Pure and Organic CBD & and Hemp Products

Effective medicine provided by mother nature

  • Powerful relaxant

  • Strong painkiller

  • Stress reduction
  • Energy booster

Why CBD?

More and more renowned scientists worldwide publish their researches on the favorable impact of CBD on the human body. Not only does this natural compound deal with physical symptoms, but also it helps with emotional disorders. Distinctly positive results with no side effects make CBD products nothing but a phenomenal success.

This organic product helps cope with:

  • Tight muscles
  • Joint pain
  • Stress and anxiety
  • Depression
  • Sleep disorder

Range of Products

We have created a range of products so you can pick the most convenient ones depending on your needs and likes.

CBD Capsules Morning/Day/Night:

CBD Capsules

These capsules increase the energy level as you fight stress and sleep disorder. Only 1-2 capsules every day with your supplements will help you address fatigue and anxiety and improve your overall state of health.

Order Now

CBD Tincture

CBD Tincture

No more muscle tension, joints inflammation and backache with this easy-to-use dropper. Combined with coconut oil, CBD Tincture purifies the body and relieves pain. And the bottle is of such a convenient size that you can always take it with you.

Order Now

Pure CBD Freeze

Pure CBD Freeze

Even the most excruciating pain can be dealt with the help of this effective natural CBD-freeze. Once applied on the skin, this product will localize the pain without ever getting into the bloodstream.

Order Now

Pure CBD Lotion

Pure CBD Lotion

This lotion offers you multiple advantages. First, it moisturizes the skin to make elastic. And second, it takes care of the inflammation and pain. Coconut oil and Shia butter is extremely beneficial for the health and beauty of your skin.

Order Now

Hemp vape cbd oil for sale by owner

High J. Vape CBD Infused CBD – SANDMAN FX w/Terpenes Oil – +



  • High J. Vape CBD Infused CBD – SANDMAN FX w/Terpenes Oil – +
  • AA. 250+ Hemp Oil Drops – FREE SHIPPING
  • Additional information
  • Vape Oils – Wax Crumbles – Terpenes THINK – CBD Vape Oil with Terpenes Not only is the FX line of vape oils the VERY BEST (IMHO), I like the Natural. FX CBD Vape Oil in an All Natural Vegetable Glycerin is Highly Concentrated The Sandman – An effect of quieting the mind and body to prepare for sleep* SKU: N/A Categories: CBD Vape Oils, Highland Farms, Terpine Infused Products Tags: Ultra-High Concentration CBD Vape Oil; Natural Flavor of Hemp Extract . Each subject received a THC-CBD (mg, 10mg respectively) piperine an initial bolus dose was followed 60 minutes later by a one hour constant infusion. gap, an online extraction, high-performance liquid chromatography coupled with Hemp nuts are mature cannabis seeds obtained after shelling and that are.

    High J. Vape CBD Infused CBD – SANDMAN FX w/Terpenes Oil – +

    Genetic variations in the human cannabinoid receptor gene are associated with happiness. Full Text Available Happiness has been viewed as a temporary emotional state e.

    Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater.

    Human metabolites of synthetic cannabinoids JWH and JWH bind with high affinity and act as potent agonists at cannabinoid type-2 receptors. Recent reports indicate that monohydroxylated metabolites of JWH and JWH retain high affinity and activity at cannabinoid type-1 receptors CB 1 Rs , potentially contributing to the enhanced toxicity of K2 compared to marijuana.

    Furthermore, a major omega hydroxyl metabolite of JWH JWHM5 binds to CB 2 Rs with fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. These results indicate that JWH, JWH and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB 2 Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB 1 and CB 2 Rs.

    Rajasekaran, Maheswari; Brents, Lisa K. The pharmacokinetics of the interstitial space in humans. Background The pharmacokinetics of extracellular solutes is determined by the blood-tissue exchange kinetics and the volume of distribution in the interstitial space in the different organs. This information can be used to develop a general physiologically based pharmacokinetic PBPK model applicable to most extracellular solutes.

    Methods The human pharmacokinetic literature was surveyed to tabulate the steady state and equilibrium volume of distribution of the solutes mannitol, EDTA, morphi Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid , on human glioma cell lines. Recently, cannabinoids CBs have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol CBD , a nonpsychoactive cannabinoid compound, on U87 and U human glioma cell lines.

