Pharmaceuticals and substances as sleep aids

Is it a good idea to use sleep aids?

Does it bother what’s restful about sleep?
How big part of it is a placebo?
Does it affect the day after?
Are they addictive?
Are all of them equally addictive?
Could I perhaps use a drink to get to bed?

Let’s start bold – some things may help you become unconscious, but sedation is not the same as sleep.

People have had trouble sleeping for quite some time, so substances to aid sleep have been used for quite some time. Opium and alcohol have been used for thousands of years. This is a large subject, but I’ll try to cover what’s useful and necessary, rather than everything – with a reminder that I’m not a physician; pharmacodynamics isn’t my strongest area, though I’ve got a good enough hunch to say a few words. Feel free to get back to me if anything is completely off…

This area gets even larger as it doesn’t just involve the pharmaceuticals, including everything people use to sleep, but also behaviors and psychology surrounding the sleep aid. Those areas are quite neglected from time to time.

An ideal substance for sleep would

Work immediately and be active the entire night or time we’d like to sleep.
Not change the sleep pattern, with depth and other mechanisms.
Not affect the day after.
Not need to be weaned off, be addictive or build tolerance.

There’s no such substance in the market, I’m afraid. There’s none available through prescription or black markets. They all bother one or the other.

One very relevant part of using a substance, except for effect itself, is the half-life. That’s how long it takes for the body to remove half of the substance from being active. If you have a couple of drinks Friday, perhaps you’d like to be able to drive a few days later, and you will – since the body metabolizes the substance. Depending on the substance, the time it takes varies. One standard drink of ~10g of alcohol which is ~4cl of booze, ~12cl of wine, or ~33cl of decent beer, takes more or less a couple of hours to metabolize. But that varies between individuals. So in the case of alcohol, you can usually more or less calculate when you can or should drive again. With drinking, you’re usually pouring your own doses as well. They’re not prescribed to you, which also makes a difference. “I’d don’t want any effect in five hours, so I’ll use this dose”. The case when using a prescribed thing is another. With most substances, half-life is more commonly used than the actual rate of how fast you metabolize it. If you use something with a long half-life and take it daily, you’ll accumulate the drug in your system. You might have more than just a dose or two a few days in. Going about your day while on the medication you use for sleeping ought to be drowsier than necessary, right?

Different kinds of substances

Benzodiazepines

The most common or known group of medications to use for troubles with sleeping or anxiety is benzodiazepines, “benzos” for short. They are a class of psychoactive drugs where the core chemical structure consists of a benzene ring and a diazepine ring. Hence the weird name, which is only logical with that knowledge. It might be worth knowing that substances have a chemical name – and then there’s usually either one or a bunch it’s sold by since the pure chemistry isn’t very salesy and consumer-friendly (try saying chlordiazepoxide three times fast!). So several words or names might refer to the same thing.

The first “invented” one was discovered by chance in 1955, “chlordiazepoxide”, and made available for use in 1960 by Hoffmann–La Roche. The same company that marketed diazepam, also known as Valium or Stesolid, since 1963. Tataa! Just slightly more than a decade, in 1977, benzodiazepines were globally the most prescribed medications. The primary mechanism behind them seems to be that they increase the effect of the neurotransmitter GABA, an inhibiting substance in the brain. They bind to the GABA receptor and increase the flow of chloride into the cell when GABA binds to it. Neurotransmitters are chemical messengers transmitting a signal from one cell or neuron to another. So, in short – you use benzodiazepines to increase a decrease in activity.

These substances are usually, often theoretically, recommended for short-term use by authorities and those in charge of “how should we do this?”. That’s rarely how they are used, however. It’s not rare to use them for months or years, whether for sleep, anxiety, or panic attacks.

Almost a third of all Americans over 65 use benzodiazepine-like substances.

They’re addictive, so you’ll get withdrawal symptoms if you quit too hastily.
You will build a tolerance for them over time, requiring bigger doses. Those bigger doses will take longer to break down and cause more side effects.
Sometimes they don’t work the entire night; do you need help the entire night?
Sometimes they’ve got an impressively long half-life that’ll affect the day after.
They suppress REM sleep, where REM is known to aid learning and creating memories.
They suppress deep sleep, which is the truly restorative part of sleep.

Chlordiazepoxide, the first one discovered and mentioned above, has a half-life of about 5–30 hours. The still active metabolite desmethyldiazepam takes 36–200 hours to decrease to half its amount. Another still active metabolite, oxazepam, takes 6-12 hours.

Diazepam/Stesolid/Valiumtakes about 50 hours. It varies from “somewhere between 20–100 hours” and gives the same still active metabolite, desmethyldiazepam. Half-life means it’s not just a small, insignificant amount left, either. You’re still notably calmer after up to 50 + 200 hours.

