Inflammation is an important process employed by the body in response to infection or injury. Without it, we could not defend against microorganisms or heal from physical injuries. Inflammation occurs when white blood cells, also known as leukocytes, detect infection or injury via the binding of various molecules on their cell surface receptors. This triggers the release of cell signaling proteins called cytokines, which attract, activate, and cause the proliferation of different leukocytes. However, excessive inflammation is linked with a wide variety of diseases. For example, up to 20% of cancers are linked to chronic inflammation, and the symptoms of autoimmune diseases result from improper activation of the immune system and its inability to distinguish healthy cells from damaged or foreign cells. There is growing evidence that inflammation contributes to the development of diverse diseases like heart disease, diabetes, and mental disorders.

Pain is a side effect of inflammation, so many people turn to anti-inflammatory drugs as a means of reducing pain and improving quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most used analgesic medications in the world, with 30 million people per day taking them. They work by inhibiting cyclooxygenase (COX) enzymes that produce inflammatory molecules called prostaglandins. NSAIDs inhibit both COX-1 and COX-2, the two forms of COX; the former is predominantly expressed in the gastrointestinal tract, while the latter is expressed at sites of inflammation. Unfortunately, research continues to unveil side effects of these medications, as prostaglandins derived from COX-1 have many important biological functions including defense of the mucous membrane in the stomach. Therefore, inhibition of COX-1 is linked with gastric adverse events including ulcers, and in some cases other problems like kidney, heart, and liver dysfunction. Given the massive use of NSAIDs by the world population and the continuing rise of inflammatory diseases, new tools are desperately needed to combat inflammation.

The Anti-Inflammatory Effects of Phytocannabinoids and the Endocannabinoid System

 
Plant-derived cannabinoids (phytocannabinoids) from cannabis represent one of the most promising classes of anti-inflammatory compounds and appear to be devoid of the classical side effects of NSAIDs. They work primarily through the reduction of pro-inflammatory cytokines via activation of various cellular receptors, although the manifestation of specific effects varies depending on the disease in question. It is remarkable how many studies demonstrate the ability of phytocannabinoids to reduce inflammation in an incredibly wide spectrum of diseases. They may one day be used as much as conventional anti-inflammatory medicines. The most prominent phytocannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD).

Phytocannabinoids exert their effects largely through the endocannabinoid system (ECS), the network of cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and synthesizing and degrading enzymes distributed throughout the body. CB1 receptors are located primarily in the central nervous system (CNS), while CB2 receptors are mainly located on various immune cells, but there is also simultaneous expression of both receptors in those and other areas of the body. An excellent review article published in 2018 led by researchers at Virginia Commonwealth University summarized the evidence well. Multiple studies indicate that endocannabinoids act through CB1 and CB2 receptors to inhibit production of pro-inflammatory cytokines and increase production of anti-inflammatory cytokines. Furthermore, endocannabinoids and phytocannabinoids can also suppress leukocyte proliferation and activation, and induce their apoptosis (programmed cell death). These effects extend to both innate immune cells like macrophages and adaptive immune cells like B cells and T cells.

Quite interestingly, the over-the-counter drug acetaminophen (Tylenol) was recently shown to relieve inflammatory pain in mice through take indirect activation of CB1 receptors. Despite its widespread use, the complete mechanisms of action of acetaminophen are not entirely known. Therefore, it will take more research to know precisely how responsible CB1 receptor stimulation is for the effect of this drug.

Many patients have reported that combining phytocannabinoids and traditional NSAIDs is effective. It is quite possible that phytocannabinoids may help prevent potential side effects of NSAIDs in addition to improving efficacy. In mice, THC has been shown to block inflammatory tissue damage in the stomach caused by the NSAID diclofenac sodium. This benefit was achieved at a remarkably low dose that did not cause THC-associated side effects. As such side effects limit the use of THC in daily practice, it would be helpful if nonintoxicating doses of THC turned out to be sufficient in humans.

