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CBD education

CBD (cannabidiol) is a non-intoxicating component of the cannabis plant with enormous therapeutic potential. Although CBD doesn’t make people feel high like THC does, it’s causing quite a buzz among scientists, health professionals, and medical marijuana patients who are using CBD-rich products to treat a wide range of conditions—chronic pain, cancer, Crohn’s, diabetes, rheumatoid arthritis, PTSD, cardiovascular disease, anxiety, antibiotic-resistant infections, multiple sclerosis, schizophrenia, and more. Academic research centers in the United States and elsewhere are currently studying the effects of CBD on these and other ailments. Scientists refer to CBD as a “promiscuous” compound because it confers therapeutic benefits in many different ways while tapping into how we function physiologically and biologically on a deep level. Extensive preclinical research and some clinical studies have shown that CBD has strong anti-oxidant, anti-inflammatory, anticonvulsant, anti-depressant, anti-psychotic, anti-tumoral, and neuroprotective qualities. Cannabidiol can change gene expression and remove beta amyloid plaque, the hallmark of Alzheimer’s, from brain cells.

CBD Science

Cannabidiol (CBD), a non-intoxicating component of the cannabis plant, has generated significant interest among scientists and physicians in recent years—but how CBD exerts its therapeutic impact on a molecular level is still being sorted out. Cannabidiol is a pleiotropic drug in that it produces many effects through multiple molecular pathways. The scientific literature has identified more than 65 molecular targets of CBD.

Although CBD has little binding affinity for either of the two cannabinoid receptors (CB1 and CB2), cannabidiol modulates several non-cannabinoid receptors and ion channels. CBDalso acts through various receptor-independent pathways—for example, by delaying the “reuptake” of endogenous neurotransmitters (such as anandamide and adenosine) and by enhancing or inhibiting the binding action of certain G-protein coupled receptors.

Here are some of the ways that CBD confers its manifold therapeutic effects.

SEROTONIN RECEPTORS

Jose Alexandre Crippa and his colleagues at the University of San Paulo in Brazil and King’s College in London have conducted pioneering research into CBD and the neural correlates of anxiety. At high concentrations, CBD directly activates the 5-HT1A (hydroxytryptamine) serotonin receptor, thereby conferring an anti-anxiety effect. This G-coupled protein receptor is implicated in a range of biological and neurological processes, including (but not limited to) anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting.

5-HT1A is a member of the family of 5-HT receptors, which are activated by the neurotransmitter serotonin. Found in both the central and peripheral nervous systems, 5-HT receptors trigger various intracellular cascades of chemical messages to produce either an excitatory or inhibitory response, depending on the chemical context of the message.

CBDA [Cannabidiolic acid], the raw, unheated version of CBD that is present in the cannabis plant, also has a strong affinity for the 5-HT1A receptor (even more so than CBD). Preclinical studies indicate that CBDA is a potent anti-emetic, stronger than either CBD or THC, which also have anti-nausea properties.

VANILLOID RECEPTORS

CBD directly interacts with various ion channels to confer a therapeutic effect. CBD, for example, binds to TRPV1 receptors, which also function as ion channels. TRPV1 is known to mediate pain perception, inflammation and body temperature.

TRPV is the technical abbreviation for “transient receptor potential cation channel subfamily V.” TRPV1 is one of several dozen TRP (pronounced “trip”) receptor variants or subfamilies that mediate the effects of a wide range of medicinal herbs.

Scientists also refer to TRPV1 as a “vanilloid receptor,” named after the flavorful vanilla bean. Vanilla contains eugenol, an essential oil that has antiseptic and analgesic properties; it also helps to unclog blood vessels. Historically, the vanilla bean has been used as a folk cure for headaches.
CBD binds to TRPV1, which can influence pain perception.

Capsaicin—the pungent compound in hot chili peppers—activates the TRVP1 receptor. Anandamide, the endogenous cannabinoid, is also a TRPV1 agonist.

