Long-Term Sativex Study: Benefits Maintained Over 434 Days With No Consistent Withdrawal Syndrome | Research

The takeaway

An open-label study of 137 MS patients using Sativex for an average of 434 days found sustained benefits without tolerance, and planned 2-week interruption in 25 patients produced no consistent withdrawal syndrome, though 42% eventually withdrew from the study.

Read this if you are considering long-term use of a cannabis-based medicine and want to know about sustained effects, tolerance, and withdrawal.

Benefits maintained over 434 days without dose escalation; no consistent withdrawal syndrome

What the researchers found

Following a 10-week placebo-controlled study, 137 MS patients entered this open-label trial and used Sativex for an average of 434 days (range 21-814 days). The improvements and dosage established during the initial study remained stable throughout long-term use, suggesting no development of tolerance.

Fifty-eight patients (42.3%) withdrew over the study period: 24 for lack of efficacy, 17 for adverse events, and the rest for other reasons. Of 292 reported unwanted effects, 86% were mild to moderate, most commonly oral pain, dizziness, diarrhea, and nausea. Four patients experienced first-ever seizures.

A planned sudden 2-week interruption of Sativex in 25 patients (of 62 approached) did not produce a consistent withdrawal syndrome, although 46% reported at least one symptom (tiredness, sleep interruption, mood changes, reduced appetite). Twenty-two of 25 (88%) restarted Sativex after the interruption.

Why it matters

Long-term cannabis-based medicine use data is critical for clinical decision-making. The finding that benefits were maintained without dose escalation (no tolerance) and that stopping produced only mild, inconsistent symptoms (no major withdrawal) addresses two key concerns about long-term cannabinoid therapy.

The numbers in context

137 patients. Average follow-up: 434 days (range 21-814). 42.3% withdrew (24 lack of efficacy, 17 adverse events). 292 unwanted effects, 86% mild-moderate. 4 first-ever seizures. Withdrawal test: 25 patients, no consistent syndrome, 46% had at least one symptom, 88% restarted.

How the study worked

Open-label extension study following a 10-week placebo-controlled trial. 137 MS patients. Average follow-up 434 days. Assessments every 8 weeks using VAS and diary scores. Planned 2-week treatment interruption in a subset of patients to assess withdrawal.

What this study cannot tell us

Open-label design (no placebo comparison for long-term efficacy). The 42% dropout rate limits conclusions about long-term tolerability for the full population. Only 25 of 62 approached patients agreed to the withdrawal test, introducing selection bias. The seizure finding needs further investigation.

How to read the evidence

Open-label extension study providing valuable long-term data but without placebo comparison. Dropout rate of 42% limits conclusions.

When this study was published

Published in 2006. Longer-term post-marketing data from Sativex use across 25+ countries has since become available.

The bigger picture

This was one of the longest follow-up studies of a cannabis-based medicine at the time. The new-onset seizures (4 patients) raised a safety signal that the authors noted required further investigation in larger studies, as seizure is a potential concern in MS patients.

Questions still open

Are the first-ever seizures related to Sativex or to MS progression? Would a longer withdrawal period reveal more consistent withdrawal symptoms? Why did 37 of 62 patients decline the withdrawal test?

Common questions

Does Sativex stop working over time?

In this study, the improvements and dosage established during the initial trial remained stable over an average of 434 days of continued use, suggesting tolerance did not develop. However, 24 patients (17.5%) eventually withdrew for lack of efficacy.

Is Sativex addictive?

A planned 2-week interruption in 25 patients did not produce a consistent withdrawal syndrome, though some patients reported mild symptoms like tiredness and sleep changes. Twenty-two of 25 patients chose to restart, but this may reflect ongoing symptom management needs rather than dependence.

Read the original research

Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis.

Multiple sclerosis (Houndmills, Basingstoke, England), 12(5), 639-45

View on PubMed ↗

Citation

Wade, D T; Makela, P M; House, H; Bateman, C; Robson, P. (2006). Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis.. Multiple sclerosis (Houndmills, Basingstoke, England), 12(5), 639-45.