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Cells
Special Issues
From Research to Legalization: How Cannabis Exploits the Endocannabinoid System
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From Research to Legalization: How Cannabis Exploits the Endocannabinoid System

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 December 2024 | Viewed by 2021

Special Issue Editors

Dr. Erik Keimpema

E-Mail Website
Guest Editor
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria
Interests: fetal development; neuropeptide signaling; psychoactive drugs; maternal drug exposure
Prof. Dr. Tibor Harkany

E-Mail Website
Guest Editor
Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria
Interests: hypothalamus development; cellular diversity; endocannabinoid signaling; drug addiction

Special Issue Information

Dear Colleague,

This Special Issue titled “From research to legalization: how cannabis exploits the endocannabinoid system” aims to bring together novel developments on the involvement of (endo)-cannabinoid signaling in fundamental brain functions in the context of the ongoing European debate on cannabis legalization. Given the increasing availability of cannabis for medicinal and recreational purposes, the selective cultivation of high-THC strains, as well as novel solutions to more efficiently consume cannabis, it is of crucial importance to put anecdotal evidence on how (endo)-cannabinoid signaling controls the nervous system straight through elegant fundamental research. Therefore, we embark on this special issue to gather the most recent original experimental research, comprehensive reviews, as well as opinion pieces from developmental biology to aging, to cannabinoid pharmacology, to health and disease, as well as translational (“human specific”) segments of science. We thus approach you, leaders in this research arena, for your contribution to help illustrate mechanisms, address societal discussion points, and provide perspectives for law and decision-makers by being involved in this special issue. We are looking forward to your feedback and contributions

Dr. Erik Keimpema
Prof. Dr. Tibor Harkany
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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • endocannabinoids
  • cannabis
  • legalization
  • THC
  • disease
  • development

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Published Papers (3 papers)

