So I recently started down a path that I for some reason have never rode down before and the insight is impressive.

My freinds use to pick on me or in some cases call me possesed because under a blacklight my skin and mainly eyes take on a strange glow. I never really knew what to make of this and most often then not attributed it to vasodialation of weed. But while looking at photos of glowing animals like I always do(what you don't spend all day looking at pictures of glowing animals?  shame on you! ) and I came across something I already knew but triggerd something to go off in my head due to recent studies looking for the source of the anxiety in some form of natural MAOI. The glow looks so much like what I and others have seen on many ocassions and I decided to look into it real quick to understand the structure better since this is a natural form of blacklight reactance and its worth a look.

As a result of the presence of Beta-carbolines in the cuticle of Scorpions, they are known to glow when exposed to certain wavelengths of ultraviolet light such as that produced by a blacklight.[3]

http://news.nationalgeographic.com/news/2009/05/photogalleries/glowing-animal-pictures/photo2.html#crab-naturally-fluorescent-glowing-animals_11835_600x450.jpg

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Over a decade I have looked for a direct source of anxiety always ending in no real conclusion.
Enter Beta Carboline.
Beta-Carboline

Pharmacology

?-carboline alkaloids are widespread in plants and animals, and frequently act as monoamine oxidase inhibitors (MAOI). As components of the liana Banisteriopsis caapi, the ?-carbolines harmine, harmaline, and tetrahydroharmine play a pivotal role in the pharmacology of the psychedelic brew ayahuasca. Some ?-carbolines, notably tryptoline and pinoline, are formed naturally in the human body. The latter is implicated along with melatonin in the role of the pineal gland in regulating the sleep-wake cycle.[citation needed] The ?-carboline can link to cerebral benzodiazepine receptors and induce inverse agonist effect.

Beta-Carboline causes anxiety as would be expected by something that directly acts in reverse from the only class of compounds that provided relief though out my years which are benzodiazapines, mainly Xanax to be specific.
Neuropharmacological antagonism of the beta-carboline-induced "anxiety" response in rhesus monkeys
JN Crawley, PT Ninan, D Pickar, GP Chrousos, M Linnoila, P Skolnick and SM Paul [*1]

A behavioral and physiological syndrome of stress-related responses was reported in primates following treatment with the benzodiazepine receptor antagonist, beta-carboline-3-carboxylic acid ethyl ester (beta- CCE). The behavioral and physiological effects of beta-CCE are similar to those observed during stressful or "anxiety"-related conditions characterized in rhesus monkeys under natural conditions. Pharmacological agents which are known to antagonize anxiety responses in other paradigms were tested for their ability to antagonize the actions of beta-CCE. Diazepam (1 mg/kg) completely blocked the effects of beta-CCE (200 micrograms/kg) on anxiety-related behaviors, heart rate and blood pressure, plasma catecholamines, cortisol, and adrenocorticotrophic hormone. A presynaptically active dose of the alpha-adrenoreceptor agonist, clonidine (10 micrograms/kg), significantly attenuated the effects of beta-CCE on all parameters, whereas the beta-adrenoreceptor agonist, propranolol (3 mg/kg), failed to alter the increases in plasma catecholamines, cortisol, or ACTH. In addition to these adrenergic agents, the serotonin antagonist, cyproheptadine (1 mg/kg), and the GABA-mimetic, 4,5,6,7- tetrahydroisoxazolo(5,4-C)pyrindin-3-ol (1 mg/kg), partially blocked the behavioral, physiological, and biochemical changes after beta-CCE. Manifestation of the complete "anxiety" syndrome evoked by beta-CCE in primates may require the functional activity of several neurotransmitter systems.

Source: http://www.jneurosci.org/cgi/content/abstract/5/2/477



Smoking:
So one of the main substances that amplified the anxiety 100xfold is plain old weed. It use to be the cure but after a few years of very heavy use and shortly after a strong LSD trip during woodstock 99 this was no longer the case and the anxiety became worse then before.  I did notice along time ago that the negative effects begun after smoking a ciggerette while stoned. I attributed this to many things and looked down many paths such as nicotine ,vasspression changes due to dehydration, Calcium loss from smoking but I think by far this is the cause for such a reaction.

