Tag Archives: sublingual

June 29, 2020

Cannabinoid Research & Pharmacology: A Q&A with Dr. Linda Klumpers

By Cannabis Industry Journal Staff

Dr. Linda Klumpers has a Ph.D. in clinical pharmacology of cannabinoids. Originally from the Netherlands, she began much of her career in studying cannabis there. She now lives and works in the United States, where she has worked on a number of projects, started her own company and is continuing her research on cannabis as an effective medicine.

After studying neuroscience at the University of Amsterdam, she went on to train at the Centre for Human Drug Research and Leiden University Medical Center, where Dr. Klumpers obtained a clinical pharmacology degree and a Ph.D. in clinical pharmacology of cannabinoids. She has been researching cannabinoids in humans since 2006. Dr. Klumpers co-authored a number of peer-reviewed cannabinoid publications and she has received five honors and awards for her work, including the BJCP Prize from the British Journal of Clinical Pharmacology.

In 2016, she moved to the United States and founded Cannify, an online tool that helps patients and clinicians with product matching and providing legitimate cannabis education based in sound science. In 2018, Dr. Klumpers joined forces with Dr. Michael Tagen, another clinical pharmacologist, to launch Verdient Science, a consulting partnership. Their work at Verdient Science includes helping clients set up human studies, advise on FDA submissions, creating course materials, adjusting product pipelines and product development strategies, among other areas of focus.

Right now, Dr. Klumpers is waiting to hear back from a grant application they submitted to study THC and CBD ratios for medical efficacy in chronic pain patients. We sat down with Dr. Klumpers to hear her story, what she is working on now and how she hopes to continue researching cannabis as an effective medicine.

Cannabis Industry Journal: Tell us about your background as a research scientist. How did you get involved in cannabis?

Dr. Linda Klumpers: During my Ph.D. work, we studied the effects of so-called cannabinoid receptor antagonists that block the effects of THC – I prefer to say “we”, as research is always done by multiple people. The problem with studying these compounds in healthy volunteers is that you can’t observe acute effects, which means that you won’t measure any effect after a single dose. To circumvent this issue, we applied a trick and developed a ‘challenge test’: after you give the ‘invisible’ blocking compound, you stimulate the cannabinoid system by giving people THC. If the subjects don’t feel the effects of THC, you know that the blocker worked. One thing lead to another and we ended up studying various administration methods, such as intrapulmonal (via the lungs) with vaporization, oral and sublingual. We studied the behavior of cannabinoids in the body and how the body responded to them.

CIJ: Can you share some information on the projects you are working on? What is Cannify and what is Verdient Science?

Dr. Klumpers: Cannify was founded in 2016 after I saw that too many people had opinions about cannabis that were more based on emotion than fact. Besides, I noticed that a majority of the scientific literature on cannabis pharmacology was left unnoticed and unapplied to the people getting exposed to cannabis, such as patients, the cannabis industry – that was in a very different stage at that time – healthcare providers and regulators. With my Ph.D. in cannabis pharmacology, I wanted to add a level of objectivity to cannabis education and research. Cannify’s goals are to understand the science of cannabis, and share this with others.

The way we do this is multi-fold:

Cannify Quiz: Patients with an interest in cannabis often want to know the science about cannabis and their condition. Our quiz helps these people by asking in-depth questions and showing them relevant scientific literature in a personalized report. After that, an overview is given with products and product matching scores. Our account system allows users to track their progress over time. Product manufacturers, dispensaries and other companies can use the quiz for their websites and their stores to help out retail employees and save them time, and to receive insight with our analytics on customer desires and behavior. Needless to say, an educated customer is a better customer. It is important that customers come and leave stores well-informed.
Education: Speaking of education, our website contains educational articles about everything cannabis: from plant to patient and from product to mechanism of action. We regularly publish educational quizzes for people to test their knowledge level. With a free Cannify account, you can find all of our educational quizzes and save your results. We also provide customized courses, and have educated a wide audience varying from industry professionals to CME-accredited courses for healthcare providers. On top of that, our educational videos in dispensaries (in collaboration with our partner, Enlighten) reach customers and retail employees.
One of Cannify’s educational graphics, showing the difference between topical and transdermal product administration

