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New Insight into Cannabinoid Effects

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

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 37123

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Guest Editor
Division of Gastroenterology and Hepatology, Meir Medical Center, Affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv 5265601, Israel
Interests: endocannabinoid; inflammatory bowel disease; cannabis use in IBD; cannabis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cannabis is the most widely used recreational drug worldwide. The cannabis plant contains as many as 100 phytocannabinoids as well as other ingredients such as terpenes and flavonoids. Phytocannabinoids exert their effects through the endocannabinoid system (ECS), which is an endogenous system with an important role in modulating mood, memory, reward homeostasis, immune regulation, and energy balance. The best-known phytocannabinoids are Δ9-tetrahydrocannabinol (THC), which is responsible for the psychotropic effect of cannabis, and cannabidiol (CBD), which does not have a central effect but is shown to have an anti-inflammatory effect.

The use of medical cannabis is rapidly increasing, and physicians are faced with an increasing demand from patients to prescribe it. Sadly, this is not accompanied by scientifically sound evidence regarding the efficacy, if any, of cannabis treatment. Very little is known about the effect of cannabis and the significance of various cannabinoid combinations or mode of cannabis consumption. On the other hand, we cannot afford to ignore the many reports about the positive effects of cannabis. More data and evidence on how cannabinoids affect physiology and pathophysiology and their therapeutic potential are urgently needed.

The open access journal, International Journal of Molecular Sciences (IJMS) (IF 5.923, ISSN 1422-0067), is therefore planning this Special Issue entitled “New Insight into Cannabinoid Effects”.

As the Guest Editor, I invite you to contribute an article to this issue. We promise you a rapid and rigorous peer review, manuscript handling, and editorial process.

Dr. Timna Naftali
Guest Editor

Manuscript Submission Information

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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

  • cannabinoids
  • endogenous cannabinoids
  • neurodegenerative diseases
  • cancer
  • pharmacology

Published Papers (11 papers)

