Sativex Was Safe and Effective for MS Spasticity Over Nearly a Year With No Tolerance Development | Research

The takeaway

In a long-term safety trial of 146 MS patients using Sativex for an average of 334 days, no tolerance developed, serious adverse events were rare, and spasticity benefits were maintained without dose escalation.

Read this if you are considering long-term Sativex use for MS spasticity and are concerned about safety.

No tolerance, no psychosis, no withdrawal symptoms over an average of 334 days

What the researchers found

One hundred forty-six MS patients entered an open-label follow-up of Sativex for spasticity. Mean treatment duration was 334 days, with an average of 7.3 sprays per day. Fifty-two patients (36%) withdrew in the first year, with 14% due to adverse events and 9% due to lack of efficacy.

Common treatment-related adverse events were dizziness (24.7%) and fatigue (12.3%), mostly mild to moderate. Serious adverse events occurred in only 5 patients (3.4%), with 2 psychiatric events in one patient. No psychoses, psychiatric trends, or withdrawal symptoms were observed upon abrupt cessation. Spasticity did not deteriorate over time, and patients reported continued benefit. No evidence of tolerance developing was found.

Why it matters

This study addresses three major concerns about long-term cannabinoid use: tolerance, psychosis risk, and dependence. All three were absent over nearly a year of treatment. For clinicians considering Sativex for their MS patients, these safety data are reassuring.

The numbers in context

146 patients entered. Mean exposure: 334 days. Mean dose: 7.3 sprays/day. 36% withdrew (14% AEs, 9% lack efficacy). Common AEs: dizziness 24.7%, fatigue 12.3%. Serious AEs: 3.4%. No psychosis, no tolerance, no withdrawal on cessation.

How the study worked

Open-label safety follow-up trial. 146 MS patients entering from a prior 6-week RCT. Self-titrated Sativex dosing. Primary outcome: safety and tolerability (AE incidence and severity). Secondary outcomes: tolerance development and dosing profile. NRS spasticity scale for efficacy.

What this study cannot tell us

Open-label design with no placebo comparison. Only patients who chose to continue from the parent trial were included, introducing selection bias. The 36% withdrawal rate means the long-term data represents completers only. Psychiatric events in one patient (2 events) may be underrepresented.

How to read the evidence

Open-label safety trial with adequate duration; moderate evidence for long-term safety and maintained efficacy.

When this study was published

Published in 2013. Sativex has accumulated additional long-term safety data since.

The bigger picture

This study provides the longest-duration safety data for Sativex at the time. The combination of maintained efficacy, no tolerance, no psychosis, and no dependence provides a comprehensive safety profile that supports the viability of long-term cannabinoid therapy for MS spasticity.

Questions still open

Would these safety findings hold over multiple years? What distinguishes the 64% who continued from the 36% who withdrew? Is the lack of tolerance specific to the Sativex formulation or common to all cannabinoid medicines?

Common questions

Is Sativex safe to use long-term?

In this trial averaging nearly a year of use, Sativex was generally well tolerated. Most side effects were mild (dizziness, fatigue). Serious adverse events were rare (3.4%). No cases of psychosis or addiction were observed, and there were no withdrawal symptoms when patients stopped. However, 36% withdrew in the first year, some due to side effects.

Will I need to keep increasing the dose?

No. This study found no evidence of tolerance developing. Patients maintained a stable average dose of 7.3 sprays per day throughout the study, and their spasticity did not worsen over time. This means the effectiveness was sustained without needing dose increases.

Read the original research

Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.

Journal of neurology, 260(1), 285-95

View on PubMed ↗Publisher’s paper ↗

Citation

Serpell, Michael G; Notcutt, William; Collin, Christine. (2013). Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.. Journal of neurology, 260(1), 285-95. https://doi.org/10.1007/s00415-012-6634-z