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Bioactive Lipids and Cannabinoids: Key Players in Neuropsychiatric Disorders and...
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Bioactive Lipids and Cannabinoids: Key Players in Neuropsychiatric Disorders and Beyond

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 4033

Special Issue Editors

Prof. Dr. Giuseppe Di Giovanni

E-Mail Website
Guest Editor
1. Department of Physiology & Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
2. Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK
Interests: serotonin; GABA; dopamine; epilepsy; addiction; mood disorders; electrophysiology; habenula; basal ganglia; serotonin2 receptors
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Mauro Maccarrone

E-Mail Website
Guest Editor
1. Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
2. European Center for Brain Research, Santa Lucia Foundation IRCCS, Rome, Italy
Interests: arachidonate cascade; bioactive lipids; biomarkers; cell membranes; endocannabinoids; resolvins; signal transduction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Our body possesses different endogenous signaling systems based on bioactive lipids of which the most investigated class is composed of endocannabinoids (eCBs), known as the endocannabinoid system (ECS). Current knowledge about the pathophysiological role of the main classes of endogenous bioactive lipids, namely glycerophospholipids/sphingolipids, classical eicosanoids and pro-resolving lipid mediators (SPMs), is still limited and further research on this subject is needed. Nevertheless, it is now clear that dysregulated lipid homeostasis contributes greatly to the pathogenesis and even progression of different neurodegenerative diseases.

The elements of ECS have been studied for a long time because they are targeted by ∆-tetrahydrocannabinol (THC) and other plant-derived cannabinoids (phytocannabinoids) and compelling evidence shows that they play a critical role in various developmental processes and brain disorders. While cannabis has an extremely bright future for therapeutic applications, it is not a miracle drug. Phytocannabinoids have been used in medicine for centuries, and over the past decade, the focus has been on their broad therapeutic potential, particularly in seizure management.

The objective of this Special Issue collection is to bring together relevant international researchers from the lipidomics and cannabinoid field to put together an international collection of well-informed opinions, perspectives, and original research articles that evaluate bioactive lipids and cannabinoid compounds in health and disease state.

We invite you to submit contributions in the form of reviews or original research articles that provide new insights into this intriguing research area.

You may choose our Joint Special Issue in Molecules.

Prof. Dr. Giuseppe Di Giovanni
Prof. Dr. Mauro Maccarrone
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lipidomics
  • bioactive lipids
  • glycerophospholipids/sphingolipids
  • classical eicosanoids
  • pro-resolving lipid mediators
  • cannabinoids
  • glycerophospholipids
  • sphingolipids
  • classical eicosanoids
  • CNS diseases

Published Papers (4 papers)

