Cannabis is the formal name of the plant commonly referred to as marijuana. Medical marijuana includes dried marijuana and marijuana oils. Medical cannabis was legalized in July 2001. Since then, medical cannabis use has progressively increased among all age groups. According to the Canadian Cannabis Survey 2020, older adults accounted for seven to 23 percent of medical cannabis consumers globally. Moreover, there were 329,038 medical cannabis users in Canada in March 2020.

It is only since 2018, when recreational cannabis was legalized in Canada, that there has been renewed interest in medical cannabis as a potential treatment for dementia-related symptoms.

Cannabis plants contain over 500 chemical substances, including over 100 bioactive compounds, collectively referred to as cannabinoids. The most well-known of these compounds are THC (Tetrahydrocannabinol) and CBD (Cannabidiol). THC is the psychoactive compound that causes a sense of euphoria or “high.”

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The term medical cannabinoid includes both the synthetic cannabinoids (such as nabilone or nabiximol) and medical marijuana.

Cannabinoids — Mechanism of Action

Cannabinoids exert their effects through endocannabinoid system (ECS), comprised of endogenous cannabinoids (produced in the body), cannabinoid receptors (mainly CB1 and CB2), and enzymes involved in synthesis and degradation of endocannabinoids. CB1 receptors are present throughout the brain and spinal cord, while CB2 receptors are present in the peripheral tissues, particularly immune cells.

Acting through the endocannabinoid system, THC and CBD modulate the way the neurons communicate with each other, thereby modifying behaviour.

 How is cannabis processed by the body?

Once cannabis enters the body, it is absorbed and distributed in the fat tissue. It is metabolized in the liver and eliminated via bile through feces and urine. Since ageing is associated with a higher body fat/protein ratio, cannabis tends to remain longer in the body in older adults. It also gets metabolized and eliminated slowly in older adults, due to ageing-related slowing of liver and kidney function.

The potency of cannabinoids is determined by the potency of THC in the cannabis strain, mode of intake, simultaneous use of tobacco and alcohol, and other drugs metabolized by the liver. When inhaled, it starts acting within minutes and peaks within three minutes (vaporized) to 45 minutes (inhaled), while its action starts later and peaks within four to eight hours, when ingested.

Is cannabis effective and safe for older adults?

Surveys sent out to older adult consumers of medical marijuana revealed that the majority of older adults reported it as safe and moderately effective in reducing chronic pain and cancer-related pain (Abuhasira et al., 2018).

Medical cannabinoids for treating behavioural symptoms of  dementia

Approved medications for Alzheimer’s disease — Donepezil, Rivastigmine, and Galantamine — help in reducing behavioural symptoms such as agitation, apathy, hallucination and delusions, only to some extent (Gauthier et al., 2002). Anti-depressants such as Citalopram and Escitalopram are beneficial mainly in mild dementia, while atypical antipsychotics such as Risperidone are reserved for situations where safety is a concern, due to serious adverse effects.

The absence of safe and effective medications to treat dementia-related behaviour symptoms has sparked interest in the potential therapeutic use of cannabis, as an alternative.

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In animal studies and cell culture studies, cannabinoids were found to improve memory and cognition and reduce pain and behavioural symptoms by regulating the release of neurotransmitters. Cannabinoids were also found to decrease amyloid plaques and tau tangles — the microscopic hallmark changes in the Alzheimer’s brain — and to slow down degeneration by reducing inflammation in the brain, production of harmful proteins, and improving the survival of neurons.

The Canadian Agency for Drugs and Technologies in Health (CADTH), an independent non-profit organization set up to provide evidence-based information to healthcare decision-makers, conducted a literature review of studies that analyzed the role of cannabinoids in treating behavioural symptoms of dementia.

Out of 12 small clinical trials that assessed the effects of cannabinoids on behavioural symptoms of dementia, a few showed evidence of decrease in agitation with cannabinoids. However, the studies so far have generally been small or of low quality, making it difficult to come to a definitive conclusion (Staples, Adcock 2018).

A recent phase 2 clinical trial conducted by Sunnybrook Health Sciences in Toronto, partly funded by the Alzheimer’s Association, studied the effect of synthetic THC (Nabilone) 1-2 mg for 14 weeks, in 33 patients with moderate to severe Alzheimer’s disease and marked agitation. The researchers observed a significant reduction in nighttime agitation and increased sleep duration, but sedation was a significant concern. The researchers emphasized the need for further large-scale studies to determine the optimum dose of Nabilone (Lanctot, K. 2018).

A phase 3 study has been launched this year, so we can watch how it unfolds.

Research in this area is still in its infancy. Therefore, large-scale clinical trials, and time to create a body of evidence for the use of these substances, are needed before cannabis-derived products can be promoted as a treatment for dementia and associated symptoms.

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It is important to also remember that cannabis is not suitable for those with serious liver, kidney, heart or lung disease, cannabis allergy, and those having a personal or family history of any serious mental illness.

Cannabinoids can interact with other medications that are metabolized in the liver, including sleeping pills, tranquillizers, pain medications, allergy/cold medications, certain antidepressants, certain heart medications and some stomach-acid medications, and can cause serious adverse reactions. Please consult with your family physician before you start using cannabis.

Conclusion

Cannabinoids could potentially benefit people with Alzheimer’s disease, in particular, those with night-time agitation, loss of appetite, and sleep disturbances. However, limited studies have been conducted to assess the benefits of cannabinoids in dementia. Nabilone seems promising but concerns around sedation remain.

The Prescribing Guidelines Committee has issued a strong recommendation to physicians to prescribe synthetic cannabinoids instead of marijuana, if they are considering medical cannabis for their patients, because of variation in the levels of THC and CBD in different strains of the plant, which makes dosing and dose-monitoring very challenging (TOP Canadian Prescribing information 2018).

The launch of new cannabis studies gives us hope that these and future studies will lead to the development of safe and effective medications to treat dementia and its related symptoms.