What question did this study set out to answer?

To evaluate the efficacy of combined CBD and THC treatment on cognitive deficits in APP/PS1 transgenic mice.

April 18, 2026Neurobiology of Aging0 citationsOpen Access

Combining Cannabidiol and Delta-9-Tetrahydrocannabinol at a 50:3 Ratio – a New Therapeutic Strategy for APP/PS1ΔE9 Transgenic Mice?

MCMadilyn Coles RPRossana Rosa Porto RCRose Chesworth

Key Points

To evaluate the efficacy of combined CBD and THC treatment on cognitive deficits in APP/PS1 transgenic mice.
Chronic treatment with 50 mg/kg CBD and 3 mg/kg THC or vehicle for 3 weeks
Assessment of behavioral effects using spatial memory and object recognition tests
Comparison of results between APP/PS1 transgenic mice and wild-type littermates
CBD+THC improved initial reward zone localization in spatial memory probes
No restoration of object recognition or spatial learning deficits observed
Social recognition impaired in APP/PS1 males, indicating off-target effects

Abstract

Preclinical evidence suggests that cannabidiol (CBD) can ameliorate Alzheimer’s disease (AD)-related pathologies, including amyloid-β aggregation and tau hyperphosphorylation, and can reverse and prevent cognitive decline in AD rodent models. Interestingly, low-dose delta-9-tetrahydrocannabinol (THC) can improve cognition in aged mice, and 1:1 CBD+THC appears to exhibit a greater therapeutic profile in AD mouse models than either phytocannabinoid alone. Here, the potential of chronic treatment with 50 mg/kg bodyweight CBD combined with 3 mg/kg THC to reverse the behavioural deficits of adult APP Swe /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. • Combined cannabinoid treatment improves retrieval memory in an AD mouse model • 50:3 CBD+THC does not restore impaired object recognition or spatial learning • Combined cannabinoid treatment impairs social recognition of APP/PS1 males • 50:3 CBD +THC treatment has mild therapeutic properties but also off-target effects

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