Deutsche Welle (English edition)
Medicinal cannabis: 'Wonder drug' or work in progress?
Cannabis is more than a recreational drug. Nonpsychoactive cannabis may have health benefits, from protecting against human coronaviruses to antibiotics.
Scientists are researching a range of possible medical applications for the chemical compounds, often synthetic ones, that can be derived from cannabis.
Forms of cannabis have been said to provide pain relief over millennia, via a history of "herbal remedies" starting in Egypt, China, India and ancient Persia.
More recently, scientists have found that terpenes, a chemical in cannabis which helps give the plant its fragrance, may work as an antiviral agent against a human coronavirus called HCoV-229E.
That's not the same coronavirus as SARS- CoV- 2, the one that's responsible for the COVID-19 pandemic.
But it is one of seven coronaviruses that infect humans. The terpene was tested in combination with a cannabis compound called cannabidiol (CBD).
Earlier in the pandemic, researchers in Canada suggested a synthetic form of cannabis may inhibit the novel coronavirus and stop it from infecting our bodies via ACE2 receptors. ACE2 receptors are gateways into the human body. They exist in lung tissue, oral and nasal mucus, kid
neys, testes, and gastrointestinal tracts.
The US Food and Drug Administration (FDA) and the EU's European Medicines Agency have approved a cannabis-derived drug called Epidiolex for treating epilepsy. Other drugs, such as Marinol and Syndros, have been approved for treating weight loss in people living with HIV/AIDS and nausea and vomiting. Some are used to treat the side-effects of cancer.
There have also been studies into the use of cannabinoids, chemical compounds derived from cannabis, for treating dementia, Type II diabetes, and cancer. But these are early days in this line of research.
Medicinal cannabis: our current understanding
We're only just beginning to understand what medicinal benefits cannabis and its variants hold. They may, for example, enhance or improve the effect of antibiotics. That's a busy area of research that we'll get into in a moment.
First, a few words on terminology. Scientists refer, on the one hand, to medicinal or synthesized forms of cannabis.
On the other hand, they talk of "crude" forms of cannabis, such as its leaves and seeds, which are most commonly what people consume recreationally and often illegally. That can be leafy marijuana (or Marihuana) or a thick resin, known colloquially as hash.
But it all starts with the Cannabaceae plant family and its descendant, Cannabis sativa L.
Cannabis consists of 540 chemical substances and at least 80, but possibly more than 100, chemical compounds. Cannabis is not all psychoactive Chemical compounds in cannabis are called cannabinoids.
The plant's two best understood compounds are delta-9tetrahydrocannabinol (THC) and cannabidiol (CBD). Both compounds are psychoactive, but to varying degrees. A psychoactive or psychotropic substance affects a person's mental state — how the brain works. It affects mood, awareness, thoughts, feelings, and behavior.
CBD is less psychoactive than THC. In fact, CBD may even reduce the psychoactive elements in THC. CBD has antidepressant and anti-inflammatory characteristics.
Cannabidiol is not to be mistaken for cannabinol (CBN). CBN was the first cannabinoid to be detected. As with CBD, CBN has anti-inflammatory properties.
Binding to the body
Cannabinoids also exist naturally in our bodies. They are called endocannabinoids and are part of the endocannabinoid system, which allows phytocannabinoids, those derived from
plants, to affect us.
THC, for instance, binds to "CB1" cannabinoid receptors in the brain, and that starts a process that releases its psychoactive effect.
Finally, it's worth mentioning "hemp." Hemp is a strain of cannabis, but it's not the same as marijuana. It is grown industrially, and its stems and seeds are used in textiles and CBD oils for skin treatments or balms.
Cannabidiol and antibiotics
Researchers are also looking at CBD (cannabidiol) as a potential solution to antibiotic resistance.
Doctors say we use antibiotics too much and that it is reducing the ability of those medicines to kill bacteria.
Antimicrobial resistance is the same idea but it includes viruses, fungi and parasites — any microbial life that poses a threat to our health.
CBD has an antibiotic effect of its own, but it has "even stronger effects when combined with other antibiotics," said Sigrun Lange, a reader in molecular pathology at the University of Westminster in the UK.
Lange and her team have looked at using CBD with antibiotics to fight a strain of Escherichia coli (E.coli), a bacterium that causes stomach cramps, diarrhea and vomiting. They also looked at a strain of staphylococcus aureus, which causes skin infections among other things.
Now, scientists typically distinguish between gram-positive and gram-negative bacteria. But we will have to save explaining that for another time.
Suffice to say: E.coli is gramnegative and staphylococcus aureus is gram-positive, and the main point here is that CBD can "enhance" the effect of specific, existing antibiotics against certain strains of those bacteria.
"You might need to use less of those antibiotics if you combined them with CBDs," says Lange, highlighting a jackpot application for cannabis in medicine.
But there is some debate about its efficacy, depending on whether the bacterium is gramnegative or gram-positive.
The catch with CBD
Other researchers in Denmark, notably Janne Klitgaard and her PhD candidate, Claes Wassmann, say CBD "appears to be ineffective against gramnegative bacteria," such as E.coli.
They also tested cannabidiol with the so-called "superbug" Methicillin- Resistant Staphylococcus aureus (MRSA) and found it to be "sensitive to CBD."
But there are many strains of both E.coli and Staphylococcus, so all this research is preliminary for now.
Plus, there's at least one other known drawback, and that's been detected by all the teams, including one at the
University of Queensland, Australia.
