Bio Business Sept/Oct 2016

feature

Cannabis research gains momentum 14

LAW

Cannabis oil offers options for patients and producers 19

moments in time

Canadians allowed cannabis for medicinal purposes but CMA calls for more research 23

september/october 2016

Championing the Business of Biotechnology in Canada

Manchester United

City unites in transformation from industrial capital to life science innovator

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inside

feature

A microscopic view of trichromes on a pre-harvest cannabis plant

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Manchester on the Move

An English city with a proud industrial past and a bright bioscience future.

Weedology

14

Cannabis Oil –

19

Championing the Business of Biotechnology in Canada

Restrictions on marijuana use may be loosening, but it’s still difficult for Canadian researchers to study cannabis.

Easier to Swallow Than Flowers

Changing policies in Canada are making cannabis oil more accessible as an alternative to cured cannabis flowers.

Photo credit: University of Manchester

standard feature

Cannabis research gains momentum 14

LaW

Cannabis oil offers options for patients and producers 19

moments in time

Canadians allowed cannabis for medicinal purposes but CMA calls for more research 23

Lean IsoLatIon WorkstatIons

septeMBer/oCtoBer 2016

DavID suzukI Biofuels are not a panacea

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Championing the Business of Biotechnology in Canada

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September/October 2016

Lean glove boxes deliver process isolation for more reliable, accurate results

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Manchester United

City unites in transformation from industrial Capital to life sCienCe innovator

Editor’s note 5 canadian news 6 worldwide news 7 moments in time 23

Cannabis Labs look to unlock scientific and commercial potential

BB_16_SeptOct_Oct17.indd 1

Do the flip!

10/17/16 11:40 AM

LB_16_SeptOct_Oct12.indd 1

to unlock the scientific and commercial potential of cannabis.

10/17/16 11:41 AM

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Cannabis

Craze

M

y inbox is overflowing with press releases about cannabis – at least a dozen that I’ve saved in the past two months alone. There were more.

I have a press release from UBC suggesting there may be some truth to the belief that marijuana use causes laziness – at least in rats.

There is a statement from Health Canada clarifying that Access to Cannabis for Medical Purposes Regulations (ACMPR) would replace the Marihuana for Medical Purposes Regulations (MMPR) as the regulations governing Canada’s medical cannabis program in August, and that Canadians who have been authorized by their health care practitioner to access cannabis for medical purposes will be able to produce a limited amount of cannabis for their own medical purposes, or designate someone to produce it for them. They will also continue to have the option of purchasing safe, quality-controlled cannabis from producers licensed by Health Canada (35 were licensed to grow and/or sell at press time).

There’s one from the Cannabis Canada Association, supportive of increased access to medical cannabis for all Canadians but concerned that the policy could increase the supply of untested, unregulated product to the black market.

There’s an update from Veritas Pharma Inc. announcing formation of a “uniquely qualified” Board of Directors, completion of Private Placement, as well as initiation of research process and progress toward identifying potentially new therapeutic strains of cannabis.

It’s all good news. In our March/April issue, I introduced you to Katie. She was first diagnosed with breast cancer at age 50 in 2004. She underwent chemo and a mastectomy. She was prescribed Cesamet for nausea associated with her treatment. Katie was allowed one pill with her chemo, one that evening, and one the following morning if needed. They brought her relief from the overwhelming nausea, with no side effects. And they were covered by her husband’s medical insurance. She took them for four months and says she’d do it again. Thankfully she didn’t have to. Though she was diagnosed with breast cancer for a second time in 2014, and again underwent chemo and a mastectomy, the drug cocktail was different this time and she didn’t experience the same side effects.

Not everyone is so lucky. We all know how debilitating some illnesses and side effects of treatments can be. If safe, regulated, proper use of medical marijuana helps, I’m Theresa Rogers for it. Let’s just make sure that’s indeed executive Editor what’s happening as the flood gates open.

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Championing the Business of Biotechnology in Canada

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canadian news

COPD Epidemic

The progressive lung disease is forecast to increase more than 150 per cent, despite decreased rates of smoking, according to a new study by the University of British Columbia. Among seniors over 75 years of age, rates of COPD will more than triple, increasing 220 per cent, which could strain healthcare systems. The study predicts that annual inpatient days related to COPD will grow 185 per cent. COPD is the leading cause of hospitalization in Canada, after heart disease.

Growth of Bioscience Sector Leads to Building of PEI BioAccelerator Complex

Single Protein Slows Tumour Growth

A study by the University of Alberta has found that tumour cells with low amounts of TMX1 are unable to boost their respiration and are resistant to cell death mechanisms.

