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Significance and therapeutic potential of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration
Contributed by David L. Garbers
Natriuretic peptides (NPs), which consist of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively), are characterized as cardiac or vascular hormones that elicit their biological effects by activation of the cGMP/cGMP-dependent protein kinase (cGK) pathway. We recently reported that adenoviral gene transfer of CNP into rabbit blood vessels not only suppressed neointimal formation but also accelerated reendothelialization, a required step for endothelium-dependent vasorelaxation and antithrombogenicity. Accordingly, we investigated the therapeutic potential of the NPs/cGMP/cGK pathway for vascular regeneration. In transgenic (Tg) mice that overexpress BNP in response to hindlimb ischemia, neovascularization with appropriate mural cell coating was accelerated without edema or bleeding, and impaired angiogenesis by the suppression of nitric oxide production was effectively rescued. Furthermore, in BNP-Tg mice, inflammatory cell infiltration in ischemic tissue and vascular superoxide production were suppressed compared with control mice. Ischemia-induced angiogenesis was also significantly potentiated in cGK type I Tg mice, but attenuated in cGK type I knockout mice. NPs significantly stimulated capillary network formation of cultured endothelial cells by cGK stimulation and subsequent Erk1/2 activation. Furthermore, gene transfer of CNP into ischemic muscles effectively accelerated angiogenesis. These findings reveal an action of the NPs/cGMP/cGK pathway to exert multiple vasculoprotective and regenerative actions in the absence of apparent adverse effects, and therefore suggest that NPs as the endogenous cardiovascular hormone can be used as a strategy of therapeutic angiogenesis in patients with tissue ischemia.
Natriuretic peptides (NPs) consist of atrial NP (ANP), brain NP (BNP), and C-type NP (CNP). They share the same intracellular signal transduction pathway for cGMP/cGMP-dependent protein kinase (cGK) as nitric oxide (NO). We have demonstrated that ANP and BNP are cardiac hormones that are produced mainly in the atrium and ventricle, respectively (1, 2). CNP, in contrast, is produced in and secreted from endothelial cells (ECs) to act as a local regulator of vascular tone and growth (3).
We recently reported that in both rabbit balloon injury and vein graft models, overexpression of the CNP gene by adenoviral vector accelerated reendothelialization and inhibited vascular smooth muscle proliferation (4, 5). This finding indicates the complex responses to NPs in different types of vascular cells, both ECs and smooth muscle cells (SMCs).
A large body of literature indicates an essential role of endothelial NO for angiogenesis. Previous studies demonstrated that vascular endothelial growth factor (VEGF) stimulates Akt/protein kinase B (6, 7), which has been shown to phosphorylate endothelial NO synthase, leading to its activation (8, 9). VEGF-stimulated proliferation of cultured ECs, triggered by endothelial NO synthase activation (10), was also shown to require intracellular signaling through cGK, Raf-1 kinase, and Erk1/2 (11, 12). Based on these findings, we hypothesized that NPs could promote vascular regeneration. To examine this hypothesis, we used a mouse model of operatively induced hindlimb ischemia (13) to investigate the effects of NPs on angiogenesis by using transgenic (Tg) mice that overexpress BNP (14) with or without Nω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase. We also applied this model to both cGK type I (cGKI)-knockout (15) and Tg mice to investigate the impact of cGKI, one of the cGK isoforms, which is present in ECs and SMCs. Finally, we examined the effect of CNP on angiogenesis by a gene-transfer approach to seek the therapeutic potentials of NPs in vascular regeneration. The present study elucidates the action of the NPs/cGMP/cGKI pathway on angiogenesis and provides a strategy for therapeutic angiogenesis by using an endogenous cardiovascular hormone to exert vasculoprotective and vasculoregenerative actions in the absence of apparent adverse effects.
Materials and Methods
BNP-Tg Mice.
Generation of BNP-Tg mice (line 55) was reported (14). BNP-Tg showed a marked increase in plasma BNP levels (1.8 ± 1.1 × 10−9 M) compared with their control littermates (non-Tg) (<0.06 × 10−9 M; refs. 14 and 16). These mice (10–15 wk) were randomly allotted to four treatment groups: BNP-Tg and non-Tg, with or without l-NAME (Nacalai Tesque, Kyoto) administration (200 mg/liter in drinking water; ref. 17).
cGKI-Knockout Mice.