Abstract

?-Carboline-3-carboxylic acid methylamide (FG 7142), an anxiogenic agent has been found in cigarette smoke condensate, but not in the cigarette itself. When a cigarette, except its filter portion, was immersed in 20 ml of potassium phosphate buffer, pH 7·4, then heated at 60°C for 2 days with or without presence of methylamine, FG 7142 was detected only in the mixture containing methylamine. Furthermore, when the mixtures of ?-carboline derivatives and various amounts of methylamine hydrochloride were heated at 60°C for 5 days, FG 7142 was formed only in the mixtures containing methylamine and 1-methyl-1,2,3,4-tetrahydro-?-carboline-3-caroxylic acid (MTCA) or 1,2,3,4-tetrahydro-?-carboline-3-carboxylic acid (TCCA). FG 7142 was also produced in the mixture of glucose,  -tryptophan and methylamine when heated at 200°C in a dry condition. These observations suggest that FG 7142 is formed through the smoking process and that methylamine in cigarette smoke may play an important role in the formation of FG 7142.

Abstract


The weed has the effect of distorting outside stimuli in oneway or another which is all fine and well until the rapid thought process caused by weed is overshadowed by an overwhelming feeling of dread and selfconscienceness. There is also the possibility that these two substances work with each other somehow but I have yet to come across it in my early studies of these compounds.

As an MAOI
Typicaly as in myself and many other I know affected simularly many drugs have an effect that is stronger then those that most people seem to experiance. This is possibly attributed to the MAOI properties of the carboline compounds. After a couple years on Lexapro I had to quit cold turkey because the side effects where killing me, literally I recently found out, in the form of Seratonin syndrome. This is well known to present itself in cases of MAOI and SSRI use but it appears relatively rare in normal SSRI use. Also the effects of diet can greatly change ones mental state when strong MAOI use is in effect such as a few cases where people have died due to hypertensive crisis due to eating cheese on an MAOI. Hypertensive issues are something that also runs in the fam and honestly my life expectancy is prob about another  15 years if theres anything to be learned from the long line of middle age dead males in my gene pool. The  possibility of being able to prevent this somehow is just to great to ignore since I do not wish to die of a heart attack or stroke over the next couple decades. Aside from all this imgine for a second if every time someone decided to eat something that had DMT in it if they suddenly where taking the equivalent of a ayahuasca type drink. The thought of something formed in the body evoking a simular response is scary to say the least.



Conclusion:

Ill reserve the rest of my thoughts and speculations other then a quick hypothesis until more study is done in this area. How on earth I avoided the pharmocology of Beta Carbolines for well over a decade now is beyond me. These are, im sure of, the most powerful tools for the study of serious mental disorders and much more research needs to be done in this area by science instead of promoting SSRIs to people as soon as they walk in the door. I feel there view on the subject is once you have gone so far down the wrong road you may as well continue on and hope it gets you back to where you should be, this is foolish when turning around and taking a new approch would benifit millions of people in this overly stressed out world.

---

Hypothesis:

Endo B-carboline(EBC) alkaloids are present in the pituitary gland in order to function as a jumpstart for the system its inverse accomplished with Meletonine. Where as Melatonin decreases and is at its highest point in the middle of the night one would expect that the Endo ?-carboline alkaloids would also be present in an equally inverse amounts thoughout the day rising in a sharp peak at wake time or periods of time that call for extended mental use such as periods of stress. If these two biological pathways are out of phase with each other one will begin to see a change in the mental state of the subject causing effects ranging from melencholia to rage. Quite possibly the root cause of disorders such as Bipolar disorder, Schizophrenia or Autism as well as others. In the later two imagine will you the effects present on a person whos EBC levels are on full steam ahead mode all the time and the patiant has not had a true sleep his entire life. Daytime dreaming would begin when areas of the brain became fatigue and started to shut down one by one and the patiant will begin to lose contact with reality as is seen in these two simular disorders. Zero control over ones actions would result in the cases of Schizophrenia where there are people talking to you that are not there and for the most part your waking life becomes just another very vivid dream. This is accordence with what I have witnessed on a few different occassions while caring for Autistic children.

For many this is more then likely an issue of genetics and over expression of somekind of the normal EBC levels. But there is also the posibility of other disorders to arise from this biopathway due to extended periods of stress and a development of to many receptors for it simular to which happens in adolesent nicotine consumption and addiction.

Thank you. I knew they contained other MAOIs as well but harmaline is all news to me. The substance discussed though appears to be something else altogether with much more action then harmaline else I can not see them producing a paper to describe its action. I'd have to wait to get the entire paper to really comment more though but perhaps this means Nicotine+ DMT mix could be smoked? Like I said its all new to me and im just trying to get a grasp on all of this.


A question:

How would I block B-Carbolines at there formation instead of blocking there receptor binding like is done with Valium or Xanax?
How are they formed in the body?
Are they stored or biosynthesised.

That or blocking there MAOI abilitys may also spell relief because at the very lest this would prevent foods from affective mood as strongly as an MAOI allows.

