Version 1.24
IMPORTANT
Many people around the world are actively contributing to expanding the science of Oilahuasca. It has not been perfected yet. What's presented here works very well for some individuals. However, countless tests have shown that there are individuals who simply cannot get effects from any allylbenzenes no matter which set of known activators they use. The exact reason for this is currently unknown. We are still searching for Oilahuasca activation formulas that will work for more people.
For 24 hours prior to using oilahuasca you must follow the Oilahuasca Diet restrictions.
For a list of herbal formulas, supplements, and dietary restrictions known to be effective in obtaining psychedelic effects from allylbenzenes please see the article Oilahuasca Activators.
THIS PAGE EXPLAINS THE OILAHUASCA THEORY. MANY FACTS ARE PRESENTED TO SUPPORT THE OILAHUASCA THEORY. HOWEVER ALL SECTIONS ON THIS PAGE SHOULD BE TREATED AS THEORETICAL UNLESS STATED AS FACT.
THIS IS A WORK IN PROGRESS. IT WILL BE UPDATED AS NEW DATA IS AVAILABLE. TO LEAVE FEEDBACK FOR THIS PAGE USE THE DISCUSS LINK AT THE BOTTOM OF THIS ARTICLE.
THE FACTS BEHIND OILAHUASCA
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
Herbs containing allylbenzenes, such as nutmeg, can produce psychedelic effects under certain circumstances. This is well documented.
Several allylbenzenes have been proven to form up to 3 alkaloid metabolites after ingestion by several animals.[2][3] They do not form amphetamines in vivo as has been speculated in the past. The alkaloids detected in animal urine are tertiary aminopropiophenones of 3 possible subtypes: dimethylamines, piperidines, and pyrrolidines.[1][2][3][4]
The allylbenzene elemicin has been proven to form all 3 different alkaloid metabolites after ingestion in animals by analyzing urine using gas-liquid chromatography and chemical ionization mass spectrometry.[1]
Safrole is also proven to form all three alkaloid metabolites after ingestion.[2]
Myristicin appears to only form piperidines and pyrrolidines. Dimethylamines of myristicin have not been detected.[3]
Allylbenzene, from which all allylbenzenes are derived, forms piperidine and dimethylamine alkaloids.[4]
Propenylbenzene and its derivatives (asarone, anethole, etc.) do not form alkaloid metabolites.[4]
While it is a fact that allylbenzenes do form alkaloids in vivo, just how this occurs is currently unknown. The current facts show that allylbenzenes first form 1'-hydroxy metabolites, and then these form 1'-oxo metabolites. The 1'-oxo metabolites probably then condense with endogenous amines in vivo without enzymatic activity. The 1'-oxo metabolite 1'-oxosafrole of the allylbenzene safrole, for example, is proven to form alkaloid adducts by simply mixing it together at room temperature with endogenous amines such as dimethylamine, piperidine, and pyrrolidine without the need for enzymatic action.[8][9] This is probably the route by which these alkaloids occurs in vivo, but this is not yet proven.
The oilahuasca theory attempts to explain this process, and appears to work using enzyme inhibitors and inducers which are shown to help coerce the human body into creating allylbenzene alkaloid metabolites in vivo.
BASIC OILAHUASCA THEORY
THIS SECTION IS THEORETICAL
NOTE: THIS DOCUMENT CONTAINS OUTDATED INFORMATION. UPDATES ARE PENDING.
The oilahuasca activation theory was originally put together by 69ron with the help of many other active forum members of herbs.maxforum.org and www.drugs-forum.com who also took part in most of the human tests done which have shown the oilahuasca activation theory appears to be a working model. The theory is still evolving as new information arrives. The current theory incorporates some elements that originated from Oswald and Peele's activation theory, as well as research by many other individuals.
The current oilahuasca theory states that all allylbenzenes must first be converted into alcohols by hydroxylation of either the 1 position of the tail or the 3 position, and then converted to either phenyl vinyl ketones or aldehydes which then condense with dimethylamine, pyrrolidine, or piperidine to form one of three corresponding alkaloid metabolites.
Many enzymes are present in humans which cause allylbenzenes to form inactive metabolites. In some people these inactive metabolites far out number the active ones, leading to little or no activity. While in others their digestive systems consistently form the active alkaloid metabolites in abundance, leading to psychoactivity.
Compounds that help activate these allylbenzenes are collectively referred to as oilahuasca activators. In essence these activators work by inhibiting enzymes which prevent activation while inducing enzymes that help activation.
The current oilahuasca theory states that the Cytochrome P450 enzymes CYP2A6, CYP2C9, CYP2E1, and sometimes CYP1A2 help activate allylbenzenes, and therefor should be induced. The primary enzymes to inhibit are CYP2D6, CYP3A4 and sometimes CYP1A2. This forces 1'-hydroxylation, and possibly 3'-hydroxylation of the allylbenzene tails turning them into alcohols.
Once the allylbenzenes are in their 1'-hydroxylated alcohol form, they are vulnerable to attack by UGT and SULT, so these must be inhibited so that they can then be converted to phenyl vinyl ketones by the action of 17bHSD2. If they are in their 3'-hydroxylated form they can still probably be attacked by UGT and SULT, so these should probably be inhibited so that they can be turned into aldehydes by a currently unknown enzyme action (probably also the action of 17bHSD2).