We developed mice with targeted disruption of the cGKI gene (15). We used homozygous cGKI mutant mice (cGKI−/−), heterozygous mutant mice (cGKI+/−), and their control littermates (cGK+/+) (10–15 wk).
cGKI-Tg Mice.
We generated cGKI-Tg mice (T.-H.C. and H.I., unpublished data). Briefly, the cDNA coding for human cGKIα, which we cloned (18), was subcloned into the expression vector pCXN2 (19), driven by the CAG promoter (pCXN2-hcGKIα). The fragment of pCXN2-hcGKIα was microinjected into a C57BL/6 mouse. We used mice with 15 copies of the transgene and their control littermates at the age of 10–15 wk. To confirm cGKI expression in cGKI-Tg mice, Northern blot analysis was performed with a human cGKIα-specific probe, a 311-bp-long fragment at the 5′ end sequence released by pCXN2-hcGKIα.
Ligation Model.
After being anesthetized with pentobarbital (80 mg/kg, i.p.), the right femoral artery and vein were exposed, dissected free, and excised (13). Experimental procedures were performed according to Kyoto University standards for animal care.
Hindlimb blood flow was assessed with a laser Doppler perfusion image (LDPI) analyzer (Moor Instruments, Devon, U.K.) as described (13).
After fixation with 4% paraformaldehyde, ischemic lower legs were embedded in OCT compound (Sakura Finetechnical, Tokyo) and frozen at −80°C. Cryostat sections (4–8 μm thick) of the tissues were stained with rat anti-mouse platelet EC adhesion molecule-1 (PECAM-1) (PharMingen), mouse anti-α smooth muscle actin (SMA) (Sigma), rat anti-mouse CD45 (PharMingen), rabbit anti-cGKI (Calbiochem), rabbit anti-guanylyl cyclase A (GC-A) and B (GC-B) antibody that we developed (20), rabbit anti-Erk1/2 and phospho-Erk1/2 (Thr-202/Tyr-204) antibody (Cell Signaling Technology, Beverly, MA), or mouse anti-CNP antibody that we developed (KY-CNP-1; ref. 21). As the negative control, rabbit preimmune serum or normal Ig fraction (DAKO) was used to show antibody specificity.
Analysis of Capillary Density and Inflammation.
Four random fields on two different sections (≈3 mm apart) from each mouse were photographed with a digital camera (Olympus, Tokyo). By computer-assisted analysis using nih image, capillary density was calculated as the mean number of capillaries stained with PECAM-1 (endothelial marker) or α SMA (vascular smooth muscle marker), and the mean number of infiltrating CD45-positive leukocytes was counted as the assessment of inflammation.
Evaluation of in Situ Reactive Oxygen Production.
The oxidative fluorescent dye dihydroethidium (2 × 10−6 M) was used to evaluate the in situ concentration of superoxide in ischemic hindlimb tissue, as described (22). We also stained 4-hydroxy-2-nonenal (4-HNE) (Nippon Oil & Fats, Tokyo), an unsaturated aldehyde that can be formed by the peroxidation of unsaturated fatty acids, such as linoleic and arachidonic acids (23).
Capillary Network Formation Assay.
Human umbilical vein ECs (Clonetics, Walkersville, MD) were grown in basic medium (EBM2) (Clonetics) containing growth supplements (EGM2) (Clonetics). They (two to three passages, 4 × 104 cells per well) were seeded at Matrigel-coated Cellware 24-well plates (Becton Dickinson) and incubated for 1 h in 100 μl of EBM2 containing 10% FBS. Serum-free medium (400 μl) containing human ANP, BNP, and CNP (Peptide Institute, Osaka) with or without Rp-8-pCPT-cGMP/PD98059 (Calbiochem) were added. After a 10-h incubation, they were fixed with 10% buffered formalin. Two random fields of view in three or four replicate wells were visualized, and images were captured by using the Olympus digital camera. Network formation was assessed by calculating the total area covered by capillaries in each field of view using nih image.
Construction of CNP Plasmid and Its Administration to Ligation Model.
