Comprehensive Review of Sativex for MS Spasticity: How It Works and What the Trials Show | Research

The takeaway

A detailed drug review found Sativex significantly reduced MS spasticity in patients who responded to an initial trial period, with dizziness and fatigue as the most common early side effects.

Read this if you have MS spasticity and want a detailed overview of how Sativex works.

Significantly more Sativex patients achieved 30% spasticity reduction vs. placebo

What the researchers found

In the largest multinational clinical trial using the approved treatment protocol, Sativex significantly reduced spasticity severity compared to placebo after 12 weeks in patients who had demonstrated initial response during a 4-week trial period. A significantly greater proportion of Sativex-treated patients achieved a 30% or greater reduction in spasticity (considered clinically relevant).

The approved protocol includes an important initial trial of therapy: only patients who demonstrate clinically significant improvement during the first 4 weeks continue treatment. This enrichment design ensures the drug is used in patients most likely to benefit.

Real-world effectiveness data from the MOVE 2 study confirmed clinical trial findings. Side effects (primarily dizziness and fatigue) were most common in the first 4 weeks and typically resolved even with continued treatment.

Why it matters

This review provides the most complete picture available of Sativex as a treatment for MS spasticity, covering everything from its mechanism of action to its real-world effectiveness. The enrichment design (initial trial period) is a model for how cannabinoid medicines can be used to identify and treat responsive patients.

The numbers in context

THC:CBD ratio approximately 1:1. Approved as add-on therapy for moderate to severe MS spasticity. Initial trial period: 4 weeks. Pivotal trial: 12 weeks double-blind. Significant 30% responder rate. Most common side effects: dizziness, fatigue (resolving within days).

How the study worked

This is a comprehensive drug review covering the pharmacology, clinical efficacy, and tolerability of Sativex (THC/CBD oromucosal spray). It synthesizes data from Phase III clinical trials, the MOVE 2 real-world study, and pharmacological characterization.

What this study cannot tell us

The enrichment design (4-week trial period) means efficacy data applies only to responders, not all MS spasticity patients. Long-term efficacy and safety data beyond clinical trial durations were limited. The review was published in a pharmaceutical journal and follows a standard drug review format that may not critically evaluate all limitations.

How to read the evidence

This review covers Phase III trial data and real-world effectiveness studies, representing strong evidence for the approved indication.

When this study was published

Published in 2014. Sativex has since been approved in additional countries and accumulated more long-term safety data.

The bigger picture

Sativex represents the most extensively studied cannabinoid medicine for a specific indication. Its approval pathway, including the initial trial period, has influenced how other cannabinoid medicines are developed and prescribed. It demonstrates that cannabis-derived medicines can meet pharmaceutical regulatory standards.

Questions still open

What proportion of MS spasticity patients respond during the initial trial period? Does long-term tolerance develop? Would Sativex be effective for spasticity from causes other than MS?

Common questions

What is the initial trial period?

Sativex is approved with a requirement for a 4-week initial trial. Only patients who show meaningful improvement during this period should continue treatment. This ensures the drug is used in patients who actually respond to it, improving overall treatment outcomes.

How does Sativex work?

THC in Sativex acts as a partial agonist at cannabinoid CB1 and CB2 receptors, modulating excitatory (glutamate) and inhibitory (GABA) neurotransmitters. CBD may contribute additional effects. Together, they reduce the excessive muscle tone that causes spasticity in MS.

Read the original research

Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis.

Drugs, 74(5), 563-78

View on PubMed ↗Publisher’s paper ↗

Citation

Syed, Yahiya Y; McKeage, Kate; Scott, Lesley J. (2014). Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis.. Drugs, 74(5), 563-78. https://doi.org/10.1007/s40265-014-0197-5