Do You Know About the Narcotic Effects of Nutmeg?

By Ibo Nagano, Entheogen Review. Posted June 5, 2009.

The easiest way to take nutmeg is to grind whole nutmegs and add them to juice. Freshly ground nutmeg is the best, because powdered nutmeg soon loses the oils that give it its distinct flavor and unique properties. I find the flavor goes with orange juice quite well--one just has to accept that the juice will be thick, if not chunky. A good way to test the potency of nutmeg is to insert a darning needle (or similar device) one centimeter into the flesh of the nut; if a drop of oil bubbles up after pulling the needle out then the nutmeg is good.

Karlos Fandango reports on Erowid.org that the active principle can be extracted by boiling nutmeg and collecting the waxy film that collects on top of the pot as the water cools (Fandango 2001). What Fandango has described is a way of extracting the fixed oil of nutmeg, otherwise known as nutmeg butter. Nutmeg butter has limited medicinal or cosmetic use, and does not contain the suspected active components of nutmeg, which are primarily myristicin, elemicin, and safrole (while myristicin alone has been shown to be psychoactive, it does not appear to completely replicate the inebriation caused by nutmeg). Nutmeg butter does contain trimyristin, which may have slight sedative effects. However, my attempts to repeat Fandango's recipe produced no sedation nor any other psychoactive effects.

Another preparation floating around the Internet is a recipe for "space paste" (Me 2001). The recipe is as follows, where one "part" equals a tablespoon.

4 parts nutmeg (ground from whole nutmeg)
4 parts almonds (soak overnight and rinse)
4 parts raw pistachios
2 parts cinnamon
1 part cumin
1 part tarragon
1 part oregano
1 part basil
1 part turmeric
1/2 part cayenne pepper
1/2 part black pepper
maple syrup (to taste)

One Internet poster, identifying himself as "Me," compared eating two tablespoons of space paste to eating marijuana brownies and reported that this dose produced mild hallucinations (Me 2001). Two tablespoons of paste would contain less than one teaspoon of nutmeg--a threshold dose at best. However, a quick search of the Internet demonstrated that "Me" was not the only individual to have success with this recipe. The following question was submitted to a medical web site:

Mother brings 14 y.o. female to emergency room. Initial exam is exceptional for elevated respiration and BP, nausea, moderate perspiration, and child complaining of colorful hallucinations. A typical LSD case, or maybe an exotic hallucinogen? Nope. Kids made a concoction out of the following ingredients: Nutmeg, almonds, raw pistachios, cinnamon, cumin, tarragon, oregano, basil, turmeric, cayenne pepper, black pepper, and Maple Syrup, mixed into a vanilla milkshake. Nice coating for pork chops, but is there anything here that would explain the patient's condition? -- Houston, TX (Houston 2006).

The questioner was advised that nutmeg was the likely culprit. However, given the low levels of nutmeg, other ingredients likely play a synergistic role in the inebriating effect. The author, "Me," declares that the recipe will not work unless all ingredients are included. Black pepper also contains high levels of myristicin, and the Winter 2003 issue of The Entheogen Review commented on how the chemical piperine from black pepper inhibits the metabolism of some drugs/chemicals, leading to an increase in their effects [TER 12(4): 134]. Capsaicin, a chemical found in cayenne pepper, is also a mild inhibitor of cytochrome P450 2E1, which is a mixed-function oxidase involved in metabolism that mediates some drug interactions. It could be that one or both of these peppers is the reason why lower doses of nutmeg seem to have stronger effects when taken via this preparation.

While few inebriating plant preparations are palatable for the average person, there are some low-dose nutmeg preparations useful as aphrodisiacs or mood-elevators that are quite agreeable. Add 1/4 to 1/2 tsp of nutmeg to a cup of hot chocolate and let it simmer until the surface of the drink becomes oily. This makes for a spicy drink that helps to allay anxiety and imbues confidence and a positive outlook.

Christian Rtsch and Claudia Mller-Ebeling (2006) offer the following recipe for "Cookies for Preventing Sadness" in their book Pagan Christmas: The Plants, Spirits, and Rituals at the Origins of Yuletide. The recipe is slightly modified for purposes of American baking measurements.

2 Tbsp ground nutmeg
2 Tbsp ground cinnamon
1.5 tsp ground cloves
3 cups flour
3/4 cup sugar
2 sticks of butter
2 eggs
pinch salt
3/4 cup chopped almonds

Mix ingredients and bake cookies at 350F for five to ten minutes. The cookies are sweet, spicy, and they lift the spirits. Perfect for the holidays.

PHARMACOLOGY & TOXICITY

Nutmeg consists of 45-60% cellulose and solid matter, 24-40% fixed oils and 5-15% volatile oils. The fixed oil (or "butter") of nutmeg is an orange-colored waxy substance. The butter contains 70-85% trimyristin, which has been shown to have a sedative effect on chickens, and it also contains myristic acid. The real power of nutmeg, however, is contained within the volatile (or essential) oil.