The full length of rat CNP cDNA (384 bp) was inserted into the pAC-CMVpLpA vector (4). The plasmid DNA was prepared from cultures of pAC-CMVpLpA-transformed Escherichia coli by the EndoFree Plasmid Kit (Qiagen, Valencia, CA). After mouse femoral artery ligation, a local injection of plasmid carrying the CNP cDNA (pAC.CMV/CNP) or none (pAC.CMV) was performed (500 μg per mouse in 200 μl of PBS in 10 injection sites). Plasma CNP level was confirmed by an EIA (Phoenix Pharmaceuticals, St. Joseph, MO).
Statistical Analysis.
Results are presented as means ± SEM. The statistical significance of differences in the studies was evaluated by ANOVA. A P value < 0.05 was considered significant.
Ischemia-Induced Angiogenesis Was Accelerated in BNP-Tg Mice.
Serial blood flow measurements by LDPI revealed that accelerated limb perfusion improvement was observed for up to 12 days in BNP-Tg mice compared with non-Tg mice (Fig. 1 a and b). The calculated perfusion ratio of ischemic to nonischemic hindlimb was 0.12 ± 0.02 for BNP-Tg vs. 0.06 ± 0.01 for non-Tg at day 4 (P = 0.002), 0.46 ± 0.06 vs. 0.24 ± 0.05 at day 8 (P = 0.006), and 0.61 ± 0.07 vs. 0.45 ± 0.04 at day 12 (P = 0.04), respectively. After 14 days, restoration of perfusion in BNP-Tg mice was close to non-Tg mice, and no significant difference was seen.
Compatible with the result of blood flow measurement, capillary density in the BNP-Tg group (2,265 ± 62 per mm2) at 10 days was significantly higher than that of the non-Tg group (1,778 ± 74 per mm2; P < 0.0001; Fig. 1 e and f). At day 28, capillary density was equivalent in both groups (Fig. 1 g and h).
Overexpression of BNP Restored Delayed Angiogenesis Induced by NO Blockade.
l-NAME administration to non-Tg mice disclosed impaired recovery in hindlimb perfusion compared with the non-Tg without l-NAME group (Fig. 1c). The ratio of ischemic/normal blood flow measured at 14 days was 0.37 ± 0.04 for the non-Tg (+l-NAME) and significantly lower compared with 0.43 ± 0.03 for the non-Tg alone (P = 0.015). After 14 days, the ratio of both groups became similar.
In contrast to non-Tg, l-NAME administration had no significant effect on the ratio of blood perfusion in BNP-Tg at any time point (Fig. 1d).
On day 10, capillary density of l-NAME-treated non-Tg mice (1,516 ± 62 per mm2) was lower than that of untreated non-Tg mice (P = 0.014; Fig. 1 e and f). In contrast, no difference was seen in BNP-Tg with (2,113 ± 27 per mm2) or without l-NAME administration (day 10). Capillary density in the l-NAME-treated BNP-Tg group was significantly higher than that of the l-NAME-treated non-Tg group (P = 0.023) (day 10). On day 28, capillary density was equivalent in these four groups (Fig. 1 g and h).
Maturity of Newly Formed Blood Vessels in BNP-Tg Mice.
From double immunostaining of ischemic hindlimb tissue with PECAM-1 and α SMA, the structure of capillaries (ECs with adhering mural cells) showed no apparent difference between BNP-Tg and non-Tg mice (data not shown). Accordingly, immunostaining of the ischemic hindlimb tissues at day 10 with anti-αSMA antibody revealed significantly increased α SMA-positive capillary density in BNP-Tg mice (2,061 ± 65 per mm2) compared with non-Tg mice (1,578 ± 79 per mm2; P = 0.0001; Fig. 2 a and b). In addition, edema or bleeding in the ischemic hindlimb tissues was not observed in BNP-Tg mice.
Focal Inflammation in BNP-Tg Mice.
In both BNP-Tg and non-Tg mice, the number of CD45-positive infiltrating leukocytes of the ischemic hindlimb tissues increased until day 5, then gradually decreased (Fig. 2c). At day 7, infiltrating leukocytes in BNP-Tg mice were significantly lower than those of non-Tg mice (P = 0.002), and no significant difference was seen at days 3, 5, and 10.
Reactive Oxygen Production in Blood Vessels of Ischemic Hindlimb Tissue.