Some MAOIs bind and stay for weeks on end and thats funny considering many psychotic syndromes appear to have a two week cycle. If this is caused by foodstock of the patiant the doors it would open in the way of controling stress and depression would be huge. Im a big fan of you are what you eat. Everything else is just a side effect.

I found this but I can not find a decent source anyware of this propertie of b-Carbolines.Not saying I disagree with alot on that page since the recent bout of anxiety was also around the time I started playing with Tesla coils but im looking for a science paper if anyone knows of any stating them as SRIs as well as MAOIs as this could be an important link.

Besides melatonine, the pineal gland also produces the ‘neuromodulator’ chemicals - called beta-carbolines - which affect the brain. Beta-carbolines are both monoamine-oxidase (MAO) inhibitors and serotonin reuptake inhibitors, which means that they prevent the breakdown of serotonin by inhibiting its uptake into the brain’s synapses.

Source:http://www.bibliotecapleyades.net/ciencia/ciencia_brain11.htm



Something no doubt also of intrest is this substance

Known as Pinoline. It is the metabolic derivative of Melatonin and may in part explain the b-carboline process in the body abit better. The more Melatonin you have increasing the need for sleep the more of this substance gets created in turn. If this chemical is stores in the pineal gland and not released right away then its a prime candidate for the source of anxiety and typical Highs and lows of many mental illnsses.

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ps. sedit: Many MAOIs inhibit monoamine oxidase irreversibly, so that the enzyme cannot function until it has been replaced by the body, which can take at least four weeks.!!!
look up "seretonin syndrome"...and weep!!!

This I am well aware of. Sadly having to much experiance with serotonin syndrome first hand I fear the results of me ingesting Beta-carblines as a standard for following test. Nightly 103 degrees F fevers is not something I wish to relive nor the constant twitching, tremors  and "LSD gut" feeling. I don't feel doctors have a full respect for the materials there handing out on a whim. It would have been safer and more then likely more productive for them to give me a prescription of Heroin or cocaine instead of an SSRI. I was lucky enough to NEVER get my hands on any type of drug around the couple years I was on this other then EtOH and weed on occassion. Some pills like hydrocodone and such but mostly just stuck to my perscription of Clonazapam and Lexapro.

Something that may intrest your hypnos
Food Causing Physical Stress
and ADHD

very interesting artice sedit me man

This means that a tiny little bit of beta-carbolines can have enormous effects.Some beta-carbolines also remain active for a very long time

Its not surprising that....

Pharmaceutical companies develop ADHD drugs that countereffect the effects of beta-carbolines and opioid peptides on these brain-receptors. Their drugs target serotonine, dopamine and / or norepinephrine metabolism.

BUT....

Of course they will not tell you what impaired that metabolism in the first place, since they just want you to buy their drugs. (once again the mighty "buck" rules supreme!!!

man o man what a truly fuckt up place this world of "dollars,shareholders and greed" can be :'(

I too 'suffer' from "highly unusual and idiosyncratic"  drug reactions...and it takes a hell of a lot of 'substantiation' from so called "specialists" in the area of "neurology and pain management.." before the "average GP" will 'believe' me!!!
I am SO often "mismanaged" by Dr Average that i have almost 'given up' trying to "explain" ANYTHING to ANY 'medico' (Next week i will be travelling 1000 K's to see some doctors that i HAVE been able to 'convince' of my "atypical" response to many (if not most 'drugs')  :PI am in their words " a most difficult and peculiar patient to treat" ) It took me over 4years and countless consultations before i was even given this 'label'..however they (finally) cannot dismiss my unusual 'metabolism anymore' after so long, and so many 'assessments
Matey i know only too well the shit you must encounter with these "egotistical nimrods" they DO NOT LIKE those of us who 'fall outside' their well defined "clinical parameters")
Ps. Nikola Tesla is one of my 'heroes'..amazing guy..its a shame he was treated as as he was..(sadly..) i think he took a lot of very esoteric knowledge to the grave with him :'(

Had a couple more hours today to poke and prod into the nature of these compounds and it gets more and more interesting the deeper I look into them.

