Jenny L Wiley1, Timothy W Lefever2, Julie A Marusich3, Rebecca M Craft4. 1. RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, United States. Electronic address: jwiley@rti.org. 2. RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, United States. Electronic address: tlefever@rti.org. 3. RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, United States. Electronic address: jmarusich@rti.org. 4. Department of Psychology, Washington State University, Pullman, WA 99164-4820, United States. Electronic address: craft@wsu.edu.
Abstract
BACKGROUND: Women report greater sensitivity to the subjective effects of Δ9-tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats. METHODS: A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure. RESULTS: Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes. CONCLUSIONS: This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC's effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology.
BACKGROUND:Women report greater sensitivity to the subjective effects of Δ9-tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats. METHODS: A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure. RESULTS: Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes. CONCLUSIONS: This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC's effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology.
Authors: Brian F Thomas; Timothy W Lefever; Ricardo A Cortes; Megan Grabenauer; Alexander L Kovach; Anderson O Cox; Purvi R Patel; Gerald T Pollard; Julie A Marusich; Richard C Kevin; Thomas F Gamage; Jenny L Wiley Journal: J Pharmacol Exp Ther Date: 2017-01-13 Impact factor: 4.030
Authors: Julie A Marusich; Timothy W Lefever; Kateland R Antonazzo; Rebecca M Craft; Jenny L Wiley Journal: Drug Alcohol Depend Date: 2014-02-12 Impact factor: 4.492
Authors: Jenny L Wiley; Reneé G Jefferson; Graeme Griffin; John Liddle; Shu Yu; John W Huffman; Billy R Martin Journal: Pharmacology Date: 2002-10 Impact factor: 2.547
Authors: Marisol S Castaneto; David A Gorelick; Nathalie A Desrosiers; Rebecca L Hartman; Sandrine Pirard; Marilyn A Huestis Journal: Drug Alcohol Depend Date: 2014-08-18 Impact factor: 4.492
Authors: Brian F Thomas; Timothy W Lefever; Ricardo A Cortes; Megan Grabenauer; Alexander L Kovach; Anderson O Cox; Purvi R Patel; Gerald T Pollard; Julie A Marusich; Richard C Kevin; Thomas F Gamage; Jenny L Wiley Journal: J Pharmacol Exp Ther Date: 2017-01-13 Impact factor: 4.030
Authors: Henry L Blanton; Robert C Barnes; Melissa C McHann; Joshua A Bilbrey; Jenny L Wilkerson; Josée Guindon Journal: Pharmacol Biochem Behav Date: 2021-01-12 Impact factor: 3.533
Authors: Christina M Ruiz; Alexa Torrens; Erik Castillo; Christina R Perrone; Jenny Cevallos; Victoria C Inshishian; Eden V Harder; Drew N Justeson; Marilyn A Huestis; Vivek Swarup; Daniele Piomelli; Stephen V Mahler Journal: Neuropsychopharmacology Date: 2020-09-14 Impact factor: 7.853
Authors: Jenny L Wiley; Daniel G Barrus; Charlotte E Farquhar; Timothy W Lefever; Thomas F Gamage Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2020-08-15 Impact factor: 5.067