By dihydroethidium staining of ischemic hindlimb tissue at day 7, in situ concentration of superoxide in the blood vessels of BNP-Tg mice was obviously lower than that of non-Tg mice (Fig. 2d). Furthermore, immunostaining of 4-HNE demonstrated that reactive oxygen production was also suppressed in BNP-Tg. From double immunostaining with CD45 in non-Tg mice, reactive oxygen production was prominent in infiltrating leukocytes around and within the blood vessels, as well as SMCs. In BNP-Tg mice, the number of reactive oxygen-positive inflammatory cells was decreased and reactive oxygen production in SMCs was diminished.
Expression of GC-A and GC-B in Ischemic Hindlimb Tissue.
Immunostaining (after antigen retrieval) of these receptors in ischemic hindlimb tissue at day 7 revealed that GC-A and GC-B were similarly expressed in the blood vessels of both BNP-Tg and non-Tg mice (Fig. 2e). Negative controls showed virtually no significant staining in these serial sections.
Expression of Erk1/2 and Phospho-Erk1/2 in Ischemic Hindlimb Tissue.
By immunostaining of Erk1/2 in ischemic hindlimb tissue at day 7, Erk1/2 was equally expressed in ECs and SMCs of both BNP-Tg and non-Tg mice. On the other hand, the expression of phospho-Erk was obviously enhanced in BNP-Tg mice, compared with non-Tg mice (Fig. 2f).
Angiogenesis Was Blunted in cGKI-Knockout Mice and Accelerated in cGKI-Tg Mice.
The constitution of the homozygous mice gradually deteriorated and most of them died before 10 wk (15). Because nutrition may influence angiogenesis, we mainly compared heterozygous mutant mice (cGKI+/−) with their control littermates (cGK+/+). By LDPI analysis, limb perfusion among cGKI+/− mice remained significantly impaired throughout the 28-day follow-up period in comparison with cGK+/+ (Fig. 3 a and b). In two cGKI-knockout mice (cGKI−/−), recovery from limb ischemia was remarkably reduced, compared with cGKI+/− or cGK+/+. Immunostaining of ischemic hindlimb tissue at day 28 with anti-PECAM-1 antibody revealed decreased capillary density in cGKI+/− (2,025 ± 51 per mm2) compared with cGK+/+ (2,302 ± 87 per mm2; P = 0.010; Fig. 3 c and d). Two cGKI−/− mice had decreased capillary density (1,845 ± 163 per mm2) compared with cGKI+/− or cGKI+/+.
By Northern blotting of cGKI-Tg mice, we confirmed overexpression of cGKI observed in the aorta and skeletal muscle compared with non-Tg mice (Fig. 3e). By immunostaining of cGKI, after antigen retrieval, high expression was also seen in the skeletal muscle and blood vessels (Fig. 3f). By LDPI analysis, cGKI-Tg mice showed significantly higher perfusion improvement at the end of the study compared with non-Tg mice (Fig. 3 g and h).
NPs Potentiated Capillary Network Formation of Cultured ECs.
NPs significantly potentiated capillary network formation of human umbilical vein ECs in a bell-shaped fashion (Fig. 4 a and b). Network formation was prominent at 10−8 M ANP, 10−8 M BNP, and 10−10 M to 10−8 M CNP. The increase of network formation induced by NPs was completely blocked by Rp-8-pCPT-cGMP, a cGK inhibitor, at a concentration of 5 × 10−6 M (Fig. 4 a and c). Furthermore, treatment with 10−5 M PD 98059, an Erk1/2 inhibitor, significantly suppressed the increase of network formation induced by NPs (Fig. 4 a and d).
CNP Gene Transfer Enhanced Angiogenesis in Ischemic Hindlimb.
CNP immunostaining was detected in skeletal muscle from the ischemic hindlimb of mice that received pAC.CMV/CNP at day 20 (Fig. 5a). Endogenous CNP was also detected in blood vessels of mice that received control vector, pAC.CMV (Fig. 5a; arrowhead). Plasma CNP level was similarly below sensitivity threshold value (<1.32 × 10−10 M) in mice injected with pAC.CMV/CNP or pAC.CMV. By LDPI analysis, mice receiving pAC.CMV/CNP showed a significant increase in blood flow at the end of the study compared with mice receiving pAC.CMV (Fig. 5 b and c). Immunostaining of ischemic hindlimb tissues at day 20 with anti-PECAM-1 antibody revealed an increased capillary density in mice injected with pAC.CMV/CNP (2,643 ± 88 per mm2) compared with pAC.CMV (2,364 ± 104 per mm2; P = 0.048; Fig. 5 d and e).
