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cannabis anti inflammatory effects

Some CBD manufacturers have come under government scrutiny for wild, indefensible claims, such that CBD is a cure-all for cancer, which it is not. We need more research but CBD may be prove to be an option for managing anxiety, insomnia, and chronic pain. Without sufficient high-quality evidence in human studies we can’t pinpoint effective doses, and because CBD is currently is mostly available as an unregulated supplement, it’s difficult to know exactly what you are getting. If you decide to try CBD, talk with your doctor — if for no other reason than to make sure it won’t affect other medications you are taking.

CBD stands for cannabidiol. It is the second most prevalent of the active ingredients of cannabis (marijuana). While CBD is an essential component of medical marijuana, it is derived directly from the hemp plant, which is a cousin of the marijuana plant. While CBD is a component of marijuana (one of hundreds), by itself it does not cause a "high." According to a report from the World Health Organization, "In humans, CBD exhibits no effects indicative of any abuse or dependence potential…. To date, there is no evidence of public health related problems associated with the use of pure CBD."

CBD has been touted for a wide variety of health issues, but the strongest scientific evidence is for its effectiveness in treating some of the cruelest childhood epilepsy syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome (LGS), which typically don’t respond to antiseizure medications. In numerous studies, CBD was able to reduce the number of seizures, and, in some cases, it was able to stop them altogether. Videos of the effects of CBD on these children and their seizures are readily available on the Internet for viewing, and they are quite striking. Recently the FDA approved the first ever cannabis-derived medicine for these conditions, Epidiolex, which contains CBD.

The bottom line on cannabidiol

Side effects of CBD include nausea, fatigue and irritability. CBD can increase the level in your blood of the blood thinner coumadin, and it can raise levels of certain other medications in your blood by the exact same mechanism that grapefruit juice does. A significant safety concern with CBD is that it is primarily marketed and sold as a supplement, not a medication. Currently, the FDA does not regulate the safety and purity of dietary supplements. So, you cannot know for sure that the product you buy has active ingredients at the dose listed on the label. In addition, the product may contain other (unknown) elements. We also don’t know the most effective therapeutic dose of CBD for any particular medical condition.

Cannabidiol (CBD) has been recently covered in the media, and you may have even seen it as an add-in booster to your post-workout smoothie or morning coffee. What exactly is CBD? Why is it suddenly so popular?

CBD is readily obtainable in most parts of the United States, though its exact legal status is in flux. All 50 states have laws legalizing CBD with varying degrees of restriction, and while the federal government still considers CBD in the same class as marijuana, it doesn’t habitually enforce against it. In December 2015, the FDA eased the regulatory requirements to allow researchers to conduct CBD trials. Currently, many people obtain CBD online without a medical cannabis license. The government’s position on CBD is confusing, and depends in part on whether the CBD comes from hemp or marijuana. The legality of CBD is expected to change, as there is currently bipartisan consensus in Congress to make the hemp crop legal which would, for all intents and purposes, make CBD difficult to prohibit.

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Exposure of guinea pigs to LPS induced a 97 ± 7% and 98 ± 3% increase in neutrophils found in bronchoalveolar lavage fluid (BAL) at 4 h and 24 h, respectively. Administration of CBD and CBG formulated with MCT oil did not show any significant effects on the LPS-induced neutrophilia measured in the BAL fluid when compared with the vehicle-treated groups. Conversely, the administration of either cannabinoid formulated with CrEL induced a significant attenuation of the LPS induced recruitment of neutrophils into the lung following both intraperitoneal (IP) and oral (PO) administration routes, with a 55–65% and 50–55% decrease in neutrophil cell recruitment with the highest doses of CBD and CBG respectively. A combination of CBD and CBG (CBD:CBG = 1:1) formulated in CrEL and administered orally was also tested to determine possible interactions between the cannabinoids. However, a mixture of CBD and CBG did not show a significant change in LPS-induced neutrophilia. Surfactants, such as CrEL, improves the dissolution of lipophilic drugs in an aqueous medium by forming micelles and entrapping the drug molecules within them, consequently increasing the drug dissolution rate. Additionally, surfactants increase permeability and absorption by disrupting the structural organisation of the cellular lipid bilayer.

The second purpose of this study was to investigate the anti-inflammatory effects of cannabinoids formulated in two different formulations. The lipophilic nature of cannabinoids is a significant challenge for developing an effective formulation and bioavailability for optimal therapeutic effect [25]. Due to their lipophilicity, cannabinoids present negligible aqueous solubility. Additionally, they are vulnerable to degradation by auto-oxidation, light and temperature [26]. The first formulation tested in this study was composed of medium-chain triglycerides (MCT). They are lipids with a carbon chain length of 6–12 carbon atoms, making MCTs easier to absorb and metabolise than long-chain fatty acids (LCTs). Due to these characteristics, MCTs have been suggested as a drug vehicle for lipophilic drugs [27]. Our second formulation was a micellar solution composed of ethanol (EtOH), Cremophor® EL (polyoxyl 35 castor oil, CrEL) and sodium chloride 0.9% in purified water (saline). EtOH, a short-chain alcohol, is widely used as a solvent and co-surfactant for lipophilic drugs. CrEL is a non-ionic hydrophilic surfactant used to emulsify and solubilise lipophilic molecules by forming micelles and entrapping the lipophilic molecules within them in aqueous solutions. CrEL can also increase drug absorption by enhancing the dissolution rate of the drug by disrupting the lipid bilayer of cells [28]. Lastly, saline is a water-based solvent included in the formulation to obtain a final isotonic mixture.