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Research

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15 pages, 2362 KiB  
Article
Prenatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters the Expression of miR-122-5p and Its Target Igf1r in the Adult Rat Ovary
by Annia A. Martínez-Peña, Kendrick Lee, Madison Pereira, Ahmed Ayyash, James J. Petrik, Daniel B. Hardy and Alison C. Holloway
Int. J. Mol. Sci. 2022, 23(14), 8000; https://doi.org/10.3390/ijms23148000 - 20 Jul 2022
Cited by 3 | Viewed by 2065
Abstract
As cannabis use during pregnancy increases, it is important to understand its effects on the developing fetus. Particularly, the long-term effects of its psychoactive component, delta-9-tetrahydrocannabinol (THC), on the offspring’s reproductive health are not fully understood. This study examined the impact of gestational [...] Read more.
As cannabis use during pregnancy increases, it is important to understand its effects on the developing fetus. Particularly, the long-term effects of its psychoactive component, delta-9-tetrahydrocannabinol (THC), on the offspring’s reproductive health are not fully understood. This study examined the impact of gestational THC exposure on the miRNA profile in adult rat ovaries and the possible consequences on ovarian health. Prenatal THC exposure resulted in the differential expression of 12 out of 420 evaluated miRNAs. From the differentially expressed miRNAs, miR-122-5p, which is highly conserved among species, was the only upregulated target and had the greatest fold change. The upregulation of miR-122-5p and the downregulation of its target insulin-like growth factor 1 receptor (Igf1r) were confirmed by RT-qPCR. Prenatally THC-exposed ovaries had decreased IGF-1R-positive follicular cells and increased follicular apoptosis. Furthermore, THC decreased Igf1r expression in ovarian explants and granulosa cells after 48 h. As decreased IGF-1R has been associated with diminished ovarian health and fertility, we propose that these THC-induced changes may partially explain the altered ovarian follicle dynamics observed in THC-exposed offspring. Taken together, our data suggests that prenatal THC exposure may impact key pathways in the developing ovary, which could lead to subfertility or premature reproductive senescence. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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35 pages, 4978 KiB  
Article
Targeting the Achilles’ Heel of Multidrug-Resistant Staphylococcus aureus by the Endocannabinoid Anandamide
by Ronit Vogt Sionov, Shreya Banerjee, Sergei Bogomolov, Reem Smoum, Raphael Mechoulam and Doron Steinberg
Int. J. Mol. Sci. 2022, 23(14), 7798; https://doi.org/10.3390/ijms23147798 - 14 Jul 2022
Cited by 5 | Viewed by 2188
Abstract
Antibiotic-resistant Staphylococcus aureus is a major health issue that requires new therapeutic approaches. Accumulating data suggest that it is possible to sensitize these bacteria to antibiotics by combining them with inhibitors targeting efflux pumps, the low-affinity penicillin-binding protein PBP2a, cell wall teichoic acid, [...] Read more.
Antibiotic-resistant Staphylococcus aureus is a major health issue that requires new therapeutic approaches. Accumulating data suggest that it is possible to sensitize these bacteria to antibiotics by combining them with inhibitors targeting efflux pumps, the low-affinity penicillin-binding protein PBP2a, cell wall teichoic acid, or the cell division protein FtsZ. We have previously shown that the endocannabinoid Anandamide (N-arachidonoylethanolamine; AEA) could sensitize drug-resistant S. aureus to a variety of antibiotics, among others, through growth arrest and inhibition of drug efflux. Here, we looked at biochemical alterations caused by AEA. We observed that AEA increased the intracellular drug concentration of a fluorescent penicillin and augmented its binding to membrane proteins with concomitant altered membrane distribution of these proteins. AEA also prevented the secretion of exopolysaccharides (EPS) and reduced the cell wall teichoic acid content, both processes known to require transporter proteins. Notably, AEA was found to inhibit membrane ATPase activity that is necessary for transmembrane transport. AEA did not affect the membrane GTPase activity, and the GTPase cell division protein FtsZ formed the Z-ring of the divisome normally in the presence of AEA. Rather, AEA caused a reduction in murein hydrolase activities involved in daughter cell separation. Altogether, this study shows that AEA affects several biochemical processes that culminate in the sensitization of the drug-resistant bacteria to antibiotics. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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22 pages, 6661 KiB  
Article
Cannabidiol Antiproliferative Effect in Triple-Negative Breast Cancer MDA-MB-231 Cells Is Modulated by Its Physical State and by IGF-1
by Alessia D’Aloia, Michela Ceriani, Renata Tisi, Simone Stucchi, Elena Sacco and Barbara Costa
Int. J. Mol. Sci. 2022, 23(13), 7145; https://doi.org/10.3390/ijms23137145 - 27 Jun 2022
Cited by 6 | Viewed by 3196
Abstract
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated [...] Read more.
