As recent studies show conflicting findings about the effects of THC on cardiovascular health, it’s vital to look at the detail, says expert.
A study led by researchers at Stanford University recently concluded that THC – the psychoactive compound found in cannabis – causes inflammation in cells that line the blood vessels and thickening of the arteries (atherosclerosis). This could later lead to heart disease and heart attack, researchers said.
But research into the effects of cannabis on cardiovascular health has been mixed, with some papers finding THC actually offers a protective effect on the heart.
One study published in April this year, for example, produced results that contradicted the Stanford findings.
The study of laboratory rats, published in Frontiers in Bioscience-Landmark, found that THC acted as a cardioprotective by improving the metabolic activity of cells in the heart, decreasing cell damage and restoring heart mechanical function.
The conflicting reports highlight the need to weigh up the evidence and “look at the detail” when it comes to scientific studies, says neurologist and chair of the Medical Cannabis Clinicians Society and the Cannabis Industry Council, Professor Mike Barnes.
Increased risk of heart disease?
Although scientists in the first study found that THC has a “significantly adverse effect on the cardiovascular system”, the study also showed that inflammation and atherosclerosis could be “blocked” by a small molecule called genistein found naturally in soy and fava beans.
“As more states legalise the recreational use of marijuana, users need to be aware that it could have cardiovascular side effects,” said Joseph Wu, MD, PhD, professor of cardiovascular medicine and of radiology, and the director of the Stanford Cardiovascular Institute.
“But genistein works quite well to mitigate marijuana-induced damage of the endothelial vessels without blocking the effects marijuana has on the central nervous system, and it could be a way for medical marijuana users to protect themselves from a cardiovascular standpoint.”
The researchers used genetic and medical data sourced from UK Biobank to analyse roughly 500,000 people aged between 40 and 69.
Of these, nearly 35,000 participants reported smoking cannabis, with 11,000 smoking more than once a month. The Stanford scientists found that the latter were “significantly” more likely than others in the study to have a heart attack. The researchers also found that frequent smokers were more likely than non-users to have their first heart attack before the age of 50.
In an effort to find a potential antidote to the inflammation and atherosclerosis reportedly caused by THC, the scientists turned to the endocannabinoid system, a complex network of neurotransmitters and receptors. The two most important receptors are referred to as CB1 and CB2.
Using machine learning techniques, the researchers scanned a large database of protein structures to find a molecule that binds to the body’s CB1 receptor hence blocking THC’s inflammatory and atherosclerotic properties.
What they came up with was a molecule called genistein, which is naturally found in soybeans. The molecule binds to CB1, blocking the drug’s harmful effects without inhibiting the psychoactive effects of THC.
“We didn’t see any blocking of the normal painkilling or sedating effects of THC in the mice that contribute to marijuana’s potentially useful medicinal properties,” said instructor of medicine, Mark Chandy, MD, PhD.
“Genistein is potentially a safer drug than previous CB1 antagonists. It is already used as a nutritional supplement and 99% of it stays outside the brain, so it shouldn’t cause these particular adverse side effects.”
Mike Barnes, chair of the Cannabis Industry Council said that people “should not take this sort of publication seriously without looking at the detail”.
Referring to Stanford University’s reliance on data from the UK, Barnes said: “The big problem here is that in the UK and most of Europe smoking a joint normally means smoking a mixture of tobacco and cannabis. And we know tobacco, of course, is harmful to the heart and circulation.
“Thus, the fact that joint smokers have more heart problems in the UK does not mean that cannabis causes it. It could easily be, and probably is, the tobacco effect.
“Remember that smoking is illegal in the UK and not the way cannabis under prescription is taken. Vaping is much safer as the temperatures are lower.”
A protective effect?
The second study aimed to test whether THC may be protective in the treatment of cardiovascular dysfunction following ischemia-reperfusion injury, the damage caused when blood supply returns to tissue, following a period of ischemia or lack of oxygen.
Results from the animal study, conducted on rat hearts, showed that THC protected the heart, evidenced by the improved recovery of cardiac function.
The authors concluded: “THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of THC as a cardioprotective drug to be, administered before onset of I/R [ischemia-reperfusion] protocol.”
Professor Barnes cautioned: “Many papers show a protective effect of most cannabinoids on the heart, although having said I would avoid prescribing cannabis within three months of a heart attack or stroke or in anyone who would not benefit from an increased heart rate which occurs with THC.”
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.
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.
Five new cannabis studies to have on your radar
The latest scientific papers exploring cannabis and its impact on health and society.
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
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.
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.
Research finds cannabis consumers may require more sedation
Consumers required higher levels of sedation during endoscopic procedures than non-users
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.
“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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