Once the allylbenzenes are in their phenyl vinyl ketone form they can be inactivated by the action of GST and probably aldehyde dehydrogenase, aldehyde oxidase, xanthine oxidase, and related enzymes. Therefore these enzymes should be inhibited. Another stumbling block present is possibly aldose reductase. This enzyme converts aldehydes back into alcohols and might do the same for phenyl vinyl ketones. Therefore aldose reductase should also probably be inhibited.
If allylbenzenes are in their aldehyde form, they can be inactivated by conversion into carboxylic acids by several enzymes which may include aldehyde dehydrogenase, aldehyde oxidase, xanthine oxidase, and related enzymes. Therefore these enzymes should be inhibited. Another stumbling block present is aldose reductase. This enzyme converts the aldehydes back into alcohols. Therefore aldose reductase should also be inhibited. GST is likely to also be a problem and should be inhibited.
The final step in activation is to provide piperidine, pyrrolidine, or dimethylamine for the phenyl vinyl ketones or aldehydes to condense with. If piperidine, dimethylamine, or pyrrolidine are not present, alkaloids cannot form, and the phenyl vinyl ketones or aldehydes are eventually metabolized into other inactive compounds.
For proper oilahuasca activation we therefore must have 17bHSD2 induced, supply NAD+ for 17bHSD2 as a coenzyme, induce the P450 enzymes CYP2A6, CYP2C9, and CYP2E1 (and sometimes CYP1A2) while inhibiting all other P450 enzymes, inhibit UGT, SULT, GST, aldehyde dehydrogenase, aldehyde oxidase, xanthine oxidase, and aldose reductase, and we must supplement with piperidine, dimethylamine, pyrrolidine, or similar amines.
THE OILAHUASCA ACTIVATION SEQUENCE
The theoretical activation sequence given in this example applies to all allylbenzenes (myristicin, safrole, etc.). In this example we use the allylbenzene elemicin.
There are two distinct sequences which are believed to lead to activity.
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
SEQUENCE A (based on work by Oswald)
NEW EVIDENCE IS SHOWING PROBLEMS IN THE SEQUENCE A THEORY
Sequence B (based on work from the Oilahuasca pioneers) appears to have more evidence to support it than Sequence A (based on work by Oswald) in humans. Unlike Sequence A, one of the alkaloid metabolites in Sequence B is proven to occur in humans. The 3 end alkaloid metabolites in the Sequence A theory are only proven to be created in animals in vivo. There is of yet no evidence to suggest that they occur in humans.
Metabolites from steps 1-3 are proven steps to occur. How Sequence A is supposed to go from step 3 to step 4 is currently unknown. And no supporting evidence has yet been found for this to happen in humans.
Over the past few years, an overwhelming amount of test results seem to indicate that Sequence A probably does not work in humans. Human Oilahuasca tests seem to point in the direction of Sequence B being the more likely activation sequence.
A big problem with Sequence A is step 2. Inhibiting CYP2C9 and CYP1A2 has been shown countless times to help activate allylbenzenes. The claimed potent inhibitors of CYP2A6, such as safrole, benzaldehyde and cinnamaldehyde also appear to be beneficial. These enzymes are known to 1'-hydroxylate allylbenzenes. If CYP2C9 and CYP1A2 are not inhibited, the chance of getting the "melatonin" effect of improperly activated elemecin is very high. It's very likely that 1'-hydroxyelemicin is the compound that causes the "melatonin" effect. Both caffeine and berberine help activate nearly all allylbenzenes. Caffeine inhibits CYP1A2. Berberine is a potent Oilahuasca admixture. It is proven to strongly inhibit CYP2C9, and also inhibit CYP2D6, and CYP3A4. The fact that inhibiting CYP2C9 and CYP1A2, and potentially inhibiting CYP2A6 is beneficial seems to indicate that 1'-hydroxylation is a route to inactivation, and not a route to activation.
SEQUENCE A - STEP 1: ORAL INGESTION (OR TOPICAL APPLICATION)
Elemicin is ingested orally (or applied topically to the skin).
SEQUENCE A - STEP 2: CONVERSION TO AN ALCOHOL
Some
elemicin is 1'-hydroxylated to the alcohol
1'-hydroxyelemicin. For most
allylbenzenes this is performed by
CYP1A2,
CYP2A6,
CYP2C9 and
CYP2E1 to some degree.
SEQUENCE A - STEP 3: CONVERSION TO A PHENYL VINYL KETONE
1'-hydroxy-elemicin is oxidized to the phenyl vinyl ketone
1'-Oxoelemicin by
17bHSD2.
SEQUENCE A - STEP 4: CONVERSION TO ALKALOIDS
The alkaloids that form in this section have been detected in vivo. But how exactly they form from 1'-oxoelemicin is unknown. A transaminase enzyme may be required, or 1'-oxoelemicin might condense spontaneously to form alkaloids.
1'-Oxoelemicin may condense with available
dimethylamine to form the
alkaloid adduct
1'-oxoelemicin-DMA, also known as
3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)propan-1-one.
1'-Oxoelemicin may condense with available
piperidine to form the
alkaloid 3-piperidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one.
1'-Oxoelemicin may condense with available
pyrrolidine pyrrolidine to form the
alkaloid 3-pyrrolidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one.
Of the possible alkaloid metabolites, the dimethylamine form has the lowest lipid solubility and the piperidine form has the highest lipid solubility. Therefore, the piperidine alkaloid form will more easily cross the blood brain barrier.
