2: Cannabis Compounds for


THC and CBD help control arthritis symptoms, which is well known. These and 15 other cannabis compounds, mainly cannabis terpenes, may help to also deter arthritis progression. The 15 are:

β-caryophyllene oxide

Fourteen of these are terpenes, the exception being the flavonoid apigenin. Appendix A: Common Cannabis Compounds provides a brief introduction to these compounds.

The traditional approach to consuming terpenes is through aromatherapy — the inhalation and topical absorption of essential oils. Aromatherapy is a well-known approach to the treatment of arthritis pain. The new element reported here is its potential use in retarding the progression of arthritis.

In addition to pure terpenes, there are also terpene-rich essential oils. Humulus lupulus (hops) is an excellent source of α-humulene and β-Caryophyllene. Bergamot orange is a good source of d-limonene. Pinus sylvestris (pine) is a good source of α-terpineol and α-pinene. Natural sources for the remaining 10 compounds are given in the Common Cannabis Compounds list.

This article is organized as a series of presentations. Each presentation ends with a door that opens onto an exposition of supporting research documented with in-text citations in the form of hyperlinked daggers. Mousing over a dagger brings up its corresponding reference hyperlinked to the supporting research[CiOn].

A discussion of salient characteristics of common kinds of arthritis provides the basis for identifying cannabis compounds that, based on animal studies, may slow the progression of arthritis.

2.1 Types of Arthritis 

According to the Arthritis Foundation, there are more than 100 different forms of arthritis, including osteoarthritis, rheumatoid arthritis, spinal arthritis, and psoriatic arthritis[arth-found].

Osteoarthritis, the most common form, is traditionally viewed as a degenerative disease caused by wear and tear. However, obesity leads to a higher prevalence of osteoarthritis in non-weight-bearing areas as well as weight-bearing areas. Inflammatory cytokines are found in arthritic joints, and they contribute to arthritis progression. Moreover, inflammatory cytokine levels increase with age. So, there is reason to believe that inflammation either causes or strongly contributes to osteoarthritis. ⮛ RESEARCH ⮛

Elevated levels of TNF-α, IL-1, and IL-6 occur in osteoarthritis — in the synovial fluid that lubricates the joints, in the membranes that hold the synovial fluid, and in the bone below a joint's cartilage. The link with obesity is that fat tissue is a source of inflammatory cytokines[Wang_2018][Greene_2019][Wang_2015].

Increasing age brings increasing levels of inflammatory and erosive chemicals throughout the body, some of which are secreted by aging cartilage. There is increased systemic inflammation, increased inflammation of the joints, and increased chemically induced deterioration of cartilage[Greene_2019].

Spinal arthritis is usually a form of osteoarthritis. It occurs most commonly in the lower back or neck. Again, inflammation plays a key role.  ⮛ RESEARCH ⮛

spine illustrationSpinal arthritis is associated with inflammation and degeneration of the vertebrae, facet joints, and disks, as illustrated in the image to the right[TBI_2016]. The degeneration leads to a narrowing (stenosis) of the spinal canal. The result is pressure on nerves leaving the spine that initially causes back pain and muscle spasms. The pinched nerves may include those associated with the lower extremities, causing pain to radiate downward through the pelvis, buttocks, legs, and knees[Regan_2019][TBI_2016]. The pinched nerves may also cause bladder problems, including urgency and frequency of urination[Eidelson_2019].

Ankylosing Spondylitis is an inflammatory arthritis of the spine. There is evidence that a particular bacterium can cause this form of arthritis. In this case, the cannabis compounds guaiol, BCPO (β-caryophyllene oxide), linalool, eucalyptol, and α-terpineol may help kill the bacterium. ⮛ RESEARCH ⮛

The implicated bacterium is Klebsiella pneumoniae[Rashid_2006]. The effectiveness of guaiol, caryophyllene oxide, linalool, eucalyptol, and α-terpineol was determined by studying traditional Australian herbal remedies, specifically, Tasmanian mountain pepperberry[Winnett_2017].

Rheumatoid arthritis is an autoimmune disease. The immune system attacks the synovial membranes that hold the fluid that lubricates the joints. Psoriatic arthritis is also an autoimmune disease. Its first symptom is usually psoriasis. With both conditions, pain is lessened, and disease progression is slowed by suppressing inflammation.

2.2 Fighting Arthritis  

In a survey of Canadian cannabis users, the most popular strains for arthritis were Sweet Skunk CBD, OG Shark, Cannatonic, and CBD House Blend. Sweet Skunk CBD is a high-CBD strain whose primary terpenes include α-pinene, β-myrcene, and trans-nerolidol. ⮛ RESEARCH ⮛

A 2018 paper presenting the research on Canadian cannabis preferences includes an outstanding review of previous relevant research. It concludes that their survey presents the first published research to explicitly address the fact that different strains have different medical benefits[Baron_2018]. The information on Sweet Skunk CBD comes from the Leafy website. The presence of trans-nerolidol in Sweet Skunk CBD is somewhat unusual[Leafy_2019].

CBD appears to reduce arthritis pain and deter joint damage. Moderate doses of CBD have proved more effective than large or small doses. THC also has an anti-inflammatory effect and has been shown to reduce pain and slow cartilage erosion. The terpene α-pinene has deterred the breakdown of cartilage and may also deter arthritis progression. ⮛ RESEARCH ⮛

The relevant cytokines are produced mainly in joint cartilage[Melchiorri_1998].