    The addition of CBD to the culture medium led to a dramatic drop of mitochondrial oxidative metabolism [3- 4,5-dimethylthiazolyl -2,5-diphenyl-2H tetrazolium bromide test] and viability in glioma cells, in a concentration-dependent manner that was already evident 24 h after CBD exposure, with an apparent IC 50 of 25 microM. The antiproliferative effect of CBD was partially prevented by the CB2 receptor antagonist N-[ 1S -endo-1,3,3-trimethylbicyclo[2,2,1]heptanyl] 4-chloromethylphenyl 4-methylbenzyl -pyrazolecarboxamide SR; SR2 and alpha-tocopherol.

    By contrast, the CB1 cannabinoid receptor antagonist N- piperidinyl 4-chlorophenyl 2,4-dichlorophenyl methyl-1H-pyrazolecarboximide hydrochloride SR; SR1 , capsazepine vanilloid receptor antagonist , the inhibitors of ceramide generation, or pertussis toxin did not counteract CBD effects.

    We also show, for the first time, that the antiproliferative effect of CBD was correlated to induction of apoptosis, as determined by cytofluorimetric analysis and single-strand DNA staining, which was not reverted by cannabinoid antagonists. Finally, CBD, administered s. In conclusion, the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.

    HCNR p5, a 0. This fragment is a clean single copy sequence by genomic blotting. In situ hybridization localizes it to 6qq Codominant segregation has been observed in 26 informative two- and three-generation CEPH pedigrees and in 14 medium-sized disease families. Full Text Available During human immunodeficiency virus HIV infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role.

    For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells MDDC. In addition, MDDC endocytic function and cytokine production were also differentially altered after alcohol and cannabinoid treatments.

    Our results show a differential effect of alcohol and cannabinoids , which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection. Nicotinamide pharmacokinetics in humans and mice. Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested.

    The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed to female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours. How important are sex differences in cannabinoid action?

    In humans as in animals, males and females are dissimilar in their genetic and hormonally driven behaviour; they process information differently, perceive experience and emotions in different ways, display diverse attitudes, language and social skills, and show sex-related differences in the brain anatomy and organization.

    Drug addiction is a widespread relapsing illness that affects both men and women. Sex-dependent differences have been frequently observed in the biological and behavioural effects of substances of abuse, including cannabis.

    Beside sex differences observed in the cannabinoid -induced effects related to cannabis abuse and dependence, cannabinoids have been shown to exert sex-dependent effects also in other physiological and behavioural aspects, such as food intake and energy balance more evident in males , or anxiety and depression more evident in females. Research has just begun to identify factors which could provide a neurobiological basis for gender-based differences in cannabinoid effects, among which, gonadal hormones seem to play a crucial role.

    Yet, cannabinoid pharmacodynamic and pharmacokinetic may also be important, as sex differences in cannabinoid effects might be due, at least in part, to differences in muscle mass and fat tissue distribution between males and females.

    Here, we will review both clinical and laboratory-based research evidence revealing important sex-related differences in cannabinoid effects, and put forward some suggestions for future studies to fill the gap in our knowledge of gender-specific bias in cannabinoid pharmacology.

    Endogenous cannabinoid receptor ligand induces the migration of human natural killer cells. Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays important physiological roles in several mammalian tissues and cells, yet the details remain ambiguous.

    In this study, we first examined the effects of 2-arachidonoylglycerol on the motility of human natural killer cells. We found that 2-arachidonoylglycerol induces the migration of KHYG-1 cells a natural killer leukemia cell line and human peripheral blood natural killer cells. The migration of natural killer cells induced by 2-arachidonoylglycerol was abolished by treating the cells with SR, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the 2-arachidonoylglycerol-induced migration.

    In contrast to 2-arachidonoylglycerol, anandamide, another endogenous cannabinoid receptor ligand, did not induce the migration. Delta9-tetrahydrocannabinol, a major psychoactive constituent of marijuana, also failed to induce the migration; instead, the addition of delta9-tetrahydrocannabinol together with 2-arachidonoylglycerol abolished the migration induced by 2-arachidonoylglycerol.

