Myristicin is aminated to MMDA in the liver

[Torsten]

This is a really old paper, but I've never had a digital copy of it and hence have never been able to post more than the abstract of it.

I regularly get involved in discussions where people claim that the biogenic conversion from myristicin to MMDA [or any allylbenzene to the respective amphetamine] is impossible and it seems the most anyone ever knows about it is Shulgin's reference to it in one of his books.

Just so I don't continually have to argue the point I am now posting the paper here.

if anyone is interested in myristicin or biogenic amination then do a search on these forums. There have been many discussion about it and some are interlinked so easy enough to find.

I've posted this in the ethnobotany forum rather than the pharmacology forum so that it is publically viewable.

Amination_of_myristicin_in_liver.pdf

Amination_of_myristicin_in_liver.pdf

Amination_of_myristicin_in_liver.pdf

[Torsten]

I keep having problems downloading this in firefox, but not in IE. Not sure what's going on there..

[Auxin]

Thanks I've wondered how much actual science was behind this at times (lots of wishful thinking in the drug communities sometimes)- its good to get a look at the paper.

Worked just fine for me in firefox. I have this site fully allowed for java and popups, maby you have java blocked?

[Pisgah]

Thanks for posting that, T. Very helpful.

Maybe I should add some rat livers to the Sassafras brews I'm running these days.

[MindExpansion]

Heheh, thanks for that info Torsten, I remember 10g of nutmeg used to go down, it was not that great, like a 3 day hangover and even while 'high', it isn't fantastic, ok, but not fantastic. Now I know why it did anything, never used to know. And how rank that nutmeg did taste!!

Peace,

Mind

[Torsten]

please keep in mind that nutmeg is not equal to myristicin. There are many other active compounds in nutmeg, including one that is highly inebriating and sedative, and which generally overrides the myristicin effect.

[MindExpansion]

Ahh ok. Cheers for the info Torsten, interesting stuff.

Peace,

Mind

[knarkkorven]

I am now posting the paper here.

Thanks! I have been looking for this one!

I have read almost everything on this forum regarding essential oils and the phenetylamine conversion.

Your reports of rubbing the oils on muscles sound promising Torsten!

I discovered about a year ago that parsnips allowed to grow into it's second year are a good source of myristicin.

I tried them (5-10g dry) last year with mild effects, will try again this year fresh to preserve the volatiles better... My kitchen was really smelly last year, haha

I am wondering about how one would do a simple extraction. I don't have a destillation setup, but was thinking about cooking plant

material in water with a bit of butter or other fat under a lid, filter the liquid and let it cool down to the point when the fat hardens enough

to be separated with the actives. Would this work?

Check this out:

"Illusions, loss of consciousness, quiet delirium; the illusions were confined to vision, and the patients stared and grasped at imaginary objects in the air, etc.; some of them did not speak at all, others only indistinctly or incoherently; two of them used inarticulate sounds; almost uninterrupted attempts to get out of bed"

"All labored under delirium tremens; they were in constant motion, talking incessantly, without knowing what they said, and fancied they saw objects which had no existence. They fought with each other and were occasionally attacked with fits of convulsive laughter. They rejected everything that was offered them and were obliged to be restrained by force."

Source: THE ENCYCLOPEDIA OF PURE MATERIA MEDICA av Timothy F. Allen http://www.nwbotanicals.org/oak/altagri/parsnips.htm

[planthelper]

I am wondering about how one would do a simple extraction. I don't have a destillation setup, but was thinking about cooking plant

everybody has a still at home...

ordinary kitchen ware can be set up to, double as a coldfinger setup!

all you need is, your material, a good size cooking pot with lid, a tea cup, lot's of ice, and your stove.

methode:

place your plant material into the pot,

place your tea pot in the centre of the pot (the plant material is spread all around this cup)

place the lid onto the pot, but in an inverted fashion (the handl of the lid is pointing down)

see thru glass lids are very good, as you can watch the progress of your work...

place ice on the lid,

place pot on top of the stove.

the essential oil, should collect in the tea cup (or what ever boil proof vessel).

alternatively, just apply heat to the material for a while, in the normal fashion as you would do, cooking vegetables, meaning with the lid on the normal way, and no collection jar in the centre...

than after, given appropiate time (maybe the plant material gets even removed at this stage and only the liquid gets prozessed further), invert the lid, place ice on it, and place the cup in the centre, and so on as above.

the alternative methode, might work well considering, one could simmer several loads of material, and than combine those liquids and than perform the distillation.

the temperature choosen is a very important factor, as for example if one were to work with camphor laurel, the lower temperatur distillations would yield different material as the higher temps. if memory serves me well, safrol would come accross as the last oil, using higher temps.

[Torsten]

I actually got some parsnip essential oil a year ago, but I haven't analysed or tried it yet. It does smell very promising. Even more promising was a vegetable we grew 2 years ago. It was one of those new re-bred purple carrots. The growing tip and skin of this beast was so rich in myristicin that I couldn't eat it wihtout peeling.

[knarkkorven]

Planthelper:

I have looked at coldfinger destillation, and yes it's simple, but is it good enough?

My concern is that the temperature don't spread evenly in the pot, might burn the plant material in the bottom

and not heat the plant material at the top?

