Δ9‐Tetrahydrocannabinolic acid alleviates collagen‐induced arthritis: Role of PPARγ and CB1 receptors

Summary & key facts

Researchers tested Δ9-tetrahydrocannabinolic acid, the natural, non-psychoactive precursor of THC, to see how it affects inflammation in joints. They used lab cells from human joint tissue and a well-known mouse model of rheumatoid arthritis. Δ9-THCA-A changed how two cell systems work: it activated PPARγ (a protein that turns down inflammation) and it acted on the brain/body cannabinoid CB1 receptor in two ways — at the receptor's usual spot and at a different spot that boosts other signals. In the mice, giving Δ9-THCA-A reduced swelling, immune cell entry into the joint, thickening of the joint lining, and cartilage damage. The protective effects stopped when researchers blocked either CB1 or PPARγ, which means both pathways are likely needed. These results are promising for thinking about new treatments for long-term joint inflammation, but they come from cells and mice, not people, so more research is needed before this could become a human therapy.

Key facts:

• Δ9-THCA-A is the natural, acidic precursor of THC and does not cause the typical psychoactive effects linked to THC.
• In lab tests, Δ9-THCA-A activated PPARγ, a protein that can reduce inflammation, and it changed how the CB1 cannabinoid receptor works by binding at the receptor's normal spot and at a separate spot that boosts CB1 activity.
• Δ9-THCA-A appeared to reduce activity of the CB2 receptor below its normal level, a behavior called inverse agonism which can lower that receptor's baseline signals.
• In human joint cells and in mice with collagen-induced arthritis, Δ9-THCA-A reduced inflammatory cell entry into joints, stopped thickening of the joint lining, and lessened cartilage damage.
• The joint-protecting effects were blocked when researchers gave drugs that stop CB1 or block PPARγ, indicating both CB1 and PPARγ pathways are important for the effects seen.
• These findings come from cell experiments and a mouse disease model, so they suggest potential for treating chronic inflammatory joint disease but do not prove safety or effectiveness in people.

Abstract

Δ9 -THCA-A modulates CB1 receptors through the orthosteric and allosteric binding sites. In addition, Δ9 -THCA-A exerts anti-arthritis activity through CB1 receptors and PPARγ pathways, highlighting its potential for the treatment of chronic inflammatory diseases such as rheumatoid arthritis.

Topics

Cannabis and Cannabinoid Research Neuroscience and Neuropharmacology Research Peroxisome Proliferator-Activated Receptors

Categories

Health Sciences Medicine Pharmacology

Tags

Agonist Allosteric modulator Arthritis Biochemistry Biology Biotechnology Cannabinoid Cannabinoid receptor Cannabinoid receptor type 2 Chemistry Endocrinology In vivo Internal medicine Inverse agonist Medicine Pharmacology Receptor

Substances

Cannabis

Conditions & symptoms

Chronic Pain Chronic pain