    It is conceivable that the endogenous ligand for the cannabinoid receptor, that is, 2-arachidonoylglycerol, affects natural killer cell functions such as migration, thereby contributing to the host-defense mechanism against infectious viruses and tumor cells. Virtual pharmacokinetic model of human eye. The model considers drug release from a polymer patch placed on sclera. The model concentrates on the posterior part of the eye, retina being the target tissue, and comprises the choroidal blood flow, partitioning of the drug between different tissues and active transport at the retina pigment epithelium RPE -choroid boundary.

    Although most straightforward, in order to check the mass balance, no protein binding or metabolism is yet included. It appeared that the most important issue in obtaining reliable simulation results is the finite element mesh, while time stepping has hardly any significance.

    Simulations were extended to , s. The concentration of a drug is shown as a function of time at various points of retina, as well as its average value, varying several parameters in the model. This work demonstrates how anybody with basic knowledge of calculus is able to build physically meaningful models of quite complex biological systems.

    Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach. Yamamoto, Yumi; Valitalo, Pyry A. Knowledge of drug concentration-time profiles at the central nervous system CNS target-site is critically important for rational development of CNS targeted drugs. Human pharmacokinetics of proguanil and its metabolites. The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking mg orally for 14 days.

    A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 CB1 and cannabinoid receptor 2 CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana.

    The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs.

    Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. Screening for the synthetic cannabinoid JWH and its major metabolites in human doping controls.

    Referred to as 'spice', several new drugs, advertised as herbal blends, have appeared on the market in the last few years, in which the synthetic cannabinoids JWH and a C 8 homologue of CP 47, were identified as major active ingredients.

    Due to their reported cannabis-like effects, many European countries have banned these substances. The World Anti-Doping Agency has also explicitly prohibited synthetic cannabinoids in elite sport in-competition.

    Since urine specimens have been the preferred doping control samples, the elucidation of the metabolic pathways of these substances is of particular importance to implement them in sports drug testing programmes. In a recent report, an in vitro phase-I metabolism study of JWH was presented yielding mainly hydroxylated and N-dealkylated metabolites. The majority of the phase-I metabolites observed in earlier in vitro studies of JWH were detected in this urine specimen and furthermore most of their respective monoglucuronides.

    The method was applied to approximately urine doping control samples yielding two JWH findings and demonstrated its capability for a sensitive and selective identification of JWH and its metabolites in human urine. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors CB2-Rs in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation.

    Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents.

    Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior.

    We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

    Transplacental pharmacokinetics of diclofenac in perfused human placenta. The aims of this study were to evaluate the transplacental transfer properties of diclofenac and to determine the effect of L-lactic acid on the transplacental transfer of diclofenac. The maternal and fetal vessels of human placenta were perfused in a single-pass mode with a solution containing diclofenac and antipyrine. The transplacental pharmacokinetic model was fitted to the time profiles of the drug concentrations in the effluent and placenta to obtain transplacental pharmacokinetic parameters.

    In addition, chloride ion in the perfusate was partially replaced with L-lactic acid to see the change in the transplacental transfer properties of diclofenac. The TPT ss value ratio of the rate of amount transferred across the placenta to that infused in the steady state of diclofenac was 2.

    The transplacental pharmacokinetic model could adequately explain the transplacental transfer of diclofenac with influx clearances from maternal and fetal perfusates to placental tissue of 0. In conclusion, human placental perfusion and transplacental pharmacokinetic modeling allowed us to determine the transplacental transfer properties of diclofenac quantitatively. Diclofenac may share transplacental transfer system s with L-lactic acid. The extraction procedure and detectionmethods of new Synthetic Cannabinoids ex: Highlysensitive analytical techniques are therefore required for trace-levelidentification and quantification of these kinds of drugs.

    We report a fullyvalidated method here developed by our team which could simultaneouslydetermine 32 new Synthetic Disposition pathways and pharmacokinetics of herbal medicines in humans. Pharmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies.

    This paper updates our current knowledge on the disposition pathways and pharmacokinetic properties of commonly used herbal medicines in humans. Some herbal ingredients are substrates of P-glycoprotein P-gp which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are determining factors for the in vivo bioavailability, disposition and distribution of herbal remedies. There are increasing pharmacokinetic studies of herbal remedies, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, sculcap, curcumin, echinacea, ginseng, ginkgo, and ginger.

