“Cannabis pills ‘do not help dementia sufferers’,” reports The Daily Telegraph.
Previous research suggested one of the active ingredients in cannabis – tetrahydrocannabinol (THC) – can have effects on the nervous system and brain, such as promoting feelings of relaxation.
In this study, researchers wanted to see if THC could help relieve some of the behavioural symptoms of dementia, such as mood swings and aggression.
They set up a small trial involving 50 dementia patients with behavioural symptoms. They found taking a pill containing a low dose of THC for three weeks did not reduce symptoms any more than a dummy pill. Other studies suggested the substance might have benefits, but these studies were not as well designed as this trial.
The study was small, which reduces its ability to detect differences between groups. But the trend was for a greater reduction of symptoms in the placebo group than the THC group, suggesting that THC would not be expected to be better, even with a larger group.
People taking the THC pills did not show more of the typical side effects expected, such as sleepiness or dizziness. This led researchers to suggest the dose of THC may need to be higher to be effective. Further studies would be needed to determine whether a higher dose would be effective, safe and tolerable.
Where did the story come from?
The study was carried out by researchers from Radboud University Medical Center and other research centres in the Netherlands and the US.
It was funded by the European Regional Development Fund and the Province of Gelderland in the Netherlands. The study drug was provided by Echo Pharmaceuticals, but they did not provide any other funding or have any role in performing the study.
The study was published in the peer-reviewed medical journal, Neurology.
The Daily Telegraph covered this story well.
What kind of research was this?
This was a randomised controlled trial (RCT) looking at the effects of tetrahydrocannabinol (THC), one of the active ingredients in cannabis, on neuropsychiatric symptoms in people with dementia.
This was a phase II trial, meaning it is a small-scale test in people with the condition. It aims to check safety and get an early indication of whether the drug has an effect.
The researchers say they had also carried out a similar trial with a lower dose of THC (3mg daily), which did not have an effect, so they increased the dose in this trial to 4.5mg daily.
People with dementia often have neuropsychiatric symptoms, such as being agitated or aggressive, delusions, anxiety, or wandering.
The researchers report that existing drug treatments for dementia have a delicate balance of benefits and harms, and non-drug treatments are therefore preferred, but they have limited evidence of effectiveness and may be difficult to put into practice.
An RCT is the best way to assess the effects of a treatment. Randomisation is used to create well-balanced groups, so the treatment is the only difference between them. This means any differences in outcome can be attributed to the treatment itself and not to other confounding factors.
What did the research involve?
The researchers enrolled 50 people with dementia and neuropsychiatric symptoms. They randomly assigned them to take either a THC pill or an identical-looking inactive placebo pill for three weeks. They assessed symptoms over that time and looked at whether these differed in the two groups.
The trial initially intended to assess people who also had pain, but the researchers could not find enough people with both symptoms to participate, so they focused on neuropsychiatric symptoms. It also intended to recruit 130 people, but did not reach this number because of delays in getting approval for the trial in some centres.
About two-thirds (68%) of the participants had Alzheimer’s disease and the rest had vascular dementia or mixed dementia. They all had experienced neuropsychiatric symptoms for at least a month. Both groups were taking similar neuropsychiatric drugs, including benzodiazepines, and continued to take these drugs during the study period.
People with a major psychiatric disorder or severe aggressive behaviour were excluded. Just over half (52%) lived in a special dementia unit or nursing home. The participants were aged about 78 years on average.
The pills contained 1.5mg of THC (or none in the case of placebo) and were taken three times a day for three weeks. Neither the participants nor the researchers assessing them knew which pills they were taking, which stops them influencing the results.
The researchers assessed the participants’ symptoms at the start of the study, two weeks later, and then at the end of the study. They used a standard questionnaire, which asked the caregiver about symptoms in 12 areas, including agitation or aggression and unusual movement behaviour, such as pacing, fidgeting or repeating actions such as opening and closing drawers.
The researchers used a second method to measure agitated behaviour and aggression, and also measured quality of life and the participants’ ability to carry out daily activities. They also assessed whether the participants experienced any side effects from treatment. The researchers then compared the results of the two groups.
What were the basic results?
Three participants did not complete the study: one in each group stopped treatment because they experienced side effects, and one in the placebo withdrew their consent for taking part.
Both the placebo and the THC pill groups had a reduction in neuropsychiatric symptoms during the trial. There was no difference in the reduction between the groups. The groups also did not differ in a separate measure of agitation and anxiety, quality of life, or ability to carry out daily activities.
Two-thirds of people (66.7%) taking THC experienced at least one side effect, and over half of those taking placebo (53.8%). The sorts of side effects that have been previously reported with THC, such as sleepiness, dizziness and falls, were actually more common with placebo.
How did the researchers interpret the results?
The researchers concluded they found no benefit of 4.5mg oral THC for neuropsychiatric symptoms in people with dementia after three weeks of treatment.
They suggested the dose of THC used may be too low because the participants did not experience the expected side effects of THC, such as sleepiness.
This small phase II trial has found no benefit of taking THC pills (4.5mg a day) for neuropsychiatric symptoms in people with dementia in the short term.
The authors say this contrasts with previous studies, which have found some benefit. However, they note the previous studies were also limited in that they were even smaller, did not have control groups, or did not collect data prospectively.
The study was small, which reduces its ability to detect differences between groups. However, the non-significant trend was for a greater reduction of symptoms in the placebo group than the THC group.
The researchers note the improvement in the placebo group was “striking” and may be the result of factors such as the attention and support received from the study team, expectations of the participants on the effects of THC leading to perceived improvement, and training of the nursing personnel in the study.
While the authors suggest the dose of THC may need to be higher, further studies are needed to determine whether a higher dose would be effective and safe.