GPR55—ORPHAN RECEPTORS

Whereas cannabidiol directly activates the 5-HT1A serotonin receptor and several TRPV ion channels, some studies indicate that CBD functions as an antagonist that blocks, or deactivates, another G protein-coupled receptor known as GPR55.

GPR55 has been dubbed an “orphan receptor” because scientists are still not sure if it belongs to a larger family of receptors. GPR55 is widely expressed in the brain, especially in the cerebellum. It is involved in modulating blood pressure and bone density, among other physiological processes.
GPR55 promotes osteoclast cell function, which facilitates bone reabsorption. Overactive GPR55 receptor signaling is associated with osteoporosis.

GPR55, when activated, also promotes cancer cell proliferation, according to a 2010 study by researchers at the Chinese Academy of Sciences in Shanghai. This receptor is expressed in various types of cancer.

CBD is a GPR55 antagonist, as University of Aberdeen scientist Ruth Ross disclosed at the 2010 conference of the International Cannabinoid Research Society in Lund, Sweden. By blocking GPR55 signaling, CBD may act to decrease both bone reabsorption and cancer cell proliferation.

PPARS – NUCLEAR RECEPTORS

CBD also exerts an anti-cancer effect by activating PPARs [peroxisome proliferator activated receptors] that are situated on the surface of the cell’s nucleus. Activation of the receptor known as PPAR-gamma has an anti-proliferative effect as well as an ability to induce tumor regression in human lung cancer cell lines. PPAR-gamma activation degrades amyloid-beta plaque, a key molecule linked to the development of Alzheimer’s disease. This is one of the reasons why cannabidiol, a PPAR-gamma agonist, may be a useful remedy for Alzheimer’s patients.

PPAR receptors also regulate genes that are involved in energy homeostasis, lipid uptake, insulin sensitivity, and other metabolic functions. Diabetics, accordingly, may benefit from a CBD-rich treatment regimen.

CBD AS A REUPTAKE INHIBITOR

How does CBD, an exogenous plant compound, get inside a human cell to bind to a nuclear receptor? First it has to pass through the cell membrane by hitching a ride with a fatty acid binding protein (FABP), which chaperones various lipid molecules into the cell’s interior. These intracellular transport molecules also escort tetrahydrocannabinol (THC) and the brain’s own marijuana-like molecules, the endocannabinoids anandamide and 2AG, across the membrane to several targets within the cell. CBD and THC both modulate receptors on the surface of the nucleus, which regulate gene expression and mitochondrial activity.

Cannabidiol, it turns out, has a strong affinity for three kinds of FABPs, and CBD competes with our endocannabinoids, which are fatty acids, for the same transport molecules. Once it is inside the cell, anandamide is broken down by FAAH [fatty acid amide hydrolase], a metabolic enzyme, as part of its natural molecular life cycle. But CBD interferes with this process by reducing anandamide’s access to FABP transport molecules and delaying endocannabinoid passage into the cell’s interior.

According to a team of Stony Brook University scientists, CBD functions as an anandamide reuptake and breakdown inhibitor, thereby raising endocannabinoid levels in the brain’s synapses. Enhancing endocannabinod tone via reuptake inhibition may be a key mechanism whereby CBD confers neuroprotective effects against seizures, as well as many other health benefits.

CBD’s anti-inflammatory and anti-anxiety effects are in part attributable to its inhibition of adenosine reuptake. By delaying the reuptake of this neurotransmitter, CBD boosts adenosine levels in the brain, which regulates adenosine receptor activity. A1A and A2A adenosine receptors play significant roles in cardiovascular function, regulating myocardial oxygen consumption and coronary blood flow. These receptors have broad anti-inflammatory effects throughout the body.

CBD AS THE ALLOSTERIC RECEPTOR MODULATOR

CBD also functions as an allosteric receptor modulator, which means that it can either enhance or inhibit how a receptor transmits a signal by changing the shape of the receptor.

