-http://en.wikipedia.org/wiki/Citalopram
for treating anxiety, doses of 10mg are administered al minimo, for depression suppression, it starts at 20mg, goes up to 40mg or even higher. assuming the 50μg/l pertains to the lowest dose of a 10mg tablet, you'd have to take 60 10mg tablets (50μg/l * 60 = 3000μg/l or 3mg/l) to reach a potentially fatal dose, and 600 10mg tablets (50μg/l * 600 = 30mg/l) to almost certainly die, at least if you won't be taken to a hospital. it is most common to sell citalopram in 20mg tablet forms, so you'd then need 300 of these.
4 documented suicide cases, that took place in Denmark, from 1989 to 1996 show that, people who died via citalopram, who's blood concentrations were measured, carried 2mg to 6.2mg of it. per kg.
-http://link.springer.com/article/10.1007/s004140050147#page-1
with 1 liter of blood having the weight of 1060mg. converting these results to mg/l gives us 1.9mg/l (2mg / 1060 *1000 ) and 5.8mg/l (6.2mg / 1060 * 1000). one of these people needed no more than 38 10mg tablets (50μg/l * 38 = 1900μg/l or 1.9mg/l).
but
"five non-fatal cases of citalopram overdose (up to 5200 mg) resulted in seizures developing in 4 cases and all (five cases) had QT prolongation, sinus tachycardia and inferolateral repolarization disturbances"
-http://www.antidepressantsfacts.com/celexa.htm
one of these people on the other hand, would have needed even more than 520 10mg tablets (or 260 20mg tablets).
what a successful suicide case looks like is shown below:
"she had been prescribed citalopram by her family doctor 3 weeks before her death for a depressive syndrome. police found in her house 3 empty blister packages of 28 citalopram tablets (20 mg) and 2 bottles of citalopram oral solution (4%, 15 mL each). "
-http://journals.lww.com/amjforensicmedicine/pages/articleviewer.aspx?
year=2005&issue=12000&article=00012&type=abstract
citalopram solution bottles usually contain 40mg per ml, and i guess this is what they meant. 2 bottles would then yield (30 * 40mg) 1200mg citalopram. the 84 tablets she swallowed, 1680mg. together 2880mg
citalopram isn't a secure way to go. you first have to consider that, although there are fatal case reports with doses that you could reach with just a handful of tablets, a massive dose like 5200mg has been shown to be not necessarily fatal. i'd go for 6000mg.
then, consider that, you might get rescued, even 8 hours after your intoxication, as it was the case with a 2000mg overdosed 52-year old female
-www.ggiz-erfurt.de/pdf/pub_2005_citalopram.pdf
who was detoxicated with charcoal and sodium sulphate. make sure nobody will find you, or make sure you take a long nap with some hypnotic substance/anaesthetic/alcohol, so nobody who will find you will notice
you're dying, or mix citalopram with something else.
"three cases of fatal serotonin syndrome (tremor, hyperpyrexia, and seizures) occurred following overdoses involving citalopram and moclobemide. the three males died within 3 to 16 hours after overdose (Neuvonen et al, 1993).
(1) citalopram serum concentration was at a therapeutic level in
one patient and 2 and 5 times therapeutic levels in the other cases.
(2) moclobemide serum concentrations were 5 times therapeutic levels in
one patient and 20 to 50 times higher in the other two cases."
-http://www.antidepressantsfacts.com/celexa.htm
"intoxications with moclobemide as single agent are usually mild; however, when combined with tricyclic or SSRI antidepressants the overdose much more toxic and potentially fatal"
-http://en.wikipedia.org/wiki/Moclobemide
"moclobemide is a benzamide, derivative of morpholine, which acts pharmacologically as a selective, reversible inhibitor of monoamine oxidase A (RIMA), a type of monoamine oxidase inhibitor (MAOI)"
-http://en.wikipedia.org/wiki/Moclobemide
it primarily inhibits monoamine oxidase A, but to a lesser extent also monoamine oxidase B. generally it is considered to be a MAOI (monoamine oxidase inhibitor) antidepressant of the type RIMA (reversible inhibitor of monoamine oxidase A)
there's more pharmaceutical drugs of this kind that you could use instead (if you can't get hold of moclobemide). these are: brofaromine, caroxazone, eprobemide, metralindole, minaprine, pirlindole and toloxatone. additionally, RIMAs also exist in nature.
