Myristicin Explained

Myristicin is a naturally occurring compound found in common herbs and spices, such as nutmeg.[1] [2] It is an insecticide, and has been shown to enhance the effectiveness of other insecticides.[1] [3]

When ingested, myristicin may produce hallucinogenic effects,[1] [4] and can be converted to MMDMA in controlled chemical synthesis.[5] It interacts with many enzymes and signaling pathways in the body,[6] [7] and may have dose-dependent cytotoxicity in living cells. Myristicin is listed in the Hazardous Substances Data Bank.[1]

Uses

Isolated myristicin has proven an effective insecticide against many agricultural pests, including Aedes aegypti mosquito larvae, Spilosoma obliqua (hairy caterpillars), Epilachna varivestis (Mexican bean beetles), Acyrthosiphon pisum (pea aphids), mites, and Drosophila melanogaster (fruit flies). Myristicin was shown to be an effective repellent, 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 compounds.[1] Because of this, it can be used in synthetic synthesis to create amphetamine derivatives, and create designer drugs like MMDMA that are similar in structure and effect to MDMA. Out of the common spices that contain myristicin, nutmeg has a high relative concentration of the compound,[2] and therefore is used to exploit the effects of myristicin.[1] [2]

Furthermore, myristicin interferes with multiple signaling pathways and enzyme processes in the body.[1]

Sources of myristicin

Myristicin can be found in the essential oil of nutmeg, black pepper, kawakawa,[8] and many members of the Umbelliferae family, including anise, carrots, parsley, celery, dill,[9] and parsnip.

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 (Nepal camphor tree),[10] and Piper mullesua ("Hill Pepper").[11]

Depending on the conditions of growth and storage of the plant, a high quality nutmeg (Myristica fragrans) seed can contain up to 13 mg of myristicin per 1 gram.[12]

Physiological effects

Psychoactive effects

At a minimum dose of about 5 g of nutmeg powder, symptoms of nutmeg intoxication can begin to emerge. Nutmeg intoxication may produce dizziness, drowsiness, and confusion, although in higher amounts, it may have effects similar to other deliriants due to its hallucinogenic effects.[1] [13]

Pharmacology

Myristicin is additionally known to be a weak inhibitor of monoamine oxidase (MAO), an 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), potentially explaining a weaker inhibitory effect.[14]

While smaller concentrations of MAOIs may not cause problems, there are additional warnings regarding drug interactions. Those taking antidepressants that are MAOIs (such as phenelzine, isocarboxazid, tranylcypromine or selegiline[15]) or taking selective serotonin re-uptake inhibiting (SSRI) antidepressants should avoid essential oils rich in myristicin, such as that of nutmeg or anise.[16]

Metabolites

Metabolism of myristicin yields 3-methoxycatechol[1] and enzymatically forms 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.[1]

Chemistry

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, a synthetic "designer drug" amphetamine derivative that is less potent than MDMA but produces comparable stimulant and hallucinogenic effects.

Myristicin is insoluble in water, and soluble in ethanol, ether, and benzene.[1]

Toxicity

In laboratory studies, myristicin is cytotoxic. Specifically, it stimulates cytochrome c release, which activates caspase cascades and induces early apoptosis in the cells.[6] Myristicin has also been shown to inhibit cytochrome P450 enzymes, which are responsible for metabolizing a variety of substrates including hormones and toxins, allowing these substrates to accumulate.[1]

The effects of nutmeg consumed in large doses are attributed mostly to myristicin: 1–7 hours following ingestion, symptoms include disorientation, giddiness, stupor, and stimulation of the central nervous system leading to euphoria.[1] [2] Also occurring are mild to intense hallucinations (similar to those induced by deliriants: walls and ceiling glitching or breathing), disorientation to time and surroundings, dissociation, feelings of levitation, loss of consciousness, tachycardia, weak pulse, anxiety, and hypertension.[1] 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 miosis, hypotension, shock, and potentially death.[1] [2]

Myristicin poisoning can be detected by testing levels of myristicin in the blood.[17] There are no known antidotes for myristicin poisoning, and treatment focuses on symptom management and potential sedation in cases of extreme delirium or aggravation.[1] [18]

