Serotonin

Serotonin is similar to skatole (structure below serotonin structure) and that causes bad smell or bitter taste in many serotonin-like hallucinogens no matter how pure and fresh they are. Serotonin or tryptophan (precursor to serotonin and building block or many proteins) both may be degraded into skatole by intestinal bacteria.

Serotonin participates in widening airways and increasing amount of air breathed. It's possible that sudden infant death syndrome with below 1 year old babies dying from lack of air due to reduced serotonin receptor activity.
Serotonin is now famous as brain neurotransmitter but it was discovered as a substance that activates smooth muscles in gastrointestinal tract. Most serotonin (about 80-90%) in body is in gastrointestinal tract and it is usually released when local enterochromaffin cells detect poisons or infections and release their serotonin stores causing nausea, vomiting and diarrhea. Many hallucinogens may cause vomiting if they happen to bind with serotonin 3 receptors (main serotonin receptor in gastrointestinal tract) but most popular recreation psychedelics avoid 5-HT3 receptors somewhat selectively.
Other serotonin receptors are mostly in nervous system. Because serotonin=5-HT, then most serotonin receptors are usually named 5-HT receptors. There are at least over 7 different 5-HT receptor classes with several subtypes (1A, 1B, 2A, 2B etc).
Serotonin 1,2,4,5,6,7 receptor agonists seem to cause bright colors, moving objects/distances/proportions, breathing objects, kaleidoscopic patterns and intense emotions.
5-HT3 receptor causes food poisoning symptoms like vomiting and diarrhea and it doesn't show relation with other serotonin receptors in BLAST search. This is the only 5-HT receptor that works as ion channel. Other 5-HT receptors influence cell metabolism.

Shivering is likely with serotonin agonists as serotonin is one substance involved in causing fever and many notorious ecstasy death were due to over 40 degree fever due para-methoxyamphetamine or some other serotogenic substance being used instead of MDMA. 

Serotonin production in brain is done by raphe nuclei in middle of brainstem (in sagittal midline of body) and from there it is sent to other areas when needed.

Possible way to control serotonin levels for few seconds: while sober trying to get emotional can cause more bright colors and ease of breathing while trying to be sleepy and unemotional makes breathing more difficult.

Blocking serotonin may cause breathing difficulties and lack of emotions.

In thermoregulation serotonin in medulla activates heat production from fat by stimulating adrenaline neurons that activate fat use and also other neurons that cause vasoconstriction.

5-HT3 antagonists reduce cold defense reactions in humans after injecting them with 4 C degree water. These antagonists reduced shivering and oxygen consumption was ~10-20% lower than in placebo group.

Article about breathing and also how serotonin is involved. During suffocation raphe nuclei release serotonin and can increase breathing for over an hour. If serotonin is blocked with serotonin antagonists or destruction of serotonin producing neurons then this reaction can also become somewhat blocked but not in cases if this more active breathing response has already started. 5-HT2 receptors seem more involved in this reaction.

CO2 receptors are in throat where they sense its level although such receptors are also in brain and brainstem. Acidity from CO2 is one trigger for suffocation reactions and no known area is only one involved in reaction. Even brainstem slices outside body start to release serotonin and noradrenaline with extra CO2. I suspect all neurons react to CO2 as it lower pH and neurons react to acids and to their positive electric charge that seems to activate all neurons. 

If CO2 pressure is increased by 1 mm HG then humans start to breath 20-30% more air.
If CO2 pressure is increased by 6 mm HG then humans breath 120% more air. 

Effects of CO2 to breathing are lessened with antagonists to glutamate and muscarinic acetylcholine receptors or with agonists to GABA receptors.

Sudden infant death syndrome (SIDS) that is a major cause of death for below 12 month old people in developed countries. In some cases there seem to be differences in their glutamate, muscarinic acetylcholine and serotonin receptor activity in their brainstem. Reduced activity of these receptors is also suspected in people with sleep apnea where breathing stops occasionally for several seconds.

When i used quetiapine (antagonist of serotonin receptors among other things) for insomnia i got breathing difficulties in minutes and it was almost forced to use mouth for breathing as nose seemed stuffy although it got extra dry.

SSRIs like paroxetine can increase effects of cannabis but they seem to block the effects of MDMA. For example pleasant experiences with paroxetine and low dose of cannabis (1, 2, 3 ). Example of panicked reaction with hot/cold flashes and head rushes.
At low doses cannabis causes release of serotonin. Increased cannabis effects may be due to increased serotonin activity combined with serotonin re-uptake inhibitors that also increase the amount of free serotonin.