Phytocannabinoids and Arthritis

 
Arthritis is the swelling and tenderness of one or more joints, and there are various forms of the condition. The most common symptoms are pain, stiffness, and mobility issues. Data from 2013-2015 revealed 54.4 million adults (22.7% of the population) in the United States had diagnosed arthritis. Inflammation is a key component of arthritis, and several studies suggest phytocannabinoids could act as anti-inflammatory agents.

The most common form of arthritis is osteoarthritis. It occurs when cartilage at the ends of bones wears down. Chinese researchers at Fourth Military Medical University applied THC to isolated cells stimulated to mimic osteoarthritis-like inflammation and found that THC reduced the production of many inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and the interleukins IL-1β, IL-6, and IL-8. There was also reduced expression of nuclear factor kappa B (NF-κB), a widely expressed protein complex that regulates genes responsible for inflammation, among many other roles. Enhanced production of cofilin-1, another protein involved in arthritis inflammation, was inhibited too. All these effects were significantly, but not completely, mediated by THC’s activation of the CB2 receptor. Benefits have also been observed in animals, with a 2007 study showing that THC blocked pain in arthritic rats through CB2 receptor activation. Anti-inflammatory effects may have been connected to this analgesic effect.

Animal studies indicate a role for CBD in fighting arthritis as well. Researchers at the Kennedy Institute of Rheumatology in London applied CBD to mice with induced arthritis, and it was revealed that CBD could protect joints against damage via reduction of the inflammatory cytokines interferon-gamma (IFN-γ) and TNF-α. Analysis with isolated cells showed CBD caused reduction of lymphocyte proliferation and partially impaired activity of granulocytes, which are innate immune cells that release antibacterial compounds from vesicles called granules.

An animal study with rats published in 2017 demonstrated a link between CBD’s anti-inflammatory effects and prevention of neuropathic pain. By reducing early inflammation during the development of osteoarthritis, CBD was shown to prevent the loss of nerve myelin and later pain associated with joint degeneration and nerve damage.

Phytocannabinoids and Inflammatory Bowel Disease

 
Inflammatory bowel disease (IBD) involves chronic inflammation of the gastrointestinal tract, with ulcerative colitis (UC) and Crohn’s disease being the primary manifestations. These conditions cause pain, discomfort, and can even lead to malnutrition due to impaired nutrient absorption.

THC may hold greater value than CBD for treating IBD. Researchers at the University of South Carolina School of Medicine conducted a study in 2020 on the effects of THC, CBD, and their combination on chemically-induced colitis (inflammation of the colon) in mice. THC administration was able to prevent colitis, but CBD had little effect. THC helped protect the colonic barrier by increasing mucus, tight junctions, and production of antimicrobial substances. CB2 activation by THC on both immune cells and colon cells was responsible for the effects. Researchers stated, “These studies also suggest how cannabinoid receptor activation can be used as a preventive and therapeutic modality against colitis.”

Although not unanimous, there is research that suggests CBD could help with colonic inflammation. A 2017 study showed CBD lowered inflammatory proteins and cytokines in human colon explants (pieces of the human colon removed during surgery). Both CB2 and TRPV1 receptors were implicated in the effects. Another preclinical study two years later indicated the ability of CBD to reduce the hyperpermeability of the colon that develops after inflammation. However, a human trial found that 10mg CBD given twice daily did not benefit Crohn’s disease. It may be that higher doses of CBD or combining it with other phytocannabinoids would be necessary to observe benefits. A rat study in 2010 by researchers in the UK revealed some ability of CBD to work with THC to reduce colonic inflammation, even though THC was indeed more effective than CBD when both were used on their own. Nonetheless, potential synergy may exist when numerous phytocannabinoids are mixed, and more research may elucidate this effect eventually.

Human studies indicate that THC can be beneficial for the treatment of Crohn’s disease in humans. A placebo-controlled study published in 2013 by researchers at Tel Aviv University found that administering cannabis cigarettes containing 115mg THC twice daily was significantly effective at reducing Crohn’s symptoms. Three patients in the THC group were able to wean off steroids, demonstrating that THC could supplant the anti-inflammatory effects delivered by steroids. The THC-using patients further reported better appetite and sleep.

