New findings suggest a chemical in marijuana can prevent some people from going blind.
Retinitis pigmentosa is a genetic eye disease that leads to severe vision loss and blindness. The disease affects 1 in 4,000 people and worsens as cells in the retina, called photoreceptors, die off.
But a study published this month in Experimental Eye Research shows chemicals in marijuana, known as cannabinoids, may be able to slow this down.
Using a synthetic form of THC, the compound responsible for marijuana’s high, researchers at the University of Alicante in Spain were able to prevent vision loss in rats with the disorder.
“These data suggest that cannabinoids are potentially useful to delay retinal degeneration in retinitis pigmentosa patients,” wrote Dr. Nicolás Cuenca, the study’s lead author.
At the end of 90 days, rats that received treatment performed better on vision tests and had 40% more photoreceptors than untreated rats. THC also seemed to protect a number of other eye structures, including inner layers of the retina.
Although encouraging, the results were not much of a surprise. As the team notes, cannabinoids have shown promise in treating a variety of degenerative disorders, ranging from Parkinson’s and Alzheimer’sto diabetes and stroke.
Marijuana has also been reported to help in other eye diseases like glaucoma.
In fact, studies show marijuana pathways exist in different parts of the eye. And as early as the 70s, scientists observed a number of interesting effects of marijuana on vision.
For example, a study published in 1978 found marijuana caused a delay in pupil adjustment, concluding that it “seems likely that marijuana or a metabolic product of marijuana acts directly on the retina to produce the delay in glare recovery.”
While the latest study did not look at the mechanisms underlying the benefits of cannabinoids in retinitis pigmentosa, the authors conclude that further research should be carried out.
With interest in marijuana research at an all time high, we spoke to the scientist who mapped the first cannabis genome.
Canadian botanist Jon Page, Ph.D, was one of the lead investigators in the first, and so far only, cannabis genome project.
Published in 2011 in the journal Genome Biology, Dr. Page’s findings unraveled the sequencing of some 30,000 genes that make up the genome of Cannabis sativa, using the popular Purple Kush strain as the source.
The genome has since been available online, and has served as a tool for other cannabis researchers around the world. Dr. Page took the time to answer some of our questions about the project and what lies ahead in the field of cannabis genomics.
Q: What inspired you to pursue the cannabis genome project?
From the time I was an undergrad, I’ve been interested in medicinal plants and plants that have beneficial effects on human health. I focus on the biochemistry of medicinal plants, and study the active chemicals and how these chemicals are produced.
When I was a postdoctoral researcher in Germany in the late 90s, I had already started doing some work on cannabis, mainly trying to figure out how the plant makes THC.
I established my own lab at the National Research Council in Saskatoon when I returned to Canada in 2003 and continued research on cannabinoid biosynthesis and things relevant to the Canadian hemp industry. Hemp is a large acreage crop, but it’s still cannabis and has a lot of similar properties to marijuana.
I was doing small scale genomic studies on cannabis when, around 2009, I was contacted by Dr. Tim Hughes, a professor at the University of Toronto who studies genomics in many different organisms including humans and yeast. Tim basically said, ‘this is a fascinating plant and nobody has even attempted to do a whole genome sequencing project on it, yet it has so many uses and so much history with humanity.’ And medical marijuana was gaining more recognition in both the US and Canada at the time.
So we decided to collaborate on the sequencing of the cannabis genome, which merged my interests in plants, enzymes and cannabis specifically and Tim’s interest in genomics. And also, with cannabis being so important culturally, we wanted to focus on a project that would have some impact for society.
Q: What did the project involve?
Our two teams got together and we were able to obtain DNA of the marijuana strain Purple Kush. The reason we picked Purple Kush was that it was a widespread medical and recreational strain being grown in Canada at the time.
I also had access to various hemp cultivars, so we did the sequencing on Purple Kush, but also some re-sequencing of the hemp genome in order to compare the two types. One of the primary goals of our study was to identify the differences between marijuana and hemp on the genomic level.
