Greetings from the surface of the sun,

Or what others might call my living room. The UK is in the grip of a heatwave, having recorded its hottest day of 2021 (31.6°C). And though hot temperatures are not what I’d consider ideal working conditions, the rising mercury is proving more productive for other portions of the industry – namely, growers.

This report, pertaining to one Bill Bilton, owner of Dunesberry Farms in Canada, makes the case for heatwaves supercharging cannabis growth. In what I can only presume was a bid to make our 31.6°C look positively paltry, British Columbia reported a record 49.5°C (121.1°F) for three days in a row in June. 

According to meteorologists, the unprecedented conditions are caused by a “heat dome” (the unofficial term given to hot air high up in the atmosphere that lingers over an area for a prolonged period of time, trapping heat below) over western Canada and parts of the US Pacific northwest.

It was so hot, mussels were literally cooking in their shells as they washed up on the beach. But Bill, who owns Kamloops’ only outdoor cannabis farm, believes his new crop has flourished as a result of the extreme heat. He estimates that plants in his most recent crop, planted just one month ago, have grown over one foot in the 10 days since the heatwave began – in part due to the smoke from distant wildfires. 

Whether you agree with Bill or not, it is hard to read the article without having a hard think about crop security in our increasingly volatile climate. When does a good thing become too much? And what will these rising temperatures mean for outdoor growers in the years to come?

Let me know at phoebe.harkin@texerepublishing.com. 

Stay cool,

Phoebe, The Cannabis Curator

Youth, use, and misuse 

Suicide accounts for approximately six percent of all adolescent deaths worldwide, making it the second leading cause of death among youths between 10 to 24 years old. Substance use is a significant risk factor for suicide and though high-risk substance use behaviors have declined since 2009, nearly one in every seven adolescents still report drug use and misuse. In this study, researchers set out to determine the demographic predictors of suicidal behaviors and associations between substance use disorders (SUD) and hospitalization for suicidal behaviors. They found that though cannabis was the most prevalent comorbid SUD among suicidal inpatients (15.3 percent), it had a statistically non-significant association with suicidal behaviors (OR 0.98; 95% CI 0.95-0.99), supporting a recent review reporting a lack of consistent evidence linking acute cannabis use to increased risk for suicidality. Perhaps unsurprisingly, alcohol use disorders were found to significantly increase odds of suicidal behaviors, with inpatients at 18 percent higher odds of hospitalization for self-harm. They theorized that alcohol could induce acute aggression and impulsivity, leading to increased suicidal behaviors in the short-term, and to biological changes and negative psychosocial events that could influence these behaviors in the long-term. 

When drugs collide 

Widespread legalization has seen the use of medicinal cannabis increase exponentially and, with it, the risk of clinically significant drug-drug interactions (DDIs). DDIs can result in serious adverse events, specifically those affecting CYP-mediated drug metabolism. But what is the likelihood of clinically significant DDIs between cannabis-based therapies and conventional medications? Researchers used supersomes to screen the inhibitory potential of cannabinoids in vitro, evaluating twelve cannabinoids at the predominant drug-metabolizing isoforms: CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2B6, and CYP2C19. The cannabinoids exhibited varied effects and potencies across the CYP isoforms. While most inhibited CYP2C19, CYP2D6, CYP3A4, and CYP2B6 were either not affected or only partially inhibited by the cannabinoids. 

We spoke to Lyndsey Anderson, Research Fellow at the Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Australia, to find out more. 

What exactly is a supersome and why did you choose it as a model?

“Supersomes are microsomal vesicles that contain a single CYP450 enzyme isoform. Human liver microsomes are rich in CYP450 enzymes and can also be used in drug metabolism and drug interaction studies. However, human liver microsomes contain a mix of drug metabolizing enzymes that can have broad genetic variability. We used Supersomes so that we could investigate the effects of the cannabinoids on drug metabolism by each CYP450 enzyme individually.”

How common are negative interactions between cannabinoids and approved drugs? 

“The most well-known drug interaction between cannabinoids and approved medications is the interaction between cannabidiol (CBD) and clobazam – a first line treatment for the severe childhood epilepsy Dravet Syndrome. Significant drug-drug interactions have been reported between either CBD or cannabis and anticonvulsants, anticoagulants, anti-platelet medications, antipsychotics, and immunosuppressants. These interactions have been attributed to interactions at CYP450 enzymes and are associated with an increased incidence of adverse events.”