CBD and THC have both reduced pain and inflammation and have prevented nerve damage in animal models of osteoarthritis[Philpott_2017][Yang_2015][Gamble_2018][Morouj_2018]. A clinical trial demonstrated a significant analgesic effect of the Sativex brand of THC+CBD in rheumatoid arthritis[Blake_2006]. The use of CBD brought improvement in an animal model of arthritis used to study rheumatoid and reactive arthritis[Hammell_2015][Malfait_2000]. One motivation for using THC is that it tends to be less toxic than the commonly used low-dose methotrexate[Morouj_2018][Kivity_2014]. THC stimulates the CB2 cannabinoid receptor, which is more highly expressed in patients with rheumatoid arthritis than in patients with osteoarthritis[Dunn_2016][Yang_2015][Fukuda_2014][Gertsch_2008].

The CB2 agonist JWH-133 has reduced inflammation and bone destruction in a mouse model of arthritis, and the same may be true of the stronger CB2 agonist β-caryophyllene (BCP)[Fukuda_2014][Gertsch_2008].

The anti-inflammatory and anti-catabolic effects of d-limonene and α-pinene in human cartilage cells have been observed by Rufino and others[Rufino_2015][Rufino_2014].

Arthritic pain and inflammation appear to be primarily caused by the four inflammatory cytokines IL-1, IL-6, TNF-α, and IL-17. These cytokines promote the initiation and progression of common forms of arthritis, including osteoarthritis, rheumatoid arthritis, septic arthritis, and post-traumatic arthritis. Much of the destruction is performed through IL-1 stimulation of nitric oxide production. An additional source of inflammation and destruction occurs when new blood vessels invade cartilage — healthy cartilage does not contain blood vessels.

For each destructive mechanism, the presentation proceeds in four steps: cannabis compounds that help, the mechanism's causal role in arthritis, conventional medicines whose success may block that mechanism, and, finally, an explanation of how the identified cannabis compounds block the destructive mechanism.

In some cases, there is a lack of research on lowering cytokines that have been elevated by arthritis. In these cases, it has been necessary to substitute educated guesses based on research into lowering cytokines that have been raised in other diseases such as cancer or rat paw edema. The same problem concerns research on preventing blood vessels from invading cartilage.

The IL-1 Cytokine

CBD, THC, BCP (β-Caryophyllene), α-humulene, geraniol, trans-nerolidol, d-limonene, α-terpineol, eucalyptol, and 4-terpineol may retard the progression of arthritis and associated pain by lowering IL-1 levels. ⮛ RESEARCH ⮛

Causal Link. People living with arthritis, including those with post-traumatic arthritis, have high levels of IL-1α, IL-1β, TNF-α, and IL‐17. These cytokines contribute to bone loss by stimulating the production of osteoclasts — cells that break down cartilage[Schett_2011][Olson_2015]. IL-1α, IFN-γ, and TNF-α all induce apoptosis (programmed cell death) in bovine cartilage. This finding is relevant to most forms of arthritis, including osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis[Schuerwegh_2003].

Conventional Treatments. Multiple studies have shown that blocking IL-1 helps. The human body already has an IL-1 antagonist that lowers IL-1, and there is a synthetic analog, anakinra (brand name Kineret), that lowers IL-1 levels and slows the progression of rheumatoid arthritis[Olson_2015][Molecular_and_Cell_Biology_2013][Pharmacology_2016][Mertens_2015]. Moreover, the body has a 'decoy' receptor that binds nitric oxide nonproductively to IL-1, again blocking its inflammatory role and helping in an animal model of arthritis[Shimizu_2015]. Since blocking IL-1 helps, it may also be the case that lowering IL-1 helps.

Cannabis Compounds. THC lowerd IL-1β in a brief human trial and in an animal model of RA[Morouj_2018][Bidwell_2018]. Both CBD and THC lowerd IL-1β in chemically stressed mouse microglial cells[Kozela_2009]. CBD lowerd IL1-β and TNF-α in a mouse model of multiple sclerosis[Mecha_2013]. BCP (Beta-caryophyllene) lowerd IL-1β and TNF-α in in vitro tests[Gertsch_2008][Rufino_2015][Medeiros_2007][Guo_2014].

Nerolidol inhibited IL1-β and TNF-α in mouse peritonitis[Fonsêca_2015]. Perillyl alcohol reduced IL-1β and TNF-α in a rat model of stroke, and eucalyptol lowerd IL-1. α-Humulene lowerd IL-1β and TNF-α in rat paw edema[Medeiros_2007]. Geraniol lowerd IL-1β and TNF-α in rat tongue cancer[Madankumar_2017]. Perillyl alcohol, a metabolite of d-limonene, lowered IL-6, IL-1β, and TNF-α in a rat model of stroke[Tabassum_2014].

The IL-6 Cytokine

CBD, THC, BCP, d-limonene, α-terpineol, 4-terpineol, eucalyptol, and apigenin may retard the progression of arthritis and associated pain by lowering IL-6 levels. ⮛ RESEARCH ⮛

Causal Link. People with osteoarthritis[Wojdasiewicz_2014][Stannus_2010] or rheumatoid arthritis[Misato_2011] have elevated IL-6, which is thought to play an active role in disease progression and increased pain.

