Cannabidiol

Cannabidiol (CBD) is a supplement that is growing in popularity. Its advocates claim that it is a safe anti-inflammatory compound that can alleviate conditions such as irritable bowel syndrome, schizophrenia, anxiety and improve sleep. What does the science say? This article will give you the answer.

What is CBD?

Cannabidiol (CBD) is one of over 100 cannabinoids found in Cannabis sativa, the marijuana plant. CBD and THC are the two primary active compounds found in the cannabis plant. They are also the best known and most scientifically studied compounds of this plant (1, 2). Unlike THC, CBD has no psychoactive effects. It cannot produce any of the negative mental effects associated with THC, such as paranoia, anxiety and memory problems. Instead, some research even suggests that CBD may naturally protect against marijuana intoxication (3, 4).

In early studies, CBD has shown promising benefits for people with a wide range of difficult-to-treat conditions (5).

Advocates attribute the following effects to CBD

May prevent seizures in rare forms of epilepsy
Has potential anti-cancer effects
Reduces inflammation and may relieve pain
May prevent or alleviate neurological disorders
May reduce anxiety
May reduce nausea and stimulate appetite
Could reduce the risk of diabetes
Could improve heart health
Could help with quitting smoking and using fewer opioids
Is well tolerated and there are few reports of side effects

Here's what skeptics say

There is not enough research done with humans
It could cause drowsiness
It could be unsafe for people with impaired immune function
There are potential interactions with medications

Potential health benefits of CBD / cannabidiol

Warning: CBD should not be used as an alternative to treatment by a doctor. Individuals who wish to include CBD in their health management or treatment plan should discuss this with their doctor in advance. CBD oil is considered an effective anti-seizure remedy, but more research is needed to determine the further benefits of CBD oil and its safety (6).

CBD oil can help with seizures

Many people claim that CBD has helped them with seizures even when nothing else has worked. This is supported by scientific research: CBD can help reduce seizures in people with epilepsy who do not respond to medication (7, 8). In 2018, the US Food and Drug Administration (FDA) approved an oral CBD solution for the treatment of two rare forms of epilepsy. This approval was based on robust study results from recent years of CBD research, but this approval is currently limited to people with Lennox-Gastaut syndrome and Dravet syndrome (9). In a three-month study of 23 children and young adults (aged 3 to 26 years) suffering from treatment-resistant epilepsy, subjects who received a purified 98% oil-based CBD extract experienced significantly fewer seizures. In 39% of the study participants, the frequency of seizures decreased by half. (7). In another study of 214 children and adults with epilepsy, CBD was similarly associated with a reduction in seizures. The researchers concluded that CBD was safe even at the maximum dosage, which was double the dosage used in the previous study (10). In a survey, parents of children with treatment-resistant epilepsy who used CBD were asked about the benefits of CBD. Of the 19 parents surveyed, 84% said that CBD reduced the frequency of seizures. Two parents said that CBD had completely resolved the problem. Parents also reported increased alertness, better sleep and improved mood in their children. Some reported side effects included drowsiness and fatigue (11). In 15 patients with epilepsy who did not respond to medication, those who took 200 to 300 mg of cannabinoid per day over a period of 4.5 months experienced fewer seizures. 7 out of 8 patients taking CBD reported an improvement, compared to only one subject in the placebo group (12).

Summary: The potential of CBD to help people with epilepsy is relatively well established and in America CBD has been approved for the treatment of 2 severe forms of epilepsy since 2018. The benefits for people with other types of seizures are still under investigation.

Inflammation and autoimmune diseases

According to some scientists, CBD could be helpful for a number of conditions associated with inflammation and pain. It acts on cannabinoid receptors, which in turn regulate inflammation, balance the immune system and protect the body from oxidative stress (13). The immune system has sensors for the cannabinoids that our body produces and for the cannabinoids that we take in from the outside. Some scientists believe that this internal cannabinoid system can become unbalanced in autoimmune diseases and inflammation (13, 14).

CBD may act directly on immune cells to trigger a series of anti-inflammatory and antioxidant responses:

Th1 and Th2 dominance

In one study, asthmatic rats receiving CBD showed lower Th1 (IL-6 and TNF-alpha) and Th2 (IL-4, IL-5, IL-13) responses. CBD has not yet been tested in humans with asthma, so its use for this purpose should be discussed in advance with the treating physician (15). A study conducted in mice found a link between CBD and reduced markers of inflammation and pain. In immune cells, CBD simultaneously led to reduced production of pro-inflammatory signals (Th1: TNF-alpha, IFN-gamma, and IL-6; Th2: IL-4 and IL-8) (16, 17).