What problems does it cause for patients and in what indications are they most prevalent?

“Drug-drug interactions at CYP450 enzymes can have significant implications for patients, especially in those treated with drugs that have a narrow therapeutic window. In our study, we found that most of the cannabinoids inhibit CYP2C9 and CYP2C19, which together metabolize nearly 25 percent of approved drugs. Noteworthy drugs metabolized by these isoforms with narrow therapeutic windows include warfarin, clopidogrel, phenytoin, amitriptyline, and sulfonylureas. Drug-drug interactions that alter the metabolism of these drugs can result in plasma concentrations outside the normal therapeutic range and lead to serious adverse events. Therapeutic drug monitoring and subsequent dose alterations may be warranted for CYP2C9 and CYP2C19 substrates.”

Who are you?

Kevin Crombie
 

Where do you work?

Postdoctoral Research Associate in the Department of Pharmacology and Toxicology, University of Wisconsin-Madison, USA
 

What are you working on?

My team currently has several ongoing projects examining the role of exercise as part of a comprehensive treatment plan for individuals with post-traumatic stress disorder (PTSD). Specifically, we are currently using computational modeling and neuroimaging approaches to examine whether moderate-intensity aerobic exercise performed shortly after fear extinction training (a lab-based model of commonly administered exposure-based therapies) improves memory consolidation and prevents the return of fear in women with PTSD.

We recently finished some pilot studies that provide preliminary evidence in support of this notion, but we now want to take a deeper dive. In addition to exercise, we are also examining pharmacological manipulations to the endocannabinoid system as a potential method for enhancing extinction learning, which may improve our targeting of the endocannabinoid system and, ultimately, increase the efficacy of exposure-based therapies.

Research + Medicine

Study finds chronic augmentation of endocannabinoid levels increases dopaminergic encoding of reward cost and motivation, providing critical insight into neurobiological mechanisms of motivational deficits. Link 

Fascinating research uncovers apparent link between chronic pain and depression, attributing condition to dynamic change of endocannabinoid signaling in the medial prefrontal cortex. Link

Cannabis is associated with improved bladder symptoms in survey of multiple sclerosis patients, with consumption leading to reported two-fold improvement in urinary frequency and urgency. Link

Cannabinoquinones 101: study summarizes the biological profile and clinical potential of aminocannabinoquinone VCE-004.8, compound with orphan drug status by EMA and FDA . Link 

Testing + Processing

MediPharm Labs receives milestone GMP pharmaceutical drug establishment licence; North America’s first domestic licence for cannabis-related manufacturing. Link 

Business + Regulation

Canadian producers destroyed over 500 tons of cannabis since 2018; clogged sales channels, low-quality production, and producers stockpiling for launch of edibles and extracts all cited as reasons. Link

US Senators unveil bill to federally legalize cannabis; “to provide for reinvestment in certain persons adversely impacted by the War on Drugs, to provide for expungement of certain cannabis offenses.” Link

Colorado signs cross-pollination law, providing potential roadmap for state’s emerging industrial hemp and marijuana industries (including proposing several-mile buffer zones between hemp and cannabis.) Link

Bitcoin for cannabis 

Get your wallets out – the CanCoin is (almost) here. The digital cannabis token is the brainchild of European crowdfunding expert and CEO of Technicorum Holdings, Daniel Daboczy, and co-founders of cannabis investment company Enexis, David Bonnier and Amaury de Poret. Their aim is simple: to solve market friction and monetization in the European cannabis market. How? By providing an antidote to pain points in the current system: namely, lack of transparency, poor supply chain tracking, mistrust in monitoring systems for both products and patients, and reluctance on the part of financial institutions to handle cannabis transactions. CanCoin uses blockchain to streamline payments and processing, management of inventory and medical cannabis cards, patient monitoring, and tracking from seed to shelf. It will also introduce NFTs (whatever the cannabis equivalent of Jack Dorsey’s first-ever tweet is) and DeFi into the ecosystem. It will come in two variants; the first tethered to an established currency, such as the dollar; the second being allowed to free float. The first of the 420 million coins to launch on Crypto exchanges on August 22, 2021, will be non-tethered, with tethered to follow later. “The European cannabis market has fallen far behind North America, which has demonstrated how cannabis tax revenues and profits can create more opportunity,” said Daboczy, in a statement. “The CanCoin is not only a chance to catch up, but truly maximize the opportunity in Europe while ensuring a secure and serious approach to this fast growing industry and expected wave of legalization.”

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