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. Biochem Biophys Res Commun. 2024 Oct 23;736:150879. doi: 10.1016/j.bbrc.2024.150879. Online ahead of print. Anxiolytic- and antidepressive-like effects of harmaline in mice are mediated via histamine H3 receptor blockade. Khakpai F(1), Golshani SP(2), Alijanpour S(3), Ebrahimi-Ghiri M(4), Zarrindast MR(5). Author information: (1)Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Iran. (2)Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. (3)Department of Biology, Faculty of Science, Gonbad Kavous University, Gonbad Kavous, Iran. (4)Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran. Electronic address: mebrahimi@znu.ac.ir. (5)Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran. Many neuropsychiatric disorders can be caused by neurotransmitter dysfunction. Experimental studies have demonstrated that histamine and the harmaline affect physiological processes through interaction with other neurotransmitter systems. The objective of these experiments was to investigate the involvement of the histaminergic system in the effects of harmaline on anxiety- and depressive-related effects in male NMRI mice. Behavioral tests were employed to evaluate anxiety-related symptoms (elevated plus maze; EPM), depressive-like symptoms (forced swim test; FST), and cognitive decline (step-down test). The histamine H3 receptor (H3R) agonist α-methylhistamine dihydrobromide (α-MH; 5 mg/kg, i.p.) had anxiolytic- and depressive-like effects, while the H3R antagonist thioperamide (10 mg/kg, i.p.) showed an antidepressive-like property. The subthreshold dose of α-MH resulted in an increase in the tendency of mice treated with the harmaline (2.5 mg/kg) to remain in the EPM open-arms. A subthreshold dose of thioperamide (5 mg/kg) increased the time spent in the open-arms in mice treated with harmaline (2.5 and 5 mg/kg) while a high dose of harmaline decreased the immobility time. Furthermore, two higher doses of harmaline resulted in a reduction in the number of open-arm entries. Similarly, mice administered with thioperamide and a low dose of harmaline decreased locomotor activity in the EPM. Ultimately, the combined thioperamide and harmaline did not impair memory retrieval of mice. These experiments demonstrate that the histaminergic system is implicated in the anxiety- and depressive-related effects of harmaline. The combination of thioperamide and harmaline is effective in treating anxiety and depression without having an adverse effect on memory formation. Copyright © 2024 Elsevier Inc. All rights reserved. DOI: 10.1016/j.bbrc.2024.150879 PMID: 39467356 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 2. Medicine (Baltimore). 2024 Oct 11;103(41):e39309. doi: 10.1097/MD.0000000000039309. Integrated network pharmacology and transcriptomics to reveal the mechanism of Passiflora against depressive disorder: An observational study. Wang W(1), Zhai GQ(1), Xin M(2), Li J(1), Liao JJ(1), Liang J(3), Li CB(2). Author information: (1)Department of Urology, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Nanning, Guangxi Zhuang Autonomous Region, PR China. (2)Agro-food Science and Technology Research Institute, Guangxi Academy of Agricultural Sciences, Nanning, Guangxi Zhuang Autonomous Region, PR China. (3)Psychopsychology Department, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, PR China. Relevant studies have pointed out that Passiflora could relieve depressive disorder (DD) related symptoms, such as anxiety and insomnia, but its mechanism in DD has not been reported. In this study, DD-related transcriptome data was extracted from the Gene Expression Omnibus (GEO) database. Subsequently, 50 differentially expressed genes (DEGs) were screened by "limma," and the enrichment analysis of these DEGs revealed that they were associated with neuro-inflammatory-related signaling pathways, including IL-17, TNF, NF-kappa B, etc signaling pathways. Then, CCDC58, CXCL5, EGR1, LOC101929855, SCML1, and THBS1 were screened as biomarkers of DD by the least absolute shrinkage and selection operator (LASSO) analysis. Moreover, Harmaline, Harmine, Quercetin, and Kaempferol were the key chemically active ingredients of Passiflora. Noticeable, THBS1 and Quercetin were connected closely. In addition, the quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the key biomarkers (EGR1 and THBS1) were significantly lowly expressed in DD samples. In summary, we identified 2 key biomarkers of DD and 4 key chemically active ingredients of Passiflora. The potential mechanism of antidepressant effect of DD associated with neuro-inflammatory responses and neurotransmitter function. These might related to the synergistic activity of its key active ingredients with TNF-α, IL-1β, IL-6, etc, which work with EGR1 and THBS1 to regulate IL-17, NF-kappa B, TNF, etc signaling pathways. These findings might help to deepen the understanding of the mechanism of Passiflora in clinical treatment of DD. Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/MD.0000000000039309 PMCID: PMC11479432 PMID: 39465851 [Indexed for MEDLINE] Conflict of interest statement: The authors report there are no competing interests to declare. 3. Exp Neurol. 2024 Dec;382:114988. doi: 10.1016/j.expneurol.2024.114988. Epub 2024 Oct 4. Nabiximols (NBX) suppresses tremor in a rat Harmaline model of essential tremor. Loomis S(1), Samoylenko E(2), Virley D(2), McCreary AC(2). Author information: (1)Jazz Pharmaceuticals Ltd., Sovereign House, Cambridge CB24 9BZ, UK. Electronic address: sally.loomis@jazzpharma.com. (2)Jazz Pharmaceuticals Ltd., Sovereign House, Cambridge CB24 9BZ, UK. BACKGROUND: Essential tremor (ET) is one of the most prevalent movement disorders; despite this, there remains an unmet need for novel therapies. The treatment of rats with harmaline modulates the rhythmicity of inferior olivary neurons, resulting in generalized tremor with a frequency of 9-12 Hz in rats, comparable to that of human ET (4-12 Hz). PURPOSE: Interestingly, cannabinoids reduce tremor, therefore we have assessed the cannabinoid nabiximols (NBX; marketed as Sativex) a complex botanical drug mixture, in the harmaline-rat model of ET. METHOD: We tested the effects of acute (single dose) and subchronic (10 days) treatment of NBX (at 5.2, 10.4 and 20.8 mg kg-1 p.o.) administered prior to harmaline and acute NBX (20.8 mg kg-1) administered post-harmaline in male SD rats. Propranolol (20 mg kg-1 i.p.) was used as a positive control. Observed Scoring (OS) was carried out prior to placement in a tremor-monitoring apparatus for the calculation of Tremor Index (TI) and Motion Power Percentage (MPP). RESULTS: Acute and subchronic NBX significantly attenuated harmaline-induced tremor at 10.4 and 20.8 mg kg-1, respectively, for each parameter (OS, TI, and MPP) when administered pre-harmaline as did propranolol (20 mg kg-1). NBX did not attenuate harmaline-induced tremor when administered post-harmaline. CONCLUSIONS: These data suggest efficacy of acute and subchronic NBX to reduce tremors, based on OS, TI and MPP readouts if administered prior to harmaline. These data are the first to indicate the preclinical effects of an oral botanical cannabinoid formulation, NBX, in an animal model of ET. Copyright © 2024 Elsevier Inc. All rights reserved. DOI: 10.1016/j.expneurol.2024.114988 PMID: 39368533 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sally Loomis reports financial support was provided by Jazz Pharmaceuticals Inc. Andrew McCreary reports financial support was provided by Jazz Pharmaceuticals Inc. David Virley reports financial support was provided by Jazz Pharmaceuticals Inc. Elena Samoylenko reports financial support was provided by Jazz Pharmaceuticals Inc. Sally Loomis reports a relationship with Jazz Pharmaceuticals Inc. that includes: employment and equity or stocks. Andrew McCreary reports a relationship with Jazz Pharmaceuticals Inc. that includes: employment and equity or stocks. David Virley reports a relationship with Jazz Pharmaceuticals Inc. that includes: employment and equity or stocks. Elena Samoylenko reports a relationship with Jazz Pharmaceuticals Inc. that includes: employment and equity or stocks. Sally Loomis has patent issued to GW Pharmaceuticals. Andrew McCreary has patent issued to GW Pharmaceuticals. David Virley has patent issued to GW Pharmaceuticals. Elena Samoylenko has patent issued to GW Pharmaceuticals. NA If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 4. Neurosci Lett. 2024 Nov 1;842:138003. doi: 10.1016/j.neulet.2024.138003. Epub 2024 Sep 26. Harmaline attenuates chemotherapy-induced peripheral neuropathy: Modulation of Nrf-2 pathway and NK-1 receptor signaling. Kadyan P(1), Singh L(2). Author information: (1)University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab 140413, India. (2)University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab 140413, India. Electronic address: lovedeep992s@gmail.com. Peripheral neuropathy, resulting from damage to peripheral nerves, manifests as weakness, numbness, and pain, primarily affecting extremities and significantly impairing quality of life, especially in the elderly. Current treatments often entail severe side effects, necessitating the exploration of alternative therapies. Harmaline, a β-carboline alkaloid derived from Peganum harmala, exhibits promising antioxidant and anti-inflammatory properties. This study aimed to assess the efficacy of harmaline in a vincristine-induced mouse model of peripheral neuropathy. Swiss albino mice received vincristine (0.1 mg/kg, i.p.) for 10 days to induce neuropathy. Harmaline (5 and 10 mg/kg, i.p.) was