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Research

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15 pages, 790 KiB  
Article
Peripheral Endocannabinoid Components and Lipid Plasma Levels in Patients with Resistant Migraine and Co-Morbid Personality and Psychological Disorders: A Cross-Sectional Study
by Sara Bottiroli, Rosaria Greco, Valentina Franco, Annamaria Zanaboni, Michela Palmisani, Gloria Vaghi, Grazia Sances, Roberto De Icco and Cristina Tassorelli
Int. J. Mol. Sci. 2024, 25(3), 1893; https://doi.org/10.3390/ijms25031893 - 04 Feb 2024
Viewed by 826
Abstract
Resistant migraine characterizes those patients who have failed at least three classes of migraine prophylaxis. These difficult-to-treat patients are likely to be characterized by a high prevalence of psychological disturbances. A dysfunction of the endocannabinoid system (ECS), including alteration in the levels of [...] Read more.
Resistant migraine characterizes those patients who have failed at least three classes of migraine prophylaxis. These difficult-to-treat patients are likely to be characterized by a high prevalence of psychological disturbances. A dysfunction of the endocannabinoid system (ECS), including alteration in the levels of endocannabinoid congeners, may underlie several psychiatric disorders and the pathogenesis of migraines. Here we explored whether the peripheral gene expression of major components of the ECS and the plasma levels of endocannabinoids and related lipids are associated with psychological disorders in resistant migraine. Fifty-one patients (age = 46.0 ± 11.7) with resistant migraine received a comprehensive psychological evaluation according to the DSM-5 criteria. Among the patients, 61% had personality disorders (PD) and 61% had mood disorders (MD). Several associations were found between these psychological disorders and peripheral ECS alterations. Lower plasma levels of palmitoiletanolamide (PEA) were found in the PD group compared with the non-PD group. The MD group was characterized by lower mRNA levels of diacylglycerol lipase α (DAGLα) and CB2 (cannabinoid-2) receptor. The results suggest the existence of peripheral dysfunction in some components of the ECS and an alteration in plasma levels of PEA in patients with resistant migraine and mood or personality disorders. Full article
(This article belongs to the Special Issue Bioactive Lipids and Cannabinoids: Key Players in Neuropsychiatric Disorders and Beyond)
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15 pages, 5916 KiB  
Article
Function of Presynaptic Inhibitory Cannabinoid CB1 Receptors in Spontaneously Hypertensive Rats and Its Modification by Enhanced Endocannabinoid Tone
by Marek Toczek, Eberhard Schlicker, Patryk Remiszewski and Barbara Malinowska
Int. J. Mol. Sci. 2024, 25(2), 858; https://doi.org/10.3390/ijms25020858 - 10 Jan 2024
Viewed by 666
Abstract
We studied whether the function of presynaptic inhibitory cannabinoid CB1 receptors on the sympathetic nerve fibres innervating resistance vessels is increased in spontaneously hypertensive rats (SHR) like in deoxycorticosterone (DOCA)–salt hypertension. An increase in diastolic blood pressure (DBP) was induced by electrical [...] Read more.
We studied whether the function of presynaptic inhibitory cannabinoid CB1 receptors on the sympathetic nerve fibres innervating resistance vessels is increased in spontaneously hypertensive rats (SHR) like in deoxycorticosterone (DOCA)–salt hypertension. An increase in diastolic blood pressure (DBP) was induced by electrical stimulation of the preganglionic sympathetic neurons or by phenylephrine injection in pithed SHR and normotensive Wistar–Kyoto rats (WKY). The electrically (but not the phenylephrine) induced increase in DBP was inhibited by the cannabinoid receptor agonist CP55940, similarly in both groups, and by the endocannabinoid reuptake inhibitor AM404 in SHR only. The effect of CP55940 was abolished/reduced by the CB1 receptor antagonist AM251 (in both groups) and in WKY by endocannabinoid degradation blockade, i.e., the monoacylglycerol lipase (MAGL) inhibitor MJN110 and the dual fatty acid amide hydrolase (FAAH)/MAGL inhibitor JZL195 but not the FAAH inhibitor URB597. MJN110 and JZL195 tended to enhance the effect of CP55940 in SHR. In conclusion, the function of presynaptic inhibitory CB1 receptors depends on the hypertension model. Although no differences occurred between SHR and WKY under basal experimental conditions, the CB1 receptor function was better preserved in SHR when the endocannabinoid tone was increased by the inhibition of MAGL or the endocannabinoid transporter. Full article
(This article belongs to the Special Issue Bioactive Lipids and Cannabinoids: Key Players in Neuropsychiatric Disorders and Beyond)
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16 pages, 1703 KiB  
Article
Antidepressant Medication Does Not Contribute to the Elevated Circulating Concentrations of Acylethanolamides Found in Substance Use Disorder Patients
by Jesús Herrera-Imbroda, María Flores-López, Nerea Requena-Ocaña, Pedro Araos, Nuria García-Marchena, Jessica Ropero, Antonio Bordallo, Juan Suarez, Francisco J. Pavón-Morón, Antonia Serrano, Fermín Mayoral and Fernando Rodríguez de Fonseca
Int. J. Mol. Sci. 2023, 24(19), 14788; https://doi.org/10.3390/ijms241914788 - 30 Sep 2023
Viewed by 692
Abstract
Circulating acylethanolamides (NAEs) are bioactive signaling molecules that modulate multiple homeostatic functions including mood and hedonic responses. Variations in their plasma concentrations are associated with substance use disorders (SUD) and recent studies suggest that psychotropic medication might influence its circulating levels, limiting its [...] Read more.
Circulating acylethanolamides (NAEs) are bioactive signaling molecules that modulate multiple homeostatic functions including mood and hedonic responses. Variations in their plasma concentrations are associated with substance use disorders (SUD) and recent studies suggest that psychotropic medication might influence its circulating levels, limiting its use as a clinical biomarker of addiction. In addition, they might have a role as mediators of the pharmacological effects of psychotropic drugs. Thus, in mild depression, the response to selective serotonin reuptake inhibitor-type antidepressants (SSRI) is associated with a marked increase in circulating NAEs. To further investigate if antidepressants are able to modify the plasma concentration of NAEs in SUD patients, we analyzed the circulating levels of NAEs in 333 abstinent and 175 healthy controls on the basis of the treatment with SSRI antidepressants. As described previously, SUD patients display higher concentrations of NAEs than those measured in a control population. This increase was not further modified by antidepressant therapy. Only marginal increases in palmitoylethanolamide (PEA), oleoylethanolamide (OEA), or docosatetraenoyl-ethanolamide (DEA) were found, and the net effect was very small. Thus, our study shows that treatment with SSRI-type antidepressants does not modify the clinical utility of monitoring enhanced NAE production as biomarkers of SUD. In addition, the possibility that a blunted NAE response to antidepressant therapy might be related to the loss of efficacy of SSRIs in dual depression emerges as an attractive hypothesis that needs to be addressed in future studies. Full article
(This article belongs to the Special Issue Bioactive Lipids and Cannabinoids: Key Players in Neuropsychiatric Disorders and Beyond)
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Review

