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Paclitaxel-Associated Mechanical Sensitivity and Neuroinflammation Are Sex-, Time-, and Site-Specific and Prevented through Cannabigerol Administration in C57Bl/6 Mice

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients. One identified mechanism underlying CIPN is neuroinflammation. Most of this research has been conducted in only male or female rodent models, making direct comparisons regarding the role of sex differences in the neuroimmune underpinnings of CIPN limited. Moreover, most measurements have focused on the dorsal root ganglia (DRG) and/or spinal cord, while relatively few studies have been aimed at characterizing neuroinflammation in the brain, for example the periaqueductal grey (PAG). The overall goals of the present study were to determine (1) paclitaxel-associated changes in markers of inflammation in the PAG and DRG in male and female C57Bl6 mice and (2) determine the effect of prophylactic administration of an anti- inflammatory cannabinoid, cannabigerol (CBG).

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Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat

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The pharmacological profile of cannabigerol (CBG), which acid form constitutes the main precursor of the most abundant cannabinoids, has been scarcely studied. It has been reported to target α2-adrenoceptor and 5-HT1A receptor. The locus coeruleus (LC) and the dorsal raphe nucleus (DRN) are the main serotonergic (5-HT) and noradrenergic (NA) areas in the rat brain, respectively. We aimed to study the effect of CBG on the firing rate of LC NA cells and DRN 5-HT cells and on α2-adrenergic and 5-HT1A autoreceptors by electrophysiological techniques in male Sprague-Dawley rat brain slices. The effect of CBG on the novelty-suppressed feeding test (NSFT) and the elevated plus maze test (EPMT) and the involvement of the 5-HT1A receptor was also studied. CBG (30 μM, 10 min) slightly changed the firing rate of NA cells but failed to alter the inhibitory effect of NA (1–100 µM).

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Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial

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Cannabigerol (CBG) is a phytocannabinoid increasing in popularity, with preclinical research indicating it has anxiolytic and antidepressant effects. However, there are no published clinical trials to corroborate these findings in humans. The primary objective of this study was to examine acute effects of CBG on anxiety, stress, and mood. Secondary objectives were to examine whether CBG produces subjective drug effects or motor and cognitive impairments. A double-blind, placebo-controlled cross-over field trial was conducted with 34 healthy adult participants. Participants completed two sessions (with a one-week washout period) via Zoom. In each, they provided ratings of anxiety, stress, mood, and subjective drug effects prior to double-blind administration of 20 mg hemp-derived CBG or placebo tincture (T0).

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Toxicity of Cannabigerol: Examination of Long-Term Toxicity and Lifespan in Caenorhabditis elegans and 14-Day Study in Sprague Dawley Rats

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Cannabigerol (CBG) is becoming widely available despite little being known about its potential toxicity or long-term effects. The present investigation involved two distinct studies. The first study explored acute and long-term effects of CBG on toxicity, lifespan, and aging in adult Caenorhabditis elegans (C. elegans). Animals were treated with CBG (0.075 lM–3.75 mM) to determine acute toxicity, mortality, and motility. Acute heat- induced stress survival (thermotolerance; 37°C for 4 h) following CBG administration (0.075–3.75 mM) was measured. Long-term toxicity of lifelong CBG administration (7.5, 75, or 375 lM CBG) was determined through changes in motility and lifespan duration. In the second study, healthy, adult, Sprague Dawley rats received 0, 35, 70, or 140 mg/kg-bw/day CBG (n = 5 per sex per group) daily for 14 days via oral gavage. Signs of gross toxicity and changes in behavior, body weight, food consumption, and serum chemistry were monitored. Liver, kidney, and adrenal gland weights were recorded, and histopathology of select tissues was examined.

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Therapeutic Potential of Phytocannabinoid Cannabigerol for Multiple Sclerosis: Modulation of Microglial Activation In Vitro and In Vivo

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Multiple sclerosis (MS) is a widespread chronic neuroinflammatory and neurodegenerative disease. Microglia play a crucial role in the pathogenesis of MS via the release of cytokines and reactive oxygen species, e.g., nitric oxide. Research involving the role of phytocannabinoids in neuroinflammation is currently receiving much attention. Cannabigerol is a main phytocannabinoid, which has attracted significant pharmacological interest due to its non-psychotropic nature. In this research, we studied the effects of cannabigerol on microglial inflammation in vitro, followed by an in vivo study. Cannabigerol attenuated the microglial production of nitric oxide in BV2 microglia and primary glial cells; concomitant treatment of the cells with cannabigerol and telmisartan (a neuroprotective angiotensin receptor blocker) decreased nitric oxide production additively. Inducible nitric oxide synthase (iNOS) expression was also reduced by cannabigerol.

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Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota

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Cannabidiol (CBD) and cannabigerol (CBG) are two pharmacologically active phytocannabinoids of Cannabis sativa L. Their antimicrobial activity needs further elucidation, particularly for CBG, as reports on this cannabinoid are scarce. We investigated CBD and CBG’s antimicrobial potential, including their ability to inhibit the formation and cause the removal of biofilms. Our results demonstrate that both molecules present activity against planktonic bacteria and biofilms, with both cannabinoids removing mature biofilms at concentrations below the determined minimum inhibitory concentrations. We report for the first time minimum inhibitory and lethal concentrations for Pseudomonas aeruginosa and Escherichia coli (ranging from 400 to 3180 µM), as well as the ability of cannabinoids to inhibit Staphylococci adhesion to keratinocytes, with CBG demonstrating higher activity than CBD.

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An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma

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Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in mesothelioma cell lines.

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Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

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The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors.

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In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa

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Authors: Ayat Zagzoog, Kawthar A. Mohamed, Hye Ji J. Kim, Eunhyun D. Kim, Connor S. Frank, Tallan Black, Pramodkumar D. Jadhav, Larry A. Holbrook & Robert B. Laprairie Published in…

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Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation

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Authors: Ester Pagano, Fabio A. Iannotti, Fabiana Piscitelli, Barbara Romano, Giuseppe Lucariello, Tommaso Venneri, Vincenzo Di Marzo, Angelo A. Izzo, Francesca Borrelli Published in Phytotherapy Research September 2020 Abstract Summary…

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Delegitimizing Cannabis Because of Its Recreational Use is the Real Lie

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Sherry Yafai, MD encourages the need for healthcare professionals to shift their perspective on cannabis in her column for Emergency Medicine News. “Delegitimizing medications based simply on their potential for recreational use or abuse is a dangerous and uninformed approach for physicians.”

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Intraocular pressure, ocular toxicity and neurotoxicity after administration of cannabinol or cannabigerol

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Author: Brenda K.Colasanti, Charles R. Craig, R. David Allara Published in Science Direct September 1984 Abstract Cannabinol or cannabigerol was administered to cats topically in doses of 250, 500 and…

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