Promising research suggests a role for cannabigerol (CBG), another nonintoxicating phytocannabinoid, as an anti-inflammatory medicine. A study by Italian researchers at the University of Naples in 2013 found that CBG possessed numerous anti-inflammatory and antioxidant functions in a mouse model of colonic inflammation. CBG normalized levels of several cytokines, and even increased activity of superoxide dismutase, one of the human body’s most powerful endogenous antioxidants. Inducible nitric oxide synthase (iNOS), an enzyme involved in inflammation, was also reduced, along with its product nitric oxide. The phytocannabinoid’s benefit was further supported in a 2020 study, in which CBG suppressed chemical-induced inflammation of the colon in mice. CBD had no effect on its own, but when combined with fish oil, which is rich in Omega-3 essential fatty acids that appear necessary for proper ECS function, it became effective. Fish oil also enhanced the anti-inflammatory effects of CBG.

Phytocannabinoids and Diabetes

 
Diabetes is a set of conditions where the body cannot process glucose correctly. The Type 1 form is believed to stem from an autoimmune reaction, where leukocytes attack beta cells in the pancreas that are responsible for producing insulin, the hormone that helps move glucose from the blood into cells. Without insulin, blood sugar remains high and causes damage to blood vessels, which can lead to other problems like heart disease or neuropathic pain. In Type 2 diabetes, insulin is still produced but the body does not utilize it as efficiently (a phenomenon known as insulin resistance), so the same deleterious effect of high blood sugar can still result.

Quite interestingly, CBD has shown potential for preventing the primary cause of Type 1 diabetes. A 2009 study by researchers in Israel examined the effects of CBD in a mouse model of Type 1 diabetes. CBD was given to mice in a latent diabetes stage or with initial symptoms, and diabetes was ultimately diagnosed in only 32% of the treated group, compared to 100% in the untreated group. The pro-inflammatory cytokine IL-12 was reduced while the anti-inflammatory cytokine IL-10 was elevated, indicating that CBD may have actually stopped the immune system from destroying beta cells. Indeed, examining the pancreas of the CBD-treated mice revealed more healthy islets (areas of the pancreas that contain beta cells) than the controls. Researchers stated, “Our data strengthen our previous assumption that CBD, known to be safe in man, can possibly be used as a therapeutic agent for treatment of type 1 diabetes.”

Several complications of diabetes can occur, including cardiomyopathy, in which the heart thickens or stiffens and function declines. A collaborative study in 2010 between researchers in the United States, Switzerland, and Israel found that CBD countered the inflammatory changes associated with diabetic cardiomyopathy in a mouse model. Other findings were reduced oxidative/nitrative stress, cell death, fibrosis, and cardiac dysfunction, indicating the multi-faceted mechanisms of CBD’s physiological actions.

Another complication is diabetic retinopathy, where damage to blood vessels resulting from sustained high blood sugar leads to vision problems. A 2006 rat study published in the American Journal of Pathology found that CBD reduced the inflammatory compounds associated with chemical-induced diabetic retinopathy, including TNF-α, vascular endothelial growth factor, and intercellular adhesion molecule-1. Cell death was prevented as well.

Phytocannabinoids and Lung Diseases

 
When inflammation affects the lungs due to disease or injury, severe damage can occur that eventually interferes with breathing. Phytocannabinoids may prevent the development of inflammation in the lungs arising from several causes. In a chemical-induced model of lung injury using mice, researchers from the University of São Paulo in Brazil showed CBD reduced neutrophil infiltration into lung tissue when administered before the injury. Neutrophils are the most abundant leukocytes in the body. Production of cytokines TNF-α and IL-6 decreased in response to CBD, as did movement-inducing cytokines known as chemokines, including monocyte chemotactic protein-2 (MCP-1) and macrophage inflammatory protein-2 (MIP-2). The adenosine A2A receptor was implicated in these effects.

Asthma is a chronic lung disorder that is associated with excessive inflammation triggered by allergens. The primary treatment involves treatment with steroids to reduce inflammation and bronchodilators to open airways. In 2015, researchers from Brazil induced asthma in rats and then injected CBD into them, causing a widespread reduction in numerous pro-inflammatory cytokines. CBD was posited to be a potential new drug for asthma based on these results.