    The pharmacokinetic data of a small number of purified herbal ingredients, including anthocyanins, berberine, catechins, curcumin, lutein and quercetin, are available. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. For a herbal medicine, the pharmacological effect is achieved when the bioactive agents or the metabolites reach and sustain proper levels at their sites of action.

    Both the dose levels and fates of active components in the body govern their target-site concentrations after administration of an herbal remedy. In this regard, a safe and optimal use of herbal medicines requires a. Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes.

    Background Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data.

    The aim of this study was to develop a physiologically based pharmacokinetic PB-PK model capable of describing and predicting terbinafine concentrations in plasma and tissues in rats and humans. It was assumed that all tissues except skin and testis tissues were well-stirred compartments with perfusion rate limitations. The uptake of terbinafine into skin and testis tissues was described by a PB-PK model which incorporates a membrane permeability rate limitation. The concentration-time data for terbinafine in human plasma and tissues were predicted by use of a scaled-up PB-PK model, which took oral absorption into consideration.

    The predictions obtained from the global PB-PK model for the concentration-time profile of terbinafine in human plasma and tissues were in close agreement with the observed concentration data for rats. The scaled-up PB-PK model provided an excellent prediction of published terbinafine concentration-time data obtained after the administration of single and multiple oral doses in humans.

    The PB-PK model developed in this study was capable of accurately predicting the plasma and tissue terbinafine concentrations in both rats and humans and provides insight into the physiological factors that determine terbinafine disposition. Synthetic cannabinoids SCBs , also known under the brand names of "Spice," "K2," "herbal incense," "Cloud 9," "Mojo" and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential.

    There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors. Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants. The largest group of users is men in their 20s who participate in polydrug use. The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain.

    Acute kidney injury has also been strongly associated with SCB use. Treatment mostly involves symptom management and supportive care. More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.

    First characterization of AKB metabolism, a novel synthetic cannabinoid , using human hepatocytes and high-resolution mass spectrometry. Since the federal authorities scheduled the first synthetic cannabinoids , JWH and JWH, new synthetic cannabinoids were robustly marketed. These pharmacological effects and the difficulty in detecting the parent compound in urine highlight the importance of metabolite identification for developing analytical methods for clinical and forensic investigations.

    Using human hepatocytes and TripleTOF mass spectrometry, we identified 17 novel phase I and II AKB metabolites, products of monohydroxylation, dihydroxylation, or trihydroxylation on the aliphatic adamantane ring or N-pentyl side chain. Glucuronide conjugation of some mono- and dihydroxylated metabolites also occurred. Oxidation and dihydroxylation on the adamantane ring and N-pentyl side chain formed a ketone. More metabolites were identified after 3 h of incubation than at 1 h.

    For the first time, we present a AKB metabolic scheme obtained from human hepatocytes and high-resolution mass spectrometry. These data are needed to develop analytical methods to identify AKB consumption in clinical and forensic testing. Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking.

    In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer BRET.

    Orexin receptor subtypes readily formed homo- and hetero di mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers.

    This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Similar was seen for the OX 1 —OX 2 interaction. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations. Herbal cannabis has been used for thousands of years for medical purposes.

    With elucidation of the chemical structures of tetrahydrocannabinol THC and cannabidiol CBD and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored. While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy.

    While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards. Where medical cannabis is legal, patients typically see a physician who "certifies" that a benefit may result.

    Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis. Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

    The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment. A literature survey of medical and scientific databases was conducted with a focus on the biological and medical potential of cannabinoids in cancer treatment. Cannabis sativa is a plant rich in more than types of cannabinoids.

    Besides exogenous plant cannabinoids , mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 CB1 and type 2 CB2 have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines.

    Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of " cannabinoid sensitizers. A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems.

    However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with. Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited.

    The plasma concentration-time profiles of the drug substances in humans after their dermal application were simulated using compartment models and the clinical pharmacokinetic parameters. These simulated plasma concentration profiles were compared with the clinical data. The result revealed that the steady-state plasma concentration of diclofenac and the maximum concentrations of nicotine, bisoprolol, rivastigmine, and lidocaine after topical application were within 2-fold of the clinical data.

    Furthermore, the simulated concentration profiles of bisoprolol, nicotine, and rivastigmine reproduced the decrease in absorption due to drug depletion from the formulation. Published by Elsevier Inc. The influence of renal function on tenofovir pharmacokinetics was investigated in human immunodeficiency virus HIV -infected patients by the use of a population approach performed with the nonlinear mixed effects modeling program NONMEM.

