Alzheimer's disease (AD) is a neurodegenerative disorder affecting a growing number of people. It is the most common form of dementia, accounting for over 60% of cases and affecting more than 33 million people worldwide. Sadly, as the population ages, this number is set to rise to 115 million by 2050.

Alzheimer's disease, explanations and evolution

Alzheimer's disease generally begins with mild deficits in short-term memory, learning, communication and spatial orientation. In the advanced stages of the disease, there is a global disruption of cognitive abilities, with severe impairments in speech and facial recognition... This makes patients dependent, and subjects them to round-the-clock care. As the disease progresses, they become increasingly vulnerable.

Scientifically speaking Alzheimer's disease is characterized by the accumulation of amyloid-β and "tau hyperphosphorylation", as well as by neuroinflammation and oxidative stress. Current treatments for AD are unable to halt or reverse the disease's progression, underscoring the need to develop new, more effective therapies...

Could cannabidiol (CBD), a non-psychoactive phyto cannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro, be a potential multifunctional treatment option for AD?

The endocannabinoid system and CBD pharmacology

A number of clinical studies have been carried out and are currently underway.

Here, we summarize the current status quo of CBD's in vivo effects in established pharmacological and transgenic animal models of AD.

Studies demonstrate CBD's ability to reduce reactive gliosis and the neuroinflammatory response, as well as promoting neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in rodent models of Alzheimer's disease. Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient in cannabis sativa, show that CBD can significantly reduce the psychoactive effects associated with THC and potentially provide greater therapeutic benefits than either phytocannabinoid alone.

The studies thus provide explicit evidence that CBD and possibly CBD-THC combinations are valid candidates for new AD therapies. Further studies should investigate the long-term potential of CBD and evaluate the mechanisms involved in the therapeutic effects described.

Why Cannabidiol?

The phyto cannabinoid cannabidiol (CBD) is a prime candidate for this new treatment strategy. CBD has been shown in vitro to be a neuroprotectant (Neurosci Lett. 2006 May) that develops several properties:

• Prevents neurodegeneration of the hippocampus and cortex (Hamelink et al., 2005),
• Has anti-inflammatory and antioxidant properties (Mukhopadhyay et al., 2011),
• Reduces hyperphosphorylation (Esposito et al., 2006a),
• Regulates microglial cell migration (Walter et al., 2003; Martín-Moreno et al., 2011).

In addition, CBD has been shown to protect against Aβ-mediated neurotoxicity (Janefjord et al., 2014) and microglia-activated neurotoxicity, reduce Aβ production by inducing APP ubiquitination (Scuderi et al., 2014) and improve cell viability (Harvey et al., 2012).

Truly, these properties suggest that CBD is perfectly placed to treat a number of pathologies typically found in AD.

In the remainder of this article, we briefly describe the exposed roles of CBD on AD-bearing animals and thus more specifically, we will establish the evaluation of the therapeutic properties of CBD (and CBD-THC combinations) using in vivo models of AD rodents.

Effects of CBD on AD (in transgenic mouse models)

In recent years, a number of scientists and doctors have studied and developed the role of the endocannabinoid system (ECS) in neurodegenerative diseases such as Alzheimer's.

Although pharmacological models of AD are useful for producing AD-like symptoms, it is necessary to study the effects of CBD in transgenic mouse models as they result from genetic mutations, which are observed in familial AD (e.g. mutations in the APP, PS1 and PS2 genes).

Furthermore, based on the pharmacological protocols used, some of the effects of CBD could be related to a direct role of the phytocannabinoid on exogenous Aβ delivery rather than the long-term effects of accumulated Aβ.(Cheng et al., 2014).

For example, extensive studies have shown that CBD has the ability to improve behavioral problems that may be at the root of Alzheimer's disease: eating disorders, deteriorating sleep patterns, anxiety, etc. This represents a more effective way of treating the disease.

In the same vein, a large-scale study was carried out in 2014 by Australian scientists. In mice, they investigated the role of CBD in the treatment of Alzheimer's disease.

School of Medical Sciences, University of New South Wales, NSW, Australia

Initially, control transgenic and AD mice were orally treated from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. The mice were then assessed in a social preference test , high conditioning plus maze and fear paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols and inflammation. It was found that AβPP × PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. In addition, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol and dietary phytosterol retention.

This subject is the first to demonstrate the ability of CBD to prevent the development of a social recognition deficit in transgenic mice with AD. These results thus provide the first evidence that CBD may have potential as a preventive treatment for AD, with particular relevance to symptoms of social withdrawal and facial recognition. The findings demonstrated that CBD is capable of enhancing the growth of certain neurons, which may have a direct impact on the deterioration of cognitive functions.

Conclusion

We have seen a number of significant advances demonstrating the impact of CBD.

Further studies in transgenic AD mouse models are therefore needed, in a dose-dependent manner, to understand the full potential and long-term effects of CBD.

It's important to note that many of these studies were conducted in mice aged between 3 and 6 months, which is quite young given that AD is usually diagnosed relatively late in the course of the disease.

Nevertheless, the studies reviewed here provide promising preliminary data, and the translation of this preclinical work into a clinical context could be achieved relatively quickly.

Time is our ally in demonstrating the range of pathologies for which cannabinoids could become the future of a more natural medicine.

Perhaps you have more specific questions about CBD and its uses?

Through our articles, we try to answer you:

• Chronic pain
• CBD and sleep disorders
• CBD and anxiety
• CBD and Alzheimer's
• Its action on the endocannabinoid system
• General dosages and tips on taking CBD
• Can CBD help your pets?

Sources

[1] - In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer's Disease (2017)

[2] - Ultrastructural differences in pretangles between Alzheimer disease and corticobasal degeneration revealed by comparative light and electron microscopy (2014)

[3] - Differentiating cognitive impairment due to corticobasal degeneration and Alzheimer disease (2017)

[4] - Alzheimer's disease

[5] - Immunotherapeutic Approaches for Alzheimer's Disease

[6] - Hamelink et al, (2005)

[7] - Mukhopadhyay et al, (2011)

[8] - Esposito et al, (2006)

[9] - Walter et al, (2003)

[10] - Janefjord et al,( 2014)

[11] - Scuderi et al, (2014)

[12] - Cheng et al, (2014)

[13] - Martín-Moreno et al,( 2011)