When levels in healthy cells are high, more treatment options are available and the tumour is less aggressive. Researchers are looking to use the TMX1 mechanism for new and more effective therapeutic approaches – blocking the protein's elimination in cases where it is low and using it to trigger tumour tissue death in cases where it is found to be high. bio business S e p t e m b e r / o c to b e r 2 01 6

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Pharmed Canada and R&D Capital Team to Create Fund

Pharmed Canada, the health industry manufacturing and outsourcing network, and the R&D Capital financing company, are joining forces to create the PharmedR&D Capital Fund. This fund, amounting to several million dollars, is specifically aimed at firms that are eligible for R&D tax credits, to help them obtain capital quickly and access training in how to seek funding and prepare a business case. The fund also provides advice on other methods of financing through a network of partners as a platform in the business finance world of the life sciences industry.

Rendering of a proposed new BioAccelerator for PEI which would include 16,000 sq. ft. of accelerator space, a 10,000-sq. ft. scale-up facility, as well as support services.

Prince Edward Island’s bioscience cluster says that the rapid growth of the sector has fully utilized available laboratory and incubation facilities and new infrastructure is required to support new business attraction and local company expansion.

PEI BioAlliance made the case for a BioAccelerator complex, a 77,000-sq. ft. facility, which is to be located at the BioCommons Research Park, and would be a service, incubation, and scale-up hub that would support the further growth of bioscience-based businesses across the province, complementing and creating new opportunities for existing facilities as well.

“We now have 46 companies and seven The BioAccelerator complex, a 77,000-sq. ft. research institutions facility, would be a service, incubation, and in the province’s scale-up hub that would support the further bioscience sector, growth of bioscience-based businesses across employing over 1,400 the province people in high-paying, full-time jobs,” says Dr. Russ Kerr, Chair of PEI BioAlliance. He also notes that 15 new companies have been added to the bioscience cluster since 2010, and export sales exceeded $200 million in 2015. Kerr points out that many of the businesses are early stage, preferring to lease space during their development phase, and building their own facilities as they move to manufacturing and sales.

“Besides the obvious benefits for our economy, these are the kind of jobs that retain and repatriate our youth, create a highly educated and trained workforce, and enhance industryresearch relationships that benefit students and researchers at UPEI and Holland College,” says Ron Keefe, Chair of the BioAccelerator Steering Committee.

The PEI BioAlliance called on provincial, federal and municipal leaders to make the BioAccelerator project a priority for PEI and Canada as proposals are considered for Phase 2 of the federal infrastructure program.

worldwide news

Secretary-General Ban Ki-moon (centre left) meets with Irina Bokova (centre right), Director-General of the UN Educational, Scientific and Cultural Organization (UNESCO); and members of his Scientific Advisory Board, to receive the final report of the Board. Photo credit: UN Photo/JC McIlwaine

Science is a public good and deserves to be valued more highly and used effectively by decision-makers at all levels, says a United Nations report. But science requires more resources to become the gamechanger it could be in dealing with global challenges.

In fact, all nations must invest more in science technology and innovation (STI), argues The Future of Scientific Advice to the United Nations, A Summary Report to the Secretary-General of the United Nations from the Scientific Advisory Board, which was presented to Ban Ki-moon by Irina Bokova, DirectorGeneral of UNESCO in September.

“STI can be a game changer in dealing with nearly all the most pressing global challenges,” the report states, asserting that STI also has a key role to play in accomplishing the 2030 Sustainable Development Goals of the United Nations. The report notes that scientists and engineers have improved the efficiency of solar panels and wind turbines faster than had been expected, raising the hope that we will be able to reduce our dependency on fossil fuels.

Yet, only 12 countries (Austria, Denmark, Finland, Germany, Israel, Japan, Republic of Korea, Qatar, Singapore, Sweden, Switzerland, and U.S.) dedicate more than 2.5% of their Gross Domestic Product (GDP) to research and development (R&D). This is far from enough considering what is at stake, say the authors of the report. They call on all countries, including the poorest, to invest at least 1% of their GDP on research and urge the most advanced countries to spend at least 3% of GDP on R&D. This effort must also focus on reinforcing science education, notably in developing countries, and on improving girls’ access to science courses.

The members of the Scientific Advisory Board contend that science should weigh more heavily on the decisions of political leaders. They note that almost 25 years passed between the scientific community’s first warnings about climate change and the adoption, in December 2015, of the Paris Agreement on that subject. “Decisions are often taken in response to short-term economic and political interests, rather than the long-term interests of people and the planet,” the report says.

Though the United Nations cannot provide solutions to all the world’s great challenges alone, it is best placed to set international objectives for doing so. “The world surely has a right to expect and even demand that the United Nations deliver what no other institution can: setting global priorities, promoting and coordinating research and action to address the most challenging problems, enabling the effective worldwide use of all data.”

