Clinical research – an overview of terminology
We are often asked why it is important to do clinical research in medical cannabis. There are lots of trials that show that it works.
Yes, there are, but many of the trials are small and therefore can not be used as other than an indication when it comes to clinical research. When cannabis is used medically, you need to investigate how it works on a very large group of people, both healthy and ill, and with a fixed content of, for example, CBD or THC. Otherwise, you cannot compare the results in the same way that you can with other medication.
One of the challenges of cannabis compared to other drugs is that it is a plant. And as something live, it behaves differently in reagard to what subspecies it is, when it is harvested, what temperature it been exposed to, what light it has been exposed to, among others. It is precisely why the rules for cultivation in Denmark are as strict as they are – so you know exactly what you get.
Within clinical research there are a lot of terms that can be difficult to relate to. Therefore, we have made a small overview:
Blinded and placebo
Placebo is a “drug” with no medicinal qualities (eg sugar pills). In a clinical trial, placebo is given to a portion of the participants to ensure that they do not indicate improvement/deterioration because they think they are given the effective medicine and indicate effects/side effects not caused by the drug. The fact that the participant does not know if he/she is getting the active substance or not, is called that the study is “blinded”
In a double-blind trial, neither the scientist nor the physician knows if the participant is given the active substance or placebo. This makes the research even more credible, as the physician may otherwise inadvertently guide the patient towards certain answers about effect or side effects.
Crossover an additional measure taken to ensure the effectiveness of the drug. Here, you will switch to the recipients of the placebo and the recipients of the drug during the study without their knowledge. That way, you are absolutely sure that you do not get “false” feedback. Crossover is used especially in pain management, where you depend greatly on the patient’s own experience.
In a randomized trial, participants are divided into groups by draw. That is, the researcher does not choose which of the participants will receive that drug (or nothing).
Preclinical studies are the studies that take place before you start testing on humans. It may be through animal testing or testing on cell-cultures (in e.g. petri dishes)
In Phase 1, you test the drug on humans for the first time. This is done by giving it to a small group of volunteer healthy people who then report back any side effects. You also examine how the product breaks down in the body.
In Phase 2, the drug is given to a group of patients. Here, it is examined whether the medicine works, how much a dose is needed and what side effects the patients experience.
In Phase 3, the drug/placebo is given to a very large group of patients (00-3000) to test the effect and possible side effects. Only then can the drug be approved by the Danish Medicines Agency.
Phase 4 occurs after the product is approved and can be prescribed for patients. Here, a close eye is kept on any unknown rare side effects. No matter how many tests you’ve done, it’s impossible to predict everything. This would require testing the product on all the people in the world before it was released.
In Denmark, most clinical trials of medical cannabis have only reached Phase 1 so far. Other countries have gotten a bit further. In Israel, in 2017: 28% in Phase 1, 69% in Phase 2 and only 3% in Phase 3, but here too, it comes to a halt before reaching Phase 4 as Phase 3 is a very costly affair.