How the Endocannabinoid System Could Both Treat MS Symptoms and Slow Disease Progression | Research

The takeaway

Beyond symptom relief, the endocannabinoid system appears to regulate neuroinflammation and neurodegeneration in MS, suggesting cannabinoids might slow disease progression in addition to easing spasticity and pain.

Read this if you have MS and want to understand the scientific rationale for cannabinoid-based treatments beyond symptom relief.

Endocannabinoid system changes found at MS lesion sites in both animal and human tissue

What the researchers found

This review examined the dual potential of the endocannabinoid system in MS: symptom management and disease modification.

For symptom relief, the evidence showed that spasticity is tonically (continuously) regulated by the endocannabinoid system, and clinical trials suggested cannabis can relieve pain, spasms, and spasticity. However, since CB1 receptors mediate both therapeutic and psychoactive effects, some unwanted effects are unavoidable.

More intriguingly, the review presented evidence that the endocannabinoid system is altered at MS lesion sites, with local perturbations in both animal models and human MS tissue. Boosting endocannabinoid activity locally at lesion sites, through increased synthesis or decreased degradation, could provide therapeutic effects while minimizing psychoactive side effects by targeting the damage site rather than the whole brain.

Additionally, CB1 and CB2 receptor stimulation showed anti-inflammatory and neuroprotective effects, suggesting cannabinoids might reduce the neurodegeneration that causes progressive disability in MS.

Why it matters

Most MS medications either treat symptoms or modify the disease course, but rarely both. This review articulated how the endocannabinoid system could potentially do both, and proposed a strategy (local endocannabinoid enhancement) to achieve therapeutic effects while minimizing psychoactive side effects.

The numbers in context

The review covered evidence from EAE models, human MS tissue, and multiple clinical trials. Local endocannabinoid system changes documented at MS lesion sites in both animal models and human tissue.

How the study worked

Narrative review of preclinical and clinical evidence on the endocannabinoid system in MS, covering experimental autoimmune encephalomyelitis models, human MS tissue studies, and clinical trials.

What this study cannot tell us

Much of the disease-modification evidence was preclinical. Clinical trials had focused on symptom relief rather than disease progression. The proposed local targeting strategy was theoretical and had not been tested in humans.

How to read the evidence

This review synthesizes preclinical and clinical evidence, providing a strong theoretical framework but acknowledging that the disease-modification hypothesis remained largely unproven in humans.

When this study was published

Published in 2008. Research into FAAH and MAGL inhibitors for neurological conditions has continued, though none have yet been approved for MS.

The bigger picture

The concept of boosting endocannabinoids locally at disease sites rather than administering cannabinoids systemically has become an important research direction, not just for MS but for other neurological conditions. This approach could theoretically provide benefits while avoiding the psychoactive effects that limit current cannabinoid medicines.

Questions still open

Can FAAH or MAGL inhibitors effectively enhance endocannabinoid levels at MS lesions without significant systemic effects? Do cannabinoids actually slow MS disability progression in humans?

Common questions

Could cannabis slow down MS?

This review presented evidence suggesting cannabinoids might have neuroprotective and anti-inflammatory effects that could slow MS progression. However, this was based largely on preclinical data. Clinical trials have focused on symptom relief, and the disease-modification question remains open.

What does "local endocannabinoid enhancement" mean?

Instead of taking cannabinoids (which affect the whole brain), this approach would use drugs that block the enzymes breaking down endocannabinoids at MS lesion sites. This could boost cannabinoid signaling where it's needed most while limiting effects elsewhere.

Read the original research

The endocannabinoid system and multiple sclerosis.

Current pharmaceutical design, 14(23), 2326-36

View on PubMed ↗

Citation

Baker, David; Pryce, Gareth. (2008). The endocannabinoid system and multiple sclerosis.. Current pharmaceutical design, 14(23), 2326-36.