Phytocannabinoids and Inflammation of the Heart

 
When the heart becomes inflamed from infection, injury, or lack of oxygen, it can be especially dangerous given the critical role of this organ. In a rat study, electrocoagulation-induced ischemia caused characteristic infarct development (areas of tissue death resulting from lack of oxygen), which was reduced in size by 17% with CBD administration. Suppression of inflammation appeared to be connected to this benefit. Another rat study published in 2007 by Israeli researchers examined heart ischemia and demonstrated a stronger effect of CBD, with infarct size decreasing by 66% in the phytocannabinoid-treated group compared to controls. In this case, reduced inflammation and lower levels of IL-6 were associated with this observation.

Inflammation of the heart muscle (myocarditis), which can be associated with infections or autoimmune reactions, can damage the heart to such an extent it causes death (the other forms of heart inflammation include endocarditis and pericarditis, which affect different heart-related tissues). A multi-country study with researchers from the United States, Taiwan, Hungary, Switzerland, and Israel looked at how CBD could potentially be used as a treatment for myocarditis. Using a mouse model, they found that CBD specifically attenuated the T cell-mediated inflammatory response, which resulted in less cardiac dysfunction. The team concluded, “CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation.”

Phytocannabinoids and Inflammation of the Pancreas

 
Pancreatitis can be caused by many factors including a side effect of medications, infection, or alcoholism. In a 2013 study of pancreatitis using mice with chemically-induced inflammation, CBD was found to reverse increases in IL-6 and TNF-α, which are especially key molecules associated with the development of pancreatitis.

Phytocannabinoids and Inflammation of the Central Nervous System

 
Meningitis is an often exceptionally severe infection of the fluid and membranes surrounding the brain and spinal cord, usually by viruses but also sometimes bacteria or fungi. In a rat model of the pneumococcal form of meningitis, which is caused by Streptococcus pneumoniae bacteria, CBD exhibited anti-inflammatory effects including reduction of TNF-α in the frontal cortex. Importantly, these effects had practical benefits, as memory impairment in the rats was prevented as well.

Phytocannabinoids and Neurodegenerative Diseases

 
The development of some diseases is driven by neurodegeneration, the process by which neurons become damaged, lose function, and eventually die. The autoimmune attack on neurons by immune cells contributes to this damage. Huntington’s Disease (HD) is caused by a gene mutation that ultimately leads to the production of toxic proteins that accumulate in neurons and facilitate neurodegeneration. Inflammation exacerbates this degeneration, but appears to be slowed down by phytocannabinoids.

A study published in ACS Chemical Neuroscience used an experimental rat model of HD to demonstrate that inflammation was countered by administration of both THC and CBD. Specifically, activation of both microglia and astroglia, which are non-neuronal cells in the nervous system involved with inflammation and support for neurons, was reduced. The inflammatory enzyme iNOS was also lower in the phytocannabinoid-treated rats. Researchers claimed their study provided preclinical evidence that the THC and CBD combination product was a “neuroprotective agent capable of delaying signs of disease progression in a proinflammatory model of HD.” CBG has also been shown to reduce inflammatory markers in a mouse model of HD, so combinations of CBG and CBD may one day be used as HD treatments.

In multiple sclerosis (MS), immune cells attack neurons in the CNS and cause progressive degeneration of neurons. Excessive activation of microglia, which act as resident macrophages of the CNS among other supportive functions, may be involved in the characteristic demyelination process of neurons, in which the loss of protective myelin leads to neurodegeneration. A 2013 study which utilized a virus-induced form of MS in mice found that CBD reduced migration of leukocytes into the CNS by downregulating the chemokines CCL2 and CCL5 and the inflammatory cytokine IL-1β. An inflammatory molecule called vascular cell adhesion molecule-1 was also reduced, and these effects appeared to be involved with reduced activation of microglia. These changes were associated with measurable benefits, as motor problems in mice were alleviated with CBD. Another study published in 2015 by Spanish researchers confirmed the above results, as a whole-plant CBD extract reduced microglial activity in mice, among other actions, and improved their motor activity.

