5-HTP : Modes of Action?

I've previously conducted two experiments with 5-HTP: 

5-HTP and its effect on my AHI and sleep in general (link)

5-HTP and its effect on my snoring profile (link) 

Both gave encouraging results. In fact they were so encouraging and surprising that I really would like to know more about how it has the effect that it does, and would it work for other people?

My studies are so small (as I am only experimenting on myself) and the potential for a pharmaceutical solution to Sleep Apnoea and Snoring so attractive that I would love to see further research and a larger trial for 5-HTP as it poses so many questions:

• Does it work for anyone other than me?
• Is it only effective for Mild Obstructive Sleep Apnoea?
• How dose-dependent are the effects? Does too high a dose limit the effectiveness (as with Melatonin)?
• Does the positive effect fade with long-term use?
• Are there any negative effects?
• Are the co-factors that I've been taking with this brand of 5-HTP (label from manufacturer's website here) partly responsible for the effect?

Although I can't find the results of any direct studies looking at AHI or snoring, there is a fair amount of medical literature relating to Serotonin (which 5-HTP is an immediate precursor to, that is 5-HTP is metabolised into Serotonin by the body).

From the existing literature I've tried to piece together possible mechanisms for the effects that I've observed.

THE EFFECTS OF SEROTONIN ANTAGONISTS IN AN ANIMAL MODEL OF SLEEP-DISORDERED BREATHING

By blocking serotonin activity in a breed of dog prone to obstructive apnea, it was possible to induce snoring whilst they were awake along with a collapse of the upper airway, which was reversed when serotonin activity was allowed to return.

Veasey SC, Panckeri KA, Hoffman EA, Pack AI, Hendricks JC
http://ukpmc.ac.uk/abstract/MED/8564132

"Veasey et al" blocked the action of serotonin (5-HT) in Bulldogs while they were awake (using agents known as 5-HT Antagonists). Daytime snoring was observed. Furthermore using live CT scanning a collapse of the upper airway was observed. These effects were reversed when the action of serotonin was unblocked.

This gives a clear indication that serotonin is essential for maintaining the muscle tone of the upper airway.

So, why does this tone drop off during sleep? During sleep (and especially during REM sleep) muscle tone is reduced. In REM sleep we undergo muscle atonia (deactivation of most muscles - this is also the cause of sleep paralysis). It is also shown that Serotonin activity is at its lowest during REM sleep. So a greatly reduced level of serotonin activity leads to a greatly reduced level of muscle activity during REM sleep.

It doesn't seem that simply activating certain Serotonin receptors can undo this muscle atonia. This is a bit of a leap on my part, but it seems that 5-HTP excites all types of serotonin receptors rather than just a few that are excited by various other pharmaceutical methods. Maybe this is because that by allowing the body to convert the extra 5-HTP to serotonin you are allowing natural metabolism of 5-HTP to 5-HT rather than just a localised or specific 5-HT receptor activity.

There are papers that support the fact that 5-HTP has an effect where 5-HT has none (albeit in motor function).

5-HT PRECURSOR LOADING, BUT NOT 5-HT RECEPTOR AGONISTS, INCREASES MOTOR FUNCTION AFTER SPINAL CORD CONTUSION IN ADULT RATS

Y. Hayashi, S. Jacob-Vadakot, E.A. Dugan, S. McBride, R. Olexa, K. Simansky, M. Murray, &  J.S. Shumsky

Exp Neurol Jan 2010

We conclude that selective 5-HT or 5-HT receptor activation was not effective in improving 2C1A hindlimb function after incomplete lesions. In contrast, the 5-HT precursor 5-hydroxytryptophan (L-5-HTP), which activates all classes of 5-HT receptors, increased both %WS and hindlimb activity

http://ukpmc.ac.uk/abstract/MED/19840787

In the following paper by Ling, Bach & Mitchell it is shown that 5-HTP has the ability to reveal and activate a latent pathway in the spinal cord in hemisected rats (similating an incomplete spinal injury).

