Lauren C Smith1,2, Lani Tieu2, Raymond T Suhandynata3, Brent Boomhower2, Melissa Hoffman3, Yadira Sepulveda4, Lieselot L G Carrette2, Jeremiah D Momper4, Robert L Fitzgerald3, Kate Hanham5, Joseph Dowling5, Marsida Kallupi6,7, Olivier George8,9. 1. Department of Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037, USA. 2. Department of Psychiatry, University of California, San Diego School of Medicine, San Diego, CA,, 92093, USA. 3. Department of Pathology, University of California, San Diego School of Medicine, San Diego, CA, 92093, USA. 4. Division of Pharmaceutical Sciences, University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, 92093, USA. 5. CV Sciences, Inc., 10070 Barnes Canyon Road, San Diego, CA, 92121, USA. 6. Department of Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037, USA. mkallupi@health.ucsd.edu. 7. Department of Psychiatry, University of California, San Diego School of Medicine, San Diego, CA,, 92093, USA. mkallupi@health.ucsd.edu. 8. Department of Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA, 92037, USA. olgeorge@health.ucsd.edu. 9. Department of Psychiatry, University of California, San Diego School of Medicine, San Diego, CA,, 92093, USA. olgeorge@health.ucsd.edu.
Abstract
RATIONALE: Cannabidiol (CBD) reduces craving in animal models of alcohol and cocaine use and is known to modulate nicotinic receptor function, suggesting that it may alleviate symptoms of nicotine withdrawal. However, preclinical evaluation of its efficacy is still lacking. OBJECTIVES: The goal of this study was to test the preclinical efficacy of a chronic CBD treatment in reducing nicotine dependence using measures of withdrawal symptoms including somatic signs, hyperalgesia, and weight gain during acute and protracted abstinence. METHODS: Male and female Wistar rats were made dependent on nicotine using osmotic minipumps (3.15 mg/kg/day) for 2 weeks, after which minipumps were removed to induce spontaneous withdrawal. Three groups received CBD injections at doses of 7.5, 15, and 30 mg/kg/day for 2 weeks, starting 1 week into chronic nicotine infusion. The control groups included rats with nicotine minipumps that received vehicle injections of sesame oil instead of CBD; rats implanted with saline minipumps received sesame oil injections (double vehicle) or the highest dose of CBD 30 mg/kg/day. Throughout the experiment, serum was collected for determination of CBD and nicotine concentrations, mechanical sensitivity threshold and withdrawal scores were measured, and body weight was recorded. RESULTS: CBD prevented rats from exhibiting somatic signs of withdrawal and hyperalgesia during acute and protracted abstinence. There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD. The saline minipump group did not show either somatic signs of withdrawal or hyperalgesia during acute and protracted abstinence, and the highest dose of CBD used (30 mg/kg/day) did not alter these results. CONCLUSIONS: This preclinical study suggests that using CBD as a strategy to alleviate the withdrawal symptoms upon nicotine cessation may be beneficial.
RATIONALE: Cannabidiol (CBD) reduces craving in animal models of alcohol and cocaine use and is known to modulate nicotinic receptor function, suggesting that it may alleviate symptoms of nicotine withdrawal. However, preclinical evaluation of its efficacy is still lacking. OBJECTIVES: The goal of this study was to test the preclinical efficacy of a chronic CBD treatment in reducing nicotine dependence using measures of withdrawal symptoms including somatic signs, hyperalgesia, and weight gain during acute and protracted abstinence. METHODS: Male and female Wistar rats were made dependent on nicotine using osmotic minipumps (3.15 mg/kg/day) for 2 weeks, after which minipumps were removed to induce spontaneous withdrawal. Three groups received CBD injections at doses of 7.5, 15, and 30 mg/kg/day for 2 weeks, starting 1 week into chronic nicotine infusion. The control groups included rats with nicotine minipumps that received vehicle injections of sesame oil instead of CBD; rats implanted with saline minipumps received sesame oil injections (double vehicle) or the highest dose of CBD 30 mg/kg/day. Throughout the experiment, serum was collected for determination of CBD and nicotine concentrations, mechanical sensitivity threshold and withdrawal scores were measured, and body weight was recorded. RESULTS: CBD prevented rats from exhibiting somatic signs of withdrawal and hyperalgesia during acute and protracted abstinence. There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD. The saline minipump group did not show either somatic signs of withdrawal or hyperalgesia during acute and protracted abstinence, and the highest dose of CBD used (30 mg/kg/day) did not alter these results. CONCLUSIONS: This preclinical study suggests that using CBD as a strategy to alleviate the withdrawal symptoms upon nicotine cessation may be beneficial.
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