From the 1960s, as the sober conservatism of the postwar generation puttered and died, smoking cannabis became the cry of a new society. “I think it’s terrible that the American public have accepted a law that makes smoking a harmless weed illegal,” shouted one fan as police hustled him away in a 1968 film. Not everyone agreed. A year earlier, Time published an article decrying the “grave hidden dangers” of the drug.
From this febrile beginning, it is remarkable how fast cannabis has become accepted across the Western world. Over half of the US population – 64% to be exact – now support legalisation, compared with only 12% in 1969. Governments have followed suit, with cannabis now legal everywhere from California to Spain. And all of this is big business: a 2016 report found that legal cannabis sales totalled $5.86 billion in the US alone.
Away from its radical past, cannabis has also become a useful tool in medicine. Over a million Americans regularly smoke the drug on prescription, mostly for pain relief. With new pharmaceutical treatments being developed all the time, cannabis could be on the edge of another revolution – one that carries potentially huge health and financial benefits.
Ticking over
Cannabis is a complex plant that contains hundreds of different chemical compounds, known as cannabinoids. One of the most prominent is tetrahydrocannabinol (THC), responsible for giving users the infamous euphoric high. Cannabidiol (CBD) has similar properties, but can be ingested without any psychological effects.
Though CBD and THC are the most famous cannabinoids, new variants keep being discovered. In 2015, a team from the University of Mississippi published a paper detailing seven such chemical compounds.
Moreover, there are numerous types of cannabis plant. While some varieties are specifically grown to promote THC content – and increase the ‘high’ – others are far gentler. These low- THC plants are known as hemp, and are popular for their high levels of CBD. They have the added advantage of being far tougher than their psychoactive cousins. While THC-based cannabis has to be carefully cultivated under special lights and at specific temperatures, hemp can be planted next to carrots and potatoes.
Despite these differences, cannabinoids share many of the same attributes. By imitating natural compounds produced in the body – so-called endocannabinoids – they promote homeostasis and mediate communication between cells. This helps keep the body ticking over smoothly, explains Ingo Michels, the recently retired head of office at the German Federal Drug Commission, which organised Germany’s recent move into medical marijuana. “Over the past 25 years, there has been a surprisingly rapid development of knowledge on the effects of cannabinoids,” he notes. “The medical applications of herbal, synthetic and semi-synthetic cannabinoids have been shown to be useful [across a range of conditions].”
High revenue
None of this is news to James Linden. He has always been interested in the medical potential of cannabis, even as he was working in sales for a pharmaceutical firm in his native Ireland. “People started coming out of the woodwork talking about using cannabis for medical conditions,” he remembers. “I ended up meeting more of these people, and my own interest was already piqued.” All this prompted Linden to set up Greenlight Medicines, a Dublin-based cannabis pharmaceutical firm.
Right from the off, Linden emphasises that CBD is at the centre of his business model. “It’s just easier to work with,” he says. “There is less legality around it.” He is quite right: due to its lack of psychoactive properties, hemp-based CBD can be bought over the counter in Irish health stores.
Although this means that Linden and his colleagues cannot yet make any medical claims about their products, the oils are particularly popular for treating a number of ailments, including the inflammation and nausea associated with chemotherapy. “There is also a drive away from the kind of toxic standard pharma approach,” he adds. “Natural therapies are on the rise, and there is more interest in deriving molecules from plants, isolating them and making them pharma appropriate.”
All this curiosity is a financial boon. “We used all this as a revenue stream for us to generate some of our own research funding and push back on investment,” Linden explains. “We could minimise the equity that we gave up on the company, and minimise the investment required.” Greenlight is not the only firm to go down this path. Marketing CBD commercially has become hugely profitable, with the Brightfield Group estimating that hemp oil sales will reach $1 billion by 2020.
Cannabinoid cures?
