Comprehensive List of CBD Research Studies

CBD Research: Addiction

Research supports the following effects of CBD for addiction:

Regulates the function of dopamine in the brain
Alleviates common symptoms of drug withdrawal syndromes
CBD may reduce cravings for tobacco

List of research studies involving CBD & addiction:

Cannabidiol as an intervention for addictive behaviors: a systematic review of the evidence. (2015)
Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage. (2015)
Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. (2013)
Cannabidiol inhibitory effect on marble-burying behaviour: involvement of CB1 receptors. (2010)
Cannabidiol is an allosteric modulator at mu-and delta-opioid receptors. (2006)

CBD Research: Anxiety

Research supports the following effects of CBD for anxiety:

Boosts GABA function in the brain
Regulates serotonin & dopamine activity
Relaxes tight or tense muscles
Alleviates inflammation in the brain
Promotes a more restorative sleep
Reduces cortisol levels

List of research studies involving CBD & anxiety:

CBD Research: Arthritis

Research supports the following effects of CBD for arthritis:

Alleviates underlying inflammation
Relieves chronic pain
Prevents T-cell infiltration in rheumatoid arthritis
Promotes recovery of the joint tissue

List of research studies involving CBD & arthritis:

CBD Research: Cancer

Research supports the following effects of CBD for cancer:

Regulates key immune cells tasked with cancer detection
May alleviate cancer-related pain
Supports sleep duration and quality
May boost hunger levels
May slow tumor growth
Alleviates nausea & vomiting associated with chemotherapy
May support anxiety & depression associated with a cancer diagnosis

List of research studies involving CBD & cancer:

CBD Research: Diabetes

Research supports the following effects of CBD for diabetes:

Helps curb appetite & reduce weight
Protects the liver
Alleviates neuropathic pain
Alleviates other side effects of diabetes
Supports insulin function
Supports faster wound healing
Protects the insulin-secreting cells in the pancreas

List of research studies involving CBD & diabetes:

CBD Research: Epilepsy

Research supports the following effects of CBD for epilepsy:

Alleviates convulsions
Protects the nerve cells
Modulates key receptors that regulate brain health
Alleviates neuro-inflammation
Supports GABA activity

List of research studies involving CBD & epilepsy:

CBD Research: IBD

Research supports the following effects of CBD for IBD:

Inhibits inflammation in the digestive tract
Prevents mast cell activation
Alleviates pain
May support microbiome diversity

List of research studies involving CBD & IBD:

CBD Research: Migraines & Headaches

Research supports the following effects of CBD for headaches:

Relieves inflammation
Blocks the transmission of pain
May prevent the release of serotonin from platelets
May reduce vascular spasms

List of research studies involving CBD & headaches:

CBD Research: Multiple Sclerosis

Research supports the following effects of CBD for multiple sclerosis:

Resists the development of autoimmunity
Reduces neuroinflammation
Keeps T-cells from congregating around the nerves
Reduces muscle spasms
Supports bladder control
Alleviates nerve pain

List of research studies involving CBD & MS:

CBD Research: Nausea

Research supports the following effects of CBD for nausea:

Increases anandamide levels in the medulla oblongata
Alleviates inflammation
Relaxes muscle cramping and pain

List of research studies involving CBD & nausea:

CBD Research: Pain

Research supports the following effects of CBD for pain:

Reduces inflammation
Alleviates common side-effects of pain
Supports nerve cell health
Activates pain receptors in the spinal cord and brain

List of research studies involving CBD & pain:

CBD Research: Sleep

Research supports the following effects of CBD for sleep:

Sedative qualities promote faster sleep onset
May reduce nightmares
Regulates the sleep cycle and sleeping patterns
Alleviates common causes of insomnia

List of research studies involving CBD & sleep:

CBD Research: Weight Loss

Research supports the following effects of CBD for weight loss:

Reduces appetite to curb eating habits
Alleviates chronic inflammation associated with obesity
Supports optimal hormone function
Alleviates digestive disorders & inflammation
Supports mitochondria function (where sugar & fat is burned for energy)
May reduce insulin resistance
Alleviates stress & anxiety

List of research studies involving CBD & weight loss:

Why CBD Research is So Important

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?

Five 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:

Level 1: Basic Research — low-level research to map the structural makeup and chemical properties
Level 2: In Vitro Studies (using cell cultures) — low-level research; begins to explore the toxicity of a substance in live cells and tissues
Level 3: In Vivo Studies (using real living organisms) — higher-level research involving living non-human animals
Level 4: Clinical Trials — conducted on real humans in 4 different stages (I, II, III, and IV)
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 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:

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

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

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:

How CBD travels through the body — how quickly and efficiently it is absorbed into the bloodstream
How CBD is broken down — whether this is done in the kidneys, liver, or elsewhere in the body
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; however, a 2011 study found doses of 200-300mg/kg to be lethal in some rhesus monkeys.
How the compound is excreted from the body — compounds may leave the body through the urine, feces, or even through the skin
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. 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.

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

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:

The pathway CBD takes through the body, from absorption to distribution to elimination
The clinical effects of CBD (ie. its health benefits)The absence or presence of side-effects
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. 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.

Randomization

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 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.

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 the 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.

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.

Examples of 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

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

Key Takeaways: What’s The Future of CBD Research?

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:

Level 1: Basic Research — early research for assessing the molecular structure and chemical properties
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
Level 3: In-Vitro Research — real testing of CBD on living systems to assess safety and effectiveness
Level 4: Clinical trials — testing on humans to assess dose, efficacy, and comparison of CBD with other compounds
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.