Introduction

Alzheimer’s Disease (AD) is the most prevalent type of dementia, accounting for two-thirds of cases in individuals aged 65 and older. Dementia is a neurodegenerative disorder with progressive impairment of behavioural and cognitive abilities.¹ AD has affected over 55 million individuals as of 2020, with numbers expected to reach 139 million cases by 2050.² Together, AD and dementia have been identified as the leading cause of death in the UK in 2022, accounting for 11.4% of all deaths.³ As the world population and life expectancy continue to increase at an exponential rate, AD presents itself as a major public health concern. Neurodegeneration in AD manifests as deficits in episodic memory, which can subsequently lead to disturbances in language, impairments in the ability to carry out motor tasks, failure to recognise or identify familiar objects and the decreased ability to perform complex tasks, planning, organising or abstract thought. Due to the progressive nature of the condition, later stages of AD have been associated with greater cognitive deficits, with an estimated death 7-10 years from diagnosis.⁴

This highlights the importance of developing treatment options which change disease progression and alleviate symptoms. Currently, there are pharmacological treatments available; however, they are regarded as a second-line option over psychotherapy due to their side effects and inconsistent positive effects. Therefore, in recent years, attention has shifted to natural alternatives, particularly medical cannabis, a plant-derived medicine. 

Medical cannabis possesses anti-inflammatory properties, which tend to be used as a last resort to enhance a patient’s quality of life when all other treatments have failed. Due to a greater understanding of the beneficial impacts medical cannabis has, it has become increasingly legalised worldwide. However, this has also resulted in backlash due to the negative stigma surrounding cannabis, particularly its use recreationally and its involvement in antisocial behaviour.⁵ Religion, culture and the level of education all play a part in influencing people’s perceptions, opinions and policies regarding medical cannabis. 

Understanding Medical Cannabis in AD

The plant cannabis contains over 70 different compounds called cannabinoids. Delta-9-tetrahydrocannabinol (THC), a primary psychoactive cannabinoid, alongside cannabidiol (CBD), a non-psychoactive cannabinoid, are the most well-known components. Both THC and CBD have been associated with anti-inflammatory properties and reducing amyloid-beta levels — the most notable hallmark of AD. In addition, they have also shown the ability to enhance neurogenesis and improve cognitive function in animal models. 

Role Of THC in AD

THC has been associated with activating the CB1 receptor, which is responsible for modulating learning and memory. When doses of THC were administered to rats, increased performances were seen in novel object recognition tests. Additionally, 12-month-old mice with THC showed the same restoration level of hippocampal gene transcription patterns as 2-month-old mice, indicating THC improves age-related cognitive decline, which may be applicable to cognitive decline in AD patients. Whilst in humans, there have been six randomised controlled trials assessing the effects of THC on AD; however, results have been inconsistent and contradictory. Some studies found that THC reduced agitation and psychiatric symptoms, as well as improved cognition in people with moderate-to-severe AD compared to a control group. Meanwhile, other studies found THC had no impact in terms of neuropsychiatric symptoms and quality of life and was instead associated with sedative effects. These studies indicate the mixed clinical efficacy of THC’s role in AD, despite it being well-tolerated at low doses in older patients with AD. Additionally, these results have only come from six studies, all of which used very small sample sizes; therefore, the validity of these results could be questioned.⁶ 

Role of CBD in AD

CBD has shown the ability to prevent cell death in relation to AD, as well as having neuroprotective properties against neurotoxicity. Preclinical studies have demonstrated the efficacy of CBD in preventing cognitive decline in AD, in which it successfully reduced social recognition memory impairments. In humans, CBD is well tolerated, with the efficacy remaining constant with chronic use, unlike THC. However, as of yet, there have been no randomised placebo-controlled clinical trials of CBD being used as a therapy for AD in humans, so conclusions should not be made prematurely.⁶

Usage of Cannabis and Public Perception Stigmatism 

Cannabis is the most commonly used psychoactive drug in the world, with an estimated 4% of the world’s population having used cannabis in the past year. In Europe, 27.3% of the adult population reported having used cannabis for recreational purposes. In Asia, the annual prevalence is estimated at 2%, representing one-third of cannabis users worldwide.⁷ Whereas in Africa, cannabis is the most consumed illegal substance, with Africans making up a third of the worldwide cannabis use as well. This highlights that cannabis is generally used worldwide, with varying prevalence across countries and cultures. 

The motive to use cannabis ranges widely, with some using it to increase mood and alter perceptions, and even as a form of escapism. These are all recreational purposes, with heavy substance abuse being associated with poor mental health, cognitive impairment and cannabis use disorder (CUD). Cannabis has also been linked to anxiety, depression, and suicidal thoughts. In addition, a meta-analysis has shown that 22% of cannabis users develop a tolerance to the drug.⁷ This reinforces the stigma associated with cannabis, as it is traditionally associated with being a recreational drug involved in criminal behaviour. Due to this public perception, patients may not even consider cannabis as a suitable treatment option for AD and may even express strong resistance to its medical applications. 

Cultural Belief Variability of Cannabis Use 

Despite the perceptions of cannabis being associated with antisocial behaviour and its harmfulness, it is essential to take into account the psycho-social-cultural considerations of cannabis use. Traditionally, cannabis was used as part of rituals and religion. For example, in India, Hindu myths describe the supreme god, Shiva, using cannabis as an agent for mystic inspiration and experience. In modern day, cannabis is still used in India as an ayurvedic medicine, a natural, holistic approach to healthcare, where it has been associated with reducing pain and anxiety as well as increasing sleep quality and relaxing muscles. Not only has cannabis been linked to its therapeutic benefits in India, but it has also been used by the Greeks, Romans and Assyrians for thousands of years. Additionally, in ancient Egypt, cannabis was consumed for spiritual and healing purposes, known as ‘Shemshemet’, where it was thought to have been created by Ra, the god of the sun.⁷ 

Cannabis was introduced to the West in the 19^th century by a physician observing its medical effects in India. Upon this introduction, hundreds of scientific articles were published with research into the link between cannabis use and its therapeutic impacts. 

Policy and Legal Frameworks 

In the 1960s, a tax was put in place along with the passing of the Controlled Substances Act to restrict cannabis use in the USA. Following this, other countries across the world followed the same restrictions, coming together as a global effort to ‘combat’ cannabis. However, in the past decade, policymakers have shifted their perceptions of cannabis, with medical cannabis becoming legal in the UK as of 2018, making it more accessible.⁷ 

Conclusion

Alzheimer’s Disease (AD) is currently on an exponential rise, presenting itself as a progressive and debilitating condition which yet remains incurable, hence requiring innovative approaches to improve the quality of life for patients and caregivers. Despite cannabis, specifically THC and CBD, having therapeutic properties in improving cognitive decline, their application remains limited due to deeply ingrained cultural stigmas and a lack of clinical evidence. Across the world, there is great variability in cannabis usage and perception, which is greatly influenced by historical, religious and socio-political factors, highlighting the importance of developing culturally sensitive education and policy-making approaches. The acceptance and integration of medical cannabis for the treatment of AD requires a balance between respecting cultural backgrounds and advancing scientific understanding. As the prevalence of AD continues to rise, with a growing population and longer life expectancies, medical cannabis could play an integral role in improving patients’ lives and improving their quality of life.