    Tenofovir pharmacokinetics was well described by a two-compartment open model in which the absorption and the distribution rate constants are equal. Pharmacokinetics of high-dose intravenous melatonin in humans. This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Blood samples were collected at baseline and 0, Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique.

    Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments Sedation, evaluated as simple reaction times, was measured at baseline and , , , and minutes after the bolus. Twelve male volunteers completed the study. Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans.

    Cannabis use has been associated with altered sensory gating and neural oscillations. However, it is unclear which constituent in cannabis is responsible for these effects, or whether these are cannabinoid receptor 1 CB1R mediated. Therefore, the present study in humans and rats examined whether cannabinoid administration would disrupt sensory gating and evoked oscillations utilizing electroencephalography EEG and local field potentials LFPs , respectively.

    LFPs were recorded from CA3 and entorhinal cortex. Moreover, this suggests that the endocannabinoid system mediates theta oscillations relevant to perception and cognition. CB2 is a part of the endocannabinoid system that plays vital role in regulation of immune response, inflammation, pain sensitivity, obesity and other physiological responses.

    Information about the structure and mechanisms of functioning of this receptor in cell membranes is essential for the rational development of specific pharmaceuticals. Here we review the methodology for recombinant expression, purification, stabilization and biochemical characterization of CB2 suitable for preparation of multi-milligram quantities of functionally active receptor.

    The biotechnological protocols include expression of the recombinant CB2 in E. The purified recombinant CB2 receptor is amenable to functional and structural studies including nuclear magnetic resonance spectroscopy and a wide range of biochemical and biophysical techniques.

    Humans can be exposed by inhalation, ingestion, or dermal absorption to methyl tertiary-butyl ether MTBE , an oxygenated fuel additive, from contaminated water sources.

    The purpose of this research was to develop a physiologically based pharmacokinetic model describing in human Bioavailability and Pharmacokinetics of Oral Cocaine in Humans. The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited.

    A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants six males with current histories of cocaine use were administered two oral doses and mg and one intravenous IV dose 40 mg of cocaine during three separate dosing sessions.

    Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry.

    Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. Oral cocaine area-under-thecurve AUC and peak concentration increased in a dose-related manner.

    AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile.

    Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites. Indole-, indazole-, or azaindole-based synthetic cannabinoids SCs , bearing a cumyl substituent are a widespread, recreationally used subgroup of new psychoactive substances NPS. Using liquid chromatography-tandem mass spectrometry and liquid chromatography-high resolution mass spectrometry techniques, the main in vivo phase I metabolites of this new substance were detected.

    Additionally, 30 urine samples were investigated leading to 22 in vivo metabolites. Moreover, 3 immunochemical assays commonly used for SC screening in urine were tested for their capability of detecting the new drug but failed due to insufficient cross-reactivity.

    Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids.

    Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken.

    For this, it was necessary to investigate the preparation of cannabinoids , appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A.

    A previously developed physiologically based pharmacokinetic PBPK model for bisphenol A BPA in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA d 6 -BPA delivered in cookies to adult humans after overnight fasting.

    The availability of the serum concentration time course of unconjugated d 6 -BPA offered direct empirical evidence for the calibration of BPA model parameters. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species.

    Metabolites of 5F-AKB, a synthetic cannabinoid receptor agonist, identified in human urine and liver microsomal preparations using liquid chromatography high-resolution mass spectrometry. New types of synthetic cannabinoid designer drugs are constantly introduced to the illicit drug market to circumvent legislation.

    This compound deviates from earlier JHW-type synthetic cannabinoids by having an indazole ring connected to an adamantyl group via a carboxamide linkage. Synthetic cannabinoids are completely metabolized, and identification of the metabolites is thus crucial when using urine as the sample matrix.

    Using an authentic urine sample and high-resolution accurate-mass Fourier transform Orbitrap mass spectrometry, we identified 16 phase-I metabolites of 5F-AKB The modifications included mono-, di-, and trihydroxylation on the adamantyl ring alone or in combination with hydroxylation on the N-fluoropentylindazole moiety, dealkylation of the N-fluoropentyl side chain, and oxidative loss of fluorine as well as combinations thereof.

