Myristicin is a naturally occurring compound found in common herbs and spices, the most well known being
nutmeg
Nutmeg is the seed or ground spice of several species of the genus ''Myristica''. ''Myristica fragrans'' (fragrant nutmeg or true nutmeg) is a dark-leaved evergreen tree cultivated for two spices derived from its fruit: nutmeg, from its seed, an ...
. It is an
insecticide, and has been shown to enhance the effectiveness of other insecticides in combination.
Myristicin is also a precursor for
substituted amphetamine derivative compounds structurally related to
MMDA and
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...
; it was believed to be metabolized in the liver into
MMDA, but unlikely since no MMDA was found in urine, in the body it produces
hallucinogen
Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorize ...
ic effects,
and can be converted to
MMDMA
5-Methoxy-3,4-methylenedioxymethamphetamine (MMDMA; 5-MeO-MDMA) is a designer drug of the substituted methylenedioxyphenethylamine
Substituted methylenedioxy- phenethylamines (MDxx) are a large chemical class of derivatives of the phenethyl ...
in controlled chemical synthesis.
It interacts with many enzymes and signaling pathways in the body,
is
cytotoxic to living cells,
and may also have
chemoprotective properties.
Uses
Isolated myristicin has proven an effective insecticide against many agricultural pests, including ''
Aedes aegypti
''Aedes aegypti'', the yellow fever mosquito, is a mosquito that can spread dengue fever, chikungunya, Zika fever, Mayaro and yellow fever viruses, and other disease agents. The mosquito can be recognized by black and white markings on its le ...
'' mosquito larvae, ''
Spilosoma obliqua'' (hairy caterpillars),
''Epilachna varivestis'' (
Mexican bean beetle
The Mexican bean beetle (''Epilachna varivestis'') is a species of lady beetle that can be an agricultural pest. It is one of the few North American lady beetles that feed on plants rather than other insects. It is found throughout Mexico and ...
s), ''
Acyrthosiphon pisum
''Acyrthosiphon pisum'', commonly known as the pea aphid (and colloquially known as the green dolphin, pea louse, and clover louse), is a sap-sucking insect in the family Aphididae. It feeds on several species of legumes (plant family Fabaceae) ...
'' (pea aphids),
mite
Mites are small arachnids (eight-legged arthropods). Mites span two large orders of arachnids, the Acariformes and the Parasitiformes, which were historically grouped together in the subclass Acari, but genetic analysis does not show clear e ...
s, and ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'' (fruit flies). Myristicin was shown to be an effective repellant, and to cause mortality via direct and systemic exposure. It also displayed a
synergistic effect when administered to insects in combination with existing insecticides.
The structure of myristicin closely resembles that of amphetamine compounds, and it is capable of producing psychotropic effects similar to
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...
compounds. Because of this, it can be used in synthetic synthesis to create amphetamine derivatives, and create designer drugs like
MMDMA
5-Methoxy-3,4-methylenedioxymethamphetamine (MMDMA; 5-MeO-MDMA) is a designer drug of the substituted methylenedioxyphenethylamine
Substituted methylenedioxy- phenethylamines (MDxx) are a large chemical class of derivatives of the phenethyl ...
that are similar in structure and effect to
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...
.
Out of the common spices that contain myristicin, nutmeg has the highest relative concentration of the compound. Therefore, it is used most frequently to isolate myristicin or exploit its effects.
Furthermore, myristicin interferes with multiple signaling pathways and enzyme processes in the body.
It is toxic to cells and also may have chemoprotective properties, making it an interesting topic for further pharmacological or therapeutic research.
ee Pharmacology, Toxicity
Sources of myristicin
Myristicin can be found in
nutmeg
Nutmeg is the seed or ground spice of several species of the genus ''Myristica''. ''Myristica fragrans'' (fragrant nutmeg or true nutmeg) is a dark-leaved evergreen tree cultivated for two spices derived from its fruit: nutmeg, from its seed, an ...
,
black pepper
Black pepper (''Piper nigrum'') is a flowering vine in the family Piperaceae, cultivated for its fruit, known as a peppercorn, which is usually dried and used as a spice and seasoning. The fruit is a drupe (stonefruit) which is about in dia ...
, and many members of the
''Umbelliferae'' family including
anise,
carrots,
parsley,
celery
Celery (''Apium graveolens'') is a marshland plant in the family Apiaceae that has been cultivated as a vegetable since antiquity. Celery has a long fibrous stalk tapering into leaves. Depending on location and cultivar, either its stalks, ...
,
dill
Dill (''Anethum graveolens'') is an annual herb in the celery family Apiaceae. It is the only species in the genus ''Anethum''. Dill is grown widely in Eurasia, where its leaves and seeds are used as a herb or spice for flavouring food.