Conventional Treatments. The drug tocilizumab lowers RA disease activity by blocking the IL-6 receptor. The experimental drug sarilumab lowered RA disease activity by lowering IL-6 levels directly, but it failed to win FDA approval due to some fatalities[Avci_2018]. These results suggest that other ways of lowering IL-6 may help as well.  

Cannabis Compounds. CBD lowered IL-6 in ischemic rat hearts and in chemically stressed mouse microglial cells[Durst_2007][Kozela_2009]. THC lowered IL-6 in a brief human trial and in an animal model of rheumatoid arthritis[Bidwell_2018][Morouj_2018]. THC also reduced IL-6 in chemically stressed macrophages and in an eternalized mouse microglial cell line[Kozela_2009][Chang_2001][Puffenbarger_2000]. BCP lowerd IL-6, IL-1β, and TNF-α in a microglia cell line used to study neuroinflammation[Guo_2014]. 

Perillyl alcohol, a metabolite of d-limonene, lowered IL-6, IL-1β, and TNF-α in a rat model of stroke[Tabassum_2014]. α-Terpineol lowerd IL-6 in human cheek cells stressed with desiccated orange juice[Held_2007]. α-Terpineol and 4-terpineol (aka terpinen-4-ol) lowerd both IL-6 and IL-1β in chemically stressed human macrophages[Nogueira_2014][Trinh_2011]. Eucalyptol lowerd IL-6, IL-1β, and TNF-α in various in vitro and animal models of inflammation[Caceres_2017][Lima_2013][Yadav_2017][Li_2016][Kennedy-Feitosa_2016][Yu_2018][Khan_2013][Trinh_2011]. The flavonoid apigenin lowerd IL-6 in chemically stressed mice[Smolinski_2003].

The TNF-α Cytokine

CBD, THC, BCP, eucalyptol, geraniol, α-humulene, α-terpineol, and apigenin may retard the progression of arthritis and associated pain by lowering TNF-α levels. ⮛ RESEARCH ⮛

Causal Link. TNF-α is implicated in destroying bone and cartilage in osteoarthritis and in post-traumatic arthritis[Schett_2011][Stannus_2010].

Conventional Treatments. The commercial TNF-α inhibitors adalimumab (Humira) and infliximab (Remicade) bind directly to TNF-α, thereby disabling it. They have demonstrated effectiveness in treating rheumatoid and psoriatic arthritis as well as psoriasis itself[Adalimumab][Infliximab]. Inflammatory hand osteoarthritis has been successfully treated by blocking TNF-α with the off-label use of etanercept (Enbrel, Benepali)[Kloppenburg_2018]. The success of TNF-α blocking drugs suggests that lowering TNF-α via cannabis compounds may help in the same way.

Cannabis Compounds. As noted above, CBD, BCP, nerolidol, perillyl alcohol, α-humulene, eucalyptol, α-terpineol, and geraniol all lower TNF-α. THC also lowerd TNF-α in an animal model of rheumatoid arthritis[Morouj_2018]

The flavonoid apigenin lowerd TNF-α in an experimental model of mouse pancreatitis[Charalabopoulos_2019]. Apigenin lowerd TNF-α and upregulated the anti-inflammatory cytokine IL-10 in mouse leukemia macrophages[Palacz-Wrobel_2017].

The IL-17 Cytokine

BCP, CBD, and THC may be of benefit in rheumatoid arthritis by slowing bone loss and lowering IL-17 levels. ⮛ RESEARCH ⮛

Causal Link. The breaking down of bone tissue is a normal part of bone metabolism. This process is carried out by specialized bone cells called osteoclasts. In rheumatoid arthritis, there are too many osteoclasts. Here's what happens: IL-23 induces synovial tissue to produce IL-17, which in turn promotes the production of new osteoclasts[Paradowska-Gorycka_2010]. These cause synovial inflammation, cartilage and bone degradation, and joint destruction according to in vitro and animal experiments[Kellner_2013]. Much of this chaos is also apparent in ankylosing spondylitis[Koenders_20016].

Conventional Treatments. Secukinumab and ixekizumab (IL-17 neutralizing agents), and perhaps brodalumab (an IL-17 receptor antagonist),  have shown promise in treating psoriasis, psoriatic arthritis, and rheumatoid arthritis[Koenders_20016][Kunwar_2016].

Cannabis Compounds. CBD lowerd IL-17 in animal studies[Giacoppo_2016][Harvey_2013]. THC lowerd IL-17 in an in vitro study[Kozela_2013]. The CB2 agonist JWH-133 lowerd IL-17 in macrophages[Norooznezhad_2016][Guillot_2013], so the same is likely to be true of the stronger CB2 agonist BCP[Gertsch_2008].

Nitric Oxide

α-Humulene, α-terpinene, α-pinene, β-pinene, and d-limonene may help with arthritis by lowering nitric oxide levels. ⮛ RESEARCH ⮛

Causal Link. Nitric oxide is produced in cartilage due to stimulation by IL-1 and, for rheumatoid arthritis, TNF-α as well[Taskiran_2002][Nagy_2008]. Nitric oxide directly stimulates the destruction of cartilage in osteoarthritis[Boileau_2002][Leonidou_2018], inflammatory arthritis[McCartney-Francis_1993], and especially rheumatoid arthritis[Farrell_1992][vant_Hof_2000].

