Evidence based

Making Sense of CBD Research

CBD research has ramped up a lot in recent years — but not all research is created equal. Learn about the different kinds of CBD research, and why they matter.

Article By
Tracey Roizman , posted 4 months ago

  • Table of Contents

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 a study looking at the effects of cannabinoids on cell cultures compared to large-scale, double-blind clinical trials involving real humans.

A quick look at the published studies provides an illustration of the cannabinoid research in the U.S and around the world over the past few decades.

To date, more than 15,000 peer-reviewed studies from around the world have been published on cannabinoids. However, up until 2009, only 33 clinical trials were conducted in the U.S [1].

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.

In this article, we’ll discuss what the world of cannabis research looks like today and what it means for the future of the cannabis industry.

The Importance of CBD Research

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.

Pharmaceutical companies are in a race to create and patent cannabinoid-based prescription drugs like Epidiolex or Sativex.

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:

  • What do we really know about the short- and long-term safety of CBD?
  • What conditions can CBD be used to support?
  • Are there health conditions that could be made worse by CBD?
  • How does CBD interact with prescription and non-prescription medications?

Analyzing the Types of CBD Research

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:

  1. Level 1: Basic Research — low-level research to map the structural makeup and chemical properties
  2. Level 2: In Vitro Studies (using cell cultures) — low-level research; begins to explore the toxicity of a substance in live cells and tissues
  3. Level 3: In Vivo Studies (using real living organisms) — higher-level research involving living non-human animals
  4. Level 4: Clinical Trials — conducted on real humans in 4 different stages (I, II, III, and IV)
  5. Level 5: Meta-analysis — a review of published preclinical and clinical research; provides the highest level of evidence possible by pooling the data from similar studies.

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.

Level 1: Basic Research — Is CBD Safe?

CBD is widely regarded as being safe and non-toxic and that’s great news. But, is CBD completely free of any and all 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, CBD in this case, are determined [3]. This early research tells us that CBD is soluble in fat but not in the water and that its molecular formula is C21H30O2.

CBD looks something like this:

Examples of structural property studies involving CBD

Study Topic Article Authors Level of Study
The Structure of Cannabidiol Mechoulam et al., 1963 1
Separating Cannabinoids Lerner., 1963 1
Identification of CBD Sub-Groups Harvey., 1976 1

A) The Structure of Cannabidiol

A 1963 study determined the chemical structure of CBD from among three possible structures suggested by an earlier report, confirming important details such as the positions of certain molecular groups and the positions of double bonds between carbon atoms [18].

Advantages & Disadvantages of This Study Type
Advantages Disadvantages
  • Advance the knowledge of CBD’s molecular structure

None; all good

B) Separating Cannabinoids

In 1963, a group of scientists devised a new method for rapidly separating the major cannabinoids from cannabis [19]. The findings of this research are still used today to isolate various cannabinoids during research and product development.

Advantages & Disadvantages of This Study Type
Advantages Disadvantages
  • Made laboratory procedures for studying CBD more expedient
  • None; all good

C) Identification of CBD Sub-Groups

A 1976 study identified subgroups of CBD, known as homologues — molecules of CBD but with an extra molecular group formed during the extraction procedure [20]. This information helps to more precisely determine the amount of CBD present in a cannabis sample.

This research has contributed a lot towards the extraction process for making CBD-infused products.

Advantages & Disadvantages of This Study Type
Advantages Disadvantages
  • Improved the accuracy of CBD extraction procedures
  • None; all good

Level 2: In Vitro Studies — Testing On Living Cells

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.

Examples of In Vitro CBD Studies

Study Topic Article Authors Level of Study
CBD & Stroke Hind et al., 2016 2
CBD & Inflammatory Bowel Disease Harvey et al., 2014 2
CBD & Cancer Cells Ramer et al., 2010 2

A) CBD & Stroke

There is some evidence that CBD protects the blood-brain barrier (BBB), a selective filtering mechanism in the brain. Medical researchers are interested in finding out whether CBD could benefit recovering stroke patients or prevent strokes from occurring in the first place.