Th17 dominance

In one study, immune cells exposed to CBD showed lower IL-17 expression and generally reduced Th17 activation. This finding suggests a potential future role in the suppression of Th17-dominant autoimmunity, but human studies have yet to be performed (18).

Neutrophils exposed to CBD also tend to switch to their anti-inflammatory state (19, 20).

Summary: CBD could be a potential treatment for autoimmune and inflammatory diseases. Some scientists believe that CBD could suppress an overactive immune system through its actions at the cannabinoid receptors, but this has not yet been studied in humans.

Neurodegenerative diseases

Some scientists believe that CBD could protect brain cells from damage. In a cell study, neurons exposed to CBD suffered less damage from toxic substances and oxidative stress, which are responsible for much of the destructive damage caused by strokes and other forms of brain damage. This early study should soon be followed by animal and human studies to further investigate these benefits (21, 22). In a small study of 5 patients suffering from movement disorders, fewer uncontrollable muscle twitches were observed in subjects using CBD and higher doses showed stronger effects. The patients received 100 to 600 mg of CBD per day over a period of 6 weeks. However, 2 of the patients suffering from Parkinson's disease experienced side effects (including worsening of tremors) at doses above 300 mg per day (23). In a study of subjects suffering from multiple sclerosis, those who received a combination of CBD and THC consistently reported fewer muscle twitches (24). However, CBD in combination with THC had no apparent effects in a study of 17 Parkinson's patients (25). Animal studies have produced largely encouraging results. In rodent models, CBD ingestion is associated with reduced brain damage, reduced beta-amyloid toxicity and improved cognitive function, suggesting that CBD may have a potential future role in the treatment of Alzheimer's and Parkinson's disease (26, 27, 28). Research conducted with animals also suggests that CBD may protect the brain from the effects of stroke and the consequences of reduced blood flow, if these results can be replicated in humans. In cell studies, CBD had a stronger antioxidant effect than vitamin C or vitamin E (29, 30, 21). CBD is currently being studied for its potential to help people with other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) (31, 32). Summary: Many scientists are currently investigating whether CBD could help people with neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis and ALS. Initial results have been largely positive, but more studies are needed.

Alleviating symptoms of multiple sclerosis

According to some scientists, cannabinoids could alleviate symptoms of multiple sclerosis. In a study of 66 subjects with multiple sclerosis and chronic pain, those who took a combination of CBD and THC over a 2-year period reported less pain. The subjects determined the dose themselves and took as much CBD as they thought they needed to relieve their pain (33). In another study of 189 subjects with multiple sclerosis, subjects using a combination of CBD and THC also reported less muscle tension, less pain, less sleep disturbance and improved bladder function (34, 35, 36). In another study of 50 patients with multiple sclerosis, those who received a CBD/THC combination reported reduced muscle tension and better sleep. Lower doses showed a weaker effect. The researchers believe that some MS patients in this study required higher doses to experience relief (37).

Schizophrenia

Unlike THC, which is also found in hemp, CBD is seen as a potential aid in preventing psychosis and reducing the symptoms of schizophrenia, although scientific studies are still lacking (38, 39, 40). While the psychoactive THC in cannabis appears to trigger psychotic episodes, particularly in people suffering from schizophrenia, CBD has antipsychotic effects. A growing number of studies suggest that CBD could be an effective natural alternative to antipsychotic medications, while having fewer side effects (41, 40). According to some studies, people experiencing psychosis may produce either too much or not enough endogenous cannabinoid signaling. CBD binds less strongly than endogenous cannabinoids to cannabinoid receptors, which is why some scientists believe it can help restore the balance of cannabinoids in the brain. THC, however, is more potent than endogenous cannabinoids (anandamide and 2-AG), which may explain why it can cause psychosis (39, 42). Of 42 patients with acute schizophrenia, those who took CBD daily reported an improvement in all symptoms after four weeks. The effects of CBD were as strong as those of a known antipsychotic drug, but CBD was much better tolerated. Interestingly, CBD was also associated with a reduced breakdown of anandamide (it blocked FAAH), which the scientists hypothesized could explain the positive effects (43, 44).

Many animal studies also support the antipsychotic effects of CBD (39).

Summary: Current research suggests that CBD has the potential to reduce some difficult-to-treat symptoms of schizophrenia. The evidence is promising, but is still considered insufficient to recommend CBD for people with schizophrenia.