Conventional Treatments. Reducing nitric oxide has reduced inflammation and inhibited cell death in cartilage and synovial membrane[Leonidou_2018][McCartney-Francis_1993][vant_Hof_2000].

Cannabis Compounds. It may also be the case that nitric oxide-suppressing cannabis compounds impede arthritis progression. α-Humulene, α-terpinene, α-pinene, and β-pinene have lowered nitric oxide levels[Coté_2017]. d-limonene has lowered nitric oxide indirectly by inhibiting IL-1β[Rufino_2015].

Blood Vessel Invasion of Cartilage

CBD, THC, BCP, BCPO, d-Limonene, and β-eudesmol may help with arthritis by preventing inappropriate angiogenesis in which new blood vessels invade cartilage. ⮛ RESEARCH ⮛

Causal Link. The destruction of cartilage by nitric oxide and other factors is followed by new blood vessels invading cartilage. This abnormal angiogenesis takes place in several types of arthritis, including osteoarthritis, rheumatoid arthritis, and chronic septic arthritis[Walsh_2007][Bonnet_2004][Elshabrawy_2015][Pessler_2008]. It is apparently stimulated by inflammation, at least in the case of osteoarthritis[Haywood_2003]. In the case of rheumatoid arthritis, angiogenesis leads to the growth of "pannus" tissue that covers the synovial membrane and releases additional chemicals that destroy cartilage, bone, tendons, ligaments, and blood vessels[Pannus_2018].

Conventional Treatments. There have been some successes in treating arthritis by inhibiting angiogenesis. In rheumatoid arthritis, blockade of TNF-α and IL-1 significantly inhibits VEGF. This key signaling protein promotes the growth of new blood vessels[Paleolog_2002]. Szekanecz and Koch have enumerated several more angiogenesis inhibitors[Szekanecz_2008].

Cannabis Compounds. Although there has been no research on slowing angiogenesis in cartilage with cannabis compounds, there have been some results on slowing angiogenesis in cancer. CBD in colon cancer[Massi_2012] and glioblastoma[Dumitru_2018]; THC in breast cancer[Caffarel_2010] and glioblastoma[Dumitru_2018]; BCP viz JWH-133 in glioma[Blázquez_2004];  BCPO in breast and prostate cancer[Park_2011]; β-eudesmol in cervical, gastric, and liver cancers[Ma_2008]; and d-limonene
in gastric cancer [Lu_2004].

Rendered according to the Citations Online architecture

CiOn. Adapting Citations and References to the Online Environment. Project overview. Williams J (bio). Page Notes. Updated 2022 January 14.

arth-found. What Is Arthritis? Article. Unattributed. Arthritis Foundation. Undated.

Wang_2018. Pro-inflammatory cytokines: The link between obesity and osteoarthritis [literature review]. Abstract. Wang T (Sichuan University), He C. Cytokine & Growth Factor Reviews. Online 2018 October 11.

Greene_2019. Aging-related Inflammation in Osteoarthritis [literature review]. Full text. Greene M (Wake Forest University), Loeser R. Osteoarthritis and Cartilage. Online 2015 November 1.

Wang_2015. Metabolic Triggered Inflammation in Osteoarthritis [literature review]. Abstract, full text. Wang (University of Tasmania), Hunter D, Xu J, Dingn C. Osteoarthritis and Cartilage. Online 2014 October 15.

TBI_2016. What is a Facet and Sacroiliac Joint (SI) Rhizotomy\? [Illustration]. Web page. Unattributed. Texas Back Institute. Updated 2018 December 14.

Regan_2019. Spinal Arthritis: Symptoms [exposition]. Full text. Regan J (bio). Remedy Health Media. Updated 2019 February 26.

Eidelson_2019. Spinal Disorders May Cause Neurogenic Bladder Disorder or Dysfunction [exposition]. Full text. Eidelson S (bio). Remedy Health Media. Updated 2019 March 3.

Baron_2018. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort [electronic survey]. Full text. Baron E (bio), Philippe L, Rades J, Hogue O. The Journal of Headache and Pain. Online 2018 May 24.

Leafy_2019. Sweet Skunk CBD [product description]. Web page. Leafy, Tilray. Privateer Holdings. Undated.

Melchiorri_1998. Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis. Abstract. Melchiorri C, Meliconi R, Frizziero L. Arthritis and Rheumatism. 1998 December.

Dunn_2016. Expression of Cannabinoid Receptors in Human Osteoarthritic Cartilage: Implications for Future Therapies. Full text. Dunn S (Sheffield Hallam University), et al. Cannabis and Cannabinoid Research. Online 2016 Jan 1.

Yang_2015. Cannabinoid receptor CB2 is involved in tetrahydrocannabinol-induced anti-inflammation against lipopolysaccharide in MG-63 cells. Full text. Yang L (Fourth Military Medical University, Xi'an, Shaanxi), Li F, Han Y, Jia B, Ding Y. Mediators of Inflammation. Online 2015 January 14.