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49 pages, 2858 KiB  
Review
Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS
by Armin Kouchaeknejad, Gunter Van Der Walt, Maria Helena De Donato and Emma Puighermanal
Int. J. Mol. Sci. 2023, 24(21), 15829; https://doi.org/10.3390/ijms242115829 - 31 Oct 2023
Viewed by 1293
Abstract
As central nervous system (CNS)-related disorders present an increasing cause of global morbidity, mortality, and high pressure on our healthcare system, there is an urgent need for new insights and treatment options. The endocannabinoid system (ECS) is a critical network of endogenous compounds, [...] Read more.
As central nervous system (CNS)-related disorders present an increasing cause of global morbidity, mortality, and high pressure on our healthcare system, there is an urgent need for new insights and treatment options. The endocannabinoid system (ECS) is a critical network of endogenous compounds, receptors, and enzymes that contribute to CNS development and regulation. Given its multifaceted involvement in neurobiology and its significance in various CNS disorders, the ECS as a whole is considered a promising therapeutic target. Despite significant advances in our understanding of the ECS’s role in the CNS, its complex architecture and extensive crosstalk with other biological systems present challenges for research and clinical advancements. To bridge these knowledge gaps and unlock the full therapeutic potential of ECS interventions in CNS-related disorders, a plethora of molecular–genetic tools have been developed in recent years. Here, we review some of the most impactful tools for investigating the neurological aspects of the ECS. We first provide a brief introduction to the ECS components, including cannabinoid receptors, endocannabinoids, and metabolic enzymes, emphasizing their complexity. This is followed by an exploration of cutting-edge imaging tools and genetic models aimed at elucidating the roles of these principal ECS components. Special emphasis is placed on their relevance in the context of CNS and its associated disorders. Full article
(This article belongs to the Special Issue Bioactive Lipids and Cannabinoids: Key Players in Neuropsychiatric Disorders and Beyond)
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