Cannflavin B ameliorates behavioural and neuronal systems alterations in adolescent rats exposed to prenatal valproic acid

“Currently, no pharmacological treatments ameliorate the core and comorbid symptoms of autism spectrum disorders, but solely target comorbid symptoms such as irritability, anxiety, and epilepsy.

There has been growing interest in using whole cannabis or cannabidiol as potential therapeutics in autism. However, there are concerns surrounding the use of whole cannabis in children, and reports examining the therapeutic efficacy of cannabidiol are inconsistent.

In this study, the potential therapeutic efficacy of cannflavin B, a non-psychoactive component of the Cannabis sativa plant, was evaluated. Using prenatal valproic acid (VPA) exposure in rats, a model widely used to study aspects of autism, sex differences in adolescent behaviour, neuronal oscillatory changes, and microglial activity in response to cannflavin B administration (0.2 mg/kg, i.p.) were assessed.

Cannflavin B was well tolerated and ameliorated most of the observed VPA-induced changes.

Cannflavin B had anxiolytic-like properties in female VPA rats, and normalized sociality in VPA animals of both sexes.

Within the prefrontal cortex, cingulate cortex, and hippocampus, most of the VPA-induced regional responses in neuronal oscillatory spectral power, coherence, and theta-gamma cross-frequency synchrony were ameliorated by cannflavin B. Cannflavin B also attenuated the sex- and brain region-specific VPA-induced elevations in the microglial marker Iba1. In vitro, cannflavin B normalized VPA-induced elevations in cortical and hippocampal neuronal activity and promoted more organized cortical firing.

These findings demonstrate cannflavin B ameliorates behavioural and neuronal systems function alterations induced by prenatal VPA in rats, and highlights the importance of researching alternative cannabis compounds in autism and other disorders.”

https://pubmed.ncbi.nlm.nih.gov/41496357

“Like THC and CBD, cannflavins are most likely highly lipophilic based on their prenylated structure, indicating that they should be able to readily cross the blood brain barrier.”

“In conclusion, this was the first study to examine the in vivo effects of cannflavin B in a model widely used to study aspects of autism. It was demonstrated that cannflavin B administration, a non-psychoactive component of the Cannabis sativa plant, could normalize many of the sex-dependent and independent alterations in behaviour and neuronal activity, as well as microglial marker levels, in adolescent rats following prenatal exposure to VPA. Cannflavin B, at the dose used, appeared to be well tolerated with no adverse effects observed.”

https://www.sciencedirect.com/science/article/pii/S0753332225011436?via%3Dihub