A Sativex-like combination of THC and CBD botanical extracts reduced brain cell death, edema, and inflammation in a rat model of Huntington's disease, working through both CB1 and CB2 cannabinoid receptors.
Read this if you are interested in cannabinoid-based neuroprotection for neurodegenerative diseases.
Both CB1 and CB2 receptors were required for the neuroprotective effects
What the researchers found
Researchers tested a 1:1 combination of THC-rich and CBD-rich botanical extracts (mimicking Sativex) in rats with striatal lesions created by the toxin malonate, which models the inflammatory component of Huntington's disease.
The phytocannabinoid combination reduced edema measured by MRI, reversed the loss of healthy neurons and the increase in degenerating cells, attenuated reactive microglia and astrogliosis (markers of brain inflammation), and reduced inducible nitric oxide synthase and IGF-1 expression. Using selective receptor antagonists, the researchers confirmed that both CB1 and CB2 receptors were required for these protective effects.
Why it matters
Huntington's disease has no treatment that slows neurodegeneration. This study demonstrated neuroprotective effects of a cannabis-based medicine already approved for other conditions, using multiple objective measures of brain cell health and inflammation.
The numbers in context
Sativex-like combination: 1:1 THC/CBD botanical extracts. Reduced edema (NMR imaging), reversed neuron loss (Nissl staining), reduced degenerating cells (FluoroJade-B), attenuated microglia (Iba-1) and astrogliosis (GFAP). Both CB1 and CB2 receptors required.
How the study worked
Rat model of HD using unilateral striatal lesions with malonate (a mitochondrial complex II inhibitor). The Sativex-like combination was administered and compared to vehicle. Multiple histological and biochemical markers were assessed. CB1 antagonist SR141716 and CB2 antagonist AM630 were used to determine receptor involvement.
What this study cannot tell us
The malonate model replicates some but not all features of human HD. The acute toxin-induced lesion differs from the progressive genetic neurodegeneration of actual HD. Doses and timing may not translate to human treatment. The combination of botanical extracts contains trace amounts of other cannabinoids that could contribute to effects.
How to read the evidence
Animal study with multiple outcome measures and receptor mechanism verification; preclinical evidence only.
When this study was published
Published in 2012. Clinical trials of cannabinoids in Huntington's disease have since been conducted with mixed results.
The bigger picture
This study added to the evidence supporting Sativex for Huntington's disease by demonstrating effectiveness in an inflammatory model, complementing previous data from oxidative stress models. The involvement of both receptor types highlights the broad-spectrum properties of combining THC and CBD.
Questions still open
- Would these neuroprotective effects translate to slowed disease progression in human HD patients? Is the combination of THC and CBD more effective than either alone? What is the optimal timing of treatment relative to disease onset?
Common questions
What is the connection between Sativex and Huntington's disease?
Why are both CB1 and CB2 receptors important?
Read the original research
Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington's disease: role of CB1 and CB2 receptors.
ACS chemical neuroscience, 3(5), 400-6
Citation
Valdeolivas, Sara; Satta, Valentina; Pertwee, Roger G; Fernández-Ruiz, Javier; Sagredo, Onintza. (2012). Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington's disease: role of CB1 and CB2 receptors.. ACS chemical neuroscience, 3(5), 400-6. https://doi.org/10.1021/cn200114w
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