Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity

Summary & key facts

This study tested the acidic form of THC, called Δ9-THCA, which comes from raw Cannabis. In experiments on cells and in mice, Δ9-THCA turned on a protein called PPARγ that helps control inflammation and cell energy. Turning on that protein with Δ9-THCA increased mitochondrial markers in nerve cells, protected cells that carry a Huntington's disease mutation, and helped mice avoid brain damage and movement problems after a toxin. These results are early and come from lab and animal tests, so we do not know yet if the same effects would happen in people.

Key facts:

• Researchers compared six cannabis-related molecules and found the acidic versions, including Δ9-THCA, bind to and activate PPARγ more strongly than their heated, non-acid forms.
• PPARγ is a protein inside cells that helps control how cells use energy and how much inflammation they make; activating it is linked to protection in some brain disease models.
• In neuroblastoma cells, Δ9-THCA increased measures of mitochondrial content, which are signs of more energy-producing parts inside cells.
• Δ9-THCA reduced cell damage in two lab models of Huntington's disease: cells that naturally carry a mutant huntingtin protein and cells forced to make a toxic huntingtin fragment.
• In mice given a chemical that causes brain damage similar to Huntington's disease, treatment with Δ9-THCA improved movement problems and prevented loss of neurons in a key brain area called the striatum.
• Δ9-THCA also lowered signs of brain inflammation in those mice, including less activation of microglia and astrocytes and lower levels of inflammatory markers.
• The protective effects seen in mice depended on PPARγ, which suggests Δ9-THCA works through that protein rather than by producing a psychoactive high.
• All tests were done in cells and in mice. The study did not test Δ9-THCA in people, so we do not know if it is safe or effective for patients yet.

Abstract

Δ9 -THCA shows potent neuroprotective activity, which is worth considering for the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases.

Topics

Cannabis and Cannabinoid Research Lipid metabolism and biosynthesis Peroxisome Proliferator-Activated Receptors

Categories

Health Sciences Medicine Pharmacology

Tags

Biochemistry Biology Cannabinoid Chemistry Gene Huntingtin Mutant Neuroprotection Pharmacology Receptor

Substances

Cannabis