How about an ethanol extraction? Making your own parsnip liquor?

Torsten:

If you bioassay the parsnip oil, let us know if it worked.

[planthelper]

i don't know how efficant this diy coldfinger would be with your applications, however let's get the prioreties right, your material is very abundant, but you don't want to spend a fortune on a still...

aswell if you are worried about, uneven temps, in the vessel, just heat up the material, in the pot in the ordinary fashion and just stir frequently... , than combine the yield and still the material.

regarding working with methanol, i say that i have used the same type set up, but naturaly you have to follow all the safty precautions (no open flame, very ventilated area, and so on).

the issue about home stilling comes up frequently at this forum, and building a still can be done in thousand of ways and various degrees of standard, a site called homedistiller shows many diy setups, aswell i think the pinned thread home apparatus at the chem forum would be a good read for you.

[t st tantra]

rastch claimed carrot leaves esp wild forms could be smoked 4 psychoactive effects.

t s t .

[knarkkorven]

This pdf contains a review of the different reports and studies, the best i've read so far. It also propose a different theory

about how allylbenzenes can be aminated to essential amphetamines.

In Sweden it's an old tradition to eat gingersnaps before christmas, and we tell each other to eat lots of it to become nicer. I discovered that this tradition goes way back in time to 1497 - 1501 when a King named "Hans" ruled Denmark, Norway and for a brief time Sweden. He had a bad temper and his doctor recommended gingerbread because it was generally known to make you happy. The pharmacist in Copenhagen apparently had records of sending several kilos of gingerbread to the king.

What do you think? Can the essential oils become aminated "in furno" ?

Christmas Gingerbread (Lebkuchen) and Christmas Cheer – Review of the Potential Role of Mood Elevating Amphetamine-like Compounds Formed in vivo and in furno

Abstract: The typical spices used in winter include nutmeg, cinnamon, clove and

anise. These spices contain two groups of chemicals, the allylbenzenes and their

isomers, the propenylbenzenes. It was suggested 40 years ago by Alexander

Shulgin that these substances act as metabolic precursors of amphetamines.

The biotransformation of these precursors to nitrogen-containing metabolites is

reviewed. These reactions have not been reported in humans. Whether or not the

pharmacology and toxicology of spices such as nutmeg can be explained on the

basis of their allylbenzene or propenylbenzene content is speculative. Humans may

be exposed to amphetamines derived from these precursors in forno, the

formation during baking and cooking, for example in the preparation of Lebkuchen,

or Christmas gingerbread. It is possible that this may be responsible, in part, for

uplifting our mood in winter. However, the role of these aromatic substances,

acting simply as odours, evoking old memories of winters past, cannot be ignored.

Whether spices have a true pharmacological effect or they act as aromatherapy

remains to be elucidated through clinical and laboratory studies.

...

there exists an alternative means by which consumption

of certain foodstuffs may lead to amphetamine exposures, and that is the

formation of these compounds during the cooking process, what I have called “in

furno.” Examination of the Lebkuchen recipe in Table 3 reveals chemical

constituents that, when heated together in furno might plausibly result in some

ammonia addition to the alkenylbenzene double bonds, which would lead to the

presence in the Lebkuchen of 4-methoxyamphetamine (PMA) from (E)-anethole

and 4-hydroxy-3-methoxyamphetamine (HMA) from eugenol. It is readily calculated

from Table 3 that just a 1% yield in these reactions could lead to amphetamine

content in excess of 80 mg per kg Lebkuchen. Unfortunately, no scientific data on

the content of these compounds in baked goods has ever been published to my

knowledge. The formal hallucinogenic doses of PMA and is 50-80 mg [6] and for

HMA is not known [6]. It may be sufficient for a person to ingest tiny amounts of

these compounds from the winter diet, in order to elevate the mood and to help

providing some added Christmas cheer.

http://pmr.cuni.cz/Data/files/PragueMedica...5-01%20Idle.pdf

[Torsten]

what a pointless paper. why didn't he just analyse the gingerbread or compare raw gingerbread with cooked gingerbread [via bioassay]. Personally I don't think 'in furno' is a viable method as at least part of the reaction is a reduction unlikely to happen under these circumstances.

[tregar]

Thanks Torsten for the article, very interesting. Yet more evidence (below) that myristicin is psychotropic?

Shulgin 1967 "The Separation and Identification of the Components of the Aromatic Ether Fraction of Essential Oils by Gas-Liquic Chromatography," Journal of Chromatography 30: 54-61 & Truitt, Jr., E.B, et al 1961. "The Pharmacology of Myristicin, A contribution to the Psychopharmacology of Nutmeg," Journal of Neuropsych. 2(4): 205-210: [Note: Hallstrom and Thuvander (1997) cite the year of this paper as 1960; while we have not seen a copy of the paper, multiple other references--including one in another article by E.B. Truiott--give the year as 1961].

Another secondary source (Shulgin et al. 1967) also citing Truitt et al. 1961, claimed symptoms from 400 mg of myristicin "at least suggestive of psychotropic effects in 6 out of 10 subjects." The original paper by Truitt et al. states that there was a "definite reaction" in each of 4 subjects, and that 2 subjects each had a "questionable reaction."