Big data exchanges around the world offer an illustration of the role the United Nations could play to favour fair access. The report notes that the United Nations and its agencies can facilitate the gathering of all types of data while overseeing both quality and access. It also calls for international collaborative projects in this area.

The Scientific Advisory Board of the United Nations Secretary-General was established in 2014 to formulate recommendations in the sciences, technology and innovation (STI) that will enlighten the work and decisions of the United Nations. The Board numbers 26 scientists of world renown appointed to take stock of scientific needs to tackle global challenges. UNESCO serves as the secretariat of the Board which produces documents on subjects such as the data revolution, the role of the sciences in meeting sustainable development goals or the Delphi Study, which identifies major scientific concerns for the future of the planet.

Targeting Fat to Treat Cancer

Researchers at Salk Institute in La Jolla, CA, have discovered cancer cells are more reliant on lipid synthesis activity than normal cells, and have found a way to obstruct the process to stifle cancer’s growth, which relies on their fat molecules to grow. There may be subsets of cancers sensitive to a drug that could interrupt that vital metabolic process. Using a combination of carboplatin and ND-646 in multiple large-scale tests in both animal models and in transplanted human lung cancer cells, the tumour mass shrank by roughly two-thirds compared to untreated animals.

Testing for Osteoporosis

More than three million bone fractures occur in Europe due to osteoporosis yearly, resulting in costs estimated at 40 billion Euro. Austrian company, TAmiRNA, develops biomarker solutions, which significantly improve early detection of serious age-related illnesses such as osteoporosis. At this year’s ASBMR meeting in Atlanta, GA, the company presented its new osteomiR test kit, a diagnostic kit for detection of osteoporosis. For now, the kit is for research use only, but its clinical utility will be investigated in the near future.

‘False’ Biosignatures Complicate Discoveries in Space

Self-assembling carbon microstructures created in a lab by University of Colorado Boulder researchers provide new clues and cautions in efforts to identify microbial life preserved in the fossil record, on Earth and elsewhere in the solar system. The microstructures are capable of self-assembling in certain conditions, even without direct biological activity. These “false” biosignatures could potentially be misinterpreted as signs of biological activity due to their strong resemblance to microbial structures. They may no longer be sure-fire microbial indicators, but they can still help reconstruct certain environmental processes.

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Realizing the Potential for Science

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regional profile

Manchester on the move

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The UK’s industrial engine room is fast becoming a life science powerhouse By hermione wilson

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alking around central Manchester, a city in the north of England, it becomes clear this is a place that welcomes innovation. From the Museum of Science and Industry, with its noisy display of steam engines, to its more than 20 libraries (including Chetham, the oldest public library in the English-speaking world), Manchester is a city as hungry for knowledge and progress now as it ever was.

This is the cradle of modern computing – Alan Turing developed his famous Baby at the University of Manchester. This is where scientist John Dalton theorized about the nature of atoms and began to study colour blindness, and where chemist Ernest Rutherford split the atom. More recently, Manchester was the birthplace of the Nobel Prize-winning one-atom-thick compound, graphene. This is a city that has always embraced progressive thinking.

In the 19th century, the growth of the cotton industry and the development of textile factories and mills transformed Manchester from a small market town to an industrial capital known as the “workshop of the world.” By the 1980s, however, the cotton industry that had been the lifeblood of Manchester had all but vanished and the region was in decline. That period of economic stagnation forced Manchester to re-evaluate and led the city to do an about-face and transform itself into a knowledgebased economy, investing in its academic institutions and the science and technology sector.

In July of 2016, a few weeks after the fateful Brexit decision, thousands of delegates converged on Manchester for the biennial EuroScience Open Forum (ESOF). Scientists, policy-makers and journalists from Europe and 90 other countries came together to share, discuss and debate new science and new ideas.

“There’s a real buzz in this area around life sciences and health care,” says Sameer Kothari, Chief Executive Director at Zilico, a biotech which develops Electrical Impedance Spectroscopy (EIS) diagnostic tools that look at the electrical properties of tissue in the detection of cancers. The company moved to Manchester from Sheffield a few years ago to get access to the talented pool of bioscience professionals, Kothari says.

“We have a very good academic and university set-up, and of course we have the

In July of 2016, a few weeks after the fateful Brexit decision, thousands of delegates converged on Manchester for the biennial EuroScience Open Forum (ESOF).

regional profile

Scientists, policy-makers and journalists from Europe and

90 other countries came to share, discuss and debate new science and new ideas.

Top: Manchester physicist and BBC TV personality Brian Cox emcees the ESOF 2016 opening ceremonies. Photo credit: Paul Worpole Photography Bottom three: Images from the 2016 ESOF exhibition hall. Photo credit: Antonia Cheng

regional profile

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teaching hospitals, so it’s a great pool to recruit, but it’s also a great pool to develop products and take that research even further,” he says.

