acid (CT-3), a potent analog of THC-11-oic acid, produces marked antiallodynic
and analgesic effects in animals without evoking the typical effects described
in models of cannabinoids. Therefore, CT-3 may be an effective analgesic for
poorly controlled resistant neuropathic pain.
Objective To examine the analgesic efficacy and safety of CT-3 in chronic neuropathic
pain in humans.
Design and Setting Randomized, placebo-controlled, double-blind crossover trial conducted
in Germany from May-September 2002.
Participants Twenty-one patients (8 women and 13 men) aged 29 to 65 years (mean,
51 years) who had a clinical presentation and examination consistent with
chronic neuropathic pain (for at least 6 months) with hyperalgesia (n = 21)
and allodynia (n = 7).
Interventions Patients were randomized to two 7-day treatment orders in a crossover
design. Two daily doses of CT-3 (four 10-mg capsules per day) or identical
placebo capsules were given during the first 4 days and 8 capsules per day
were given in 2 daily doses in the following 3 days. After a washout and baseline
period of 1 week each, patients crossed over to the second 7-day treatment
Main Outcome Measures Visual analog scale (VAS) and verbal rating scale scores for pain; vital
sign, hematologic and blood chemistry, and electrocardiogram measurements;
scores on the Trail-Making Test and the Addiction Research Center Inventory–Marijuana
scale; and adverse effects.
Results The mean differences over time for the VAS values in the CT-3–placebo
sequence measured 3 hours after intake of study drug differed significantly
from those in the placebo–CT-3 sequence (mean [SD], −11.54 [14.16]
vs 9.86 [21.43]; P = .02). Eight hours after intake
of the drug, the pain scale differences between groups were less marked. No
dose response was observed. Adverse effects, mainly transient dry mouth and
tiredness, were reported significantly more often during CT-3 treatment (mean
[SD] difference, −0.67 [0.50] for CT-3–placebo sequence vs 0.10
[0.74] for placebo–CT-3 sequence; P = .02).
There were no significant differences with respect to vital signs, blood tests,
electrocardiogram, Trail-Making Test, and Addiction Research Center Inventory–Marijuana
scale. No carryover or period effects were observed except on the Trail-Making
Conclusions In this preliminary study, CT-3 was effective in reducing chronic neuropathic
pain compared with placebo. No major adverse effects were observed.