CBD is one of the most well-researched compounds in the natural world.
There’s been a lot of research published on the health benefits of cannabis and CBD products over the last few decades — but not all research is created equal.
There’s a big difference between cell culture studies compared to large-scale, double-blind clinical trials involving real humans.
Now that we’re in a new era of hemp and cannabis legalization, research efforts are ramping up to fill in the gaps in what we know — and just as importantly, what we don’t know about the health effects of cannabinoids.
To date, there have been well over 15,000 individual studies involving CBD.
Most of these studies are molecular analysis and in vitro research — which offer limited evidence for the benefits of CBD.
More recently, there’s been an aggressive push towards more high-quality in vivo and clinical trial studies. These are the studies that are really moving the needle when it comes to our academic understanding of cannabinoids.
CBD is no longer stigmatized, and the early body or research has done enough to prove the safety of CBD. Now all eyes are on the future — what is CBD capable of?
Does CBD actually work? Is there enough evidence to back up the suggested health benefits of this infamous cannabinoid?
Research supports the following effects of CBD for addiction:
List of research studies involving CBD & addiction:
Research supports the following effects of CBD for anxiety:
List of research studies involving CBD & anxiety:
Research supports the following effects of CBD for arthritis:
List of research studies involving CBD & arthritis:
Research supports the following effects of CBD for cancer:
List of research studies involving CBD & cancer:
Research supports the following effects of CBD for diabetes:
List of research studies involving CBD & diabetes:
Research supports the following effects of CBD for epilepsy:
List of research studies involving CBD & epilepsy:
Research supports the following effects of CBD for IBD:
List of research studies involving CBD & IBD:
Research supports the following effects of CBD for headaches:
List of research studies involving CBD & headaches:
Research supports the following effects of CBD for multiple sclerosis:
List of research studies involving CBD & MS:
Research supports the following effects of CBD for nausea:
List of research studies involving CBD & nausea:
Research supports the following effects of CBD for pain:
List of research studies involving CBD & pain:
Research supports the following effects of CBD for sleep:
List of research studies involving CBD & sleep:
Research supports the following effects of CBD for weight loss:
List of research studies involving CBD & weight loss:
Since the prohibition on cannabis was lifted in the Western world, there’s been a great deal of confusion as to how to best regulate CBD and other cannabis-based products.
On the supply side, botanical extract manufacturers are keen to meet growing market demands, but at the same time must carefully navigate an uncertain regulatory environment.
The convergence of these conflicting interests is a recipe for trouble and raises some important areas of concern:
As the CBD industry continues to evolve — there’s an endless supply of questions scientists will continue to seek answers for.
Answering these questions will rely on scrutinous scientific exploration. Through different levels of research, CBD can be vetted to the same stringent standards for safety and efficacy as any other drug or botanical extract.
CBD research falls into three main categories:
So, how does the scientific process work, and what are the methods and stages of research that will ultimately tell us everything we need to know about the benefits and risks of CBD?
Let’s take a closer look at the different levels of scientific research for studying CBD.
Here we provide a glimpse into the painstaking process behind the splashy headlines that appear on an almost daily basis about CBD being nature’s cure for everything from acne to cancer.
CBD is widely regarded as being safe and non-toxic and that’s great news. But, is CBD completely free of any side effects?
This is what basic research studies are designed to explore. Rather than looking at specific benefits of a compound, they assess how much of the compound is needed to produce toxic effects on the body and explore the chemical makeup of CBD or other cannabis extracts.
A common method of assessing toxicity is to give increasing doses of a compound (like CBD) to rats until 50% of the sample population dies. This gives us the LD50 of a compound (lethal dose for 50% of the population).
Careful observation is noted on how the rats die, which gives us a clue as to the toxic side-effects of the compound.
During the first phases of basic research, the structural, molecular, and chemical properties of a substance are determined. This early research tells us that CBD is soluble in fat but not in water and that its molecular formula is C21H30O2.
It’s because of this research that we know CBD looks like this:
Once the structural and chemical properties of CBD are measured and cataloged, researchers introduce controlled amounts of the compound to cell and tissue cultures.
Tissue cultures consist of living cells that are grown in test tubes and Petri dishes (in vitro, literally translated, means “in glass”). The goal of this research is to begin to find out how it will interact with living cells using highly controlled environments.
The in vitro process allows scientists to create precisely controlled environments using a single cell or tissue type, in which all variables can be controlled.
In this phase of research, it’s possible to design an experiment that asks and answers a single question about CBD — which is not possible in a living human with many systems communicating and influencing each other at all times.
The next level of research is in vivo research — which is conducted on live animals and allows scientists to obtain more accurate information about the effectiveness, safety, and toxicity of the substance. By using real living systems, researchers can test how a compound will affect the organism as a whole. In vivo testing can compare effects across different species. Usually, mammals are chosen for in vivo medical research since their physiology is most similar to ours.
Gradually, the research is advanced from rodent species (mice, rats, rabbits, etc.) to larger species (cats, dogs, non-human primates). This can reveal how response differs from one species to another and can also help researchers narrow down a safe starting dose when it comes time to test on humans.
With this information, we can start to understand how CBD is likely to travel into and through the body, and how much the body can safely handle. This information is used as a basis for the next stages of research that look closer at the actual interaction CBD has on the body.
