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The Journal Club: Opioids, chronic pain and titrating cannabinoids

Grow Pharma shares what to expect in the latest issue of the Journal Club.

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Grow Pharma launched the Journal Club to help educate UK doctors on the latest medical cannabis research. Here, Luca Marelli, shares a taste of what to expect in the latest issue.

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For this edition of the journal club, the focus is on opioids. Opioid analgesic overdose mortality continues to rise globally, driven by increases in prescribing for chronic pain. Several recent observational studies have reported reductions in opioid intake with medical cannabis [1], [2], raising the question of whether cannabis could help combat the opioid epidemic. 

A landmark 2014 investigation [3] found that state-level medical cannabis laws in the USA were associated with significantly lower state-level opioid overdose mortality rates. However, a subsequent study found this association to be spurious [4]. Hsu et al (2021) – the first study featured in this journal club – suggest that these inconsistent findings could be due to the focus up until now being on legalisation events rather than access to cannabis itself.

They argue that state legalisation does not always correlate with cannabis being widely available; for example, some states that legalised cannabis do not provide legal allowances for stores (‘dispensaries’) to sell cannabis. Additionally, even in states that have legalised sale of cannabis, there is often a significant time lag between legislation being passed and patients actually being able to access cannabis. 

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In their study, Hsu et al (2021) therefore examine the association between active cannabis dispensary operations (as a more direct measure of legal cannabis availability than state legalisation alone) and age-adjusted opioid related mortality rates at the USA county level over the period 2014-2018.

In total, 812 counties with medical and/or recreational cannabis dispensaries were included in the research. Overall, cannabis (medical and/or recreational) dispensary counts were associated with reduced opioid related mortality rates at the county level. A doubling of cannabis dispensaries was associated with a 17 per cent reduction in the age-adjusted mortality for all opioid types. This association was particularly strong for deaths associated with synthetic opioids (e.g fentanyl).

The second study included in this edition of the journal club is a practical recommendation by a panel of Canadian specialists on how to safely introduce and titrate cannabinoids, acting as a companion piece to the Bhaskar et al (2021) [5] consensus recommendation covered in the first edition of the journal club (published December 1st, 2021).

In addition, however, this recommendation also includes guidance on when and how to taper opioids in patients taking cannabis for chronic pain. The guideline suggests opioid tapering should be considered when either the cannabis dose has been optimised, the patient reports an improvement in function, or seeks less as-needed medication to control pain.

Importantly, it is emphasised that opioid tapering should not begin at cannabinoid initiation or at a pre-specified cannabinoid dose. When initiating tapering, a gradual opioid dose reduction of five to 10 per cent of the morphine equivalent dose (MED) every one to four weeks is recommended, with a goal of reducing it to < 90mg MED. The timeline for the frequency of dose reduction is broad to allow for patient tailoring.

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If you are a doctor and would like to discuss either of the clinical papers featured in this edition of the journal club or the broader medical cannabis literature, please reach out on [email protected]

 

References:
1 Piper.B et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep (2017). J Psychopharmacol 31(5):569-575
2 Lucas.P, Boyd.S, Milloy.M et al. Cannabis significantly reduces the use of prescription opioids and improves quality of life in authorised patients: results of a large prospective study (2021). Pain Med 22(3):727-739
3 Bachhuber.M, Saloner.B, Cunningham.C et al. Medical cannabis laws and opioid analgesic overdose mortality in the US, 1999-2010. (2014). JAMA Internal Medicine 174(10):1668-1673
4 Shover CL, Davis CS, Gordon SC, et al. Association between medical cannabis laws and opioid overdose mortality has reversed over time (2019). Proc Natl Acad Sci USA 116:12624-6.
5 Bhaskar.A, Bell.A, Boivin.M et al. Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process (2021). Journal of Cannabis Research 3:22

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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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