Zilico makes its home at Alderley Park, a former AstraZeneca stronghold situated in the Cheshire countryside, just outside of central Manchester. When the multinational pharmaceutical decided in 2014 it wanted to move to a smaller site in Cambridge, it turned over its 400acre site and facilities to Manchester Science Partnerships (MSP).

“Alderley is a fascinating example of how you can manage when a large pharma company exits any particular geography,” says Neil Murray, CEO of Redx Pharma, another biotech that makes its home at Alderley. “There were a lot of people wringing their hands when AstraZeneca announced that they were going to move from Alderley to Cambridge. I’d say, on account of the true northern way, people did that for five minutes and then said, ‘right, what are we going to do about it?’”

What they did was transform it into a place that would foster life science innovation in the northwest.

“There was a UK government taskforce set up to look at what to do with this site,” says Chris Doherty, MSP’s Site Director at Alderley Park. “This was the strategy: keep it life science, leave the structure, the people who are not leaving are the key assets for this site.”

Two years later, AstraZeneca is still in the process of leaving, but instead of leaving an economic vacuum in its wake, it will leave a 400,000 square-foot facility now home to 45 companies, 3,000 staff, and a life science incubator that has spawned 12 new biotech startups so far. Those startups are making use of the assets AstraZeneca left behind, such the NMR imaging suites, MRIs, PET and CT scanning facilities, and a variety of other specialized biotech services and facilities.

Alderley Park has been chosen as the site of both a Medicines Discovery Catapult, a government-funded innovation centre focused on translational research, and the new Antimicrobial Resistance Centre, announced at the ESOF conference, “formed to improve the pipeline of antibiotics in the world,” Doherty says. Aside from the world-class facilities, Alderley Park has a low operating cost base, he says, charging tenants rents that are lower than other major English cities like Cambridge, Oxford and London.

“My vision is to create a large, vibrant ecosystem of bioscience companies who can benefit from this asset,” Doherty says.

Jackie Oldham is hoping to do the same thing in the heart of downtown Manchester.

She is the Director of Health Innovation for Corridor Manchester, an organization looking to develop Manchester’s Oxford Road corridor into an “innovation district”.

Stretching from the Central Library to the Whitworth Art Gallery, the corridor is home to the University of Manchester, the Manchester Metropolitan University (MMU), the Central Manchester University Hospitals NHS Foundation Trust (CMFT) (which pulls several hospitals together on one site), the National Graphene Institute, about 250 SMEs, and a number of global companies.

In terms of fostering life science innovation, Corridor Manchester’s collaborative approach has borne fruit. For the past few years, Corridor Manchester has also been working with MSP to embed science parks in the heart of the city. The result was

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Alderley Park has been chosen as the site of both a Medicines Discovery Catapult, a governmentfunded innovation centre focused on translational research, and an Antimicrobial Resistance Centre

Clockwise from above: Aerial view of the University of Manchester campus.

Photo credit: University of Manchester Lab at Alderly Park.

Photo credit: Jonty Wilde Aerial view of the Alderly Park campus.

Photo credit: MSP Zilico’s ZedScan device.

Photo credit: Zilico

CityLabs 1.0, a biomedical incubator that offers companies access to clinical resources, expertise from researchers and proximity to the CMFT campus.

Plans to build CityLabs 2.0 and 3.0 were announced at ESOF. The city has also been chosen as the initial location for the Precision Medicine Catapult’s regional centre of excellence.

A number of innovations have come out of Manchester’s innovation district: Zilico’s tissue diagnostic tool, a blood recovery system that can recycle and reuse blood recovered from swabs in the operating room, mag needles that can remove fluid from swollen limbs, and a portable ECG technology, to name a few. The city also happens to be one of the best recruiting sites for commercial clinical trials in the UK, Oldham says.

“We recruit over 45,000 patients per year,” she says. “That’s about nine per cent of the total population, but greater Manchester only covers five per cent of the geography, so we’re punching above our weight.”

“Manchester is very much in the ascendancy in relation to bioscience and biotechnology,” says Mike Birch, CEO of F2G, a small biotech focused on developing antifungals for immune-compromised patients.

Its drug, an antifungal that targets the environmental mold aspergillus, was discovered in Manchester. F2G was a spinout from the University of Manchester, which has a strong fungal research group, and continues to collaborate with researchers there, Birch says.

“It’s helped us enormously in understanding the... mechanisms of action of the drug and the biology, or what happens to the organism when it’s treated with the drug,” he says. “We do things like live imaging of fungal cells.

They’ve got some pretty cool equipment over there that we couldn’t afford as a small biotech.”