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has been discussed for its safety and efficacy in cancer treatments. For this reason, we have inquired into its use on triple-negative human breast cancer. Analyzing the biological effects of CBD on MDA-MB-231, we have demonstrated that both CBD dosage and serum concentrations in the culture medium influence its outcomes; furthermore, light scattering studies demonstrated that serum impacts the CBD aggregation state by acting as a surfactant agent. Pharmacological studies on CBD in combination with chemotherapeutic agents reveal that CBD possesses a protective action against the cytotoxic effect exerted by cisplatin on MDA-MB-231 grown in standard conditions. Furthermore, in a low serum condition (0.5%), starting from a threshold concentration (5 µM), CBD forms aggregates, exerts cytostatic antiproliferative outcomes, and promotes cell cycle arrest activating autophagy. At doses above the threshold, CBD exerts a highly cytotoxic effect inducing bubbling cell death. Finally, IGF-1 and EGF antagonize the antiproliferative effect of CBD protecting cells from harmful consequences of CBD aggregates. In conclusion, CBD effect is strongly associated with the physical state and concentration that reaches the treated cells, parameters not taken into account in most of the research papers. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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16 pages, 3774 KiB  
Article
The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity
by Elad Ben-Cnaan, Anna Permyakova, Shahar Azar, Shira Hirsch, Saja Baraghithy, Liad Hinden and Joseph Tam
Int. J. Mol. Sci. 2022, 23(10), 5610; https://doi.org/10.3390/ijms23105610 - 17 May 2022
Cited by 7 | Viewed by 4152
Abstract
Obesity is a global medical problem; its common form is known as diet-induced obesity (DIO); however, there are several rare genetic disorders, such as Prader–Willi syndrome (PWS), that are also associated with obesity (genetic-induced obesity, GIO). The currently available therapeutics for treating DIO [...] Read more.
Obesity is a global medical problem; its common form is known as diet-induced obesity (DIO); however, there are several rare genetic disorders, such as Prader–Willi syndrome (PWS), that are also associated with obesity (genetic-induced obesity, GIO). The currently available therapeutics for treating DIO and GIO are very limited, and they result in only a partial improvement. Cannabidiolic acid (CBDA), a constituent of Cannabis sativa, gradually decarboxylates to cannabidiol (CBD). Whereas the anti-obesity properties of CBD have been reasonably identified, our knowledge of the pharmacology of CBDA is more limited due to its instability. To stabilize CBDA, a new derivative, CBDA-O-methyl ester (HU-580, EPM301), was synthesized. The therapeutic potential of EPM301 in appetite reduction, weight loss, and metabolic improvements in DIO and GIO was tested in vivo. EPM301 (40 mg/kg/d, i.p.) successfully resulted in weight loss, increased ambulation, as well as improved glycemic and lipid profiles in DIO mice. Additionally, EPM301 ameliorated DIO-induced hepatic dysfunction and steatosis. Importantly, EPM301 (20 and 40 mg/kg/d, i.p.) effectively reduced body weight and hyperphagia in a high-fat diet-fed Magel2null mouse model for PWS. In addition, when given to standard-diet-fed Magel2null mice as a preventive treatment, EPM301 completely inhibited weight gain and adiposity. Lastly, EPM301 increased the oxidation of different nutrients in each strain. All together, EPM301 ameliorated obesity and its metabolic abnormalities in both DIO and GIO. These results support the idea to further promote this synthetic CBDA derivative toward clinical evaluation in humans. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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19 pages, 3088 KiB  
Article
Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes
by Camilla Di Meo, Daniel Tortolani, Sara Standoli, Clotilde Beatrice Angelucci, Federico Fanti, Alessandro Leuti, Manuel Sergi, Salam Kadhim, Eric Hsu, Cinzia Rapino and Mauro Maccarrone
Int. J. Mol. Sci. 2022, 23(10), 5430; https://doi.org/10.3390/ijms23105430 - 12 May 2022
Cited by 11 | Viewed by 4550
Abstract
The decriminalization and legalization of cannabis has paved the way for investigations into the potential of the use of phytocannabinoids (pCBs) as natural therapeutics for the treatment of human diseases. This growing interest has recently focused on rare (less abundant) pCBs that are [...] Read more.
The decriminalization and legalization of cannabis has paved the way for investigations into the potential of the use of phytocannabinoids (pCBs) as natural therapeutics for the treatment of human diseases. This growing interest has recently focused on rare (less abundant) pCBs that are non-psychotropic compounds, such as cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) and cannabigerolic acid (CBGA). Notably, pCBs can act via the endocannabinoid system (ECS), which is involved in the regulation of key pathophysiological processes, and also in the skin. In this study, we used human keratinocytes (HaCaT cells) as an in vitro model that expresses all major ECS elements in order to systematically investigate the effects of CBG, CBC, THCV and CBGA. To this end, we analyzed the gene and protein expression of ECS components (receptors: CB1, CB2, GPR55, TRPV1 and PPARα/γ/δ; enzymes: NAPE-PLD, FAAH, DAGLα/β and MAGL) using qRT-PCR and Western blotting, along with assessments of their functionality using radioligand binding and activity assays. In addition, we quantified the content of endocannabinoid(-like) compounds (AEA, 2-AG, PEA, etc.) using UHPLC-MS/MS. Our results demonstrated that rare pCBs modulate the gene and protein expression of distinct ECS elements differently, as well as the content of endocannabinoid(-like) compounds. Notably, they all increased CB1/2 binding, TRPV1 channel stimulation and FAAH and MAGL catalytic activity. These unprecedented observations should be considered when exploring the therapeutic potential of cannabis extracts for the treatment of human skin diseases. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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14 pages, 5773 KiB  