Perhaps had those 6 subjects done some strenuous muscle activity or running they may have experiencedmore pronounced effects...

Page 22 of Vernal Equinox 2008 Entheogen Review "Myristica Fragrans, An Exploration of the Narcotic Spice":

Myristicin's psychoactive properties were confirmed by a study on ten human participants in 1961 (Hallstrom & Thuvander 1997, citing Truitt et al. 1961). Each of the participants was administered 400mg of myristicin, or approximately 6-7 mg/kg by body weight. Only four of the participants experienced psychoactive effects, including euphoria, anxiety, and trouble concentrating. That only four participants experienced psychoactive effects at this level suggests that 400mg or (6-7mg/kg) is a threshold effective dose for nearly half of the population. Time of onset was between two and three hours after ingestion. Interestingly, 400mg of myristicin is around twice the amount of myristicin that would be present in a moderate-high psychoactive dose of nutmeg.

Myristicin generally makes up 4-8% of nutmeg's volatile oil and has been found in concentrations as high as 1.3% of nutmeg by weight (C.E.F.S. 2005). the myristicin content of mace is generally double that of nutmeg, making it potentially more potent than nutmeg.

I'll try and get a copy of the paper if possible and post it in a few days. I've attached a hard to read 10 page paper on "Explorations with Myristica Fragrans" in the Spring 2008 edition of "The Entheogen Review" by Ibo Nagano, but again as Torsten states, the oil (even bad oil) is better than the ground up nutmeg. Concerning muscle activity: being a weight lifter, I know that strenuous muscle activity causes the release of Arachidonic acid (eicosa-5,8,11,14-enoic acid) among other things. Arachidonic acid is the body's core "anabolic fat" It is an omega-6 fatty acid that serves as the principle building block for the synthesis of dienolic prostaglandins among other things but I doubt that has anything to do with anything. Arachidonic Acid just be came available as a supplement a few years ago. Arachidonic acid begins to display its anabolic activity early during exercise. This nutrient is relased from your muscle fibers as they are damaged during intense training, triggering a localized inflammatory and anabolic response. This is part of the same biological process that causes you to be sore a day or two following a good workout. But again, I doubt this has anything to do with this.

Theres mention of MMDA in Eisners book "e for estacy" (add Ammonia to Myristicin to get MMDA. - If only....) 'Its like E but more visuals' seems to summ it up. nice.

Naranjo:

The most important quality I found in MMDA--a sense of what I call "the eternal now"--was something that I was particularly ready to apprreciate, in view of an unexpected source of frustration that I had just encountered in my attempts to conduct therapy under MDA.

Schultes and Hofmann. The Botany and Chemistry of Hallucinogens. p. 121:

Myristicin constitutes about two thirds of the aromatic ether

fraction, but it cannot account entirely for the psychoactivity

of nutmeg. Those occurring at more than 10 mg per 20 g are myristicin

(210 mg), elemicin (70 mg), safrole (39 mg), methyleugenol (18 mg),

and methylisoeugenol (11 mg). A 400-mg dose of myristicin, almost twice

the amount present in 20 gm of nutmeg (20 gm being assumed to be the

quantity required to produce psychotropic effects) produces only mild

effects.

Again, as Torsten and friends have discovered, there appear to be additional means (such as muscle activity) of activating the metabolic pathways to much stronger effects albleit shorter lasting.

Page 21 of Vernal Equinox 2008 Entheogen Review "Myristica Fragrans, An Exploration of the Narcotic Spice":

Capsaicin, a chemical found in cayenne pepper, is also a mild inhibitor of cytochorome P450 2E1, which is a mixed-function oxidase involved in metabolism that mediates some drug interactions. It could be that one or both of these peppers is the reason why lower doses of nutmeg seem to have stronger effects when taken via this preparation. Black pepper also contains high levels of myristicin.

Sangalli, B.C. and W. Chiang 2000. "Toxicology of Nutmeg Abuse," Clinical Toxicology 38(6):671-678.

Myristicin is active at the 5-HT receptors in the brain, and has been shown to have hypotensive, sedative, anti-depressant, anesthetic, hallucinogenic, and serotonergic properties (Sangalli & Chiang 2001). Large doses generally cause hyperexcitability, followed by CNS depression. Myristicin is fairly unique as a hallucinogen (if it may be classified as such), because it lacks a nitrogen atom. It is also rare for a compound lacking a nitrogen group to show activity at the brain's 5-HT receptors.

A 1998 analysis found East Indian oil to contain the most myristicin:

http://cat.inist.fr/?aModele=afficheN&cpsidt=1675799

Shulgin, who has tried to work out the biochemistry of nutmeg's hallucinogenic action, has assumed [22] for the moment that the myristicin fraction of the oil (with its more than 25 per cent content of elemicin) is, indeed, the active principle. He has noted that the metabolism of the aromatic ethers found in essential oil is "virtually unknown" except for a detoxication mechanism by which safrol is converted to piperonylic acid. This reaction indicates a capacity to oxidize an olefinic side chain. Shulgin has suggested that, if this degradative process is "applicable to myristicin, or especially to elemicin, a theoretical intermediate, a vinyl alcohol, could undergo transamination producing the known psychotomimetic drug, 3,4,5-trimethoxy amphetamine (TMA) ". The recent description of the new synthetic hallucinogen - 3-methoxy-4, 5-methylenedioxy amphetamine (MMDA) - which might be derived by an analogous process from myristicin, itself, is even more suggestive of a psychotropic function for this component of nutmeg.

