Sativex is an endocannabinoid system modulator
principally containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD).
During a 6-week randomised controlled trial, Sativex had a clinically relevant
effect on spasticity associated with multiple
sclerosis (MS).
Patients self-titrated oromucosal Sativex to symptom relief or maximum
tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to
evaluate the safety and
tolerability of long-term treatment by
recording the incidence and severity of adverse events (AEs). Secondary
outcomes were to determine evidence of developing tolerance and to assess the
long-term dosing profile of Sativex. A validated 11-point Numerical Rating
Scale of spasticity severity was used to assess efficacy. A total of 146
patients elected to enter this open-label follow-up safety trial. Mean
treatment exposure was 334 days (standard deviation,
SD = 209 days), and patients administered on average 7.3
(SD = 4.42) actuations per day. Fifty-two (36 %)
patients withdrew from the study in the first year, 14 % due to AEs
and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity.
Common (>10 %) treatment-related AEs were dizziness (24.7 %) and
fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with
two psychiatric events reported by one patient. No psychoses, psychiatric AE
trends, or withdrawal symptoms occurred following abrupt cessation of treatment.
Baseline symptoms including spasticity did not deteriorate but were maintained
to study completion in those patients who did not withdraw. No new safety
concerns were identified with chronic Sativex treatment, and serious AEs were
uncommon. There was no evidence of tolerance developing, and patients who
remained in the study reported continued benefit.
This study showed
that a large number (36%) of people who were committed to take Sativex for
spasticity stopped because of side-effects. As the side-effects reported were
only serious in five people, we conclude that the benefits the other 31 people
perceived were not sufficient to be persistent in regular treatment. This
is disappointing, but it is not news for us. Maybe Mouse Doctor will let you
know again about the projects under way to make cannabinoids have better
efficacy and less side-effects: molecules that do not cross the blood-brain
barrier and "other tricks".