Anxiety

A single dose of 400 mg CBD was associated with reduced anxiety in a study of 10 subjects with seasonal affective disorder using brain imaging techniques. The subjects experienced reduced blood flow to the parts of the limbic system that are often overactive during anxiety. At the same time, blood flow increased to another region of the brain (the posterior cingulate cortex), which is important for cognition and motivation (45, 46). In a study of 10 healthy volunteers, those who took CBD felt less anxiety after the stressful task of public speaking. In 24 volunteers with social anxiety, taking CBD before public speaking was associated with reduced anxiety, reduced discomfort and improved cognition (47, 48). In another study, 8 volunteers experienced less anxiety when taking CBD in combination with THC compared to THC alone (49). Future studies will further investigate the potential benefits of CBD for people with different types of anxiety including panic disorder, obsessive-compulsive disorder and post-traumatic stress disorder (50).

Summary: CBD is a promising anxiety-relieving compound that has shown positive effects in several early small studies. Future research will clarify whether CBD could be an effective treatment for different types of anxiety.

Pain

According to numerous promising studies, cannabinoids could potentially represent a new class of painkillers that many scientists believe could help millions of people with chronic pain (51, 52).

The human body has receptors for cannabinoids distributed throughout the body, with the first type (CB1) having a particularly high density in the pain pathways of the brain, spine and nerves. The second type (CB2) is more important for the immune system, but is also involved in inflammation. According to some scientists, CBD could reduce both pain and inflammation through its actions on these receptors (53).

In a large-scale analysis of 18 clinical trials, the authors concluded that cannabinoids strongly and safely reduced different types of chronic pain. These included neuropathic pain, arthritis pain, fibromyalgia pain, HIV-related pain and pain due to multiple sclerosis. (52).

Another study review, which looked at 16 studies, found significant evidence for the benefits of CBD in people with chronic pain. The authors of this second review observed little difference between CBD and a placebo in terms of tolerability, meaning that CBD was not associated with side effects in most studies. However, they also noted that the studies that examined tolerability were of very low quality (54).

In several studies of people with multiple sclerosis and chronic pain, those taking a CBD/THC combination reported reduced pain. This combination was well tolerated over a two-year period and was used regularly (33, 34, 35, 36).

Cannabidiol/THC combinations have produced limited but promising results in studies of postoperative pain, chronic pain, cancer pain, rheumatoid arthritis and neuropathic pain (55, 56, 57, 58, 59).

According to an open-label study, unlike opioids and most other painkillers, CBD appears to be much less likely to lead to long-term habituation (33).

Summary: CBD is currently being studied as a potential non-addictive painkiller that acts at the cannabinoid receptors of the nervous system and immune system. The data are promising, but further research is needed.

Rheumatoid arthritis

As natural anti-inflammatory and antioxidant compounds, cannabinoids have the potential to relieve joint pain and swelling. In studies conducted with arthritic animals, the animals receiving CBD suffered less joint destruction and slower progression of inflammatory disease (60, 13, 61).

In a human study, subjects taking a CBD/THS combination (Sativex) reported reduced symptoms of rheumatoid arthritis. Taken over a period of 5 weeks, this combination was associated with reduced pain at rest and during movement, better sleep and reduced inflammation. The study also reported no adverse side effects (56).

Nausea and appetite

THC is a compound approved for the treatment of nausea and vomiting in humans (dronabinol), but clinical evidence of such an effect with CBD is limited (62). In an animal study, animals given typical doses of CBD vomited less and showed fewer symptoms of nausea due to toxic drugs. However, when administered in high doses, CBD appeared to increase symptoms of nausea or became ineffective (63, 64).

An older study suggests that CBD and THC in combination are better than either drug alone when it comes to increasing appetite and reducing nausea. THC increases appetite, but its psychoactive effects are perceived as unpleasant by patients. The authors believe that CBD can reduce the psychoactivity of THC without reducing appetite stimulation (65).

Diabetes

Although marijuana can increase appetite and calorie intake, it has been linked to a lower BMI, less obesity and a reduced risk of developing diabetes (66).

In a study of nearly 5,000 people, current and former marijuana users had lower fasting blood glucose and insulin levels (by 16%), lower waist circumference and BMI, lower insulin resistance (by 18%), and higher levels of "good" HDL cholesterol. All of these factors are associated with the development of diabetes (67).

In a study of young mice susceptible to diabetes, the animals given CBD were less likely to develop diabetes. Only 30% of CBD-treated mice developed diabetes, compared to 86% of non-treated mice (68, 69).

