Letter to the Editors

Nutmeg and psychosis

Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography–tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14–0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996–0.997) for all three compounds at 0.5–300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4–11 % and 2.5–11 %, respectively; bias ranged from − 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.

Quality nutmeg is characterized by a delicate aroma. Next to quality nutmeg, other – lower - grades exist on the market, such as extracted material (spent) or ground shell or dried fruit pulp. Strong fluctuations in the price of nutmeg lead to rapid changes in market dynamics and marketing opportunities, and unfortunately results in illegal commingle of ground quality nutmeg with low-grade material. In this study, we examined fingerprints of volatile and non-volatile compounds of high quality and low-grade nutmeg material by Proton Transfer Reaction Mass Spectrometry and Flow Infusion ElectroSpray Ionization Mass Spectrometry, respectively. They were compared with data from classical measurements such as total ash, acid insoluble ash, moisture and volatile oil contents. Differences in composition were examined by univariate and multivariate statistical methods. Furthermore, one-class classification models for quality nutmeg were estimated using different algorithms and their performances were examined with quality nutmeg and low-grade material, as well as mixtures thereof. Distinct differences between quality nutmeg and low-grade nutmeg samples were observed for both their volatile and non-volatile fingerprints. Intensities of volatiles and non-volatiles are highly correlated, but this phenomenon diminishes gradually and even reverses with rising molecular mass of the non-volatiles. Results showed that both techniques allowed a nearly 100% correct prediction of quality nutmeg and low-grade nutmeg samples. Therefore, both approaches are promising and with further database extension, they may become a valuable addition to the analytical authentication toolbox in addition to the classical methods and help to detect future ‘nutmeggers’.

Nutmeg is commonly used as a spice in various dishes; it is a component of teas and soft drinks, and can also be mixed in milk and alcohol. In this study, we investigated the effect of chronic consumption of nutmeg on the stomach of adult Wistar rats. Rats of both sexes (n = 24), with an average weight of 200 g, were randomly assigned into two treatment groups (A and B, n = 8 for each group) and one control group (C, n = 8). The rats in the treatment groups received 1 g of nutmeg in group A and 2 g of nutmeg in group B. The nutmeg was thoroughly mixed with feed and given daily for 32 days. Group C received an equal amount of feed daily without nutmeg for 32 days. The rats had free access to water. On day 33 of the experiment, the rats were sacrificed by cervical dislocation. The stomachs were carefully dissected out and immediately fixed in 10% formal saline for histological study. Hematoxylin and eosin staining showed that rats in groups A and B showed varying degrees of distortion in the epithelial cells of the stomach. Obvious signs of proliferation, hyperplasia, and atrophic changes in the treated stomach sections were more marked in group B than in the other groups. These findings indicate that nutmeg may have some deleterious effects on the microanatomy of the stomach of adult Wistar rats.

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.

To characterize the neuropharmacological effects of different nutmeg extracts, administered orally and intraperitoneally, in comparison to Δ⁹-terahydrocannabinol, amphetamine, and morphine.

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.

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.

Different behavioral effects were observed that varied by the type of extract as well as by the route of administration.