Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors

Navarro, Gemma; Varani, Katia; Lillo, Alejandro; Vincenzi, Fabrizio; Rivas‐Santisteban, Rafael; Raïch, Iu; Reyes‐Resina, Irene; Ferreiro‐Vera, Carlos; Borea, Pier Andrea; Medina, Verónica Sánchez de; Nadal, Xavier; Franco, Rafael

doi:10.1016/j.phrs.2020.104940

Cited by 60 publications

(80 citation statements)

References 63 publications

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“…CBDa was inactive at CB1R and displayed weak partial agonism at CB2R in our cell culture assays. Navarro et al 12 reported higher than anticipated affinity and activity of CBDa in both [ 3 H]CP55,940 binding for CB1R and CB2R in CHO cells and signaling in HEK-293T cells, which were similar to our findings. In vivo, CBDa produced significant hypolocomotive and anxiolytic effects in the OFT.…”

Section: Discussionsupporting

confidence: 92%

“…Similarly, Navarro et al 12 observed that CBDV was nearly inactive at CB1R with greater activity at CB2R. However, the binding affinity of CBDV to CB2R was greater in our experiments compared to those of Navarro et al 12 . This difference may be due to differing radioligand concentrations and/or differential expression of the receptor in our cell models.…”

Section: Discussionsupporting

confidence: 61%

“…CBDV displayed little to no activity at CB1R but did display demonstrable affinity and activity at CB2R. Similarly, Navarro et al 12 observed that CBDV was nearly inactive at CB1R with greater activity at CB2R. However, the binding affinity of CBDV to CB2R was greater in our experiments compared to those of Navarro et al 12 .…”

Section: Discussionsupporting

confidence: 48%

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

Zagzoog

Mohamed

Kim

et al. 2020

Sci Rep

120

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The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of the less-abundant plant-derived (phyto) cannabinoids. The best-studied transducers of cannabinoid-dependent effects are type 1 and type 2 cannabinoid receptors (CB1R, CB2R). Partial agonism of CB1R by ∆9-THC is known to bring about the ‘high’ associated with Cannabis use, as well as the pain-, appetite-, and anxiety-modulating effects that are potentially therapeutic. CB2R activation by certain cannabinoids has been associated with anti-inflammatory activities. We assessed the activity of 8 phytocannabinoids at human CB1R, and CB2R in Chinese hamster ovary (CHO) cells stably expressing these receptors and in C57BL/6 mice in an attempt to better understand their pharmacodynamics. Specifically, ∆9-THC, ∆9-tetrahydrocannabinolic acid (∆9-THCa), ∆9-tetrahydrocannabivarin (THCV), CBD, cannabidiolic acid (CBDa), cannabidivarin (CBDV), cannabigerol (CBG), and cannabichromene (CBC) were evaluated. Compounds were assessed for their affinity to receptors, ability to inhibit cAMP accumulation, βarrestin2 recruitment, receptor selectivity, and ligand bias in cell culture; and cataleptic, hypothermic, anti-nociceptive, hypolocomotive, and anxiolytic effects in mice. Our data reveal partial agonist activity for many phytocannabinoids tested at CB1R and/or CB2R, as well as in vivo responses often associated with activation of CB1R. These data build on the growing body of literature showing cannabinoid receptor-dependent pharmacology for these less-abundant phytocannabinoids and are critical in understanding the complex and interactive pharmacology of Cannabis-derived molecules.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 61%

See 1 more Smart Citation

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

Zagzoog

Mohamed

Kim

et al. 2020

Sci Rep

120

View full text Add to dashboard Cite

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“…In a variety of different ways, CBG seems to reside, pharmacologically, in between Δ9-THC and CBD. From the receptor binding data presented in Table 1, CBG is more like Δ9-THC at the CB1/CB2 receptors than CBD, but with a lower affinity (by a factor of between 5-fold and 27-fold) (Pertwee, 2008;Cascio et al, 2010;Pollastro et al, 2011;Rosenthaler et al, 2014;Navarro et al, 2018;Navarro et al, 2020). However, a 2012 study of CBG in human cell culture demonstrated negligible binding affinities for CBG at CB1 and CB2 receptors (Granja et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

The Pharmacological Case for Cannabigerol

Nachnani

Raup‐Konsavage

Vrana

2020

J Pharmacol Exp Ther

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“…CB1 and CB2 signaling involves alterations in Cyclic adenosine monophosphate (cAMP) levels, Extracellular regulated kinase 1/2 (ERK1/2) phosphorylation, and β-arrestin-2 recruitment [ 2 ]. They can also form heterodimers and lead to a biased agonistic response [ 4 ]. Alterations in concentrations of the endogenous endocannabinoid ligands, receptor expression or activity, or endocannabinoid metabolic enzyme activity have been found to be associated with varied pathological conditions [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Chronological Review and Rational and Future Prospects of Cannabis-Based Drug Development

et al. 2020

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Despite the surge in cannabis chemistry research and its biological and medical activity, only a few cannabis-based pharmaceutical-grade drugs have been developed and marketed to date. Not many of these drugs are Food and Drug Administration (FDA)-approved, and some are still going through regulation processes. Active compounds including cannabinergic compounds (i.e., molecules targeted to modulate the endocannabinoid system) or phytocannabinoid analogues (cannabinoids produced by the plant) may be developed into single-molecule drugs. However, since in many cases treatment with whole-plant extract (whether as a solvent extraction, galenic preparation, or crude oil) is preferred over treatment with a single purified molecule, some more recently developed cannabis-derived drugs contain several molecules. Different combinations of active plant ingredients (API) from cannabis with proven synergies may be identified and developed as drugs to treat different medical conditions. However, possible negative effects between cannabis compounds should also be considered, as well as the effect of the cannabis treatment on the endocannabinoid system. FDA registration of single, few, or multiple molecules as drugs is a challenging process, and certain considerations that should be reviewed in this process, including issues of drug–drug interactions, are also discussed here.

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Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors

Cited by 60 publications

References 63 publications

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

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

The Pharmacological Case for Cannabigerol

Chronological Review and Rational and Future Prospects of Cannabis-Based Drug Development

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