Growth ...
,
and
parsnip
The parsnip ('' Pastinaca sativa'') is a root vegetable closely related to carrot and parsley, all belonging to the flowering plant family Apiaceae. It is a biennial plant usually grown as an annual. Its long taproot has cream-colored skin an ...
.
Trace amounts have also been isolated from a variety of plant species including ''
Ridolfia segetum'' (harvest fennel), species of the ''
Oenanthe'' genus (water dropworts), species of the ''
Lamiaceae'' family (mint, sage, or deadnettle families), ''
Cinnamomum glanduliferum
''Camphora glandulifera'', common name false camphor tree or Nepal camphor tree, is a tree in the genus ''Cinnamomum'' of the family Lauraceae.
Description
''Cinnamomum glanduliferum'' is an evergreen tree reaching a height around . Leaves are ...
(''Nepal camphor tree), and ''Piper mullesua'' ("Hill Pepper").
Depending on the conditions of growth and storage of the plant, a high quality nutmeg (''
Myristica fragrans
''Myristica fragrans'' is an evergreen tree indigenous to the Maluku Islands of Indonesia. It is important as the main source of the spices nutmeg and mace. It is widely grown across the tropics including Guangdong and Yunnan in China, Taiwan, ...
)'' seed can contain up to 13 mg of myristicin per 1 gram, or 1.3%. In the isolated
essential oils, myristicin constitutes on average 13.24% of nutmeg oil, 6.32% of parsley leaf oil, 7.63% of dill herb oil, and 0.18% of celery seed oil.
Physiological effects
Psychoactive effects
There is more research needed on the exact mechanism of action of myristicin in the body. A 400 mg dose of myristicin has been shown to produce “mild cerebral stimulation” in 4 out of 10 human subjects. Myristicin is most commonly consumed in nutmeg, and 400 mg would be contained in approximately 15 g of nutmeg powder. However, at a minimum dose of about 5 g of nutmeg powder, symptoms of nutmeg intoxication can begin to emerge, indicating the interaction of other compounds contained in nutmeg.
elemicin
Elemicin is a phenylpropene, a natural organic compound, and is a constituent of several plant species' essential oils.
Natural occurrence
Elemicin is a constituent of the oleoresin and the essential oil of ''Canarium luzonicum'' (also referred ...
,
eugenol
Eugenol is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds. It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, ...
, and
safrole
Safrole is an organic compound with the formula CH2O2C6H3CH2CH=CH2. It is a colorless oily liquid, although impure samples can appear yellow. A member of the phenylpropanoid family of natural products, it is found in sassafras plants, among oth ...
are also components of nutmeg that, while at lower concentrations than myristicin, are thought to contribute to the hallucinogenic and physiological symptoms of nutmeg intoxication.
Nutmeg, in terms of effects, feels very similar to
THC
Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...
, if not identical in some ways (nutmeg is a cannabinoid, which explains this), except for feeling more sedating, tiring, heavy, and an overall more 'matured' high with bad physical side effects such as previously mentioned above. In higher doses where hallucinations are present, in which the main nutmeg high consists of mostly a deeper weed like feeling, the hallucinations are very similar to
Diphenhydramine
Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...
except you're not overly sedated and delirious, you see everything glitch all around you, breath and morph. You might also get some closed eye visuals. Overall, nutmeg is more alike to that of a cannabinoid than a hallucinogenic until you get into high doses.
See toxicity for more information on psychoactive effects.
Pharmacology
Myristicin is additionally known to be a weak inhibitor of
monoamine oxidase (MAO), a liver enzyme in humans that metabolizes neurotransmitters (e.g.,
serotonin, dopamine, epinephrine, and norepinephrine). It lacks the basic nitrogen atom that is typical of MAO inhibitors (
MAOIs
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especi ...
), potentially explaining a weaker inhibitory effect.
While smaller concentrations of MAOIs may not cause problems, there are additional warnings regarding drug interactions. Those taking antidepressants that are
MAOIs
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especi ...
(such as
phenelzine
Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine an ...
,
isocarboxazid,
tranylcypromine or
selegiline) or taking selective
serotonin re-uptake inhibiting (
SSRI
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracellul ...
) antidepressants should avoid essential oils rich in myristicin, such as that of nutmeg or anise.
Metabolites
Myristicin has been noted to be enzymatically hydroxylated into
1'-hydroxymyristicin and enzymatically formed
5-allyl-1-methoxy-2,3-dihydroxybenzene (oxidation of the methylenedioxy group). Myristicin is also formed into
demethylenylmyristicin,
dihydroxymyristicin, and elemicin is formed into
O-demethylelemicin,
O-demethyldihydroxyelemicin, and safrole to
demethylenylsafrole.