Parkinson’s Disease (PD) is another neurodegenerative disorder of the CNS that causes movement issues. It is especially characterized by loss of dopamine-producing neurons. While MS is more formally categorized as an autoimmune condition, emerging research suggests autoimmunity plays a role in PD as well. A 2005 study which featured Dr. Raphael Mechoulam, the scientist who discovered THC, examined the impact of both THC and CBD on mice with chemically-induced PD symptoms. Both phytocannabinoids reduced neurodegeneration in mice, which the authors posited may have been due to antioxidant and/or anti-inflammatory effects.

Alzheimer’s Disease (AD) is the most prominent form of dementia and is characterized by the accumulation of abnormal proteins that interfere with neuronal transmission. Too much inflammation further damages neurons and likely contributes to the development of AD. A team from multiple universities and clinics in France showed how CBD could inhibit inflammation in a cell model of AD, in addition to other beneficial effects. THC has been demonstrated to block the toxic inflammatory response in a similar AD cell model. Importantly, whole-plant extracts of THC and CBD were shown to work better together than alone at reducing activity of microglia, astroglia, and pro-inflammatory compounds in a genetic mouse model of AD. These anti-inflammatory effects were related to perseveration of memory and reduced learning impairment.

Amyotrophic lateral sclerosis (ALS) is a difficult-to-treat neurodegenerative condition affecting the CNS. This leads to the loss of nearly all motor functions, even breathing. Inflammation of nervous tissue appears to contribute to the progression of ALS. In 2019, Italian researchers conducted a study where CBD and CBG were tested in a cellular model of ALS. Many beneficial effects were observed, including reduction of TNF-α, iNOS, and NF-κB activation. Moreover, the anti-inflammatory cytokines IL-10 and IL-37 were increased, as was the transcription factor protein Nrf2, which protects cells from damage by increasing endogenous antioxidant production. The phytocannabinoids also reduced apoptosis by normalizing the balance between the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax. Therefore, both CBD and CBG were associated with comprehensive anti-inflammatory, antioxidant, and cell survival effects, demonstrating their multi-faceted functions.

A 2019 survey of ALS patients in Berlin confirmed the benefits of THC and CBD in humans. Based on the questionnaire, high average satisfaction levels of phytocannabinoid treatment were reported in the domains of effectiveness, convenience, and global satisfaction. Further research that examines the impact of CBG is warranted given the potential indicated by the above preclinical study.

Phytocannabinoids and Inflammatory Chronic Pain

 
Inflammatory pain is associated with numerous conditions, and some studies looking at THC and CBD on the pain associated with arthritis were mentioned earlier. Other experiments have explored analgesic effects of phytocannabinoids, including a study in 2012 on CBD and chemical-induced inflammatory pain in mice and rats. CBD successfully suppressed pain via targeting of alpha-3 glycine receptors.

In 2019, researchers with the Center for Substance Abuse Research at Temple University in Philadelphia found that CBD could reduce pathological inflammation that occurred after mice were subjected to spinal cord injury. This anti-inflammatory effect may have been responsible for the subsequent protection against thermal sensitivity observed in the CBD-treated mice.
Being too sensitive to heat can result in thermal hyperalgesia, which is a heightened and often painful response to warm or cold temperatures. In a chemically-induced rat model of acute inflammation, CBD eliminated thermal hyperalgesia via activation of TRPV1 receptors, without involvement of CB1 or CB2 receptors. As these studies show, CBD is quite varied in how it produces analgesic effects.

