Worldwide, there are plants known as psychoactive plants that naturally contain psychedelic active components. They have a high concentration of neuroprotective substances that can interact with the nervous system to produce psychedelic effects. Despite these plants' hazardous potential, recreational use of them is on the rise because of their psychoactive properties. Early neuroscience studies relied heavily on psychoactive plants and plant natural products (NPs), and both recreational and hazardous NPs have contributed significantly to the understanding of almost all neurotransmitter systems. Worldwide, there are many plants that contain psychoactive properties, and people have been using them for ages. Psychoactive plant compounds may significantly alter how people perceive the world.
1. Drug Test Anal. 2022 Apr;14(4):604-612. doi: 10.1002/dta.3193. Epub 2021 Nov 24. Quantification of hordenine in a complex plant matrix by direct analysis in real time-high-resolution mass spectrometry: Application to the "plant of concern" Sceletium tortuosum. Appley MG(1), Chambers MI(1), Musah RA(1). Author information: (1)Department of Chemistry, University at Albany, State University of New York, Albany, New York, USA. Recently, there has been an increase in the recreational abuse of several psychoactive plants, resulting in the United Nations Office on Drugs and Crime creating a list of "plants of concern." One such material is Sceletium tortuosum and products derived from it. Regulation of these materials is challenging because of their innocuous appearance, the cumbersome sample preparation steps required to render the material into a form amenable to analysis by conventional techniques, the requirement for nuanced sample analysis protocols, and lengthy analysis times. It is demonstrated here that direct analysis in real time-high-resolution mass spectrometry (DART-HRMS) can be used to not only identify S. tortuosum material based on the detection of characteristic biomarkers including hordenine and several mesembrine alkaloids, but also quantify the amount of hordenine present. Using hordenine-d6 as an internal standard, a protocol, validated according to US Food and Drug Administration (FDA) Guidelines for the Development and Validation of Bioanalytical Methods, was devised for the quantification of the psychoactive component hordenine. The method was then applied to the quantification of hordenine in six commercially available products derived from the foliage and stems of S. tortuosum. By this method, the lower limit of quantification (LLOQ) was found to be 1 μg/ml. Observed hordenine concentrations ranged from 0.02738 to 1.071 mg of hordenine per gram of plant material. The developed technique provides an effective and quick means for the detection and quantification of hordenine in S. tortuosum, which can be extended to analysis of other hordenine-containing products. © 2021 John Wiley & Sons, Ltd. DOI: 10.1002/dta.3193 PMID: 34750996 [Indexed for MEDLINE] 2. J Ethnopharmacol. 2018 Sep 15;223:135-141. doi: 10.1016/j.jep.2018.05.010. Epub 2018 May 22. Effect of Zembrin(®) and four of its alkaloid constituents on electric excitability of the rat hippocampus. Dimpfel W(1), Franklin R(2), Gericke N(3), Schombert L(4). Author information: (1)Justus-Liebig-University, Giessen, Germany. Electronic address: Wilfried.Dimpfel@pharma.med.uni-gissen.de. (2)HG&H Pharmaceuticals (Pty) Ltd., Bryanston, South Africa. (3)5 Loquat Walk, cape Town, South Africa. (4)NeuroCode AG, Wetzlar, Germany. ETHNOPHARMACOLOGICAL RELEVANCE: Sceletium tortuosum (Mesembryanthemaceae), a succulent plant indigenous to South Africa. is consumed in the form of teas, decoctions and tinctures and is sometimes smoked and used as snuff. In recent years, Sceletium has received a great deal of commercial interest for relieving stress in healthy people, and for treating a broad range of psychological, psychiatric and inflammatory conditions. MATERIAL AND METHODS: The whole extract (Zembrin®) was tested ex vivo in the hippocampus slice preparation after one week of daily oral administration of 5 and 10 mg/kg. Four alkaloids - mesembrine, mesembranol, mesembrenol and mesembrenone - were tested directly in vitro. All four were also tested in the presence of different glutamate receptor agonists. RESULTS: Zembrin® ex vivo as well as all alkaloids in vitro attenuated the amplitude of the population spike during electric stimulation as single shock as well as theta burst stimulation. Only Mesembranol and Mesembrenol having a hydroxyl group at position C6 instead of carbonyl group as in mesembrine and mesembrenone acted by attenuation of AMPA receptor mediated transmission as documented for the whole extract. DISCUSSION: The current experimental series revealed a new physiological effect of Zembrin® on the electric activity of the hippocampus. Attenuation of AMPA mediated transmission has been related to successful adjunctive treatment of epileptic patients. Administered doses of 5 and 10 mg/kg are in line with a dosage of 50 mg/subject as tested clinically. CONCLUSION: We have discovered a new structure activity relationship for Sceletium alkaloids. Since attenuation of AMPA mediated transmission has been related to successful adjunctive treatment of epileptic patients), Mesembrenol and Mesembranol may serve as new chemical leads for the development of new drugs for the treatment of epilepsy. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.jep.2018.05.010 PMID: 29758341 [Indexed for MEDLINE] 3. Planta Med. 2012 Feb;78(3):260-8. doi: 10.1055/s-0031-1280367. Epub 2011 Nov 21. In vitro permeation of mesembrine alkaloids from Sceletium tortuosum across porcine buccal, sublingual, and intestinal mucosa. Shikanga EA(1), Hamman JH, Chen W, Combrinck S, Gericke N, Viljoen AM. Author information: (1)Department of Chemistry, Tshwane University of Technology, Pretoria, South Africa. Sceletium tortuosum is an indigenous South African plant that has traditionally been used for its mood-enhancing properties. Recently, products containing S. tortuosum have become increasingly popular and are commonly administered as tablets, capsules, teas, decoctions, or tinctures, while traditionally the dried plant material has been masticated. This study evaluated the in vitro permeability of the four major S. tortuosum alkaloids (i.e., mesembrine, mesembrenone, mesembrenol, and mesembranol) across porcine intestinal, sublingual, and buccal tissues in their pure form and in the form of three different crude plant extracts, namely water, methanol, and an acid-base alkaloid-enriched extract. The permeability of mesembrine across intestinal tissue was higher than that of the highly permeable reference compound caffeine (which served as a positive control for membrane permeability) both in its pure form, as well as in the form of crude extracts. The intestinal permeability of mesembranol was similar to that of caffeine, while those of mesembrenol and mesembrenone were lower than that of caffeine, but much higher than that of the poorly permeable reference compound atenolol (which served as a negative control for membrane permeability). In general, the permeabilities of the alkaloids were lower across the sublingual and the buccal tissues than across the intestinal tissue. However, comparing the transport of the alkaloids with that of the reference compounds, there are indications that transport across the membranes of the oral cavity may contribute considerably to the overall bioavailability of the alkaloids, depending on pre-systemic metabolism, when the plant material is chewed and kept in the mouth for prolonged periods. The results from this study confirmed the ability of the alkaloids of S. tortuosum in purified or crude extract form to permeate across intestinal, buccal, and sublingual mucosal tissues. © Georg Thieme Verlag KG Stuttgart · New York. DOI: 10.1055/s-0031-1280367 PMID: 22105579 [Indexed for MEDLINE] 4. J Org Chem. 2005 Sep 16;70(19):7711-4. doi: 10.1021/jo0511039. Opening of aryl-substituted epoxides to form quaternary stereogenic centers: synthesis of (-)-mesembrine. Taber DF(1), He Y. Author information: (1)Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA. Taberdf@udel.edu [reaction: see text] Cycloalkanones are easily converted into aryl-substituted cyclic alkenes by the addition of an aryl Grignard reagent followed by dehydration. These alkenes are good substrates for asymmetric epoxidation. We have found that the addition of allylic and benzylic Grignard reagents can occur preferentially at the benzylic position of the derived epoxides to give the quaternary stereogenic center. This approach led to a short synthesis of the nanomolar serotonin re-uptake inhibitor (-)-mesembrine. DOI: 10.1021/jo0511039 PMCID: PMC3248819 PMID: 16149803 [Indexed for MEDLINE] 5. Chem Pharm Bull (Tokyo). 2005 May;53(5):457-70. doi: 10.1248/cpb.53.457. Development of a novel synthetic method for ring construction using organometallic complexes and its application to the total syntheses of natural products. Mori M(1). Author information: (1)Health Sciences University of Hokkaido, Tobetsu, Hokkaido 061-0293, Japan. Organometallic complexes are useful tools in synthetic organic chemistry. We investigated a novel synthetic method for ring construction using organometallic complexes and synthesized natural products and biologically active substances using these methods. Metalacycles formed from an early transition metal and diene, enyne, and diyne are stable under the reaction conditions and they are easily converted into compounds with functional groups by the addition of various agents. We have developed a novel synthetic method of heterocycles from enyne and diene using Cp2ZrBu2. The total syntheses of (-)-dendrobine, (+/-)-mecembrane, and (+/-)-mecembrine were achieved using this procedure. To synthesize these natural products as a chiral form, a novel palladium-catalyzed asymmetric allylic amination was developed, and chiral 2-arylcyclohexenylamine derivatives were synthesized. From these compounds, the total syntheses of (-)-mesembrane, (-)-mesembrine, (+)-crinamine, (-)-haemanthidine, and (+)-pretazetine were achieved. By further development of this procedure, a chiral 2-siloxymethylcyclohexenylamine derivative could be synthesized and the novel synthesis of indole derivatives was developed from this compound. From this indole derivative, (-)-tsubifoline and (-)-strychnine were synthesized. DOI: 10.1248/cpb.53.457 PMID: 15863913 [Indexed for MEDLINE]