Q: What were the major findings?
One major finding was that marijuana type cannabis and hemp type cannabis don’t actually differ by that much. For example, there are no extra copies of the genes for the enzymes of the cannabinoid pathway in the marijuana genome. And yet the plant makes much more THC and other cannabinoids. For example, we think Purple Kush contains around 20% THCA, the acid precursor to THC, and the hemp types contain approximately 5% CBDA.
So the differences don’t seem to be in the number of genes for these enzymes, but the fact that the expression of the cannabinoid pathway is turned up in the marijuana type. We suspect that there are specific regulatory controls, called transcription factors, that increased the expression of the genes for the cannabinoid pathways in marijuana. What this points to is that humans have probably been breeding for more potent marijuana by selecting for transcription factors that turn up the expression of these enzymes.
(Photo: Gagne et al., 2012)
The other major finding, which wasn’t new but was reinforced by our genomic analysis, is what really differentiates the cannabinoids found in marijuana versus hemp is a single enzyme at the last step of the cannabinoid pathway. In marijuana it’s the THCA synthase enzyme, and it’s the CBDA synthase enzyme in hemp.
Up to that point, the metabolic pathway is the same. But then there’s a genetically encoded switch, in which the allele that dominates differs in marijuana versus hemp. Sometimes you get both. For example, if you cross a THCA type plant and a CBDA type plant, the offspring will have each allele.
Others had described that at the genetic level, but they hadn’t really done it at the genomic level. So we proved that it was the split in the pathway at the last enzyme step that was responsible for this important chemical difference.
Q: Why map the cannabis genome as a whole?
Cannabis is an amazing plant: it produces fibre, edible seed, oil and of course cannabinoids like THC. Sequencing the cannabis genome is an important step in understanding the plant’s properties, and improving them for agriculture and medicine.
We felt making the genome itself available for researchers worldwide could really benefit research on all forms of this plant, both the hemp and marijuana types.
There are a lot of limitations on doing research on cannabis. It’s not an easy plant to have in your lab, as you need to obtain a special exemption or license to work with it. But we made the data available publicly through the web, so other researchers interested in things like cannabis evolution, sex determination, etc. could study aspects of the plant’s biology, even without having to grow the plant.
We really think it was an important step to make the genomic resources available and we hope it encourages others to do research on the plant.
The paper has been read by many people since being published, in the sense that it has been accessed more than 47,000 times through the journal website (genomebiology.com/2011/12/10/R102). It’s also been cited by a number of other papers. For example, a recent study from the UK, where they were attempting to breed hemp for different oil profiles.
Q: Is there anything particularly unique about the cannabis genome?
Cannabinoid production is unique to cannabis. No other plants that we know of have that capacity. So the genes that encode the enzymes required to produce cannabinoids are absolutely unique to the cannabis genome.
But overall, there wasn’t anything in the genome that we found exceptionally different from other plants closely related to it. For example, apples and strawberries are in a similar group as cannabis, and their genomes are known and cannabis was comparable to those.
Also, cannabis is closely related to hops. Humulus (hop) and Cannabis are the only two members of the Cannabaceae family. So those two plants are really, really close.
Q: What applications are there for cannabis genomics?
Plant breeding more and more relies on genomic tools. So as plant breeders want to develop new varieties of plants – whether they work on crop plants like wheat or medicinal plants like marijuana – the genome can be used to identify variations in the plants that are desirable. For example, you could breed for specific cannabinoid profiles if you knew the combinations of genes that are involved.
The other application is being able to sort out different strains and different variants in the hemp and marijuana areas. Marijuana in particular has thousands of strains, which have all sorts of interesting names, smells and shapes. What underlies all that variation are differences in the genome.
So applied genomics could be used to understand what makes different strains useful and interesting or also to identify them. For example, understanding the difference between Indica versus Sativa, which scientifically is not very well known at this point.
Q: What about genetically modified cannabis?