Of the possible alkaloid metabolites, the dimethylamine form is the most likely to be vulnerable to attack by MAO-A or MAO-B enzymes. Dimethylamines are often primary substrates of MAO. For example N,N-dimethyltryptamine and N,N-dimethyl-4-hydroxyphenylethylamine (hordenine) are primary substrates of MAO.
At this time it is not known which of the possible alkaloid metabolites might be the main active metabolite for each of the allylbenzenes. Other amines may also form.
It’s important to note that in the case of the allylbenzene myristicin, piperidine and pyrrolidine metabolites have been detected but dimethylamine metabolites have not. This indicates that the dimethylamine metabolites might possibly be more vulnerable to attack by enzymes such as MAO-A, MAO-B, etc., leading to their complete destruction prior to being excreted in urine.
THIS SECTION IS THEORETICAL
SEQUENCE B (based on work from the Oilahuasca pioneers)
Sequence B appears to have more evidence to support it than Sequence A in humans. Unlike Sequence A, one of the alkaloid metabolites in Sequence B is proven to occur in humans. Some of the alkaloid metabolites theoretically created by Sequence A have only been found in some animals so far.
Please note that steps 1-3 are proven to occur for some allylbenzenes such as methyl eugenol. Step 4 is a proven alkaloid metabolite for methyl chavicol (see the article 4-Methoxycinnamoylglycine for more details). These sequences will lead to similar alkaloids as produced in Sequence A. In Sequence A the step before alkaloid creation is a ketone. Ketones tend not to form adducts as easily as aldehydes. Because step 3 is an aldehyde in Sequence B, this greatly increases the likelihood of alkaloids forming in vivo. Many aldehydes such as cinnamaldehyde are proven to form adducts with amino acids and other amines very easily without the need for a catalyst. See the article Cinnamaldehyde for more details on aldehyde adducts.
For activation Sequence B, it's important to inhibit the 1'-hydroxylation pathway. This is theorized to be a route to inactivation. Enzymes known to cause 1'-hydroxylation include CYP1A2, CYP2A6, and CYP2C9.
SEQUENCE B - STEP 1: ORAL INGESTION (OR TOPICAL APPLICATION)
Elemicin is ingested orally (or applied topically to the skin).
SEQUENCE B - STEP 2: CONVERSION TO AN ALCOHOL
Elemicin is 3'-hydroxylated to the alcohol 3'-hydroxyisoelemicin. The enzymes responsible for this action are currently unknown but theorized to be CYP2E1 and possibly other enzymes.
SEQUENCE B - STEP 3: CONVERSION TO AN ALDEHYDE
3'-Hydroxyisoelemicin is oxidized to the aldehyde 3,4,5-Trimethoxycinnamaldehyde (also known as 3'-oxoelemicin) possibly by 17bHSD2, CYP2E1, or alcohol dehydrogenase.
SEQUENCE B - STEP 4: CONVERSION TO ALKALOIDS
The alkaloids in this section are purely theoretical for elemicin, but a glycine adduct alkaloid metabolite has been proven for methyl chavicol. The glycine metabolite 4-Methoxycinnamoylglycine is found in human urine after ingestion of methyl chavicol (see the article 4-Methoxycinnamoylglycine for more details). This is very strong evidence for the theoretical glycine alkaloid metabolite also being created in humans after the ingestion of elemicin.
A proposed alternate glycine adduct is {(Z)-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]amino}acetic acid. Cinnamaldehyde is known to create a similar adduct with potassium glycine. See the Cinnamaldehyde article for more details.
Theoretical alternate glycine adduct alkaloid metabolite of elemicin |
alkaloid adduct made from mixing potassium glycine and cinnamaldehyde |
{(Z)-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]amino}acetic acid |
CHEMBL3752982 |
 |
![potassium_%7B(E)-[(2E)-3-phenyl-2-propen-1-ylidene]amino%7Dacetate.png](http://herbpedia.wdfiles.com/local--resized-images/attachments/potassium_%7B(E)-[(2E)-3-phenyl-2-propen-1-ylidene]amino%7Dacetate.png/medium.jpg) |
3-(3,4,5-Trimethoxyphenyl)propionic acid is a metabolite of elemicin found in rat urine. 3-(3,4,5-Trimethoxyphenyl)propionic acid is a product that would form from the action of monamine oxidase enzymes on 1-(3,4,5-trimethoxycinnamoyl)dimethylamine, indicating that 1-(3,4,5-trimethoxycinnamoyl)dimethylamine formed in the rats but was enzymatically converted to 3-(3,4,5-trimethoxyphenyl)propionic acid by monamine oxidase enzymes before being excreted into the urine.
The following alkaloids are theorized to be possible active metabolites of elemicin made from it's aldehyde metabolite 3,4,5-trimethoxycinnamaldehyde forming adducts with the endogenous amines dimethylamine, piperidine, and pyrrolidine, all of which are abundant amines in humans.
