Analgesic Effect of the Synthetic Cannabinoid CT-3 on Chronic Neuropathic Pain

Karst, Matthias; Salim, Kahlid; Burstein, Sumner; Conrad, I.; Hoy, Ludwig; Schneider, Udo

doi:10.1001/jama.290.13.1757

Cited by 304 publications

(206 citation statements)

References 20 publications

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“…[25,26,33] Cannabinoids are analgesic in patients with neuropathic pain [12,13,20,24,34] and show promise in cancer pain. [32] Cannabinoids activate two receptors types: cannabinoid receptor 1 and 2 (CBr1 and CBr2, respectively).…”

Section: Introductionmentioning

confidence: 99%

“…CBr1s are localized in the spinal dorsal horn, periaqueductal grey [9,11] and dorsal root ganglion (DRG). [24,40] In neuropathic pain, cannabinoids act at central and peripheral nerve CBr1s [20,34], and at CBr2s on keratinocytes. [18,20] Cannabinoid's analgesic action in cancer pain is less clear.…”

Section: Introductionmentioning

confidence: 99%

“…[24,40] In neuropathic pain, cannabinoids act at central and peripheral nerve CBr1s [20,34], and at CBr2s on keratinocytes. [18,20] Cannabinoid's analgesic action in cancer pain is less clear. [2,10,19] In a murine bone sarcoma pain model, systemic cannabinoids act through CBr1.…”

Section: Introductionmentioning

confidence: 99%

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Peripheral cannabinoids attenuate carcinoma-induced nociception in mice

Guerrero

Quang

Dekker³

et al. 2008

Neuroscience Letters

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We investigated the cannabinoid receptor (CBr) agonists Win55,212-2 (non-selective) and AM1241 (CBr2 selective) and the peripheral receptor (CBr1) in carcinoma-induced pain using a mouse model. Tumors were induced in the hind paw of female mice by local injection of a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 18 days. Local administration of Win55,212-2 (10 mg/kg) and AM1241 (10 mg/kg) significantly elevated withdrawal thresholds, indicating an antinociceptive effect. Ipsilateral expression of CBr1 protein in L5 DRG was significantly upregulated compared to ipsilateral L4 DRG and in normal tissue. These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Peripheral cannabinoids attenuate carcinoma-induced nociception in mice

Guerrero

Quang

Dekker³

et al. 2008

Neuroscience Letters

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“…14 Other drugs reported to manage DPNP are "anticonvulsants," 15,16 selective serotonin reuptake inhibitors, 17 controlled-release oxycodone, 18,19 and the synthetic cannabinoid CT-3. 20 Duloxetine hydrochloride (Cymbalta ® , Eli Lilly and Company, Indianapolis, IN) is a selective 5-HT and NE reuptake inhibitor that is relatively balanced in its affinity for both 5-HT and NE reuptake inhibition. 21 Because central sensitization is believed to be involved in the development and maintenance of chronic neuropathic pain, including DPNP, patients with DPNP may benefit from duloxetine therapy.…”

Section: Introduction Dmentioning

confidence: 99%

Duloxetine versus Routine Care in the Long-Term Management of Diabetic Peripheral Neuropathic Pain

Raskin

Smith

Wong³

et al. 2006

Journal of Palliative Medicine

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Introduction: Duloxetine hydrochloride is a dual reuptake inhibitor of both serotonin and norepinephrine. In the present open-label study, the safety of duloxetine at a fixed-dose of 60 mg twice daily (BID) for up to 52 weeks was evaluated and compared to routine care in the therapy of patients diagnosed with diabetic peripheral neuropathic pain (DPNP).Methods: Patients who completed a 13-week, double-blind, duloxetine and placebo acute therapy period were rerandomly assigned in a 2:1 ratio to therapy with duloxetine 60 mg BID (N ‫؍‬ 161) or routine care (N ‫؍‬ 76) for an additional 52 weeks. Routine care consisted primarily of gabapentin, amitriptyline, and venlafaxine. The study included male or female outpatients 18 years of age or older with a diagnosis of DPNP caused by type 1 or type 2 diabetes.Results: A higher percentage of routine care-treated patients experienced 1 or more serious adverse events. No statistically significant therapy-group difference was observed in the overall incidence of treatment-emergent adverse events (TEAEs). The TEAEs reported by 10% or more of duloxetine 60 mg BID-treated patients were nausea, and by the routine care-treated patients were peripheral edema, pain in the extremity, somnolence, and dizziness. Duloxetine did not appear to adversely affect glycemic control, lipid profiles, nerve function, or the course of DPNP. There were no statistically significant therapy-group differences observed in the 36-item Short-Form Health Survey subscales or in the EuroQol 5-Dimension Questionnaire.Conclusions: In this study, duloxetine was safe and well tolerated compared to routine care in the long-term management of patients with DPNP.

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“…In fact, AjA suppresses THC-induced catalepsy in mice [Burstein, 1999]. Moreover, administration of 80 mg/day AjA for 1 week to patients with neuropathic pain relieved symptoms and did not induce behavioral changes [Karst et al, 2003].…”

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confidence: 99%

Suppression of fibroblast metalloproteinases by ajulemic acid, a nonpsychoactive cannabinoid acid

Johnson

Stebulis

Rossetti

et al. 2006

J of Cellular Biochemistry

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Production of matrix metalloproteinases (MMP) in joint tissue of patients with inflammatory arthritis facilitates cartilage degradation and bone erosion, and leads to joint deformities and crippling. Thus, MMPs are important targets for agents designed to treat inflammatory arthritis. Oral administration of ajulemic acid (AjA), a synthetic, nonpsychoactive cannabinoid acid, prevents joint tissue injury in rats with adjuvant arthritis. AjA binds to and activates PPARg directly. Therefore, we investigated the influence of AjA on MMP production in human fibroblast-like synovial cells (FLS), and examined the role of PPARg in the mechanism of action of AjA. FLS, treated or not with a PPARg antagonist, were treated with AjA then stimulated with TNFa or IL-1a. Release of MMPs-1, 3, and 9 was measured by ELISA. The influence of AjA on MMP-3 release from stimulated PPARg positive (PPAR þ/À ) and PPARg null (PPAR À/À ) mouse embryonic fibroblasts (MEF) was also examined. Addition of AjA to FLS suppressed production of MMPs whether or not PPARg activation was blocked. Secretion of MMP-3 was also suppressed by AjA in both TNFa-and IL-1a-stimulated PPARg þ/À and PPARg À/À MEF. Suppression of MMP secretion from FLS by AjA appears to be PPARg independent. Prevention by AjA of joint tissue injury and crippling in the rat adjuvant arthritis model may be explained in large part by inhibition of MMPs. These results suggest that AjA may be useful for treatment of patients with rheumatoid arthritis and osteoarthritis.

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Analgesic Effect of the Synthetic Cannabinoid CT-3 on Chronic Neuropathic Pain

Cited by 304 publications

References 20 publications

Peripheral cannabinoids attenuate carcinoma-induced nociception in mice

Peripheral cannabinoids attenuate carcinoma-induced nociception in mice

Duloxetine versus Routine Care in the Long-Term Management of Diabetic Peripheral Neuropathic Pain

Suppression of fibroblast metalloproteinases by ajulemic acid, a nonpsychoactive cannabinoid acid

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