A clinical trial can’t be performed without sufficient basic research so an in vitro experiment was set up using a tissue culture model comprised of human cells to simulate the BBB [4]. First, they caused a “stroke” by depriving the experimental BBB of oxygen, then they measured the permeability of the BBB with and without the presence of CBD.

Advantages & Disadvantages of This In-Vitro Model
Advantages Disadvantages
  • This study allowed researchers to look at key biomarkers in the brain involved with stroke — something not possible to assess directly in the brain cells of live human patients
  • The BBB model used human brain cells
  • The experimental model cannot accurately depict the effects that would occur in a whole, functioning human brain

B) CBD & Inflammatory Bowel Disease

An in vitro study used a tissue culture of human colon cells to determine the potential anti-inflammatory benefits of CBD for patients with inflammatory bowel disease (IBD) [5].

The researchers added inflammatory molecules to the colon cells to cause inflammation and cell damage similar to what happens in IBD.

Three treatment arms were then set up in which the damaged cells were incubated with one of the following treatment groups:

  1. Steroids — the conventional medical treatment
  2. Anandamide — a naturally occurring endocannabinoid produced by the body
  3. CBD — the primary compound the researchers wanted to test

Results: The cells improved in all three treatments. CBD and hydrocortisone were similarly effective at reducing the inflammatory response and both were slightly more effective than anandamide.

Advantages & Disadvantages of This In-Vitro Model
Advantages Disadvantages
  • Very cost-effective study model to setup
  • Used real human colon cells
  • The timeframe of this study was significantly shorter than a clinical trial
  • Although this study used cultured human colon cells it lacks the full-fledged immune response and other modulating effects that would occur in an animal or person.

C) CBD & Cancer Cells

Cannabis has been found to have certain anticancer effects, but the psychoactive effects of medical cannabis limit the dose that can be used.

If CBD by itself can demonstrate anticancer benefits it might be useful as a cancer treatment, either by itself or in combination with medical cannabis.

But before human cancer patients can be treated with CBD preliminary studies need to be conducted, so an in vitro experiment was set up using cancer cell lines from two different types of highly invasive cancer: human cervical cancer and lung cancer to determine whether CBD might inhibit the cells from invading surrounding healthy cells [6]. These types of cancer are known for their ability to aggressively infiltrate surrounding, healthy tissues.

Results confirmed decreased invasiveness of cancer cells (ability to infiltrate new tissues) within 24 hours, with effects continuing throughout the 72-hour period of the study.

Additionally, four concentrations of CBD were used, each 10 times greater than the last, and even at the lowest concentration level tested CBD was able to significantly inhibit invasiveness.

Advantages & Disadvantages of This Study
Advantages Disadvantages
  • Researchers could control a single component of the cancer cells while eliminating many factors that would be present in a human from affecting the results
  • Results were delivered in a matter of hours, rather than days or weeks
  • Cancer cells in a petri dish behave differently than cancer cells in a person, so the data don’t provide a complete picture of the effects of CBD on these types of cancer in living animals or people

Level 3: In Vivo Studies — Testing On Live Animals

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:

  1. How CBD travels through the body — how quickly and efficiently it is absorbed into the bloodstream
  2. How CBD is broken down — whether this is done in the kidneys, liver, or elsewhere in the body
  3. How safe or toxic CBD and its metabolites are — sometimes a compound is found safe through in vitro research but shows toxic effects when given to live animals. For example, currently there is no known LD50 for CBD in humans [17]; however, a 2011 study found doses of 200-300mg/kg to be lethal in some rhesus monkeys [2].
  4. How the compound is excreted from the body — compounds may leave the body through the urine, feces, or even through the skin
  5. The effects of CBD for certain conditions or symptoms — using animals with health issues, we can test CBD to see if it improves the condition or makes it worse

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 [7]. 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 [8]. 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.

