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Cannabis & Alzheimer’s/Dementia

Agitation, poor sleep, aggression, anxiety, and caregiver stress are all issues of Alzheimer’s and Dementia that put new challenges and strain on an aging population. Can cannabis help make life easier for a family suffering with an aging family member?

One thing that is important to mention early in this article is that Alzheimer’s Disease (AD) and dementia are different. AD is a type of dementia and a disease with no cure. Dementia is a syndrome and potentially reversible. A person with dementia does not always have AD. Dementia describes progressive diseases of the mind. Alzheimer’s is a specific type of dementia, a fatal disease that with time can affect all parts of the brain. The cause of AD is unknown, the cause of dementia is usually associated with physical brain trauma (disease, stroke, tumors, metabolic issues).

Alzheimer’s disease is a slow and painful diagnosis for both the patient and their loved ones. AD is the cause of 60-70% of cases of dementia [1,2]. AD usually starts with short term memory loss, difficulty handling money, losing things, and placing items in odd places. As the disease progresses, symptoms include language issues, disorientation, changes in mood and behavior and the loss of self care. Eventually, simple bodily functions can be lost that result in the need for around the clock care from family or paid caretakers. Watching as a loved one slowly loses their ability to to take part in family events or become aggravated when they cannot remember where the kitchen is located, becoming aggressive or physically striking out when they are confused or scared takes a physical, emotion and financial toll on family.

There are no medical treatments to stop or reverse AD. Most of the treatments available for AD are symptomatic, they help reduce the symptoms of the disease, but do not alter the progression. These treatments included antidepressants, antipsychotics, mood stabilizers, anti-anxiety or tranquilizers. Antipsychotics are usually the first medication prescribed, but this is not usually a great option as there is little benefit with serious side effects and an increased risk of early death [3,4]. With so little relief and heavy side effects, people have turned to cannabis as an option for potential symptomatic relief.

The focus on cannabis for AD is on neuropsychiatric symptoms. This includes appetite stimulation, insomnia, night agitation, and physical agitation/aggression during the day. For these specific symptoms, there are no animal models that allow for testing in a laboratory setting. There are physical animal models for AD and Dementia, but the experiments are measured by examining brain slices or other physical samples of the animals effected with AD post mortem. As a consequence most of the evidence used to help guide people with cannabis dosing for AD comes from human clinical trials. As of 2019, there are five published human clinical trials testing the effects of THC on patients with AD/Dementia, with two more clinical studies expected to be published in 2019 and 2020. These five studies are initial clinical trails, where you start with a small group of patients with moderate to severe AD.

Below are the five clinical studies in chronological order that have been published using cannabis to treat the neuropsychiatric symptoms of Alzheimer’s disease of dementia.

1.Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease.

In 1997, a human clinical trail was conducted on 15 human patients with Alzheimer’s disease. A common symptom of advanced Alzheimer’s is food refusal. The patient simply refuses to eat. This study was a double-blind placebo-controlled crossover design using Dronabinol on a fixed dose schedule. Dronabinol is synthetic THC that is available in the USA with a prescription from a medical doctor. In a double blind study, patients are equally divided in to two groups. One group will receive the medication being tested. One group will receive a blank version. Halfway though the study, the medication will be switched and the placebo group will receive the medication and the medication group will receive the placebo. During this time researches and patients will not know which group is receiving the medication or the placebo until the end of the trial. Patients received 2.5 mg Dronabinol or placebo in the morning and noon by capsule. During the 12 week Dronabinol treatment, patients gained an average of 7 pounds and caretakers noted a decline in disturbed behavior.

Food refusal and disturbed behavior in AD can be a major source of stress for families and caretakers. This touches on emotional and ethical issues in the care of AD family members. If they simply refuse to eat and act aggressively when food is presented, causing an altercation of anger and confusion from the patient and irritation from the care giver, do you simply stop feeding them to make life simpler? Or do you attempt to force the food down their throats just so they can get some form of nourishment that day? If there was a product that could give them “the munchies” and help keep them calm, care givers should know about the options available in the cannabis retail market.

https://www.ncbi.nlm.nih.gov/pubmed/9309469

2.Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia.

In 2006, an open-label human clinical trial was conducted on 6 human patients with dementia (5 with Alzheimer’s). An open-label study is different then a double-blind placebo controlled study. In an open-label study, both researchers and patients are aware of the medication and the dose being tested. Patients received 2.5mg of Dronabinol every night at 7PM for two weeks. Dronabinol is synthetic THC that is available in the USA with a prescription from a medical doctor. After two weeks of Dronabinol treatment, nocturnal motor activity was reduced by an average of 59% and reduction was noticed within the first two days of treatment. Further analysis showed a reduction in agitation, nighttime motor behaviors and appetite disturbances. Simply put, the patients slept better, were less anxious and consumed more food.

