CT-3 reduzierte chronischen neuropathischen Schmerz signifikant gegenüber Placebo (VAS, p=0,02).
Zusammenfassung
n=21 Patienten mit chronisch-neuropathischem Schmerz (≥6 Monate); CT-3 (synthetisches Cannabinoid, 40–80 mg/d) vs. Placebo crossover. VAS-Differenz 3 h nach Einnahme: CT-3/Placebo-Sequenz −11,54 vs. +9,86 (p=0,02). Keine schwerwiegenden Nebenwirkungen; vorübergehende Mundtrockenheit und Müdigkeit häufiger unter CT-3 (p=0,02). Kein Dosis-Wirkungs-Effekt beobachtet.
P
PopulationErwachsene mit chronischem neuropathischen Schmerz (≥6 Monate), mit Hyperalgesie (n=21) und Allodynie (n=7), n=21, Alter 29–65 Jahre
I
InterventionSynthetisches Cannabinoid CT-3 (1',1'-Dimethylheptyl-Δ8-THC-11-Oic Acid), oral 40–80 mg/Tag in 2 Tagesdosen über 7 Tage
C
KontrolleIdentische Placebo-Kapseln
O
OutcomeSignifikante Schmerzreduktion (VAS) 3 Stunden nach Einnahme für CT-3 vs. Placebo (mittlere Differenz −11,54 vs. +9,86; p=0,02); 8 Stunden nach Einnahme weniger ausgeprägt
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Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
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Ungenauigkeit
Qualitätsprofil
Größe★★★★★
VerblindungDoppelblind
EffektstärkeKlarer Nutzen
Zitate / Jahr★★★★★
Autoren
Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U.
<h4>Context</h4>1',1'dimethylheptyl-Delta8-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.<h4>Objective</h4>To examine the analgesic efficacy and safety of CT-3 in chronic neuropathic pain in humans.<h4>Design and setting</h4>Randomized, placebo-controlled, double-blind crossover trial conducted in Germany from May-September 2002.<h4>Participants</h4>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).<h4>Interventions</h4>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.<h4>Interventions</h4>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-Cannabis scale; and adverse effects.<h4>Results</h4>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-Cannabis scale. No carryover or period effects were observed except on the Trail-Making Test.<h4>Conclusions</h4>In this preliminary study, CT-3 was effective in reducing chronic neuropathic pain compared with placebo. No major adverse effects were observed.