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CBN discovery could lead to new treatments for Alzheimer’s, say researchers

A new study suggests CBN has the potential for treating age-related neurodegenerative diseases.

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CBN shows potential for Alzeimer's

More findings on the cannabinoid CBN could lead to the development of new treatments for neurodegenerative diseases such as Alzheimer’s and Parkinson’s, say researchers.

A new study by scientists at the Salk Institute in California, suggests CBN has the potential for treating age-related neurodegenerative diseases, like Alzheimer’s.

Derived from the cannabis plant, CBN is similar to THC, but is not psychoactive and is less heavily regulated by bodies such as the FDA. 

Previous research by senior author Pamela Maher, a research professor and head of Salk’s Cellular Neurobiology Laboratory, found that CBN had neuroprotective properties, but it wasn’t clear how it worked. 

Now, these new findings, published in the journal Free Radical Biology and Medicine, explain the mechanism through which CBN protects brain cells from damage and death.

“We’ve found that cannabinol protects neurons from oxidative stress and cell death, two of the major contributors to Alzheimer’s,” says Maher.

“This discovery could one day lead to the development of new therapeutics for treating this disease and other neurodegenerative disorders, like Parkinson’s disease.”

Maher’s team looked at the process of oxytosis, which is thought to occur in the ageing brain, and which growing evidence suggests may be a cause of Alzheimer’s disease. 

In the study, the scientists treated nerve cells with CBN, and then introduced an agent to stimulate oxidative damage.

They found that the CBN worked by protecting mitochondria, the cell’s powerhouses, within the neurons. In damaged cells, oxidation causes the mitochondria to curl up like donuts—a change that’s also been seen in ageing cells taken from the brains of people with Alzheimer’s disease. 

However, treating cells with CBN prevented the mitochondria from curling up and kept them functioning well.  

To confirm the interaction between CBN and mitochondria, researchers then replicated the experiment in nerve cells that had the mitochondria removed. In these cells, CBN no longer demonstrated its protective effect.

“We were able to directly show that maintenance of mitochondrial function was specifically required for the protective effects of the compound,” Maher said.

Potential for other diseases

In another key finding, researchers showed that CBN did not activate cannabinoid receptors, which are required for cannabinoids to produce a psychoactive response. Thus, CBN therapeutics would work without causing the individual to become “high.”

First author Zhibin Liang, a postdoctoral fellow in the Maher lab, said: “CBN is not a controlled substance like THC, the psychotropic compound in cannabis, and evidence has shown that CBN is safe in animals and humans. And because CBN works independently of cannabinoid receptors, CBN could also work in a wide variety of cells with ample therapeutic potential.”

In addition to Alzheimer’s, the findings have implications for other neurodegenerative diseases, such as Parkinson’s, which is also linked to glutathione loss.

“Mitochondrial dysfunction is implicated in changes in various tissues, not just in the brain and ageing, so the fact that this compound is able to maintain mitochondrial function suggests it could have more benefits beyond the context of Alzheimer’s disease,” Maher said.

She added that the study shows the need for further research into CBN and other lesser-studied cannabinoids.

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How THC and CBD work together in the brain – new study

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How THC and CBD work together in the brain – new study

New findings on how CBD and THC – the psychoactive compound in cannabis – affect the brain when administered together, could help to develop new cannabinoid therapeutics, scientists say.

A study has investigated the impact on the brain of CBD and THC, both as separate entities and when co-administered.

Researchers at University College London (UCL) analysed data from previous studies, including one which used functional Magnetic Resonance Imaging (fMRI) technology to measure brain activity in participants taking CBD and THC.

For the first time, they explored the response of the striatum region of the brain – a major part of the motor and reward systems. This is a critical component of numerous aspects of cognition, including motor and action planning, decision-making and motivation.

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One study compared inhaled cannabis containing 8 mg THC, 8 mg THC + 10 mg CBD and a placebo. It showed strong disruptive effects of both THC and THC + CBD on connectivity in the associative and sensorimotor networks.

However it also identified a “specific effect of THC” in the limbic striatum network which was not present in the THC + CBD condition.

In a second study, testing oral 600 mg CBD versus placebo, CBD increased connectivity in the associative network, but produced only relatively minor disruptions in the limbic and sensorimotor networks.

The study concludes that THC “strongly disrupts striato-cortical networks” but that this effect is mitigated by the co-administration of CBD.

It states: “Oral CBD administered has a more complex effect profile of relative increases and decreases in connectivity.

“The insula [part of the brain implemented in diverse functions including emotions and self-awareness] emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis-related disorders, and the development of cannabinoid therapeutics.”

This is the first report in human subjects of data from THC, THC + CBD and CBD use achieved “using a unified set of analysis methods, and with all comparisons performed in a placebo-controlled, double-blind design”.

Read the full report here.

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Five new cannabis studies to have on your radar

The latest scientific papers exploring cannabis and its impact on health and society.

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Five new cannabis studies to have on your radar

Get up to date with the latest cannabis-related research from across the globe.

Over the past few weeks, we’ve seen papers published around inaccurate labelling, the effects of cannabis on Covid-19, the impact of legalisation in Uruguay and how cannabis users might require more sedation during medical procedures.

Read on for five significant studies to dive into.

Lower Covid-19 severity among cannabis users

A recent study has discovered an association between lower Covid-19 severity and cannabis use among hospitalised patients.

The researchers aimed to assess whether current cannabis users hospitalised for Covid-19 had different outcomes compared to non-users through a retrospective analysis of 1,831 patients admitted to UCLA Medical Centre in California.

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Analysis of the data found that cannabis users had significantly better outcomes compared to non-users, shorter hospitalisation, lower ICU admission rates and less need for mechanical ventilation.

