Behavioral and Neurobiological Effects of Medical Cannabis Treatment in Mouse Model of Autism Spectrum Disorder
Translational Pediatrics, 2021
Shani Poleg1, Emad Kourieh1, Angela Ruban2, Guy Shapira3, Noam Shomron3, Boaz Barak4,5,Daniel Offen1,3,4
1Sackler Faculty of Medicine, Human Molecular Genetics & Biochemistry, Felsenstein Medical Research Center, Tel-Aviv University, Tel Aviv, Israel; 2The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 4Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel; 5The School of Psychological Sciences, Faculty of Social Sciences, Tel Aviv University, Tel Aviv, Israel.
Autism spectrum disorder (ASD) is a neurodevelopmental disease with a wide spectrum of manifestations. The core symptoms of ASD are persistent deficits in social communication, and restricted and repetitive patterns of behavior, interests, or activities. These are often accompanied by intellectual disabilities. At present, there is no designated effective treatment for the core symptoms and co-morbidities of ASD. Recently, interest is rising in medical cannabis as a treatment for ASD, with promising clinical data. However, there is a notable absence of basic pre-clinical research in this field.
The aim of this laboratory study conducted on mice by the Tel Aviv University, was to investigate the behavioral and biochemical effects of long-term oral treatment with Avidekel Oil, Erez Oil, and pure CBD and THC oil, in a human mutation-based Shank3 mouse model of ASD. This study found that the treatment with Avidekel alleviates anxiety and decreases repetitive grooming behavior by over 70% in treated mutant mice compared to non-treated mutant mice. Furthermore, brain samples revealed changes in mRNA expression of several neurotransmission-related genes post treatment. The study found that Erez oil also has positive effects on social behavior, in addition to relieving excessive repetitive grooming behavior.
STUDY POPULATION: lab mice.
Decrease in repetitive and anxiety behaviors – Avidekel treatment improved repetitive and anxiety behaviors, but not social deficits, in the mouse model of ASD. The pivotal effect of the Avidekel oil treatment was in relieving excessive repetitive grooming behavior, as compared with the control group. Additionally, the mice treated with Avidekel oil spent significantly more time exploring the open arms in a maze, indicating lower levels of anxiety. Erez treatment had favorable effect on social behavior in addition to alleviation of repetitive grooming behavior.
Decrease in glutamate concentration – Increased glutamate levels have been reported in persons with autism. The treatment with Avidekel oil significantly decreased glutamate concentration in the cerebrospinal fluid one-hour post-treatment, showing a decrease of over 90% compared with the control group.
Changes in mRNA expression – Avidekel oil treatment modified mRNA expression of neurotransmission-related genes in the cerebellar brain of the mice. This might contribute to the alleviation of excessive repetitive grooming behavior.
Side effects – Chronic treatment with Avidekel did not impair the well-being of the mice. Results showed that the treatment did not harm the cognitive function, mood, or appetite of the mouse.