Table of Contents
Elemicin is an allylbenzene essential oil found in large quantities in Zingiber niveum and an elemicin chemotype of Cinnamon myrtle essential oil, and also found in the essential oils of nutmeg, ginger grass, elemi and many other plants. It's believed to be partially responsible for the hallucinogenic effects of nutmeg.
Both elemicin and myristicin are often quoted as having "anticholinergic effects in humans". This appears to be very popular misinformation based on the study of the ingestion of nutmeg nuts in humans, not the study of elemicin and myristicin. This anticholinergic effect is likely attributed to the large content in nutmeg of the anxiogenic depressant trimyristin1. A vast search of several databases found absolutely no evidence of elemicin and myristicin being anticholinergic in humans. As of June 2015, there have been absolutely no studies published that evaluated the psychoactivity of elemicin in humans available on PubMed, or anywhere else that could be easily verified. All verifiable studies have been only animal studies, and they show that elemicin acts as a 5-HT2A agonist, a hallucinogen, just like LSD and mescaline.
In humans elemicin is metabolized to a wide array of mostly inactive metabolites. Elemicin is structurally similar to mescaline and under certain circumstances in animals it was proven to produce 3 different mescaline-like alkaloid metabolites in vivo after ingestion (proven by analyzing urine using gas-liquid chromatography and chemical ionization mass spectrometry). One or more of these metabolites might occasionally occur in humans, and could potentially produce effects similar to those of mescaline.
Elemicin itself is believed to be inactive. Activity is possibly caused by one of its alkaloid metabolites created in vivo in humans. In order to coerce the human metabolism of elemicin in favor of creating possible active alkaloid metabolites, specific enzymes may need to be inhibited and induced. The theory behind this process of enzyme manipulation is known as oilahuasca. In many people mescaline-like effects are not possible without the use of oilahuasca activation techniques. However some people are able to experience mescaline-like effects from ingesting elemicin without enzyme manipulation. Elemicin appears to be one of the most difficult allylbenzenes to achieve psychedelic effects from. Many people are unable to experience mescaline-like effects from elemicin even when using proper oilahuasca activation techniques (the reason for this is currently unknown).
Tests performed on rats administered elemicin intraperitoneally at 80mg/kg concluded that elemicin had distinct agonist effects on 5-HT2A showing symptoms in rats that are typical of psychedelics like LSD and mescaline. This essentially proves that elemicin or one or more of it's metabolites can cause psychedelic effects, at least in rats. 5-HT2A is the main site responsible for psychedelic activity from drugs such as LSD and mescaline.
However, the study did not determine that elemicin itself caused the agonist effects on 5-HT2A. Because it is known that rats specifically metabolize elemicin into 3 known mescaline-like alkaloids, the actual agonist effects of elemicin on 5-HT2A could have been caused by one or more of the three mescaline-like alkaloid metabolites of elemicin, and not by elemicin itself.
|Plant||Origin||Part||Contents of Essential Oil|
|Backhousia myrtifolia Hook (Cinnamon myrtle, elemicin chemotype)||Eastern Australia||leaf||91% |
|Cinnamomum cecidodaphne||Wood||Unspecified 2|
|Cinnamomum cecidodaphne||Fruit Rind||6.8% |
|Cinnamomum cordatum||Bark||2.5% |
|Cinnamomum glanduliferum||Unspecified 3|
|Cinnamomum glaucescens (Nees) Meissn||Northeast India||leaf||92.9%|
|Collinsonia canadensis L.||Plant||3.6% |
|Cymbopogon martini var. sofia (Ginger Grass)||India||Grass||17.77% |
|Cymbopogon microstachys (Hook.f.) Soenarko||Grass||25.3% |
|Cymbopogon pendulus (Nees ex Steud) Wats||India||Grass||53.7% |
|Cymbopogon travancorensis Bor (Poaceae)||Grass||17% |
|Danish Tarragon||Denmark||Plant||1.23-10.31% |
|Daucus carota L. subsp. carota||Tunis, Tunisia||?||31.5 - 35.3%4|
|Daucus glaber Forssk||Northern Nile Delta||stem||6.04%|
|Daucus glaber Forssk||Northern Nile Delta||fruit||32.69%|
|Daucus glaber Forssk||Northern Nile Delta||leaves||18.16%|
|Daucus gracilis||?||aerial parts||35.3%|
|Mosla dianthera||?||?||16.51% |
|Peucedanum pastinacifolium||Golpaygan mountain||air-dried aerial parts||31.1%|
|Piper krukoffii||North Brazil||leaves||2.8% |
|Piper krukoffii||North Brazil||twigs||3.0% |
|Tarragon (Russian/Siberian)||Latvia||Plant||16.1-57.21% |
|Zingiber niveum Mood & Theilade||Laos||Root and rhizome||60.97% |
Alkaloid Metabolites Created In Vivo
By analizing urine of animals using gas-liquid chromatography and chemical ionization mass spectrometry, these alkaloid metabolites have been detected in urine after ingesting elemicin.