It might help keep Greenlight in the black, but marketing CBD in shops is just one branch of a wider strategy. For their part, Linden and his colleagues are working to turn cannabinoids into genuine alternatives to prescription medicines, with addiction as one area of interest. “We know CBD in particular helps people to get off prescription drugs, especially painkillers,” Linden explains. “We want to understand the mechanism that allows people to be relieved of their addicted state.”
Linden is just as excited about his work with other cannabinoids. “People think that because we’re selling CBD in pharmacies, we just look at CBD. CBD is really interesting, and it is doing a lot of great stuff for people, but we’re interested in all kinds of [cannabinoids]. At the moment, we are preparing systems and assays that will allow us to test all the cannabinoids.”
Nor is Linden alone here. Though the evidence is far from conclusive, researchers are keen to use new cannabinoids in combating several different illnesses. Like other areas of medical research, cancer gets a lot of attention. Cannabinoids like JWH-133 can apparently fight the spread of breast cancer, while other research suggests that combining cannabinoids with regular medication can also work. For example, a recent study published in Cell Death and Disease found that pairing cannabinoids with gemcitabine – a traditional chemotherapy drug – can help destroy pancreatic cancer cells.
Linden is clearly enthusiastic about all this but he admits that pharmaceutical companies are not quite ready to release cannabis-based cancer drugs to patients. “The evidence is essentially anecdotal until you put it into a clinic,” he says. Other scientists, however, have marched ahead. Epidiolex is a CBD-based drug that can battle a range of epilepsy disorders, including Dravet syndrome and infantile spasms. Unlike similar oncological drugs, epidiolex already has FDA clinical trial approval and support from the American Epilepsy Society.
Further insights
With all this activity, no wonder Linden is optimistic about the future of cannabis-based pharmaceuticals. “We, and a number of other companies, are developing cannabinoid medicines for the pharmaceutical marketing authorisation route,” he says. “In five years time, I would like to think that we’ve developed a couple of interesting pharmaceutical products.” Michels agrees, adding that he expects “further insights to emerge from our experience [of using cannabinoids] over the next few years.”
And though the cannabis plant still has plenty of secrets to reveal, researchers have started hunting for cannabinoids from other sources. “There are other [items] that contain cannabinoids, like echinacea,” Linden says. “You’re starting to find them in lots of plants.”
Supermarket shoppers may not realise it, but even basic foods like black pepper and chocolate contain useful compounds too. Research is just starting out, but previous successes are leading scientists forward, Linden adds. “Before, when the molecules were not identified, it was more difficult to find them in a [plant] when you did not know what you were looking for.”
Advances in cannabinoid pharmaceuticals are likely to be shadowed by the continued rise of pure medical cannabis, Michels believes. “The German experience [legalising medical cannabis], in addition to the experiences of countries like Israel, Canada and the US, will contribute to a significant increase in the use of cannabis as a medicine,” he says. “The ability to produce pharmaceutical-quality cannabis will increase the pressure on governments to allow pilot projects for controlled procurement.”
More broadly, manufacturers have started developing new delivery systems for cannabinoids. Though the clichés of peace-and-love hippies die hard, Linden says there will soon be different ways of administrating a dose beyond smoking. “Within five years, we will have more pharmaceutical medicines that contain cannabinoids, [and use] different delivery systems, be they creams or slow-release technologies.”
Because they direct cannabinoids straight into the body – without making the user splutter – inhalers are particularly intriguing, Linden says. “We know that smoking cannabis is brilliant for quick relief from pain symptoms. Smoking is one of the fastest delivery methods. It enters the lungs and blood very quickly. [Certain companies] are trying to replicate that, but in an inhaler.” All this can be complemented by sticking specific matrices to cannabinoids, directing them to the organs most in need of help.
With all this activity, it is difficult to know exactly how doctors and patients will be using cannabinoids a decade from now. The pace of change is simply too fast. But the flower children of the 60s who first brought cannabis to global attention can surely be confident the drug will stay as revolutionary as ever.
