Cannabidiol Targets Mitochondria to Regulate Intracellular Ca2+ Levels

@article{Ryan2009CannabidiolTM,
  title={Cannabidiol Targets Mitochondria to Regulate Intracellular Ca2+ Levels},
  author={Duncan Ryan and Alison J. Drysdale and Carlos Lafourcade and Roger G. Pertwee and Bettina Platt},
  journal={The Journal of Neuroscience},
  year={2009},
  volume={29},
  pages={2053 - 2063}
}
Cannabinoids and the endocannabinoid system have attracted considerable interest for therapeutic applications. Nevertheless, the mechanism of action of one of the main nonpsychoactive phytocannabinoids, cannabidiol (CBD), remains elusive despite potentially beneficial properties as an anti-convulsant and neuroprotectant. Here, we characterize the mechanisms by which CBD regulates Ca2+ homeostasis and mediates neuroprotection in neuronal preparations. Imaging studies in hippocampal cultures… 

Figures from this paper

Regulatory Effects of Cannabidiol on Mitochondrial Functions: A Review
TLDR
This review focuses on understanding the mechanisms of CBD-mediated regulation of mitochondrial functions, with an emphasis on findings in neural cells and tissues and therapeutic relevance based on human pharmacokinetics.
Cannabidiol induces intracellular calcium elevation and cytotoxicity in oligodendrocytes
TLDR
It is suggested that cannabidiol causes intracellular Ca2+ dysregulation which can lead to oligodendrocytes demise.
Endocannabinoid system and anticancer properties of cannabinoids
TLDR
Effects of cannabinoids showing low affinity to CB receptors is mediated probably by induction of reactive oxygen species production, and there is a necessity to conduct more experiments to assess the real potential of these compounds.
Studies investigating the mechanisms of the cardioprotective effects of cannabidiol
TLDR
The characterisation of the pharmacology of CBD in vivo showed that; firstly, CB1 receptor activation causes a hypotensive response which can be dose-dependently inhibited by AM251; secondly, both CBD and AM251 alone can induce vasodepressor responses and finally, CBD can potentiate the AM251-mediated hypotension when co-administered, suggesting possible cross-talk between the CB1 and GPR55.
Endocannabinoid system and anticancer properties of cannabinoids
TLDR
Knowledge of antitumor activity of cannabinoids is still based only on preclinical studies and there is a necessity to conduct more experiments to assess the real potential of these compounds.
Knockdown siRNA Targeting the Mitochondrial Sodium-Calcium Exchanger-1 Inhibits the Protective Effects of Two Cannabinoids Against Acute Paclitaxel Toxicity
TLDR
Data indicate that decreases in neuritic mNCX-1 corresponded closely with decreased protection after siRNA treatment, supporting the observed siRNA effects on mechanism.
Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death
TLDR
The findings indicate that CBD treatment leads to a biphasic increase in intracellular calcium levels and to changes in mitochondrial function and morphology leading to cell death, and the inhibition of VDAC1 by CBD may be responsible for the immunosuppressive and anticancer effects of CBD.
Cannabidiol Protects Dopaminergic Neuronal Cells from Cadmium
TLDR
CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity and is partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 88 REFERENCES
Cannabidiol-induced intracellular Ca2+ elevations in hippocampal cells
Interactions of cannabidiol with endocannabinoid signalling in hippocampal tissue
TLDR
Interactions between CBD (1 µm) and the endocannabinoid system in cultured rat hippocampal cells are characterized to highlight the interaction between exogenous and endogenous cannabinoid signalling, and provide evidence for the presence of an additional pharmacological target, sensitive to endoc cannabinoidoids and to AM281.
Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL‐2H3 mast cells
TLDR
It is demonstrated that CBD augments β‐hexosaminidase release, a marker of cell activation, from antigen‐stimulated and unstimulated cells via a mechanism, which is not mediated by Gi/Go protein‐coupled receptors but rather is associated with a robust rise in intracellular calcium levels sensitive to clotrimazole and nitrendipine.
CGP37157 modulates mitochondrial Ca2+ homeostasis in cultured rat dorsal root ganglion neurons.
Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression
TLDR
It is demonstrated that CBD has the ability to enhance adenosine signaling through inhibition of uptake and provide a non-cannabinoid receptor mechanism by which CBD can decrease inflammation.
Cannabinoids: mechanisms and therapeutic applications in the CNS.
TLDR
Understanding of the therapeutic relevance of cannabinoids will rely on further investigations into the neuroprotective and neurotoxic potency of cannabinoids in animal models and humans, as much as on a further advancement of the general understanding of the endocannabinoid system and the development of specific compounds devoid of unwanted psychoactive side effects.
Plant-Derived Cannabinoids Modulate the Activity of Transient Receptor Potential Channels of Ankyrin Type-1 and Melastatin Type-8
TLDR
The findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.
Mitochondrial Ca2+ Uptake Requires Sustained Ca2+ Release from the Endoplasmic Reticulum*
TLDR
The data indicate that efficient mitochondrial Ca2+ uptake depends on the preservation of highCa2+ microdomains at the mouth of ER Ca 2+ release sites close to mitochondria, and this in turn depends on continuous Ca2- release balanced by Ca1+ reuptake into the ER and maintained by Ca3+ influx from the extracellular space.
Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants.
TLDR
Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or alpha-tocopherol, indicating it to be a potent antioxidant, and data suggest that the naturally occurring, nonpsychotropic cannabinoid, cannABidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.
Neuropharmacology and therapeutic potential of cannabinoids
TLDR
Future research is likely to be directed at characterizing the endogenous cannabinoid system more completely, at obtaining more conclusive clinical data about cannabinoids with regard to both beneficial and adverse effects, and at developing improved cannabinoid formulations and modes of administration.
...
1
2
3
4
5
...