Manchester may be outside of “the golden triangle of Oxford-LondonCambridge,” says Charles Blundell, Chief Technology Officer of C4X, but space is cheap in comparison. It also means that the biotech is closer to its alma mater. C4X is another spinout of the University of Manchester that has developed a new way of looking at the dynamic structure of molecules. “We

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regional profile

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regional profile

use these great big magnets, magnets as big as this room, to look at a tiny, tiny molecule that you can’t even see,” Blundell says. He describes it as a new kind of microscope and it may never have been developed if not for the university.

“Manchester University has a particularly good technology transfer department,” Blundell says. “If they hadn’t have been so supportive, I probably wouldn’t have started, personally speaking.” The intellectual property terms for academic founders are some of the best in the country, he says, unlike some universities that automatically claim 55 per cent of the IP so they can have a controlling stake. That’s all part of the University of Manchester’s focus on spinning out companies, Blundell says. C4X has maintained close ties with the university and borrows magnets from time to time.

“A number of people have said to me, ‘Why is it that Manchester has got so much happening?’” Oldham says.

“I think it’s this collaborative [environment] but it’s also because we’ve said it must be easy for you to do your work here, and what can we do to facilitate you getting through all the hurdles, through the research process into practice. It’s about creating the right environment.” BB

The Wonder Material

Of all their accomplishments, the Manchester science community is particularly proud of graphene. At the University of Manchester in 2004, Andre Geim and Konstantin Novoselov isolated the unique two-dimensional nanomaterial from graphite found in an ordinary pencil using adhesive tape. They earned themselves a Nobel Prize in Physics for it in 2010.

Graphene is one atom thick and with its great surface area, highly electrically conductive. Scientists have been able to create semiconductive ink that can be printed on any surface and used in a variety of electronic and biomedical applications.

“We’ve been using graphene on a screen printing process where you’re just putting layers of graphene ink together on top of each other,” says Ray Gibbs, CEO of Haydale Graphene Industries, describing the biomedical sensor the company is developing for diabetics to monitor their blood glucose levels. Gibbs says Haydale is looking to replace silver, traditionally used in diabetic sensors, because it is potentially toxic. “[Graphene] is carbon, it’s environmentally friendly, it’s recyclable, so you’ve got something that’s automatically going to go back into the chain.”

Haydale is also working with Fraunhofer in Germany on a reelto-reel process that uses its graphene screen printing technology to diagnose pathogens. “The aim of that, if we get it right, is to actually replace the need for animal testing,” Gibbs says.

We are entering an age of two-dimensional materials, Geim says. Much like other ages that preceded it – stone, iron, bronze – graphene will have a far-reaching and wholly unexpected impact in years to come.

“It usually takes 10, 50 years for a material to go from an academic lab to a commercial environment,” Geim says. “Now, it’s taken a short five years for people to start doing applications on graphene.”

Computer-generated image of Citylabs 2.0 and 3.0, slated for construction in spring 2017 and summer 2018 respectively.

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“A number of people have said to me, ‘Why is it that Manchester has got so much happening?’ I think it’s this collaborative [environment] but it’s also because we’ve said it must be easy for you to do your work here, and what can we do to facilitate you getting through all the hurdles, through the research process into practice. It’s around creating the right environment.”

– Jackie Oldham , Director of Health Innovation, Corridor Manchester

Top: Detaching graphene from graphite using adhesive tape is known as the “Scotch Tape Method.”

Bottom: Manchester’s National Graphene Institute, which opened March 2015.

Photo credit: University of Manchester

feature storY

weed logy By hermione wilson

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Ever since the federal Liberal government declared its intention to legalize marijuana

(the dried leaves and flowers of the cannabis plant) discussion around the pros and cons of the controversial drug has been heating up.

On one hand, there are the therapeutic benefits of the cannabis plant when it is used to treat chronic pain, nausea, anxiety, spasticity, and a variety of other conditions.

On the other hand, there are the plant’s psychoactive properties which make it popular for recreational use.

feature story

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Have regulatory hurdles had a chilling effect on cannabis research?

A PPS scientist shows tissue culture propagation of a cannabis plant.

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“I like to compare it to two rivers,” says Mark Ware, Director of Clinical Research at McGill University Health Centre’s Alan Edwards Pain Management Unit. “One is the patient knowledge that people have tried this for themselves and there’s a huge volume of patient-reported claims that cannabis helps with pain and sleep and spasticity and nausea and so on. The other river is the scientific understanding of the endocannabinoid system... that we have in our bodies, that appears to play an important role in the way that our bodies and our brains manage information, movement, memory, emotions, and so on. You put these two things together and it becomes a scientific rationale as to why it is that patients may report improvement in neuropathic pain. The challenge now is to bring those two rivers together and say, well, can we explore these claims with robust science.”

