726 P. R o b s o n
tion of THC and CBD, or matched placebo at doses determined by titration against
symptomrelieforunwantedeffectswithintherange2.5–120mg/24h(1–48sprays).
Eligible patients had neurogenic symptoms which had responded poorly to stan-
dard treatments, and the majority had MS or SCI. Patients recorded symptom,
well-being and intoxication scores on a daily basis using visual analogue scales
(VAS), completed standard measures of disability, mood and cognition on regular
clinic visits, and recorded adverse events. Average dose following self-titration
in the active treatment groups was around 9 sprays/24 h. At the nursing assess-
ments, all three CBMEs significantly improved the subjective measure of spasticity
in comparison with placebo, and both THC CBME and THC: CBD CBME im-
proved muscle spasm. Patients’ daily diaries showed that THC CBME significantly
improved VAS scores of pain, muscle spasm and spasticity, THC: CBD CBME sig-
nificantly improved spasm and sleep, and CBD CBME significantly improved pain.
Four patients withdrew due to unwanted effects, and the percentage of patients
with at least one adverse event was considerably higher when THC was not accom-
panied by an equal proportion of CBD (55% vs 30%). The authors concluded that
CBME can improve neurogenic symptoms unresponsive to standard treatments,
and that unwanted effects were predictable and generally well tolerated.
An important trial funded by the UK Medical Research Council (“CAMS” study)
has explored the effects of synthetic THC (Marinol) and a cannabis extract (“Can-
nador”) given orally on spasticity and other symptoms related to multiple sclerosis
(Zajicek et al. 2003). This was a randomised, placebo-controlled trial involving 33
centres and 630 patients, and the primary outcome measure was change in overall
spasticity score as represented by the Ashworth scale.
The results of the study were mixed, and a large placebo effect was noted. There
was no change in Ashworth score following 15 weeks of treatment with either THC
or Cannador, but both active treatments demonstrated significant improvements
in subjective measures of spasticity, muscle spasms, pain and sleep, and also in an
objective measure of mobility. No effect was apparent on irritability, depression,
tiredness, tremor or loss of energy. The authors noted an unexpected reduction
in hospital admissions for relapse in the two active treatment groups. The known
interaction of cannabinoids with the immune system, and the fact that MS is still
regarded as an auto-immune condition led them to comment that this finding was
worthy of further investigation. Minor unwanted effects were frequently reported
in all three treatment groups, with a higher prevalence for the active treatments.
The small number of serious adverse events were evenly spread across the three
groups.
ThelimitationsoftheAshworthscaleinmeasuringsuchacomplexphenomenon
as spasticity is well known (Hinderer and Gupta 1996) and is acknowledged by
the authors. They also noted that the evidence in support of currently available
standard drug treatments for spasticity (and many other MS-related symptoms)
is weak. Although the study incorporated a titration phase, the fixed twice daily
dosing routine was not ideal in seeking to allow patients to optimise the balance
between positive and negative effects given the known variations in individual
response. An accompanying Lancet editorial (Metz and Page 2003) drew attention
to the high variability in degree of spasticity among the trial patients and com-