Mark Blaskovich and his lab used a chemically synthesized CBD in mouse models. They say it was effective against MRSA, gonorrhoea, meningitis and legionnaires disease.
But they found also CBD works better externally — on the surface of the skin, for instance — rather than when it's used to treat an infection that's in the blood.
"There are a couple of possible explanations," Blaskovich told DW. "One is that CBD degrades within the body when it binds to other compounds [Ed.: like proteins or lipids/fats]." The drawback, however, is that "once it's in the body, CBD gets absorbed by all the tissues and everything else, and there's very little CBD left to kill the bacteria."
Clearly, there is work still to be done, but the potential is great, as Lange suggests:
"CBD has been used for thousands of years as a therapeutic strategy against all sorts of bacteria, viruses and parasites, even the hunter-gatherers used it in medicine," she says. "So, I don't think it would have the same story as antibiotics in terms of resistance. But, then again, we've yet to explore that deeply. So, it's hard to predict."
produce billions of doses by the end of 2021.
Second, logistics experts have to ensure appropriate distribution of the vaccine, and political leaders have to decide who gets the vaccine first.
Read more: Can a vaccine be given out fairly?
In the end, though, it will be up to each individual to decide. A 2020 survey of more than 13,000 people in 35 countries most affected by COVID-19 showed that the majority of people asked would choose to get vaccinated.
A survey by YouGov in January found that the willingness to be vaccinated increased in some European countries, whereas the trend isn't as clear in other regions of the world.
How fast can vaccines be developed?
It can take several years to develop an effective and safe vaccine. On average, it takes between 10 and 12 years, but it can take longer. The search for a vaccine against HIV has been going since the early 1980s — so far without success.
In the case of COVID-19, researchers are racing to shorten the time it usually takes because of the ongoing pandemic. Despite the pressure that that brings, vaccine developers, manufacturers and the World Health Organization (WHO) say there will be no compromises on safety.
Research teams are aiming to accelerate, or limit, the time it takes to get to approval during the pandemic to an average duration of 16 months.
That will only be the beginning. Once clinical trials are successfully completed and a vaccine is approved and produced, researchers start phase IV, during which they observe the progress of vaccinated patients.
Which types of COVID-19 vaccine are in development?
Researchers are pursuing 13 different approaches for vaccines against COVID-19.
Most of the vaccine candidates use a protein-based subunit — so, instead of using a complete pathogenic virus, they are built on a small component of it, such as a protein found in its outer shell.
That protein is administered to patients in a high dose, with the aim of inducing a fast and strong reaction by the human immune system.
The hope is that the immune system will "remember" the protein and trigger a similar defense reaction if or when it comes into contact with the actual virus.
Vaccines against hepatitis
B and HPV ( human papillomavirus), for example, are based on this principle.
Four additional approaches have made it to phase III.
Nonreplicating viral vectors are a type of so-called recombinant vaccines: Researchers modify the virus's genetic information by switching on or off or altering certain functions. By doing that they can, for example, reduce the infectiousness of a virus. Such genetic modifications, however, require that science already has detailed knowledge about which parts of a virus' genetic material are responsible for which functions in order for them to be able to manipulate them effectively. The term "nonreplicating" means that the virus in the vaccine enters cells in the human body but is unable to reproduce there on its own.
Inactivated vaccines use a "dead" version of the pathogen. They tend to provide a lower level of protection than live vaccines. Some vaccines in this class have to be administered several times to achieve sufficient immunity. Examples of inactivated vaccines include ones against influenza and hepatitis A.
RNA vaccines follow a different strategy, without using any "real" component of the virus at all. Instead, researchers aim to trick the human body into producing a specific virus component on its own. Since only this specific component is built, no complete virus can assemble itself. Nevertheless, the immune system learns to recognize the non-human components and trigger a defense reaction.
Vaccines based on viruslike particles use another approach: Researchers only use the empty virus envelope — without any genetic material inside of it — to train the immune system.
With DNA-based vaccines, patients are injected with the virus's genetic makeup for the human body to produce virus particles itself without being actually infected. Confronted with these self-produced virus particles, the immune system is supposed to learn to recognize and fight the actual virus.
Who is working on a COVID-19 vaccine?
At time of writing, there were well over 100 research teams worldwide developing a COVID-19 vaccine. So far, 24 teams have advanced their vaccines to the third phase of clinical trials. Although some of these vaccines have already been approved in some countries, they still continue to be tested in clinical trials in parallel.
Five teams stand out for conducting the most extensive clinical trials:
Belgian company Janssen Pharmaceutical is testing its candidate vaccine, which is based on a nonreplicating viral vector, on about 574,500 people in South Africa, Belgium, the United States, Argentina, Brazil and Colombia.
The US companyModerna is testing its RNA-based vaccine on 78,000 people in the US, Canada, France and Japan
In a public- private partnership between the University of Oxford and the British company AstraZeneca, researchers are testing their vaccine candidate on approximately 57,000 people in the US, Chile, Peru and the UK. Their vaccine is based on a similar principle to Janssen's.
The Chinese company Sinopharm is working in various constellations with the Beijing Institute and Wuhan Institute. Taking all trial series together, they are testing an "inactivated" vaccine on around 55,000 people in Bahrain, Jordan, Egypt, Morocco, Argentina and Peru.
A German company, BioNTech, is pursuing a different approach: It is focusing on RNAbased technology and testing the BioNTech-Pfizer candidate vaccine on about 51,000 people in the US, Argentina and Brazil, among other countries.