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10th November 2022
Cannabidiol (CBD) given as a full-spectrum (i.e. containing all the components in the plant) solution, significantly reduced anxiety levels but also appeared to improve scores on several cognitive-related tests according to the results of a small, open-label study by US researchers.
A 2013 systematic review estimated that globally, anxiety disorders affect 7.3% of the population but can be as high as 10.4% in Euro/Anglo cultures. Whilst there are several effective anxiolytic therapies available, only about 60% of patients respond to those treatments to any significant degree and many have residual symptoms or remain treatment refractory.
Cannabidiol is the most abundant non-psychoactive component of cannabis and has received growing attention due to its anxiolytic and antidepressant properties, representing a promising new agent in the treatment of anxiety and mood disorders. For example, CBD has been found to be effective in patients with generalised social anxiety disorder although to date, only one randomised trial has been undertaken. In this trial, teenagers with social anxiety disorder, received either cannabis oil containing 300 mg of CBD or placebo every day for 4 weeks and saw significant reductions in anxiety.
Although cognitive functioning has rarely been examined in CBD studies, some evidence from studies of those using medical marijuana have found improvements in the multi-source interference test (MSIT), which is a measure of executive function and cognitive control. This finding is at variance to other evidence that suggests chronic, heavy recreational of marijuana use is related to cognitive decrements.
While previous research has examined the anxiolytic action of CBD, this is usually with a highly purified version. In the present study, the US researchers wondered about the anxiolytic effect of a full-spectrum product. The researchers speculated that CBD in its natural form would not only improve anxiety but might also help other related outcomes such as mood, sleep and quality of life.
Moreover, given the suggestion that use of medical marijuana appeared to improve cognition, this too was examined as a secondary outcome. Anxiety was assessing using the Beck Anxiety Inventory (BAI) and for which values > 16 represent at least moderate anxiety.
However, several other anxiety related measures were also included. Participants were required to be either cannabis naive or abstinent from regular use. The cannabidiol extract was homogenised into a solution and given as a 1 ml dose (containing 9.97 mg/ml of CBD) sublingually three times a day. Cognitive assessments included a battery of tests to assess executive function and memory.
cannabidiol and improvement in anxiety
A total of 14 participants with a mean age of 41.36 years (21.4% male) were enrolled. The mean BAI score was 20.29 and this reduced by 79.9% to a mean of 16.21 (p < 0.001) at week 4. In addition, there were significant reductions in all of the other anxiety measures after 4 weeks of treatment. Moreover, self-reported measures of mood, sleep and quality of life were also all significantly improved compared to baseline. Furthermore, the product was well tolerated with no serious adverse events noted.
In terms of cognition, there were also significant improvements in several of the measures assessed, in particular the MSIT which was significantly reduced compared to baseline (p < 0.006).
The authors concluded that the data supported both the efficacy and tolerability of a high cannabidiol product for anxiety and suggested that future clinical studies would focus on the cognitive impact of the formulation.
Citation
Dahlgren MK et al. Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial. Commun Med 2 2022.
19th July 2022
Noradrenergic drugs produce a small but significant improvement in global cognition and apathy in patients with Alzheimer’s disease(AD) with no important effects on any other measures according to the findings of a meta-analysis by UK researchers.
The World Health Organization (WHO) defines dementia as a syndrome in which there is deterioration in cognitive function beyond what might be expected from the usual consequences of biological ageing. WHO also estimates that worldwide in 2021, there were approximately 55 million people living with dementia and that AD, which is the most common form of dementia, may contribute to 60-70% of all cases.
The neurotransmitter noradrenaline is released by the locus coeruleus and has become recognised as a contributor to various aspects of cognition, including attention, behavioural flexibility, working memory, and long-term mnemonic processes. Furthermore, the locus coeruleus is one of the first sites of tau deposition in AD and with noradrenergic dysfunction being an early sign in patients with AD, it would seem logical to use noradrenergic drugs as a treatment for the disease.
Nevertheless, trials examining the value of noradrenergic drugs in AD have generally proved to be unsuccessful. Despite this, there has been no attempt to assess the overall impact of this drug class in AD which was the purpose of the present study.
The UK team performed a systemic review and meta-analysis to assess the degree to which drugs, whose principle action is as a noradrenergic agent, could improve the cognition and behavioural aspects of AD.
They searched for trials that included patients with AD in which noradrenergic drugs, that increased levels of noradrenaline, were compared against placebo and where the studies reported on cognitive and neuropsychiatric (e.g., agitation, apathy) changes. The outcomes of interest were changes in measure of both global cognition and neuropsychiatric symptoms.
Noradrenergic drugs and Alzheimer’s disease outcomes
The search identified a total of 19 trials with 1811 patients and all of the studies were prospective, randomised trials and with a treatment duration of between 2 and 52 weeks. The most commonly used noradrenergic drugs were noradrenaline re-uptake inhibitors, alpha1 adrenergic receptor antagonists, alpha2 receptor agonists, alpha2 receptor antagonists and beta adrenergic receptor blockers.
For global cognition, the overall pooled effect size was small but statistically significant in comparison to placebo (standardised mean difference, SMD = 0.14, 95% CI 0.03 – 0.25, p = 0.01). To provide some perspective for this effect, the authors included the SMD for cholinesterase inhibitors from studies in AD which was 0.38. Although noradrenergic drugs had a positive effect on semantic memory (SMD = 0.20), the drugs had no significant effect on any of the other cognitive measures.
For neuropsychiatric measures the only measure for which there was a significant effect was apathy with a pooled SMD of 0.45 (95% CI 0.16 – 0.73, p = 0.002).
The authors concluded that pharmacotherapies targeting the noradrenergic system appeared to improve both cognition and apathy. In addition, they suggested these data provided a strong case for further trials to examine the value of these drugs in AD and other neurodegenerative diseases.
Citation
David MCB et al. Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer’s disease: systematic review and meta-analysis J Neurol Neurosurg Psychiatry 2022
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