Nabiximols for multiple sclerosis
Fact-checked by What is nabiximols for MS?
Nabiximols is a cannabis-based oral spray that is approved in some countries for easing spasticity — involuntary muscle spasms and stiffness — in people with multiple sclerosis (MS). It has not been approved for use in the U.S., however.
The medication contains an equal mix of two of the main compounds found in the cannabis plant, delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Although its mechanism of action is not fully understood, nabiximols is thought to help balance out abnormal nerve signals that contribute to MS spasticity.
The therapy, marketed by CNX Therapeutics, is approved under the brand name Sativex in 29 countries, including Canada and most of Europe, where it is used as an add-on therapy to manage moderate or severe spasticity in MS patients who have failed to respond to other anti-spastic treatments.
In all countries where it was not already approved, including the U.S., nabiximols’ clinical development was discontinued in 2022 by the therapy’s previous developer, Jazz Pharmaceuticals.
Therapy Snapshot
| Treatment name: | Nabiximols |
| Administration: | Oral spray |
| Clinical testing: | Approved in some countries, but not in the U.S, where development was discontinued. |
How is nabiximols administered?
Nabiximols is available as a liquid solution designed to be sprayed into the mouth. Each spray delivers about 100 microliters of a solution containing 2.7 mg of THC and 2.5 mg of CBD.
In MS patients, nabiximols has been studied at doses of up to 48 sprays per day. However, its prescribing information in the U.K. recommends patients start with one spray per day, then gradually increase the number of daily sprays over the course of two weeks. This enables patients to find a dosage that offers symptom relief without unacceptable side effects.
The maximum number of sprays per day should not exceed 12, and there should be a gap of at least 15 minutes between each spray, according to the U.K. label.
For patients who don’t experience clinically significant easing of spasticity during the first month, the therapy is typically discontinued.
Nabiximols in clinical trials
Several clinical trials have evaluated nabiximols for treating MS spasticity. Results from early studies were mixed, which researchers attributed to the fact that a subset of patients does not respond to nabiximols at all.
Subsequent studies used an updated trial design to identify patients who could benefit from the therapy. This involved treating all participants with nabiximols for one month, then selecting only those with a substantial easing of spasticity (at least 20%) to continue into the randomized portion.
- A European Phase 3 trial (NCT00681538) enrolled 572 MS patients with moderate-to-severe spasticity that had not fully resolved with anti-spasticity medication. Nearly half responded to treatment in the first month and were randomly assigned to continue nabiximols or switch to a placebo for about three months. The results showed that patients who continued on nabiximols tended to experience a sustained reduction in spasticity scores, whereas spasticity tended to worsen in those who switched to a placebo, with the difference being statistically significant. Nabiximols was also associated with fewer daily muscle spasms and less difficulty sleeping due to spasticity relative to th eplacebo.
- A similarly designed Phase 2 study called SAVANT showed comparable benefits, with significantly more participants given nabiximols achieving a 30% or greater improvement in spasticity scores after three months compared to those on a placebo (77.4% vs. 32.1%). Nabiximols also reduced average spasticity and pain scores, as well as the severity of spasms and trouble sleeping, compared with placebo.
- Another Phase 3 trial, RELEASE MSS1 (NCT04657666), enrolled 68 MS patients with leg muscle spasticity. The results showed no significant reduction in leg spasticity in patients given nabiximols versus a placebo, prompting Jazz to discontinue further clinical development of the therapy.
RELEASE MSS1 was one of three trials intended to support a U.S. submission. But the other two trials also faced significant recruitment delays during the pandemic, and Jazz began prioritizing other treatment candidates, leading to program discontinuation. Ongoing trials of nabiximols were also terminated.
Nabiximols side effects
Side effects from nabiximols are most common when starting treatment, and tend to wear off after a few days. The most common side effects associated with the therapy include:
- dizziness
- fatigue
- drowsiness
Some of these side effects, such as dizziness or drowsiness, may make it unsafe to drive or operate heavy machinery.
Nabiximols is not recommended for people who are pregnant, children younger than 18 years old, or people with a history of psychotic problems.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
