ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 247 citations in OpenAlex.
- Does cannabidiol reduce the adverse effects of cannabis in schizophrenia? A randomised, double-blind, cross-over trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Topical Cannabidiol for Established Chemotherapy-Induced Neuropathy: A Pilot Randomized Placebo-Controlled Trial.Cannabis and cannabinoid research · 2024Trial
- Cannabidiol in Alzheimer's disease: evidence-weighted molecular mechanisms and translational challenges.Molecular biology reports · 2026Review
- Endocannabinoid system and skeletal muscle health: Insights from cannabidiol.Molecular metabolism · 2026Review
- The Therapeutic Paradox of Endocannabinoid Immunomodulation: Molecular Mechanisms and Strategic Frameworks.International journal of molecular sciences · 2026Review
- The synthetic cannabinoid THJ-2201 modulates mitochondrial activity and enhances mitochondrial recruitment to newly-forming neurites during neurodifferentiation of NG108-15 cells.Archives of toxicology · 2026Article
- Protective effects of cannabidiol against acute stress: behavioral responses and corticosterone concentrations in female Wistar rats.Frontiers in pharmacology · 2026Article
- Cannabidiol-Induced Tumor Cell Death: Molecular Mechanisms and Translational Perspectives in Cancer Therapy.Drug design, development and therapy · 2026Review
- Elucidating the transcriptomic response of adult-derived mHypoA-2/12 mouse hypothalamic neuron cell line to cannabidiol (CBD) exposure.Journal of applied genetics · 2025Article
- The effects of Cannabidiol on podocytes in vitro.Biochemical and biophysical research communications · 2025Article
- Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.Molecular psychiatry · 2025Article
- Cannabidiol Prevents Heart Failure Dysfunction and Remodeling Through Preservation of Mitochondrial Function and Calcium Handling.JACC. Basic to translational science · 2025Article
- Review
- A novel insight into the antidepressant effect of cannabidiol: possible involvement of the 5-HT1A, CB1, GPR55, and PPARγ receptors.The international journal of neuropsychopharmacology · 2025Review
- Successful management of refractory epilepsy in creatine transporter deficiency with cannabidiol and clobazam: A case report.Epilepsia open · 2025Article
- Combination CBD/THC in the management of chemotherapy-induced peripheral neuropathy: a randomized double blind controlled trial.Frontiers in oncology · 2025Article
- Cannabidiol (CBD) modulates the transcriptional profile of ethanol-exposed human dermal fibroblast cells.Journal of applied genetics · 2024Article
- Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models.Nature communications · 2024Article
- JWH-182: a safe and effective synthetic cannabinoid for chemotherapy-induced neuropathic pain in preclinical models.Scientific reports · 2024Article
- Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 Ca(2+) homeostasis and mediates neuroprotection in neuronal preparations. Imaging studies in hippocampal cultures using fura-2 AM suggested that CBD-mediated Ca(2+) regulation is bidirectional, depending on the excitability of cells. Under physiological K(+)/Ca(2+) levels, CBD caused a subtle rise in [Ca(2+)](i), whereas CBD reduced [Ca(2+)](i) and prevented Ca(2+) oscillations under high-excitability conditions (high K(+) or exposure to the K(+) channel antagonist 4AP). Regulation of [Ca(2+)](i) was not primarily mediated by interactions with ryanodine or IP(3) receptors of the endoplasmic reticulum. Instead, dual-calcium imaging experiments with a cytosolic (fura-2 AM) and a mitochondrial (Rhod-FF, AM) fluorophore implied that mitochondria act as sinks and sources for CBD's [Ca(2+)](i) regulation. Application of carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP) and the mitochondrial Na(+)/Ca(2+) exchange inhibitor, CGP 37157, but not the mitochondrial permeability transition pore inhibitor cyclosporin A, prevented subsequent CBD-induced Ca(2+) responses. In established human neuroblastoma cell lines (SH-SY5Y) treated with mitochondrial toxins, CBD (0.1 and 1 microm) was neuroprotective against the uncoupler FCCP (53% protection), and modestly protective against hydrogen peroxide- (16%) and oligomycin- (15%) mediated cell death, a pattern also confirmed in cultured hippocampal neurons. Thus, under pathological conditions involving mitochondrial dysfunction and Ca(2+) dysregulation, CBD may prove beneficial in preventing apoptotic signaling via a restoration of Ca(2+) homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.