Some substances are very similar to benzos in function and mechanics even though they are dissimilar in molecular structure; nonbenzodiazepines or “benzodiazepine-like substances”. The pharmacodynamics are almost entirely the same as benzos, they increase the effect of the GABA, and therefore you get similar results – including benefits, side effects, and risks.

Common substances in this group are

Zopiclone, known as Imovane, Zimovane, and Somnol – with a half-life of give or take 5 hours, but it seems to be close to double in the elderly.

Zolpidem, known by many names where Ambien and Stillnoct might be the most common, has a half-life of about 3 hours. The number of different names and, therefore, products with said name ought to say something about how lucrative the business is and how well spread the drugs are. In this case, it could be to hide some bad reputation when people do weird things while affected by the drug. I’ve met and heard of people who use it, and things don’t go as expected. Horrific nightmares. Sleepwalking. Sleep paralysis. Moving on as usual, but with a completely altered personality – and they don’t have a clue what they did afterward. Interesting, but not necessarily what they wanted.

A list of the names used for the compound from 2018 includes the following:

Adorma, Albapax, Ambien, Atrimon, Belbien, Bikalm, Cymerion, Dactive, Dalparan, Damixan, Dormeben, Dormilam, Dormilan, Dormizol, Eanox, Edluar, Edluar, Flazinil, Fulsadem, Hypnogen, Hypnonorm, Intermezzo, Inzofresh, Ivadal, Ivedal, Le Tan, Lioram, Lunata, Medploz, Mondeal, Myslee, Nasen, Niterest, Nocte, Nottem, Noxidem, Noxizol, Nuo Bin, Nytamel, Nyxe, Olpitric, Onirex, Opsycon, Patz, Polsen, Sanval, Semi-Nax, Sleepman, Somex, Somidem, Somit, Somnil, Somnipax, Somnipron, Somno, Somnogen, Somnor, Sonirem, Sove, Soza, Stilnoct, Stilnox, Stilpidem, Stimin, Sublinox, Sucedal, Sumenan, Vicknox, Viradex, Xentic, Zasan, Zaviana, Ziohex, Zipsoon, Zodem, Zodenox, Zodium, Zodorm, Zolcent, Zoldem, Zoldorm, Zoldox, Zolep, Zolfresh, Zolip, Zolman, Zolmia, Zolnox, Zolnoxs, Zolodorm, Zolnyt, Zolpeduar, Zolpel, Zolpi, Zolpi-Q, Zolpic, Zolpidem, Zolpidem tartrate, Zolpidemi tartras, Zolpidemtartraat, Zolpidemtartrat, Zolpidemum, Zolpigen, Zolpihexal, Zolpimist, Zolpineo, Zolpinox, Zolpirest, Zolpistar, Zolpitop, Zolpitrac, Zolpium, Zolprem, Zolsana, Zolta, Zoltar, Zolway, Zomnia, Zonadin, Zonoct, Zopid, Zopidem, Zopim, and Zorimin

Anti-histamines

These are sometimes used to calm down, sedation or sleep. Those are not addicting physiologically, which is a lovely thing.

Hydroxyzine, known as Atarax with a half-life of 15-24 hours.

Promethazine, known as Lergigan, has a half-life of about 13 hours.

Alimemazine, known as Theralen, got a half-life of 4-6, which might be quite adequate. I’ve had clients who’ve compared this one to a rubber mallet, but with incredible nightmares included resulting in waking up extremely exhausted.

Propiomazin, known as Propavan with a half-life of about 8 hours.

Mirtazapine is an antidepressant that isn’t uncommon from what I’ve seen. It’s also used for weight gain if you’d like two for one. As usual with antidepressants, this one should be used continuously to avoid symptoms that usually appear when changing the dosage of antidepressants.

Alcohol

This is likely among the most commonly used substances, regardless of how much benzos are prescribed and how much weed people smoke. It has been used as a sedative for quite some time and is what they call a “central nervous system depressant” like the Benzos. Relaxing and highly available. That makes it widely used.

The problem is that metabolizing the substance is a stressor. That, and the rebound effect once the sedating effect gets less, are likely what bothers sleep. Tachycardia and anxiety from being “wound up” are two common side effects when waking up. The same stress makes you sleep more shallowly throughout the night, making sleep less restful.

It makes you sleepy and relaxed, but it generally bothers the quality and the quantity of sleep. Waking up more than usual is common. In more significant amounts, it can delay how fast some fall asleep. For most, it’s lovely regarding that part. You fall asleep just fine, but the rest isn’t as great. You sleep more shallowly and not rarely less. If you’re really drunk, as in practically “sedated”, it could result in more and longer – but still worse.