Experiments performed in this study reveal actions of NPs on vascular regeneration in response to ischemia. BNP overproduced systemically in mice accelerated angiogenesis in the setting of tissue ischemia with activation of Erk1/2 in blood vessels. This evidence was confirmed by a combination of LDPI analysis and capillary density measurement. In addition, overproduction of BNP compensated for impaired neovascularization because of l-NAME treatment. We also succeeded in demonstrating that ischemia-induced angiogenesis is significantly potentiated in cGKI-Tg mice, but attenuated in cGK-knockout mice. Furthermore, CNP gene delivery in the ischemic hindlimb could significantly enhance angiogenesis. These results indicate that the NPs/NO/cGMP/cGK pathway is critical for neovascularization in vivo.
NPs stimulate two biologically active receptors, GC-A and GC-B. We and others have demonstrated that ANP and BNP show high affinity for GC-A, whereas CNP selectively binds to GC-B (24). We have already reported that BNP-Tg mice show skeletal phenotypes through activation of the CNP/GC-B pathway (16, 24). It is important to clarify, therefore, whether the effects of BNP in the hindlimb ischemia model of BNP-Tg mice are mediated through GC-A, GC-B, or both. By immunostaining of these receptors in the ischemic hindlimb of BNP-Tg mice, we confirmed that both GCs expressed in ECs and SMCs. Considering the finding that CNP also enhanced angiogenesis in our model, activation of GC-B is more likely in BNP-Tg mice; however, the analyses of GC-A-knockout mice (25), which we recently developed, would provide answers to that question.
To supplement these in vivo findings with genetically engineered mouse models, we performed several in vitro experiments. In cultured ECs, NPs significantly increased capillary network formation at the concentrations of 10−10 to 10−8 M, which were the same as the plasma BNP level in BNP-Tg mice (14, 16). Early studies, including our own report, have shown that NPs inhibit EC proliferation (26) and migration (27). The concentrations of NPs used in these reports are much higher than physiological (1, 2) and, thus, the EC growth inhibition by NPs seems to be a result of a pharmacological effect. We also confirmed that NP-induced capillary network formation was significantly blocked by Rp-8-pCPT-cGMP and PD98059, indicating the involvement of cGK and Erk1/2 in this phenomenon. Furthermore, we recently observed that ANP increases cultured EC proliferation and migration in vitro by activating the cGK and subsequent Akt/PKB and Erk1/2 pathways (28). These results indicate that NPs can act directly on ECs and potentiate endothelial regeneration.
To achieve recovery from tissue ischemia, not only ECs but also SMCs must migrate and proliferate to produce functionally mature vessels (29). Early studies, including our own report, have shown that NPs inhibit cell growth of vascular SMCs (3). From these reports, it is anticipated that newly formed vessels of BNP-Tg mice in our model might represent immature capillaries without adequate mural cell coating. However, we confirmed that ECs possessed adhering mural cells, and the capillary structures were not different in BNP-Tg or non-Tg mice. Furthermore, the α SMA-positive capillary density in BNP-Tg mice was significantly increased compared with non-Tg mice. These results suggest that antiproliferative effects of NPs on SMCs may not play a role in angiogenesis.
Recently, the participation of inflammation in angiogenesis has been an area of focus. Arras et al. (30) reported monocyte activation with the production of cytokines and vessel proliferation might associate with angiogenesis in a rabbit hindlimb ischemia model. Izumi et al. (31) reported that infarct size after myocardial ischemia/reperfusion injury was smaller in mice lacking GC-A, accompanied with decreases in neutrophil infiltration. From these results, angiogenesis in our model could be explained in part by potential proinflammatory effects of NPs. However, we confirmed that the number of infiltrating leukocytes in the ischemic limb of BNP-Tg mice was similar or even lower than that of non-Tg mice. This finding indicates that possible proinflammatory effects of NPs do not play a role in angiogenesis.