SEROTONIN REVEALS INEFFECTIVE SPINAL PATHWAYS TO CONTRALATERAL PHRENIC MOTONEURONS IN SPINALLY HEMISECTED RAT 

Liming Ling, Karen B. Bach, Gordon S. Mitchell

Exp Brain (June 1994)

These results indicate that serotonin converts ineffective crossed phrenic pathways in the spinal cord to effective pathways. It remains to be determined whether serotonin is both necessary and sufficient in this modulatory process, or if it is a nonspecific result of increased phrenic motoneuron excitability.

http://ukpmc.ac.uk/abstract/MED/7843300

5-HYDROXYTRYPTOPHAN-INDUCED RESPIRATORY RECOVERY AFTER CERVICAL SPINAL CORD HEMISECTION IN RATS

Shi-Yi Zhou & Harry G. Goshgarian

J. Applied Physiol (June 2000)

Because experiments were conducted on animals subjected to C2 spinal cord hemisection, the recovery was most likely mediated by the activation of a latent respiratory pathway spared by the spinal cord injury. The results suggest that serotonin is an important neuromodulator in the unmasking of the latent respiratory pathway after spinal cord injury. 

http://ukpmc.ac.uk/abstract/MED/11007592

So we have two potential mechanisms by which 5-HTP could work: 

1. By loading with 5-HTP it allows the body to metabolise it to 5-HT activating all classes of 5-HT receptors thereby reducing the effects of muscle atonia in REM without completely inhibiting REM atonia.
2. By possibly activating a dormant pathway in the spine to the phrenic nerve (increasing breathing effort). 

As we've seen by my sleep-study results, my sleep apnoea is obstructive in nature, so it is unlikely that increasing breathing effort would reduce my AHI as I still make breathing movements but they are rendered ineffective by the obstruction in my upper airway.

If 5-HTP does work in these two ways then it's possible that 5-HTP may have a positive effect on both Obstructive and Central sleep apnoea as item 1 above relates to OSA while item 2 relates to some forms of CSA. 

Snoring Remedies? Results for 5-HTP

Using the method detailed in this post I decided to see if 5-HTP had any effect on my snoring.

I was keen to try out 200mg of 5-HTP first, given that it had previously had such a positive effect on my AHI.

My thinking was that if 5-HTP had been able to reduce the gross movements of my airways that are responsible for obstructive sleep apnoea, then maybe it would also be able to reduce the smaller movements that are responsible for snoring. However, I suspected that as it hadn't been able to completely prevent airway restrictions that it wouldn't have an effect on the smaller movements. 

It seems that I was wrong. The results were promising to say the least. 

5-HTP was able to reduce my snoring further than that offered by just sleeping on my side.

Given that from my data alone there are two indications that 5-HTP is beneficial to sleep (AHI reduction and a reduction in snoring) I would love to see a larger scale experiment or trial take place, after all I am just "n=1".

Prior to taking 5-HTP I researched it in medical literature with regards to dosage and possible side-effects. After seeing my results I went back to the literature and started looking for a possible mechanism or explanation as to why 5-HTP might have this effect.

I'm working on a summary of what I've found and will post it in the near future.

For the future:

• I'm curious as to whether the 5-HTP would reduce my supine snoring index, given that my snoring is at its loudest and most frequent when on my back so I will record a three-night mean of 5-HTP sleep when I will be free to move and produce supine and free-to-move snoring indexes via the Visi-Download software.
• I'm also curious to see what different doses would achieve, so I'll carry out three night mean trials of side-sleep + 50mg, 100mg and 300mg of 5-HTP and measure the effect on my AHI, snoring profile and sleep stage data.

Sleep Paralysis as a Result of Nocturnal Disturbances and Respiratory Events?

A few years ago I had three instances of sleep paralysis in the same night, leading to finally meeting "The Stranger In The Room". Since then I haven't been afraid of sleep paralysis, in fact I've welcomed it as it's a fairly easy way to initiate a lucid dream.