BLAST comparison

Serotonin receptors were structurally similar to other stimulating neurotransmitter receptors like histamine, serotonin receptors 1-2 and 4-7 were similar with each other while 5-HT3 was similar to nicotinic acetylcholine receptors. Unlike with the opioid and cannabinoid receptor tree i made serotonin receptor didn't have unfamiliar names. All i found were few similar neurotransmitter receptors and even if i compared human 5-HT receptors to fruit fly receptors. 

These were almost all the different names i found when comparing 5-HT4 with other human proteins. I may have missed receptor with some other number.

Closest "relatives" to 5-HT1 receptors are adrenaline and dopamine receptors with acetylcholine and histamine receptors as more distant relatives.



Almost identical names and relation distances showed up when comparing human 5-HT1 with fruit fly receptors. Octbeta receptor is like adrenaline receptor for invertebrates.

Personal experiences

One thing i've consistently experienced with drugs that increased serotonin receptor activity (2 SSRIs, LSA and 2 types of psilocin mushrooms) was electric tingling in body that moved like some wave with occasional shivering and also easier breathing.

First drug of this class was paroxetine which mostly felt like nothing. I used it when i was 17. At some point (maybe after quitting) i did notice i had some wavelike electric feelings that went up the spine and through the brain. In erowid these waves were described as "head rush". They most mostly pleasant distractions in otherwise boring classes. Other time it caused some notable symptoms was during some evening when i was out with a tobacco smoking group. Almost every time i smelled this smoke i got these pleasant electric waves from spine to scalp area. I still suspect these waves were K-complexes that usually happen while falling asleep with possible involvement of low serotonin levels that happen during sleep and probably after withdrawal from SSRIs.
One notable side effect that made me stop using paroxetine was that i could not orgasm with that. Maybe after week of using it i noticed it became very difficult. I had to be very fast and even then it took about 5-10 minutes. Often i gave up because my hand got tired before i got close to orgasm. After about a week without orgasms i stopped taking them and things were soon back to normal. I knew SSRIs had been used against premature ejaculation and SSREs (selective serotonin reuptake enhancers) make orgasms easier to achieve but i don't know how much effect would these have.

My first experience with psychedelic type drug was when i was 17 year old with LSA (from 200 morning glory seeds). In few minutes i got nausea that made me regret eating these. Finally it got so bad i went to toilet and i vomited without having to but fingers in back of my mouth. Immediately after that i felt almost reborn with huge relief and euphoria even before i exited the toilet. From then on this day was nice. I thought about being better towards others and i got some mild hallucinations. Mostly they were just simple patterns like Japanese flag during WWII but with many colors in different stripes. Sometimes these stripes formed next to each other and other times they grew as whole from darkness one after the other. Body had constant electric tingling for hours. Not much happened later that day. Due to pleasant feeling after that i tried it few more times but never again did vomiting cause this good feeling.

1-2 years later i had weirder experience with LSA. I took those with barely any effects during evening but also without vomiting. I took some alprazolam and quetiapine for sleep. Next morning i felt exhausted and started to see the most clear hallucinations i have seen with LSA. I tried to sleep but i kept seeing stuff like water droplets forming in some wooden chair i saw with closed eyes and these droplets kept dripping off. This state was unsuitable for sleep so i waited it out. Mixture of numbed emotions with quetiapine and feeling of deep realization due to LSA made this morning weird. I envied people around me who were sober that day and could peacefully relax. Also this was first time i felt like sober state is pleasant due to some fun neurotransmitters keeping people somewhat happy and motivated.

Some years later i tried LSA again with 300 seeds but i vomited over 5 times and that was the last one. I threw leftover seeds to dumpster. My veins got so narrow i could barely see them on my wrist. My skin was very pale and mood was miserable with nausea and waves of hot and cold. Even anti-psychotics could not get me relaxed. There were barely any hallucinations and mostly just thoughts about sobriety being underestimated in terms of peacefulness and body high. My limbs twitched and shaked often. Electric tingling in body was distracting and i waited about 6 hours before i could go to sleep. Luckily watching some shows was nice distraction from nausea and endless inner stress but i drank lot of water and waited for it to exit through bladder. Mostly i had nagging thoughts replaying that serotonin is awful choice against boredom as i knew by then it was involved in vomiting and also that such thin veins can't be healthy.

Around that time i had worst experience with cannabis after taking some other SSRI (i think sertaline). This experience was similar to this experience but i stayed quiet during that. Several times i thought about calling ambulance but i didn't see much benefit in that. I had intense anxiety and restlessness. Only time i felt anxiety similar to that was with high dose of mushrooms during a bad trip.
Caffeine overdose anxiety feels quite similar to this restlessness from SSRI's and cannabis and shrooms.

