Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol, the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone.
These properties suggest that CBD is perfectly placed to treat a number of pathologies typically found in AD. In the following, we will outline in brief the endocannabinoid system and the pharmacological profile of CBD before discussing recent advances in the evaluation of the therapeutic properties of CBD using in vivo AD rodent models.
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CBD effects in pharmacological rodent models of AD The in vivo therapeutic potential of CBD in AD has not been widely documented there are a number of studies that have reported the effect of CBD in pharmacological models of AD. These studies have described anti-inflammatory and neuroprotective effects of CBD. The in vivo anti-inflammatory effects of CBD were confirmed in a mouse model of AD where the mice were intrahippocampally injected with human Aβ42 and then treated daily with intraperitoneal injections of CBD for 7 days.
One study to date has investigated the effects of CBD on cognition in a pharmacological model of AD. Three-month old mice were intraventricularly injected with 2.5 μg of fibrillar Aβ. They were then treated with 20 mg/kg CBD using daily i.p. injections for 1 week and then 3 times/week for the following 2 weeks.
CBD effects in transgenic mouse models of AD Although pharmacological models of AD are useful in producing AD-like symptoms, it is necessary to investigate the effects of CBD in transgenic mouse models as they result from gene mutations, which are seen in familial AD. Furthermore, based on the pharmacological protocols used, some effects of CBD could be related to a direct effect of the phytocannabinoid on exogenous Aβ administration rather than the long-term effects of the accumulated Aβ. Initially, two studies were conducted in our laboratories to elucidate the remedial and preventative potential of chronic CBD treatment in AD transgenic mice.
The study did report a complex interaction between CBD treatment, AD genotype and cholesterol and phytosterol levels, suggesting they may be involved in the mechanisms behind the beneficial effects of CBD. There was also a subtle impact of CBD on inflammatory markers of the brain.
Sativex, a combination therapy using a 1:1 ratio of CBD and THC is approved as an anti-inflammatory drug treatment against spasms in multiple sclerosis and does not appear to be associated with any adverse THC effects, suggesting that CBD effectively blocks those at the ratio chosen.