* Possible production of a known psychotomimetic agent from myristicin. (see figure below).

Thus far, human pharmacological data are inadequate to support the contention that myristicin is psychoactive or that it is an active principle of whole nutmeg. Shulgin has written [22] : "... some combination of factors in total nutmeg is capable of producing a psychotropic response: the structure of elemicin or myristicin wanting only an ammonia molecule to become a recognized mental agent must be accepted as at least an intriguing coincidence."

Ammonia production in muscle: The data also suggest that type I muscle fibers can be a major source of ammonia (NH3) in humans. http://jap.physiology.org/cgi/content/abstract/63/4/1457

http://ajpcell.physiology.org/cgi/content/...ract/250/6/C834

Ammonia content of various foods (such as grape wine, etc.) http://www.ajcn.org/cgi/reprint/26/5/487.pdf

Myristica_Fragrans.pdf

Myristica_Fragrans.pdf

Myristica_Fragrans.pdf

Edited July 9, 2008 by tregar

[AndyAmine.]

the temperature choosen is a very important factor, as for example if one were to work with camphor laurel, the lower temperatur distillations would yield different material as the higher temps. if memory serves me well, safrol would come accross as the last oil, using higher temps.

So you have successfully done factional distillation with this setup PH?

Interesting, I guess it wouldn't be hard once you got the hang of it and had the correct temperatures for what your after.

I would have imagined that a stove top would be hard to keep at a steady temp though, I always found they fluctuated a lot?

[planthelper]

hehe, you got me there, no i have never done this myselfe!

however, as you said it would not be too difficult with some experience.

and it's not like you get only one chance, i guess you can do this again and again till close to perfect.

[tregar]

I could not attach the very interesting 1961 paper by Truitt where 10 humans were given 400mg of myristicin and the effects they experienced due to it being 3.95 megabytes. Give me a few days and I'll transcode it into a notepad file for upload. Each of the subjects in the paper give a detailed description (one or more paragraphs) of the effects they felt after taking the myristicin. Some subjects were given an oil placebo pill, none of the subjects nor investigators knew who got the placebo or the myristicin in the beginning.

Myristicin, along with any of the other volatile components (namely phenylpropanoids), are definitely the active agent.

Myristicin's psychoactive properties were confirmed by a study on ten human participants in 1961 (Hallstrom & Thuvander 1997, citing Truitt et al. 1961). Each of the participants was administered 400mg of myristicin, or approximately 6-7 mg/kg by body weight. Only four of the participants experienced psychoactive effects, including euphoria, anxiety, and trouble concentrating. That only four participants experienced psychoactive effects at this level suggests that 400mg or (6-7mg/kg) is a threshold effective dose for nearly half of the population. Time of onset was between two and three hours after ingestion. Interestingly, 400mg of myristicin is around twice the amount of myristicin that would be present in a moderate-high psychoactive dose of nutmeg. Myristicin generally makes up 4-8% of nutmeg's volatile oil and has been found in concentrations as high as 1.3% of nutmeg by weight (C.E.F.S. 2005). the myristicin content of mace is generally double that of nutmeg, making it potentially more potent than nutmeg.

Experience of one of the subjects who had a definite reaction:

The subject took her 400mg capsule of myristicin at 7:30 am. At 8:45 during a psychoanalytic hour there was flushing, sweating, a sense of light-headedness and a feeling of being detached. The subject felt that she talked more freely and had less of a tendency to weigh and measure her words. She experienced a mild perceptual distortion and a general feeling that the physical surroundings were somewhat fluid. Distances seemed variable. On leaving the analytic hour there was a sense of detachment which the subject felt led to reckless driving and a feeling that nothing would happen. Throughout the day the subject experienced periodic flushing and a feeling of euphoria. The subject was talkative, laughed a great deal and felt rather insensitive about what others might think or say. There was some difficulty in concentrating and a general feeling of restlessness.

Compare with MMDA effects wikipedia: http://en.wikipedia.org/wiki/MMDA_(psychedelic) it is likely that MMDA has multiple mechanisms of action, and probably acts both as a 5HT2A agonist in a similar manner to hallucinogenic amphetamines such as DOM, and also as a serotonin releaser by reversing the direction of the serotonin reuptake transporter in a similar manner to MDMA.

Since the quantity of myristicin ingested by the previous subjects did not reproduce the character or intensity of response elicited by ground nutmeg, the question arose as to whether or not the response is dependent upon myristicin. Accordingly, two of us ingested 10 grams of nutmeg which had been previously deprived of all its volatile constituents. The characteristic psychopharmacologic effects of whole ground nutmeg were eliminated but some undesirable side effects remained. These consisted of occasional flushing, lower intestinal discomfort and unusually heavy sleep in one case; and lower intestinal discomfort and insomnia in the other case. This suggest that the other volatile constituents (safrol, eugenol, etc.) in nutmeg contribute markedly to its psychopharmacologic effect in man.