First experience with psilocybin/psilocin mushrooms was with 40 psilocybe semilanceata mushrooms. That was by war the most pleasant drug experience. I put them in cup, poured boiling water on them and let the tea cool for 10-15 minutes. After drinking maybe quarter of it i waited about 5 minutes and noticed happy mood with electric tingling through my body with some happiness and colors seemed more intense or funny. I drank rest of it and within about 5 minutes i started to laugh hysterically and that went almost 45 minutes after which i started to get tired of laughing and effects started to fade. I could not stay serious for long because face muscles tried to make my face smile constantly. During the last half hour after laughing ended i still had a tired smile that slowly faded. I did see some pattern like hallucinations. With eyes open i saw like semitransparent tiny triangles growing out from middle of visual field and they formed larger triangle like shapes but that was boring compared to the mood i got from my favorite songs. Later hours were mostly bored as my emotions felt bit burnt out but i was content with this experience. Shows i watched from computer looked bit different. Sometimes i wondered if moving object had trails due to shrooms or due to low quality video as i kept noticing fuzzy low quality areas. Short term memory was similar to cannabis high with fast thoughts that i forgot fast.
Surprising long term effect that this trip left was that when i try to remember how this feels i often start to laugh. Like flashback to manic laughter every time i think about it and the ~20 dollars i spent on this experience felt worth this new type of memory. Like that 45 minute laughter burned into my memory with unnatural intensity. 

Second experience with shrooms was mostly awful. I took 1,55 gram of psilocybe cubensis although seller advised to take 1 gram and that he got bad experience with 1,8 grams but i got too confident due to previous mushroom experience.
I did tea like previously and drank it all. For first few minutes nothing happened. I started to watch "Dirty Jobs" as it was slow, anchored in reality and i liked the host due to his humility and pleasant attitude (it remained best distraction i found during first few hours). 3 minutes into first episode i started to see flashes of light in sides of vision field and familiar terrible anxiety i got with SSRI and cannabis. Nausea started fast and it was not affected by seeing nasty things in that show. Drinking water made nausea worse but i didn't vomit. Mostly for first few hours i tried to not move and let the shroom tea absorb more slowly so not too many 5-HT3 receptors could activate at once.
I have experienced several stimulants (nicotine, reboxetine, pregabalin and caffeine) and shrooms stimulate in very different way. It didn't give me pleasant energy. Instead it felt like a battery formed in my body and started to electrically shock different parts of my nervous system at different times. Several times in first 15 minutes i took off my earphones because i felt like my head was being electrocuted with unpleasant electric waves going from side to side. Sometimes my vision got bit blinded by bright flashes that flickered maybe 5 times per second. Other times i felt sudden electric waves from one side of body to other. Several times my muscles started to twitch and shake. In first 2 attempts of drinking water all these symptoms got much worse so i stopped drinking water for about 1-2 hours. Occasionally my legs started to shake without feeling cold although mostly i shivered feeling cold. I was in quiet peaceful place with 25 C temperature but it didn't keep me from shivering. Even sense of body posture became confused. I held my head up on my hands but within seconds it felt like i forgot in what posture i was in this confused state. Sometimes i checked my hands to see what was holding my head. It felt like my body parts could not coordinate with other body parts due to very fuzzy thinking. When i went to bathroom i noticed some mild balance problems. This time my veins got very narrow again so i looked very white with no red patch on the skin. Veins on wrist were barely visible. I heard from seller that someone who took them and used to drink stopped drinking for years after that. I felt that such experience could scare people sober.
Only hallucination i saw with eyes open were red and orange patches on white background but any white light made the stress worse. With eyes closed i saw what i expected. Sometimes there were tiny patterns that slowly changed. Other times i saw tiny square images with copies of them side by side. Larger copies were in the side of visual field and they kept flowing to one side so i became too dizzy and nauseous to hold my eyes closed.
For first couple of hours i kept thinking that serotonin agonists make awful recreational drugs and repeated that serotonin is hormone to food poisoning and shaking during cold. After watching about 3 episodes (i barely remember anything from them but they were good distraction) i started to feel close to normal. Veins started to widen and my skin started to get small red patches until in 4-5 hours my normal color got back. Evening became good about 3-4 hours later when i smoked cannabis that usually causes anxiety. I relaxed and got rid of nausea and finally started to enjoy the evening. I smoked a lot and didn't get anxious. I even went out for walk although i usually don't dare to go out high. It felt like my ability to worry had burnt out and i could enjoy almost everything without stress. I started with tea around 6-7 pm and bad parts lasted to about 9 pm (8.00-8.30 was definitely miserably nauseous and stressful). I started smoking at 10 pm and stayed awake until 3.30 am.
Next day i was mostly just tired and bored. Another day after that i got mild headache for few minutes. 
2 people i knew took both half of what i took and they barely felt anything while i felt i took a overdose so it looks like increasing dose increases subjective effects exponentially.