Chronic cannabidiol (CBD) treatment did not exhibit beneficial effects in 4-month-old male TAU58/2 transgenic mice.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, motor impairments, and accumulation of hallmark proteins, amyloid-beta (Aß) and tau. Traditionally, transgenic mouse models for AD have focused on Aß pathology, however, recently a number of tauopathy transgenic models have been developed, including the TAU58/2 transgenic model. Cannabidiol (CBD), a non-toxic constituent of the Cannabis sativa plant, has been shown to prevent and reverse cognitive deficits in Aß transgenic mouse models of AD. Importantly, the therapeutic properties of CBD on the behavioural phenotype of tauopathy mouse models have not been investigated. We assessed the impact of chronic CBD treatment (i.e. 50 mg/kg CBD i.p. administration starting 3 weeks prior to behavioural assessments) on disease-relevant behaviours of 4-month-old TAU58/2 transgenic males in paradigms for anxiety, motor functions, and cognition. TAU58/2 transgenic males demonstrated reduced body weight, anxiety and impaired motor functions. Furthermore, they demonstrated increased freezing in fear conditioning compared to wild type-like animals. Interestingly, both sociability and social recognition memory were intact in AD transgenic mice. Chronic CBD treatment did not affect behavioural changes in transgenic males. In summary, 4-month-old TAU58/2 transgenic males exhibited no deficits in social recognition memory, suggesting that motor deficits and changes in anxiety at this age do not impact on social domains. The moderate increase in fear-associated memory needs further investigation but could be related to differences in fear extinction. Future investigations will need to clarify CBD's therapeutic potential for reversing motor deficits in TAU58/2 transgenic mice by considering alternative CBD treatment designs including changed CBD dosing.

In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-ß and tau hyperphosphorylation as well as neuroinflammation and oxidative stress. Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. Thus, it is investigated as a potential multifunctional treatment option for AD. Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD. The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models. Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), 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. The studies provide "proof of principle" that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies. Further investigations should address the long-term potential of CBD and evaluate mechanisms involved in the therapeutic effects described.