the alkaloid piperine can be found in white or black pepper, which is obtained from the pepper plant (piper nigrum). "the unripe, unpeeled, dried, wrinkly fruits of a size of 3 - 6 mm are known as black pepper, while white pepper is obtained from the fully ripe fruit by removing (peeling) the outer pericarp after 2 - 3 days' fermentation and drying the seeds to yield smooth, yellow to dirty yellow peppercorns of a size of 2 - 4 mm." "fresh peppercorns contain approx. 5 - 9% piperine"
-http://www.tis-gdv.de/tis_e/ware/gewuerze/pfeffer/pfeffer.htm#selbsterhitzung
it's also part of tailed pepper and long pepper. extraction methods vary, here's a desription of one that uses ethanol + KOH + acteone/hexane:
"place 30g of finely ground black pepper in a porous thimble in the central chamber of a soxhlet extractor and 175ml of 95% ethanol in a RB flask. gently heat solvent under reflux for 6 hours. concentrate the solution to a volume of 20-30ml on a rotary evaporator and add 30ml of warm 2M ethanolic potassium hydroxide (this is ESSENTIAL to keep all the acidic components in solution). after shaking the warm mixture well, filter the solution and remove any insoluble materials (quite a bit). while keeping the solution warm over a water bath, and water until no more yellow solid forms. allow the resulting solution to stand overnight and then isolate yellow precipitate that has formed by filtration. recrystalise the crude product in hot 3:2 acteone/hexane, cooling in ice bath if necessary to promote recyrstallisation. the resulting product (piperine) is in the form of spectacular yellow needles, a yield of around 2g (in my case) was obtained."
-http://www.erowid.org/archive/rhodium/chemistry/3base/piperonal.pepper/piperine.pepper/
recipe_piperine_piperic_acid.txt
that's a lot of work that sadly can't be avoided (and on top of that a rotary evaporator isn't exactly cheap). ready-to-swallow capsules are available prescriptionfree. they contain approx 10mg of piperine, per unit (capsule). that's 100 capsules just to reach an intake of 1g of piperine. more on that later.
the half maximal inhibitory concentration (IC50) "indicates how much of a particular drug or other substance (inhibitor) is needed to inhibit a given biological process (or component of a process, i.e. an enzyme, cell, cell receptor or microorganism) by half. "
-http://en.wikipedia.org/wiki/IC50
49.3 μM (M stands for molecular concentration) is the IC50 inhibitory value of piperine against MAO A. (and 91.3 μM against MAO B)
-http://www.ncbi.nlm.nih.gov/pubmed/15120460
6μM is the IC50 inhibitory value of moclobemide against MAO A (and against MAO B it appears to be only slightly effective with an insignificantly high IC50 value of >1000 μM)
-https://www.google.de/url?
sa=t&rct=j&q=&esrc=s&source=web&cd=4&cad=rja&uact=8&ved=0CEoQFjAD&url=http%3A%2F
%2Fonlinelibrary.wiley.com%2Fdoi%2F10.1111%2Fj.1527-3458.2002.tb00229.x
%2Fpdf&ei=OwMmU6DWCIOHtQa3sIDADg&usg=AFQjCNF3iwkDNaQAjjInItaQKLawsFFQlQ&bvm
=bv.62922401,d.Yms
this means moclobemide is a (49.3 / 6 =) 8.2 times more effective MAO A inhibitor than the naturally occuring piperine. in the 3 fatal case reports that were previously mentioned, the moclobemide
concentrations were 5, 20, 50 times the "normal therapeutic level"
a typical dose for most patients is 300mg per day, sometimes it is raised up to 600mg
-http://de.wikipedia.org/wiki/Moclobemid
let's assume the worst case scenario where the "normal therapeutic level" stands for 600mg. then the fatal doses (in conjunction with citalopram) would have been as follows: (5 x 600mg =) 3g, (20 x 600mg =) 12g, (50 x 600mg =) 30g.
if one simply ignores the higher potency of piperine as a MAO B inhibitor, and only takes the effects on MAO A into account (= makes piperine look weaker than it actually is compared to moclobemide), the equivalent fatal doses of piperine (when taken together with citalopram) would have been:
(8.2 x 3g =) 24.6g, (8.2 x 12g =) 98.4g, (8.2 x 30g =) 246g.
if 30g black pepper yields 2g piperine, like it was the case in the extraction tutorial above, the concentration there then was (100% / (30 / 2) =) 6.7%. this means, to aim for the lowest of these 3 known fatal doses, 24.6g of piperine, you'd need (if your pepper also has a concentration of 6.7%) an amount of (100% / 6.7 * 24.6g =) 367g of black pepper. for the other 2 doses you'd need (100% / 6.7 * 98.4g =) 1469g and (100% / 6.7 * 246g =) 3672g respectively.