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Research

21 pages, 1479 KiB  
Article
FAAH Inhibition Reverses Depressive-like Behavior and Sex-Specific Neuroinflammatory Alterations Induced by Early Life Stress
by Anna Portugalov and Irit Akirav
Cells 2024, 13(22), 1881; https://doi.org/10.3390/cells13221881 - 14 Nov 2024
Viewed by 373
Abstract
Early life stress (ELS) increases predisposition to major depressive disorder (MDD), with neuroinflammation playing a crucial role. This study investigated the long-term effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on ELS-induced depressive-like behavior and messenger RNA (mRNA) of pro-inflammatory cytokines [...] Read more.
Early life stress (ELS) increases predisposition to major depressive disorder (MDD), with neuroinflammation playing a crucial role. This study investigated the long-term effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on ELS-induced depressive-like behavior and messenger RNA (mRNA) of pro-inflammatory cytokines in the medial prefrontal cortex (mPFC) and CA1 regions. We also assessed whether these gene expression alterations were present at the onset of URB597 treatment during late adolescence. ELS induced a depressive-like phenotype in adult male and female rats, which was reversed by URB597. In the mPFC, ELS downregulated nuclear factor kappa B1 (nfκb1) in both sexes, while URB597 normalized this expression exclusively in males. In females, ELS downregulated interleukin (il) 6 and tumor necrosis factor alpha (tnfα) but upregulated il1β and corticotropin-releasing factor (crf); URB597 normalized il6, il1β, and crf. In the CA1, ELS downregulated il1β and tnfα in males and upregulated il1β expression in females, which was reversed by URB597. Some of these effects began in late adolescence, including mPFC-nfκb1 expression in both sexes, mPFC-il6 and mPFC-il1β in females, CA1-il1β and CA1-tnfα in males, and CA1-il1β in females. These findings highlight URB597 as a therapeutic approach for reversing ELS-induced depressive-like behavior by associating with changes in the gene expression of neuroinflammatory cytokines, with notable sex differences. Full article
(This article belongs to the Special Issue From Research to Legalization: How Cannabis Exploits the Endocannabinoid System)
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17 pages, 2428 KiB  
Article
Functional Adaptation in the Brain Habenulo–Mesencephalic Pathway During Cannabinoid Withdrawal
by Sonia Aroni, Claudia Sagheddu, Marco Pistis and Anna Lisa Muntoni
Cells 2024, 13(21), 1809; https://doi.org/10.3390/cells13211809 - 1 Nov 2024
Viewed by 612
Abstract
The mesolimbic reward system originating from dopamine neurons in the ventral tegmental area (VTA) of the midbrain shows a profound reduction in function during cannabinoid withdrawal. This condition may underlie aversive states that lead to compulsive drug seeking and relapse. The lateral habenula [...] Read more.
The mesolimbic reward system originating from dopamine neurons in the ventral tegmental area (VTA) of the midbrain shows a profound reduction in function during cannabinoid withdrawal. This condition may underlie aversive states that lead to compulsive drug seeking and relapse. The lateral habenula (LHb) exerts negative control over the VTA via the GABA rostromedial tegmental nucleus (RMTg), representing a potential convergence point for drug-induced opponent processes. We hypothesized that the LHb–RMTg pathway might be causally involved in the hypodopaminergic state during cannabinoid withdrawal. To induce Δ9-tetrahydrocannabinol (THC) dependence, adult male Sprague–Dawley rats were treated with THC (15 mg/kg, i.p.) twice daily for 6.5–7 days. Administration of the cannabinoid antagonist rimonabant (5 mg/kg, i.p.) precipitated a robust behavioral withdrawal syndrome, while abrupt THC suspension caused milder signs of abstinence. Extracellular single unit recordings confirmed a marked decrease in the discharge frequency and burst firing of VTA dopamine neurons during THC withdrawal. The duration of RMTg-evoked inhibition was longer in THC withdrawn rats. Additionally, the spontaneous activity of RMTg neurons and of LHb neurons was strongly depressed during cannabinoid withdrawal. These findings support the hypothesis that functional changes in the habenulo–mesencephalic circuit are implicated in the mechanisms underlying substance use disorders. Full article
(This article belongs to the Special Issue From Research to Legalization: How Cannabis Exploits the Endocannabinoid System)
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19 pages, 5498 KiB  
Article
Gestational CBD Shapes Insular Cortex in Adulthood
by Daniela Iezzi, Alba Cáceres-Rodríguez, Jessica Pereira-Silva, Pascale Chavis and Olivier Jacques José Manzoni
Cells 2024, 13(17), 1486; https://doi.org/10.3390/cells13171486 - 4 Sep 2024
Viewed by 692
Abstract
Many expectant mothers use CBD to alleviate symptoms like nausea, insomnia, anxiety, and pain, despite limited research on its long-term effects. However, CBD passes through the placenta, affecting fetal development and impacting offspring behavior. We investigated how prenatal CBD exposure affects the insular [...] Read more.
Many expectant mothers use CBD to alleviate symptoms like nausea, insomnia, anxiety, and pain, despite limited research on its long-term effects. However, CBD passes through the placenta, affecting fetal development and impacting offspring behavior. We investigated how prenatal CBD exposure affects the insular cortex (IC), a brain region involved in emotional processing and linked to psychiatric disorders. The IC is divided into two territories: the anterior IC (aIC), processing socioemotional signals, and the posterior IC (pIC), specializing in interoception and pain perception. Pyramidal neurons in the aIC and pIC exhibit sex-specific electrophysiological properties, including variations in excitability and the excitatory/inhibitory balance. We investigated IC’s cellular properties and synaptic strength in the offspring of both sexes from mice exposed to low-dose CBD during gestation (E5–E18; 3 mg/kg, s.c.). Prenatal CBD exposure induced sex-specific and territory-specific changes in the active and passive membrane properties, as well as intrinsic excitability and the excitatory/inhibitory balance, in the IC of adult offspring. The data indicate that in utero CBD exposure disrupts IC neuronal development, leading to a loss of functional distinction between IC territories. These findings may have significant implications for understanding the effects of CBD on emotional behaviors in offspring. Full article
(This article belongs to the Special Issue From Research to Legalization: How Cannabis Exploits the Endocannabinoid System)
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