I can say it hasn’t been achieved yet, in the sense that there is no genetically modified cannabis plants. As a scientist, I’m not opposed to genetic modification as a general concept, it just hasn’t been successfully applied in cannabis.
Also, a lot of what we’re finding is modern techniques of breeding can achieve many of the same outcomes of genetic modification. So I’m not 100 percent convinced that we need genetic modification in cannabis. But it’s probably something that will be attempted, and we may be seeing it in the next 5 years or so.
Q: Are you pursuing more projects in this field?
Yes. Our team who did the first study are going to be continuing to refine and improve the genome. We have a newly funded CIHR grant to continue this work. My new affiliation is with the University of British Columbia’s Botany Department, where I am an Adjunct Professor.
I’m also starting a company, Anandia Laboratories, to attempt to apply some of these genomic findings towards cannabis with improved therapeutic properties. The name Anandia derives from the endocannabinoid molecule anandamide.
Q: Is there more interest in cannabis genomics now than before?
Oh yeah, it’s amazing. For a number of years, I slogged along as kind of a lone voice in the wilderness working on cannabinoid biochemistry. Everyone was always interested in that work on the scientific level, but it’s a controversial plant and you always got the pot jokes whenever I gave a seminar.
But just in the last 6 or 8 months, there’s been a lot of interest in the genomic and biochemical research that I have done. I think there are two things that are driving it: the changes in regulations in Canada, which seem to have spurred a ‘green rush’, and the changes in Colorado and Washington State.
The new U.S. farm bill also allows research on hemp in 9 or 10 states, which they never were able to do before. So everything is sort of coming together, where cannabis was hot before, but now it’s suddenly white hot in terms of a research area.
Talk of marijuana legalization is taking place all over the world.
The conversation took off in late 2012, when Washington and Colorado voted to legalize marijuana, and only grew louder after Uruguay did the same in December.
While Uruguay is so far the only country to fully legalize marijuana, a number of others look ready to join.
Argentina’s Supreme Court decriminalized personal possession of drugs, including marijuana, in 2009.
But legalization may be on the horizon. Last December, after Uruguay legalized marijuana, Argentina’s drug czar said his country should consider following suit.
Personal drug possession is also permitted in Brazil, although traffickers are still punished.
But this month, a federal judge took the legal community by surprise when he acquitted a marijuana dealer and ruled the country’s marijuana laws unconstitutional.
While the decision is being appealed, some believe it could lead to a serious reconsideration of the nation’s marijuana policies.
With a federal election due in 2015, a lot of attention is being paid to legalizing marijuana. The leader of Canada’s Liberal Party, Justin Trudeau, has been an outspoken supporter of regulating marijuana like alcohol.
While Canada’s medical marijuana program is currently transitioning to a commercial market, legalizing recreational marijuana is now part of the Liberal Party’s official campaign platform.
President Otto Perez Molina was one of the loudest supporters of drug policy reform at the U.N. General Assembly last fall. In his address, the President of Guatemala praised Uruguay and the states of Washington and Colorado for taking a “visionary” approach to marijuana policy.
President Molina also announced that his country would undertake a study of alternate approaches to drug laws.
Despite a long cultural tradition of marijuana use, Jamaica has lagged behind more progressive countries when it comes to reform.
But just in the past year, medical marijuana has garnered significant support from top politicians, including the nation’s health minister. Changes in Uruguay and the U.S. have also given legalization activists new hope.
Federal law in Mexico remains tough on all drugs, including marijuana, despite the flourishing drug trade that fuels local cartels. On the other hand, personal possession of drugs has been decriminalized since 2009.
More drastic change could be coming soon to the nation’s capital. This month, Mexico City lawmakers introduced a bill that would legalize the sale of recreational marijuana.
The small African country happens to be the world’s top hash producer. In fact, hash is estimated to contribute as much as 10% to the nation’s economy, and many Moroccan farmers rely on marijuana crops to sustain their livelihood.