Research: To expand the knowledge on cannabis, performing and especially sharing research is essential. We have already performed and published some of Cannify’s results on descriptive statistics and effect prediction during conferences, as well as a review paper on cannabis therapeutics in a peer-reviewed journal and a book chapter. This year, we expect to co-publish the results of a survey in different sleep patient groups. We collaborated with the Centre of Excellence for Epilepsy and Sleep Medicine in the Netherlands on a peer-reviewed paper from which we expect new research to follow to benefit these patients. We have also co-submitted a grant to study THC and CBD ratios in chronic pain patients: fingers crossed! Another important next step is to test a healthcare provider-specific version of Cannify’s quiz in the clinic once COVID dies down. I want to add that after working in a clinical lab for many years, it is important to combine the results of clinical trials to what people do in real life, which is what we do with Cannify.

And here’s some information on Verdient Science:

Verdient Science is a consulting partnership I have with clinical pharmacologist Dr. Michael Tagen. We provide clinical and translational pharmacology expertise to improve the quality of product development & clinical testing. While both working as independent consultants, we decided from 2018 to start working together to offer better services. Since then, our work has been very variable and includes helping clients set up human studies, advise on FDA submissions, creating course materials, adjusting product pipelines and product development strategies to make them more efficient and cheaper, performed scientific due diligence and much more. When clients want additional services that are beyond our expertise, we are typically able to introduce them to various people per expertise area, or refer them to our partner companies, Complex Biotech Discovery Ventures (CBDV) with Dr. Markus Roggen, and Via Innovations with Dr. Monica Vialpando. A benefit of working with the same partners includes smooth handovers and the feeling of a one stop shop.

CIJ: How does Cannify match available products to consumer needs? Is there an algorithm you developed that matches moods or feelings to cannabinoids or chemical profiles?

Dr. Klumpers: That is a great question and the core of what we do! So back to the Cannify quiz: there are three steps:

Users fill in questions;
A personalized report is generated with the relevant science;
The user gets a product overview with product matching scores.

Another Cannify educational graphic, showing THC distribution throughout the body over time

The report and the matching scores are generated using algorithms that are regularly updated. These algorithms are based on various data sources:

Literature: There is a lot of available literature, and we make sure to select the most relevant and reliable studies;
Raw data: There is only so much one can find in the literature, and lots is hidden in the raw data. Therefore, we piled up data from studies done at various research institutions, including the University of Kentucky and Johns Hopkins University, and used them in our algorithms;
Internal studies: From the thousands of users filling in their results, there is a lot of information that we should learn from. This feedback loop helps us to better understand how the lab relates to real life situations.

CIJ: The world of cannabis research has been historically stymied by red tape, DEA interference and a host of federal regulations. How have you managed to work through all that? Do you have a DEA license? What did it take to get it?

Dr. Klumpers: Luckily, a majority of our research was and is done outside of the US. You still need to obtain the appropriate licenses, but I was perhaps lucky to have filled in every form very thoroughly and we got the licenses within months. The process is quite meticulous, as you need separate licenses for almost every step from manufacturing to administration. An additional complication is that our cannabis is not stored in our own building, but in the hospital pharmacy across the street, involving transport via the public road. Despite the roadblocks, including a legal procedure about this matter that was going on in parallel, I had no major issues getting our work done. For our research in the US, we were lucky to have been working with partners that already have the required license.

Also with publishing, I have never had an issue with the cannabis stigma. Generally, in my field of science, good quality science is very much welcomed and appreciated, and this was even before the time that there were four different cannabis-related journals, as is the case nowadays.

CIJ: Looking to the future, where do you hope to focus your research efforts? Where do you think the cannabis community should be focusing their efforts in the next 5-10 years?

