Cannabis has been used to treat diseases for thousands of years. Recent legislative changes and scientific discoveries have led to a renaissance in medical research on the plant’s active compounds and their effects on the human nervous system. Research suggested that patients with dementia can benefit from a short treatment with cannabinoids, and that cannabinoids may even prevent the progression of Alzheimer’s disease.
The Endocannabinoid System
Neuropsychiatric symptoms of dementia are difficult to treat; agitation especially so. They are a major cause of a deterioration in quality of life, repeated hospitalization and increased morbidity and mortality. They can be very difficult for loved ones to deal with as well. Studies over the past decade suggest that both synthetic and naturally occurring cannabinoids (phyto-cannabinoids) may alleviate these persistent symptoms. Today, several larger-scale clinical studies are underway, and these may provide more conclusive evidence.
Most people who live with dementia will eventually experience neuropsychiatric symptoms (NPS) such as agitation, aggressiveness, apathy, walking about and eating disorders over the course of their dementia. These symptoms have major impacts on the illness and mortality of people living with dementia, often requiring additional medication, hospitalization and institutionalized care. These outcomes can in turn affect caregivers’ health. Current treatment of NPS includes nonpharmacological behavioural interventions and additional pharmacological treatment, in the form of off-label use of atypical antipsychotics, antidepressants and antiepileptic medications. Unfortunately, these medications are not very effective here, and they also can have incapacitating side effects. There is widespread agreement among clinicians, patients, caregivers and policy-makers about the pressing need for alternative therapeutic options for these debilitating symptoms.
The human endocannabinoid system (ECS) has recently come on the radar for treatment of dementia symptoms. The endocannabinoid system (ECS) has three main elements:
- Endocannabinoids, which are cannabinoid molecules produced inside the body.
- Receptors located on the surface of human cells, which bond with cannabinoids and transmit inter-cellular signals. The most-studied receptors are CB1 receptors on brain cells and CB2 receptors on immune system and blood cells.
- Enzymes, which break down cannabinoids.
Both phyto- and synthetic cannabinoids can bind to the ECS receptors, altering neural communication via neurotransmitters such as acetylcholine, GABA, dopamine and serotonin. Disrupted activity of the neurotransmitter acetylcholine in the brain, for instance, directly impairs processes such as learning, memory, restful sleep and other cognitive functions. Indeed, many of dementia symptoms are linked to disruption in acetylcholine (neuro-muscular) activity and this neurotransmitter is a primary target of current dementia medications. Critically, the ECS has been repeatedly shown to modulate the neural communication associated with acetylcholine (as well as other important neurotransmitters), an understanding that has led scientists to examine whether manipulation of the endocannabinoid system can be used to alleviate dementia symptoms, or even slow the progression of the disease. Clinical trials show cannabinoids are safe for people with dementia.
Randomized, controlled clinical trials provide the most reliable evidence for the safety and efficacy of medical treatments. In the past 20 years, only seven such trials have assessed the effectiveness of cannabinoids for NPS in the various types of dementia, and most of these had major methodological flaws. Doing clinical trials with cannabis has been extremely challenging given the historical legal status of cannabis.
In 1997, a group from the US reported that patients with Alzheimer’s disease, who were given Dronabinol orally twice a day for six weeks, experienced increased appetite and a reduction of disturbed behavior as rated by caregivers (CMAI score). Similar results were later reported in two patients with Alzheimer’s who were given a similar dose for only 14 days.
Several larger studies were conducted in the Netherlands in 2015 and 2017 (another 2015 study can be found here), where patients with different types of dementia received synthetic THC two or three times a day for periods between four days and 12 weeks. While these studies suggested that the treatment is safe in terms of unwanted side effects, there were no clinically significant improvements on a wide range of dementia symptoms.
Still, according to a recent scientific review looking at the use of cannabinoids for symptoms of dementia, such preliminary results are encouraging. The studies involved people with different types of dementia, and such ‘heterogeneous’ sampling can mask meaningful clinical effects. Furthermore, the use of relatively small doses of THC, and the co-administration of other medications, makes it harder still to draw firm conclusions.
In May 2019, a Canadian group tried to address some of these kinds of shortcomings. This well-controlled and statistically robust study included 40 participants, all with a diagnosis of Alzheimer’s disease. It revealed that a similar dose of synthetic THC was effective for the treatment of agitation. Forty-five percent of patients in this study, however, experienced sedation but not at levels that required them to stop the treatment.
