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Analgesic Effect of the Synthetic Cannabinoid CT-3 on Chronic Neuropathic Pain
A Randomized Controlled Trial
Matthias Karst, MD, PhD;
Kahlid Salim, MS;
Sumner Burstein, PhD;
Ingomar Conrad, MD;
Ludwig Hoy, PhD;
Udo Schneider, MD, PhD
JAMA. 2003;290:1757-1762.
Context 1',1'Dimethylheptyl- 8-tetrahydrocannabinol-11-oic 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 period.
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 Test.
Conclusions In this preliminary study, CT-3 was effective in reducing chronic neuropathic pain compared with placebo. No major adverse effects were observed.
Author Affiliations: Department of Anesthesiology, Pain Clinic (Drs Karst and Conrad and Mr Salim), Department of Biometrics (Dr Hoy), and Department of Clinical Psychiatry and Psychotherapy (Dr Schneider), Hannover Medical School, Hannover, Germany; and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester (Dr Burstein).
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