Edited July 10, 2008 by tregar

[t st tantra]

suggests that 400mg or (6-7mg/kg) is a threshold effective dose for nearly half of the population.

or maybe not everyone can metabolise it effectively?

On leaving the analytic hour there was a sense of detachment which the subject felt led to reckless driving and a feeling that nothing would happen.

so they dosed them and sent them off to drive home!!!

t s t .

[tregar]

Ammonia is produced as a byproduct of muscle activity.

Ammonia is produced as a byproduct of muscle activity. As exercise intensity or exercise duration increases ammonia production rate also increases (Graham et al. 1995). During high intensity exercise ammonia production comes from the purine nucleotide cycle (PNC) this cycle typically occurs in the fast-twitch fibers (MacLean et al. 1991). In prolonged sub-maximal exercise ammonia production comes from the breakdown of branched chain amino acids. The production site for ammonia during branch chain amino acid metabolism is generally in the slow-twitch fibers (Graham et al. 1995). Not much is known about the pathway of ammonia from blood to the sweat glands. Czarnowski and Gorski (1991) theorize that the ammonia in perspiration is due to diffusion from high pH in the blood to a lower pH in the sweat glands.

Yuan and Chan (2000) found that after fifteen seconds of intense sprinting exercise ammonia production is at its peak. Also, during their study higher blood ammonia levels were collected when exercised on the bicycle ergometer than from a treadmill. They theorize that this was due to a larger recruitment of the fast-twitch fibers in relation to running on a treadmill. Ammonia is postulated to play a role in muscle fatigue. Muscular fatigue is commonly defined as a failure to maintain the required or expected force or power output (Fushimi et al. 2001). The causes of muscular fatigue involve specific impairments within the muscle itself, including transmission of the neural stimulus to the muscle at the motor end plate and propagation of that stimulus throughout the muscle. Other events that result in muscle fatigue include disruption of calcium release and uptake within the sarcoplasmic reticulum, substrate depletion and various other metabolic events that impair energy provision and muscle contraction. Fatigue can also result from alterations within the central nervous system (CNS). Although essentially nothing is known about the specific mechanisms underlying this type of fatigue, ammonia build-up in the CNS could lead to altered function, which would impair motor function, lethargy, convulsions, ataxia and even coma (Davis 1995).

Peripheral fatigue may also play a role in muscle fatigue. This occurs at the level of the sarcomere and involves failure at the neuromuscular junction, sarcolemma and transverse tubules. Muscle fatigue desensitizes muscle spindle threshold, thereby decreasing afferent feed-back to the CNS (Meyers et al. 1999).

At rest, the liver removes ammonia as urea (Wagenmakers 1998). During exercise, blood is shunted from the liver and kidneys to supply muscles with more oxygen. This means that the liver is removing little or no ammonia. Some of the ammonia is released into the blood and another portion is retained in the muscle then released into the blood during recovery. Ammonia is also utilized in the formation of alanine and glutamine within the muscle (Czarnowski and Gorski 1991). In the branch chain amino acid cycle an amine group is removed and a carbon skeleton is left. The carbon skeleton is oxidized to make glucose through gluconeogenesis or converted into fat for storage. The amine group picks up another hydronium ion and leaves as ammonia (Houston 1995).

Possible clearance routes for ammonia in the blood are sweat and expiration (Graham et al. 1995). As blood ammonia increases the equilibrium concentrations are changed and the need for ammonia to be cleared increases. Ammonia then diffuses from the plasma to the sweat glands where it is excreted (Czarnowski and Gorski 1991).

Back in the day, several bodybuilders used to make transdermal preparations of testosterone base, they would mix the powdered testosterone base with everclear and spray the solution onto the skin, the transdermal preparation was very effective in transferring approximately 10 to 30% of the test through the skin and into the bloodstream, I even went and had a blood test done at a clinic after spraying such a preparation onto the skin and had my test level checked a few hours later and the blood draw for the lab test came back at an astounding 2200 ng/dl ! compared with my normal test level of 400 ng/dl (which I have had checked on 3 seperate occasions, and each time my normal test was in the low 400's). Other bodybuilders at that time reported similar results from transdermal applications. One on the forum reported around 3400 ng/dl. The tests are not cheap, and run around $80 to do. This only works with testosterone freebase, if an acetate, propionate, or cypionate are attached, then the testosterone molecule then becomes too large to pass the skin barrier into the subcutaneous blood flow beneath. I had only sprayed the solution on my arms. It definately jacked me up. I could feel the mental and physical effects of such a steep rise in a short time quite strongly. The absorption would then remain at a fairly consistent steady state over the next 8 hours or so, when you would then have to reapply the solution to keep it going. There are lots of papers on this, many at http://www.mindandmuscle.net

Testosterone has a molecular weight of 288.4, so it has no problem crossing the skin barrier and making it into the blood stream, Dan Duchaine was the 1st person to experiment with this procedure back in the late 80's. Any molecule less than about 325, is small enough to cross over from what I remember from the article. The transdermal alcohol increases the permeability of the testosterone through the skin barrier by an extra 10 to 15% or more. I also have a bottle of isopropyl myristate, and when 15% of this added to a transdermal isopropyl or everclear solution, it will increase the permeability of small molecules through the skin by another approximately 5 to 7%. A small percentage of added propylene glycol would also increase absorption. But for now, I'll just stick with the everclear solution. For those that don't have access to everclear, 95 to 99% isopropyl works great for transdermal applications as well. When you put the solution onto the skin, the fumes are strong for a few minutes, but have a fan blowing and a window open and it's easier to handle, just don't stand near anything flammable or you're liable to go up in flames.

