Studies & Science
This is a collection of various studies conducted over the years, regarding nutmeg and more specifically myristicin. None of these works are original, you can find the original texts and the authors who wrote them at the links I provide within the titles. Everything here is meant to entertain and/or inform, and in no way am I making any claims regarding the medicinal uses of nutmeg either way…
That said, here’s some brain food.
An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg)
Myristica fragrans Houtt. (nutmeg) has been mentioned in Unani medicine to be of value in the management of male sexual disorders. The present study was undertaken to evaluate the aphrodisiac effect of 50% ethanolic extract of nutmeg along with its likely adverse effects and acute toxicity using various animal models.MethodsThe suspension of the extract was administered (100, 250 and 500 mg/kg, p.o.) to different groups of male rats daily for seven days. The female rats involved in mating were made receptive by hormonal treatment. The general mating behaviour, libido and potency were studied and compared with the standard reference drug sildenafil citrate. Likely adverse effects and acute toxicity of the extract were also evaluated.Results
Oral administration of the extract at the dose of 500 mg/kg, produced significant augmentation of sexual activity in male rats. It significantly increased the Mounting Frequency, Intromission Frequency, Intromission Latency and caused significant reduction in the Mounting Latency and Post Ejaculatory Interval. It also significantly increased Mounting Frequency with penile anaesthetisation as well as Erections, Quick Flips, Long Flips and the aggregate of penile reflexes with penile stimulation. The extract was also observed to be devoid of any adverse effects and acute toxicity.Conclusion
The resultant significant and sustained increase in the sexual activity of normal male rats without any conspicuous adverse effects indicates that the 50% ethanolic extract of nutmeg possesses aphrodisiac activity, increasing both libido and potency, which might be attributed to its nervous stimulating property. The present study thus provides a scientific rationale for the traditional use of nutmeg in the management of male sexual disorders.
Abstract
Seeds of nutmeg are used as spice, but they are also abused because of psychotropic effects described after ingestion of large doses. It was postulated that these effects could be attributable to metabolic formation of amphetamine derivatives from the main nutmeg ingredients elemicin (EL), myristicin (MY), and safrole (SA). In a case of a suspected nutmeg abuse, neither such amphetamine derivatives nor the main nutmeg ingredients could be detected in urine. The metabolites of EL, MY, and SA were identified using gas chromatography-mass spectrometry in rat urine and their presence in human urine of the nutmeg abuser was confirmed. The identified metabolites indicated that EL, MY, and SA were once and twice hydroxylated at the side chain. In addition, EL was O-demethylated at 2 positions followed by side chain hydroxylation. MY and SA were demethylenated and subsequently methylated. In the human urine sample, the following metabolites could be identified: O-demethyl elemicin, O-demethyl dihydroxy elemicin, demethylenyl myristicin, dihydroxy myristicin, and demethylenyl safrole. As in the human urine sample, neither amphetamine derivatives nor the main nutmeg ingredients could be detected in the rat urine samples. Finally, toxicologic detection of nutmeg abuse was possible by identification of the described metabolites of the EL, MY, and SA in urine applying the authors’ systematic toxicologic analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction of analytes, and microwave-assisted acetylation of extracted analytes.
Nutmeg is a common household spice sometimes abused for its hallucinogenic properties (8). This abuse is well reported in the medical literature over the last century. Ingestion of less than 1 tablespoon of Nutmeg can produce symptoms similar to those of an anticholinergic toxic episode (9).
Common presenting complaints are hallucinations, palpitations, and feelings of impending doom. A study reports on a case of intentional Nutmeg intoxication in a 23-year-old college student (10).Other reports are similar. Several intoxications were reported after ingestion of approximately 5 g of Nutmeg, corresponding to 1 – 2 mg myristicin/kg body weight. The authors suggested that although the symptoms may be ascribed to the actions of myristicin, it is likely that other components of Nutmeg are also involved. Other authors have stated that 6 – 7 mg/kg b.w. may be enough to cause psychopharmacological effects in man. Intake estimations indicate that nonalcoholic drinks may be the most important single source of myristicin intake. Based on available data, it seems unlikely that the intake of myristicin from essential oils and spices in food, estimated at a few mg per person and day in this report, would cause adverse effects in humans (9).Side-effects associated with the abuse of Nutmeg occasionally generate emergency department referrals and may be frightening. A 13-year-old female who ingested 15-24 g of Nutmeg over a 3-hour period, and smoked and shared 2 joints of marijuana, developed bizarre behaviour and visual, auditory, and tactile hallucinations. She also experienced nausea, gagging, hot/cold sensations, and blurred vision followed by numbness, double, and “triple” vision, headache, and drowsiness. Nystagmus, muscle weakness, and ataxia were present (11).A fatal case of poisoning has also been reported. In a 55-year-old woman who died from Nutmeg poisoning, the post-mortem serum level of myristicin was documented to be 4 microg/ml. From 1996 to 1998, in a series of cases, 7 poisonings with Nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed. In 1 of these cases, a myristicin blood level of 2 microg/ml was measured 8 hours after ingestion of 2 to 3 tablespoonsful of Nutmeg powder (approx. 14-21 g, or 280-420 mg/kg) (12).