The compound that is responsible for marijuana’s psychoactive effect is delta-9-tetrahydrocannabinol (THC) and as researchers at the University of British Columbia have discovered, it has a very specific effect on decision-making.

THC is a cannabinoid, a chemical compound derived from the cannabis plant that acts on and modifies the human brain’s endocannabinoid system. As with everything pertaining to the brain, the endocannabinoid system, a network of endogenous cannabinoid receptors, is very complex and little understood. As far as scientists can tell, at least one of those receptors, called CB1, acts as a necessary break in the process by which nerves connect and communicate with each other. When a nerve signal is passed from one nerve cell to the other, the nerve cell that is receiving the message sends a message back to the previous nerve saying that the message has been received and that there is no need to keep sending neurotransmitters. The cannabinoid system is integral in that process, Ware says.

“Once your nerve cells have communicated with each other, the cannabinoid system acts to suppress further activity, and that’s happening in everybody all the time,” he says. “We’re continuously using this system to keep our movements and our thoughts and our emotions smooth and controlled. When that system goes out of whack, then patients appear to need cannabinoids to help resume the normal endogenous tone of the cannabinoids.”

Catharine Winstanley is the senior author of a study out of UBC that investigated the effect THC had on rats’ ability to perform cognitively challenging tasks. The study found that while THC didn’t actually impair the rats’ ability to perform the tasks, it affected their willingness to complete the harder tasks. In other words, it made them lazy.

“It’s a very specific cognitive change, just a change in decision-making without the change in ability to do the demanding task,” Winstanley says. And THC seems to be the only cannabinoid that has this effect. Cannabidiol (CBD), the cannabinoid thought to be responsible for much of the therapeutic benefits of the plant, does not impair cognition at all.

Testing cannabis samples at the PPS Research Lab.

feature story

Supervising cannabis production in one of PPS’s specialized cannabis growth chambers.

If we knew how THC works to alter cognition then maybe we could find a way of modulating it so that even if people did want to take the plant marijuana, then maybe we could provide them with a drug they could take at the same time that would stop THC from having bad effects.

Cannabinoid analysis at the PPS Quality Control Laboratory.

“There are companies that are trying to create medicinal products based on cannabis that have higher levels of cannabidiol to THC in them and they’re suggesting that by increasing the level of cannabidiol they can overcome any negative effects of THC,” Winstanley says. “Unfortunately, when we tried to mimic that ratio, cannabidiol to THC, in our experiments - so giving equal amounts of both basically at the same time to the animals - we couldn’t stop THC from altering decision-making.”

That’s a problem for patients who are looking to reap the therapeutic benefits of cannabis without getting high.

Winstanley says she and her colleagues are still hoping to find a way to moderate the effects of THC while preserving the beneficial qualities of cannabis.

“If we knew how THC works to alter cognition then maybe we could find a way of modulating it so that even if people did want to take the plant marijuana, then maybe we could provide them with a drug they could take at the same time that would stop THC from having bad effects,” she says.

Research like the UBC study is important, not just to patients who seek relief in medical marijuana, but to those who have developed a dependency on the drug. Winstanley and her colleagues are planning to join forces with researchers from the University of Toronto to explore the risk factors for addiction in young people and develop a cognitive assessment of people who are likely to abuse marijuana.

The cannabis plant has been used for centuries in a medicinal capacity, but because of its controversial nature and controlled substance status, research into why it has those beneficial effects have been stunted. It is very difficult to obtain cannabis for the purposes of research and requires special licenses that restrict the amount of cannabis researchers can possess.

“It normally takes around two to three years to get that license proposal deemed satisfactory by the government,” says Tegan Adams, Director of Business Development at

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– Catharine Winstanley, The University of British Columbia

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Experchem Laboratories, a product testing facility in Ontario. “To get that approval you have to include as much detail as possible about what you’re doing at the site, and then when they come and visit, it needs to match up.” That slows down the research process considerably, as Larry Holbrook can attest to.

Holbrook is Chief Science Officer at Prairie Plant Systems (PPS), a plant biotech company and licensed producer of cannabis in Saskatchewan.

The company has a pharmaceutical focus with a particular emphasis on purifying cannabis compounds and exploring different delivery methods such as oils. Prairie Plant Systems has been collaborating with CanniMed and researchers at McGill University and Dalhousie University on a clinical study looking at the ratio of THC to CBD that would be beneficial to pain relief in older patients with osteoarthritis.

The trial was the first-ever to be approved and registered with Health Canada in 2014. Holbrook says Prairie Plant Systems is now in the process of recruiting patients.