Examples of In Vivo CBD Research

Study Topic Article Authors Level of Study
CBD for Wound Healing Klein et al., 2018 3
CBD for Fear & Anxiety Norris et al., 2016 3
CBD for Epilepsy Jones et al., 2010 3

A) CBD for Wound Healing

An in vivo study on the ability of CBD to speed wound healing was performed on rats [9]. The animals, which sustained small wounds, received abdominal injections of CBD in one of two doses daily for 7 days.

By the third day, the CBD-treated lesions were significantly less inflamed. However, the improvement didn’t continue through the 7-day experiment and on the last day the CBD-treated wounds had similar levels of inflammation to the control group.

Advantages & Disadvantages of this in vivo model
Advantages Disadvantages
This test took into account the entire immune system of the animal, rather than single, isolated cellsThis study gave insight into the different stages of inflammation, rather than just one isolated process The test subjects were given injections of CBD, which isn’t a common way people use CBD in practiceThe study used synthetic CBD rather than naturally-extracted CBDThe CBD extract in the study didn’t include any other cannabinoids or hemp terpenesThe study only lasted 7 days and didn’t cover the entire time necessary for wound healing
Advantages Disadvantages
  • This test took into account the entire immune system of the animal, rather than single, isolated cells
  • This study gave insight into the different stages of inflammation, rather than just one isolated process
  • The test subjects were given injections of CBD, which isn’t a common way people use CBD in practice
  • The study used synthetic CBD rather than naturally-extracted CBD
  • The CBD extract in the study didn’t include any other cannabinoids or hemp terpenes
  • The study only lasted 7 days and didn’t cover the entire time necessary for wound healing

B) CBD for Fear & Anxiety

CBD is known for its calming effects on the nervous system. To find out if CBD can help reduce fear and anxiety researchers set up an in vivo experiment in which they conditioned a group of rats to have a certain fear and then injected CBD directly into the emotional control areas of the rats’ brains [10].

They found that CBD helped to diminish the fear response by activating receptors for serotonin, one of the brain’s calming neurotransmitters.

To find out if CB1 receptors were also involved they set up an arm of the experiment in which they blocked CB1 receptors. They got the same results, indicating that CBD’s effect on serotonin was solely responsible.

In another arm of the study they investigated CBD’s effect on dopamine, a brain neurotransmitter heightens the fear response, and GABA, which has calming effects. They found that CBD reduced activity in dopamine-promoting areas and simultaneously increased activity of GABA.

Additionally, they used a range of doses so they were able to determine the most effective dose among those levels.

Advantages & Disadvantages of this In Vivo Model
Advantages Disadvantages
  • Using animals enabled researchers to observe behavioral changes in response to a conditioned fear rather than looking for physiological changesCBD was administered directly into the rat brains, ensuring high doses were achieved
  • The researchers were able to set up a number of separate study arms and collect a considerable amount of data easily and simply in the laboratory environment.
  • Injecting CBD directly into the brain doesn’t reflect how CBD is used in practice

C) CBD for Epilepsy

One of CBD’s most widely studied effects, and the only one, to date, for which a CBD-based drug has received FDA approval, is its anti-seizure activity.  

An in vivo study used rats in which an epilepsy-like condition was induced by blocking the activity of the brain-calming neurotransmitter GABA [11]. The rats were then given one of three different doses of CBD and seizure activity was recorded.

When the results were tallied they showed that CBD didn’t prevent the onset of seizures, but, at the highest dose level the severity of the seizures was dramatically reduced, with 53% developing the most severe types of seizures without CBD to only 7% in the CBD-treated animals.

Advantages & Disadvantages of this In Vivo Model
Advantages Disadvantages
  • The animal model effectively simulated a type of seizure disorder in humans
  • The delivery method — injection into the abdomen, doesn’t reflect the way most CBD users or medical patients will use CBD

Level 4: Clinical Research — Testing 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:

  1. The pathway CBD takes through the body, from absorption to distribution to elimination
  2. The clinical effects of CBD (ie. its health benefits)The absence or presence of side-effects
  3. The optimal dose needed for CBD to be used effectively in humans

The quality of clinical trials can vary widely, and there are some key elements to consider when assessing the quality of a particular trial.