The volatile oil of nutmeg is a pale-yellow, nearly colorless liquid, with a distinct smell of nutmeg. The volatile oil contains 80% monoterpenes and 5% monoterpene alcohols with the remainder made up by aromatic ethers and miscellaneous compounds (Forrest & Heacock 1972). The aromatic ether fraction contains myristicin, elemicin, and safrole, along with other alkyl-benzene derivatives, such as estragole, eugenol, iso-elemicin, iso-eugenol, methyl-eugenol, methyl-isoeugenol, and methoxy-eugenol (Kalbhen 1971; Forrest & Heacock 1972; Shulgin 1967; Shulgin et al. 1967; Duke 2008), and it is believed to be responsible for the psychoactive effects of nutmeg.

It has been speculated that the psychoactivity of myristicin, elemicin, and safrole is due to their metabolizing into known psychoactive compounds. Alexander Shulgin proposed in 1967 that the compounds would metabolize in the body as follows: myristicin to MMDA; elemicin to TMA; and safrole into MDA (Shulgin 1967). However, studies that have tried to confirm this process were unable to detect amphetamine-type compounds in the urine of rats that were administered myristicin and safrole (Forrest & Heacock 1972, citing Oswald et al. 1971).

The psychoactive effects of nutmeg are still not well understood, and only myristicin has been tested on human subjects.

Myristicin, or methoxysafrole, is a benzodioxole with slight MAO-inhibiting properties. Myristicin is a colorless oil that generally does not crystallize, even at extremely low temperatures (i.e., -30C). Myristicin is mostly stable upon storage, but still subject to gradual changes in composition. Myristicin is insoluble in water and only slightly soluble in ethanol. The best solvents for extracting myristicin are benzene and diethyl ether.

Myristicin generally makes up 4-8% of nutmeg's volatile oil and has been found in concentrations as high as 1.3% of nutmeg by weight (C.E.F.S. 2005). The myristicin content in mace is generally double that of nutmeg, making it potentially more potent than nutmeg.

Myristicin is active at the 5-HT receptors in the brain, and has been shown to have hypotensive, sedative, anti-depressant, anesthetic, hallucinogenic, and serotonergic properties (Sangalli & Chiang 2001). Large doses generally cause hyper-excitability, followed by CNS depression. Myristicin is fairly unique as a hallucinogen (if it may be classified as such), because it lacks a nitrogen atom. It is also rare for a compound lacking a nitrogen group to show activity at the brain's 5-HT receptors.

Myristicin's psychoactive properties were confirmed by a study on ten human participants in 1961 (Hallstrom & Thuvander 1997, citing Truitt et al. 1961). Each of the participants was administered 400 mg of myristicin, or approximately 6-7 mg/kg by body weight. Only four of the participants experienced psychoactive effects, including euphoria, anxiety, and trouble concentrating.1

That only four participants experienced psychoactive effects at this level suggests that 400 mg or (6-7 mg/kg) is a threshold effective dose for nearly half of the population. Time of onset was between two and three hours after ingestion. Interestingly, 400 mg of myristicin is around twice the amount of myristicin that would be present in a moderate-high psychoactive dose of nutmeg, suggesting that myristicin is not the sole psychoactive agent in nutmeg.

Myristicin is found elsewhere in nature, notably in black pepper, carrots, celery, dill weed, parsley, and parsnip. Myristicin is almost completely processed in the body within 48 hours of ingestion. This long processing period may help to explain the extraordinary length of nutmeg's effect.

Because of myristicin's close relationship with safrole, it has long been considered a "suspected carcinogen." However, scientific data is lacking on this point. Several studies indicate possible carcinogenicity, but the results have been statistically insignificant. Myristicin has shown mild DNA binding properties, an indicator of carcinogenicity, but has not been found to be genotoxic (Hallstrom & Thuvander 1997).

In one study, twelve rats were administered 10 mg/kg of myristicin per day for twenty-six days. After this period, no differences in body weight were discernible from the control group and no abnormalities were detected in the liver or kidneys. The LD-50 (lethal dose for 50% of the population) in rats was shown to be greater than 1000 mg/kg (Hallstrom & Thuvander 1997). For comparison sake, the threshold effective dose in humans stands around 6-7 mg/kg.

Myristicin has also been suspected as a potential hepatotoxin, but the studies available suggest that rather than being hepatotoxic, myristicin may in fact be hepatoprotective (Morita et al. 2003).