Theoretical dimethylamine adduct alkaloid metabolite A |
Theoretical dimethylamine adduct alkaloid metabolite B |
1-(3,4,5-Trimethoxycinnamoyl)dimethylamine |
(2E)-N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-iminium |
dimethylamine.png/medium.jpg) |
-N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-iminium.png/medium.jpg) |
Theoretical piperidine adduct alkaloid metabolite A |
Theoretical piperidine adduct alkaloid metabolite B |
1-(3,4,5-Trimethoxycinnamoyl)piperidine |
1-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]piperidin-1-ium |
piperidine.png/medium.jpg) |
![1-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]piperidin-1-ium.png](http://herbpedia.wdfiles.com/local--resized-images/attachments/1-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]piperidin-1-ium.png/medium.jpg) |
Theoretical pyrrolidine adduct alkaloid metabolite A |
Theoretical pyrrolidine adduct alkaloid metabolite B |
1-(3,4,5-Trimethoxycinnamoyl)pyrrolidine |
1-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]pyrrolidin-1-ium |
pyrrolidine.png/medium.jpg) |
![1-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]pyrrolidin-1-ium.png](http://herbpedia.wdfiles.com/local--resized-images/attachments/1-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-ylidene]pyrrolidin-1-ium.png/medium.jpg) |
OILAHUASCA ACTIVATION VIA ENZYME MANIPULATION
This section details all the known enzymes to induce and inhibit in order to optimize the psychedelic and/or stimulant actions various allylbenzenes are capable of producing when fully activated. In some people allylbenzenes are extremely difficult to activate. Failure to follow these guidelines completely can lead to little or no effects from the various allylbenzenes available.
The single most important enzyme to induce is Estradiol 17beta dehydrogenase type 2 (17bHSD2). This enzyme is required. If 17bHSD2 is inhibited by drinking tea or consuming other drinks, supplements, or food items that inhibit 17bHSD2, then allylbenzenes activation will not take place. Without the action of 17bHSD2, allylbenzenes cannot form alkaloids in vivo.
For additional information on inducers and inhibitors used successfully by several individuals see the article: Oilahuasca Activators
17bHSD2 Induction
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
Estradiol 17beta dehydrogenase type 2 (17bHSD2) oxidative action needs to be induced. This enzyme creates phenyl vinyl ketones from allylbenzenes in their 1'-hydroxy form. For example, the phenyl vinyl ketone 1'-oxoestragole is proven to be created from the alcohol 1'-hydroxyestragole (a metabolite of the allylbenzene methyl chavicol) by the action of estradiol-17beta-dehydrogenase Type 2 (17bHSD2).[13] This metabolite is then proven to be capable of forming adducts with glutathione (GSH) leading to inactivation, or forming adducts with endogenous amines.[13] The latter action is believed to be required for the psychedelic effects of methyl chavicol and related allylbenzenes.
For information on 17bHSD2 inducers and inhibitors see the article here: Estradiol 17beta dehydrogenase type 2
UGT1A9 And UGT2B7 Inhibition
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UGT1A9 and UGT2B7 are proven to inactivate allylbenzenes once in their 1'-hydroxy form. These add a glycosyl group to an available hydroxy position on hydroxylated allylbenzenes making them inactive. For example, it turns 1'-hydroxyelemicin into 1'-hydroxyelemicin glucuronide. Inhibitors must be used. UGT2B7 is more important to inhibit than UGT1A9. For information on inhibitors see their articles here: UGT1A9, UGT2B7.
The metabolite of methyl chavicol known as 1'-hydroxyestragole is proven to undergo glucuronidation primarily by the action of UGT2B7 followed by UGT1A9, with a very small amount carried out by UGT2B15.[14] These enzymes are assumed to be responsible for the glucuronidation of all related allylbenzenes.
Substrate |
UGT |
End Product |
1'-Hydroxyelemicin |
|
1'-Hydroxyelemicin glucuronide |
 |
|
 |
Cofactor |
|
Byproduct |
UDPglucuronate |
|
UDP |
SULT1A1 And SULT1A3 Inhibition
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
SULT1A1 and SULT1A3 are proven to inactivate allylbenzenes once in their 1'-hydroxy form. For example, the alcohol 1'-hydroxyelemicin becomes 1'-sulfoxyelemicin by these enzymes. Inhibitors must be used. For information on inhibitors see the articles here: SULT1A1, SULT1A3.
The metabolite of methyl chavicol known as 1'-hydroxyestragole is preven to undergo sulfation by the action of SULT1A1 and SULT1A3.[15] These pathways prevent 1'-oxoestragole from forming. These enzymes are assumed to be responsible for the sulfation of all related allylbenzenes.
Substrate |
SULT |
End Product |
1'-Hydroxyelemicin |
|
1'-Sulfoxyelemicin |
 |
|
 |
Cofactor |
|
Byproduct |
3'-phosphoadenylylsulfate |
|
adenosine 3',5'-bisphosphate |
GST Inhibition and Glutathione Depletion
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
Glutathione is proven to inactivate allylbenzenes once in their phenyl vinyl ketone form. For example, the phenyl vinyl ketone 1'-oxoestragole is proven to be inactivated by forming adducts with glutathione.[13]
GST adds glutathione to the 1'-oxo position of the phenyl vinyl ketones making them unable to form alkaloids. For example, it turns 1'-oxoelemicin into 3'-(glutathion-S-yl)-1'-oxoelemicin by the addition of glutathione preventing alkaloid formation by 1'-oxoelemicin.
It's not known to what degree glutathione S-transferase (GST) is involved in this inactivation.
Glutathione is proven to condense with phenyl vinyl ketones without the need for enzyme interaction (see the article 1'-Oxoestragole for more details). This means inhibiting glutathione S-transferase (GST) is not enough. We also need to deplete glutathione to prevent it from inactivating allylbenzenes (see the article Glutathione for details on ways to safely deplete glutathione).
There are several subsets of glutathione S-transferase (GST). The exact ones responsible for this action are currently unknown, as is there level of interaction in this adduct process. Inhibitors must be used. For information on inhibitors see the article here: Glutathione S-transferase.
