Prosocial Effects of Nonpsychotropic Cannabis sativa in Mice

Abstract

Introduction:Cannabis sativa L. (C. sativa) is used since ancient times to produce fabrics, baskets, and cords. Later, different ethnic groups used to burn the leaves and flowers of psychotropic cultivars with high Δ9-tetrahydrocannabinol (D9-THC) levels, during the religious or propitiatory rites to alter the state of consciousness. To date, it is not known whether also nonpsychotropic cultivars of C. sativa were used during these rites, and whether these varieties could have an effect on human behavior. This study aimed to evaluate the behavioral effects of an extract of nonpsychotropic C. sativa (NP-CS) in mice. Materials and Methods: An extract of a nonpsychotropic cultivar of C. sativa dissolved in medium-chain triglyceride oil was used and the different phytochemical components were evaluated. The relative composition in terms of phytocannabinoid content was assessed by reverse phase high-performance liquid chromatography coupled to UV detection (RP-HPLC-UV), and the volatile components were analyzed by gas chromatography-mass spectrometry (GC-MS). In addition, the behavioral effect of NP-CS was assessed on a wild-type mouse model. The animals were treated for 14 days (oral gavage) and motility, anxiety, and social effects were assessed. Results: RP-HPLC-UV analysis demonstrated that D9-THC was present in lower concentration with respect to other cannabinoids, like cannabidiol. Furthermore, the GC-MS analysis revealed the presence of several terpenoids. Concerning in vivo studies, chronic treatment with NP-CS did not alter body weight, motility, and anxiety and increased social interaction. Conclusions: This study highlighted the prosocial effects of NP-CS.

Keywords: Cannabis sativa; behavior; cannabidiol; sociability; Δ9-tetrahydrocannabinol.

FIG. 1.

RP-HPLC-UV analysis showing the relative abundance of phytocannabinoids in NP-CS oil. NP-CS, nonpsychotropic C. sativa; RP-HPLC-UV, reverse phase high-performance liquid chromatography coupled to UV detection.

FIG. 2.

Behavioral effects of NP-CS oil in mice. (A) Daily body weight and food intake (B) variation of mice subjected to treatment with NP-CS oil or MCT oil (VH). Body weight and food intake data are expressed as mean±SEM and were analyzed by two-way repeated measures ANOVA, followed by Holm-Sidak's multiple test for the comparison of individual means. No weight changes and food intake were observed between the two experimental groups. (C) Data collected in the open field test by automatically measuring the total distance travelled. NP-CS oil does not induce significant changes in exploratory behavior and locomotor activity compared to VH. (D) EPM test performance. Mice treated with NP-CS oil showed the same time (%) in the open arm compared to VH. (E, F) Effect of NP-CS oil treatment on social behavior in mice by the male-male reciprocal social interaction test. The experimental mice were individually housed during the 5 days preceding the behavioral test. Both mice in the pair were treated either with the same drug or with vehicle and used for a 10-min social test. (E) Social investigation includes first contact latency, nose-nose sniffing, anogenital sniffing, body sniffing, and following. (F) The following nonsocial activities were evaluated: exploring and self-grooming. ***p<0.0001 versus VH. (G, H) Effect of NP-CS oil treatment on social behavior in mice by the male-female reciprocal social interaction test. The social (G) and nonsocial activities (H) considered are the same as assessed for male-male interaction. Data are expressed as mean±SEM; **p<0.005 versus VH. ANOVA, analysis of variance; EPM, elevated plus maze; MCT, medium-chain triglycerides; SEM, standard error of mean; VH, vehicle.