Monoamine oxidase type A (MAO-A) is an enzyme which normally inactivates tryptamines, though it can be chemically blocked to prevent their destruction and thus facilitate their activity. Some of the older antidepressant drugs work this way. In general, though with some reservations, beta-carbolines will inhibit this enzyme.
...
...
Certain endogenous beta-carbolines can also inhibit this (re)uptake of the serotonin (10). These two routes, MAO metabolism or (re)uptake into pre-synaptic vesicles,
account for most of the inactivation of endogenous tryptamines, and some endogenous beta-carbolines can inhibit both pathways. Pinoline
(6-methoxytetrahydro-beta-carboline) and tetrahydro-beta-carboline are good examples of this, and both have been shown to possess specific binding sites in the pineal,

adrenals and specific areas of the brain (11).
...
Since these same Psychoactive tryptamines occur in humans, it is possible that their activity may be promoted by the actions of endogenous beta-carbolines for normal psychological processes; e.g. the production of visual / emotive imagery in sleep. The periodic altering of consciousness in sleep may even be necessary for the maintenance of normal mental health, since only a few days of sleep deprivation will result in a seepage of hallucinatory phenomena into the waking state. On a similar line of reasoning, an offset dreaming mechanism may explain some aspects of hallucinatory psychoses. The willful induction of a psychedelic state presents us with another option which is probably an extension of an intrinsic desire, at least in some, to know. Such an experience offers a unique glimpse of the soul as a temporary dream-like state. Thus it seems quite normal that some choose to induce such a state for the purpose of examining the psyche within the frame work of a waking state of mind.

Source:http://www.maps.org/news-letters/v04n2/04230cal.html

Stating that MAO-I type A inhibitors is what degrades tryptamines normaly in ones body theres a good bet that I am looking for a potant endogenous beta-carboline that inhibits this site strongly. Pinoline is mentioned to perform both of these task quite well but as stated already the levels in normal and mentally ill patiants is not work noting according to the quote taken from Tihkal. However there are some alterations to the structure of these compounds which may prove otherwise. Im starting to get the feeling that there may be a genetic factore that alters the structures in a very small population of these chemicals but does so in such extreme potancy they potentially go un-noticed. The final highlighted line makes note that an out of phase action could possibly be whats causing psychosis which is exactly my hunch from the start so its promising that credible researchers are also feeling the vibe....


There is also the case of beta-carboline-3-carboxylic acid ethyl ester which is isolated from brain tissue and urine is an extremely potent displacer of diazepam from brain benzodiazepam receptors and has shown afinity for the disruption of Shiga Toxins which are the cause of many food born illnesses possibly sheding light on one of there primary roles in mammals biochemistry.
References: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=105078#safety

Another 3-carboxylic acid derivative, the totally aromatic material without the 1-methyl group, has been found as a natural material in trace amounts in human urine, in fact the yield was a total of 1.78 milligrams from 1800 liters. This is the ethyl ester of bC-3-carboxylic acid. It is an extraordinarily potent inhibitor of brain benzodiazepine receptors but, surprisingly, totally without any affinity for serotonin receptors. The hydrogenated version, THbC-3-COOH, as well as the harman analogue above (THH-3-COOH) are normal components of both beer and wine, being present at the several ppm level............................tetrahydroharman can come from the union of tryptamine and acetaldehyde...... A parallel reaction takes place in the human body between acetaldehyde and the neurotransmitter serotonin.

Source: http://isomerdesign.com/PiHKAL/read.php?domain=tk&id=44#rxa5429

The more I research the more im left to wounder just how large this biochemical subclass extends. The carboline structure forms from the reaction of an indole with any number of substances in the body leading to a variety of child structures all with different activitys ranging from causing anxiety to relieving it. Waking someone up and putting them to sleep. Ect...ect... And as a icing on the cake.... In the absence of light the human body begins to convert Pinoline into DMT. This plays out the same for all of them turning into various typtamines during periods light deprevation.




After a day looking over Pub-Med and Pub-Chem files I have come to the conclusion that Beta-carbolines are more of receptor whores then phenylethylamines and thats saying  alot. These compounds bind with GABA receptors working as either agonist or inverse agonist. They can cause hallucinations or cause them to cease..... They appear to affect almost every area of the nervous system one way or another in a completley reversible way where it can alter its structure invivo to counteract itself... Its appearing like this is some sort of regulatory compound that functions as a feed back loop for a number of pathways in the human body. Take a close look at the following two images and focus closely on the b-carboline ring because its the structure for 80% of your CNS drug needs and possibly more judging from the hint mentioned about the Shiga toxin.
 
Beta-Carboline anti-anxiety medications and research chemicals.
Abecarnil

ZK-93423

I been studying anxiety a lot myself but this route hasn't occurred to me because I've been looking at and experience the effects of an over whacked adrenal system. 
Are you saying you think your body overexpresses/produces beta carbolines - is it possible that it is an overshoot reaction due to being overstressed and therefore the body goes nuts trying to re-establish balance? 