Dementia & Cannabis
The idea that cannabinoids might alleviate neuropsychiatric symptoms of dementia seems intuitively correct, as cannabis is widely used for relaxation and anxiety reduction due to its pharmacological and neurobiological effects on the human brain. But some scientists envision that cannabinoids may also be useful as modulators of the neurodegeneration itself, which is the main neuropathology of dementia.
Researchers see potential for cannabidiol (CBD) in preventing progression of Alzeheimer’s disease. CBD has very low toxicity, is rapidly distributed and can pass through the blood–brain barrier. A number of studies provide evidence that this phytocannabinoid indeed has various properties including neuroprotection, anti-inflammatory and antioxidant effects: all important factors for delaying neurodegeneration.
Unfortunately, to date there have not been any clinical trials evaluating the therapeutic potential of CBD for dementia. But trials in animal labs and cell cultures show that CBD and THC/CBD combinations can reduce the production and accumulation of the harmful proteins and plaque (Aβ and tau), which cause neurodegeneration in Alzheimer’s disease. In a number of studies, a short course of CBD treatment in mice was even found to reduce destruction of neurons in the hippocampus (an area of the brain involved in memory formation) and to promote the formation of new cells. Beyond protecting neurons, CBD was also found to have therapeutic behavioral effects in preventing the onset of impaired social recognition in adult lab mice with Alzheimer’s-like conditions. As the journal of Behavioural Pharmacology optimistically summarized, “CBD could well provide symptomatic relief and/or prevent disease progression for Alzheimer patients.”
In the UK, a large clinical trial on dementia patients is commencing in late 2019, and is expected to provide more robust evidence on the efficacy of cannabinoid in symptomatic treatment of dementia. The study would be the first to use a cannabis-based mouth spray containing THC and CBD (Nabiximols). Another large clinical trial in Israel is currently running and is expected to terminate in mid-2020. This trial would be the first to employ a locally-engineered cannabis oil (Avidekel), the main ingredient of which is CBD.
Randomized clinical trials are tightly regulated and provide a high level of evidence, but they are also time-consuming and resource-hungry. For this reason, researchers and physicians also use cohort studies and case reports to try and assess the usefulness of a therapy.
Several such studies point more clearly toward cannabinoids as effective treatments for NPS in dementia. In 2014, a cohort of 40 patients with different types of dementia was found to be less agitated and aggressive, and more rested after a higher dose of a THC analogue than was used in clinical trials. Two years later, an Israeli team reported similar results from a group of 11 patients with Alzheimer’s, who were given medical cannabis oil (containing a similar dose of THC and varying amounts of cannabidiol) at similar doses for 28 days. In 2019, a hospital in Geneva provided evidence that a higher dose of oral cannabis extract with THC and CBD, administered for two months with a gradual increase in dosage, was tolerated well and greatly improved behavioral issues, muscle rigidity and daily care in 10 female patients with dementia. Finally, several anecdotal case reports of patients treated with varying doses of THC analogs reported reductions in behavioral and psychological symptoms of dementia.
There are considerable international and national variations, and constant changes and developments in the legal status and regulation of medical cannabis and different cannabinoid products. Table 1 (and the map below) summarizes current regulatory statuses according to the previous National Conference of State Legislators, as published in the article, “Clinician’s guide to cannabidiol and hemp oil”.
Below you will find state cannabis programs based on data presented at the National Conference of State Legislators (November 2018).
- Adult recreational and medically regulated programs: AK, CA, CO, DC, MA, ME, MI, NV, OR, VT, WA
- Adult recreational use without medically regulated programs: MP
- Comprehensive medical cannabis programs: AR, AZ, CT, DE, FL, HI, IL, LA, MD, MN, MO, MT, ND, NH, NJ, NM, NY, OH, OK, PA, RI, UT, WV
- CBD/Low THC program (hemp-derived products): ID, KS, NE, SD
- Adult recreational and medically regulated programs: the Netherlands, Portugal (medical program since 2018, recreational use decriminalized), Uruguay
- Comprehensive medical cannabis programs: Germany (142,000 prescriptions were issued in 2018), Israel (approx. 50,000 prescriptions issued in 2018), UK (medical program poorly adopted by physicians)
Notably, the US federal government has not legalized CBD-rich medical cannabis, even though there is little or no THC included. This is despite hemp-derived CBD products being widely sold in, for example, health food stores, tobacconists and on Amazon, and despite its legalization in many US states. And despite the diversity of legal statuses in different states, CBD can be purchased online and delivered legally to most states.