Placebo-Control

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. In order 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 [12].

Randomization

In order 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

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 response. 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. 

Blinding For Statisticians is Important Too

Further, even the statistician — the study team member who crunches the numbers to determine the results of the experiment, should be blinded to group assignments until after all the numbers have been crunched.

At any point in a clinical study, the process can be halted if a drug is determined to be ineffective or too toxic to be used safely by humans for its intended purpose.

For pharmaceutical companies seeking to develop a CBD-based drug, there are four phases (or “hoops”, depending on your perspective) of clinical trials that a drug has to go through before it can be marketed for human use [13].

Different Levels of Clinical Trials

A) Phase I Trials

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.

B) Phase II Trials

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.

C) Phase III Trials

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 a fourth phase of trials.

D) Phase IV 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 [13]. They also tend to cover several months, or even years to collect long-term health data.

E) Epidemiological Research

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 [14].

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.

Clinical Trials Involving CBD

Study Topic Article Authors Level of Study
CBD for Crohn’s Disease Naftali et al., 2017 4
CBD for Anxiety and Insomnia Shannon et al., 2019 4
CBD for Healthy People Taylor et al., 2018 4

A) CBD for Crohn’s Disease

Basic research shows that CBD has strong anti-inflammatory activity, but can it help reduce inflammation in Crohn’s disease, an autoimmune inflammatory disease of the intestines?

A small randomized trial involved 20 Crohn’s disease patients. Participants received 10 mg of CBD orally or placebo twice per day for 8 weeks [25].

Results: CBD and placebo both reduced the patients’ symptoms by about 35%. No adverse effects occurred, confirming safety, but because CBD did not outperform the placebo it couldn’t be considered effective.

Advantages & Disadvantages of This Clinical Trial
Advantages Disadvantages
  • The study used a wide age range of patients, from 18-75 years
  • All patients had moderate (vs. minor or severe) symptoms, which adds consistency, particularly with a study like this where there is a small number of participants
  • Use of a placebo increased the reliability of the results
  • This study used isolated CBD, rather than full-spectrum CBD extracts

B) CBD for Anxiety and Insomnia

A study of patients with anxiety and sleep problems was conducted to find out if CBD lives up to its reputation as an anti-anxiety and sleep aid [15]. The participants, all psychiatric clinic patients, were given CBD in addition to their regular treatments. At regular intervals they completed questionnaires about their symptoms, progress, and side effects.

Results showed dramatic improvements in both anxiety and sleep, with only 3 participants experiencing side effects that required discontinuation of CBD.

Advantages & Disadvantages of This Clinical Trial
Advantages Disadvantages
  • The study collected data on actual patients with medically documented anxiety and sleep issues
  • It included a large group of about 100 people, making the results more significant and reliable
  • The study was not placebo-controlled or blinded; participants were all given CBD and they all knew they were taking CBD

C) CBD for Healthy People

A study was set up to find out what doses of CBD are safe in healthy individuals and how food consumption may affect the way CBD is absorbed and utilized.

This study had three arms [16]:

  1. Single-dose — one-time doses of 1500 mg, 3000 mg, 4500 mg, and 6000 mg
  2. Multiple doses —  twice-daily doses of 750 mg or 1500 mg for six days
  3. Food effect — A 1500 mg single dose given with a high-fat meal (fed) or on an empty stomach (fasted)

Results: All single and multiple-dose levels were well tolerated. Adverse effects were mild and included headache, nausea, dizziness, and rash; though none of the participants had to drop out due to intolerable side effects.

Interestingly, there was a higher occurrence of side effects in the fed group (possibly due to more efficient absorption of CBD).