administered 30 min before vincristine and continued until day 14 to evaluate its protective effects. Behavioral assessments were conducted on days 7 and 14. Vincristine treatment significantly heightened sensitivity to cold, measured by cold plate and acetone drop tests, and to heat, assessed via the hot plate test, while also impairing motor coordination. Biochemical analyses revealed decreased levels of GSH and Nrf-2, alongside elevated TBARS and IL-1β levels in sciatic nerve tissue. Harmaline administration markedly alleviated both behavioral and biochemical alterations induced by vincristine, with the 10 mg/kg dose exhibiting the most pronounced effects. Notably, harmaline treatment elevated GSH and Nrf-2 levels while reducing TBARS and IL-1β. Furthermore, substance-P treatment reversed the protective effects of harmaline, implicating the NK-1 receptor in its mechanism of action. In conclusion, harmaline demonstrates significant potential in mitigating vincristine-induced peripheral neuropathy by reducing oxidative stress through Nrf-2 activation and lowering IL-1β levels, likely via NK-1 receptor inhibition. Copyright © 2024 Elsevier B.V. All rights reserved. DOI: 10.1016/j.neulet.2024.138003 PMID: 39341332 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 5. Rev Bras Parasitol Vet. 2024 Sep 16;33(3):e001824. doi: 10.1590/S1984-29612024053. eCollection 2024. In vitro anti-parasitic effect of the alkaloids harmaline and piperine on Toxoplasma gondii. Carreira DSS(1), Sato CE(1), Silva WBD(2), Bittencourt TCBDSC(2), Costa SL(3), Uzêda RS(1). Author information: (1)Laboratório de Toxicologia e Fitoterapia, Hospital de Medicina Veterinária, Universidade Federal da Bahia - UFBA, Salvador, BA, Brasil. (2)Escola de Medicina Veterinária e Zootecnia, Universidade Federal da Bahia - UFBA, Salvador, BA, Brasil. (3)Departamento de Bioquímica e Biofísica, Universidade Federal da Bahia - UFBA, Salvador, BA, Brasil. Toxoplasma gondii is a coccidian protozoan of zoonotic importance that causes toxoplasmosis. Although the current treatments for toxoplasmosis may be associated with adverse effects and limited efficacy for different biological forms of the parasite, evidence suggests that alkaloid molecules such as harmaline and piperine exhibit antiparasitic effects against protozoa parasites. This investigation aimed to evaluate the in vitro effect of harmaline and piperine against T. gondii tachyzoites in infected Vero cell cultures. After 24 hours of host cell infection, the cultures were treated with harmaline or piperine (0.49 to 15.63 µg/mL). Negative and positive controls were RPMI/DMSO (0.1%) and sulfadiazine (200 µg/mL). Harmaline significantly reduced parasite multiplication by 20% compared to the negative control, while piperine decreased between 55.56% and 88.89% in a dose-dependent manner. According to an intracellular parasite proportion scale, it was observed that the Vero cells with low or moderate parasitic proliferation were more prevalent after the alkaloid treatment. The study demonstrated that the alkaloids had antiparasitic effects on T. gondii, with piperine being the most effective. Additional studies must be carried out to clarify other aspects of the action of the alkaloids on parasites. Toxoplasma gondii é um protozoário coccídio de importância zoonótica, causador da toxoplasmose. Embora os tratamentos atuais para a toxoplasmose possam estar associados a efeitos adversos e à eficácia limitada para as diferentes formas biológicas do parasita, evidências sugerem que moléculas alcaloides, como a harmalina e a piperina exibem, efeitos antiparasitários contra protozoários parasitas. Essa investigação teve como objetivo avaliar o efeito in vitro da harmalina e da piperina contra taquizoítos de T. gondii em culturas de células Vero infectadas. Após 24 horas da infecção das células hospedeiras, as culturas foram tratadas com harmalina ou piperina (0,49 a 15,63 µg/mL). Os controles negativo e positivo foram RPMI/DMSO (0,1%) e sulfadiazina (200 µg/mL), respectivamente. Harmalina reduziu significativamente a multiplicação parasitária em 20% em comparação ao controle negativo, enquanto a piperina diminuiu entre 55,56% e 88,89%, de forma dose-dependente. De acordo com uma escala de proporção intracelular de parasitas, observou-se que células Vero com baixa ou moderada proliferação parasitária foram mais prevalentes após tratamento com alcaloides. O estudo demonstrou que os alcaloides tinham efeitos antiparasitários sobre o T. gondii, sendo a piperina mais eficaz. Estudos adicionais devem ser realizados para esclarecer outros aspectos da ação dos alcaloides sobre os parasitas. DOI: 10.1590/S1984-29612024053 PMCID: PMC11452066 PMID: 39292065 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest: The authors declare that they have not competing interests.