The other night I experienced sleep paralysis which progressed to an Out of Body Experience (OOBE) then to a Lucid Dream, and it's given me more of an insight into a possible mechanism, which seems to fit with the episode that occurred a few years ago, only this time I was wearing 2 sleep monitors so I've been able to "capture" some elements of it and piece together my theory of the events.

This has led me to realise that there are common factors in the events leading up to sleep paralysis and the subsequent spontaneous lucidity.

I'll begin by describing what happened several years ago. I'm well aware that it didn't happen literally, but bear with me as I think it's best to describe it as it appeared before taking it apart scientifically. I've put the account in a quote-box, so if you really can't bear hearing other people's dreams you can easily skip over it...

I briefly mentioned in this post that as far as getting over the fear of sleep paralysis goes, the turning point for me was a night several years ago when my son had a chest infection causing his nocturnal oxygen levels to drop lower and more frequently than usual meaning that I had to carry out assisted coughing and nasal suction several times. Needless to say our night was very disturbed and we were both very tired. This was the second such night in a row.

On three occasions when I returned to my bed I suffered from sleep paralysis. It was something that I'd grown used to because it had been occurring roughly once every couple of months from the age of around 13.

I'd be laying in bed listening out for his oximeter alarm, then I'd get the familiar whistle in my ears, a crackling noise, then my body would feel crushed and each muscle would feel as if someone had deflated it squashing me further into the bed. Then the familiar (but still frightening) feeling of someone watching me as I lay there struggling trying to talk but only managing a throaty "uugh" noise.

By the third time I almost found it funny (maybe because it had never happened to me so frequently, so this time it felt familiar, almost to the point that I knew I was safe). I kept telling myself that my body was effectively asleep. "Okay, so my body is asleep but somehow I (whatever makes me me) is awake, so that 'me' is going to get up".

"I" then rose above my sleeping self about a foot or two, rolled left (now facing the wall), then floated to the foot of the bed and ended up standing on the floor looking back at my sleeping-self.

This all seemed normal at the time. 

It was then that I could finally see the person that had been watching me. He was standing next to me at the foot of the bed. He stepped aside, smiled and gestured towards the mirror at the end of my bed. Then I passed through the mirror, through the wardrobe and then through the wall into my son's room next door. A few moments later I was back in my bed, awake and able to move.

The feeling was incredible, even if it did leave me a bit confused as to whether I was really awake this time. From that moment on I have not been afraid of sleep paralysis.

Now here's a brief account of the episode I had the other night, then I'll draw some parallels between the two nights...

I'd had little sleep the previous night as I had to be awake around 3am for a journey to Manchester. When I got home I was tired, so after dinner I made a point of not staying up late (bed by 9pm). Keen to carry on my experiments with 5-HTP I took 200mg of 5-HTP, connected some channels of the Black Shadow sleep monitor (SPO2, Pulse, Airflow, Body Movement and Sound), put the Zeo headband on, started to record the raw Zeo data with ZeoScope and went to sleep. I was also wearing the Rematee belt (as is normal for me now).

I was asleep within 6 minutes (a fair indicator of sleep-debt). Another indicator of sleep-debt is the fact that I was briefly in REM sleep within 9 minutes of getting into bed!

At 4:02am (I know this from the raw data) I was woken from REM by a noise near my bedroom window. I woke suddenly thinking that I had an intruder. I shuffled round the bed a bit listening for more noises and then lay there replaying the noise in my head trying to make it fit with a known noise. At the time I also considered that it was a hypnagogic noise. It was a multiple banging noise, and I imagined it was probably a picture falling off the wall and bouncing on the wooden floor.