    The results were compared to human liver microsomal HLM incubations, which predominantly showed time-dependent formation of mono-, di-, and trihydroxylated metabolites having the hydroxyl groups on the adamantyl ring. The results presented here may be used to select metabolites specific of 5F-AKB for use in clinical and forensic screening. Even less is known about other active cannabinoids.

    In contrast to atmospheric pressure chemical ionization, electrospray ionization was associated with extensive ion suppression in plasma and urine samples. Thus, the atmospheric pressure chemical ionization assay was validated showing a lower limit of quantification ranging from 0. Human pharmacokinetics of iohexol. A new nonionic contrast medium. The apparent volume of distribution was 0.

    The biologic half-life was minutes, comparable with that of other intravascular contrast media. A comparison of iohexol and chromium 51 Cr -EDTA clearances indicates that iohexol is mainly excreted by glomerular filtration. The 51 Cr-EDTA clearance was the same when injected separately and concomitantly with iohexol, indicating that glomerular filtration rate is not affected by iohexol.

    Iohexol pharmacokinetics are in correspondence with previously reported data on intravascular contrast media. Effect of the Cannabinoid Receptor-1 antagonist SRA on human adipocyte inflammatory profile and differentiation. Full Text Available Abstract Background Obesity is characterized by inflammation, caused by increase in proinflammatory cytokines, a key factor for the development of insulin resistance. Therefore, we studied the effect of SRA on human adipocyte inflammatory profile and differentiation.

    Methods Adipocytes were obtained from liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. Triglyceride accumulation was observed using oil red-O staining. Cholesterol was assayed by a fluorometric method. Lastly, no effect of SRA was detected on human pre-adipocyte differentiation, although the compound enhanced adiponectin gene expression, but not secretion, in differentiated pre-adipocytes. Conclusion We show for the first time that some clinical effects of SRA are probably directly related to its anti-inflammatory effect on mature adipocytes.

    This fact reinforces that adipose tissue is an important target in the development of tools to treat the metabolic syndrome.

    The metabolites detected were a 4-monohydroxycyclohexylmethyl metabolite M1 N- 1-amino-3,3-dimethyloxobutanyl 4-hydroxycyclohexyl methyl -1H-indazolecarboxamide and a dihydroxyl 4-hydroxycyclohexylmethyl and tert-butylhydroxyl metabolite M11 N- 1-aminohydroxy-3,3-dimethyloxobutanyl 4-hydroxycyclohexyl methyl -1H-indazolecarboxamide.

    Their concentrations were 2. Cannabinoids on the Brain. Full Text Available Cannabis has a long history of consumption both for recreational and medicinal uses.

    Recently there have been significant advances in our understanding of how cannabis and related compounds cannabinoids affect the brain and this review addresses the current state of knowledge of these effects. Cannabinoids act primarily via two types of receptor, CB1 and CB2, with CB1 receptors mediating most of the central actions of cannabinoids.

    The presence of a new type of brain cannabinoid receptor is also indicated. Important advances have been made in our understanding of cannabinoid receptor signaling pathways, their modulation of synaptic transmission and plasticity, the cellular targets of cannabinoids in different central nervous system CNS regions and, in particular, the role of the endogenous brain cannabinoid endocannabinoid system.

    Cannabinoids have widespread actions in the brain: Cannabinoids may also be protective against neurodegeneration and brain damage and exhibit anticonvulsant activity. Some of the analgesic effects of cannabinoids also appear to involve sites within the brain.

    These advances in our understanding of the actions of cannabinoids and the brain endocannabinoid system have led to important new insights into neuronal function which are likely to result in the development of new therapeutic strategies for the treatment of a number of key CNS disorders. Full Text Available Cannabinoids have been used to treat pain for many centuries. However, only during the past several decades have rigorous scientific methods been applied to understand the mechanisms of cannabinoid action.

    Cannabinoid receptors were discovered in the late s and have been found to mediate the effects of cannabinoids on the nervous system. Several endocannabinoids were subsequently identified. Many studies of cannabinoid analgesia in animals during the past century showed that cannabinoids block all types of pain studied. These effects were found to be due to the suppression of spinal and thalamic nociceptive neurons, independent of any actions on the motor systems.

    Spinal, supraspinal and peripheral sites of cannabinoid analgesia have been identified. Endocannabinoids are released upon electrical stimulation of the periaqueductal gray, and in response to inflammation in the extremities. These observations and others thus suggest that a natural function of cannabinoid receptors and their endogenous ligands is to regulate pain sensitivity.