THC, which is well known for its ability to reduce the central perception of pain due to psychoactive properties, also exerts anti-inflammatory effects and may block pain signaling through those mechanisms. A 2016 study by Chinese researchers showed that THC could enhance the anti-inflammatory function of mesenchymal stem cells (MSCs), which are primarily involved in making and repairing skeletal tissue but also fight harmful inflammation. This effect was observed in cell models as well as a mouse model, where THC-treated MSCs were injected into the tails of mice with surgically-induced neuropathic pain. The mice subsequently experienced less early thermal hyperalgesia and mechanical allodynia (painful sensations from normally non-painful touching) compared with non-treated MSCs, although the effect weakened after 7 days, suggesting that THC’s augmentation of MSC anti-inflammatory effects is time limited. Repeated administration of THC-treated MSCs or THC itself is likely required to sustain effects. Consistent with observations in the cell model, pro-inflammatory cytokines like TNF-α, IL-1β and IL-6 decreased in mice after the MSC administration, while the anti-inflammatory cytokine IL-10 increased. Importantly, THC alone was shown to reduce pro-inflammatory cytokines from microglia. Since cannabis medicines themselves will always be easier to obtain than advanced therapies like THC-treated MSCs, it is certainly good that THC also shows direct anti-inflammatory effects.

A 2019 study in the International Journal of Molecular Sciences further indicated the analgesic effects of THC that result from its anti-inflammatory functions. Researchers tested the benefits of THC on female mice with chemical-induced vulvodynia, a chronic pain condition of the vulva. Topical THC administration was associated with decreased sensitivity to pressure along with reduced levels of mast cells which contribute to the sensation of pain through release of inflammatory mediators.

Phytocannabinoids and Skin Inflammation

 
The presence of microorganisms like bacteria, tissue damage, and/or autoimmune reactions can lead to skin inflammation. A 2018 study by researchers in Italy found CBD was very effective in reducing pro-inflammatory cytokine release from keratinocytes (primary skin cells) in a cell model of allergic contact dermatitis (ACD). In ACD, allergens trigger an inflammatory response in the skin leading to a rash. Beyond the inflammation caused by direct activation of leukocytes by allergens, keratinocytes also contribute to the inflammation as well. Stopping inflammation in both cell types may be important for anti-dermatitis effects. Importantly, several other phytocannabinoids beyond CBD, including CBG, cannabigerolic acid (CBGA), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabichromene (CBC), cannabigevarin (CBGV), tetrahydrocannabivarin (THCV), and tetrahydrocannabivarinic acid (THCVA), were shown to inhibit inflammatory effects through lowering levels of cytokines IL-6, IL-8, TNF-α, and the chemokine MCP-2. Of all the compounds, CBD possessed the strongest anti-inflammatory effect. Another study confirmed the anti-inflammatory effects of several phytocannabinoids (CBC, CBCV, CBD, CBDV, Δ8-THCV, Δ8-THC, Δ9-THC) in a mouse model of ear dermatitis, with reduced ear swelling seen after topical application.

THC has also been shown to alleviate ACD, as indicated by a mouse study published in 2013 by German researchers. Topically applying THC to chemical-induced dermatitis decreased ear swelling and infiltration of immune cells, which was associated with inhibited production of IFN-γ by T cells and of chemokines CCL2, CCL8, and CXL10 by keratinocytes. Although THC often works by activating CB1 and/or CB2 receptors, they were not implicated in the effects of THC in this case.

A patent filed in 2018 described the use of a combination of CBG and CBD in treating psoriasis, with CBG present at levels two to three times higher than CBD. Topical application was effective when the 15% CBG/CBD oil treatment was utilized, but the 3% CBG/CBD treatment was ineffective. The mechanism was theorized to be related at least partially to CBD’s and potentially CBG’s ability to rebalance Th1 and Th2 cell activity, inhibiting the former and increasing the latter. Th1 and Th2 cells are different kinds of helper T cells, and their dysregulation may be involved in numerous inflammatory processes.

Epidermolysis bullosa (EB) is a particularly aggressive skin disorder in which skin fragility leads to repeated blistering, pain, and infections. Case reports published in 2018 by researchers in West Virginia and California found that topical application of CBD resulted in faster wound healing, less blistering, and reduced pain in three patients, which was likely connected to CBD’s anti-inflammatory effects. Another case series the next year by researchers in the Netherlands, which also analyzed three EB patients, found that an internally-ingested THC and CBD medicine was effective for reducing pain, itching, and the need for pain drugs, suggesting that anti-inflammatory properties can be useful when experienced externally or internally.