Cannabis research in Canada may have been stunted by years of prohibition, but it is quickly gaining momentum. Holbrook knows of three clinical trials currently being set up in Canada: a study in Toronto looking into using cannabis to treat Tourette syndrome, another at the University of Guelph on cannabis’ anti-nausea effect, and a clinical trial in Saskatchewan looking at children with epilepsy. Ware mentions a PostTraumatic Stress Disorder study that has been launched in British Columbia. “There certainly is a broad interest in trying to facilitate clinical research with cannabinoids in Canada,” Ware adds.

Part of the difficulty of doing clinical trials involving cannabis is the difficulty of obtaining materials for research and getting such a study approved by the government. The other barrier in researchers’ way, Holbrook says, is that there isn’t much financial support from the pharmaceutical industry.

“Pharmaceutical companies liked to have small drugs that they could synthesize and patent, in the past,” he says. “Something that is natural, from a plant, they never really liked because it didn’t give them a lot of intellectual property benefit.”

Still, the cannabis industry is clearly ripe for potential and with the prospect of a loosening, or at the very least a redefinition, of restrictions surrounding the substance, big pharma can’t help but take notice. If they have though, they’re playing it close to the chest, says Adams. “Until they actually have the results and publish them, or they’re useful, they’ll keep those data sets close to the chest,” she says. “They don’t want someone else to get it or figure out what they’re doing.” BB

Restrictions on the possession and use of cannabis make it difficult to conduct cannabis research.

Top left: UBC researcher Catharine Winstanley. Photo credit: Martin Dee Top Right: Mark Ware. Photo credit: McGill University Health Centre Middle and bottom: Experchem Laboratories.

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Cannabis Oil Easier to Swallow than Flowers

By David Wood and Lydia Wakulowsky

ith several successful financings closing and general positive media coverage through 2016, Canada’s federally regulated medical cannabis program under the Access to Cannabis for Medical Purposes Regulations (the “ACMPR”) continues to grow in number of patients, social acceptance and variety of products. Many would consider cured cannabis flowers to be the default medical cannabis product. However, as seen in both medical and adult-use cannabis markets in the United States, the popularity of cannabis oil continues to increase in the Canadian medical cannabis industry.

Cannabis oil is provided to patients throughout Canada under the ACMPR by mail delivery from large-scale licensed producers. The ACMPR is interim successor legislation that replaced the Marihuana for Medical Purposes Regulations (the “MMPR”) on August 24, 2016. Initially the MMPR allowed only sale of “dried marihuana”, meaning dried and cured cannabis flowers. This restriction did not survive a challenge under the Canadian Charter of Rights and Freedoms (R v Smith, 2015 SCC 34).

In response to Smith, Health Canada began issuing licenses under the Controlled Drugs and Substances Act (the “CDSA”), allowing licensed producers who met other criteria to produce and sell cannabis oil, in addition to cured cannabis flowers. As of September 16, 2016, a total of 21 licenses for production and/or sale of cannabis oil have been issued under the CDSA and continued under the ACMPR, compared with a total of 35 licenses for production and/or sale of cannabis flowers.

The ACMPR regulate cannabis oil in detail. Cannabis oil for ingestion or topical use may be sold by licensed producers to patients. Details in the ACMPR effectively exclude cannabis oil suitable for smoking or vaporizing. In addition, the only authorized dosage form for cannabis oil is a capsule or similar dosage form for use either as a pill or a suppository. As a result, the ACMPR excludes infused food or flavoured beverage products including cannabis oil from sale by licensed producers.

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The ACMPR provisions excluding oils suitable for smoking or vaporizing, and excluding infused food or flavoured beverage products, are consistent with the role of cannabis oil as a medicine, as opposed to broader non-medical adult use of cannabis oil.

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The ACMPR restricts cannabis oil without a dosage form to a maximum concentration of 30 mg/ml total delta9-tetrahydrocannabinol (“THC”) and delta-9-tetrahydrocannabinolic acid (“THCA”). Cannabis oil that is sold in capsules is restricted to a maximum of 10 mg total THC and THCA per dosage. There is no legislative limit to the amount of cannabidiol (“CBD”) or cannabidiolic acid (“CBDA”) that may be included in cannabis oil by volume or by dosage form.

The cannabis oil must be liquid at room temperature. Butane and other organic solvents are not permitted in cannabis oil – some licensed producers use olive oil, grapeseed oil, or coconut oil. No additives may be included in cannabis oil other than those necessary to maintain the product’s quality and stability.

The ACMPR provisions excluding oils suitable for smoking or vaporizing, and excluding infused food or flavoured beverage products, are consistent with the role of cannabis oil as a medicine, as opposed to broader non-medical adult use of cannabis oil. Such products may be found in some retail medical cannabis dispensaries, which are common in parts of British Columbia and Ontario. While some dispensaries may have municipal zoning approval, sale of cannabis (cannabis oil or otherwise) from dispensaries is outside of the ACMPR and contravenes the CDSA. As such, cannabis dispensaries are subject to closure and seizure of assets by police officers, although enforcement is inconsistently applied in some municipalities.