Adverse reactions may extend beyond central nervous system effects. Acute Nutmeg poisoning occurred in a 16-year-old youth who had ingested the substance for recreational purposes. He developed a number of neurological symptoms and signs along with non-specific electrocardiographic changes and anti-cholinergic-type symptoms
Glutathione S-transferase (GST) assay-guided fractionation of parsley leaf oil from the edible plant Petroselinum sativum Hoffm. (Umbelliferae) led to the isolation of myristicin. Myristicin showed high activity as an inducer of the detoxifying enzyme GST in the liver and small intestinal mucosa of female A/J mice. Reduction of myristicin yielded dihydromyristicin that retained the GST-inducing activity. Myristicin and dihydromyristicin were tested for their capacity to inhibit benzo[a]pyrene (B[a]P)-induced tumor formation in female A/J mice. A 65% inhibition of the tumor multiplicity in the lung was observed as the result of treatment of myristicin. Dihydromyristicin produced small or insignificant reduction of lung tumor formation. In the forestomach, myristicin showed a 31% inhibition of tumor formation; while dihydromyristicin exhibited a 27% inhibition. Comparison of the structures and activities indicated that the saturation of the isolated double bond in myristicin resulted in a significant decrease in the inhibitory activity against B[a]P-induced tumorigenesis. The present results showed that myristicin, an active inducer of GST activity, is an effective inhibitor of B[a]P-induced tumorigenesis in mice. Stimulation of GST activity by myristicin could be a major mechanism for its inhibition of B[a]P or other carcinogens that may be detoxified in the same manner. As a culinary herb parsley is regularly consumed by humans. Parsley leaf oil is also used extensively for garnishing and seasoning. The results of this study indicate that as a major volatile aroma constituent of parsley myristicin may be an effective cancer chemopreventive agent.
Synergism between myristicin and xanthotoxin, a naturally cooccurring plant toxicant
Myristicin, a methylenedioxyphenyl (MDP)-containing phenylpropene constituent of the leaves of many plants in the family Umbelliferae, is a highly effective Synergist of the cooccurring furanocoumarin xanthotoxin. As little as 0.10 % in an artificial diet can increase the toxicity of xanthotoxin toHeliothis zea (Lepidotera: Noctuidae) fivefold. In addition to increasing the proportion of caterpillars dying at a given xanthotoxin concentration, myristicin also increases the rate at which they die and increases the time to molt of surviving larvae. That there was no increase in the deterrency of xanthotoxin in the presence of myristicin suggests that the mechanism of synergism is not behaviorial but rather is biochemical, via MDP competitive inhibition of microsomal mixed function oxidases.
The transformation of myristicin and elemicin to the corresponding amphetamines can readily be achieved by chemical means, but it has been indicated that these transformations can also be effected biologically. Hydroxylation of the allyl group is a known biological process, and subsequent transamination (also a known process) would immediately yield an amphetamine. Both myristicin and intact nutmeg have been shown to possess central nervous system activity (Truitt et al., 1961), and myristicin has been shown to increase brain serotonin levels (Truitt et al., 1963), which would result in an increase in satiety. It has been variously suggested that myristicin and elemicin may also be converted by transamination in the brain into amphetamine-like substances with hunger-suppressant effects (Shulgin, 1966), or that myristicin, which has a weak mono-amine oxidase inhibiting effect, could compete with noradrenaline as a substrate for mono-amine oxidase, thus increasing noradrenaline levels with consequent hunger-suppressant actions (Truitt, 1967). It is probable that these enzymatically-mediated changes do indeed occur in the human body to some extent, since this would explain the similarity of the physiological activities of myristicin to those of the amphetamines. In view of the lack of peripheral activity of myristicin, it is also probable that the substance passes the blood-brain barrier and undergoes further transformation in the central nervous system. Since the molecule is lipophilic, it would cross the blood-brain barrier readily, and may exert an anorexic effect, of value in inducing weight loss, by inhibition of the hunger centre.
