Hi everyone,
I’ve been suffered for insomnia for 4 years. Literally I tried all the drugs, therapies and supplements for sleeping improvement.
Here I want to record some of my medication history and my own sleeping supplement, since sleeping is one of the three pillars of longevity.
Correct me if I make any mistake.
Many hormones and neurotransmitters regulate sleep.
- GABA
GABA is the primary inhibitory neurotransmitter in the central nervous system. GABA Receptor Agonist is the most traditional class of sleeping medicine. It mainly targets the GABA-A Receptors, enhancing the effects of GABA, to slow down brain function. What’s more, GABA is also important for maintaining deep, uninterrupted sleep.
Benzodiazepines and Non-Benzodiazepine Receptor Agonists are the mostly popular medicine. I have used lorazepam and eszopiclone for years, but every one of psychiatrists I met told me to try to stop using these drugs since they all have risks like dependence.
GABA system disorder characterized by difficulty falling asleep or easy to wake up at midnight. A few years ago, my insomnia mainly manifested as this problem, so those drugs above really effective to me, but now it does not like that anymore.
- Orexin (Hypocretin)
Orexin affects lots of behavior and functions like, promotes and maintains arousal, keeping you awake during the day. Theoretically this system would be suppressed at night by GABA, and maintains your sleep state until 7-8 hours later, along with GABA and Melatonin system.
One of my symptoms is, I take lorazepam or eszopiclone but I still cannot maintain a long, deep sleep.
Block orexin A and B can suppress the “wake” signals in the brain. This is the newest class of insomnia medications. Instead of actively causing sedation, they work by blocking wakefulness.
These medicines are relatively expensive, but it does prolong my sleep and improve quality.
- Melatonin
Melatonin is actually a hormone, not neurotransmitter. In the evening, it signals to the body that it’s “time to sleep,” helping to induce sleep. Give yourself 30-60 minutes to fully relax may be helpful for better sleep.
Melatonin correlates with Serotonin and Cortisol. Basically, Serotonin transforms into Melatonin, Cortisol drops when Melatonin rises and vice versa. If melatonin secretion is delayed or insufficient, it can lead to difficulty falling asleep, a situation particularly common in delayed sleep-wake phase disorder.
Take Melatonin directly or Melatonin Receptor Agonists can help regulate circadian rhythm, which is really effective for fixing delayed sleep-wake phase. However, these supplements or medicines is not really helpful for my current insomnia.
- Serotonin
Serotonin is a fundamentally neurotransmitter that has lots of functions. Serotonin is a precursor for the synthesis of melatonin. A decrease in serotonin levels can indirectly lead to insufficient melatonin production, thereby causing difficulty falling asleep. That is one of the reason that many patients who suffer from Anxiety or Depression may have insomnia.
Interestingly, almost every one of psychiatrists I met tend to prescribe SSRI to treat long-term insomnia patients, rather than Melatonin Receptor Agonists.
- Histamine
Histamine is highly active during the day to maintain alertness. It also involves in immune response, allergy, and blood pressure regulation.
The disorder (or unstable) of Histamine usually manifested as you cannot maintain a “long night” deep sleep.
Histamine Receptor Antagonists are a pretty common OTC sleep-promoting medicine, but it has risks like dementia for long-term use.
- Acetylcholine
I put Acetylcholine here because Histamine Receptor Antagonists can also help downregulate Acetylcholine. This neurotransmitter mainly functioning for learning, wakefulness and REM sleep.
It does not directly affect sleep process but it is one of the victim of Histamine Receptor Antagonists. That’s why I think Histamine or Acetylcholine is not great target to treat insomnia, even if Diphenhydramine is useful for most people.
- Cortisol
Cortisol is such a popular hormone in longevity community, it has lots of fundamental function like immune, anti-inflammation, glucose regulation.
The body’s cortisol levels naturally begin to rise around 3 hours before you wake to prepare for morning wakefulness, a phenomenon known as the “Cortisol Awakening Response” (CAR). If this process starts too early or the rise is too sharp, it can lead to waking up too early. Stress and anxiety can significantly affect the rhythm of cortisol and are important causes of early awakening.
