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

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.

Serpell, Michael G et al.·Journal of neurology·2013·Moderate EvidenceObservational
RTHC-00733ObservationalModerate Evidence2013RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Observational
Evidence
Moderate Evidence
Sample
N=146

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
No tolerance, no psychosis, no withdrawal symptoms over an average of 334 days
Evidence Grade:
Open-label safety trial with adequate duration; moderate evidence for long-term safety and maintained efficacy.
Study Age:
Published in 2013. Sativex has accumulated additional long-term safety data since.
Original Title:
Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.
Published In:
Journal of neurology, 260(1), 285-95 (2013)
Database ID:
RTHC-00733

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

Watches what happens naturally without intervening.

What do these levels mean? →

Frequently Asked 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 More on RethinkTHC

Cite This Study

RTHC-00733·https://rethinkthc.com/research/RTHC-00733

APA

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

MLA

Serpell, Michael G, et al. "Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis.." Journal of neurology, 2013. https://doi.org/10.1007/s00415-012-6634-z

RethinkTHC

RethinkTHC Research Database. "Sativex long-term use: an open-label trial in patients with ..." RTHC-00733. Retrieved from https://rethinkthc.com/research/serpell-2013-sativex-longterm-use-an

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.