Interestingly, the researchers also found that active users had lower levels of inflammatory markers upon admission than non-users.

The authors of the study concluded: “This retrospective cohort study suggests that active marijuana users hospitalised with COVID-19 had better clinical outcomes compared with non-users. However, our results need to be interpreted with caution given the limitations of a retrospective analysis.

“Prospective and observational studies will better help elucidate the effects of marijuana use in COVID-19 patients.”

Cannabis users require more sedation for endoscopy

According to new research, patients who use cannabis required higher levels of sedation during gastric endoscopies than non-users.

As cannabis is legalised in more places and usage continues to rise, researchers in Canada said clinicians should be aware of patients’ cannabis consumption and prepare themselves for increased sedation and the risks that come with it.

The authors of the study conducted a prospective cohort study of 419 adult outpatients undergoing endoscopic procedures at three Canadian centres. Procedures were conducted under conscious sedation, which leaves the patient relaxed and comfortable but partially conscious during the procedure.

Cannabis use was associated with increased odds of requiring higher total sedation during gastroscopy, an endoscopic procedure that begins with the insertion of a tube and camera through the throat.

Legalisation not associated with increased cannabis use among young people

A recent study from researchers in Uruguay found that the use of cannabis following legalisation decreased among teenagers.

Uruguay was the first country in the world to legalise and regulate recreational cannabis. Since legalising the drug in 2016, the country is now regarded as a pioneer, paving the way for other countries like Canada, Mexico and Malta.

Using data from cross-sectional surveys of secondary students in Uruguay and Chile, the study evaluated changes in the prevalence of past-year, past-month and any risky and frequent cannabis use following the enactment and implementation of cannabis legalisation

“The legalisation of recreational cannabis in Uruguay was not associated with overall increases in either past-year/past-month cannabis use or with multi-year changes in any risky and frequent cannabis use among young people,” the authors stated in the paper’s abstract.

Current cannabis labelling system “doesn’t tell you much”

Labels like indica, sativa and hybrid—commonly used to distinguish one category of cannabis from another—tell consumers little about what’s in their product and could be confusing or misleading, suggests a new study of nearly 90,000 samples across six states in America.

Published on 19 May in the journal PLOS One, the research constitutes the largest analysis to date of the chemical composition of cannabis products.

It finds that commercial labels “do not consistently align with the observed chemical diversity” of the product. The authors are now calling for a “weed labelling system” akin to the Food and Drug Administration’s “nutrition facts panel” for food.

“Our findings suggest that the prevailing labelling system is not an effective or safe way to provide information about these products,” said co-author Brian Keegan, an assistant professor of Information Science at CU Boulder.

“This is a real challenge for an industry that is trying to professionalise itself.”

Cannabis dependence treatment is effective in tackling common co-morbidities

Earlier this month, Australian researchers released a paper looking into the effectiveness of cannabis dependency treatment on common co-morbidities, including mood, sleep and pain problems.

The researchers found that the treatment helped decrease anxiety, stress and sleep disturbance among the cohort of 128 cannabis-dependent participants.

The analysis used data from a 12-week double-blind placebo-controlled trial testing the effectiveness of the cannabis-based medicine nabiximols against placebo in reducing illicit cannabis use.

The researchers found that there was “no evidence” that nabiximols treatment is a barrier to reducing co-morbid symptoms. In fact, they found that the treatment reduced illicit cannabis use and improved comorbidity symptoms, even when participants were not able to achieve abstinence.

 

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Research finds cannabis consumers may require more sedation

Consumers required higher levels of sedation during endoscopic procedures than non-users

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Research finds cannabis consumers may require more sedation

Experts have highlighted the need for doctors to be more aware of their patients cannabis use, as research suggests consumers may require higher levels of sedation.

As cannabis is legalised in more places and usage continues to rise, researchers in Canada said clinicians should be aware of patients’ cannabis consumption, and prepare themselves for increased sedation and the risks that come with it.

It comes as a new study has associated cannabinoid use with increased odds of requiring higher total sedation during gastric endoscopies – a procedure that begins with the insertion of a tube and camera through the throat – than non-users.

The authors of the study conducted a prospective cohort study of 419 adult outpatients undergoing endoscopic procedures at three Canadian centres.

Procedures were conducted under conscious sedation, which leaves the patient relaxed and comfortable but partially conscious during the procedure.

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Researchers did not examine its impact on propofol sedation, which is more commonly used in the UK and US so more research would be needed to determine the wider impact of cannabis use on sedation.

“Patients didn’t have increased awareness or discomfort during procedures, but they did require more drugs,” said Yasmin Nasser, MD, PhD, lead researcher on the study and assistant professor at Snyder Institute for Chronic Diseases at the University of Calgary.

Each patient completed two questionnaires, one before the procedure about their cannabis use and another afterwards, indicating their awareness and comfort level during the procedure. The questionnaires were analysed along with details about the use of the sedatives midazolam, fentanyl and diphenhydramine during the procedure.

Cannabis use was associated with increased odds of requiring higher total sedation—defined as more than 5 mg of midazolam, or more than 100 mcg of fentanyl, or the need for diphenhydramine.

Interestingly, cannabis use was not associated with higher use of sedation during colonoscopy. Researchers said this could be because gastroscopy generally requires more sedation than colonoscopy due to the irritation caused in the upper part of the gastrointestinal tract.

Cannabinoid use was not independently associated with fentanyl use or adverse events, nor was it associated with intra-procedural awareness or discomfort, the authors found.

This study looked at whether patients were users or non-users of cannabis, but did not examine the timing, quantity or route of cannabis intake prior to the procedure. Researchers say these variables could be the basis for future studies.

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