One study consisted of injecting mice with LPS (lipopolysaccharide) and d-GaIN (d-galactosamine), both liver toxins, and measuring the changes in levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase), both enzymes that indicate liver injury. A single oral dose of myristicin at quantities of 50, 100 and 200 mg/kg was shown to inhibit serum elevations of both ALT and AST in the injected mice (Morita et al. 2003). Further, DNA fragmentation generally caused by the liver toxins LPS and d-GaIN was effectively suppressed by a single oral dose of 200 mg/kg of myristicin (Morita et al. 2003).

Several studies on mice suggest that myristicin may reduce the frequency of and inhibit the growth of tumors. One study showed that myristicin significantly reduced tumor formation in the lungs and forestomachs of mice with benzo(a)pyrene-induced carcinogenicity (Hallstrom & Thuvander 1997). Myristicin has also been shown to be an inducer of GST (glutathione S-transferase), a substance that inhibits tumorigenesis. Myristicin was shown to cause a fourfold increase in GST activity in the liver and a threefold increase in the small intestine (C.S.W.G. 1997).

Studies on other animals have been less promising. Cats orally administered 400 mg/kg of myristicin experienced fatty degeneration of the liver while rabbits and guinea pigs administered myristicin subcutaneously experienced both brain and liver lesions (Forrest & Heacock 1972).

Studies on chronic and reproductive toxicity and carcinogenicity of myristicin are still lacking. Further studies on myristicin's hepatoprotective and tumor-inhibiting properties are also needed.

Elemicin, one of the other suspected psychoactive components of nutmeg, is similar to myristicin in that it lacks a nitrogen group and is also active at the brain's 5-HT receptors. Elemicin has displayed anti-depressant, hallucinogenic, anti-histamine, hypotensive and anti-serotonergic properties (Sangalli & Chiang 2000). There is some evidence of DNA binding and genotoxicity with elemicin (C.E.F.S. 2005). Studies on hepatocarcinogenicity have been inconclusive.

Safrole is also suspected of contributing to the psychoactive properties of nutmeg, but there is sparse evidence to support this theory. Safrole makes up 75-80% of oil of sassafras, which has been used medicinally for hundreds of years and has never been reported to be hallucinogenic (Forrest & Heacock 1972). The FDA considers safrole to be carcinogenic--a finding that some herbalists take issue with based on its long history of safe use by various Native American groups (Buhner 1998).

The terpenes are generally not suspected of contributing to the psychoactivity of nutmeg. However, many compounds from the terpenic fraction of nutmeg are structurally similar to known CNS stimulants. Overdoses on some terpene-containing medicines have also been reported to produce similar reactions to those caused by nutmeg (Forrest & Heacock 1972). Whether psychoactive or not, the terpenes may still contribute to the effect of nutmeg by irritating the gastrointestinal tract and thus facilitating absorption of the suspected psychoactive compounds (Kalbhen 1971).

While the toxicity of nutmeg is still in question, there are numerous reports of accidental poisonings and emergency room visits that help provide some extra information. In poisoning cases vitals are taken and organs are checked and monitored for abnormalities. Several case studies merit brief mention. The Journal of Internal Medicine reported on the case of a thirty-two-year-old man who sought emergency room care after ingesting seven grams of ground nutmeg (Sjoholm et al. 1998). The hospital ran tests on the man and found that his blood count, electrolyte levels, calcium and liver enzymes were all within normal ranges. The Journal of Clinical Toxicology also reported on a nutmeg poisoning case involving a thirteen-year-old who had ingested 15-25 grams of nutmeg (Sangalli & Chiang 2000). Tests conducted on the boy showed that electrolyte levels, renal and liver function, urinalysis, hematology, and a pelvic ultrasound all returned without abnormality. Almost all cases of nutmeg poisoning are resolved without note and most emergency room visits are accounted for by accidental poisonings or by panic reactions.

There are two recorded deaths involving nutmeg poisoning. The first case involved an eight-year-old boy who ingested fourteen grams of nutmeg, or the equivalent of 560 mg/kg of myristicin by body weight (Stein et al. 2001). The boy fell into a coma and died twenty-four hours after ingestion. There do not appear to be any other explanations beyond nutmeg poisoning for the boy's death. The second case involved the death of a fifty-five-year-old woman (Stein et al. 2001). The woman was found with toxic, but not fatal, concentrations of flunitrazepam (Rohypnol) in her blood. Blood tests also showed the presence of myristicin, with a speculated dose of between 560 and 840 mg/kg of myristicin by body weight. While the myristicin levels in the two fatal cases are comparable, it is believed that the combination of a high dose of nutmeg and a toxic dose of flunitrazepam was the cause of death. Other instances from emergency rooms and poison control centers report that cases of nutmeg poisoning involving up to eighty grams of nutmeg (or up to 1100 mg/kg of myristicin by body weight) have occurred without the presence of life-threatening symptoms (Stein et al. 2001).

CONCLUSIONS

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