Combining cannabidiol and delta-9-tetrahydrocannabinol at a 50:3 ratio – a new therapeutic strategy for APP/PS1ΔE9 transgenic mice?

/PS1ΔE9 (APP/PS1) AD transgenic mice was evaluated. 14-month-old male and female transgenic mice and their wild type-like littermates were used. They were treated via daily intraperitoneal injection with CBD+THC treatment (or vehicle) for 3 weeks prior to and throughout behavioural assessment. CBD+THC significantly improved the initial localisation of the reward zone during a spatial memory probe trial in APP/PS1 mice and restored the increased acoustic startle response of APP/PS1 females. APP/PS1 mice had deficient object recognition memory and impaired spatial learning, neither of which were restored following combined cannabinoid treatment. Interestingly, CBD+THC impaired social recognition of APP/PS1 males. Treatment reduced sensorimotor gating in females. In males, treatment decreased risk assessment behaviour, and reduced acoustic startle. CBD+THC treatment had mild therapeutic properties but also off-target effects, suggesting that CBD+THC might be less preferable than CBD alone in a mouse model of advanced AD. Further research into alternate cannabinoid dosage and dose ratios is required to elucidate the potential of cannabinoid combination therapies for AD more comprehensively.