CYP1A2, CYP2A6, CYP2C9, and CYP2E1
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
CYP1A2, CYP2A6, CYP2C9, and CYP2E1 play a pivotal role in 1'-hydroxylation of many allylbenzenes, creating alcohol. This is the first major step towards activation. However, this is not the only action each of these enzymes can perform. Many human based Oilahuasa tests have shown that CYP1A2 has undesirable effects on most allylbenzenes. CYP1A2 can perform ALDH-like activity, which is not good. CYP1A2 can also demethylenate myristicin, and probably other methylenedioxy allylbenzenes. Elemicin's non-psyechedelic "malatonin" effect appears to be primarily caused by the action of CYP1A2. The only allylbenzene believed to require CYP1A2 for 1'-hydroxylation is methyl eugenol. Very few Oilahuasca tests are being done with methyl eugenol currently. For all of the other allylbenzenes CYP1A2 appears to be very detrimental. And despite some tests showing that CYP1A2 is needed for 1'-hydroxylation of methyl eugenol, it's possible the tests are incomplelete, and another enzyme can also perform this in humans.
The alcohol 1'-hydroxyestragole is proven to be created from the allylbenzene methyl chavicol in human liver in vitro primarily by the P450 enzymes CYP1A2, CYP2A6 and CYP2E1.[12][13] However, several Oilahuasca tests with methyl chavicol have shown CYP1A2 to be detrimental.
In humans the alcohol 1′-hydroxymethyleugeol is proven to be created from the allylbenzene methyl eugenol by the P450 enzyme CYP1A2.[12] Some in vitro reports state that it is primarily catalyzed by both CYP1A2 and CYP2C9 and that CYP2C19 and CYP2D6 also play a minor role.[11] Human liver in vitro tests show that methyl eugenol is not metabolized by CYP2A6.[11]
The alcohol 1'-hydroxysafrole is proven to be created from the allylbenzene safrole by the P450 enzymes CYP2C9 and CYP2E1, and to a lesser degree CYP2A6 and CYP2D6 according to one human in vitro study.[10] Several Oilahuasca tests with safrole have shown CYP1A2 to be detrimental.
Substrate |
1'-hydroxylation |
End Product |
Elemicin |
|
1'-Hydroxyelemicin |
 |
|
 |
CYP3A4
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
CYP3A4 is proven to O-demethylenate the allylbenzene myristicin, an action that breaks the methylenedioxy group of myristicin, replacing it with 2 hydroxy groups.[17] The cytochrome P450 enzyme CYP1A2 plays a minor role in this action. Therefor CYP3A4 needs to be inhibited for myristicin and probably other allylbenzenes with methylenedioxy groups. All allylbenzenes that are O-demethylenated are not known to have psychedelic action. This enzyme may also have some undesirable effects on other allylbenzenes without methylenedioxy groups.
Substrate |
O-demethylenation |
End Product |
Myristicin |
|
Demethylenyl myristicin |
 |
|
 |
CYP2D6
THIS SECTION IS BACKED BY SCIENTIFIC FACTS
The allylbenzene eugenol is proven to be O-demethylated to hydroxychavicol by the action of CYP2D6 in vitro.[16] CYP2D6 performs this action on hundreds of compounds and very likely also performs this action on other allylbenzenes and should therefor be strongly inhibited. No allylbenzene that is O-demethylated is known to have psychedelic action.
Substrate |
O-demethylation |
End Product |
Elemicin |
|
Methoxyeugenol |
 |
|
 |
CYP2B6
THIS SECTION IS PARTIALLY BACKED BY SCIENTIFIC FACTS
CYP2B6, CYP3A4, CYP1A2, and CYP2J2 but not CYP2E1 can all perform ALDH-like activity.[18] They should therefor probably be strongly inhibited. ALDH-like action directly interferes with the two main activation theories presented on this page. For more details on this type of ALDH-like action of cytochrome P450 enzymes see the article here: Aldehyde Dehydrogenase
SSAO Inhibition
THIS SECTION IS BASED ON ANECDOTAL DATA ONLY
SSAO inhibitors appear to be greatly beneficial for
elemicin,
methyl chavicol,
methyl eugenol and possibly several other
allylbenzenes.
SSAO inhibitors work at any point during the effects, giving a very noticeable boost in effects for elemicin, methyl chavicol, methyl eugenol and possibly several other allylbenzenes. SSAO inhibitors can even bring back the effects if taken shortly after the effects of the allylbenzenes appear to have subsided.
The exact reason for potentiation by SSAO inhibition is unknown.
SSAO is not capable of deaminating dimethylamine, piperidine, or pyrrolidine alkaloids. It deaminates only simple amines such as mescaline, phenethylamine, methylamine and similar compounds. It's possible that some ammonia adducts form in vivo from allylbenzenes such as 1'-oxoelemicin-amine, or 1'-oxoelemicin-PEA, which could be substrates of SSAO.
For details on SSAO inhibitors and inducers please see the article found here: SSAO.