Advantages & Disadvantages of This Clinical Trial
Advantages Disadvantages
  • This study checks all the boxes for a gold standard clinical trial — randomized, double-blind, and placebo-controlled
  • The results of this study can be easily applied to someone looking to use CBD in their daily health regimen
  • It demonstrates the differences of using CBD with food vs. on an empty stomach
  • It assesses the potential side-effects of CBD in this particular dose
  • The study included 56 participants, so was moderate in size and could be repeated on a larger scale to provide more reliable dataSome of the calculations used for this study to determine dose may have been flawed

Level 5: Meta-Analysis — Comparing Data From Multiple Studies

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.

Examples of Meta-Analysis Involving CBD

Study Topic Article Authors Level of Study
CBD for Epilepsy de Carvalho Reis et al., 2019 5
CBD for Stroke England et al., 2015 5
Effects of CBD on the Circulatory System Wade et al., 2010 5

A) CBD for Epilepsy

A study sought to find out how effective CBD and medical cannabis are for difficult-to-treat forms of epilepsy across all age groups. Their search criteria produced 236 clinical studies, from which they selected 16 to perform individual analyses and ultimately, four were included in the meta-analysis [22].

The researchers concluded that CBD is effective for reducing seizure frequency.

Advantages & Disadvantages of This Meta-Analysis
Advantages Disadvantages
  • For the CBD portion of the meta-analysis, they filtered the original group of studies to select out placebo-controlled studies, increasing the quality of their results
  • Meta-analysis was used to determine the side effect profile of CBD
  • The low number of studies used in the meta-analysis limited the total amount of data that was analyzed
  • Researchers were unsure if the articles they used contained overlapping samples
  • The writeup doesn’t indicate which studies were used for the meta-analysis or report the results separately from the individual analyses

B) CBD for Stroke

This study was a systematic review with meta-analysis of cannabinoids for treating stroke. The search criteria produced 111 results, from which 34 were individually analyzed and all were subjected to meta-analysis [23].

Results showed that cannabinoids significantly reduced the area of the brain damaged by stroke and that they provided benefits when used immediately after a stroke as well as days later.

Advantages & Disadvantages of This Meta-Analysis
Advantages Disadvantages
  • They were able to identify specific areas where the data is lacking and more studies are needed. For example the involvement of CB2 receptors, which are less prevalent in the brain compared to CB1 receptors. 
  • The study used animal studies so the results are not directly applicable to humans
  • A range of cannabinoids, including CBD, was included, though the authors note that in one study, in particular, CBD showed benefits when administered as long as 3 days after the strokeSearch criteria were limited to prominent journals and may have missed relevant studies published in lesser-known journals
  • Only 10 studies used randomization and only 4 used blinding of the statisticians  

C) Effects of CBD on the Circulatory System

This study evaluated the safety and effectiveness of Sativex, a cannabinoid-based prescription drug with a 1:1 ratio of CBD to THC, for treating multiple sclerosis symptoms [24]. It included three randomized, placebo-controlled, double-blind studies comprising a total of 666 patients.

Results showed that the drug reduced muscle spasticity symptoms and was well-tolerated.  

Advantages & Disadvantages of This Meta-Analysis
Advantages Disadvantages
  • The researchers used high-quality studies
  • The meta-study included a large number of patients
  • The patients were similar in terms of symptom profile  
  • The studies were sponsored by the manufacturer, which introduces potential bias, though the analysis was performed by an independent company
  • There was variation among the studies in terms of measurement techniques

Summing It All Up: CBD Research Types

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:

  • How safe is CBD?
  • What can CBD be used to help?
  • Can CBD worsen any conditions?
  • How does CBD interact with medications?

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:

  1. Level 1: Basic Research — early research for assessing the molecular structure and chemical properties
  2. Level 2: In-Vivo Research — highly-controlled research for assessing beneficial and toxic effects of CBD on isolated cells and tissues grown in test tubes
  3. Level 3: In-Vitro Research — real testing of CBD on living systems to assess safety and effectiveness
  4. Level 4: Clinical trials — testing on humans to assess dose, efficacy, and comparison of CBD with other compounds
  5. Level 5: Meta-Analysis — continued data analysis of multiple similar studies on a particular effect profile

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.

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