It was initially hypothesized that elemicin and myristicin can form known hallucinogenic drugs following amination processes (formation of
3,4-methylenedioxy-5-methoxyamphetamine from myristicin and mescaline from elemicin) since the only structural modification is said amination; this pathway was initially doubted to occur and has not been demonstrated in vivo. Other studies on the metabolism of myristicin or elemicin, either in vitro or in vivo, have failed to detect either mescaline or amphetamine-like compounds and measuring human urine following nutmeg ingestion has failed to find the aforementioned amphetamine derivative. Research on breakdown of myristicin.
Myristicin also has potential
chemoprotective properties. In mouse liver and small intestine mucosa, myristicin induced higher levels of
glutathione ''S''-transferase (GST), which catalyzes a reaction that detoxifies activated
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...
s. This indicates that myristicin may act as an inhibitor of
tumorigenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
.
It is still unknown how much the tendency of myristicin to induce apoptosis in cells contributes to its chemoprotective abilities.
Toxicity
Myristicin has been proven to be
cytotoxic, or toxic to living cells. Specifically, it stimulates
cytochrome c release, which activates
caspase cascades and induces early
apoptosis in the cells.
In human
neuroblastoma
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in th ...
SK-N-SH cells, myristicin led to apoptosis and observable morphological changes, as well as chromatin condensation and
DNA fragmentation
DNA fragmentation is the separation or breaking of DNA strands into pieces. It can be done intentionally by laboratory personnel or by cells, or can occur spontaneously. Spontaneous or accidental DNA fragmentation is fragmentation that gradually a ...
.
This indicates a definite cytotoxic effect, and a potential
neurotoxic
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
effect that requires further investigation.
Myristicin has also been shown to inhibit
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
enzymes in humans, which is responsible for metabolizing a variety of substrates including hormones and toxins, allowing these substrates to accumulate.
This can compound its own toxicity and/or lead to increased bioavailability of other substances, which can lower the threshold for
overdose
A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. from other drugs that may be in the body.
The effects of nutmeg consumed in large doses are attributed mostly to myristicin, where 1–7 hours following ingestion symptoms include disorientation, giddiness, stupor, and/or stimulation of the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
leading to
euphoria, mild to intense
hallucination
A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
s (similar to deliriants, walls and ceiling glitching or breathing), disorientation to time and surroundings,
disassociation
Dissociation, as a concept that has been developed over time, is a wide array of experiences, ranging from a mild emotional detachment from the immediate surroundings, to a more severe disconnection from physical and emotional experiences. The m ...
, feelings of levitation, feeling of fuzziness similar to
THC
Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...
but heavier, head feeling pressurized, loss of consciousness,
tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
, weak pulse,
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, and
hypertension. Symptoms of nutmeg intoxication further include nausea, abdominal pain, vomiting, minor to severe muscle spasms (severe in extreme overdose), headache, dryness of mouth,
mydriasis or
,
hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
,
shock
Shock may refer to:
Common uses Collective noun
*Shock, a historic commercial term for a group of 60, see English numerals#Special names
* Stook, or shock of grain, stacked sheaves
Healthcare
* Shock (circulatory), circulatory medical emergen ...
, and potentially death.
Myristicin poisoning can be detected by testing levels of myristicin in the blood. There are currently no known antidotes for myristicin poisoning, and treatment focuses on symptom management and potential sedation in cases of extreme
delirium or aggravation.
Chemistry
![Amphetamine_derivative_and_myristicin_structures](https://upload.wikimedia.org/wikipedia/commons/a/af/Amphetamine_derivative_and_myristicin_structures.svg)
With a chemical structure resembling amphetamines and other precursors, myristicin can also be used to synthesize illicit hallucinogenic drugs. Under controlled conditions, myristicin isolated from nutmeg oil can be converted into
MMDMA
5-Methoxy-3,4-methylenedioxymethamphetamine (MMDMA; 5-MeO-MDMA) is a designer drug of the substituted methylenedioxyphenethylamine
Substituted methylenedioxy- phenethylamines (MDxx) are a large chemical class of derivatives of the phenethyl ...
, a synthetic "designer drug" amphetamine derivative that is less potent than
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...
but produces comparable stimulant and hallucinogenic effects.
Myristicin is soluble in
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
,
ether
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...
, and
acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
, but insoluble in water
References
{{phenylpropene
Plant toxin insecticides
Monoamine oxidase inhibitors
Phenylpropenes
O-methylated phenylpropanoids
O-methylated natural phenols
Benzodioxoles
Allyl compounds
Pyrogallol ethers
Plant toxins