Fukuda_2014. Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis [in vitro and animal studies]. Full text. Fukuda S (Tokyo Medical and Dental University), Kohsaka H, Takayasu A, Yokoyama W, et al. BMC Musculoskelatal Disorders. Online 2014 August 12.

Gertsch_2008. Beta-caryophyllene is a dietary cannabinoid [animal study]. Full text. Gertsch J (bio), Leonti M, Raduner S, et al. Proceedings of the National Academy of Sciences (U.S.). Online 2008 June 23.

Philpott_2017. Attenuation of early phase inflammation by Cannabidiol prevents pain and nerve damage in rat osteoarthritis. Full text. Philpott H, O'Brien M, McDougall J. Pain. 2017 September 1.

Gamble_2018. Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Full text. Gamble L (Cornell University), et al. Frontiers in Veterinary Science. 2018 July 23.

Morouj_2018. Anti-Inflammatory, Antioxidative, and Hepatoprotective Effects of Trans Δ9-Tetrahydrocannabinol/Sesame Oil on Adjuvant-Induced Arthritis in Rats. Full text. Morouj I (Beirut Arab University), et al. Evidence-Based Complementary and Alternative Medicine. Online 2018 June 25.

Blake_2006. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis [small scale trial]. Abstract, full text. Blake D (Royal National Hospital for Rheumatic Diseases), Robinson P, Ho M, et al. Rheumatology. Online 2005 November 9.

Hammell_2015. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Abstract. Hammell D (University of Kentucky), Zhang L, Ma F, et al. European Journal of Pain. Online 2015 October 30.

Malfait_2000. The nonpsychoactive cannabis constituent cannabadiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Full text. Malfait A (Kennedy Institute of Rheumatology, London), Gallily R, Sumariwalla F, et al. Proceedings of the National Academy of Science (U.S.). Online 2000 August 1.

Kivity_2014. Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients [case series]. Abstract. Kivity S (The Chaim Sheba Medical Center, Ramat-Gan, Israel), et al. Autoimmunity reviews. Online 2014 August 27.

Rufino_2015. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. Abstract. Rufino A (University of Coimbra, Coimbra, Portugal), Ribeiro M, Sousa C, et al. European Journal of Pharmacology. Online 2015 March 5.

Rufino_2014. Anti-inflammatory and Chondroprotective Activity of (+)-α-Pinene: Structural and Enantiomeric Selectivity [In vitro study]. Full text. Rufino A (University of Coimbra, Coimbra, Portugal), Ribeiro M, Fernando J et al. Journal of Natural Products. Online 2014 January 23.

Schett_2011. Effects of inflammatory and anti-inflammatory cytokines on the bone [Literature review]. Full text. Schett G (University of Erlangen-Nuremberg). European Journal of Clinical Investigation. Online 2011 May 25.

Olson_2015. Therapeutic Opportunities to Prevent Post-Traumatic Arthritis: Lessons from the Natural History of Arthritis after Articular Fracture [animal study]. Full text. Olson S (Duke University Medical Center), Furman B, Kraus V, Huebner J, Guilak F. Journal of Orthopedic Research. Online 2015 June 7.

Schuerwegh_2003. Influence of pro-inflammatory (IL-1 alpha, IL-6, TNF-alpha, IFN-gamma) and anti-inflammatory (IL-4) cytokines on chondrocyte function [in vitro study]. Full text. Schuerwegh A (University of Antwerp, Belgium), Dombrecht E, Stevens W, et al. Osteoarthritis and Cartilage. Online 2003 September 1.

Molecular_and_Cell_Biology_2013. Interleukin 1 receptor antagonist [exposition]. Full text. WikiProject Molecular and Cell Biology. Wikipedia. Updated 2013 December 6.

Pharmacology_2016. Anakinra [exposition]. Full text. WikiProject Pharmacology. Wikipedia. Updated 2016 September 27.

Mertens_2015. Anakinra for rheumatoid arthritis: a systematic review [exposition]. Full text. Mertens M (Minneapolis VA Medical Center), Singh J. The Journal of Rheumatology. Online 2009 May 15.

Shimizu_2015. IL-1 receptor type 2 suppresses collagen-induced arthritis by inhibiting IL-1 signal on macrophages [animal study]. Abstract. Shimizu K (Tokyo University of Science), Nakajima A, Sudo K, et al. Journal of Immunology. Online 2015 February 27.

Bidwell_2018. A Novel Observational Method for Assessing Acute Responses to Cannabis: Preliminary Validation Using Legal Market Strains [observational study]. Full text. Bidwell L (University of Colorado), et al. Cannabis and Cannabinoid Research. Online 2018 March 1.

Kozela_2009. Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells. Full text. Kozela E (Weizmann Institute of Science), Pietr M, Juknat A, Rimmerman N, Levy R, Vogel Z. Journal of Biological Chemistry. Online 2009 November 12.

Mecha_2013. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors [animal study]. Full text. Mecha M (Cajal Institute, Madrid), Feliú A, Iñigo P, Mestre L, Carrillo-Salinas F, Guaza C. Neurobiology of disease. Online 2013 July 11.

Medeiros_2007. Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw. Full text]. Medeiros R (Universidade Federal de Santa Catarina, Brazil), Passos G, Vitor C, et al. British Journal of Pharmacology. Online 2007 April 30.