Notes and References

  1. Web site: Myristicin . PubChem, US National Library of Medicine . 14 May 2023 . 13 May 2023.
  2. Web site: Nutmeg . Drugs.com . 14 May 2023 . 21 November 2022.
  3. Lichtenstein EP, Casida JE . 1963. Naturally Occurring Insecticides, Myristicin, an Insecticide and Synergist Occurring Naturally in the Edible Parts of Parsnips . Journal of Agricultural and Food Chemistry. 11. 5. 410–415. 10.1021/jf60129a017 .
  4. Stein U, Greyer H, Hentschel H . Nutmeg (myristicin) poisoning--report on a fatal case and a series of cases recorded by a poison information centre . Forensic Science International . 118 . 1 . 87–90 . April 2001 . 11343860 . 10.1016/s0379-0738(00)00369-8 .
  5. Clark CR, DeRuiter J, Noggle FT . 1996-01-01. Analysis of 1-(3-Methoxy-4,5-Methylenedioxyphenyl)-2-Propanamine(MMDA)Derivatives Synthesized from Nutmeg Oil and 3-Methoxy-4,5-Methylenedioxybenzaldehyde . Journal of Chromatographic Science. 34. 1. 34–42. 10.1093/chromsci/34.1.34 . free.
  6. Lee BK, Kim JH, Jung JW, Choi JW, Han ES, Lee SH, Ko KH, Ryu JH . 6 . Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells . Toxicology Letters . 157 . 1 . 49–56 . May 2005 . 15795093 . 10.1016/j.toxlet.2005.01.012 .
  7. Yang AH, He X, Chen JX, He LN, Jin CH, Wang LL, Zhang FL, An LJ . 6 . Identification and characterization of reactive metabolites in myristicin-mediated mechanism-based inhibition of CYP1A2 . Chemico-Biological Interactions . 237 . 133–40 . July 2015 . 26091900 . 10.1016/j.cbi.2015.06.018 .
  8. 24-27.
  9. Rahman NA, Fazilah A, Effarizah ME . 2015 . Toxicity of Nutmeg (Myristicin): A Review . International Journal on Advanced Science, Engineering and Information Technology . 5 . 3 . 212–215 . 10.18517/ijaseit.5.3.518 . free . 10.1.1.920.6379 .
  10. Shulgin AT . Possible implication of myristicin as a psychotropic substance . Nature . 210 . 5034 . 380–4 . April 1966 . 5336379 . 10.1038/210380a0 . 1966Natur.210..380S . 4189608 .
  11. Srivastava S, Gupta MM, Prajapati V, Tripathi AK, Kumar S . 2001. Insecticidal Activity of Myristicin from Piper mullesua . Pharmaceutical Biology. en. 39. 3. 226–229. 10.1076/phbi.39.3.226.5933 . 83947896.
  12. Nowak J, Woźniakiewicz M, Gładysz M, Sowa A, Kościelniak P . 2015. Development of Advance Extraction Methods for the Extraction of Myristicin from Myristica fragrans . Food Analytical Methods. en. 9. 5. 1246–1253. 10.1007/s12161-015-0300-x . free.
  13. Roeters van Lennep JE, Schuit SC, van Bruchem-Visser RL, Özcan B . Unintentional nutmeg autointoxication . The Netherlands Journal of Medicine . 73 . 1 . 46–48 . January 2015 . 26219944 .
  14. Truitt EB, Duritz G, Ebersberger EM . Evidence of monoamine oxidase inhibition by myristicin and nutmeg . Proceedings of the Society for Experimental Biology and Medicine . 112 . 3 . 647–50 . March 1963 . 13994372 . 10.3181/00379727-112-28128 . 44996415 .
  15. Web site: Monoamine oxidase inhibitors (MAOIs) . Mayo Clinic . 12 September 2019 .
  16. Book: 10.1016/b978-0-443-06241-4.00004-7 . Kinetics and dosing . Essential Oil Safety . 2014 . Tisserand R, Young R . 39–67 . 978-0-443-06241-4 . https://books.google.com/books?id=DbEKAQAAQBAJ&pg=PA39 .
  17. Book: Baselt RC . Disposition of toxic drugs and chemicals in man. 2008. Biomedical Publications. 978-0-9626523-7-0. 8th. Foster City, Ca. 243548756.
  18. Demetriades AK, Wallman PD, McGuiness A, Gavalas MC . Low cost, high risk: accidental nutmeg intoxication . Emergency Medicine Journal . 22 . 3 . 223–5 . March 2005 . 15735280 . 1726685 . 10.1136/emj.2002.004168 .