To evaluate the hepatoprotective activity of spices, 21 different spices were fed to rats with liver damage caused by lipopolysaccharide (LPS) plus d-galactosamine (D-GalN). As assessed by plasma aminotranferase activities, nutmeg showed the most potent hepatoprotective activity. Bioassay-guided isolation of the active compound from nutmeg was carried out in mice by a single oral administration of the respective fractions. Myristicin, one of the major essential oils of nutmeg, was found to possess extraordinarily potent hepatoprotective activity. Myristicin markedly suppressed LPS/D-GalN-induced enhancement of serum TNF-alpha concentrations and hepatic DNA fragmentation in mice. These findings suggest that the hepatoprotective activity of myristicin might be, at least in part, due to the inhibition of TNF-alpha release from macrophages. However, further studies are needed to elucidate the hepatoprotective mechanism(s) of myristicin.
Roles of human liver cytochrome P450 3A4 and 1A2 enzymes in the oxidation of myristicin.
The aim of this work was to identify the form(s) of human liver cytochrome P450 (CYP) involved in the hepatic transformation of myristicin to its major metabolite, 5-allyl-1-methoxy-2,3-dihydroxybenzene. When microsomes prepared from different human liver samples were compared, the activity of 5-allyl-1-methoxy-2,3-dihydroxybenzene formation was well correlated (r(2)=0.87) with nifedipine oxidation (a marker of CYP3A4). With a microsomal sample having high CYP3A4 activity, microsomal oxidation of myristicin to the major metabolite (5-allyl-1-methoxy-2,3-dihydroxybenzene) was markedly inhibited by gestodene and ketoconazole, selective inhibitors of CYP3A enzymes, but not by any of several other P450 inhibitors. Antibodies raised against CYPs 3A4 and 1A2 could also inhibit the oxidation of myristicin, but antibodies recognizing other CYPs had no effect. The oxidation of myristicin to 5-allyl-1-methoxy-2,3-dihydroxybenzene was catalyzed by purified bacterial recombinant CYPs 3A4 and 1A2. These results provide evidence that CYP3A4 (and possibly other CYP3A enzymes) and CYP1A2 play roles in the formation of the major metabolite, 5-allyl-1-methoxy-2,3-dihydroxybenzene.
Myristicin, or methoxysafrole, is the principal aromatic constituent of the volatile oil of nutmeg, the dried ripe seed of Myristica fragrans. Myristicin is also found in several members of the carrot family (Umbelliferae). Several intoxications have been reported after an ingestion of approximately 5 g of nutmeg, corresponding to 1-2 mg myristicin/kg body weight (b.w.). Although these intoxications may be ascribed to the actions of myristicin, it is likely that other components of nutmeg may also be involved. The metabolism of myristicin resembles that of safrole. No information is available, however, concerning the quantitative importance of the different metabolic pathways. The acute toxicity of myristicin appears to be low. No toxic effects were observed in rats administered myristicin perorally at a dose of 10 mg/kg b.w., while 6-7 mg/kg b.w. may be enough to cause psychopharmacological effects in man. A weak DNA-binding capacity has been demonstrated, but there are no indications that myristicin exerts carcinogenic activity in short-term assays using mice. Intake estimations indicate that nonalcoholic drinks may be the most important single source of myristicin intake. Based on available data, it seems unlikely that the intake of myristicin from essential oils and spices in food, estimated to a few mg per person and day in this report, would cause adverse effects in humans. It is, however, at present not possible to make a complete risk assessment, as studies regarding genotoxicity and chronic toxicity, including reproductive toxicity and carcinogenicity, are still lacking.
Increased Concentration of Myristicin and 6-Methoxymellein in Carrot Root upon Irradiation with UV Light
Myristicin has not been reported to possess antifungal activity, and therefore is not a phytoalexin according to the standard interpretation of this term (1). It does, however, potentiate the activity of the insecticide, paraoxon, in flies by inhibiting its degradation (2), and may in similar manner potentiate the action of phytoalexins of carrot root (falcarinol, falcarindiol, 6-methoxymellein) (3,4). The presence of myristicin in carrots is of interest to nutritionists because of its biological properties (5), and its chemical similarity to safrole, a mild carcinogen (6).
Results of Wulf et al (7) show that carrot roots obtained from a supermarket contain myristicin; Imperator variety carrots contain an average of 15 parts per million (ppm). Recently harvested, unprocessed carrots only rarely contain myristicin (8). The presence of myristicin in supermarket carrots and its absence in recently harvested ones indicate that its increased concentration may have been induced by some elicitor following harvest.
Myristicin in Cigarette Smoke
The pharmacologically active aromatic ether, myristicin, was isolated from the smoke of commercial cigarettes. The compound was identified by spectrometry (infrared, ultraviolet, and mass) and gas chromatography. The amount of myristicin in smoke is relatively low, and its contribution, if any, to the physiological action of cigarette smoke is unknown.