Guo_2014. Trans-caryophyllene suppresses hypoxia-induced neuroinflammatory responses by inhibiting NF-κB activation in microglia [in vitro study]. Abstract. Guo K (Huazhong University of Science and Technology, Wuhan, China), Mou X, Huang J, Xiong N, Li H. Journal of Mocular Neuroscience. Online 2014 February 4.

Fonsêca_2015. Nerolidol exhibits antinociceptive and anti-inflammatory activity: involvement of the GABAergic system and proinflammatory cytokines [animal study]. Abstract. Fonsêca D (Federal University of Paraíba, Brazil), Salgado P, de Carvalho F, et al. Fundamental & Clinical Pharmacology. Online 2015 November 2.

Madankumar_2017. Geraniol attenuates 4NQO-induced tongue carcinogenesis through lowering the activation of NF-κB in rats. Abstract. Madankumar A (University of Madras, India), Tamilarasi S, Premkumar T, et al. Molecular and Cellular Biochemistry. Online 2017 April 10.

Wojdasiewicz_2014. The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis [literature review]. Full text. Wojdasiewicz P, Poniatowski Ł, Szukiewicz D (Medical University of Warsaw, Poland). Mediators of Inflammation. Online 2014 April 30.

Stannus_2010. Circulating levels of IL-6 and TNF-α are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults [small scale study]. Full text. Stannus O (University of Tasmania, Hobart, Australia), Jones G, Cicuttini F. Osteoarthritis and Cartilage. Online 2010 Sep 16.

Misato_2011. The Roles of Interleukin-6 in the Pathogenesis of Rheumatoid Arthritis [Review]. Full text. Misato H M, Mihara (Chugai Pharmaceutical, Shizuoka, Japan), M. Arthritis. Online 2011 May 26.

Avci_2018. Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What's the Difference\? [literature review]. Abstract. Avci A (Life Hospital, Antalya, Turkey), Feist E, Burmester G. BioDrugs. Online 2018 November 29.

Durst_2007. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury [animal study]. Full text. Durst R, Danenberg H, Gallily R, et al. American Journal of Physiology. Online 2007 December 1.

Chang_2001. Effects of cannabinoids on LPS-stimulated inflammatory mediator release from macrophages: involvement of eicosanoids [animal study]. Abstract. Chang Y (National Taiwan University), Lee S, Lin W. Journal of Cellular Biochemistry. Online April 23, 2001.

Puffenbarger_2000. Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells. Abstract. Puffenbarger R (Virginia Commonwealth University), Boothe A, Cabral G. Glia. Published 2000 January 1.

Tabassum_2014. Perillyl alcohol improves functional and histological outcomes against ischemia-reperfusion injury by attenuation of oxidative stress and repression of COX-2, noS-2 and NF-κB in middle cerebral artery occlusion rats. Abstract. Tabassum R (Hamdard University, New Deli, India), Vaibhav K, Shrivastava P, et al. European Journal of Pharmacology. Online 2014 September 18.

Held_2007. Characterization of alpha-terpineol as an anti-inflammatory component of orange juice by in vitro studies using oral buccal cells. Abstract. Held S (Deutsche Forschungsanstalt für Lebensmittelchemie), Schieberle P, Somoza V. Journal of Agricultural and Food Chemistry. Online 2007 September 1.

Nogueira_2014. Terpinen-4-ol and alpha-terpineol (tea tree oil components) inhibit the production of IL-1β, IL-6 and IL-10 on human macrophages. Abstract. Nogueira M (School of Dentistry Araraquara, Brazil), Aquino S, Rossa Junior C, Spolidorio D. Inflammation Research. Online 2014 June 20.

Trinh_2011. Artemisia princeps Pamp.- Essential oil and its constituents eucalyptol and α-terpineol ameliorate bacterial vaginosis and vulvovaginal candidiasis in mice by inhibiting bacterial growth and NF-κB activation. Abstract. Trinh H (Kyung Hee University, Seoul, Korea), Lee I, Hyun Y, Kim D. Planta Medica. Online 2011 August 9.

Caceres_2017. Transient Receptor Potential Cation Channel Subfamily M Member 8 channels mediate the anti-inflammatory effects of eucalyptol [animal study]. Full text. Caceres A (Duke University, Durham, NC), Liu B, Jabba S, et al. British Journal of Pharmacology. Online 2017 March 23.

Lima_2013. 1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-κB activity in mice. Abstract. Lima P (Federal University of Ceará, Brazil), de Melo T, Carvalho K, et al. Life Sciences. 2013 May 20.

Yadav_2017. Suppression of inflammatory and infection responses in lung macrophages by eucalyptus oil and its constituent 1,8-cineole: Role of pattern recognition receptors TREM-1 and NLRP3, the MAP kinase regulator MKP-1, and NFκB [in vitro study]. Full text. Yadav N (University of Cincinnati, Ohio), Chandra H. PloS One. Online 2017 November 15.

Li_2016. 1, 8-Cineol Protect Against Influenza-Virus-Induced Pneumonia in Mice. Abstract. Li Y (Guangzhou University of Chinese Medicine), Lai Y, Wang Y, et al. Inflammation. Online 2016 June 28.