Now, two leading political parties have begun to discuss the legalization of medical and industrial cannabis as a way of stimulating the country’s economic growth and legitimizing the trade for farmers who depend on it.
The Netherlands has long been recognized for its liberal approach to marijuana. Since the 70s, coffee shops throughout the country have been permitted to sell marijuana to both residents and tourists.
However, many have been critical of the country’s failure to legalize production and distribution – creating a ‘back door problem’ that forces coffee shops to illegally obtain their supply.
With such an obvious hole in the law, it’s no surprise that mayors of 35 cities have come together to call for a fully legalized marijuana system.
9. United States
Federal law still considers marijuana as Schedule I substance. And despite President Barack Obama’s interesting comparison of marijuana and alcohol, there isn’t much sign of the law changing soon.
On the other hand, the kick-off of legal marijuana sales in Colorado has drawn significant public attention. Washington’s new marijuana laws will also come into play later this year.
Without a major disaster occurring in the two states, it’s likely that, over time, lawmakers will face increasing pressure to legalize marijuana on the federal level.
Breast cancer cell visualized by a scanning electron microscope. (Photo: National Cancer Institute/Wikimedia Commons)
For more than a decade, researchers in Spain have been studying compounds in marijuana as treatments for cancer.
Cristina Sánchez, PhD, is a molecular biologist at Complutense University in Madrid, Spain. Over the past twelve years, Dr. Sánchez and her team have conducted extensive research on the anti-tumor effects of cannabinoids.
Her lab is not the only one to investigate the unique potential of these cannabis-derived compounds. In fact, researchers in many parts of the world, including the U.S., have demonstrated the ability of cannabinoids to combat tumors in various models.
Dr. Sánchez: “We started working on this project 12-15 years ago, and it was basically by chance. We were working with astrocytes at the time, and we decided to change the model and work with astrocytoma cells; the tumoral cells.
We observed that when we treated these cells with cannabinoids, THC, the main psychoactive component of cannabis, it was killing the cells in our Petri dishes. We were killing the cells. So we said that we were facing some potential anti-tumoral responses.”
Exploring cannabinoids in the treatment of cancer…
Dr. Sánchez: “We decided to analyze these compounds in animal models of breast and brain tumors. The results we have obtained are telling us that cannabinoids may be useful for the treatment of breast cancer.
We started to do experiments in animal of models of glioblastomas – brain tumors – and we observed that cannabinoids were very potent in reducing tumoral growth.
Cells can die in different ways, and after cannabinoid treatment, they were dying in the ‘clean’ way. They were committing suicide (also known as apoptosis), which is something you really want when you have an anti-tumoral effect.
One of the advantages of cannabinoids and cannabinoid-based medicines would be that they target specifically the tumoral cells. They do not have any toxic effect on normal, non-tumoral cells. This is an advantage in respect of standard chemotherapy that targets basically everything.
When we started to see this anti-tumor and cell-killing effects on cancer cells, we decided to set aside our metabolic studies and to focus on cancer.”
On the verge of human studies…
Dr. Sánchez: “We are in contact with doctors in Spain, neurooncologists and breast cancer specialists, that are willing to test these compounds in human patients.
The plant, besides THC, produces cannabidiol. This compound is very special because it is not psychoactive. It has been demonstrated that this has very, very potent (antioxidant properties).
It protects the brain from stress and from damage, kills cancer cells, and when combined with THC, it produces synergistic effects, which means that the effect of THC is potentiated.
At this point, we have enough pre-clinical evidence supporting the idea that cannabinoids may have anti-tumoral properties.”
Colorado plans to spend most of its tax revenue from legal marijuana on preventing substance abuse, according to a FY 2014-2015 budget proposal released on Wednesday.
The proposal allocates $99 million of next year’s budget to the state’s top priority, which is “creating an environment where negative impacts on children from marijuana legalization are avoided completely.”
$45.5 million will go towards youth use prevention, $40.4 million for substance abuse treatment and $12.4 million for public health.