Article
Potential Pro-Inflammatory Effect of Vitamin E Analogs through Mitigation of Tetrahydrocannabinol (THC) Binding to the Cannabinoid 2 Receptor
by Anjela Manandhar, Mona H. Haron, Samir A. Ross, Michael L. Klein and Khaled M. Elokely
Int. J. Mol. Sci. 2022, 23(8), 4291; https://doi.org/10.3390/ijms23084291 - 13 Apr 2022
Cited by 2 | Viewed by 2002
Abstract
Vitamin E acetate, which is used as a diluent of tetrahydrocannabinol (THC), has been reported as the primary causative agent of e-cigarette, or vaping, product use-associated lung injury (EVALI). Here, we employ in vitro assays, docking, and molecular dynamics (MD) computer simulations to [...] Read more.
Vitamin E acetate, which is used as a diluent of tetrahydrocannabinol (THC), has been reported as the primary causative agent of e-cigarette, or vaping, product use-associated lung injury (EVALI). Here, we employ in vitro assays, docking, and molecular dynamics (MD) computer simulations to investigate the interaction of vitamin E with the membrane-bound cannabinoid 2 receptor (CB2R), and its role in modulating the binding affinity of THC to CB2R. From the MD simulations, we determined that vitamin E interacts with both CB2R and membrane phospholipids. Notably, the synchronized effect of these interactions likely facilitates vitamin E acting as a lipid modulator for the cannabinoid system. Furthermore, MD simulation and trajectory analysis show that when THC binds to CB2R in the presence of vitamin E, the binding cavity widens, facilitating the entry of water molecules into it, leading to a reduced interaction of THC with CB2R. Additionally, the interaction between THC and vitamin E in solution is stabilized by several H bonds, which can directly limit the interaction of free THCs with CB2R. Overall, both the MD simulations and the in vitro dissociation assay results indicate that THC binding to CB2R is reduced in the presence of vitamin E. Our study discusses the role of vitamin E in limiting the effect of THCs and its implications on the reported pathology of EVALI. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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18 pages, 4166 KiB  
Article
Chemical Synthesis, Pharmacokinetic Properties and Biological Effects of JM-00266, a Putative Non-Brain Penetrant Cannabinoid Receptor 1 Inverse Agonist
by Tania Muller, Laurent Demizieux, Stéphanie Troy-Fioramonti, Chloé Buch, Julia Leemput, Christine Belloir, Jean-Paul Pais de Barros, Tony Jourdan, Patricia Passilly-Degrace, Xavier Fioramonti, Anne-Marie Le Bon, Bruno Vergès, Jean-Michel Robert and Pascal Degrace
Int. J. Mol. Sci. 2022, 23(6), 2923; https://doi.org/10.3390/ijms23062923 - 08 Mar 2022
Cited by 2 | Viewed by 2271
Abstract
Targeting cannabinoid 1 receptors (CB1R) with peripherally restricted antagonists (or inverse agonists) shows promise to improve metabolic disorders associated with obesity. In this context, we designed and synthetized JM-00266, a new CB1R blocker with limited blood–brain barrier (BBB) permeability. Pharmacokinetics were tested with [...] Read more.
Targeting cannabinoid 1 receptors (CB1R) with peripherally restricted antagonists (or inverse agonists) shows promise to improve metabolic disorders associated with obesity. In this context, we designed and synthetized JM-00266, a new CB1R blocker with limited blood–brain barrier (BBB) permeability. Pharmacokinetics were tested with SwissADME and in vivo in rodents after oral and intraperitoneal administration of JM-00266 in comparison with Rimonabant. In silico predictions indicated JM-00266 is a non-brain penetrant compound and this was confirmed by brain/plasma ratios and brain uptake index values. JM-00266 had no impact on food intake, anxiety-related behavior and body temperature suggesting an absence of central activity. cAMP assays performed in CB1R-transfected HEK293T/17 cells showed that the drug exhibited inverse agonist activity on CB1R. In addition, JM-00266 counteracted anandamide-induced gastroparesis indicating substantial peripheral activity. Acute administration of JM-00266 also improved glucose tolerance and insulin sensitivity in wild-type mice, but not in CB1R−/− mice. Furthermore, the accumulation of JM-00266 in adipose tissue was associated with an increase in lipolysis. In conclusion, JM-00266 or derivatives can be predicted as a new candidate for modulating peripheral endocannabinoid activity and improving obesity-related metabolic disorders. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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Review

