Cannabidiol Recovers Dopaminergic Neuronal Damage Induced by Reserpine or α-synuclein in Caenorhabditis elegans

Neurochem Res. 2023 Aug;48(8):2390-2405. doi: 10.1007/s11064-023-03905-z. Epub 2023 Mar 25.


Progressive neurodegenerative disorders such as Parkinson Disease (PD) lack curative or long-term treatments. At the same time, the increase of the worldwide elderly population and, consequently, the extension in the prevalence of age-related diseases have promoted research interest in neurodegenerative disorders. Caenorhabditis elegans is a free-living nematode widely used as an animal model in studies of human diseases. Here we evaluated cannabidiol (CBD) as a possible neuroprotective compound in PD using the C. elegans models exposed to reserpine. Our results demonstrated that CBD reversed the reserpine-induced locomotor alterations and this response was independent of the NPR-19 receptors, an orthologous receptor for central cannabinoid receptor type 1. Morphological alterations of cephalic sensilla (CEP) dopaminergic neurons indicated that CBD also protects neurons from reserpine-induced degeneration. That is, CBD attenuates the reserpine-induced increase of worms with shrunken soma and dendrites loss, increasing the number of worms with intact CEP neurons. Finally, we found that CBD also reduced ROS formation and α-syn protein accumulation in mutant worms. Our findings collectively provide new evidence that CBD acts as neuroprotector in dopaminergic neurons, reducing neurotoxicity and α-syn accumulation highlighting its potential in the treatment of PD.

Keywords: Caenorhabditis elegans; Cannabidiol; Parkinson Disease.

MeSH terms

  • Aged
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins* / metabolism
  • Cannabidiol* / pharmacology
  • Disease Models, Animal
  • Dopaminergic Neurons / metabolism
  • Humans
  • Neurodegenerative Diseases* / metabolism
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Parkinson Disease* / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Reserpine / metabolism
  • Reserpine / toxicity
  • alpha-Synuclein / metabolism


  • alpha-Synuclein
  • Cannabidiol
  • Reserpine
  • Caenorhabditis elegans Proteins
  • Neuroprotective Agents
  • NPR-19 protein, C elegans
  • Receptors, G-Protein-Coupled