In vivo research also determines:
A potential limitation of in vivo research on CBD is that each species contains different receptor counts. Although all mammals have endocannabinoid systems, the densities and distributions of endocannabinoid receptors can vary a lot from one species to the next — therefore changing the effects of CBD.
For example, rats and rhesus monkeys have higher cannabinoid receptor densities than humans in some parts of their brains and lower density in other parts. This makes it difficult to extrapolate how CBD will act in a human compared to an experimental animal.
Currently, the FDA and associated regulatory agencies are requiring researchers to provide data to substantiate their choice of animal species for their studies. But even with these precautions in place, it’s important to keep in mind that drugs that prove safe and effective in animal testing might have different effects on humans.
Once sufficient in vitro and in vivo research has been conducted to establish that CBD might be reasonably effective and safe for a particular purpose clinical studies, i.e. experiments on human volunteers, can begin.
Clinical research is considered the highest level of experimental research because it’s done directly on humans. These studies can be used to confirm the pharmacokinetics from in vivo studies and test whether the benefits in laboratory animals can be replicated in humans.
Clinical trials may be used to assess the following:
The quality of clinical trials can vary widely, and there are some key elements to consider when assessing the quality of a particular trial.
A placebo control is a critical component of a clinical trial to ensure the results of the study weren’t caused by the participants’ expectations. To apply a placebo control, a sham treatment is given to one group (an inactive compound that looks like CBD but isn’t).
This procedure is designed to eliminate the placebo effect — where symptoms may improve after a patient believes they were using a medication, even if there were no active compounds in the treatment. The placebo effect has been found to occur in about 40% of study participants.
To make sure there are no patterns in the treatment group or placebo control groups that may affect results, statistical randomization is used to separate the participants.
This process assures that the participants are equally distributed to each arm of the study.
Randomization prevents all participants with a particular characteristic, such as age, sex, or a genetic risk factor to be placed in the same group. It also prevents conscious or subconscious researcher bias from influencing the experiment, such as placing all of the participants most likely to have a good (or bad) response in the same group.
Blinding is used to make it unknown to the study participants and researchers which participants are getting a dose of CBD or placebo. This eliminates bias by not revealing which treatment is being administered.
There are two categories of blinding:
Single-blind — the participant is not informed of which treatment they are receiving
This prevents the participants’ preconceived ideas or expectations from influencing their responses. Single blinding can help eliminate the placebo effect.
Also, many studies rely on subjective reports by participants about their symptoms and overall experience. Single blinding eliminates these potential biases. If they think they’re getting the treatment, they may answer the questions differently than if they knew they were taking the placebo. So it’s best to keep this part a mystery until the trial is over.
Double-blind — both the participant and the researcher don’t know which treatment is being administered to which participant. This prevents the researcher from consciously or subconsciously behaving differently toward participants in ways that could influence the results of the study.
The best clinical trials use double-blinding in their research model.
Phase I trials are the first studies in which a drug is given to a small group of people (up to 80). In this phase, the best route of administration, i.e. by mouth, inhaled, topical, injected into the bloodstream, etc. is determined, as well as ideal dosing levels and frequency.
If this study proves safe and shows improvement, the study can move on to phase II.
Phase II clinical trials obtain further safety information and begin to collect data on effectiveness. These studies involve larger numbers of participants — usually between 100 to 300.
Phase III clinical trials compare the new drug to a drug that is commonly used as the standard of care for a particular condition. These studies use large numbers of participants (from 300 to 3,000 or more).
Once a drug is approved by the FDA, the manufacturer may elect or they may be required by regulatory agencies to conduct the fourth phase of trials.
Phase IV clinical trials determine long-term side effects and the risk-to-benefit ratio for someone who may need to use the drug ongoing over a long period of time. These studies use the greatest number of people, with participants potentially numbering in the thousands . They also tend to cover several months, or even years to collect long-term health data.
Once a CBD-based drug has been FDA-approved it can be included in epidemiological research. Epidemiology seeks to understand the frequency and distribution patterns of a disease or health condition.
Part of epidemiology involves studying the effects of interventions, which can include eliminating exposure to environmental toxins and pollutants, changing lifestyle behaviors that predispose people to develop certain conditions, and also the effects of drugs or other substances, such as CBD, on the distribution of a particular disease within the population.
To better understand the value of clinical CBD studies, the types of information they provide, and their drawbacks, let’s take a close look at a few examples.
A meta-analysis is a type of systematic review — a study of studies — in which the data from multiple studies on a particular aspect of CBD are compiled and evaluated together. A meta-analysis can include either pre-clinical or clinical studies.
The higher the level of studies used in the meta-analysis the stronger the evidence will be for a particular effect. For example, a meta-analysis that uses double-blind, placebo-controlled, randomized human trials will produce stronger evidence than a meta-analysis of animal studies.
Cannabis research was curtailed for nearly 80 years due to prohibition. Now scientists are working hard to fill in the gaps but at the same time the regulatory landscape is uncertain and the information available to CBD consumers can be confusing.
Scientists are using different research models to answer some of the biggest questions we have around the use of CBD:
Knowing some of the how’s and why’s of scientific research can help you interpret the latest headlines about CBD so you can be an informed consumer.
Scientific medical studies can be divided into five different categories:
Through continued research, building up from basic research all the way up to large-scale meta-analysis, we can seek a deeper understanding of how CBD works, and how to use it both safely and effectively for a wide range of different symptoms and health conditions.