Alcohol Dehydrogenase (ADH)
THIS SECTION IS HIGHLY THEORETICAL
Alcohol dehydrogenase (as well as alcohol oxidase) should convert the 3-hydroxyl alcohol forms of allylbenzenes into their aldehyde forms which can then possibly be aminated to form dimethylamine, piperidine, and pyrrolidine alkaloids. CYP2E1 may also have the same action as alcohol dehydrogenase. For this reason alcohol dehydrogenase and possibly CYP2E1 should not be inhibited. Note that 17bHSD2 performs this action for phenyl vinyl ketones and might also perform this action on the aldehyde forms of allylbenzenes. There is currently no evidence showing which enzyme preforms this action on the aldehyde forms of allylbenzenes, although the action is proven to take place.
For details on alcohol dehydrogenase inhibitors to avoid see the article here: Alcohol Dehydrogenase
Aldehyde Dehydrogenase (ALDH)
THIS SECTION IS HIGHLY THEORETICAL
Anecdotal reports have shown that aldehyde dehydrogenase and similar enzymes (such as xanthine oxidase and aldehyde oxidase) which hydroxylate aldehydes into acids contribute to the inactivation of allylbenzenes.
CYP2B6, CYP3A4, CYP1A2, and CYP2J2 but not CYP2E1 can all perform ALDH-like activity and should therefor probably be strongly inhibited. ALDH-like action directly interferes with the two main activation theories presented on this page. CYP1A2 might be needed for the activation of certain allylbenzenes such as methyl eugenol. In this case it might be best not to inhibit CYP1A2.
For details on aldehyde dehydrogenase inhibitors see the article here: Aldehyde Dehydrogenase
TRANSDERMAL USE VERSUS ORAL USE
THIS SECTION IS BASED ON ANECDOTAL DATA ONLY
Tests performed by several individuals have shown that topical application of these allylbenzenes can produce effects that are 5-10 times stronger than that of oral use. When used topically, the onset of the effects are also quicker and the overall duration of the effects are shortened as well. With topical use there are also less side effects.[5]
ALLYLBENZENE POLLS
After hundreds of votes have been made, the allylbenzene polls have consistently shown the same results year after year. As of May 2015, a total of 689 votes have been collected for the 2 polls. The results show very clearly that one of the three oils is by far the most effective in most people. It's interesting to note however, that the votes are not unanimous. The fact that the least effective essential oil is also the most effective essential oil for a minority of the people polled, shows just how different people are in how they are affected by these essential oils.
The nutmeg poll found in the article Nutmeg gives very strong evidence that the Oilahuasca theory is correct, which states that the allylbenzenes must be activated in the body before they can become psychedelic. If they were psychedelic without needing activation, they would be psychedelic in everyone all the time, but they clearly are not. The nutmeg poll results have been running for several years and the results are the same year after year. They show that most people find nutmeg to be psychedelic sometimes. However, not everyone does. A large minority finds nutmeg is never psychedelic.
The difficulty of activating elemicin, methyl chavicol, or myristicin varies from person to person. Some people can only easily activate one of these and have great difficulty trying to activate the others. Few people are able to easily activate all three. Many people have difficulty even activating just one of these. Hopefully, in the future, the Oilahuasca theory will advance enough to change this reality, making all three easy to activate in all people. Right now, that is not the case.
One major problem in advancing the Oilahuasca theory is finding people who are unable to get any hallucinogenic effects from allylbenzenes who are also willing to take part in the study. These people, because they don't initially get any results, are usually skeptics and right it all off as nonsense and aren't willing to further advance the Oilahuasca techniques. This is unfortunate. These are the very people who need to help advance the Oilahuasca theory. Their bodies are especially resistant to Oilahuasca techniques. If the reason for this resistance could be determined, it could greatly advance the Oilahuasca techniques for everyone. Currently, most of the individuals working on advancing Oilahuasca techniques are people who are already occasionally getting it to work.
To view the results of these polls, you need to cast your vote.
These polls are live polls hosted by www.pollsnack.com and are 100% anonymous. You don't need to log in to vote.
ALLYLBENZENE P450 ENZYME SPECIFICS
NOTE: This section refers to the actions of fully activated allylbenzenes via oilahuasca activation. For example, eugenol fully activated is a stimulant, but when not fully activated its a sedative (as is the case for most allylbenzenes when not fully activated).
For all allylbenzenes with methylenedioxy bridges such as myristicin, safrole, apiole, dillapiole, sarisan, and croweacin, it is vital to inhibit CYP2D6 and CYP3A4, and CYP1A2. CYP3A4 is the primary enzyme proven to O-demethylenate myristicin (CYP1A2 plays a minor role) into 5-Allyl-1-methoxy-2,3-dihydroxybenzene. CYP2D6 is proven to O-demethylenate and O-demethylate dozens of compounds. It is proven to O-demethylate eugenol and can probably also perform this action on other allylbenzenes. O-demethylenation and O-demethylation lead to non-psychedelic action for all allylbenzenes. O-demethylenation of the psychedelic myristicin changes it to the stimulant 5-Allyl-1-methoxy-2,3-dihydroxybenzene. O-demethylenation of the psychedelic safrole changes it to the stimulants hydroxychavicol, eugenol, and chavibetol.
For all allylbenzenes with methoxy groups such as elemicin, gamma-asarone, methyl eugenol, and methyl chavicol, it is vital to inhibit CYP2D6, and CYP1A2. CYP2D6 is proven to O-demethylate dozens of compounds. It is proven to O-demethylate eugenol and can probably also perform this action on other allylbenzenes (anecdotal reports indicate that it does). O-demethylation changes the psychedelic elemicin into the stimulant methoxyeugenol. O-demethylation changes the psychedelic methyl chavicol into the stimulant chavicol. O-demethylation changes the psychedelic methyl eugenol into the stimulants hydroxy chavicol, eugenol, and chavibetol.