Dr. Klumpers: Besides continuing to analyze the data generated from Cannify, I keep my fingers crossed for the grant application I mentioned earlier on THC and CBD ratios in chronic pain patients. Although we know that CBD is able to influence THC-induced effects, it is not known at what dosages, which ratios and how the effects are related to each other. For example: is CBD able to decrease certain side-effects of THC without decreasing pain-relieving effects?

Whatever is done, wherever in the community: good quality data are keyNext to that, I am also interested in other neurological and psychiatric disorders, and, of course, my Ph.D. love: the cannabinoid antagonists. Sadly, all the research efforts on this compound group were halted more than a decade ago. However, there is a renewed interest. I would love to help turn these compounds into effective and safe medicines.

Regarding the cannabis community: 5-10 years sounds really far away for an industry that is relatively new to many, but a lot has already changed since I started cannabis research more than 14 years ago and time has flown by. Some changes have been positive and others less so. Whatever is done, wherever in the community: good quality data are key. Many companies gather data and even publish them in peer-reviewed journals, but that does not always mean that the data are useful or that the studies were done well. Only a few minor changes to how and which data are gathered, and so much more can be done. What can help with achieving this is to let the right people do the right thing: many call themselves a ‘cannabis scientist’ or ‘cannabis expert’, but that does not mean anything. What has someone truly achieved and what is their exact expertise? A Ph.D. in chemistry is not going to help you in setting up effect studies, neither will I be able to improve your product’s shelf life or extraction yield. Getting the right people in the right place is key. Lastly: the cannabis community should stay critical. The length of one article in Cannabis Industry Journal wouldn’t be enough to lay out all the misconceptions that people have about cannabis. Make sure that those misconceptions do not live on and do not be afraid to admit you don’t know something, irrespective of the branch you work in: only then, can the cannabis community progress to the benefit of all.

December 30, 2019

How to Grow Cannabis Plants for Concentrate Production

By Andrew Myers

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While flower is still the most popular way to consume cannabis, the concentrates market is booming. Some predict concentrates will be nearly as popular as flower by 2022, with an estimated $8.5 billion in retail sales. That’s a lot of concentrates and, chances are, cannabis producers are already feeling the pressure to keep up.

Concentrates refer to products made from processing cannabis – often resulting in much higher THC or CBD percentages. The category includes oils, wax, dabs, shatter, live resin and hash. Consumers are increasingly drawn to these cannabis products for their near-immediate and intense effects. They’re often consumed through vaporization, dabbing or sublingual absorption and are sometimes favored by those who want to avoid smoking. Cannabis growers who have traditionally focused on flower yields may decide to prioritize quality and potency levels in order to tap into these changing consumer tastes.

What Growers Should Focus on to Produce High Quality Concentrates
We’ll let you in on a little secret: making good concentrates starts with good flower. If you’re starting with low-quality flower, it’s impossible to create a high-quality concentrate. Whatever qualities inherent to the flower you’re starting with will be amplified post-processing. So, really, the concentrate-making process starts at the seedling level, requiring the right care and attention to coax out the results you’re looking for.

Tetrahydrocannabinol (THC), just one of hundreds of cannabinoids found in cannabis.

But what makes good flower? While this can be a subjective question, those producing concentrates generally look for flowers with big, abundant trichomes. Trichomes are the small, dewy structures found across the cannabis plant on buds, leaves and even the stem. They’re responsible for producing the plant’s cannabinoids and terpenes – the chemical compounds that give a strain its unique benefits, aroma and taste. Evolutionarily, trichomes attract pollinators, deter hungry herbivores and provide some defense against wind, cold and UV radiation.

Generally, trichomes indicate how potent the flower is. Plus, what we’re most often looking for when making concentrates is higher cannabinoid and terpene profiles, while also ensuring absolute safety.

