation under control may facilitate a stronger response to the same dose of prescription medicine. Things like Magnesium and Tryptophan are helpful additions.

[Galaxyshock]

Quetiapine at 25mg works OK, at 50mg works extremely well. I am saddened by the fact that upon further researching into low-dose Quetiapine finding credible studies pointing to significant risks and adverse effects. Among the more alarming studies is a Danish one with a large data pool which specifically discussed low doses intended for sleep. There are other studies pointing to long-term low-dose Quetiapine leading to weight gain in almost every single user(!) including other metabolic disorders, increased risk of cardiovascular events, etc.

 

Thanks for pointing out that Quetiapine may be harmful even in low doses. Definitely not an ideal choice long-term in this case.

 

The author appears to praise GHB for sleep. I never took GHB seriously in terms of therapeutic use.  

 

GHB is too dangerous in my opinion. Some may be able to use it therapeutically for sleep, but to my understanding the sleep-promoting effect only lasts about 4 hours and you need to redose in the middle of the night? There are horror stories of people taking GHB for the euphoriant properties recklessly and then facing bad withdrawals. Just check Bluelight or some other forum for anecdotes and you'll see that it's probably not the route you want to get into.

 

Getting supplementation under control may facilitate a stronger response to the same dose of prescription medicine. Things like Magnesium and Tryptophan are helpful additions.

 

 

I agree, if night-time supplements and herbs alone don't work well enough, they can at least augment a prescription med to minimize harm/tolerance etc.

 

Mirtazapine is sometimes prescribed off-label for insomnia, may be look into it if it's lesser evil than Quetiapine or so.

[fall]

Getting supplementation under control may facilitate a stronger response to the same dose of prescription medicine. Things like Magnesium and Tryptophan are helpful additions.

Great point. I am leaning towards this approach. I will continue researching a bit more but as of now thinking magnesium + glycine + a less harmful sleep medicine. I need to read up more orexin antagonists, and trazodone.
Tryptophan is not an option as I take 600 mg moclobemide and ~ 1mg selegiline daily. Tryptophan, tyramine, and 5-HTP are all theoretically capable of producing serotonin syndrome during MAOI treatment. Somehow a slew of people on reddit are taking MAOI+tryptophan and even recommends it. I am not so much concerned about acute SS, but moreso of producing potentially neurotoxic states. Indeed some of the most euphoric moments I have experienced (chemically induced) probably coincided with some of the most neurotoxic events. So the people who feel really good with this combo is not necessarily a good thing IMO. Besides reddit can really be a dangerous site to find medical advice. While the people on bluelight (and sometimes erowid) are even more crazy, at least they admit it lol, they can be honest about a danger and blatantly ignorant to it, reddit seems to have a bigger problem with naivety.. idk
Glycine might be better than tryptophan in my case. Again will do more research and try it. So far finding a lot of studies which seem promising - in terms of improving sleep and reducing day time fatigue/concentration.
Many thanks!

Thanks for pointing out that Quetiapine may be harmful even in low doses. Definitely not an ideal choice long-term in this case.


GHB is too dangerous in my opinion. Some may be able to use it therapeutically for sleep, but to my understanding the sleep-promoting effect only lasts about 4 hours and you need to redose in the middle of the night? There are horror stories of people taking GHB for the euphoriant properties recklessly and then facing bad withdrawals. Just check Bluelight or some other forum for anecdotes and you'll see that it's probably not the route you want to get into.


I agree, if night-time supplements and herbs alone don't work well enough, they can at least augment a prescription med to minimize harm/tolerance etc.

Mirtazapine is sometimes prescribed off-label for insomnia, may be look into it if it's lesser evil than Quetiapine or so.

You're welcome!

Yes I agree, GHB seems farfetched even for a desperate fool like myself! I wouldn't be surprised if you'd had to redose it too. I often had to do this exact thing on zolpidem, I'd wake up after exactly 4hrs and feel the need to redose, however, when I was mentally sound and didn't suffer from severe anxiety and depression I didn't need the second dose as I would fall asleep naturally. Right now I feel pretty ok mentally, but falling asleep remains an issue.

I believe I had similar concerns about mirtazapine, namely too many potentially serious adverse effects. Right now I am looking into orexin antagonists, trazodone, and still testing agomelatine. I will likely augment with glycine+magnesium since it seems I mostly respond to strongly sedative medicines - hoping an effective but less potent sedative will work better along with these supplements. I will also see if I can find a strong hypnotic without serious side-effects, hypnotics along with sedatives appears to be most effective in terms of sleep-onset.

Edited by fall, 31 January 2025 - 11:30 PM.

[gamesguru]

Great point. I am leaning towards this approach. I will continue researching a bit more but as of now thinking magnesium + glycine + a less harmful sleep medicine. I need to read up more orexin antagonists, and trazodone.
Tryptophan is not an option as I take 600 mg moclobemide and ~ 1mg selegiline daily. Tryptophan, tyramine, and 5-HTP are all theoretically capable of producing serotonin syndrome during MAOI treatment. Somehow a slew of people on reddit are taking MAOI+tryptophan and even recommends it. I am not so much concerned about acute SS, but moreso of producing potentially neurotoxic states. Indeed some of the most euphoric moments I have experienced (chemically induced) probably coincided with some of the most neurotoxic events. So the people who feel really good with this combo is not necessarily a good thing IMO. Besides reddit can really be a dangerous site to find medical advice. While the people on bluelight (and sometimes erowid) are even more crazy, at least they admit it lol, they can be honest about a danger and blatantly ignorant to it, reddit seems to have a bigger problem with naivety.. idk
Glycine might be better than tryptophan in my case. Again will do more research and try it. So far finding a lot of studies which seem promising - in terms of improving sleep and reducing day time fatigue/concentration.
Many thanks!

 

Mg and Glycine are a good start.

 

1 mg of Seleg won't cause any MAO-A inhibition. Moclobemide won't cause issues at typical doses since it's a reversible MAOI. I would stay away from 5-HTP; it's associated with heart valve dysfunction and the 5-HT1B receptor. Tryptophan causes a milder and less peripheral boost in 5-HT and doesn't have the same associations. MAOIs reduce oxidation of monoamines, and a good portion of toxicity associated with recreational euphoriants comes from an unmitigated cascade of oxidative stress. MAOIs are neuroprotective at therapeutic doses. Out of an abundance of caution, I would limit it to 500 mg or 1000 mg of Tryptophan at the most and not increase my dose of Moclobemide or Selegiline under any circumstances.