Similar corresponding alkaloids have also been detected after the ingestion of safrole.
The exact mechanism that produces these alkaloids in vivo is current unknown.
The dimethylamine metabolite created in vivo is known as 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)propan-1-one or 1'-oxoelemicin-DMA.This alkaloid has an XLogP3-AA of 1.5.
The piperidine metabolite created in vivo is known as 3-piperidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one or 1'-oxoelemicin-piperidine.
This alkaloid has an XLogP3-AA value of 2.3 allowing it to more easily cross the blood brain barrier compared to the dimethylamine form.
The pyrrolidine metabolite created in vivo is known as 3-Pyrrolidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one or 1'-oxoelemicin-pyrrolidine.
Non-Alkaloid Metabolites Found in Humans
O-Demethyl dihydroxy elemicin
O-demethyl dihydroxy elemicin is detectable in human urine as the primary metabolite of elemicin following the ingestion of nutmeg. This compound has no known route to alkaloid formation in animals or humans. It's not currently known for certain how this metabolite forms. It is likely a metabolite created directly after elemicin forms the metabolite methoxyeugenol.
Because this metabolite is still an allylbenzene it might possibly be further metabolized in vivo into alkaloid metabolites, as has been proven for other allylbenzenes. The alkaloid forms of methoxyeugenol are theorized to produce stimulant effects similar to those of the presumed effects of alkaloid metabolites of eugenol. The predicted effects are possibly stimulation and strong tingling sensations, with no psychedelic action.
1'-Hydroxyelemicin us usually found in it's conjugated form as 1'-hydroxyelemicin glucuronide created by glucuronosyltransferase (UGT) and as 1'-sulfoxyelemicin created by sulfotransferase (SULT).
Elemicin's metabolite 1'-hydroxyelemicin is often reported to be created by CYP1A2 and CYP2A6 primarily, but there are other enzymes said to cause this metabolite to form, with some reports giving very conflicting information. It's possible that many other enzymes can produce this metabolite under certain conditions.
This inactive metabolite is detected in human and rat urine when pure elemicin is ingested. Curiously, 1'-hydroxyelemicin was found to be absent from urine samples when humans or rats ingested nutmeg containing elemicin. The reason for this is unknown but assumed to be related to possible enzyme inhibitors present in nutmeg which prevent the formation of this inactive metabolite of elemicin. 
Non-Alkaloid Metabolites Found In Animals
Small amounts of the epoxide of the 3-O-demethylated derivative of elemicin were identified in the urine.
The major metabolic reactions in rats of elemicin follow the cinnamoyl pathway or the epoxide-diol pathway. The cinnamoyl pathway gives 3-(3,4,5-Trimethoxyphenyl)propionic acid and its glycine conjugate as major metabolites.
PubChem Compound ID: 10248
Molecular Weight: 208.25364 [g/mol]
Molecular Formula: C12H16O3
H-Bond Donor: 0
H-Bond Acceptor: 3
IUPAC Name: 1,2,3-trimethoxy-5-prop-2-enylbenzene
Canonical SMILES: COC1=CC(=CC(=C1OC)OC)CC=C
Solubility: Several vendors state its soluble in chloroform and ethyl acetate, without giving references to these details.
- Methyl Chavicol
- Methyl Eugenol
- Oilahuasca Activation
- Phenyl Vinyl Ketones
- 1'-Hydroxyelemicin Glucuronide
- 3,4,5-Trimethoxycinnamic acid