CBD Found to Improve Survival in Worm Models of Parkinson’s
New study findings support cannabidiol as anti-parkinsonian therapy
Treatment with cannabidiol (CBD) prevented nerve cell death, extended survival, and reduced toxic protein clumps in nematode worm models of Parkinson’s disease, a new study reports.
“These findings supported CBD as an anti-parkinsonian drug,” the researchers wrote, adding that “this CBD neuroprotective action might be due to its antioxidative … properties.”
CBD is a compound derived from the cannabis plant. CBD is not psychoactive — meaning it does not induce a “high” — but emerging research has shown the molecule to possess anti-inflammatory and antioxidant properties, and its potential applications in Parkinson’s and other disorders are being explored.
Testing CBD in Parkinson’s worms
In this study, researchers in China used a number of tests to evaluate the effect of CBD treatment in Caenorhabditis elegans, a type of nematode worm that is well-characterized as a laboratory model.
First, the researchers tested various concentrations of CBD in healthy worms, with doses ranging from 0.025 to 0.4 micromolar (mM). Results showed that doses of 0.2 mM or higher were toxic to the worms, so for subsequent experiments, the team used three non-toxic doses: 0.025, 0.05, and 0.1 mM.
The scientists then tested these CBD concentrations in worms with modeled Parkinson’s, inducted via 6-OHDA. Parkinson’s is caused by the death of dopamine-producing cells in the brain; 6-OHDA is a chemical that is toxic for these cells.
The C. elegans model used in this study was genetically engineered to express fluorescent proteins in dopamine-making neurons. That allowed the scientists to easily detect these disease-relevant cells.
6-OHDA substantially reduced the fluorescent signal in these worms, indicating a reduction in numbers of dopaminergic neurons. Treatment with CBD at concentrations of 0.025, 0.05, and 0.1 mM increased this fluorescent signal by 24.66%, 52.41%, and 71.36%, respectively, suggesting that CBD prevented dopaminergic nerve cell death in this model.
Further results showed that CBD pretreatment extended survival times for worms on 6-OHDA, by 28.8% at the highest tested dose. In another worm model — one without the fluorescent cell — CBD pre-treatment extended survival by up to 45.1%.
The use of CBD also normalized food-seeking behavior, which is disrupted in nematode worms given 6-OHDA because dopamine — a chemical messenger used for communication by nerve cells — is important for governing feeding behavior in C. elegans.
Parkinson’s is characterized by the formation of toxic aggregates, or clumps, containing the protein alpha-synuclein, These aggregates are thought to contribute to neuronal death and dysfunction in the disease.
In a series of further experiments, the researchers tested CBD’s effects in worms that were genetically engineered to produce a clumping form of alpha-synuclein with a fluorescent tag.
Results showed that CBD treatment reduced the fluorescent signal in these mice — by 40.6%, 56.3%, and 70.2% at doses of 0.025, 0.05, and 0.1 mM, respectively — indicating that it reduced toxic alpha-synuclein clumping.
Further analyses confirmed the reduction in alpha-synuclein clumping, and showed that CBD treatment helped normalize the activity of certain fatty molecules that are disrupted by aggregated alpha-synuclein.
CBD treatment increased the activity of a cellular “garbage disposal” system called the ubiquitin-like proteasome system (UPS), and it also showed antioxidant activity, reducing levels of toxic molecules called reactive oxygen species.
While the researchers emphasized that more research is needed to fully define CBD’s biological mechanisms of action and its potential therapeutic benefits in Parkinson’s, they said these findings broadly support CBD as a potential anti-Parkinson’s therapy.
They noted that this study “is the first report on the anti-parkinsonism role of CBD in C. elegans” Parkinson’s disease models.
“The worms have an easy culture method, a short life cycle with a simple neuron network, and a conserved nervous system pathway,” the team wrote.