I dug up a few pounds of fresh sassafras root (very aromatic! but now my back and arms are killing me) from the woods about 1/2 hour from here and put it in freezer in a sealed container, in a few days, I'll take it out of the freezer and wash it off and chop it up and add about 20 to 25 grams to a small jar solution of 95% alcohol (everclear) and let it mix for a couple days, when the time is up, I'll apply the everclear solution to the leg muscles, then do a 20 rep squat routine and some in-place running to see if I can get effects similar to what Torsten experienced from sassafras oil applied to the legs. It is also noted that vigorous muscle activity increases ammonia production in the muscles quite a bit, whether this has any effect on the oxidation and amination process to convert the oil to the corrresponding amphetamine equivalent for a short while is up in the air. Torsten mentions that he has had some very strong mda-like trips lasting 20 to 30 minutes when applying sassafras oil to the muscles back in the day then working out those muscles by running or dancing, so I'm gonna see if I can duplicate his effects.

By the way, safrole has a molecular weight of only 162.1, so it should have no problem crossing the skin barrier and making it into the bloodstream, and what percentage? Possibly anywhere from 40% to 60% or more. Weight of myristicin = 192.2

I should hopefully experience 30 minutes of something akin to an MDA like trip, will see and report back in about 2 weeks.

There is around 80% of safrole in the oil component of sassafras bark root and safrole is soluble in everclear. Torsten mentioned than an alcohol extract should be very effective for extracting the safrole. A high percentage of freebase molecules of small molecular size have an easy time passing the skin barrier and making it into the blood stream, I would imagine especially when using a transdermal alcohol preparation.

Absorption of safrole through monkey and human skin, the paper states around 40% absorption! occured in human skin using a simple transdermal prep consisting of 6% oleth or propylene glycol, whereas without it, they got only 15%. Propylene glycol, isopropyl myristate can be added at 15% to 20% or so to an alcohol transdermal to further increase its effectiveness, they are available by the gallon for less than $20.

http://books.google.com/books?id=KsEUmx-kL...7&ct=result

WARNING: On 9-12-98 three individuals took 1 Tablespoon of Sassafras Essence Oil and two became sick within 20 minutes. Vomiting, and a tired "really crappy" feeling was experienced for 4-5 hours, although they did report triping, just the sickness overpowered the trip most of the time. The third individual was fine, experienced a mild euphoric amphetamine high for about 5-6 hours, upon the onset of the vomiting. It lasted for several hours, but the "trip" was intense and sense of "place in time" was completely lost. They all decided not to take the oil form again. The internal use of the Oil can be fatal.

1 tablespoon = 15ml, crap!!! Torsten only used 1 to 3ml if I remember correctly. No plans here to ingest oil, transdermal application only, and if all goes well according to the study above, 40% and higher absorption will result with the use of just one 6% application of transdermal agent (propylene glycol), this easily goes up to 50 or 60% with more additions...ie everclear, isopropyl alcohol, isopropyl myristate, etc. Expect only 15% absorption if using just the oil by itself. Start low, work up from there. For the sake of science, why not try it at least once with the everclear extract of ground fresh rootbark having soaked. Of course if would be best to use just the boiling point fraction that boils over at 230 degrees C (as this is just the essential oils portion ie what gives the pleasant visual and stimulating effects according to Torsten) but that's not possible yet. Here is an article about log p and transdermals: http://www.mindandmuscle.net/node/71

Torsten: "Rubbing the oil on the leg muscles seemed to be the most effective and efficient method. It reduced any physical discomfort, eliminated flavoured burps, and sped up absorption, the effects of nutmeg (pre 1997 only) and sassafras oil are almost identical to MDA, but only last for about 20 to 30 minutes after strenuous muscle excercise. It is now clear that we only need to look at safrole and myristicin. Given the lower potency of MMDA it may turn out to be mostly a matter of safrole. When the sassafras oil was still freely available it was a popular way of getting the effects--an idea I started after hearing about the bioamination of myristicin. An no, you won't find bioamination of safrole in the papers---you have to do it yourself."

Edited July 23, 2008 by tregar

[knarkkorven]

Good work tregar!

I read about your destillation plans at The Nook, I'm in the process of building a setup myself. Found about 800g parsnip roots a few weeks ago, now stored in my freezer. Also, I've ead reports from other swedes getting a stoned, trippy feeling from 20-30g fresh roots. Looks promising!

what a pointless paper. why didn't he just analyse the gingerbread or compare raw gingerbread with cooked gingerbread [via bioassay]

Yes, I thought the same thing. lots of hypothesis without any evidence or experiments to make something out of it...

Edited July 23, 2008 by knarkkorven

[tregar]

Thanks knarkkorven. Good luck with your setup as well in the future.