Results

The discovery of the endocannabinoid system (ECS) has enabled the growth of scientific evidence supporting the use of cannabis and cannabinoids as therapeutic agents for various diseases. The ECS is a complex lipid cell-signalling system comprised of: the cannabinoid receptors (CBRs; CB1 and CB2); the endogenous cannabinoids (endocannabinoids, ECs), anandamide (N-arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG); the AEA transporter protein (TP) and the enzymes responsible for the synthesis and degradation of endocannabinoids (fatty acid amide hydrolase, FAAH, or monoacylglycerol lipase, MGL) [6].

Studies with Cannabis Sativa plant extracts and endogenous agonists of cannabinoid receptors have demonstrated anti-inflammatory, bronchodilator , and antitussive properties in the airways of allergic and non-allergic animals. However, the potential therapeutic use of cannabis and cannabinoids for the treatment of respiratory diseases has not been widely investigated, in part because of local irritation of airways by needing to smoke the cannabis, poor bioavailability when administered orally due to the lipophilic nature of cannabinoids, and the psychoactive effects of Δ9-Tetrahydrocannabinol (Δ9-THC) found in cannabis. The primary purpose of this study was to investigate the anti-inflammatory effects of two of the non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) alone and in combination, in a model of pulmonary inflammation induced by bacterial lipopolysaccharide (LPS). The second purpose was to explore the effects of two different cannabinoid formulations administered orally (PO) and intraperitoneally (IP). Medium-chain triglyceride (MCT) oil was used as the sole solvent for one formulation, whereas the second formulation consisted of a Cremophor® EL (polyoxyl 35 castor oil, CrEL)-based micellar solution.

Cannabis, often referred to as marijuana, is a botanical product derived from the Cannabis Sativa L. plant, a dioicous species of the Cannabaceae and broadly distributed all over the world [1]. The use of the cannabis plant for its medicinal properties, source of textile fibre (hemp), and psychoactive/medical effects, stretches back approximately 5000 years. The term ‘cannabinoid’ or ‘phytocannabinoid’ (plant-based cannabinoids) refers to a group of lipophilic and pharmacologically active, oxygenated C21-22 aromatic hydrocarbon compounds found in the leaves and flowering plants of the Cannabis Sativa plant [2]. Since the isolation of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) [3], more than 144 unique cannabinoid compounds, 100 terpenes, and 20 phenolic compounds synthesised by the cannabis plant have been identified [4]. In addition to the plant-derived cannabinoids, many structurally and biologically associated compounds have been created, which are known as synthetic cannabinoids [5].

Data were independently extracted by the first author (M.G.L.) using a structured form and reviewed by the senior author (T.M.F.). The following variables were extracted: (1) author’s name, (2) year of publication, (3) country where the study was conducted, (4) sample size, (5) sample characteristics, (6) study design, (7) age range of the sample, (8) statistical analysis performed, (9) instrument(s) utilized, (10) exposure covariates, (11) outcome measures, (12) major findings, and (13) study limitations. Discrepancies were resolved by consensus, and a third author (E.B.) was consulted when needed. Data concerning cannabis use and its relationship with inflammatory markers were described, when available. It was not possible to describe or standardize cannabinoid consumption for all papers reviewed because many of them did not mention smoke patterns and also because articles applied very heterogeneous measurement methods. Publication including only cannabidiol or synthetic cannabinoids was not included.

The authors have no conflicts of interest to declare.

Data Analysis

Inflammatory mediators and biological function according to Abbas et al. [21]

Killestein et al. [27] performed a randomized controlled trial (RCT) in Germany with 16 volunteers: 10 had secondary progressive MS and 6, primary progressive MS. The aim of this paper was to evaluate immune function in MS patients treated with orally administered cannabinoids. This 2-fold study treated their volunteers with identical-appearing capsules containing dronabinol, Cannabis sativa plant extract or placebo. Volunteers were treated with 84 capsules for 4 weeks each. The study found modest increase in TNF-α and no significant changes in T-cell proliferation, leukocyte subsets, or cytokines. The small sample size is also a limitation to this study.

Responding to potential aggressions, the immune system activates the innate and adaptive immunities by producing inflammatory cytokines, which mediate and potentiate the inflammatory process [19] that, in turn, signals an alteration of homeostasis. Although the immune system in normal conditions addresses potential aggressions and pathogen antigens, several dysfunctions turn the system to recognize the autoantigens as an aggressor and cause autoimmune diseases. Detailed information about immune cytokines, interleukins, and inflammatory cell function is presented in Table 1.