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?
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.
How is cannabidiol different from marijuana?
CBD is commonly used to address anxiety, and for patients who suffer through the misery of insomnia, studies suggest that CBD may help with both falling asleep and staying asleep.
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.
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.
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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 . Due to their lipophilicity, cannabinoids present negligible aqueous solubility. Additionally, they are vulnerable to degradation by auto-oxidation, light and temperature . 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 . 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 . Lastly, saline is a water-based solvent included in the formulation to obtain a final isotonic mixture.
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.
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.
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 . 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 . Since the isolation of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) , more than 144 unique cannabinoid compounds, 100 terpenes, and 20 phenolic compounds synthesised by the cannabis plant have been identified . In addition to the plant-derived cannabinoids, many structurally and biologically associated compounds have been created, which are known as synthetic cannabinoids .
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) .
Various studies have suggested the use of cannabinoids as possible treatments for inflammatory diseases in the airways, such as chronic obstructive pulmonary disease (COPD) [7,8]. The phytocannabinoids Δ 9 -THC , cannabidiol (CBD)  and cannabigerol (CBG)  are of particular interest due to their important effects on inflammation and the immune system, including inhibiting the activation of pro-inflammatory cells and the synthesis of pro-inflammatory mediators or reducing intracellular and mitochondrial oxidative stress . Additionally, it has been reported that CBD exhibits apoptotic properties in immune cell populations, leading to cannabinoid-induced immunosuppression . CBD and CBG alone, and in combination, have demonstrated apoptotic effects in tumour cells, in addition to their off-target effects essential for effective palliative care such as increased appetite, analgesic and anxiolytic properties . On the other hand, CBD  and CBG  have been demonstrated to exhibit anti-apoptotic properties in healthy cells under oxidative and inflammatory conditions. The anti-apoptotic effects of cannabinoids are mainly associated with cytokine modulation and antioxidant activity via downregulation of nitric oxide production .
COPD is a chronic respiratory disease with considerable unmet medical needs . In 2017, 3.91 million people died from COPD worldwide, and because of its growing prevalence and mortality rate, COPD is expected to become the world's third most common cause of death by 2030 . COPD includes a group of chronic lung conditions characterised by poorly reversible airflow obstruction, abnormal and chronic non-allergic inflammation of the airway, mucous plugging and airway remodelling . This chronic and pathological airway response can result in excessive cough and mucus production (chronic bronchitis), alveolar destruction (emphysema) and/or lesions in the smaller conducting airways (bronchiolitis) . The aberrant inflammatory response in the lungs, particularly in the small airways, is the outcome of the innate and adaptive immune responses to long-term exposure to toxic particles and gases, especially cigarette smoke and other oxidant pollution . Other sources may trigger the development of the disease, such as alpha1-antitrypsin deficiency and telomerase polymorphisms . This response is associated with an increased number of activated macrophages, neutrophils (both part of the innate immune response), T lymphocytes (Tc1, Th1 and ILC3 cells; adaptative immunity)  and in some cases, eosinophils . These activated inflammatory cells release inflammatory mediators such as interleukin 8 (IL-8), leukotriene B4 (LTB4), and tumour necrosis factor α (TNF-α), which orchestrate the pathological structural and airway changes in COPD. These changes include tissue remodelling, chronic airways inflammation, oxidative stress, proteinase imbalances and accelerated ageing . As the disease progresses, the degree of inflammation driven primarily by neutrophils also evolves .