As did I spend over a decade now pouring over the adrenal system with everything appearing to be... off. No conclusion or cause that seems to fit the bill yet these substance, atlest for the time being, I strongly feel have the answer Im looking for. As far as what im saying... not 100% sure at the moment. An over expession does not seem to be the case since these substances appear level thruout the entire population so it seems prudent to look for one of several other things and see what turns up.

1: Alteration to the structure of the beta carbolines, Possible metabolism malfunction along the way either not destroying these compounds or metabolizing them to something much worst in small amounts. There are some of these that are very specific and potent meaning only a small amount need be present to cause a large effect.
    It must be STRONGLY noted... These are only Beta Carbolines iv been studing so far. This does not make mention of the stimulating effects of gamma-carbolines. There are alpha carbolines and Iso carbolines of all these substances. This is a Large field to study and science appears to have hardly scratched the surface.

2: The balance between this and another substance more then likely Melatonin would be my main target if I where able to do a professional study. A constant measure of plasma levels of the carbolines and tryptamines thru out a couple day period should give a clue as to the validity of my thoughts.

I liken it to imagine how you would feel if everytime you got sleepy someone shocked you awake everytime you started to dose off. I have spent time caring for autistic and spent many hours with watchful eyes and I can say they rarely sleep. Not to mention issues with metabolism and food desire are both very obvious.

3: Sorry I have no references for this one at the momnt but In cases of Nicotine addiction the bdy has increased the amount of receptors that nicotine bind to due to the massive influx of nicotine and when you stop taking the nicotine these receptors go crazy in a sence and don't function correctly. This could be a cause of the ups and downs and apparent Endocrine activity of the carbolines because it means the body has been hard wired for stress.. once this level of overload is experienced the body will Never feel the same leading to things like PTSD because your body is no longer getting the natural drugs it needs one can start on a train of withdrawl effects even if its a naturally occuring substance. With a little refinement I feel that this may hold more weight then the other possibilitys at the moment.

My partner is Aspergers and he experiences very odd drug metabolism too - also hyperfast food metabolism.  Ritalin just about killed him as did SSRI's with blood pressure problems.  And most drugs affect him differently than others. 

This I feel is in large effect due to te MAOI abilitys of these compounds and I am spending much of my time looking for a way to block the MAOI abilitys of the carboline familys so I will let you know when/if I find one.


Iv recently been considering lookinginto it but to be completely honest the effects people talk about with modifnl sond very simular to wha happens to me when I smoke weed with the talk about hyperfocus with blunted emotions. This has made me very curious because I have never found another substance act like weed and that has held me up for years.


I would say moe but my computer is jaming up right now and I gotta d something with thi damn thing right now.


[/quote]

I have come to the conclusion that Beta-carbolines are more of receptor whores then phenylethylamines

LOL

 sedit  you  make mention of genetics playing a factor,and i have no doubt you're right...here in 2010 there are some VERY unusual variations floating about---how about that girl in d US who is 17yo
 

She’s mentally around 6 months old, and looks about the same.  Her behavior is a mix of a child around that age and her actual age of 16.  She cannot talk and must be fed through a feeding tube while in her swing.  She also attends a special education school.  Age wise she should be a junior in  high school.

the human machine is an extraordinarily complex one, i am sure WE have only scratched the surface and the interaction of various substances (both endogenous and exogenous) upon each person,is far from "consistent"
 I think that as much as Beta Carbolines affect us, there are many other neurotransmitters that are yet to be 'recognised' for their contribution to our state of either wellbeing, or mindfuck!!!
personally i am not inclined to put all my eggs in one basket,as far as 'trying to understand" this stuff...
 Some substances are 'more consistent' than others, with less possibility for "negative" interactions, which is why i think you're right when you say

It would have been safer and more then likely more productive for them to give me a prescription of Heroin or cocaine instead of an SSRI

and again, personally i am inclined to agree...although our understanding of these alkaloids is definately "lacking" :'( due to some wowsers puritanical attitudes initiating the restriction of these (and all the other...) well known compounds.......at least these have a 5000+year history of use
 
 hence why i am here.........the fuckers force me to "make my own"
 

I'd doublecheck that guys info if he really thinks cocaine grows in poppies!!
"Cocaine, produced by the Opium poppy, is a tropane alkaloid, like atropine which is produced by the potato family of plants. Cocaine is a dopamine inhibitor. Dopamine is another neurotransmitter based on tryptophan. "

Seems to me also that I would NO like anything that blocked my dopamine!!

salat

I decided to add this beta-carboline structure here since hidden in its structure is that of MDA. It appears there goal was to make a drug that cures sexual dysfunctions.