In another study, CBD was associated with lower rates of destruction of insulin-producing cells in the pancreas. It was also associated with reduced levels of pro-inflammatory cytokines in diabetic mice and a shift in immune response from Th1 (autoimmune) to Th2. These results suggest potential benefits for people with type 1 diabetes where autoimmunity is a primary factor. However, no human studies have yet been conducted on this topic (69).

Summary: According to some researchers, CBD may play a role in both type 1 and type 2 diabetes, which appears to be particularly the case in the early stages. However, further clinical studies are needed to confirm these results.

Heart health

Some studies conducted with animals and cell cultures suggest a role for CBD in protecting the heart by relaxing blood vessels, reducing inflammation and combating oxidative stress. CBD has been associated with more relaxed arteries and less damage to blood vessels in animal models of heart disease. In various animal studies, it has been linked to a smoother heart rhythm, reduced heart rate and blood pressure in response to stress, as well as reduced damage to the heart and brain from clogged blood vessels. Therefore, some scientists believe that CBD may protect against heart attacks and strokes, but no human studies have yet been conducted on this topic (70, 71, 72, 73, 74). In one study, platelets exposed to CBD clumped together less, reducing their potential to clog blood vessels. In white blood cells, CBD is associated with reduced inflammatory responses. Both of these effects may help explain CBD's potential to improve heart health (75, 76).

Summary: Cellular and animal studies show a link between CBD and an improvement in markers of heart health. However, further studies are needed to investigate whether CBD can prevent heart disease in humans.

Cancer symptoms

According to initial research, CBD and other chemicals found in cannabis show promising anti-cancer properties. Interestingly, THC has also been studied for its potential anti-cancer effects, but its psychoactive effects are considered too strong when used in high doses. Cannabinoids similar to THC were first used to reduce nausea and pain, as well as improve appetite in cancer patients. Some synthetic cannabinoids are still used for this indication today. More recently, scientists have discovered the potential of natural cannabinoids such as CBD and their possible role in fighting cancer (77). CBD is a non-psychoactive compound that is currently being studied for its potential role in cancer treatment. It could one day be used to improve the efficacy of a standard treatment, or be used on its own as an anti-cancer agent. Until then, however, further scientific research is needed. For now, cancer patients should ask their doctor about adjunctive treatment with CBD to see if CBD fits into their current treatment protocol (78).

Cell studies

Cervical, thyroid, colon and blood cancer cells died or were no longer able to grow when directly exposed to CBD (79, 80, 81, 82, 83). Human brain tumor cell growth and the spread of the tumor in the brain also decreased in the presence of CBD. These results could give new hope to people struggling with this difficult-to-treat and deadly type of cancer (84, 85). Other cell studies suggest that CBD could help fight breast and prostate cancer. Some experts believe that CBD could directly reduce tumor size, relieve pain, and increase the effectiveness of conventional medications (86, 87, 88). Scientists have conducted many studies to investigate the potential mechanisms of CBD against cancer. They believe that CBD may work by depriving cancer cells of energy, making them more sensitive to the body's immune response, and blocking a newly discovered cannabinoid-related cancer pathway (GPR55) (79, 89, 83, 85, 90, 91). However, while these studies are exciting, most of them are currently limited to cell cultures. It is not yet known whether CBD can also help fight cancer in humans.

Summary: Scientists are investigating the effects of CBD on cancer. Studies to date are limited to cells and more human studies are needed before conclusions can be drawn.

Depression

Mice suffering from depression that were given CBD recovered quickly from this depression. The effect was persistent and as strong as that of standard antidepressants (92, 93, 94).

In humans, CBD is better studied for the treatment of anxiety than for the treatment of depression. Future studies will determine whether it can also play a role in depression.

Inflammatory bowel disease

In animals with inflammatory bowel disease, those given CBD showed less inflammation of the gut (95, 96, 87). In another study, mice suffering from inflammatory bowel disease that were administered CBD showed reduced inflammation and normal bowel movements. Tissues and cells exposed to CBD were less inflamed and showed fewer signs of symptoms associated with inflammatory bowel disease (98, 99, 100). In cells, the presence of CBD was associated with increased activation of PPAR-gamma, an important inflammation-reducing metabolic pathway (101, 102).

Summary: Animal and cellular studies suggest that CBD may be beneficial in inflammatory bowel disease. This is not surprising considering the anti-inflammatory properties of CBD. However, human studies are still needed to confirm these benefits.