I'd spent around 10 minutes trying to work out a cause of the noise as I dozed in and out of sleep, then the familiar whistling noise of Sleep Paralysis stirred me. I got excited and tried to turn it into an OOBE by pushing "myself" from my head, but that just stopped the noise so I stopped too. Then the whistling returned and I tried rolling "myself" out of my body. It worked, I sat on the edge of the bed and felt sad that I'd actually woken myself up. It turned out to be a false-awakening because I then floated to the end of the bed, realised that I was still dreaming, and from that moment on was in a lucid dream (albeit of the out-of-body variety).

I went to my bedroom door, floated out into the hallway (something I've never been able to do before as doors usually take me to the wrong place).

It was dark, so I put my hand into the adjacent room and tried to put the light on except there wasn't a switch, just a lump of plastic. Again, this prompted me to stay lucid. So I went to the front door (in search of the cause of the noise). As I got to the front door I hesitated because I really wanted the door to take me outside and I was afraid that it would take me to the wrong place (despite the earlier door working correctly), so I "poured" myself through the letterbox and ended up outside on the driveway.

It was still dark outside, and I had trouble seeing, I imagined that this was because I knew that my eyes were shut because I was asleep, so I took my dream-hands and prised open my dream-eyelids in a way that only someone who has ever had conjunctivitis will know. Then it became daylight.

On my driveway was a postman in a bright red fleece. Instantly I was standing next to him and he acknowledged me. I was confused because I knew that this was a dream so expected that I was ghost-like and he wouldn't be able to see me. (I didn't realise it at the time but I was losing lucidity and becoming the observer of the dream again rather than the creator).

The postman apologised for the noise and said that he'd been trying to get a large parcel through the tiny letterbox.

I thanked him, took the parcel and opened my front-door, only to find myself back in bed and waking up.

I then pressed then event-marker on the Black Shadow Monitor and recorded what I remembered of the dream before getting out of bed.  

There are a few key similarities that I think are worthwhile extracting from these accounts, and some I've only become aware of in light of the lucid-dream I had the other night.

• Sleep debt from previous night
• Disturbed Sleep that night
• Waking and being fully alert during the night before returning to bed
• Remaining alert for an anticipated noise
• Sleep Paralysis leading to a dream which became lucid ending with me going off in search of the source of the noise.

In the morning I was keen to playback the audio recording of the night's sleep to see if the sound was real, or hypnagogic in nature. I also wanted to see what the various monitors managed to show of this experience.

It turned out the sound was real and the Black Shadow's microphone was sensitive enough to capture it. It was possible to hear a car driving past the house (causing me to stir) followed 6 seconds later by the sound that I heard: it sounded like a rat-a-tat-tat on the letterbox but I still couldn't identify the noise.

The first sound is much clearer through headphones or good speakers.

The next morning when I went to my car I found the cause of the noise. The passing car had lost a plastic hubcap which had hit the front of my house (my bedroom wall) and spun on the concrete before settling down, in a similar way to a spinning coin running out of energy on a tabletop.

Looking at the graphs from the Black Shadow and the Zeo, it became fairly clear that this wasn't the trigger for the dream, but it was a very important factor because it caused me to wake up fully. I was very alert as I listened out for the cause of the noise, I was anxious and to be honest a little afraid. This likely put me in a state of heightened awareness and self-consciousness, which on some level carried over for the next few minutes into the dream.

I've annotated the 30 minutes covering the noise and finally waking from the lucid dream (click for a larger version).

The raw single-channel EEG data is displayed at the top. I've selected the point that I first woke after hearing the noise. This section aligns with the marker in the brainwave frequency lines (coloured as indicated by the key). 

The hypopneas were the likely cause of the sleep paralysis. I suspect the third one was the trigger as body movement is shown after the first and second along with the noise of bedclothes moving, so sleep paralysis had not set in by then.

