Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder

IntroductionCannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasing popularity due to its purported therapeutic efficacy for numerous off-label conditions including anxiety and autism spectrum disorder (ASD). Those with ASD are commonly deficient in endogenous cannabinoid signaling and GABAergic tone. CBD has a complex pharmacodynamic profile that includes enhancing GABA and endocannabinoid signaling. Thus, there is mechanistic justification for investigating CBD’s potential to improve social interaction and related symptoms in ASD. Recent clinical trials in children with ASD support CBD’s beneficial effects in numerous comorbid symptoms, but its impact on social behavior is understudied.MethodsHere, we tested the prosocial and general anxiolytic efficacy of a commercially available CBD-rich broad spectrum hemp oil delivered by repeated puff vaporization and consumed via passive inhalation in the female cohort of the BTBR strain, a common inbred mouse line for preclinical assessment of ASD-like behaviors.ResultsWe observed that CBD enhanced prosocial behaviors using the 3-Chamber Test with a different vapor dose-response relationship between prosocial behavior and anxiety-related behavior on the elevated plus maze. We also identified that inhalation of a vaporized terpene blend from the popular OG Kush cannabis strain increased prosocial behavior independently of CBD and acted together with CBD to promote a robust prosocial effect. We observed similar prosocial effects with two additional cannabis terpene blends from the Do-Si-Dos and Blue Dream strains, and further reveal that these prosocial benefits rely on the combination of multiple terpenes that comprise the blends.DiscussionOur results illustrate the added benefit of cannabis terpene blends for CBD-based treatment of ASD

CNS Delivery Via Adsorptive Transcytosis

Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics

Immunological properties of peptic fragments of bovine serum albumin.

The effect of peptic degradation on the immunological and antigenic properties of bovine serum albumin (BSA) was investigated. Molecular fragments obtained after various times of digestion (3-360 min) were studied. Enzymatic digestion resulted in a rapid loss of serologically defined antigenic determinants. The immunogenicity of the fragments as measured by the level of reaginic and total anti-BSA antibody response in BDF1 mice was also diminished. Pre-treatment of mice with fragments exhibiting a low density of B-cell interacting determinants before immunization with BSA, resulted in significant suppression of both the primary and secondary antibody response. The most effective immunosuppressive fragments were obtained following removal of peptides which bound to anti-BSA antibodies. The suppression was shown to be antigen specific. It was concluded that separate determinants on the BSA molecule were responsible for the immunogenic and suppressive properties of the antigen