in the light of these enormous amounts of source material that one needs to obtain useful amounts of piperine, it's unlikely you could poison yourself sufficiently by simply eating powdered black pepper. or by ingesting some of these readily available capsules with a piperine content that is no more than 10mg. (you'd need 2460 capsules to reach the lowest fatal dose) laboratory equipment is a must then.
another naturally occuring RIMA could be the flavonoid quercetin (at the time of writting this, it has not yet been confirmed whether quercetin is "selective" and "reversible" but it certainly inhibits MAO A)
-http://www.ncbi.nlm.nih.gov/pubmed/19013512
"capers contain more quercetin per weight than any other plant"
-http://en.wikipedia.org/wiki/Capers
234mg are contained in 100g of raw capers (that's a concentration of 0.234%)
-http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/Flav/Flav_R03.pdf
the IC50 against MAO A is 18μM
-http://www.ncbi.nlm.nih.gov/pubmed/19013512
so moclobemide is 3 times as effective as quercetin, and the lowest of the known fatal doses of moclobemide is 3g (in conjunction with citalopram). you'd have to consume 9g of quercetin (in conjunction with citalopram) al minimo.
now, the amount of raw capers that would theoretically yield 9g of quercetin is (100% / 0.234 = 427; 9g x 427 =) 3.8kg. you can't possibly eat that much. it, however, is quite possible to extract quercetin via methanol. i'm not going to descend into details, though. because i've never tried it myself and the information on this procedure is sparse. let me just mention that there are ready-to-ingest capsules you can buy (prescription free) that contain 250mg quercetin per unit. you'd gain a 9g quercetin augmentation in your body after only (9g / 0.25 =) 36 capsules. that's a quite realistically realizable meal. the other 2 known lethal doses of moclobemide were, as mentioned earlier, 12g and 30g. the equivalent of 36g and 90g of quercetin. 36g is what 144 capsules provide. (that's still swallowable) 90g is contained in 360 capsules. (that'll be a
challenge, but is theoretically also swallowable).
1 package (120 capsules) mixed with as many citalopram as you can get (also small doses might suffice, though), is what i'd go for.
resveratrol, a phytoalexin, is a RIMA with a MAO A inhibitory potency of IC50 25μM
-http://www.scbio.de/datasheet-205254-cis-resveratrol.html
moclobemide is (25 / 6 =) 4.2 times as effective as resveratrol. the latter can be found in all sorts of fruits, like for example grapes (an in those most of all in their skin). freshly pressed red grape juice has a concentration of 1.1mg per liter while red wine apparently has a concentration of 2mg to 12mg per liter.
-http://de.wikipedia.org/wiki/Resveratrol
so can you achieve a deadly dose of resveratol by drinking wine? no. (3g x 4.2 =) 12,6g would be the minimum that, combined with an SSRI, could lead to death. 250mg are contained in one of those commercially available capsules, which are far more suitable for suicide. you can get them prescription free. you'd need a minimum of 51 capsules (+ citalopram).
harmine is another naturally occuring MAOI antidepressant, which reversibly and selectively inhibits MAO-A (monoamine oxidase A), peganum harmala seeds contain harmine, an amount of 0.44 of it in percentage terms
-http://www.ncbi.nlm.nih.gov/pubmed/18980138
or even more according to other sources. and they contain at least 0.25% of harmaline (a reversible (non-selective) inhibitor of monoamine oxidase A)
-http://www.ncbi.nlm.nih.gov/pubmed/17723604
the IC50 (against MAO-A) of harmine lies somewhere between 2μM and 5μM, so, it is more or less equivalent, possibly even more potent than moclobemide (with an IC50 ranging between 3.9μM and 6μM. the IC50 (against MAO-A) of harmaline seems to be around* 4.5μM
-http://books.google.de/books?
id=c8rg6rPsvUYC&pg=PA91&lpg=PA91&dq=harmaline+ic50+mao+nm&source=bl&ots=goIjYRYrnT&s
ig=halyCeFLfK-v5G0ccuuQgrMLpX4&hl=de&sa=X&ei=CF44U8P5D8PdtAaeoB4&
ved=0CGUQ6AEwBQ#v=onepage&q=harmaline%20ic50%20mao%20nm&f=false
*i've seen values between 2.5μM and 8μM
also harmaline seems to be at least equivalent to (if not, even stronger than) moclobemide.