What measures can growers take to produce crops that are ideal for concentrate production? Start with the following:

Avoiding Contaminants
Just like you would wash your fruits and vegetables before consumption, consumers want to be sure there’s no dangerous residuals in the concentrate they are ingesting. Growers can avoid any post-process residuals by taking a few key steps, including:

Photo: Michelle Tribe, Flickr

Cutting out the pesticides. Any pesticides that are on your flowers before they go through processing will show up in your concentrates, often even more – you guessed it – concentrated. This is a serious health concern for consumers who might be sensitive to certain chemicals or have compromised immune systems. It’s dangerous to healthy consumers, too. Rather than spraying hazardous chemicals, growers could consider integrated pest management techniques, such as releasing predatory insects.
Limiting foliar spraying. Some growers will use foliar spraying to address nutrient deficiency or pest-related issues through delivering nutrients straight to the leaves. However, this can also result in contaminated concentrates. If you really need to spray, do it during the vegetative stage or investigate organic options.
Taking the time to flush the crop. This is a critical step in reducing potential contaminants in your concentrate, especially if you’re using a non-organic nutrient solution or fertilizer. Flushing simply means only giving your plants water during the final two weeks of flowering before harvest, resulting in a cleaner, non-contaminated flower and therefore a cleaner concentrate.

Perfecting the Indoor Environment
When cultivating cannabis indoors, growers are given ultimate control over their crop. They control how much light the plants receive, the lighting schedule, temperature and humidity levels. Creating the ideal environment for your cannabis crop is the number one way to ensure healthy plants and quality concentrates. There are many factors to consider when maintaining an indoor grow:

Temperature regulation. Trichomes are sensitive to temperature changes and start to degrade if they’re too hot or too cold. To maintain the best trichome structure, you’ll want to maintain an ideal temperature – for most strains, this falls between an idyllic 68 and 77 degrees.
Adequate light. For plants to perform photosynthesis indoors, they’ll need an appropriate light source – preferably one that is full-spectrum. Full-spectrum LEDs are able to closely replicate the sun and provide ample, uniform light to your crop. Another selling point for LEDs is their low heat output, making it much easier for growers to regulate ambient heat.
Rows of cannabis plants drying and curing following harvest
CO2. Another necessary ingredient for photosynthesis is CO2. Providing your indoor crops with CO2 can boost plant size and yields and, therefore, provides more surface area for trichomes to develop and thrive.
Cold snap prior to harvest. Some growers rely on this age-old tactic for one last push before harvest – lowering their temperature for a few days right at the end of the flower cycle. They believe this puts the plants into a defense mode and will produce more trichomes in order to protect themselves.

Following Best Practices Post-Harvest
You made it to harvest – you’re almost done!

When harvesting and storing your plants, handle them with care to reduce damage to trichomes. If you’re planning on immediately making concentrates, you can move forward to the drying and curing process. If you’re going to wait a few weeks before processing, freeze your plants. This will preserve the cannabinoid and terpene profiles at their peak.

As the cannabis industry continues to expand, more consumers are likely to reach for concentrates at their local dispensaries. It makes sense that businesses want to diversify their offerings to satisfy customers looking for the most effective way to consume cannabis. As with any cannabis-derived product, producers will want to prioritize quality and safety – especially in the concentrate market.

October 28, 2019

From MedTech to Cannabis: A Q&A with Jennifer Raeder-Devens

By Aaron G. Biros

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Project Yosemite, a cannabis product innovation and brand development company, announced earlier this month the appointment of Jennifer Raeder-Devens as their new Chief Scientific Officer. Raeder-Devens is a veteran of the MedTech industry, working for companies like Becton Dickinson, Cardinal Health, Medtronic and 3M.

Prior to joining Yosemite, she was the Vice President of Research & Development at Becton, Dickinson, where she oversaw product development and technology strategies to launch infection prevention products including the ChloraPrep first-in-the-US sterile solution patient preoperative topical antiseptic. She was previously the Vice President of R&D, Strategy and Innovation at Cardinal Health. She’s also held roles at Medtronic, 3M Drug Delivery Systems and 3M Skin Health Division and she has a number of patents in drug delivery and medical devices.