Bacterial infections

CBD has shown antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) bacteria, which often cause difficult-to-treat hospital infections. This research has so far been limited to a cell culture study, so it is currently unclear whether CBD could be effective against bacteria or other microbes, but further research is underway (13).

BSE

In a fascinating study, mice were infected with a prion disease - a type of infectious protein that causes degeneration of the nervous system. Half of these mice were treated with CBD and the mice in the CBD group survived almost a week longer than the mice in the control group (104).

BSE and other prion diseases are notoriously difficult to treat and there is no known cure to date. Further research will show whether CBD could play a role in the emerging science of prions (105).

Diseases of the bones

Although it is less well known, human bones also have receptors for cannabinoids that have been little studied.

In mice, CBD has been associated with better healing of broken limbs. Both CBD and THC were tested, but only CBD showed the potential to activate genetic pathways that strengthen collagen structure (106).

Insomnia

Cannabis users with sleep problems prefer cannabis strains with higher CBD content as a sleep aid. According to a survey of 163 adults who used medical cannabis, the risk of dependence is also lower with these CBD-rich and THC-poor cannabis strains. In addition, THC has been associated with poorer sleep quality in the long term (107, 108).

CBD's potential as a sleep aid could simply be due to its relaxing, anxiolytic effects (50).

Substance abuse disorders

In the Western world, an increasing number of people are suffering from the consequences of opioid abuse. According to promising initial research, CBD could help these people kick their addiction to opioid painkillers. People with chronic pain who use cannabis tend to use less opioid painkillers than people who do not use cannabis (109).

In a rat study, animals given CBD showed less addictive behavior and were less likely to turn to morphine or heroin. The authors suspect that CBD could influence the reward system in the brain (110, 111).

Smoking cessation

In a pilot study of 24 smokers, those who received cannabidiol smoked about 40% fewer cigarettes and reported fewer cravings for nicotine. Larger studies will be needed to confirm whether CBD can help with smoking cessation (112).

Acne

In a study of human skin tissue, CBD was associated with reduced oil production and a reduced number of oil-producing glands. The skin tissue to which CBD was applied also showed fewer markers of inflammation. All of these effects would be very helpful for people with acne. Hopefully, future human studies can determine whether CBD skin creams can be effective against acne (113).

Psoriasis

In one study, CBD was associated with reduced skin cell division. Excessive cell division contributes to the development and symptoms of psoriasis. The authors of the study concluded that CBD could have a potential role in future psoriasis treatments (114).

CBD side effects and safety

CBD is generally well tolerated and rarely shows side effects even when used in high doses and over a long period of time (115).

However, some people should take extra precautions. These include:

People with weakened immune systems, should avoid CBD or use it sparingly. In one cell study, CBD was associated with reduced activity of T and B immune cells. This implies that CBD could increase the likelihood of infections and exacerbate HIV, tumor growth, metastases and asthma (17).
People taking medication. CBD may reduce the activity of liver enzymes called cytochrome P450s, which are responsible for metabolizing more than 60% of all prescription drugs. People taking prescription drugs should consult their doctor before using CBD to rule out any interactions (116, 117).

People taking CBD have reported side effects in rare cases, including a slight reduction in blood pressure, dry mouth, dizziness and drowsiness. In combination with THC, CBD could impair learning and motivation (118, 119, 120). Megadoses could induce or exacerbate anxiety (via activation of TRPV1 receptors (121).

Although CBD counteracts THC intoxication at normal doses, a study conducted with monkeys suggests that large amounts of CBD may enhance the effects of THC. According to some scientists, high doses of CBD mimic serotonin, which can enhance the psychoactive effects of THC (122).

CBD preparations

Since cannabinoids such as CBD do not mix well with water, they must be administered as oils. In addition, the amount of CBD absorbed through the digestive tract can vary and large amounts are not absorbed. New products such as CBD/cannabinoid patches, nasal sprays and mucosal absorbable tablets for better absorption are under development (123)

CBD may be more appealing to patients than synthetic cannabinoids and THC as it has no psychoactive effects. Many people say they want to avoid the high, paranoia and drowsiness that THC can cause (124).

Conclusion

Cannabidiol (CBD) is a non-psychoactive cannabinoid extracted from the cannabis plant. It is approved in the USA for the treatment of two rare forms of epilepsy. According to many early studies, it also has the potential to treat autoimmune disorders, inflammatory diseases, anxiety, neurological disorders, substance abuse disorders and more, although additional research is needed to confirm these benefits. CBD is generally well tolerated, but people with compromised immune systems and those taking prescription medications may be at increased risk for side effects.