Nitrates, which are clinically used to relieve coronary vasoconstriction, might be useful for the management of vascular obstructions because NPs and NO share the same intracellular signal-transduction pathway. However, there is growing evidence that nitroglycerin-induced production of oxygen-derived free radicals such as superoxide plays an important role in mediating the tolerance and endothelial dysfunction in response to long-term treatment (32). However, the present study revealed that NPs suppress reactive oxygen production in inflammatory cells and blood vessels. Therefore, our findings suggest that NPs possess clinical advantages over nitrates.
The time course of vascular regeneration was different between BNP-Tg mice and cGKI-Tg/knockout mice. The changes in vascular regeneration in cGKI-Tg and cGKI-knockout mice were clearly opposite ("mirror image") and the continuous activation or inactivation of cGKI might result in the final augmentation or suppression of vascular regeneration, which indicates the significance of the cGKI activation level to determine the extent of vascular regeneration. On the other hand, no significant difference in the blood flow or capillary density was seen between BNP-Tg and non-Tg mice at the end of our study. Attenuation of overactivation of the cGMP/cGKI pathway can be one of the possible explanations; however, the expression of GC-A/GC-B showed no apparent difference between BNP-Tg and non-Tg mice at day 7, and also before ischemia (data not shown). Therefore, even if the attenuation of overactivation of cGKI might be the cause, it must not have occurred at the level of regulation of receptor expression.
Clinical applications of cardiovascular gene therapy have been launched during the last several years. However, we know very little about either the therapeutic or toxic effects of overexpressing angiogenic proteins, including VEGF. VEGF overexpression could accelerate atherosclerosis (33), promote pathological angiogenesis (34), or develop limb-threatening peripheral edema. Less adverse effects, such as edema, are seen in patients treated with ANP (35). We have demonstrated that NPs are the vasculoprotective factor against atherosclerotic lesion (4, 5). Furthermore, in the present study, we confirmed that angiogenesis was enhanced in hindlimb-ischemic mice after CNP gene transfer. From these results, NPs in clinical use seem to possess multiple coordinate actions that result in vascular protection and regeneration. In addition, inhibition of NPs can be a potential target of antineoplastic drugs for suppression of angiogenesis.
In conclusion, we have revealed an activity of the NPs/cGMP/cGKI pathway and suggest that NPs, as endogenous cardiovascular hormones, have significant advantages for the treatment of tissue ischemia. Thus, NPs can be used as a promising strategy for therapeutic angiogenesis in patients with tissue ischemia.
↵† To whom correspondence should be addressed at: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: hiito{at}kuhp.kyoto-u.ac.jp.
- natriuretic peptide;
- atrial NP;
- brain NP;
- C-type NP;
- cGK,
- cGMP-dependent protein kinase;
- endothelial cell;
- smooth muscle cell;
- Tg,
- transgenic;
- l-NAME,
- Nω-nitro-l-arginine methyl ester;
- laser Doppler perfusion image;
- platelet EC adhesion molecule-1;
- smooth muscle actin, GC, guanylyl cyclase;
- vascular endothelial growth factor
- Accepted December 31, 2002.
