Evidence for the Biogenic Formation of Amphetamine Derivatives from Components of Nutmeg

Braun, U.; Kalbhen, D.A.

doi:10.1159/000136402

Cited by 39 publications

(22 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The metabolism of myristicin has been investigated in several types of in vitro systems [Braun and Kalbhen, 1973;Casida et al,1966;Kamienski and Casida, 1970;Scheline, 1991].…”

Section: Kinetics and Metabolism Data In Vitromentioning

confidence: 99%

Toxicological evaluation of myristicin

Hallström

Thuvander

1997

Natural Toxins

View full text Add to dashboard Cite

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. Nat.

show abstract

“…The metabolism of myristicin has been investigated in several types of in vitro systems [Braun and Kalbhen, 1973;Casida et al,1966;Kamienski and Casida, 1970;Scheline, 1991].…”

Section: Kinetics and Metabolism Data In Vitromentioning

confidence: 99%

Toxicological evaluation of myristicin

Hallström

Thuvander

1997

Natural Toxins

View full text Add to dashboard Cite

show abstract

“…So far, the hypothesis has not been experimentally supported. Inconsistent animal findings and lack of detection of the amphetamine-like metabolites in biological fluids of nutmeg abusers led to reevaluation of the validity of the hypothesis (Braun 1973;Beyer et al 2006). Further experimental data have ascribed several additional nervous system effects to nutmeg.…”

Section: Introductionmentioning

confidence: 99%

Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract

El‐Alfy

Joseph

Brahmbhatt

et al. 2016

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Nutmeg [Myristica fragrans Houtt. (Myristicaceae)] has a long-standing reputation of psychoactivity. Anecdotal reports of nutmeg use as a cheap marijuana substitute, coupled to previous studies reporting a cannabimimetic-like action, suggest that nutmeg may interact with the endocannabinoid system. Objective: The study evaluates nutmeg fractions for binding capacity with various CNS receptors and their potential interaction with the endocannabinoid system. Materials and methods: Dichloromethane (DF) and ethyl acetate (EF) fractions were prepared from the methanol extract of powdered whole nutmeg. The HPLC-profiled fractions were assayed by the NIMH Psychoactive Drug Screening Program (PDSP) in a panel of CNS targets at a 10 lg/mL concentration. The fractions were also screened for fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition, initially at a concentration of 500 lg/mL, then by concentration-dependent inhibition studies.Results: None of the tested fractions showed significant binding to CNS receptors included in the PDSP panel. However, both fractions exerted significant inhibition of the FAAH and MAGL enzymes. The DF fraction inhibited FAAH and MAGL enzymes at IC 50 values of 21.06 ± 3.16 and 15.34 ± 1.61 lg/mL, respectively. Similarly, the EF fraction demonstrated FAAH and MAGL inhibition with IC 50 values of 15.42 ± 3.09 and 11.37 ± 6.15 lg/mL, respectively. Discussion and conclusion: The study provides the first piece of evidence that nutmeg interacts with the endocannabinoid system via inhibition of the endocannabinoid catabolizing enzymes. This mechanism provides insight into reported cannabis-like action as well as expands the potential therapeutic utility of nutmeg.ARTICLE HISTORY

show abstract

“…Similarly, eugenol derivatives have also been found to possess activity in the PTZ seizure test (Dallmeier and Carlini, 1981). The weak proconvulsant activity of nutmeg oil for clonic seizures may be due to the myristicin and elemicin, which are metabolized in vivo into amphetamine-like compounds (Shulgin, 1966;Kalbhen, 1971;Braun and Kalbhen, 1973). Another major constituent of nutmeg oil terpinene-4-ol, has not been studied extensively for its CNS effects, and therefore may contribute to the CNS activity of nutmeg oil.…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant activities of nutmeg oil of Myristica fragrans

Wahab

Haq

Ahmed

et al. 2008

Phytotherapy Research

View full text Add to dashboard Cite

The purpose of this study was to investigate the anticonvulsant activity of the volatile oil of nutmeg, the dried seed kernel of Myristica fragrans Houtt, using well-established animal seizure models and to evaluate its potential for acute toxicity and acute neurotoxicity. The volatile oil of nutmeg (nutmeg oil) was tested for its effects in maximal electroshock, subcutaneous pentylenetetrazole, strychnine and bicuculline seizure tests. All the experiments were performed at the time of peak effect of nutmeg oil. Nutmeg oil showed a rapid onset of action and short duration of anticonvulsant effect. It was found to possess significant anticonvulsant activity against electroshock-induced hind limb tonic extension. It exhibited dose dependent anticonvulsant activity against pentylenetetrazole-induced tonic seizures. It delayed the onset of hind limb tonic extensor jerks induced by strychnine. It was anticonvulsant at lower doses, whereas weak proconvulsant at a higher dose against pentylenetetrazole and bicuculline induced clonic seizures. Nutmeg oil was found to possess wide therapeutic margin, as it did not induce motor impairment when tested up to 600 microL/kg in the inverted screen acute neurotoxicity test. Furthermore, the LD(50) (2150 microL/kg) value was much higher than its anticonvulsant doses (50-300 microL/kg). The results indicate that nutmeg oil may be effective against grand mal and partial seizures, as it prevents seizure spread in a set of established animal models. Slight potentiation of clonic seizure activity limits its use for the treatment of myoclonic and absence seizures.

show abstract

Evidence for the Biogenic Formation of Amphetamine Derivatives from Components of Nutmeg

Cited by 39 publications

References 6 publications

Toxicological evaluation of myristicin

Toxicological evaluation of myristicin

Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract

Anticonvulsant activities of nutmeg oil of Myristica fragrans

Contact Info

Product

Resources

About