Jennifer Raeder-Devens, Chief Scientific Officer at Project Yosemite

In November of 2018, Project Yosemite launched their first product, OLO, which is an infused, controlled-release sublingual strip. Part of Raeder-Devens’ new role at the company is the continued development and expansion of the OLO sublingual strip technology platform. Andrew Mack, CEO and founder of Project Yosemite, says he’s thrilled to have Raeder-Devens on the team. “Jennifer is an extremely accomplished scientist and engineer with extensive experience driving innovation and R&D in the pharmaceutical and medical device industries,” says Mack.

We caught up with Jennifer over the phone to talk about her background in the MedTech space, why she decided to jump ship to join the cannabis industry and what she’s excited to work on now.

Cannabis Industry Journal: Can you tell us about your background, including your work with 3M and Medtronic?

Jennifer Raeder-Devens: I’m coming directly from Becton Dickinson, a global med tech company, where I supervised the development of drug-device combination products for topical antiseptics. I spent about 10 years there, mostly in topical drug and combination product development. Prior to that, I was at 3M and Medtronic working in drug-device combination products. At 3M, I was supervising a team of technology developers for the 3M Drug Delivery Systems business. I had experience working with designing and manufacturing transdermal, nasal, buccal and inhalation drug delivery mechanisms for pharmaceutical partners.

I worked on implantable drug delivery systems at Medtronic, which included working on the biocompatibility of things like pacemakers and drug infusion pumps and optimizing them to reduce infection and enhance healing after the implantation procedure.

CIJ: What made you consider joining the cannabis industry?

Jennifer: With my work in topicals, transdermal and inhalation drug delivery, I had an easy understanding of the different routes of administration we see today in the cannabis industry. And so, from the technology standpoint, I thought this was a place I could contribute to immediately. And then what got me really excited about it was thinking about cannabis, and just like any other drug, with oral drug delivery, you’ve got first class metabolism and side effects from the 11-Hydroxy-THC that are undesirable and you’d rather not have delivered through the gut.

OLO sublingual strips have a 10-minute onset time

I got excited when I saw the development of things like sublingual strips that were focusing on alternatives to smoking that would preserve that relatively fast onset and mitigate some of the side effects of edibles.

The other thing I really like about the cannabis industry: Previously I have been very focused on known drugs that are already approved and repurposing them into a new delivery system. What really interests me about the cannabis industry is the active cannabinoids and terpenes are somewhat known and somewhat unknown, so there is this really interesting challenge there of trying to separate the wheat from the chaff in terms of producing therapeutic effects.

It is a really interesting space where the indications of certain molecules are evolving along with the delivery technology. So, it is a really exciting and eye-opening way to take the next step in my career and have this wide-open space in front of me, both in terms of the different cannabinoids, their effects and the delivery systems we can use.

CIJ: How might you be prepared, given your background, for some of the challenges in the cannabis space?

Jennifer: I think the challenges in cannabis delivery are not different from the challenges in pharmaceutical drug delivery. It’s just that we have this additional complexity of the entourage effect. We can be engineering not just the main ingredient of THC, but also all the other cannabinoids and terpenes. So, for example, with my background in infection prevention, we build a product that we know reduces the risk of infection, but we are really challenged to actually prove it reduces the risk of infection. We have a similar situation in the cannabis industry, where we can get the THC, or CBG or CBN where we want it to go, but then we are really challenged to figure out how we can find, what we call in the pharmaceutical industry, a surrogate end point for efficacy, so that we can test that product and really believe that when we put the product on the market, even though we haven’t tested thousands of users or conducted large randomized clinical trials, that the effect will be shown. We are networking and partnering with a good scientific community to build the right product and do some testing at a small scale that really demonstrates the product achieves the effect that we are really looking for.

CIJ: Can you tell us a little about your new role with Project Yosemite?