In Israel, medical cannabis is not formally indicated for dementia, although it is prescribed ‘off label’ to patients who symptomatically benefit from treatment, and who are referred by a geriatrician.
In the UK, medical specialist doctors have since November 2018 been able to legally prescribe medical cannabis for any condition, as cannabis was moved from schedule 1 to schedule 2. However, while Nabiximol is licensed for the treatment of multiple sclerosis and epilepsy, other standardized plant preparations have not been formally licensed, and prescribing guidance have not been established (this is due in October 2019).
In 2015, the Canadian government introduced new “marijuana for medical purposes” regulations, which allow physicians to authorize medical marijuana use for almost any health condition for which it may be considered beneficial. Supply is facilitated by licensed commercial producers. Consequently, physicians there can prescribe medically approved cannabinoids products for dementia.
Dementia is often thought of as a single disease or syndrome, but it’s actually a way of describing a group of symptoms that can have a number of different causes. Dementia refers to a decline in cognitive and behavioral ability that is severe enough to interfere with your daily life.
Dementia affects around 50 million people worldwide, or 5-8% of the general population aged over 60, including 850,000 people in the UK. Nearly 10 million people are diagnosed with dementia each year. As our population ages and people get older, dementia is only becoming more and more common. It is already one of the leading causes of disability worldwide. As a disease, it not only impacts the individual affected, but also the loved ones around them.
There are a few different types of dementia. Most of them are progressive, meaning that they get worse over time, but some types of dementia are reversible and can be cured with treatment.
The most common types of dementia are:
- Alzheimer’s disease occurs when beta-amyloid protein plaques and fibrous protein tangles build up in the brain, damaging healthy neurons. It’s estimated that 60-70% of people with dementia have Alzheimer’s disease or a combination of Alzheimer’s and another type.
- Vascular dementia occurs when the blood vessels that carry blood to your brain are damaged or occluded, leading to the death of brain cells.
- Lewy body disorder refers to abnormal protein clumps, called Lewy bodies, that are found in the brains of people with Lewy body dementia, Alzheimer’s, or Parkinson’s disease.
- Frontotemporal dementia is when the nerve cells in the frontal and temporal areas of the brain break down.
- Mixed dementia displays elements of the other types of dementias Most causes of dementia are mixed, usually a combination of Alzheimer’s and vascular dementia.
The exact symptoms of dementia can vary, depending on the type of dementia, but they all share certain main symptoms:
- Memory loss, particularly short-term memory
- Difficulty with communication and language, like forgetting common words
- Struggling to concentrate and focus
- Loss of judgement and reasoning
- Diminished visual perception
Some other symptoms of dementia include:
- Personality changes
- Inappropriate behavior
- Depression and anxiety
- Agitation and restlessness
People with dementia tend to have difficulty managing complex tasks, like finding a wallet and paying a bill, struggle to remember new faces, and find it hard to remember appointments. They often get confused in unfamiliar surroundings or when faced with a number of connected tasks, like planning and preparing a meal.
When to see a doctor
Many people struggle with memory loss as they get older, so some difficulty remembering things may just be normal aging and not necessarily dementia. But if someone you love has notable memory loss, together with a loss of thinking skills and any other of the main symptoms of dementia, it’s important to go to the doctor for an evaluation. Early evaluation makes it possible to treat any possible preventable causes of dementia and allows for treatments and therapies that make the most of the individual’s time before the disease progresses.
It’s difficult to diagnose dementia because many of the symptoms overlap with common medical issues. Along with taking a full medical history, carrying out a physical examination, and reviewing your symptoms, your doctor is likely to set a number of tests to identify which type of dementia you have. These include:
- Cognitive and memory tests and a neurological evaluation, to measure your loss of function and set a benchmark to track the progression of your dementia
- CT and MRI scans, to check for evidence of a stroke or bleeding within the brain, which could be the cause of your symptoms
- PET scans to look for amyloid protein deposits which are a hallmark of Alzheimer’s
- Blood tests for medical issues that could be affecting your brain function, like an underactive thyroid or vitamin B-12 deficiency
- Psychiatric evaluation for mental health issues that could be contributing to your symptoms
Sometimes, you’ll be referred to a neurologist or other specialist to diagnose which type of dementia you have.
