Table of Contents
Effects on P450 Enzymes
Metabolites of Methyl Chavicol in Human Urine
In a study by Sangster (1987), methyl chavicol (100 μg; 0.675 μmol) administered orally to humans was eliminated primarily in the urine and as CO2 in expired air. 65% of the total dose was recovered in urine and examined. No amount of methyl chavicol could be detected in urine. Methyl chavicol was completely metabolized by oxidative O-demethylation, and various oxidations of the side chain. In urine, six metabolites were identified:
|Chavicol (p-allylphenol) (47%)1||4-methyoxybenzoyl-N-glycine (12%)2|
|4-methoxyphenyllactic acid (4%)||4-methoxycinnamoylglycine (0.8%)|
|4-methoxyphenylacetic acid (0.5%)||1'-hydroxyestragole (0.3%)|
Another test by Zeller, Horst, and Rychlik, found the following metabolites in human urine after the ingestion of fennel tea containing methyl chavicol:
|Chavicol (p-allylphenol) (17%)||1'-Hydroxyestragole (0.41%)|
Methyl chavicol appeared to be completely metabolized. No methyl chavicol was detected in human urine.
Metabolites of Methyl Chavicol in Vitro
Chavicol is the O-demethyl metabolite of methyl chavicol. This compound is itself an allylbenzene and can undergo bioactivation possibly leading to the formation of alkaloids in vivo as has been proven for similar allylbenzenes. The alkaloid forms of this allylbenzene are predicted to have stimulant action and no psychedelic action in man. P450 enzymes capable of O-demethylating allylbenzenes are typically CYP2D6 and CYP3A4 (CYP3A4 usually works in conjunction with CYP1A2 to carry out O-demethylation). CYP2C9 has also been shown to O-demethylate some compounds, and could potentially be involved in this reaction.
1'-Hydroxyestragole is created from methyl chavicol in human liver in vitro primarily by the P450 enzymes CYP1A2, CYP2A6 and CYP2E1 by 1-hydroxylation of methyl chavicol.
This metabolite also undergoes glucuronidation primarily by the action of UGT2B7 followed by UGT1A9, with a very small amount carried out by UGT2B15. It undergoes sulfation by the action of SULT1A1 and SULT1A3. These pathways prevent 1'-oxoestragole from forming.
1'-Oxoestragole is created from 1'-hydroxyestragole by the action of estradiol-17beta-dehydrogenase Type 2 (17beta-HSD2). This metabolite is then capable of forming adducts with glutathione (GSH) leading to inactivation, or forming adducts with endogenous amines. The latter action is believed to be responsible for the psychedelic effects methyl chavicol is capable of producing in humans under certain conditions. For more details see the article: 1'-Oxoestragole.
Most allylbenzenes are capable of producing dimethylamine, piperidine, and pyrrolidine metabolites in vivo. This has been proven for safrole, elemicin, and several other allylbenzenes (see their individual articles for references). For this reason its highly probable that methyl chavicol also produces the same corresponding alkaloid metabolites.
The methyl chavicol metabolite 1'-Oxoestragole is capable of forming adducts with endogenous amines. This action is believed to be responsible for the psychedelic effects methyl chavicol is capable of producing in humans under certain conditions.
The alkaloids in this section are all adducts of 1'-oxoestragole and endogenous amines.
1-(4-methoxyphenyl)-3-(piperidin-1-yl)propan-1-one is an adduct of 1'-oxoestragole and piperidine.
Alkaloid metabolites of methyl chavicol are presumed to be responsible for the psychedelic effects it produces under certain conditions in some human test subjects.
Methyl chavicol is active both orally and transdermally. Transdermal use is approximately 5-10 times more effective than oral use.
A single exposure to methyl chavicol without using oilahuasca activation techniques normally produces only very mild cannabis-like sedative effects without any psychedelic effects. Psychedelic effects are normally only achieved when used with various oilahuasca activators or on repeated use. Methyl chavicol appears to produce reverse tolerance. Anecdotal reports show that methyl chavicol's psychedelic effects are more pronounced when its used several times in a row in combination with several Oilahuasca Activation techniques.
Unlike many of the other allylbenzenes, methyl chavicol can be used as its own oilahuasca activator in some people. It also helps to activate other allylbenzenes. The exact reason for this is currently unknown. For details on how to help coerce psychedelic effects from methyl chavicol see the article on Oilahuasca Activation.
|Plant||Origin||Part||Contents of Essential Oil|
|Sweet Basil||Thailand||Plant||93% |
Synonyms: Estragole; 4-Methoxyallylbenzene
PubChem Compound ID: 8815
Molecular Weight: 148.20168 [g/mol]
Molecular Formula: C10H12O
Appearance: colorless liquid
Boiling Point: 216 C @ 764 mm Hg
Solubility: SOL IN ALCOHOL, CHLOROFORM; Solubility in water at 25 deg C is 0.178 g/L.
IUPAC Name: 1-methoxy-4-prop-2-enylbenzene
Canonical SMILES: COC1=CC=C(C=C1)CC=C