Two Years of Sativex Use for MS Pain Showed Sustained Relief With No Tolerance

In 28 MS patients who completed approximately two years of Sativex treatment, pain relief was maintained without dose increases, though 25% dropped out due to side effects.

Rog, David J et al.·Clinical therapeutics·2007·Moderate EvidenceLongitudinal Cohort
RTHC-00290Longitudinal CohortModerate Evidence2007RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Longitudinal Cohort
Evidence
Moderate Evidence
Sample
N=63

What This Study Found

This open-label extension followed 63 MS patients with central neuropathic pain for up to 917 days (over 2.5 years) of Sativex (THC/CBD mouth spray) treatment.

Of the 63 patients who entered the extension, 34 (54%) completed more than one year, and 28 (44%) completed the full follow-up. Among these 28 completers, mean pain scores decreased from 3.8 (end of the original trial for the treatment group) to 2.9 in the final week, suggesting continued improvement over time.

Critically, the mean number of sprays remained stable throughout, providing no evidence of tolerance. Intoxication ratings also remained stable, not increasing over time.

However, 92% of patients experienced at least one adverse event (dizziness 27%, nausea 18%, feeling intoxicated 11%), and 25% withdrew specifically due to adverse events. Two serious adverse events (cardiac) occurred in one patient but resolved after stopping treatment.

Key Numbers

63 patients entered extension. 28 (44%) completed full follow-up (mean 839 days). Mean pain score at completion: 2.9/10. 92% experienced adverse events. 25% withdrew due to adverse events. Dizziness (27%), nausea (18%), intoxication (11%). 2 serious cardiac events (1 patient, resolved).

How They Did This

Uncontrolled, open-label extension of a previous 5-week randomized trial. 63 MS patients with central neuropathic pain self-titrated Sativex dosing. Primary endpoint was adverse event monitoring. Pain scores, drug usage, and intoxication levels were tracked as secondary endpoints.

Why This Research Matters

One of the biggest concerns about long-term cannabinoid use is tolerance, where patients need escalating doses for the same effect. This study showed no tolerance over approximately two years, which was unusual and encouraging for the field.

The Bigger Picture

This was one of the longest published follow-ups of any cannabis-based medicine at the time. The absence of tolerance and the stable dosing pattern challenged assumptions about long-term cannabinoid use and supported the development of Sativex for chronic conditions.

What This Study Doesn't Tell Us

No placebo control in the extension phase, so sustained benefit could reflect placebo effects, natural disease changes, or selection bias (patients who benefited were more likely to continue). The 56% dropout rate means results represent only the most successful patients.

Questions This Raises

  • ?Would the patients who dropped out due to side effects have benefited if those side effects were managed?
  • ?Does the lack of tolerance extend beyond two years?

Trust & Context

Key Stat:
Pain relief maintained for ~2 years with no dose escalation (mean pain: 2.9/10)
Evidence Grade:
This is an uncontrolled, open-label extension study. While the long duration is valuable, the lack of placebo control and significant dropout limit the strength of the evidence.
Study Age:
Published in 2007. Longer-term follow-up data on Sativex has continued to accumulate, generally confirming the lack of tolerance finding.
Original Title:
Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.
Published In:
Clinical therapeutics, 29(9), 2068-79 (2007)
Database ID:
RTHC-00290

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-ControlFollows or compares groups over time
This study
Cross-Sectional / Observational
Case Report / Animal Study

Follows a group of people over time to track how outcomes develop.

What do these levels mean? →

Frequently Asked Questions

What does "no tolerance" mean?

Tolerance means needing more of a drug over time to get the same effect. In this study, patients used the same amount of Sativex spray over two years and continued getting the same pain relief, indicating their bodies did not become tolerant to the medication.

Why did so many patients drop out?

About 25% withdrew specifically due to side effects (dizziness, nausea, feeling intoxicated). This is an important consideration: while the drug worked well for those who tolerated it, a significant minority could not continue.

Read More on RethinkTHC

Cite This Study

RTHC-00290·https://rethinkthc.com/research/RTHC-00290

APA

Rog, David J; Nurmikko, Turo J; Young, Carolyn A. (2007). Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.. Clinical therapeutics, 29(9), 2068-79.

MLA

Rog, David J, et al. "Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.." Clinical therapeutics, 2007.

RethinkTHC

RethinkTHC Research Database. "Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuro..." RTHC-00290. Retrieved from https://rethinkthc.com/research/rog-2007-oromucosal-delta9tetrahydrocannabinolcannabidiol-for-neuropathic

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.