More to come later…If you have any studies, points to raise, comments, etc, feel free to contribute through leaving a comment, sending an email, or whatever. Full studies, or access to full studies, is very much appreciated.
Update: more studies! Hooray.
Towards a better understanding of the psychopharmacology of nutmeg: Activities in the mouse tetrad assay.
ETHNOPHARMACOLOGICAL RELEVANCE: Nutmeg, the seeds of Myritica fragrans (family Myristicaceae), is a well known kitchen spice with a long-standing reputation as a psychoactive herb. Nutmeg at high doses is considered a cheap substitute to several drugs of abuse. Earlier reports have attributed amphetamine-like activities to nutmeg. AIM OF THE STUDY: To characterize the neuropharmacological effects of different nutmeg extracts, administered orally and intraperitoneally, in comparison to Delta(9)-terahydrocannabinol, amphetamine, and morphine. MATERIALS AND METHODS: Methanolic (ME), dichloromethane (DE), and hexane (HE) extracts were obtained from a chromatographically fingerprinted batch of nutmeg. Biological evaluation was conducted in sets of 6-8 mice in the tetrad assay at doses ranging from 100 to 500 and 500 to 1000 mg/kg for i.p. and oral administration, respectively. RESULTS: While oral administration of all the nutmeg extracts at 500 mg/kg caused a significant increase in locomotor activity, the i.p. administration of DE showed significant reduction in rectal temperature along with a significant increase in tail flick latency at 300 mg/kg. A significant decrease in core body temperature was observed with HE at 100 mg/kg, while higher doses caused significant increases in hot plate latency. CONCLUSION: Different behavioral effects were observed that varied by the type of extract as well as by the route of administration.
Antidepressant-like activity of n-hexane extract of nutmeg (Myristica fragrans) seeds in mice.
The present study was undertaken to investigate the effect of an n-hexane extract of Myristica fragrans seeds on depression in mice by using the forced swim test (FST) and the tail suspension test (TST). M. fragrans extract (5, 10, and 20 mg/kg) was administered orally for 3 successive days to different groups of Swiss male young albino mice. M. fragrans extract significantly decreased immobility periods of mice in both the FST and the TST. The 10 mg/kg dose was found to be most potent, as indicated by the greatest decrease in the immobility period compared with the control. Furthermore, this dose of the extract was found to have comparable potency to imipramine (15 mg/kg i.p.) and fluoxetine (20 mg/kg i.p.). The extract did not have a significant effect on locomotor activity of mice. Prazosin (62.5 microg/kg i.p.; an alpha (1)-adrenoceptor antagonist), sulpiride (50 mg/kg i.p.; a selective D(2) receptor antagonist), and p-chlorophenylalanine (100 mg/kg i.p.; an inhibitor of serotonin synthesis) significantly attenuated the M. fragrans extract-induced antidepressant-like effect in the TST. Thus, extract of M. fragrans elicited a significant antidepressant-like effect in mice, when assessed in both the TST and the FST. The antidepressant-like effect of the extract seems to be mediated by interaction with the adrenergic, dopaminergic, and serotonergic systems.
Effect of volatile oil from nutmeg on liver microsomal cytochrome P450 in mice
BJECTIVE: To study the effect of the volatile oil from nutmeg on liver microsomal cytochrome P450 in mice. METHOD: Mice were administered the volatile oil from nutmeg at 0.4, 0.8 and 1.2 mg x g(-1), respectively, twice a day for 10 days. And then, the contents of liver microsomal cytochrome P450 (CYP), cytochrome b5 (Cytb5), MDA and GST in serum were examined by UV chromatography method. RESULT: The contents of liver CYP, Cytb5 and GST in serum were increased significantly (P < 0.01) and the contents of MDA was reduced significantly (P < 0.01). CONCLUSION: The volatile oil from nutmeg showed induction effect on the hepatic microsomal CYP in mice.
More on nutmeg as an aphrodisiac.
BackgroundSpices are considered as sexual invigorators in the Unani System of Medicine. In order to explore the sexual function improving effect of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) an experimental study was conducted in normal male mice.MethodsThe extracts (50% ethanolic) of nutmeg and clove were administered (500 mg/kg; p.o.) to different groups of male Swiss mice. Mounting behaviour, mating performance, and general short term toxicity of the test drugs were determined and compared with the standard drug Penegra (Sildenafil citrate).ResultsThe extracts of the nutmeg and clove were found to stimulate the mounting behaviour of male mice, and also to significantly increase their mating performance. The drugs were devoid of any conspicuous general short term toxicity.ConclusionThe extracts (50% ethanolic) of nutmeg and clove enhanced the sexual behaviour of male mice.