The effects are slightly individual, and to some degree, it varies with age. Youngsters don’t mind much, and then, as you get older, it’ll bother you more and more. To some degree, it’s likely a matter of practice. If you go pro, you might not be as bothered, but that’s nothing to aim for.

If it is used for this purpose, just one drink is the preferred dose not to bother sleep once the substance metabolizes. The more widely spread tech to measure sleep has widened many eyes regarding this.

Alcohol increases activity levels, decreases REM sleep, seems connected to insomnia, and exacerbates sleep apnea and snoring.

Melatonin

“Natural”? Well, it’s a hormone, so sure. Pro bodybuilders don’t go as natural when they add hormones. But you might..? Speaking of hormones and bodybuilders. They generally use what’s referred to as “anabolic androgenic steroids”. Stuff related to how very masculine you are and highly related to sex and reproduction. Some things point to the fact that melatonin could interfere with similar things. This study includes this in the abstract: “Melatonin can, therefore, influence the gonadal function indirectly–via its effect on gonadotropin-releasing hormone and/or gonadotropins secretion. It may also act directly; several data show that melatonin can be synthesized in gonads.”

The list is often incredibly long when you look at the side effects of anything. For melatonin, you could find these, in addition to the previously mentioned: Headache, Dizziness, Nausea, Daytime drowsiness, Vivid dreams or nightmares, Short-term feelings of depression, Irritability, Stomach cramps, Diarrhea, Constipation, Decreased appetite, Urinary incontinence at night, Increased risk of falls, Increased risk of seizures, Confusion or disorientation, Mood swings, Reduced alertness.

So anything and everything could happen.

The first four are the most common, but it seems safe and works well for people short term. It’s what you produce yourself when darkness falls, and it’s getting closer to bedtime, so the function is quite well established – but the long-term effects from supplementing it are less researched.

Since you produce this on your own, it might work long-term. Perhaps you help your brain to time things and nothing more. Or… Back to the parallel of bodybuilders, when they introduce exogenous hormones, their own endogenous production usually decreases, which might have long-term consequences. As far as I know, this isn’t researched particularly well regarding melatonin.

This could be an excellent tool from time to time or when poking your circadian rhythm in the right direction after being jet lagged. As far as we know, it’s not a bad choice. It’s considered harmless enough in a lot of countries for you to be able to get it as easy as getting groceries.

So, we don’t know the long-term consequences, but I guess this isn’t a horrible choice if you need help. It doesn’t ruin sleep like most other substances do and has no apparent long-term consequences.

Marijuana and weed-products

With tetrahydrocannabinol or THC, they seem to sedate. That’s the bad part, making your sleep dysfunctional and you’re unconscious, but without getting the helpful parts as much as you’d like, like REM sleep.

Without THC is still tricky. 300-600 mg of CBD oil might decrease cortisol. That’s likely a good thing. But when you add to it that another study concludes that 25 mg is more effective than 175 mg to counter anxiety when going to bed, it becomes confusing.

This is never used as a prescribed sleep aid or as a legal recreational thing around here, so it’s rarely relevant to reflect on.

Consequences of using sleep aids

Rebound effect

Getting the opposite after having used calming things?!

An opposite reaction happens after getting the substances out of your system. The purpose of the substance is to decrease physiological activity. According to the systems that try to regulate homeostasis, that’s a bad idea. They prefer to have things even, so while things are suppressed, they try to up-regulate. Once the substance is out of your system, that attempt to up-regulate shows quite well. You get more active than before ingesting the substance. The rebound effect seems most potent when using substances with short active duration, like those used to fall asleep rather than keep sleeping and those used to manage anxiety attacks. Fast relief – and then amplification of it all afterward. Which, of course, can be solved with another dose… if you’d like to keep going forever.

Getting the effect when you don’t want it…

Getting “residual effects” from sleep aids is common.

That inhibiting effect they work by – and the long half-life they’ve got – might bother us the day after. Do you remember the phrase, “you use benzodiazepines to increase a decrease in activity”? If activity is generally decreased in the brain, you’ll get slower in both mental and physical performance. Reaction time will be longer, and coordination will be worse. You’ll feel tired, and you’ll do worse, in short. How much worse depends on the substance and likely varies from person to person. A longer half-life gives a longer effect. That makes the substances more bothersome the next day.

Psychology

The psychology around the aid is often more important than most think. Using something to help sleep often builds habit and dependence regardless of if it’s addicting or not. It affects and is affected by thoughts and emotions. In part, that’s the placebo, even if sleep aids aren’t entirely placebo. The placebo effect could also mean that you’ll get an increased effect. In the long run, using pills to sleep will teach you that using a drug equals sleep.

Learning that pills = sleep.