Inflammation also contributes to the growth of some skin cancers. Researchers at the University of Bonn in Germany showed that THC reduced the growth of melanoma tumors in mice by lowering infiltration of macrophages and neutrophils. The effect was quite significant, as the THC-treated mice had 50% smaller tumor volumes than untreated mice.

Phytocannabinoids and Drug-Associated Inflammatory Conditions

 
Inflammation occurs because of many lifestyle behaviors, including consumption of certain drugs. The inflammation associated with alcohol consumption may be responsible for some of its harmful effects. In a 2017 study using mice, alcohol consumption induced several pathological changes including liver inflammation. CBD attenuated that effect by reducing pro-inflammatory cytokines along with the accumulation and function of neutrophils. Another study with mice published by Brazilian researchers found CBD also reduced cocaine-induced liver inflammation.

Antimicrobial Effects of Phytocannabinoids

 
Since infections by microorganisms and viruses are a major cause of inflammation, direct antimicrobial effects of phytocannabinoids would be quite valuable. Indeed, a 2008 study published in the Journal of Natural Products determined that THC, CBD, CBC, CBG, and cannabinol (CBN) exerted antibacterial activity against several strains of methicillin-resistant Staphylococcus aureus (MRSA), one of the most challenging bacterial species affecting humans. Results were further supported by a 2020 study by Pakistani researchers, who demonstrated that phytocannabinoids and terpenes derived from cannabis could synergistically work together to decrease numbers of Gram-positive and Gram-negative bacteria.

Another 2020 study demonstrated the ability of phytocannabinoids to fight MRSA, including by inhibiting biofilm formation and eradicating preformed biofilms. The formation of biofilms, which are collections of microorganisms embedded in a protective extracellular matrix, impart resistance to the resident organisms from many conventional antibiotics. CBD was further demonstrated to interfere with biofilm formation of the fungus Candida albicans in a 2021 study.

The essential oils of cannabis, which are rich in terpenes rather than phytocannabinoids, also have strong antibacterial properties, as suggested by the above Pakistani study. In 2019, researchers from Italy tested seventeen different essential oils of hemp, a form of cannabis that is more readily available due to low levels of THC, on Gram-positive bacteria, finding that six of them had good antibacterial activity. It was suggested that hemp essential oil could be used in the food processing industry to reduce microorganism contamination.

The antibacterial benefits appear to extend to control of dental plaque, which is a specific form of biofilm that develops on teeth and degrades them over time. In a 2020 study, researchers from Belgium collected plaques from sixty adults and tested various products on them, including various phytocannabinoids including CBD, CBG, CBC, CBN, and CBGA. The compounds were more effective at reducing bacteria from the plaques than the commercial products Oral B and Colgate. Researchers concluded, “Cannabinoids have the potential to be used as an effective antibacterial agent against dental plaque-associated bacteria.”

It is interesting how much research was published in 2020 concerning antibacterial effects of phytocannabinoids, as yet another study that year examined the impressive effect of cannabichromenic acid (CBCA) against MRSA. Importantly, CBCA outperformed vancomycin, the dominant drug of choice for treating MRSA, with faster and more potent killing action. Normal mammalian cells did not display decreased viability after exposure to CBCA, demonstrating safety of the compound.

Evidence suggests phytocannabinoids also possess antiviral activity. A study in 2011 tested THC on rhesus macaques who were infected with simian immunodeficiency virus (SIV), which shares some characteristics with human immunodeficiency virus (HIV). Sustained administration of THC resulted in decreased early mortality as well as reduced viral load. In cell studies, THC decreased viral replication, which may have been responsible for the lower viral load in the rhesus macaques. Given the rise of medical cannabis use in the 1980s due to the AIDS epidemic, it is tempting to speculate whether THC may have been helping directly fight the HIV virus in addition to improving appetite and other symptoms.

Summary

 
The remarkable array of anti-inflammatory effects associated with phytocannabinoids is incredible and likely helps explain why so many people report efficacy from medical cannabis use. Far more human research is required to confirm how many of these preclinical benefits extend to humans, but based on the limited trials done so far, there is real promise that phytocannabinoids could be introduced as anti-inflammatory agents in mainstream medicine.