Agitation, sleep disturbances, and other neuropsychiatric symptoms of Alzheimer’s Disease are challenging to treat. Could THC play a role?
Alzheimer’s Disease in our society is a lot like a slow motion train crash. We know it’s coming, but so far we have been powerless to stop it. It is the most common cause of dementia and has very limited treatment options. It affects nearly 50 million people worldwide and it’s prevalence is growing with our aging population. It progresses slowly, with patients often needing care for many years as their memories and ability to care for themselves fade. This taxes both the mental health of family and caregivers, but also our entire healthcare system with costs expected to be in the hundreds of billions. One experimental treatment after another has failed, proving this will be one of the most challenging diseases to treat for the foreseeable future.
So why is the US government slowing down research into using cannabinoids to help Alzheimer’s patients? Stop and read this article: Marijuana could hold the key to treating Alzheimer’s, but drug laws stand in the way, says scientists. A long bureaucratic delay to get approval from the DEA just to do studies in mice is unacceptable.
Now let’s turn to the science…what has been discovered about cannabinoids and Alzheimer’s?
- Part I (below): Could cannabinoids help treat certain Alzheimer’s symptoms?
- Part II: Could cannabinoids help slow down disease progression?
Alzheimer’s Disease & Neuropsychiatric Symptoms
Alzheimer’s is a neurodegenerative disease characterized by cognitive decline and memory impairments. It is progressive, meaning that it gets gradually worse over time. It can be categorized into several stages:
- Mild: Some cognitive deficits, although patients are still highly functional
- Moderate: Deficits are manifested in every day activities
- Severe: Significant dementia requiring around the clock care.
One significant component of Alzheimer’s is neuropsychiatric symptoms. These can be disabling and lead to greater caregiver stress. These symptoms include:
- Agitation & aggression
- Delusions & hallucinations
- Depression & apathy
- Sleep disturbances
Current Treatment for Alzheimer’s
Alzheimer’s treatments fit into one of two categories:
- Symptomatic = Help reduce symptoms of the disease without changing the rate of disease progression
- Disease modifying = Actually slows the rate of disease progression (or if we are to be optimistic, even stops it)
Current treatment options are extremely limited and they are only symptomatic. Several high-profile attempts at disease modifying drugs failed to show efficacy in late-phase clinical trials. However, even just providing additional symptomatic relief would be tremendously valuable.
There are several treatments available for the neuropsychiatric symptoms listed above:
- Mood stabilizers
However, these do not always work and some (especially the antipsychotics) can have serious side effects. New options are needed and so cannabinoids have been studied as a potential treatment.
Treating Neuropsychiatric Symptoms of Alzheimer’s with Cannabinoids
Cannabinoids have been tested for treating several neuropsychiatric symptoms, including agitation, sleep disturbances, and reduced eating, There are no animal models for many of these symptoms, and yet they can be assessed in a relatively short human study. For this reason, most of the evidence we have comes directly from human studies.
Below are 5 clinical studies that have been published on using cannabinoids (mostly THC) to treat the neuropsychiatric symptoms of Alzheimer’s or dementia.
- Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease.This 1997 placebo-controlled crossover study assessed dronabinol in 15 Alzheimer’s patients who were refusing food. During the dronabinol treatment period, patients gained more weight and had decreased severity of disturbed behavior. Adverse events occurred more commonly during dronabinol treatment, but they did not require discontinuation.
- Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia.This 2006 open-label pilot study assessed nighttime agitation in 6 patients with dementia (including 5 with Alzheimer’s) treated with 2.5 mg dronabinol for 2 weeks. Dronabinol led to reduction in nocturnal motor activity and improved neuropsychiatric symptoms.
- Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. This 2014 study was based on a retrospective systematic chart review of 40 patients diagnosed with dementia and treated with dronabinol. The addition of dronabinol to patients’ treatment regimens was associated with significant improvements in agitation, sleep and eating.
- Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial.This 2015 study examined neuropsychiatric symptoms using a randomized, double-blind, placebo-controlled design. 50 patients were randomized to receive placebo or 1.5 mg dronabinol 3 times daily for 3 weeks. Dronabinol did not differentiate from placebo, but the low-dose THC treatment was well tolerated.
- Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial.This 2015 study also assessed neuropsychiatric symptoms using a randomized, blinded, crossover design. 22 patients received, 0.75 mg twice daily, 1.5 mg twice daily, and placebo for 3 days at a time. Neither dose differentiated from placebo, but both THC doses were well tolerated.
These studies provide some preliminary evidence of the utility of THC to treat certain neuropsychiatric symptoms. However, the two largest controlled studies did not show much effect. One reason for this may be that the doses used were simply too low. At least one ongoing study (described below) is testing higher doses.
Ongoing and Future Studies of the Neuropsychiatric Symptoms of Alzheimer’s
There are two ongoing trials of synthetic THC in Alzheimer’s (based on the clinicaltrials.gov database). The primary purpose of these studies is to assess the symptom of agitation. To show you the need for better treatments of this symptom, I’ll quote from the first study below:
Severe agitation is important to treat because it not only increases progression of AD and physical health problems (increased falls and weight loss), but it also decreases quality of life and increases caregiver stress. Currently prescribed treatments (i.e., antipsychotics) for agitation in AD do not work in everybody and when they do work the effect is small and they increase the risk of harmful side effects, including death.
Here are brief descriptions of these two ongoing studies:
This is a randomized, blinded, crossover study assessing placebo against THC (the actual dose wasn’t clear) for 6 weeks each in a total of 40 patients. The study will complete in late 2017.
This is a randomized, blinded, parallel group study of placebo versus THC in a total of 160 patients. The dose will start at 2.5 mg THC twice daily for the first week and then increase to 5 mg twice daily. The study started in early 2017 and is expected to complete in 2020.
I’m looking forward to seeing the results of these studies when they are available. However, there will still be some missing pieces.
One thing that I’m surprised about is the lack of studies on CBD. Antipsychotics have shown some efficacy, but with concerning side effects in this patient population. Anxiolytics can also be helpful. CBD has both antipsychotic and anxiolytic properties, but with better tolerability relative to most antipsychotics. CBD alone or in combination with THC should be considered for future studies of the neuropsychiatric symptoms of Alzheimer’s Disease.
Stay tuned for Part II, where I will look at evidence that cannabinoids could slow disease progression. This area has much more potential, but is also much harder to study.
[Featured image: Pixabay]
Last modified: September 17, 2017