Australian scientists report that CBD acts as a “positive allosteric modulator” of the GABA-A receptor. In other words, CBD interacts with the GABA-A receptor in a way that enhances the receptor’s binding affinity for its principal endogenous agonist, gamma-Aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. The sedating effects of Valium and other Benzos are mediated by GABA receptor transmission. CBD reduces anxiety by changing the shape of the GABA-A receptor in a way that amplifies the natural calming effect of GABA.

Canadian scientists have identified CBD as a “negative allosteric modulator” of the cannabinoid CB1 receptor, which is concentrated in the brain and central nervous system. While cannabidiol doesn’t bind to the CB1 receptor directly like THC does, CBDinteracts allosterically with CB1 and changes the shape of the receptor in a way that weakens CB1’s ability to bind with THC.

As a negative allosteric modulator of the CB1receptor, CBD lowers the ceiling on THC’s psychoactivity—which is why people don’t feel as “high” when using CBD-rich cannabis compared to when they consume THC-dominant medicine. A CBD-rich product with little THC can convey therapeutic benefits without having a euphoric or dysphoric effect.

ENDOCANNABINOID SYSTEM

Cannabis has been at the center of one of the most exciting—and underreported—developments in modern science. Research on marijuana’s effects led directly to the discovery of a hitherto unknown biochemical communication system in the human body, the Endocannabinoid System, which plays a crucial role in regulating our physiology, mood, and everyday experience.

The discovery of receptors in the brain that respond pharmacologically to cannabis—and the subsequent identification of endogenous cannabinoid compounds in our own bodies that bind to these receptors—has significantly advanced our understanding of human biology, health, and disease.

Does Using CBD Hemp Oil Result in a Positive Drug Test for THC or Marijuana?

FALSE POSITIVE – Whether you agree with it in principle or not, testing for illicit drug use is a reality for many workers in the United States. Drug testing is mandatory for federal employees, and although it isn’t required in the private sector, more employers are implementing some kind(s) of drug screening.

When drug testing is mandated, employers almost always follow the SAMHSA (Substance Abuse and Mental Health Services Administration) guidelines because it puts them on solid legal ground. Typically, there is an overlap between testing guidelines and accepted cutoff levels for drugs and drug metabolites in confirmatory testing and screening.

Because THC is widely recognized as being responsible for marijuana’s psychoactivity and euphoria, a routine urine drug screen for marijuana use consists of an immunoassay with antibodies that are made to detect it, and its main metabolite, 11-nor-delta9-caboxy-THC (THC-COOH). SAMHSA has set the cutoff level for a positive urine screen in the immunoassay at 50 ng/mL. When the immunoassay screen is positive at the > 50 ng/mL level, a confirmatory GC/MS (Gas Chromatography/Mass Spectrometry) test is performed to verify the positive urine screen. The confirmatory GC/MS has a cutoff level of 15 ng/mL and is specific only to the 11-nor-THCCOOH metabolite.

Fortunately, the urine drug screen for THC-COOH is known to have very little cross-reactivity to other cannabinoids that are not psychoactive, such as CBD (cannabidiol), CBG (cannabigerol), CBN (cannabinol), and others. This is good news for “normal” consumers of CBD/hemp oil.

That said, individuals using unusually large doses of a cannabinoid-rich hemp oil product (above 1000-2000 mg of hemp oil daily) could theoretically test positive during the initial urinary screen IF the product carry less than .3% THC in them. Although very rare, the urine screen in these cases would likely represent a “false positive” due to other non-THC metabolites or compounds, which may cross-react with the immunoassay. When this is the case, the confirmatory GC/MS test would be negative, since CBD and other cannabinoids will not be detected by the more accurate (and specific) GC/MS screen. Most products on BuyLegalMeds.com carry no THC, there are some that carry the legal limit of .3% delta 9 THC. Please read the descriptions of each product and know what you’re buying in reference to this information on this page. Buy and consume at your own risk.

Keep in mind that most of the high-quality, reliable CBD-rich hemp oil products contain much less THC than marijuana. For example, hemp contains anywhere from 1/10th to 1/300th of the THC concentration found in marijuana. An individual consuming 1000-2000 mg per day of hemp oil would thus consume approximately 3-6 mg of THC. This exceedingly high dose may result in detection of positive urine screen in up to 11% to 23% of assays.