so, (0.25 + 0.44 =) 0.69% of potent MAOI alkaloids can be found in peganum harmala seeds. (100 / 0.69 = 145; 3g x 145 =) 435g of such seeds is what you'd need for a minimum lethal dose
it's unlikely you'd be able to eat enough. unless if you grind and fill these seeds into 435 capsules and then manage to actually ingest such a large amount, you'd have to go through following steps of Albert
Most's recipe
"the crushed seeds are covered with three times their weight of water containing 30 g. of acetic acid per liter of water, the seeds swell as they absorb the liquid and form a thick dough which is pressed after 2 or 3 days.
the pressed seeds are once more treated as above with twice their weight of dilute acetic acid and, after maceration, the liquid is again pressed out. to the combined liquors, sodium chloride (100 g., liter of liquid) is added to transform the acetates of harmine and harmaline into the hydrochlorides which are insoluble in cold sodium chloride solutions and are precipitated during cooling. the supernatant liquid is siphoned off, the crystaline residue filtered with suction and redissolved in hot water. addition of sodium chloride to the filtered solution results in the precipitation of the hydrochlorides as a crystalline mush and this process is repeated until the hydrochlorides have acquired a yellow color. the separation of harmaline from harmine is based on the fact that when a warm aqueous solution of the hydrochlorides is alkalinized with ammonia, harmaline is liberated only after the decomposition of harmine hydrochloride is complete. the appearance of harmaline is readly detected under the microscope since it consists of plates while harmine forms long needles. the addition of ammonia, therefore, is stopped as soon as crystals of harmaline are detected, the harmine is filtered off and the harmaline recovered from the filtrate by the addition of ammonia, the bases are then further purified by recrystallization of their hydrochlorides."
-isolation of harmine and harmaline, "Ann. chim (10) 7,15l" from 1927
besides citalopram (which can induce death all by itself in high doses) there's other SSRIs (which are not very likely to become lethal all by themselves) that can bring about peace of mind² when combined with
MAOIs. these are: dapoxetine, escitalopram, fluoxetine, fluvoxamine, indalpine, paroxetine, sertraline, zimelidine. since they are less effective compared to citalopram, you'd have to dose them higher. other than that, the preceding text in this chapter applies also to them.
serotonine syndrom the ultimate cause of convulsions, coma & disseminated intravascular coagulation. the latter, leading to the formation of small blood clots inside the blood vessels throughout the body, is also known as "death is coming" or DIC for short, and disrupts blood flow to all sorts of organs, and causes them to go on strike. this is a potentially pleasant way to go, because you'd fall into a coma prior
to dying unconsciously. but, if you don't dose high enough to reach a comatose state, you'll be stuck in process 1, convulsions.
"she took all of her anti-depressant medication, including mood stabilizers and who knows what else, but it was a total of 60 pills [...] she then changed her mind on taking her own life, so she sought help, but it was too late to pump her stomach. she is now in hospital in an induced coma, and on a ventilator. they have diagnosed her with extreme serotonin syndrome. they have attempted to bring her out of her coma 3 times in the last 3 days, without success. her convulsions were very bad, so they put her back into the coma. when you talk to her, her heart rate increases, which apparently means that she can hear us sub-consciously. the doctors aren't giving us anything, because they are very scared to give us false hope in case there is a backlash."
- posted on a web forum, by djcandiflip, http://www.drugs.com/forum/featured-conditions/acute-serotoninsyndrome-fentanyl-prozac-effexor-xr-43361-2.html
025 appendix
about irreversible MAOIs & tyramine
seeing as the this chapter introduced MAOI inhibitors of the RIMA type, it seems appropriate to conclude the topic with a brief discourse about the remaining MAOIs. presented to you as an appendix.
-http://www.psychiatrictimes.com/major-depressive-disorder/irreversible-monoamine-oxidase-inhibitorsrevisited
so, besides reversible inhibitors of monoamine oxidase A (RIMAs) there's also irreversible MAOIs: phenelzine, isocarboxazid, tranylcypromine, clorgyline, resagline (mainly for MAO-B inhibition), nialamide, selegiline (mainly for MAO-B inhibition). and a few more, which have been completely withdrawn from the market.
