What Was Known About Cannabis for MS Spasticity and Pain in 2002 | Research

The takeaway

A review found growing evidence from 8 clinical trials and animal models that cannabinoids reduced spasticity, pain, tremor, and bladder problems in multiple sclerosis, with effects mediated by both CB1 and CB2 receptors.

Read this if you have MS and want to understand the scientific basis for cannabinoid treatments.

8 MS trials showed relief from spasticity, pain, tremor, and nocturia

What the researchers found

Clinical evidence from 8 trials in MS patients and 1 in spinal cord injury showed that cannabis, THC, and nabilone produced objective or subjective relief from spasticity, pain, tremor, and nocturia. Animal models using mice with chronic relapsing experimental allergic encephalomyelitis (CREAE) strongly supported cannabinoid receptor involvement in these effects.

Endocannabinoid concentrations were elevated in the brains and spinal cords of mice with spasticity, suggesting the body's own cannabinoid system was responding to the disease. Spasticity could be reduced by inhibiting endocannabinoid breakdown, pointing toward a therapeutic strategy that would enhance the body's natural response rather than introducing external cannabinoids.

Why it matters

This review was published at a critical moment when large-scale clinical trials of cannabinoids for MS were being planned. The convergence of patient reports, small clinical trials, and robust preclinical evidence helped justify the investment in larger trials that would ultimately lead to the approval of Sativex.

The numbers in context

Eight clinical trials in MS and 1 in spinal cord injury were reviewed. Both CB1 and CB2 receptors were implicated in the therapeutic effects.

How the study worked

This was a narrative review synthesizing clinical trial data from 9 trials, questionnaire-based anecdotal evidence, and preclinical research using CREAE mouse models of MS. It evaluated both the clinical evidence and the biological mechanisms underlying cannabinoid effects on MS symptoms.

What this study cannot tell us

The clinical trials reviewed were small, and the review acknowledged that more conclusive evidence was needed. Animal models of MS do not perfectly replicate human disease. The review did not systematically assess the quality of the included trials.

How to read the evidence

This is a narrative review synthesizing clinical and preclinical evidence, providing moderate-level evidence through convergent findings.

When this study was published

Published in 2002, before the large CAMS trial and the approval of Sativex for MS spasticity.

The bigger picture

The research directions outlined here were largely vindicated. Sativex (THC:CBD) was approved for MS spasticity in multiple countries. The discovery that endocannabinoid levels were elevated in spastic conditions opened research into drugs that enhance endocannabinoid signaling, an approach that continues to be explored.

Questions still open

Does increased endocannabinoid production occur in human MS as it does in the mouse model? Would drugs that inhibit endocannabinoid breakdown be more effective or better tolerated than direct cannabinoid receptor agonists?

Common questions

Is cannabis approved for MS symptoms?

Sativex (nabiximols), a cannabis-based mouth spray containing THC and CBD, was subsequently approved in multiple countries for MS spasticity. This review documented the evidence base that contributed to that approval.

What are endocannabinoids and why were they elevated in MS?

Endocannabinoids are the body's own cannabis-like compounds. Their elevation in spastic conditions suggested the body was attempting to use its own cannabinoid system to fight spasticity, supporting the rationale for cannabinoid treatment.

Read the original research

Cannabinoids and multiple sclerosis.

Pharmacology & therapeutics, 95(2), 165-74

View on PubMed ↗

Citation

Pertwee, Roger G. (2002). Cannabinoids and multiple sclerosis.. Pharmacology & therapeutics, 95(2), 165-74.