Scientists know that dementia is caused by changes to the brain cells, but no one knows exactly what causes those changes. Although dementia becomes more common as you get older, some people can live 100 year without experiences symptoms of dementia. A significant amount of research is dedicated to both finding the cause and possible solutions for dementia.
There are some disorders that frequently lead to dementia, including:
- Huntington’s disease is caused by a genetic mutation. It makes nerve cells in your brain and spinal cord waste away, causing symptoms of dementia.
- Parkinson’s disease generally leads to symptoms of dementia.
- Traumatic brain injury (TBI), caused by repetitive or severe trauma to the brain, can cause symptoms of dementia, although these symptoms might not appear until several years after the injury.
- Creutzfeldt-Jakob disease is a rare brain disorder that also causes dementia symptoms.
Sometimes, symptoms of dementia can be caused by reversible factors and go away once the underlying cause is dealt with. These can include:
- Mood disorders such as anxiety and depression. As a matter of fact, severe depression is sometimes diagnosed as pseudodementia because the signs and symptoms overlap so much they can be indistinguishable.
- Side effects from your medication.
- Your body’s immune system attacking infections, or malfunctioning to attack nerve cells
- Unbalanced metabolism, like low blood sugar, too little or too much calcium and sodium. in the bloodstream, or an underactive thyroid.
- Vitamin deficiencies like a lack of B vitamins, copper, and thiamin.
- Subdural hematomas, or bleeding on the brain.
- Brain tumors.
- Environmental toxins like lead, pesticides, heavy alcohol use, or certain drugs
- Hypoxia, when your organs don’t get enough oxygen due to an asthma attack, heart attack, or carbon monoxide poisoning.
It’s not clear whether you can prevent yourself from developing dementia, but there are some ways to lower your risk:
- Exercise regularly
- A diet rich in vegetables and light on meat and dairy
- Avoid excessive alcohol intake
- Take steps to lower your blood pressure and cholesterol levels
- Avoid obesity and lose weight if needed
- Quit smoking
- Seek out to learn new things and maintain active social relationships
- Ensure healthy sleep and treat causes of poor sleep
If you have dementia, there’s no way to cure it or to stop it. Lifestyle changes as described above can potentially slow the progression. Prescription medications can help cope with it. Many people find that the right combination of medication, therapies, nutritional supplements, and lifestyle changes can slow down the progression of their dementia symptoms and extend their independence.
There are very few medications that treat dementia itself. The main options are:
- Cholinesterase inhibitors like donepezil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne) that slow down the progression of dementia. They are mainly used to treat Alzheimer’s disease.
- Menatine (Namenda) that regulates the activity of glutamate, which is involved in many brain processes.
Your doctor may also prescribe medications that treat some of the symptoms of dementia, like drugs to help against insomnia, depression, hallucinations, agitation, or parkinsonism.
Various behavioral and cognitive therapies can help reduce the impact of dementia:
- Occupational therapy teaches people with dementia how to cope better with their symptoms and avoid falls and injuries.
- Cognitive stimulation therapy (CST) is usually carried out as a group therapy to improve your problem-solving skills, language, and memory.
- Cognitive rehabilitation trains you to use other parts of your brain that are still working to compensate for the parts that have been damaged.
Various therapies like aromatherapy, music therapy, massage therapy, pet therapy, and art therapy can also help.
Although there’s no clear evidence, some people find that certain nutritional supplements and herbal remedies can help slow down dementia. These include curcumin (turmeric extract), ginkgo biloba, vitamin E, and omega-3 fish oils.
Changes to your lifestyle can go a long way to combatting the effects of dementia. These can include:
- Exercise, especially regimens like yoga and tai chi that strengthen muscles and improve balance and coordination.
- Diet, particularly the MIND diet which is rich in fiber, leafy green vegetables, whole grains, oily fish, and olive oil, and avoids fried foods, processed foods, red meat, and hydrogenated fat.
- Setting up rituals and habits, which are easier to remember and help to soothe agitation and paranoia.