u/MaltaPrivacy

I’m a relatively severe lifelong insomniac. Over the last year or so I’ve been studying sleep physiology and pharmacology, and I recently learned about gaboxadol. From Hamilton Morris’s writings about it to reading the actual studies, I’ve become very interested in it for its medicinal use as a hypnotic to improve sleep quality (namely sleep onset latency) and architecture. Unlike Z-drugs and benzodiazepines, it does not suppress deep sleep or dependence. It actually robustly enhances N3 sleep, but unlike say phenibut, gabapentin, etc. does not seem to cause addiction/tolerance, preserves REM and overall produces a much more physiologically natural sleep architecture, and does not have the harmful neurological effects of α2δ calcium channel inhibition. In fact, it really has very few downsides to speak of compared to other hypnotics or CNS depressants, with the exception of orexin antagonists, and has uniquely beneficial effects on sleep architecture. This might be due to its selectivity for δ-subunit containing GABA_A receptors, which are highly expressed in the arousal/wakefulness-promoting regions in the thalamus, or due to its tonic GABA_A inhibition rather than the phasic inhibition of other drugs. It might also be because the α4β3δ receptors for which gaboxadol has the highest selectivity and activity are positively modulated by histamine, so agonizing them might cause a homeostatic braking effect on the histaminergic tuberomamillary nucleus, but that's just a hypothesis I invented.

I think orexin receptor antagonists (both DORAs like daridorexant, lemborexant, etc.) and 2-SORAs (seltorexant) are excellent drugs with broad applicability and terrific therapeutic indexes, but I wish they were powerful enough for severe insomnia like I have. Instead I have to partially rely on drugs like trazodone, zaleplon, and zolpidem which create concerns for long-term use. And while ORAs were an improvement over Z-drugs by not significantly suppressing slow wave sleep (Z-drugs do so slightly, but less than benzodiazepines), they are known more for increasing REM. Again, while this does not come at the expense of SWS, it is not optimal either. N3/SWS sleep is most implicated in brain function and cognitive health, via mechanisms like glymphatic system activity, memory consolidation, synaptic pruning, metabolic restoration, well as other physical health benefits like exercise recovery, insulin sensitivity, etc. You can actually completely kill your REM sleep with an MAOI and be more or less fine, but lack of deep sleep is terrible. True that gaboxadol is not the only drug that increases delta and theta band power; other agents include GHB, phenibut, gabapentin, and pregabalin, but these all have profound downsides which gaboxadol apparently does not. Ultimately, I think gaboxadol is unmatched in its ability to promote restorative sleep.

Is pretty well studied in humans (at least by the standards of the stuff we usually talk about in these circles…), and while it definitely has some recreational/abuse potential, it seems people are taking around 80mg+ to get mild hallucinogenic effects compared to 10–15mg for sleep. I really recommend reading Hamilton Morris’s article, or even just the Wikipedia article. He even said that after publishing it, more chemists and employees from Merck reached out to him to express confusion as to why they abandoned phase III trials given how well it was doing. Development of gaboxadol for insomnia was cancelled during a time when there was heightened fear among regulators (and pharmaceutical executives, apparently) of parasomnias caused by Ambien, but gaboxadol does not cause these. Not only is it a superior to zolpidem as a hypnotic, but it also seems to have less abuse potential. And zolpidem's is already pretty low in my opinion...

I have not been able to find it on the grey market for a remotely reasonable price. There are research chemical suppliers (i.e. actual research chemical vendors like Sigma-Aldrich who sell only to legitimate institutions and registered businesses, conduct customer audits, do not ship to residential addresses, etc.) selling it for about $200 per 100mg (about ten doses worth). It is completely legal as a research chemical and unpatented, although the synthesis might be a little tedious.

Often in this space there are compounds that sound interesting but are stymied by safety problems. Sometimes, compounds seem promising but lack safety data to provide necessary peace of mind. Some compounds may have an auspicious-sounding mechanism, but lack research to actually confirm that they work as expected or are even effective. And then of course there are completely safe supplements that do absolutely nothing. And, if you know where to look, you can usually find someone willing to sell you any of these questionable substances with even more questionable authenticity and purity. Gaboxadol is a drug with a well understood mechanism, confirmed safety and efficacy in large-scale human RCTs, and extremely promising benefits superior to most current options—but I still can't get my paws on it!

I have spent many years in drug abuse via opioids & Thc. I as well have been in a fair amount of accidents over the years that have caused some debilitating back & Neck pains. I don’t take any prescription drugs, drink, smoke or take sketchy z drugs anymore. I’ve been through a 90 day rehabilitation and have been on the up and up since.

The body pain definitely is still prevalent however “magnesium glycinate” seems to knock a good dent in aiding some of these issues with its calcium channel regulation, nmda receptor antagonism & Gaba modulation makes for soothing reaction when I’m in a good deal of pain. I typically use this at night as it can relax me a little too well given the day I suppose.
(7/10)

An even better tool for chronic pain I’ve found is “Magnolol” extract. Possibly the strangest nootropic I have ever come across in my life, given its effectiveness for me as well as its wide range of benifits. It’s a powerful anti inflammatory, antioxidant, GABA A modulator, endocanebanoid modulator, neuroprotectant & an anti cancer agent. And I’ve noticed it to help for occasional panic attacks however it’s anxiolytic and muscle relaxation benifits are what stopped me in my tracks about it not to mention the sleep.
(10/10)

“Ashwaghanda” is a nifty tool to have on hand however not as effective or therapeutic as magnolol but it is one of the few nootropics to cause a noticeable difference. Mine is a combination of Withania somnifera & Ksm66 it’s a light gaba modulator as well as a powerful antioxidant. Helps me stay asleep on nights where I get up and have issues going back to bed. Also the cortisol lowering is a magical thing for stress which I find myself in often.
(7-8/10)

The “B-Complex” & “CoQ10” have an amazing synergy of energy for me I’ve noticed. I’m extremely sensitive Caffine and have swarm off for a few weeks working myself down with a taper. So these two guys do some heavy lifting for me and I typically take them in the morning as not to keep me up at night and it gives me clean sustainable energy through out the day without crashes, jitters or anxiety.
(9/10)

“Nac” was a last ditch effort for relief during my post acute withdrawals from opioids and I couldn’t really tell that it was helping me out anyway but I took it just to make sure out of desperation however it’s a great antioxidant and I’m sure has many uses and benefits for others !
(😟/10)

“L-Theanine” an absolute classic and should be in every back pack or purse of anyone with anxiety disorders. I would say just to use sparingly as needed as many report fast tolerance build up however suntheanine doesn’t have this problem for most. Also there is definitely a bit of a mental clarity and focus that come along with it lending itself to many study stacks all across the world.
(8-9/10)

“Omega Complex”
Seems to help me with depressive symptoms a fair amount not to mention as well as supporting brain cognition (great anti-inflammatory as well)
(7/10)

“Vitamin E”
Antioxidant protection, Cardiovascular support, skin health/repair, immune function, neurological protection & eye health.
(10/10)