Torsten random comments "Rubbing the oil on the leg muscles seemed to be the most effective and efficient method. It reduced any physical discomfort, eliminated flavoured burps, and sped up absorption, the effects of nutmeg (pre 1995 only) and sassafras oil are almost identical to MDA, but only last for about 30 minutes after strenuous muscle excercise. It is now clear that we only need to look at safrole and myristicin. Given the lower potency of MMDA it may turn out to be mostly a matter of safrole. When the sassafras oil was still freely available it was a popular way of getting the effects--an idea I started after hearing about the bioamination of myristicin. An no, you won't find bioamination of safrole in the papers---you have to do it yourself."

I'll report back with the results of my experiments in a couple weeks. Some more interesting news:

If you ingest a BCAA (branch chained amino acid) supplement, approximately 77mg per kg of body weight (5 to 6 grams) before and/or after you exercise, you can effectively double the amount of ammonia that is produced by the muscles (as well as reduce the breakdown of muscle tissue so it grows larger), so if the amination process (also) takes place in or near muscle tissue (as Torsten suspects) then you "could perhaps" effectively double the conversion rate of safrole to MDA via the biogenic oxidation/amination process. Also I believe that using an effective transdermal prep will keep the conversion process at a relatively stable level, so you may actually get several hours of activity instead of just 30 minutes, as there is a constant turnover taking place for approximately 4 hours or more from the use of the constant rate of transdermal absorption once steady state is reached, but there is no way to know for sure until the experiments are done with the everclear extracts of the sassafras roots applied transdermally, as safrole is soluble in alcohol. My transdermal prep consists of 85% everclear and 15% isopropyl myristate. 20 grams of aromatic fresh root bark chips have been soaking in the 100% everclear (95% ethanol, 5% water) for a couple days, then 15% isopropyl myristate is added and the mixture mixed and applied to thigh muscles with vigorous muscle activity of the leg muscles to take place.

Branched-chain amino acids augment ammonia metabolism. Contribution of BCAA in ammonia production:

net ammonia production after 1 leg muscle exercised: 1,112 mumol/kg

net ammonia production when taking BCAA supplement at 77mg/kg (and exercising same leg muscle) = 1,670 mumol/kg

Something else to experiment with would be the ingestion of an arginine supplement to trigger nitric oxide production.

Medline:

Branched-chain amino acids augment ammonia metabolism while attenuating protein breakdown during exercise.

MacLean DA, Graham TE, Saltin B.

School of Human Biology, University of Guelph, Ontario, Canada.

In this study, five men exercised the knee extensor muscles of one leg for 60 min (71 +/- 2% maximal work capacity) with and without (control) an oral supplement (77 mg/kg) of branched-chain amino acids (BCAA). BCAA supplementation resulted in a doubling (P < 0.05) of the arterial BCAA levels before exercise (339 +/- 15 vs. 822 +/- 86 microM). During the 60 min of exercise, the total release of BCAA was 68 +/- 93 vs. 816 +/- 198 mumol/kg (P < 0.05) for the BCAA and control trials, respectively. The intramuscular BCAA concentrations were higher (P < 0.05) for the BCAA trial and remained higher (P < 0.05) throughout exercise. In both trials, substantial quantities of NH3 were released, and when NH3 production equivalent to IMP accumulation was subtracted the net NH3 production was 1,112 +/- 279 and 1,670 +/- 245 mumol/kg (P < 0.05) for the control and BCAA trials, respectively. In contrast, the release of the essential amino acids (EAA) was much lower for the BCAA than the control trial (P < 0.05). When the BCAA were subtracted from the EAA (EAA-BCAA), the total release of EAA minus BCAA was lower (P < 0.05) for the BCAA (531 +/- 70 mumol/kg) than the control (924 +/- 148 mumol/kg) trial. These data suggest that BCAA supplementation results in significantly greater muscle NH3 production during exercise. Furthermore, the increased intramuscular and arterial BCAA levels before and during exercise result in a suppression of endogenous muscle protein breakdown during exercise.

Edited July 25, 2008 by tregar

[Torsten]

Torsten random comments "Rubbing the oil on the leg muscles seemed to be the most effective and efficient method. It reduced any physical discomfort, eliminated flavoured burps, and sped up absorption, the effects of nutmeg (pre 1995 only) and sassafras oil are almost identical to MDA, but only last for about 30 minutes after strenuous muscle excercise. It is now clear that we only need to look at safrole and myristicin. Given the lower potency of MMDA it may turn out to be mostly a matter of safrole. When the sassafras oil was still freely available it was a popular way of getting the effects--an idea I started after hearing about the bioamination of myristicin. An no, you won't find bioamination of safrole in the papers---you have to do it yourself."

I need to add a few things to this.

1) Rubbing on muscle is the best method in reference to nausea and in the hieght of the peak that is possible. However my wording that it is the most efficient would not hold up when you are considering quantity of oil. Ingestion of these oils will probably always require less substance than external application. However, I think that even though more is applied to the outside of the body, the amount in the bloodstream is probably less than when ingested. So, if you have any consideration for your liver then external wins on more fronts than internal.