- Copyright © 2003, The National Academy of Sciences
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Hey Madison, you'll want to check with your doctor on this first. I can say that eating lots of fibrous vegetables will aid in your fiber consumption and when you do eat meat, choosing the highest quality, fattier cuts will be key to getting all the beneficial nutrients you need. You could also try out our Greens Powder which will help with consuming a full spectrum of vitamins and minerals. You can check that out here: https://shop.perfectketo.com/products/perfect-keto-micros-greens-powder. Additionally, the scientific literature behind keto and seizure control is very extensive and many many people have found success with it. But like I said – it's best to check with your doctor first. #ketogenic diet
I have achieved all my goals and more…I have lost 35 pounds and have gone from a size 12/13 to a size 5/6. My waist size has changed dramatically – when I began seeing Samantha, I was squeezing myself into a size 32 waist in jeans. Now, I can easily fit into a size 27 which feels fantastic! I tell Samantha and Chris that they are the best thing that ever happened to me and I mean that from the bottom of my heart! I feel like a totally different person now than I did 6 months ago. I am actually excited for beach season this year and I cannot wait to go bathing suit shopping. I can't remember another time in my life in which I had more confidence in my appearance. I have changed my lifestyle and my entire view on health and fitness. I love the food I eat and I am never hungry! I enjoy exercising now and have all the energy I need to get through the day and more. I feel that I am living to my true potential; I have a healthy body, mind and spirit. Samantha gave me the tools and guidance I needed to change my life and I embraced them whole-heartedly. I can say that, without a doubt, I feel 100% better than I did before I started with her. I start each day by looking at myself in the mirror and actually being HAPPY with the person I see looking back at me. Now, I look the way I have always wanted to look and my husband can't believe the results either! I can honestly say that my results have surpassed even my expectations. Don't spend another day feeling bad about yourself or your appearance. You have the power to change your life for the better and to maintain an active lifestyle. I will never allow myself to go back to my old habits. I am a new person thanks to Samantha and Chris at Pure Health & Fitness Studios!" --- Sara
Just like on a standard keto diet, the key is to trade in your starchy veggies for low-carb vegetarian options and also be sure to get in a hearty dose of healthy fats and protein. By cutting down on your intake of carbohydrates, your body is forced to start burning up fats to use for fuel instead of sugar, putting you into a metabolic state known as ketosis and allowing the health benefits to start racking up.
During the five months we've worked with Samantha I've - Lost over 40 pounds and 10 inches from my waistline - Gained a solid foundation in the mental and physical aspect of working out with weights - Learned how to push my body to new limits while becoming so much more in tune with my body's needs - Learned how to manage my food to keep not only keep the weight off but also to keep my body functioning at peak athletic performance - Increased my average cycling speed by over 4 MPH
You may already be exercising, but adding Tabata training to your routine may help speed up your weight loss. 'Tabata' intervals are quick, 20-second bouts of heavy exertion (to the point where your breathing is very labored), followed by 10 seconds of rest—repeating the cycle a total of 8 times. Whether you jump rope, ride your bike or do other cardio, studies have shown this magic formula seems to help your body continue to burn calories long after you finish your workout, says Gretchen Zelek, co-creator of Do or Die Fitness.
High-fat dairy - Nutritionists claim milk products are likely the best sources of high-quality protein [4]. That's because milk proteins contains all 9 essential amino acids and are easier to digest than either beef or soy proteins. Just make sure you're going for products higher in fat to make it more keto. Examples include sour cream, cheese, and full-fat yogurt.
Some people, however, go into the diet in hopes of controlling a chronic illness or just to ensure that they are eating more whole foods and fewer processed ones in their everyday lives. "How someone monitors their diet will depend on their desired health outcomes. Although there is usually quite a bit of initial weight loss, losing one to two pounds per week is ideal. Any more, and you're likely not eating enough and the diet won't be sustainable," says Henry-Barron. Check out 14 amazing before-and-after pictures of people who followed the keto diet.
The right types of oils are great for a ketogenic diet because they're entirely made of fat. MCT's in particular are a type of fat that is metabolized quicker than most and broken down into useable energy. It also can easily cross the blood-brain barrier, which is why they are so beneficial to our mental clarity and performance. Perfect Keto made a convenient MCT Oil Powder just for this reason, and more can be found in our article Are MCT Supplements Worth Taking? Here are some more great options:
Removing just two teaspoons of sugar from your daily cup of coffee may not seem like a big deal, but it can save you 32 extra calories a day or three extra pounds a year, says Morgan. If you're a coffeehouse fiend and make two trips a day, consider this: Skipping that afternoon latte could save you an extra 54,750 calories (more than 15 pounds!)—and almost a thousand bucks—by the end of the year.
We implement a variety of security measures to maintain the safety of your personal information when you place an order or enter, submit, or access any information on our website. We incorporate physical, electronic, and administrative procedures to safeguard the confidentiality of your personal information, including Secure Sockets Layer (SSL) for the encryption of all financial transactions through the website. We use industry-standard, 256bit SSL encryption to protect your personal information online, and we also take several steps to protect your personal information in our facilities. For example, when you visit the website, you access servers that are kept in a secure physical environment, behind a locked cage and a hardware firewall. After a transaction, your credit card information is not stored on our servers.