OILAHUASCA DIET
For 24 hours prior to using oilahuasca you must follow the Oilahuasca Diet restrictions.
Human diet is a major factor in getting oilahuasca working. Many people consume food, drinks and supplements known to inhibit 17bHSD2. Drinks as commonplace as tea and grapefruit juice potently inhibit 17bHSD2. These and other detrimental dietary items explained in this article must be avoided for at least 24 hours prior to using oilahuasca if psychedelic effects are desired. Failure to adhere to these dietary guidelines can completely prevent oilahuasca from working. The 17bHSD2 enzyme is critical for oilahuasca to work. If this enzyme is inhibited by drinking tea or ingesting similar 17bHSD2 inhibitors, it can be impossible to get oilahuasca working. This has been verified by several people. Please adhere to these diet guidelines if you want any success with oilahuasca.
SUPPLEMENTS AND FOODS TO AVOID
Oxidative 17bHSD2 Inhibitors to Avoid
All inhibitors of oxidative 17bHSD2 will prevent activation of allylbenzenes. This enzyme must be induced, not inhibited. It's the single most important enzyme to induce. If oxidative 17bHSD2 is not functioning, allylbenzenes cannot produce psychedelic activity.[5]
Several tests using the potent 17bHSD2 inhibitor quercetin orally in human test subjects have proven that quercetin can completely inactivate allylbenzenes for 3-4 hours if taken prior to taking allylbenzenes.[5] For this reason all sources of quercetin and other potent inhibitors of 17bHSD2 must be avoided.
Naringenin also potently inhibits 17bHSD2. Grapefruit contains large amounts of naringenin, and also prevents the psychedelic action of allylbenzenes if taken before allylbenzenes. Inhibition lasts approximately 4-8 hours.
Galangin, kaempferide, and kaempferol also inhibit 17bHSD2 and need to be avoided.
Here's a list of all known 17bHSD2 inhibitors that should be avoided 4-8 hours prior to using allylbenzenes:
See the articles 17bHSD2, Quercetin and Naringenin for more details and references to the facts stated above.
CYP2A6 Inhibitors to Avoid
CYP2E1 Inhibitors to Avoid
- Disulfiram
- Garlic EO
- Kava
Dimethylamine Boosters to Avoid in Some Cases
It's not known which metabolites of the allylbenzenes are the preferred alkaloid metabolites. Avoid these substances if you specifically want to avoid making too many dimethylamine metabolites.
Anecdotal reports indicate that supplementation with piperidine sources improves activation, and supplementation with dimethylamine sources reduces psychedelic activity. The exact reason for this is currently unknown. Some reports indicate that methyl eugenol and myristicin can be inactive in some cases unless used with piperidine supplements.
The dimethylamine alkaloid metabolites of allylbenzenes are probably more easily destroyed by MAO-A or MAO-B or both. The piperidine metabolites, although probably not psychedelic, may act to protect the dimethylamine metabolites from enzyme destruction.
See the articles Choline, Dimethylamine and Piperidine for more details and references to the facts stated above.
BENEFICIAL SUPPLEMENTS
These have been found to be beneficial based on anecdotal reports. For more details see the article Oilahuasca Activators.
Berberine is one of the most powerful activators tested. It potently inhibits CYP2D6, and inhibits CYP2C9 and CYP3A4, while leaving CYP2E1 active. There may be other unknown actions at play. When used with caffeine (inhibits CYP1A2) and steviosides (theorized to inhibit UGT2B7), it's been able to activate elemicin at doses smaller than any other activator tested. It works better than black pepper tea, and produces a cleaner experience. Black pepper has sedative effects in the doses used, and colors up the experience.
It's believed that berberine's lack of sedative effects and it's potent inhibition of CYP2D6 and it's inaction on CYP2E1 are why it's more effective than black pepper. CYP2D6 appears to be extremely detrimental to activation and CYP2E1 appears to be vital. Piperine found in black pepper has been shown to inhibit CYP2E1[19] to some degree in humans, which is not good.
Black Pepper Tea
Black pepper tea appears to greatly increase the activity of most allylbenzenes. It's not known how this works.
Black pepper tea provides piperidine. Piperidine is known to condense with the 1'-oxo metabolites of allylbenzenes to form piperidine alkaloids such as 1'-oxoelemicin-piperidine, 1'-oxoestragole-piperidine, etc. But it's not known if the piperidine alkaloids are active. Another action by black pepper may be at play.
To supplement with piperidine from black pepper, make black pepper tea from about 5-10 grams of black pepper. Brew with 1 cup of hot water. Then filter out the solids. This will provide a substantial amount of piperidine. To make the black pepper tea more palatable, one can use the hot black pepper tea to make Cup Noodles soup.
Note that black pepper contains piperine and other alkaloids in addition to piperidine. Piperine inhibits CYP3A4 which is good, but it also has some other actions, such as inhibiting CYP2E1[19] to some degree, which is not good. More tests need to be performed on isolated piperine to determine it's effectiveness. When making black pepper tea, filtering out the solids removes a lot of the piperine. Piperine’s solubility in water is only 9.4 mg per cup. However, piperine is potent, and 10-20 mg of piperine can inhibit CYP3A4. 5 grams of black pepper contains about 500 mg of piperine, but only 9.4 mg will be extracted into 1 cup of water. The rest remains in the solid black pepper grounds. 1 cup of water can hold all the piperidine in black pepper.
