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

February 3, 2017
Georgia Watt and Tim Karl

Abstract

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-β 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.

Conclusions

AD is a debilitating neurodegenerative disease that is becoming increasingly common in today's society. Unfortunately, there is still no effective treatment that stops or reverses the disease progression.

The studies reviewed in this mini review provide “proof of principle” for the therapeutic benefits CBD and possibly CBD-THC combinations pose for AD therapy (summarized in Table ​Table1).1).

However, further dose-dependent investigations into transgenic mouse models of AD are necessary to understand the full potential and the long-term effects of CBD. Importantly, many of the discussed studies were conducted in mice aged between 3 and 6 months, which is quite young considering AD diagnosis is usually relatively late in the disease progression.

Furthermore, it is necessary to investigate the effects of CBD in tauopathy mouse models specific to AD and in female mouse models as all studies reviewed were conducted in male mice only.

Nevertheless, the studies discussed here provide promising preliminary data and the translation of this preclinical work into the clinical setting could be realized relatively quickly: CBD is readily available, appears to only have limited side effects (Bergamaschi et al., 2011) and is safe for human use (Leweke et al., 2012).