Kennedy-Feitosa_2016. Eucalyptol attenuates cigarette smoke-induced acute lung inflammation and oxidative stress in the mouse. Abstract. Kennedy-Feitosa E, (Universidade Federal do Rio de Janeiro, Brazil) Okuro R, Pinho-Ribeiro V, et al. Pulmonary Pharmacology & Theraputics. Online 2016 September 4.

Yu_2018. Treatment with eucalyptol mitigates cigarette smoke-induced lung injury through suppressing ICAM-1 gene expression [animal study]. Full text. Yu N (The First Hospital of China Medical University), Sun Y, Su X, et al. Bioscience Reports. Online 2018 July 6.

Khan_2013. 1,8-cineole (eucalyptol) mitigates inflammation in amyloid Beta toxicated PC12 cells: relevance to Alzheimer's disease [animal study]. Abstract. Khan A (Hamdard University, New Deli), Vaibhav K, Javed H, et al. Neurochemical Research. Online 2013 December 31.

Smolinski_2003. Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew). Abstract. Smolinski A (Michigan State University, East Lansing), Pestka J. Food and Chemical Toxicology. Online 2003 July 1.

Adalimumab. Adalimumab. Full text. WikiProject Pharmacology. Wikipedia. Updated 2019 August 9.

Infliximab. Infliximab [exposition]. Full text. WikiProject Pharmacology. Wikipedia. Updated 2019 July 15.

Kloppenburg_2018. Etanercept in patients with inflammatory hand osteoarthriti (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial [large scale trial]. Abstract. Kloppenburg M (Leiden University Medical Center), Ramonda R, Bobacz K, et al. Annals of Rheumatic Diseases. Online 2018 October 3.

Charalabopoulos_2019. Apigenin Exerts Anti-inflammatory Effects in an Experimental Model of Acute Pancreatitis by Down-regulating TNF-α [animal study]. Full text. Charalabopoulos A (Broomfield Hospital, Essex, UK), Davakis, Lambropoulou M, et al. In Vivo. Online 2019 July 3.

Palacz-Wrobel_2017. Effect of apigenin, kaempferol and resveratrol on the gene expression and protein secretion of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in RAW-264.7 macrophages. Abstract. Palacz-Wrobel M (Silesian Medical College in Katowice, Poland), Borkowska P, Paul-Samojedny M, et al. Biomedicine & Pharmacotherapy. Online 2017 July 20.

Paradowska-Gorycka_2010. IL-23 in the Pathogenesis of Rheumatoid Arthritis [exposition]. Full text. Paradowska-Gorycka A (Institute of Rheumatology, Warsaw), Grzybowska-Kowalczyk A, Wojtecka-Lukasik E, Maslinski S. Scandinavian Journal of Immunology. Online 2010 February 22.

Kellner_2013. Targeting interleukin-17 in patients with active rheumatoid arthritis: rationale and clinical potential [exposition]. Full text. Kellner H (Hospital Neuwittelsbach, Munich). Therapeutic Advances in Musculoskeletal Disease. Published 2013 June.

Koenders_20016. Secukinumab for rheumatology: development and its potential place in therapy [exposition]. Full text. Koenders M (Radboud University Medical Center, Nijmegen, the Netherlands), van den Berg W. Drug Design. Development and Therapy, Online 2016 June 24.

Kunwar_2016. Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials meta analysis]. Abstract. Kunwar S (University of New England, Laconia, NH), Dahal K, Sharma S. Rheumatology International. Online 2016 April 22.

Giacoppo_2016. Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis [animal study]. Abstract. Giacoppo S (Bonino-Pulejo, Messina, Italy), Pollastro F, Grassi G, Bramanti P, Mazzon E. Fitoterapia. Online 2016 November 25.

Harvey_2013. Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model. Abstract. Harvey B (University of Adelaide, South Australia), Sia T, Wattchow D, Smid S. Cytokine. Online 2013 November 13.

Kozela_2013. Cannabinoids decrease the th17 inflammatory autoimmune phenotype [in vitro study]. Abstract. E Kozela (Tel Aviv University), A Juknat, N Kaushansky, et al. Journal of Neuroimmune Pharmacology. Online 2013 July 28.

Norooznezhad_2016. Cannabinoids: Possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation [essay]. Abstract. Norooznezhad A (Kermanshah University of Medical Sciences, Kermanshah, Iran), Norooznezhad F. Medical Hypotheses. Online 2016 December 14.

Guillot_2013. Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver. Full text. Guillot A (Université Paris-Est), Hamdaoui N, Bizy A, et al. Hepatology. Online 2013 November 19.

Taskiran_2002. Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1 [animal tissue study]. Abstract. Taskiran D (University of Pittsburgh), Stefanovic-Racic M, Georgescu H, Evans C. Biochemical and Biophysical Research Communications. Online 2002 May 25.

Nagy_2008. Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis. Abstract. Nagy G (Semmelweis University, Budapest), Clark J, Buzas E, et al. Immunology Letters. Online 2008 March 19.

Boileau_2002. The in situ up-regulation of chondrocyte interleukin-1-converting enzyme and interleukin-18 levels in experimental osteoarthritis is mediated by nitric oxide [animal study]. Full text. Boileau C (Université de Montréal). Martel-Pelletier J, Moldovan F, et all. Arthritis and Rheumatism, Online 2002 October 16.