I suspect the evening went something like this:

1. Initial car and hubcap noise occurred
2. I woke suddenly causing a rise in delta wave "noise" as I moved.
3. My heartrate more than doubled to 101 bpm (startled and fear) (in line with the delta increase)
4. I lay in bed listening for further sounds until...
5. I drifted to sleep and quickly went into REM
6. My respiratory issues are exacerbated by REM so hypopneas followed (yellow blocks)
7. I had micro-awakenings due to the hypopneas (shown by the blue blocks and reduced pleth)
8. Due to my heightened state I failed to go back into normal REM and became aware that I was asleep.
9. Possibly the final hypopnea ended the dream.
10. I laid still for a few moments before dictating the contents of the dream into the microphone

So I suspect that to reliably induce sleep paralysis and/or lucid dreaming two factors are required;

1. True wakefulness in the night, not just snoozing a 4am alarm
2. A cause of micro-arousals / micro-awakenings.

Wild speculation...

I was hoping for a clear indication of something on the EEG and frequency tracings.

The brainwave frequency analysis in more detail with the purple section believed to be the dream.

If I had to be pushed to look for a trend then I'd say that there was a slight increase in Alpha waves (blue) during the time identified as the dream-period also becoming nearly equal to the Theta wave activity (green) at one point, which declines as I wake, but that is possibly stretching things too far at the moment. However, this overlapping (or meeting) of Theta and Alpha occurs in other places in my sleep (and wake) without any memory of lucidity, so I imagine that finding a simple pattern from a single EEG site is unlikely as things are likely a lot more complicated than that.

For the future

I hope to record the events surrounding more sleep paralysis / lucid dreaming episodes and document any trends that arise rather than just basing my hypothesis on one night.

I'd like to learn to signal to the Zeo that I'm dreaming using eye movements, so that I can further pinpoint when lucidity occurs. Maybe this signal could be on a regular basis (or as regular as the dream permits) to help pinpoint when lucidity begins and ends and normal dreams take over.

 Links

The Stranger in the Room / The Presence / The Dweller on the Threshold / Guardian of the Threshold in literature, religion and folklore

Sleep paralysis and psychopathology - Mume & Ikem "Sleep paralysis occurs frequently after arousal from REM sleep""

5-HTP, Serotonin and Sleep

 

For the last 5 days I've been taking 5-HTP.

5-HTP is a precursor to serotonin (that is, it becomes serotonin once metabolised by the body).

I've previously used 5-HTP for experimenting with my sleep composition, and to try to reliably trigger lucid dreams. The dosage that I was taking then was 50 - 100mg at night.

This time I tried a brand that contained "co-factors". These are associated vitamins and minerals that help the body to metabolise the 5-HTP into serotonin. 

I decided on 200mg each night about 10 minutes before getting into bed. 100mg is the recommended maximum daily dose of this brand, although I have seen others that give a maximum daily dose as 300mg.

I have also seen medical literature that cites doses of 150mg-300mg as a daily dose (as a trial for treating depression), so toxicity at this dose seemed unlikely.

Why did I take 5-HTP?

The rather lazy answer is that (as I mentioned above) I've taken it before without ill effect, and that it is mentioned to have a positive effect on sleep, even being cited as having a positive effect on a severe case of insomnia 

A rather cheeky and over-simplified answer is that I have already shown that a depressant (alcohol) increases my AHI, so I wondered if something that has antidepressant properties would have the opposite effect and reduce my AHI.

I have also seen medical literature that suggests a link between depression and sleep apnoea (both as a cause and effect of sleep apnoea). 

Depression is more complicated that just having low serotonin levels, but low serotonin does play a part. Serotonin is a neurotransmitter (it is used in the body's sending and receiving of nerve impulses), so I wondered if increasing my levels would mean that I would have stronger signals to breathe during sleep and that the muscle tone in my airways would be that much "sharper".

Okay, so how did the 5 days go?

I noticed the following effects (sleep related and non-sleep related):

• I wasn't as tired in the evenings, so went to bed later
• I found it easier to wake up
• I didn't feel as hungry during the day, generally ate once at 2pm, then didn't eat in the evening.

Throughout these experiments, I go to bed when I am tired.