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15 pages, 1883 KiB  
Review
The Origin and Biomedical Relevance of Cannabigerol
by Anna Jastrząb, Iwona Jarocka-Karpowicz and Elżbieta Skrzydlewska
Int. J. Mol. Sci. 2022, 23(14), 7929; https://doi.org/10.3390/ijms23147929 - 19 Jul 2022
Cited by 25 | Viewed by 5393
Abstract
The constant search for new pharmacologically active compounds, especially those that do not exhibit toxic effects, intensifies the interest in plant-based ingredients and their potential use in pharmacotherapy. One of the plants that has great therapeutic potential is Cannabis sativa L., a source [...] Read more.
The constant search for new pharmacologically active compounds, especially those that do not exhibit toxic effects, intensifies the interest in plant-based ingredients and their potential use in pharmacotherapy. One of the plants that has great therapeutic potential is Cannabis sativa L., a source of the psychoactive Δ9-tetrahydrocannabinol (Δ9-THC), namely cannabidiol (CBD), which exhibits antioxidant and anti-inflammatory properties, and cannabigerol (CBG)—a biologically active compound that is present in much smaller quantities. CBG is generated during the non-enzymatic decarboxylation of cannabigerolic acid, a key compound in the process of biosynthesis of phytocannabinoids and consequently the precursor to various phytocannabinoids. By interacting with G-protein-coupled receptors, CBG exhibits a wide range of biological activities, inter alia, anti-inflammatory, antibacterial and antifungal activities, regulation of the redox balance, and neuromodulatory effects. Due to the wide spectrum of biological activities, CBG seems to be a very promising compound to be used in the treatment of diseases that require multidirectional pharmacotherapy. Moreover, it is suggested that due to the relatively rapid metabolism of cannabigerol, determination of the concentration of the phytocannabinoid in blood or oral fluid can be used to determine cannabis use. Therefore, it seems obvious that new therapeutic approaches using CBG can be expected. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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32 pages, 2135 KiB  
Review
Cross-Talk between the (Endo)Cannabinoid and Renin-Angiotensin Systems: Basic Evidence and Potential Therapeutic Significance
by Krzysztof Mińczuk, Marta Baranowska-Kuczko, Anna Krzyżewska, Eberhard Schlicker and Barbara Malinowska
Int. J. Mol. Sci. 2022, 23(11), 6350; https://doi.org/10.3390/ijms23116350 - 06 Jun 2022
Cited by 2 | Viewed by 2701
Abstract
This review is dedicated to the cross-talk between the (endo)cannabinoid and renin angiotensin systems (RAS). Activation of AT1 receptors (AT1Rs) by angiotensin II (Ang II) can release endocannabinoids that, by acting at cannabinoid CB1 receptors (CB1Rs), modify [...] Read more.
This review is dedicated to the cross-talk between the (endo)cannabinoid and renin angiotensin systems (RAS). Activation of AT1 receptors (AT1Rs) by angiotensin II (Ang II) can release endocannabinoids that, by acting at cannabinoid CB1 receptors (CB1Rs), modify the response to AT1R stimulation. CB1R blockade may enhance AT1R-mediated responses (mainly vasoconstrictor effects) or reduce them (mainly central nervous system-mediated effects). The final effects depend on whether stimulation of CB1Rs and AT1Rs induces opposite or the same effects. Second, CB1R blockade may diminish AT1R levels. Third, phytocannabinoids modulate angiotensin-converting enzyme-2. Additional studies are required to clarify (1) the existence of a cross-talk between the protective axis of the RAS (Ang II—AT2 receptor system or angiotensin 1-7—Mas receptor system) with components of the endocannabinoid system, (2) the influence of Ang II on constituents of the endocannabinoid system and (3) the (patho)physiological significance of AT1R-CB1R heteromerization. As a therapeutic consequence, CB1R antagonists may influence effects elicited by the activation or blockade of the RAS; phytocannabinoids may be useful as adjuvant therapy against COVID-19; single drugs acting on the (endo)cannabinoid system (cannabidiol) and the RAS (telmisartan) may show pharmacokinetic interactions since they are substrates of the same metabolizing enzyme of the transport mechanism. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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14 pages, 2481 KiB  
Review
Lipid-Drug Conjugates and Nanoparticles for the Cutaneous Delivery of Cannabidiol
by Aleksandra Zielińska, Amanda Cano, Tatiana Andreani, Carlos Martins-Gomes, Amélia M. Silva, Marlena Szalata, Ryszard Słomski and Eliana B. Souto
Int. J. Mol. Sci. 2022, 23(11), 6165; https://doi.org/10.3390/ijms23116165 - 31 May 2022
Cited by 3 | Viewed by 2555
Abstract
Lipid nanoparticles are currently used to deliver drugs to specific sites in the body, known as targeted therapy. Conjugates of lipids and drugs to produce drug-enriched phospholipid micelles have been proposed to increase the lipophilic character of drugs to overcome biological barriers. However, [...] Read more.
Lipid nanoparticles are currently used to deliver drugs to specific sites in the body, known as targeted therapy. Conjugates of lipids and drugs to produce drug-enriched phospholipid micelles have been proposed to increase the lipophilic character of drugs to overcome biological barriers. However, their applicability at the topical level is still minimal. Phospholipid micelles are amphiphilic colloidal systems of nanometric dimensions, composed of a lipophilic nucleus and a hydrophilic outer surface. They are currently used successfully as pharmaceutical vehicles for poorly water-soluble drugs. These micelles have high in vitro and in vivo stability and high biocompatibility. This review discusses the use of lipid-drug conjugates as biocompatible carriers for cutaneous application. This work provides a metadata analysis of publications concerning the conjugation of cannabidiol with lipids as a suitable approach and as a new delivery system for this drug. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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10 pages, 632 KiB  
Review
Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection
by Marcin Janecki, Michał Graczyk, Agata Anna Lewandowska and Łukasz Pawlak
Int. J. Mol. Sci. 2022, 23(8), 4170; https://doi.org/10.3390/ijms23084170 - 10 Apr 2022
Cited by 20 | Viewed by 4633
Abstract
The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have [...] Read more.
The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant’s compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases. Full article
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
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