Leonidou_2018. Inducible nitric oxide synthase as a target for osteoarthritis treatment [opinion]. Abstract. Leonidou A (Aristotle University, Greece), Lepetsos P, Mintzas M, et al. Expert opinion on Therapeutic Targets. 2018 March 05.

McCartney-Francis_1993. Suppression of arthritis by an inhibitor of nitric oxide synthase [animal study]. Abstract, full text. McCartney-Francis N (National Institute of Dental Research, Bethesda), Allen J, Mizel D, et al. The Journal of Experimental Medicine. Published 1993 August 1.

Farrell_1992. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases [human tissue study]. Full text. Farrell A (London Hospital Medical College), Blake D, Palmer R, Moncada S. Annals of the Rheumatic diseases. Published 1992 November.

vant_Hof_2000. Nitric oxide is a mediator of apoptosis in the rheumatoid joint [human tissue study]. Full text. van't Hof R (University of Aberdeen), Hocking L, Wright P, Ralston S. Rheumtology. Published 2000 September 1.

Coté_2017. Anti-Inflammatory, Antioxidant, Antibiotic, and Cytotoxic Activities of Tanacetum vulgare L\. Essential Oil and Its Constituents [in vitro study]. Full text. Coté H (Université du Québec à Chicoutimi), Boucher M, Pichette A, Legault J. Medicines. Online 2017 May 25.

Walsh_2007. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis [human study]. Full text. Walsh D (University of Nottingham), Bonnet C, Turner E, et al. Osteoarthritis and Cartilage. Online 2007 March 22.

Bonnet_2004. Osteoarthritis, angiogenesis and inflammation [literature review]. Full text. Bonnet C (University of Nottingham), Walsh D. Rheumatology. Online 2004 August 03.

Elshabrawy_2015. The pathogenic role of angiogenesis in rheumatoid arthritis [literature review]. Full text. Elshabrawy H (University of Illinois at Chicago), Chen Z, Volin M, et al. Angiogenesis. Online 2015 July 22.

Pessler_2008. Increased angiogenesis and cellular proliferation as hallmarks of the synovium in chronic septic arthritis [human tissue study]. Full text. Pessler F (The Children's Hospital of Philadelphia), Dai L, Diaz-Torne C, et al. Chronic septic Arthritis. Online 2008 July 30.

Haywood_2003. Inflammation and angiogenesis in osteoarthritis [small-scale study]. Full text. Haywood L (University of Nottingham), McWilliams D, Pearson C, et al. Arthritis and Rheumatism. Online 2003 August 01.

Pannus_2018. Pannus. Full text. WikiProject Medicine. Wikipedia. Updated 2018 July 26.

Paleolog_2002. Angiogenesis in rheumatoid arthritis [Literature review]. Full text. Paleolog E (Imperial College of Science, Technology and Medicine, London). Arthritis Research. Online 2002 May 9.

Szekanecz_2008. Targeting Angiogenesis in Rheumatoid Arthritis [literature review]. Full text. Szekanecz Z (University of Debrecen, Hungary), Koch A. Europe PMC. Online 2008 November 01.

Massi_2012. Cannabidiol as potential anticancer drug [literature review]. Full text. Massi P *University of Milan), Solinas M, Cinquina V, Parolaro D. British Journal of Clinical Pharmacology. Online 2012 Apr 17.

Dumitru_2018. Cannabinoids in Glioblastoma Therapy: New Applications for Old Drugs [literature review]. Full text. Dumitru C (Nordstadt Hospital Hannover), Sandalcioglu I, Karsak M. Fronteers in Molecular Neuroscience. Online 2018 May 16.

Caffarel_2010. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition [human tissue study]. Full text. Caffarel M (Complutense University, Madrid, Spain), Andradas C, Mira E. Molecular Cancer. Online 2010 July 22.

Blázquez_2004. Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas [case series]. Full text. Blázquez C, González-Feria L, Álvarez L. Cancer Research. Online 2004 August 15.

Park_2011. β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation [in vitro study]. Abstract. Park K (Kyung Hee University, Seoul, Republic of Korea), Nam D, Yun H, et al. Cancer Letters. Online 2011 August 26.

Ma_2008. Beta-eudesmol suppresses tumour growth through inhibition of tumour neovascularisation and tumour cell proliferation [in vitro study]. Abstract. Ma E (Shenyang Pharmaceutical University), Li Y, Tsuneki H, et al. Journal of Asian Natural Products Research. Online 2008 February.

Lu_2004. Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene. Full text. Lu X (Dalian Medical University, China), Zhan L, Feng B, et al. World Journal of Gastroenterology. Online 2004 July 15.

Rashid_2006. Ankylosing Spondylitis Is Linked to Klebsiella--the Evidence [literature survey]. Abstract. Rashid T (King's College London), Ebringer, A. Clinical Rheumatology. Online 2006 December 21.

Winnett_2017. Inhibition of Klebsiella Pneumoniae Growth by Selected Australian Plants: Natural Approaches for the Prevention and Management of Ankylosing Spondylitis [in vitro studies]. Abstract. Winnett V (Griffith University, Queensland, Australa), Sirdaarta J, White A, Clarke F, Cock I. Inflammopharmacology. Online 2017 February 27.