This was the first study to use objective measures to show that small doses of THC can be an effective treatment option for patients with severe dementia who suffer from behaviors and day to night rhythm disturbances. The late evening and bedtime can be very difficult for caretakers of AD patients. After the constant and exhausting work of helping to care for their loved one during that day, AD patients start to show more agitation and confusion in the evening hours and bed-time. This is commonly known as Sundowners syndrome and behaviors can include increased confusion, anxiety and aggression. This can also be a time of exhaustion and exasperation for the caretakers of AD, so there are cannabis options to help an AD patient sleep and not lash out during the difficult evening hours. Allowing the caretaker some much needed rest themselves.

https://www.ncbi.nlm.nih.gov/pubmed/16521031

3.Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. 

In 2014, 40 human patients were retroactively accessed using systematic chart review to access the effectiveness of Dronabinol for behavior and appetite disturbances. This was a study where researches went back to look over the medical charts of inpatient Geriatric Neuropsychiatry patients who were being prescribed Dronabinol by their medical doctors. This means that Dronabinol was already being prescribed by doctors in the Geriatric unit for behavior and appetite disturbances and researchers wanted to quantify the results in a clinical publication. The researchers noted that the addition of Dronabinol to patients’ existing treatments was associated with significant decreases in agitation. They also noted an increase in sleep duration and appetite, confirming the previously published data from 1997 and 2006.

This was an important study because it had an increase of participants, 40 human patients. This study also shows that many medical doctors were already prescribing Dronabinol for their AD patients and confirming the success of THC to help alleviate the symptoms of AD.

https://www.ncbi.nlm.nih.gov/pubmed/23597932

4.Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial.

In 2015, 50 human patients with dementia were administered THC to access the treatment of dementia-related neuropsychiatric symptoms. This study was a double-blind placebo-controlled crossover design using Dronabinol on a fixed dose schedule. Dronabinol is synthetic THC that is available in the USA with a prescription from a medical doctor. In a double blind study, patients are equally divided in to two groups. One group will receive the medication being tested. One group will receive a blank version. Halfway though the study, the medication will switch and the placebo group will receive the medication and the medication group will receive the placebo. During this time researches and patients will not know which group is receiving the medication or the placebo until the end of the trial. Patients received 1.5 mg Dronabinol or placebo three times daily for three weeks. During the 6 week treatment (3 weeks Dronabinol, 3 weeks placebo) patients showed no change in neuropsychiatric symptoms, but Dronabinol was well-tolerated. This adds valuable information for the use of THC in dementia; it did not make things worse or cause an adverse event. This means that for family or care givers of AD patients, trying low doses of THC is an option to see if can help their loved one without the fear of causing harm.

https://www.ncbi.nlm.nih.gov/pubmed/25972490

5.Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial.

In 2015, 22 human patients with dementia were administered THC to access the treatment of dementia-related neuropsychiatric symptoms. This study was a double-blind placebo-controlled repeated crossover design using Dronabinol on a fixed dose schedule. Dronabinol is synthetic THC that is available in the USA with a prescription from a medical doctor. In a double blind repeated crossover study, patients are equally divided in to two groups. One group will receive the medication being tested. One group will receive a blank version. Halfway though the study, the medication will switch and the placebo group will receive the medication and the medication group will receive the placebo. This is then repeated three more times with two different doses of THC. During this time researches will not know which group is receiving the medication or the placebo until the end of the trail. Patients received 0.75 mg Dronabinol or placebo twice daily for three days, followed by four days of placebo. This is then repeated with 1.5mg Dronabinol or placebo twice daily for three days, followed by four days of placebo. During the treatment (3 days Dronabinol, 4 days placebo) patients showed no change in neuropsychiatric symptoms, but Dronabinol was well-tolerated. This confirms the previous 2015 study for the use of THC in dementia; it did not make things worse or cause an adverse event. This means the for family or care givers of AD patients, trying THC combined with previously published studies is an option to see if can help their loved one. Most researchers agrees that both studies published in 2015 are using a Dronabinol dose that is too low to see an effect on behavior, but without these studies showing a low dose is well tolerated, future studies supporting higher doses of THC would not have gone forward.

I look forward to seeing the published results of clinical trails testing higher doses on more patients in 2019 and 2020!

https://www.ncbi.nlm.nih.gov/pubmed/26560511

Works Cited:
1.Burns A, Iliffe S (February 2009). “Alzheimer’s disease”. BMJ. 338: b158. doi:10.1136/bmj.b158. PMID 19196745.
2.”Dementia Fact sheet”. World Health Organization. 12 December 2017.
3.National Institute for Health and Clinical Excellence. “Low-dose antipsychotics in people with dementia”. National Institute for Health and Care Excellence (NICE). Archived from the original on 5 December 2014.
4.”Information for Healthcare Professionals: Conventional Antipsychotics”. US Food and Drug Administration. 16 June 2008.

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