When are they necessary to use? The prescription might say they’re to be used “when it’s necessary” rather than daily. But… Who decides when that is? Perhaps it’s always troublesome to get to rest and sleep well. More or less. Always more so without the tablet. Here’s a little scenario that isn’t uncommon with these.

You look for help, and you get it. You get a prescription.

Many reason “that it can’t be that bad” once they get what they asked for, their first prescription. Then they continue sleeping horribly for a couple of nights, surrender, take one, and often sleep like babies after being exhausted.

Trust that the pills will help – and they do. You sleep like that peaceful baby. Sure, you’re tired the next morning, but not at all as frustrated and disappointed as when you don’t get to sleep “at all”.

You’re pleased with your new skill called being able to sleep. Either that, you didn’t get enough to use them every night, or perhaps you don’t want to use pills… regardless of the reason, it’s common to skip the pill as you feel confident you’ll sleep well anyway. If you just slept the other night, you know how to… right?

And then you sleep horribly or barely at all. So, as you get tired of being tired, you use the pills again – and sleep wonderfully.

Suddenly you know, since you’ve learned, that you need the pills to sleep. You sleep with them, and you don’t sleep without them. Obvious connection, and it’s easier and more likely since there’s plenty of anxiety when you don’t use the pills.

So… what’s happening here?

They do help. They sedate, and they calm you. They might work wonders, and then some, these pills. Some are used to drug people regardless of whether they want it or not, so they’re powerful substances, no doubt. The actual calming part is there.
Another part of it is that sleep pressure might have built up in a few days if you haven’t slept. That helps you to fall asleep alongside using the pills, as the pills reduce the activity level incredibly. You build sleep pressure from sleeping horribly and then add the calming agent on top of that.
Placebo is a part of it. Some get relaxed as soon as they get the pill behind their teeth. The placebo isn’t bad. It’s a lovely thing and works great. It’s hope giving you a pure pharmacological effect.
As you fall asleep quicker, you don’t have to toss and turn as long. That’ll help you get past the anxiety of not being able to sleep. If you don’t have time on your side there – by using the pills – you’ll be in bed enough time to escalate the anxiety that bothers you because you can’t sleep.
The rebound effect, where you try to suppress activity, and the brain tries to counter that, is a part of the problem – particularly if you don’t use the aid every night. That function will be there every day after using a pill, so using them helps that night but makes the next worse.

This leads to L-E-A-R-N-I-N-G. You connect the pills with a great night’s sleep. Particularly if you use it intermittently, meaning once in a while and only sometimes. We’ve seen that intermittent reinforcement is far superior to something that works “every time”. Trying to avoid the pills but getting sleep once in a while when you use tablets will teach you how well they work even better than if you used them daily.

The desire to not use the tool is common. There are side effects, you don’t want to be dependent, “you just shouldn’t,” or something else. Those opinions make people more likely to avoid them and to let go as often as possible. They try to sleep without the aid, fail, get frustrated, and continue using the tool.

A typical pattern is to succeed more or less every other night. That underlines the learned behavior even more. The point gets proven time and time again. Every time you try to avoid using something to sleep, you fail. The night after, you’re fine.

When are you dependent?

You’re not addicted if they’re not used daily, are you?

You can go on without them, you don’t really feel a craving.

It’s not like you’re taking bigger and bigger doses.

You still got your job, and you’re FINE!

But if you do need the substance to sleep, regardless of if the addiction is psychological, where you don’t “think” you can sleep without it (and that’s the result you see as well), or physiological, where you get the shakes and feel horrible without the drug, does it matter? You still require something to be able to do something quite basic, such as sleep.

What if you’re dependent, and that doesn’t matter? “Go with the flow, this works, and I don’t mind.” Using it for a while will build tolerance, and you’ll need more. The dose needs to increase over time, generally. Perhaps just another small pill or just another half. Regardless, small steps can get you to big doses.

Sometimes people set a deadline or similar behaviors; “If I don’t fall asleep before x, I’ll use one” and then they keep track of time until it’s okay. This is generally not useful since you’ll be awake and actively checking the time, waiting and thinking until then.

There are plenty of ways to learn that they are lovely. Once you get your hands on it, it’s easy to get comfortable. Becoming dependent on pills isn’t at all a strange thing. If you get one tool and one tool only to solve a problem, it would rather be strange if you didn’t become dependent on that tool to solve the problem.

Using Cognitive Behavioral Therapy is meant to teach you how to handle sleep without pills. The calming effect of the pill decreases your activity level. Timing that and going for a drug when you’ve got high sleep pressure will get you to sleep like a baby. But there are other ways to achieve the same thing without substances. That way, you’ll get the good parts of sleeping well but without the negative aspects that might come with the substances you need.