In my opinion, Cortisol is not really a good target for most healthy, not stressful people, since it is such an “underlying signal” for your whole body, it has its own natural logic. Also, there is not really good (or “safe”) drug to regulate it smartly. Simply lowering it does not means good, let it perform its correct rhythms is more important.
- Adenosine
The main function of Adenosine is act as a “Sleep Pressure Signal”. It accumulates throughout the day during wakefulness, creating a drive to sleep.
Caffeine is the most well-known antagonist of it.
Adenosine does not directly take you into sleep but it give you and your body the signal to start all the system to sleep.
Hence, do not take caffeine and do not nap within 8 hours before you sleep, let your brain drown in Adenosine naturally.
- Norepinephrine
This is a major arousal and stress neurotransmitter, the key component of the “fight-or-flight” system. When an individual is under stress or anxiety, norepinephrine levels rise, leading to cortical activation, keeping the person alert and thus making it difficult to fall asleep.
PTSD patients often need to downregulate Norepinephrine system, a more stable Norepinephrine system is crucial for them.
Like serotonin, Norepinephrine is also a target to treat depression, these patients need higher Serotonin and Norepinephrine.
Also like Serotonin, Norepinephrine is not a direct controller of sleep, but it need to be stable when sleep.
10+. Dopamine, Glutamate and more
Actually many systems are involved in sleep process.
Generally speaking, Neurotransmitters like Dopamine and Glutamate works mostly in day, and these systems need to be more peaceful at night. If these neurotransmitter malfunction at night, you could feel you mind is so active so you cannot sleep.
Even Prostaglandins, Progesterone and all other hormones acts as a key factor in sleep.
In short, you can sleep better when these hormones and neurotransmitters are functioning well and effective:
- GABA
- Melatonin
- Serotonin (stable, to be precise)
- Adenosine
- Prostaglandins
- ……
And these hormones and neurotransmitters better be more peaceful at night, act actively only if at the right time:
- Orexin
- Histamine
- Acetylcholine
- Cortisol
- Norepinephrine
- Dopamine
- Glutamate
- ……
The reason I wrote so much stuffs is that I find it really difficult to maintain a long, stable and deep sleep for most days. Sometimes I cannot fall into sleep, sometimes I wake up really early, sometimes I wake up a few times at midnight.
It is a good choice for insomnia patient to take a full test to know which systems causes your insomnia. Since these systems affects each other and usually malfunction at the same time, severe patients like me need to find out which systems is the main cause.
In summary, there are many different types of insomnia, my experience is:
- Sleep-onset Insomnia
Literally, it manifested as having trouble falling asleep. A few people feel overactive so they cannot fall asleep, and others feel peaceful but still cannot fall asleep.
GABA, Norepinephrine, Orexin, Melatonin and Serotonin may be the main reason for this, so these corresponding medicine may be helpful.
Using medicine or supplement to trigger these systems quickly is the key.
- Sleep-maintenance Insomnia
Sleep-maintenance insomnia is characterized by frequent awakenings during the night and difficulty falling back to sleep. This is related to insufficient sleep depth and abnormal activation of the arousal system.
GABA, Orexin, Cortisol, Serotonin and Histamine seems like can be the reason for this type of insomnia. For example, Orexin and Serotonin medicine can be used for prolong sleep and make the whole sleep process stable.
Melatonin and Cortisol can be a safer and non-dependence target, but I find it not so useful for long-term severe patients.
- Early-morning Awakening Insomnia
Early-morning awakening insomnia refers to waking up earlier than the desired time and being unable to fall back to sleep, which is particularly common in the elderly.
Depression is a common reason for this type of insomnia, it may because of an unstable serotonin supply rhythms and earlier cortisol rise up.
A simple experiment I am carrying on with my doctor is every time I try one or two kinds of drug, and test it for a few month until they fails. But I still could not get a 7+ hours sleep after 4 years of trying……