2) Myristicin and safrole are not the only actives, but what I was trying to point out was that the allylbenzenes are the substances to aim for [this would include many other allylbenzenes, such as apiol, dillapiol, sarisan, croweacin, etc. The other constituents of nutmeg and sassfras oil have other effects - mostly sedative.

The one thing that puzzles me about all of this is the duration of effect. If MDA [or whatever essential amphetamine] is made in the muscles, but the effect is in the brain, then there would need to be a certain level of drug in the bloodstream to elicit effects. Once such a level is attained one would expect the experience to last the same time period as if the substance was injected into the blood. ie, if it takes 10mg of iv MDA to have a good [unmistakable] experience, then a similar biogenic experience would have to also have attained a level of 10mg of MDA in the blood. So if a 10mg iv experience lasts 4 hours, why does the comparable biogenic experience only last 30 minutes?

Could it be that the muscles only do the first step of the conversion, so that there is actually no MDA in the blood, while the brain does the second part of the conversion, but only at a tiny rate. That would mean testing for MDA in the blood would be futile. Rather one would have to test for MDA metabolites to show how much of the allylbenzene was converted to MDA and then metabolised.

[tregar]

Good to hear from you Torsten. The duration of the effect that has been reported is the only thing that bothers me too.

This is from that gingerbread paper further into it, but I don't know if it has anything at all to do with duration:

When oral administration of myristicin, safrole, isosafrole, elemicin, eugenol was made in either rats or guinea pigs, the animals became "highly active and excited" in the first 15 to 30 minutes post dose, thereafter the animals became "very sedated, immobile and non-responsive to sound and motion for up to 2 hours".

The implicit suggestion of these authors is that amphetamine-like metabolites are formed from allybenzenes only transiently, and then converted to the observed aminopropiophenone urinary metabolites, with a corresponding alteration of pharmacological response.

The key word I pick up from the paper is "transient", but still it makes no sense that the "good effects" would be only transient. I'll go ahead and attach the paper whether it matters or not. Is the implicit suggestion of the authors correct?

When bodybuilders used the 85% ethanol and 15% isopropyl transdermal with testosterone base that was sprayed onto the skin, (this was a concotion known as "androsol") a steady state level of penetration of the testosterone was reached quickly within 1/2 to 1 hour and then steady continuous penetration of it through the skin barrier into the subcutaneous bloodstream beneath was possible for many hours (around 6 hr before it had to be reapplied again), so I'm wondering if it is somehow possible for safrole to achieve a similar conversion rate for many hours since we know that it should be possible to get a steady penetration rate with safrole as well, as the study I linked to earlier showed a 40% penetration of safrole through skin with just a primitive transdermal formula consisting of only 6% propylene glycol mixed with the safrole was applied to skin....who know? maybe or maybe not. It would be nice if the effects would last longer than 20 to 30 minutes. I'll try and get down experientially to the bottom of this and let you know what I find from the experiments. The nice thing about safrole as well is that the molecular weight is very small, much smaller than even testosterone base, so it has no problem penetrating the skin--the study found 15% penetration of safrole through the skin barrier all by itself when applied, but then it jumped to 40% penetration when mixed with only a small amount of propylene glycol. But the "duration" is the main thing that I'm curious about as well.

Still, the following experiences are interesting as they show a longer duration of experience perhaps possible:

Experience of one of the four subjects who had a "definite" prolonged reaction to oral myristicin 400mg: (unable to post entire paper as it takes up more than required upload memory due to photo copy) "The Pharmacology of Myristicin, A Contribution to the Psychopharmacology of Nutmeg" reference:

The subject took her 400mg capsule of myristicin at 7:30 am. At 8:45 during a psychoanalytic hour there was flushing, sweating, a sense of light-headedness and a feeling of being detached. The subject felt that she talked more freely and had less of a tendency to weigh and measure her words. She experienced a mild perceptual distortion and a general feeling that the physical surroundings were somewhat fluid. Distances seemed variable. On leaving the analytic hour there was a sense of detachment which the subject felt led to reckless driving and a feeling that nothing would happen. Throughout the day the subject experienced periodic flushing and a feeling of euphoria. The subject was talkative, laughed a great deal and felt rather insensitive about what others might think or say. There was some difficulty in concentrating and a general feeling of restlessness.

Experience of one of the other subjects who took 400mg myristicin:

About 2 hours after taking the drug, this subject noticed a mild feeling of increased altertness. The subject was more free in making comments at a staff conference than usual and in general felt more wide awake during the morning and immediately after lunch than is usual. There was a slight feeling of restlessness but no tachycardia. At one point there was a rather unusual feeling of tingling and numbness about the face and the mouth, this was rather mild and lasted only a few moments. Sixteen hours after taking the drug, the subject suffered an attack of diarrhea.

the_Potential_Role_of_Mood_Elevating_Amphetamine_like_Compounds_Formed_in_vivo_and_in_furno.pdf

the_Potential_Role_of_Mood_Elevating_Amphetamine_like_Compounds_Formed_in_vivo_and_in_furno.pdf

the_Potential_Role_of_Mood_Elevating_Amphetamine_like_Compounds_Formed_in_vivo_and_in_furno.pdf

Edited July 25, 2008 by tregar