Cannabis oil is a product with some advantages over cured cannabis flowers. Consistent dosage is simplified, particularly if the cannabis oil is provided in a dosage form. The 30 mg/ml maximum total THC/THCA, sold in some cases at lower concentrations of about 20 mg/ml or 10 mg/ml, provides for reasonable dosing with a dropper.

Acceptance may be facilitated both by physicians and by patients unfamiliar with cannabis, particularly when the label, container and other branding is clean, professional, and similar in feel to other medical products. Such presentation keeps physicians and patients closer to the conventional comfort zone of pharmaceutical therapies because cannabis oil presents more like a pharmaceutical drug, compared with cured cannabis flowers, in appearance and how it is used.

Cannabis oil, particularly with the correct presentation,

may resemble a pharmaceutical drug, but cannabis oil is uniquely regulated in Canada. “Cannabis” is a controlled substance listed in schedule II of the CDSA. Cannabis is defined in the CDSA and the ACMPR as including cannabis resin. “Cannabis resin” includes extracts of plant matter, such as ethanol or CO2 extracts dissolved in a carrier oil.

THC, CBD, and cannabinol (“CBN”) as pure compounds are also each specifically within the definition of “cannabis”.

Sale of cannabis oil as a drug per se would, as with any substance, be subject to compliance with the Food and Drug Regulations (“FDR”). Sativex buccal spray, which includes THC and CBD, and Marinol capsules, which include THC, are examples of drugs indicated for a condition in compliance with the FDR, and which include “cannabis” as defined in the CDSA. Unlike drugs including defined amounts of THC and/ or CBD, cannabis oil is not indicated for any particular condition and has not been authorized for sale as a drug by Health Canada under the FDR. However, sale of cannabis oil by licensed producers to patients in accordance with the ACMPR is exempted from application of the FDR by the Cannabis Exemption (Food and Drugs Act) Regulations, which are issued pursuant to the FDA. The ACMPR regulates production, processing, and labelling of cannabis oil to ensure that information relating to quality, safety and dosing are available. The provisions of the ACMPR in this respect are unique and specific to cannabis oil, and distinct from similar provisions applicable to drugs generally in the FDR. While cannabis oil is not indicated for any specific medical condition, the greater level of consistency that is likely available with cannabis as opposed to cured flowers may be a first step toward greater standardization of cannabis formulations. Many licensed producers who offer cannabis oil to their patients sell blends that are high in THC, high in CBD, and balanced. Some licensed producers categorize their oils as sativa, indica, or hybrid subspecies according to the plant matter that the cannabis oil was sourced from. As the

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solutions as compared with cured cannabis flowers, cannabis oil offers a product that licensed producers may find more attractive from a business perspective. Significant value to the patient may be added by preparing cannabis oil, which may translate into a stronger profit margin than with cured cannabis flowers. Patents, trade secrets, or both may be leveraged where appropriate to protect specific formulations, dosage forms, and methods for manufacturing cannabis oil.

Intellectual property may also be applied to protect packaging and devices for facilitating dosing of cannabis oil. At least one partnership between a licensed producer and an extraction company from the commercially mature Colorado market has been announced and more are likely to follow as the Canadian medical cannabis market matures. With an industry based on cured cannabis flowers only as the departure point, cannabis oil offers more options for patients and licensed producers, and also points the way forward to greater standardization and understanding of medical cannabis. BB

David Wood is a lawyer and patent agent in the Calgary office of Borden Ladner Gervais LLP. He practises intellectual property and regulatory law. His regulatory practice is specific to the Canadian medical cannabis industry. Lydia Wakulowsky is a Partner in the Toronto office of Borden Ladner Gervais LLP. She practises corporate and commercial law, focusing on the health sector.

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industry matures, approaches to formulation, manufacturing, and labelling may become more standardized as between licensed producers. Divergence of product lines among licensed producers within that standardized framework may follow as some licensed producers distinguish and brand themselves with unique and in some cases proprietary cannabis oil products (as seen in the various state markets in the United States).

In addition to greater convenience and a more comfortable social transition from better known pharmaceutical

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moments in time

Legalize It I

n 1999, Canada’s Minister of Health announced a clinical trials program for medical marijuana and procedures for patients looking to access the drug for medicinal purposes. In 2000, the courts ruled Canadians have a constitutional right to use cannabis for medicinal purposes. In an extract from a 2000 report on the decision prepared by the Canadian Foundation for Drug Policy, the Canadian Medical Association commented it had argued for the decriminalization of the possession of marijuana since 1981, but that it deplored “the absence of more systematic scientific research on the topic.� BB

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With information from Canadian Press and the Canadian Foundation for Drug Policy.

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