Cannabidiol in Neurological and Neoplastic Diseases: Latest Developments on the Molecular Mechanism of Action

Ożarowski, Marcin; Karpiński, Tomasz M.; Zielińska, Aleksandra; Souto, Eliana B.; Wielgus, Karolina

doi:10.3390/ijms22094294

Cited by 40 publications

(34 citation statements)

References 97 publications

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“…In adolescent and adult mice, in vivo brain administration of 5-MDMB-PICA produced anxiety-like and compulsive states [ 67 ]. The effects on neuronal development have been also studied.…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Giorgetti

Pascali

Fais

et al. 2021

Life

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Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions.

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“…In adolescent and adult mice, in vivo brain administration of 5-MDMB-PICA produced anxiety-like and compulsive states [ 67 ]. The effects on neuronal development have been also studied.…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Giorgetti

Pascali

Fais

et al. 2021

Life

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“…Despite its structural similarity, CBD has low selectivity for both CB1R and CB2R [15]. It seems that CBD carries out its anti-seizure action by interacting with G protein-coupled receptor 55 (GPR-55) and transient receptor potential vanilloid 1 (TRPV-1) channel, by anti-inflammatory effect and influence on the adenosine pathway [15][16][17][18][19][20][21][22][23][24].…”

Section: Mechanism Of Action Of Cbd In Epilepsymentioning

confidence: 99%

“…Microglia are considered to be the macrophages of the brain that act as sentinel immune cells [15]. CBD has been shown to have an anti-inflammatory effect by blocking microglia activation [20]. Juknat et al identified cannabinoid-regulated microribonucleic acids (miRNAs) in resting and in lipopolysaccharide (LPS)-activated microglia.…”

Section: Neuroinflammationmentioning

confidence: 99%

Use of cannabidiol in the treatment of epilepsy

Zawadzka

Mazurkiewicz-Bełdzińska

2022

Neurol Neurochir Pol.

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Introduction.Cannabis sativa has been cultivated for human use for about 5,000 years, and has likewise been used in the treatment of epilepsy for thousands of years.State of the art. Cannabidiol (CBD), which was isolated from cannabis sativa in 1940, has an anti-seizure effect and no psychoactive activity. Its effectiveness in reducing various types of seizures has been proven in animal seizure and epilepsy models. Recent randomised, placebo-controlled trials have confirmed its effectiveness in patients with drug-resistant epilepsy.Clinical implications. The aim of this position paper was to present the specific mechanism of CBD's anti-seizure action and current indications for CBD's use in epilepsy. The only cannabis-derived drug that has successfully passed clinical trials and has obtained United States Food and Drug Administration and European Medicines Agency approval for epilepsy is Epidiolex®. This paper presents the outcomes of the completed clinical trials with the use of this drug.Future directions. CBD may be an effective drug in drug-resistant epilepsy, particularly in Dravet Syndrome, Lennox-Gastaut Syndrome and seizures associated with tuberous sclerosis complex. Additional randomised, placebo-controlled studies with CBD are needed.

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“…In this regard, SR141716 (Rimonabant) and CBD are well-known CB1R antagonists. Specifically, CBD can also act as inverse agonist/negative allosteric modulator at CB1R and partial agonist at CB2R [ 120 , 121 ]. In addition, several reports demonstrated that it can activate TRPV1, PPAR-γ and antagonise GPR55 [ 122 , 123 , 124 ].…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Endocannabinoid System and Tumour Microenvironment: New Intertwined Connections for Anticancer Approaches

Iozzo

Sgrignani

Comito

et al. 2021

Cells

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The tumour microenvironment (TME) is now recognised as a hallmark of cancer, since tumour:stroma crosstalk supports the key steps of tumour growth and progression. The dynamic co-evolution of the tumour and stromal compartments may alter the surrounding microenvironment, including the composition in metabolites and signalling mediators. A growing number of evidence reports the involvement of the endocannabinoid system (ECS) in cancer. ECS is composed by a complex network of ligands, receptors, and enzymes, which act in synergy and contribute to several physiological but also pathological processes. Several in vitro and in vivo evidence show that ECS deregulation in cancer cells affects proliferation, migration, invasion, apoptosis, and metastatic potential. Although it is still an evolving research, recent experimental evidence also suggests that ECS can modulate the functional behaviour of several components of the TME, above all the immune cells, endothelial cells and stromal components. However, the role of ECS in the tumour:stroma interplay remains unclear and research in this area is particularly intriguing. This review aims to shed light on the latest relevant findings of the tumour response to ECS modulation, encouraging a more in-depth analysis in this field. Novel discoveries could be promising for novel anti-tumour approaches, targeting the microenvironmental components and the supportive tumour:stroma crosstalk, thereby hindering tumour development.

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Cannabidiol in Neurological and Neoplastic Diseases: Latest Developments on the Molecular Mechanism of Action

Cited by 40 publications

References 97 publications

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Use of cannabidiol in the treatment of epilepsy

Endocannabinoid System and Tumour Microenvironment: New Intertwined Connections for Anticancer Approaches

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