I calculated my average bedtime using the Zeo data. As I am doing these 5-day comparisons on weekdays (except the alcohol test - see separate blog for that), the time that I had to wake up was the same each day, hence later to bed meant less time in bed, which oddly with the 5-HTP didn't feel like a bad thing.

 

I wondered if my body "needed" more sleep, afterall I am used to roughly an extra hour (and still crave more), but on two mornings of the week (Fri and Sat) I can have a bit of a lie-in if I need to but I didn't want to lie in when taking 5-HTP at night (It's Saturday and I'm typing this at 7am, after waking up at my normal weekday time of 6:30am)!

It is known that some anti-depressants can decrease the amount of REM sleep that you have, so I suspected that my percentage of REM would decrease.

As percentages, the figures do not show this. In fact they show an increase in the percentage of deep sleep, along with a slight increase in REM and wake...

However, as REM is more abundant at the end of the night, it follows that the less time one spends in bed, the less opportunity there is for REM sleep, hence my actual 5-day-mean time in REM fell by 11 minutes from my baseline of 98 minutes, although it put it more inline to the average for my age of 90 minutes.

My actual time in slow-wave sleep (deep) rose by a mean of 3 minutes.  My mean deep sleep (34 minutes) is still way below the average for my age (69 minutes) but within limits, so I am pleased with this small increase.

I'm not sure if these changes are actually significant, perhaps a longer trial may reveal more?

So, even if 5-HTP didn't affect my AHI, it still had positive effects on several aspects of my sleep composition. 

However, it did have a positive effect on my AHI and it was much more noticeable... 

I've graphed my 5-day-mean AHI alongside the other 5-day-mean AHIs for alcohol and my baseline.

It brings my mean AHI down to a level that puts me in the "normal" category (<5 AHI = normal). Maybe this is the reason for not wanting to sleep so early and finding it easier to wake in the mornings.

For the sake of showing that this is a consistent effect, I also graphed the data on a night by night basis... 

For now, this seems too good to be true: 

• Lower AHI
• Normal bedtimes
• Less time in bed
• Increase in slow-wave sleep

So what now? Keep on taking the tablets?

Based on my limited data, I wouldn't dare go so far as to claim that this is a effective treatment for mild (very mild) obstructive sleep apnoea, nor would I suggest that it would work for others, but it is intriguing and does need looking at further.

It leaves me wanting to know more about the mechanism behind this effect. Yes, it's good that it has helped me as far as my AHI is concerned, but I want to know how. In a previous post, I noted that my sleep apnoea seems to be REM related. Serotonin related activity drops dramaticaly during REM sleep, so maybe the higher levels due to 5-HTP reduced that effect?

Is my pseudo-science hypothesis correct, or is there more to it than that?

I'd be interested to see if this effect carried on, or if my body got used to the 5-HTP and the effect faded.

I'd also like to try this with a lower dose of 5-HTP (after all, why take a high dose if you don't need to)? I'd also like to see if sustained-release 5-HTP is more effective.

I was planning to try the mandibular advancement device next, but after such a positive effect, I think I'll stay with 5-HTP for a while and see if I can improve on the results even more. I'd like to bring my sleep latency (time to sleep onset) down.

Yes, this is good news but I can't help feeling a little like Lizzy in "Drop Dead Fred", she knows that she's taking a pill that will stop her seeing things that others can't. Will taking 5-HTP, increasing my serotonin levels and bringing my AHI down stop me from having sleep paralysis, lucid dreams and seeing/hearing the sleep-wake border imagery that I have grown so used to? 

I hope not.

I'll explain how and why I came to like sleep paralysis in an upcoming blog-post. Hopefully it may be of use to anyone that fears it as I used to.

I have to say that this is a test with a tiny sample size, and of limited duration. I am not suggesting that anybody should try this, and certainly not use it in place of recognised treatments. 

Update on Saturday, May 12, 2012 at 7:54PM by Hypnagogia Blog

I've also found that 5-HTP helped reduced residual snoring after lowering my AHI with positional therapy.

Snoring Remedies? Results for 5-HTP