Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial

JAMA. 2003 Oct 1;290(13):1757-62. doi: 10.1001/jama.290.13.1757.


Context: 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.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Non-Narcotic / therapeutic use*
  • Chronic Disease
  • Cross-Over Studies
  • Double-Blind Method
  • Dronabinol / analogs & derivatives*
  • Dronabinol / therapeutic use*
  • Female
  • Humans
  • Hyperalgesia / complications
  • Hyperalgesia / drug therapy
  • Male
  • Middle Aged
  • Pain / complications
  • Pain / drug therapy*
  • Pain Measurement


  • 1',1'-dimethylheptyl-delta(8)-tetrahydrocannabinol-11-oic acid
  • Analgesics, Non-Narcotic
  • Dronabinol