Federal funding makes up 43% of the state’s substance abuse budget and 15% of its youth prevention budget.
A breakdown of the spending shows $5.8 million for a three-year statewide media campaign to educate Coloradans “on the impact of marijuana,” and $1.9 million for a Department of Transportation “Drive High, Get a DUI” campaign.
$7 million will also be used to purchase new beds for substance treatment centers, thereby “increasing the capacity for treating marijuana misuse.”
In total, the state expects to see $184 million in marijuana-related revenue between January 1, 2014 and June 30, 2015.
$40 million of that has already been set aside for public school construction.
“Our administration is committed to the responsible regulation of adult-use marijuana and the effective allocation of resources to protect public safety and health and to prevent underage use,” Gov. John Hickenlooper wrote in a letter accompanying the proposal.
Canadian health regulators have created a new industry that allows what The National Post describes as marijuana ‘mega-farms.’
Come April 1st, these operations are supposed to supply medical marijuana for some 40,000 patients. And these patients are not your average smokers. Last year, they were licensed to consume a total of 190,000 kg of medical marijuana.
But the focus for most of these companies is likely the long-term. According to Health Canada, the number of Canadians using medical marijuana will rise to somewhere between 300,000 to 400,000 by 2024.
When Did It Begin?
In June 2013, Health Canada announced a new medical marijuana program called the Marihuana for Medical Purposes Regulations (MMPR). The MMPR outlined a massive overhaul to the previous medical marijuana program, known as the MMAR.
Complaints about the old program came from multiple sources.
For patients, it was difficult to sign up for medical marijuana. The MMAR required extensive paperwork that doctors had to fill out, which then had to be reviewed by Health Canada for final approval.
Then-Health Minister Leona Aglukkaq announced the MMPR on June 10 (Photo credit: Health Canada)
The MMPR introduces a much simpler prescription-based system, more like the systems of certain states in the U.S.
For law enforcement, the MMAR also created problems by allowing patients to grow in their own homes. Some license holders would use it as a cover-up to grow marijuana for the black market. While others didn’t, privacy laws made it difficult for law enforcement to monitor crime.
The MMPR bans home-grows, forcing patients to register with a commercial producer and purchase their medicine online.
Who Owns the Mega-Farms?
The MMPR allows any commercial entity to apply for a license to produce marijuana. Regulations are strict, which makes the cost of starting a MMPR business high. Thus, those who can afford to meet the regulations also can afford to operate large-scale grows.
Since June, the total number of MMPR applicants has exceeded 400. But the vetting process has been slow. As of now, Health Canada says it has approved 8 companies under the MMPR. But only 4 are listed on the government’s official website. According to Health Canada, the other 4 are not ready to register patients yet.
Tweed CEO Chuck Rifici standing in the empty Hershey’s factory (Photo credit: The Canadian Press/Adrian Wyld)
Hopeful applicants include a company called Tweed, which has purchased an abandoned Hershey’s Chocolate factory in Smith Falls, Ontario with 470,000 square ft. of space. Privateer Holdings, a U.S. private equity firm focused on marijuana, has also purchased a 35,000 square ft. facility in Nanaimo, B.C. through its new Canadian subsidiary Lafitte Ventures.
One company already approved is Prairie Plant Systems, which was the only supplier contracted by Health Canada to supply patients under the MMAR. The company revealed last October that it undertook a $24 million retrofit of its production facility, allowing it to grow 5 times more than before.
Tjalling Erkelens, CEO of Dutch medical marijuana company Bedrocan BV (Photo credit: Bedrocan BV)
Another approved producer, Bedrocan Canada, will initially import product from its Dutch sister company Bedrocan BV, which has supplied European pharmacies with medical marijuana for years. The company plans on beginning production in Canada by late 2014.
What Will Happen on April 1?
Licenses for personal cultivation will expire. Patients will be expected to get their marijuana from a commercial producer.