See the articles Black Pepper, 1'-oxoelemicin-piperidine, 1'-Oxoestragole-Piperidine, and Piperine for more details and references to the facts stated above.
Gallic acid induces 17bHSD2, an essential enzyme required for activation. It also induces SULT1A1 and SULT1A3 and must be pared with potent inhibitors of SULT1A1 and SULT1A3, such as EGCG.
See the articles Gallic acid and 17bHSD2 for more details and references to the facts stated above.
Genistein induces 17bHSD2, an essential enzyme required for activation. It also inhibits UGT, SULT, and GST. Genistein is still being researched. It's effectiveness has been called into question. Until more data is available, it might be better to avoid genistein. Kudzu, from which it is extracted, was found to reduce psychedelic action by interacting with 5-HT1A, 5-HT2A, and 5-HT2C receptors.
See the articles Genistein and 17bHSD2 for more details and references to the facts stated above.
Glycerol
Glycerol induces CYP2E1.
Acts as an SSAO inhibitor. When using glucosamine to inhibit SSAO it's probably best use it 1 hour before and then again combined with coffee at the time the allylbenzenes are ingested, and a few times periodically throughout the experience to boost the psychedelic effects. Doses of 1500 mg glucosamine HCl have been tested along with coffee producing very good results. Its possible that lower doses are effective but they have not been tested. Glucosamine has a half life of approximately 15 hours. It's SSAO inhibition is likely to last at least 15 hours or more.
See the articles Glucosamine and SSAO for more details and references to the facts stated above.
L-Lysine (causes piperidine formation in vivo)
Piperidine is naturally found in the human body. Piperidine is made mostly in the large intestine (colon) from excess L-lysine. Some people are low in this amine.
Theoretically the body uses piperidine to make piperidine alkaloids from allylbenzenes.
Piperidine supplementation appears to greatly increase the activity of most allylbenzenes. It's not known how this works. Piperidine is known to condense with the 1'-oxo metabolites of allylbenzenes to form piperidine alkaloids such as 1'-oxoelemicin-piperidine, 1'-oxoestragole-piperidine, etc. While these piperidines are probably not psychedelic, they may act as enzyme inhibitors protecting the actual psychedelic metabolites of allylbenzenes from rapid enzyme destruction.
It can take 3 or more hours for food to reach the colon (this varies dramatically from person to person, and depends highly on other contents in the digestive system). For this reason L-lysine supplements should be take several hours before taking allylbenzenes.
To supplement your piperidine levels using L-lysine, take at least 1000 mg or more of L-lysine approximately 3 or more hours before using the allylbenzenes.
See the articles L-Lysine and Piperidine for more details and references to the facts stated above.
Niacinamide
Niacinamide supplementation increases NAD+ in humans. The 17bHSD2 enzyme uses NAD+ as a cofactor. Without NAD+, 17bHSD2 is not effective.
Steviosides
Steviosides is theorized to act as a competitive inhibitor of UGT2B7. See the article on Steviosides for more details.
Vitamin D3
Vitamin D3 induces 17bHSD2, an essential enzyme required for activation. It also induces glutathione and should be pared with a good depleter of glutathioine such as cinnamon oil (which contains cinnamaldehyde).
Vitamin A
Vitamin A induces 17bHSD2, an essential enzyme required for activation.
THE OLD OSWALD AND PEELE ALLYLBENZENE ACTIVATION THEORY
One of the original theories proposed by James D. Peele Jr and Edward O. Oswald states that “Allylbenzene is first oxidized on the benzylic carbon to form 1′-hydroxyallylbenzene, which is further oxidized to form phenyl vinyl ketone, which condenses with the secondary amines piperidine and dimethylamine to form tertiary aminopropiophenones (Mannich bases).” [4]
Here we outline their steps using elemicin as an example.
Step 1: Oral Ingestion
Elemicin is ingested orally.
Step 2: Oxidation
Elemicin is oxidized on the 1'-position to form 1'-hydroxyelemicin.
Step 3: Dehydrogenation
1'-hydroxyelemicin is dehydrogenated on the 1'-position to form 1'-oxoelemicin.
Step 4: Alkaloid Creation
1'-Oxoelemicin then condenses at the 1' position with dimethylamine, piperidine, or pyrrolidine and rearranges to form one of 3 proven alkaloid metabolites 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)propan-1-one, 3-piperidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one, or 3-Pyrrolidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one.



See Also
Other Related Links
Bibliography
1. E.O. Oswald, L. Fishbein, B.J. Corbett, M.P. Walker.
Metabolism of naturally occuring propenylbenzene derivatives : II. Separation and identification of tertiary aminopropiophenones by combines gas—liquid chromatography and chemical ionization mass spectrometry. Journal of Chromatography A, Volume 73, Issue 1, 8 November 1972, Pages 43-57
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(
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2. E.O. Oswald, L. Fishbein, B.J. Corbett, M.P. Walker.
Identification of tertiary aminomethylenedioxy-propiophenones as urinary metabolites of safrole in the rat and guinea pig. Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 230, Issue 2, 23 February 1971, Pages 237-247
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3. E.S. Oswald, L. Fishbein, B.J. Corbett, M.P. Walker. Urinary excretion of tertiary amino methoxy methylenedioxy propiophenones as metabolites of myristicin in the rat and guinea pig. Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 244, Issue 2, 19 August 1971, Pages 322-328
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