"the older, non-selective, irreversible drugs have very severe and prolonged toxicity in overdose and potentially life-threatening interactions with tyramine"
-http://curriculum.toxicology.wikispaces.net/Monoamine+oxidase+inhibitors+(Detail)
irreversible MAOIs are very toxic all by themselves, and they are also difficult to obtain. if you however did get hold of such an antidepressant, but only in small amounts, and have no SSRIs at hand, you can instead mix it with tyramine. in order to cause a hypertensive crisis. reversible MAOIs most likely won't be strong enough to cause a fatal hypertension (high blood pressure) when combined with tyramine, but with irreversible ones things look different, and might build up to an "acute impairment of one or more organ systems (especially the central nervous system, cardiovascular system and/or the renal system)"
-http://en.wikipedia.org/wiki/Hypertensive_emergency
aka hypertensive crisis. if this won't soon lead to organ failure, followed by death, it will do so later. the probability to die within the following year following a non-immediately-fatal hypertensive crisis lies at 80%
-http://emedicine.medscape.com/article/1952052-overview
-http://en.wikipedia.org/wiki/Tyramine
more than 25mg leads then to a hypertensive crisis. the following drink can be useful to achieve that:
tap beer, a 355ml portion, may contain around 38mg tyramine
-http://www.mc.vanderbilt.edu/documents/neurology/files/Tyramine%20Menu%20Book%2006227101.pdf
but it'll probably be less. it seems to depend on whether it was "produced by bottom fermentation (lagers) and brewed by a secondary fermentation process"
-http://www.ncbi.nlm.nih.gov/pubmed/8151003
or not. if you get hold of tap beer, since it possibly won't be too potent after all, and contain less than 25mg of tyramine per liter, drink more than 1 liter. i'd recommend 2.
note that ordinary (canned/bottled) beer, per 355ml bottle, only contains around 1.5mg, and therefore is not useful. soya products look promising, they are thought to be replete with tyramine, but there aren't any concrete concentration values to guide us.
"the enzyme monoamine oxidase exists as 2 subtypes, MAO-A and MAO-B. MAO-A metabolizes serotonin and norepinephrine (NE) [...] MAO-B preferentially metabolizes dopamine and trace amines, including phenethylamine. tyramine is metabolized by both MAO-A and MAO-B"
-http://www.psychiatrictimes.com/major-depressive-disorder/irreversible-monoamine-oxidase-inhibitorsrevisited
most MAOIs mainly inhibit MAO-A, and MAO-B only a little bit if at all. the effect on MAO-A of irreversibles is thorough enough, however, it does not really matter whether MAO-B gets neglected or not. but if you'd be trying to achieve a hypertensive crisis with the much more common reversibles, inhibiting MAO-B in addition to MAO-A, instead of just MAOA alone, will lead to a more excessive build-up of tyramine, and increase your (otherwise rather slim) chances for success.
among the naturally occuring RIMAs, paeonol's Inhibition of MAO-B corresponds to an IC50 of 42.5μM, and it is also noteworthily effective against MAO-A (54.6μM)
-http://www.ncbi.nlm.nih.gov/pubmed/15120460
paeonol (a phenolic compound), also known as paeonolum, contained (for example) in the paeonia suffruticosa, native to China, hasn't been mentioned in in the main part of 025, mostly because it's not known (to me) how high the concentration is you'd encounter in any of the plants harboring it. this being so, i can't
provide any information of how much plant you need to get what's needed out of it, and it's not being sold in pure form in most of the world (= except for China). but let's mention paeonol here, because, herbal extracts with a paenol concentration of 98%-99% can, after all, be ordered from China, (for example) from Shanghai, in 1kg bags, for a 3-digit sum per bag.
other sources of paeonol (btw) are paarisaema erubescens, dioscorea japonica, luculia intermedia, rosmarinus officinalis, exacum affine, primula auricula, cynanchum paniculatum and prosopis cineraria (see Sumitra Singh's, Vijay Naresh's and Surendra Kr Sharma's "isolation of novel phytoconstituents from the bark of wonder tree" for a tutorial of how to get paeonol out of the bark of the prosopsis cinaria tree).
maybe you'll be able to get to the bottom of the mystery (of how much of the aforementioned plants you need to reach a lethal dose of paeonol in conjunction with tyramine) yourself. MAO-A and MAO-B is almost equally suppressed, so, you won't need any extra MAOI that would take care of any remaining enzyme. more than paeonol (in large amounts) and tyramine (>25mg) is not needed.
besides MAOI irreversibles, tricyclic antidepressents are also highly toxic, usable as a sole means to kill yourself, and unfortunately also very difficult to obtain nowadays. therefore, let's skip them and let's move on to easier accessible "mood-enhancers".
Fuck you and this blog, stop doing this shit
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