On the other hand, there is some data demonstrating that at daily doses of 0.5mg of THC from 3-5 servings of most commercial CBD-rich hemp oil products, the positive urine screen rate is < 0.2%. Again, most servings of typical high-quality, high-purity CBD-based hemp oil products contain well below 0.1mg of THC and therefore have over 400-600 times less THC than marijuana products. What does all this mean? Put simply, a consumer who uses a high-quality, scientifically vetted hemp-based product at the standard serving size is highly unlikely to test positive for THC and/or THC-COOH. However, it’s important to be cognizant that extremely high doses may result in a positive urine screen (that would be subsequently shown to be false via GC/MS). Ultimately, consumers need to be fully informed of the specific regulations posed by their employers and adjust their consumption of cannabinoid products accordingly.

Note: Most research suggests that for infrequent or ‘non-daily’ users of cannabis, a typical high-dose marijuana cigarette (containing about 40mg to 50mg of THC) would result in a positive THC metabolite screen for up to two days at this cutoff level. However, for routine and regular users of cannabis, this same screen could be positive for weeks, but this depends on many factors including, but not limited to:

This article is based on SAMHSA standards. Other organizations’ drug testing standards may vary, so keep in mind that the findings presented in this article may differ under alternative standards. If you have any concern about testing positive for THC when using CBD-containing hemp oil, please seek advice from your health care professional.

References:
Gustafson RA, Kim I, Stout PR, Klette KL, George MP, Moolchan ET, Levine B, Huestis MA. Urinary pharmacokinetics of 11-nor-9-carboxy-delta9-tetrahydrocannabinol after controlled oral delta9-tetrahydrocannabinol administration. J Anal Toxicol. 2004 Apr; 28(3):160-7
Gustafson RA, Levine B, Stout PR, Klette KL, George MP, Moolchan ET, Huestis MA. Urinary cannabinoid detection times after controlled oral administration of delta9-tetrahydrocannabinol to humans. Clin Chem. 2003 Jul; 49(7):1114-24.
Kemp PM, Abukhalaf IK, Manno JE, Manno BR, Alford DD, Abusada GA. Cannabinoids in humans. I. Analysis of delta 9-tetrahydrocannabinol and six metabolites in plasma and urine using GC-MS. J Anal Toxicol. 1995 Sep; 19(5):285-91.
Huestis MA, Mitchell JM, Cone EJ. Urinary excretion profiles of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol in humans after single smoked doses of marijuana. J Anal Toxicol. 1996 Oct;20(6):441-52.
Wall ME, Perez-Reyes M. J Clin Pharmacol. The metabolism of delta 9-tetrahydrocannabinol and related cannabinoids in man. 1981 Aug-Sep; 21(8-9 Suppl):178S-189S.
Note: BuyLegalMeds.com is not responsible in any way if you fail a drug test.

Shipping

To make shopping as easy as possible for you, we are more than happy to ship your purchase right to your doorstep using USPS! Every order is processed in our warehouse within 3 business days from the time you order. Shipping starts the following day after the order is processed. You will get a tracking number once your order is ready to ship.

Shipping within the United States is 2-3 business days once it’s shipped from our warehouse. The shipping time is not guaranteed by the post office unless specified differently on the product page. Processing time at the warehouse to send your package is up to 2-3 business days.

If you order on a Friday after 3pm PST (even using express shipping), the 2-3 business days processing time will begin on Monday. Processing time is not shipping time. Weekends don’t count as shipping or processing days! 
No shipping takes place on the weekends. All orders that take place after 3pm PST the day of the purchase, processing time will begin the next business day.

If shipped out of the USA, BuyLegalMeds.com is not responsible for any packages not being delivered or being confiscated buy customs or their government agencies. Buy at your own risk.
Out of country customers are responsible for any applied fees by customs or any other agency if applicable. 

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