Jennifer: My job description falls into three buckets: The first part is that we are forming a scientific advisory board and we are working with some of the leading cannabinoid researchers around the country and around the world. These are the people identifying whether or not certain cannabinoids could reduce cancer cell metabolism or whether cannabinoids contribute to weight loss or diabetes control and other things of that nature. We are trying to reach as far upstream as we can to grasp the emerging understanding of the performance of cannabinoids and terpenes in the endocannabinoid system. So, part of my job is to chair that scientific advisory board, get the thought leaders together in the room and have them bring their knowledge and explore with our own knowledge what cannabis can really do.

The OLO sublingual strips

I have worked in topical, transdermal, buccal, nasal, inhalation drug delivery. In the second bucket of my job, we are trying to understand a given indication or experience that our users want to have, what would be the right route for them. We are challenging our sublingual delivery mechanism to see how fast of an onset we can really get. Right now, we are at 10 minutes for drug delivery in sublingual and we are still trying to get an even faster onset time for the sublingual strip.

For other indications, like chronic pain, we may want to think about a sustained release, so sort of aligning the different indications with which different cannabinoids and terpenes will work for it and see which delivery platform will work for what we are trying to accomplish in each indication. So, we do not plan to remain solely a sublingual strip company, but will build out additional delivery platforms as we develop new indications.

Right now, we are working upstream with the growers and the processors to get cannabis oil and extracts. Some of the growers are working on different genetics in their cultivars to grow plants that have different ratios of different cannabinoids that we know from the emerging research will have an impact on people’s experience. Now we are working with growers to really get ahead of the curve on how to formulate products with various cannabinoids.

We have an R&D team in house that I supervise. We are always working with our production team to make small improvements such as the faster onset and the dissolution rate and things like flavors, which covers a downstream focus as well.

December 6, 2017

New Drug Delivery Mechanisms For Cannabis Products

By Aaron G. Biros

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Next Frontier Biosciences announced the launch of their new product line, Verra Wellness, in the Colorado market this week. The products are designed with relatively new concepts for the cannabis market, including nasal, sublingual and topical administration.

The company claims their product is the first-ever cannabis nasal mist. Co-founded by biotech executives Marc Graboyes and Dr. Paul Johnson, Ph.D, Next Frontier Biosciences is developing this product line with three formulations, each with a different ratio of THC and CBD. According to a press release, Next Frontier Biosciences is focused on developing cannabis products with these new drug delivery methods, and even offering a microdosing option.

“We believe that leveraging science and research is the key to optimizing product development,” says Dr. Johnson, one of the co-founders. “With the introduction of our Verra Wellness line of products, we are reshaping the cannabis industry by offering trusted products that provide uniform composition, formulation and dosing in highly consistent modes of administration.”

Their topical salves in the Verra Wellness product line are “designed to permeate skin and muscle tissue deeply without penetrating the blood stream or causing psychoactive effects,” reads a press release. In addition to the nasal mist and topical salve, they also launched a sublingual spray.

Marc Graboyes, chief executive officer and co-founder of Next Frontier Biosciences

According to Marc Graboyes, chief executive officer and co-founder of Next Frontier Biosciences, drug delivery mechanisms like a nasal mist are superior to smoking, vaporizing and edible administration. “Nasal administration is among the most effective delivery technologies due to the extensive vascularization and large surface area of the nasal cavity, allowing for rapid uptake and reliable results,” says Graboyes. “The cannabis nasal mist is a novel technology that other brands have not yet tapped into.”

He says this drug delivery mechanism is efficient, fast acting and a healthy alternative to smoking. “For many, nasal delivery is a desirable alternative delivery mechanism because it does not present the health risks associated with smoking,” says Graboyes. “In addition, as previously mentioned, the large surface area of the nasal cavity permits high drug absorption, and the fine-mist sprayer allows for accurate, consistent dosing and an excellent safety profile. Further, nasal delivery avoids first-pass metabolism by the liver, where a large fraction of orally delivered cannabinoids are inactivated.”

While the Verra Wellness product line is available in Colorado starting this week, the company has plans to expand into a number of other states as well. “We are executing a multi-state expansion, with plans to move into the California, Oregon, Washington and Nevada markets in the coming year,” says Graboyes.