    The therapeutic potential of cannabinoids remains an important topic for future investigations, with previous work suggesting utility in clinical studies of cancer and surgical pain. Projecting human pharmacokinetics of therapeutic antibodies from nonclinical data: What have we learned? The pharmacokinetics PK of therapeutic antibodies is determined by target and non-target mediated mechanisms. These antibody-specific factors need to be considered during prediction of human PK based upon preclinical information.

    Principles of allometric scaling established for small molecules using data from multiple animal species cannot be directly applied to antibodies. Here, different methods for projecting human clearance CL from animal PK data for 13 therapeutic monoclonal antibodi Full Text Available Cannabinoids are used clinically on a subacute basis as prophylactic agonist antiemetics for the prevention of nausea and vomiting caused by chemotherapeutics.

    Cannabinoids prevent vomiting by inhibition of release of emetic neurotransmitters via stimulation of presynaptic cannabinoid CB1 receptors. Cannabis-induced hyperemesis is a recently recognized syndrome associated with chronic cannabis use. It is characterized by repeated cyclical vomiting and learned compulsive hot water bathing behavior.

    Although considered rare, recent international publications of numerous case reports suggest the contrary. The syndrome appears to be a paradox and the pathophysiological mechanism s underlying the induced vomiting remains unknown.

    Although some traditional hypotheses have already been proposed, the present review critically explores the basic science of these explanations in the clinical setting and provides more current mechanisms for the induced hyperemesis. In addition, human and animal findings suggest that chronic exposure to cannabis may not be a prerequisite for the induction of vomiting but is required for the intensity of emesis.

    Full Text Available The endocannabinoid system is comprised of cannabinoid receptors CB1 and CB2, their endogenous ligands endocannabinoids, and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects.

    The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia. Quantitative imaging of the type 1 cannabinoid receptor CB1R opens perspectives for many neurological and psychiatric disorders.

    Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K i and fractional uptake rate FUR were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined.

    A reversible two-tissue compartment model using a global k 4 value was necessary to describe brain kinetics. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K i. The test-retest variability of K i and FUR was 18 F]MK specific binding can be accurately determined using FUR values requiring a short scan 90 to min after tracer administration. Our results suggest that [ 18 F]MK plasma kinetics can be assessed using a few venous samples. Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry.

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Anal Bioanal Chem Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.

    Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine. Pharmacokinetic Profile of Oral Cannabis in Humans: Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral "edible" preparations comprise an increasing segment of the cannabis market.

    Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility.

    Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of.

    Mixed-effects modelling of the interspecies pharmacokinetic scaling of pegylated human erythropoietin. A total of serum concentrations from rats, 6 rabbits, 34 monkeys, and 9 dogs obtained after a single dose of PEG-EPO, administered by the i. An open two-compartment model with first-order absorption and lag time Tlag and linear elimination from the central compartment was fitted to the data using the NONMEM V software.

    Body weight WT was used as a scaling factor and the effect of brain weight BW , sex, and pregnancy status on the pharmacokinetic parameters was investigated. The final model was evaluated by means of a non-parametric bootstrap analysis and used to predict the PEG-EPO pharmacokinetic parameters in healthy male subjects.

    The systemic clearance CL in males was estimated to be 4. In females, the CL was The volumes of the central Vc and the peripheral Vp compartment were characterized as Intercompartmental flow was estimated at 2. Absorption rate constant Ka was estimated at 0. The interindividual variability in the population pharmacokinetic parameters was fairly low parametric bootstrap confirmed the accuracy of the NONMEM estimates. The mean model predicted pharmacokinetic parameters in healthy male subjects of 70 kg were estimated at: The population pharmacokinetic model developed was appropriate to describe the time course of PEG-EPO serum concentrations and their variability in different species.

    Full Text Available The pharmacokinetics of a liposomal subunit antigen vaccine system composed of the cationic lipid dimethyldioctadecylammonium bromide DDA and the immunostimulatory agent trehalose 6,6-dibehenate TDB 8: Compartment modelling and physiologically based pharmacokinetics PBPK were used to predict the administration site muscle and target site lymph temporal concentration profiles and factors governing these. Initial estimates using compartmental modelling established that quadriceps pharmacokinetics for the liposome demonstrated a long half-life A mouse minimal-PBPK model was developed and successfully predicted quadriceps liposome and antigen pharmacokinetics.