But there are problems. For one, patients have launched a Constitutional Challenge to prevent the MMPR’s ban on home-grows, which many say would make medical marijuana unaffordable. If they win, they could stop the ban from happening. If they don’t, some say it’ll take more than a policy change to stop them from growing.
Canadians rally on Parliament Hill for 4/20 (Photo credit: Patrick Doyle/Reuters)
Another issue is a shortage of supply. Growing enough cannabis for 40,000 patients isn’t easy.
According to Privateer Holdings CEO Brendan Kennedy, Health Canada expressed concern about a shortage as early as last June. But today, the department says it’s “confident that there will be adequate production levels” for the new program.
However, with only 4 to 8 companies ready to meet the April 1 deadline, it’s unclear whether the MMPR will be sufficiently supplied at the start. And at this point, even if companies like Tweed or Lafitte Ventures are approved before April 1, it seems unlikely they can have product ready by then.
Bedrocan's product sold in Europe (Photo: Sensi Seeds)
Last week, Bedrocan Canada was granted a license to sell medical cannabis under the country’s new program.
Bedrocan Canada was formed by Bedrocan BV, the sole supplier of medical marijuana in Holland and other European countries. It is also now one of 8 companies to be approved by Health Canada under the new program.
The program, called the MMPR, introduces a commercial industry for medical marijuana. Beginning April 1, some 40,000 Canadians will be required to purchase their medicine from companies like Bedrocan, instead of growing it themselves.
Despite Bedrocan’s operations in Europe, the company says it has much to look forward to in Canada. We spoke to CEO of Bedrocan Canada Marc Wayne about the company’s history and what’s in store for Canadians.
Q: How did Bedrocan get started?
Bedrocan started as a family business and it’s still run by two brother-in-laws in Holland. They’ve been in the agricultural business in the north of Holland for 30 years. They got into the production of cannabis seeds when cannabis seeds were legal in the 90s in Holland.
They moved into cannabis production when the government was looking for producers of medical marijuana for the Dutch program. Two companies were selected, but one company fell off, and Bedrocan became the sole provider.
Q: What does Bedrocan do today in Europe?
Bedrocan services all the patients in the medical cannabis program in Holland, which is around 3,000. The Dutch program distributes through pharmacies, so all of Bedrocan product is distributed through the pharmacy system.
It’s also covered by the largest health insurer in Holland, but that’s just been for the past couple years. Those are the type of initiatives we’re going to try and work on in Canada, because there’s precedent over there.
Tjalling Erkelens, CEO of Bedrocan Canada’s parent company Bedrocan BV (Photo: Bedrocan)
Q: So Canadians can hope for insurance coverage?
One of the initiatives we want to take on is how to get insurance coverage in Canada similar to Holland, to enable cost coverage for patients as much as possible.
Bedrocan product is pharmaceutical grade and standardized from batch to batch. We’re hoping that type of quality will help in the argument to the insurance companies, so they know the product they’re covering isn’t different every time.
We believe standardization and quality are, obviously, top priority.
Q: How does Canada’s MMPR program compare to Europe?
The European market for Bedrocan is strongly influenced by government and government regulations.
The MMPR is the next step, in our opinion, in the development of cannabis becoming a more common medicine in Canada, produced and distributed by professional companies.
The MMPR also allows for more competition compared to Europe. The European production is organized usually through contractual agreements between government and producers, which limits the development of a good market model for medicinal cannabis to mature.
Bedrocan BV’s growing facility (Photo: Bedrocan)
But the MMPR puts physicians in a role to give patients access to cannabis like in Europe. That’s a similarity.
Overall, medical cannabis is becoming more of a private industry in Canada, which should hopefully help with pricing in the long run. There’s more competition, so perhaps pricing will come down over time for the patients.
Q: Will the MMPR help cannabis become more accepted in Canada?
You can already see, since the regulations came out, how much more mainstream it’s become in Canada as a topic.
As more companies get involved, and more visibility gets involved, and more people accept medicinal cannabis as an option, it should help provide better access for everybody.