    Predictions for the popliteal lymph node PLN aligned well at earlier time-points. A local sensitivity analysis highlighted that the predicted AUCmuscle was sensitive to the antigen degradation constant kdeg resulting in a 3-log change more so than the fraction escaping the quadriceps fe resulting in a fold change, and the predicted AUCPLN was highly sensitive to fe.

    A global sensitivity analysis of the antigen in the muscle demonstrated that model predictions were within the 50th percentile for predictions and showed acceptable fits. To further translate in-vitro data previously generated by our group, the mouse minimal-PBPK model was extrapolated to humans and predictions made for antigen pharmacokinetics in muscle and PLN.

    Global analysis demonstrated that both kdeg and fe had a minimal impact on the resulting simulations in the muscle but a greater impact in the PLN. In summary, this study has predicted the in-vivo fate of DDA: H1 in humans and demonstrated the roles that formulation degradation and fraction escaping the depot site can play upon the overall depot effect within the site of administration.

    Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized -liver mice. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate s were investigated in control and humanized -liver mice. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans.

    The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized -liver mice and that control and humanized -liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized -liver mice. Leuven, Laboratory of Radiopharmacy, Leuven Belgium. Models to predict short and long term accumulation of uranium in the human kidney are reviewed and summarised.

    These are generally first order linear compartmental models or pseudo- pharmacokinetic models such as the retention model of the ICRP. Pharmacokinetic models account not only for transfer from blood to organs, but also recirculation from the organ to blood. The most recent information on mammalian and human metabolism of uranium is used to establish a revised model.

    The model is applied to the short term accumulation of uranium in the human kidney after a single rapid dosage to the blood, such as that obtained by inhaling UF6 or its hydrolysis products. It is shown that the maximum accumulation in the kidney under these conditions is less than the fraction of the material distributed from the blood to kidney if a true pharmacokinetic model is used.

    The best coefficients applicable to man in the authors' view are summarised in model V. We conclude that one must use true pharmacokinetic models, which incorporate recirculation from the organs to the blood, in order to realistically predict time dependent uptake in the kidneys and other organs.

    We do not add any flavoring to our FX line of vape juice as we believe it should be all the healthy goodness you want, without anything unnecessary added!

    Ingredients include 10ml and 30ml size: The Flavor — Aroma Profile: Sandman does not typically make you sleepy. It makes you relax and unwind and calm so you CAN sleep.

    Due to the High Concentration of CBD and thickness of the oil, you will need to have a vaporizer pen that can handle thicker juices. We recommend the EGO-C Twist with variable voltage as the ideal battery along with the Aspire Nautilus X as the ideal vape oil tank, both of which can be purchased elsewhere.

    Consult your doctor before using. Remember Me Log in. Description Additional information Description.

    AA. 250+ Hemp Oil Drops – FREE SHIPPING

    There are 5 major cannabinoids THC, CBD, CBN, CBC and CBG. Each strain of . How To Make Olive Oil Infused with Cannabis / Medical Marijuana. In short. Buy Legal Hemp is your Dream dispensary, with us your information is secret and . Buy High Grade Medical Marijuana | Weed For Sale | THC and CBD Oil For .. Learn how to make a cannabis CBD salve from CBD infused oil. . Beauty Products That Do Way More Than Calm You Down | Revelist. JAY .. Forex Cenneti. the of and to in a is that for it as was with be by on not he i this are or his from at still back right know place every government too high old different states take year james temperature christian volume kept review significant j former meaning rapes prakash paperbacks naylor polaris borderlands cbd bossuet ignominy.

    Additional information



    There are 5 major cannabinoids THC, CBD, CBN, CBC and CBG. Each strain of . How To Make Olive Oil Infused with Cannabis / Medical Marijuana. In short.


    Buy Legal Hemp is your Dream dispensary, with us your information is secret and . Buy High Grade Medical Marijuana | Weed For Sale | THC and CBD Oil For .. Learn how to make a cannabis CBD salve from CBD infused oil. . Beauty Products That Do Way More Than Calm You Down | Revelist. JAY .. Forex Cenneti.

    Add Comment