So what's the difference between a vegan and vegetarian keto diet? Unlike vegetarians, vegans are more restricted in their use of animal products. While both diets eliminate meat entirely from the diet, vegetarians can include non-meat animal foods like eggs, grass-fed butter and ghee to help meet their protein and fat needs while vegans rely solely on plant products such as nuts, seeds and veggies.
Another food you'll find to be a good source of protein on your vegetarian keto diet is cheese, which I'm sure you could have guessed. Cheese comes in a variety of of textures, tastes and colors, but don't let this delicious ingredient fool you -it'll help you hit your protein goals! One thing to note, however, is the varying carb count in different cheeses. It ranges from a low .10 net carbs per 1 oz serving of Gruyere cheese to a higher 1.5 net carbs per 1 oz serving of Swiss cheese.
"Physiologically speaking, to lose weight, you have to burn more than you eat. It requires a 3,500-calorie deficit to lose a pound," says Meg Sharp, director of personal training for the Cambridge Group of Clubs. "This can be done through either diet or exercise alone, but the human body is complicated. It's a bit of an oversimplification that you can choose to either burn your calories or reduce their intake."
Okay, I kid, but seriously. I have been skipping breakfast for as long as I can remember. I really only eat it on special occasions, if ever. It makes my calorie goals much easier to attain, and my body is totally cool with it. I don't often wake up hungry. If you think you could handle waiting until noon to eat for the first time, give intermittent fasting a try. Even harder is to only do one meal a day, OMAD. This isn't for everyone, especially if you get really hangry really quickly, but it is a great way to cut costs.
These omega-3 fats provide building blocks for cellular structures throughout the body and aid in the prevention of cardiovascular disease. Fish oil is the most common source of DHA and EPA, but a good vegan source—and one that, arguably, offers a better concentration of DHA—is algae (which is where those oily fish get their omega-3s from anyway). By supplementing with algae oil, you're effectively cutting out the middle-fish. Aim for about 300mg/day.
You may already be exercising, but adding Tabata training to your routine may help speed up your weight loss. 'Tabata' intervals are quick, 20-second bouts of heavy exertion (to the point where your breathing is very labored), followed by 10 seconds of rest—repeating the cycle a total of 8 times. Whether you jump rope, ride your bike or do other cardio, studies have shown this magic formula seems to help your body continue to burn calories long after you finish your workout, says Gretchen Zelek, co-creator of Do or Die Fitness.
I think if you halved or quartered the higher net carbs mirepoix components and remember this makes 6 servings, this could be keto adapted. I just wonder if the flavor will get lost. I am trying to stay below 19g of net carbs per day. I will try this, doing everything it takes to keep a serving under 9g and report back. I love the idea of it and it does seem like it would be delicious. Always looking for one pot meals to plan lunches for the week.
Taking cues from your body on what to eat on a daily basis can help you eat less, says Jasia Steinmetz, a registered dietitian and author of Eat Local: Simple Steps to Enjoy Real, Healthy & Affordable Food. Next time you're hungry, pay attention to what foods seem appealing to you—and why. Craving sweets, for example, may be a cue that you need energy. If you really want a Snickers, for instance, enjoy a bite-size. Don't limit yourself—if nothing is off limits, you may find yourself craving nutritional food as well. "The vitamins and minerals that are so essential to the various functions of your body will come from a wide variety of foods, and choosing which foods appeal to you each day will help you tune into your body. Paying attention before, during and after you eat will help you respond to the positive feeling you get from eating healthfully and lovingly."
"I have had people I've known for years but haven't seen in awhile not recognize me. I love that. I love the way I feel, the way clothes fit, and being able to shop in regular clothing stores. Mostly I stay motivated for the years, days, hours and minutes I'm hopefully putting on the end of my life. I've got two adult daughters and amazing wife, and I want to be here with them for as long as possible." #keto

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Abel James, Alyson Rose, chicken, chicken enchiladas, egg tortillas, enchilada sauce, fat burning foods, fat burning man, Fat-Burning Recipes, Fat-Burning Tips, Featured, low carb, Mexican, mexican food, Paleo, paleo salad recipe, recipe, Recipes, The Wild Diet, wild chicken enchiladas, wild diet, wild diet recipes, wild enchilada sauce
Knock out a pan of comfort food like these low-carb Wild Chicken Enchiladas – a favorite in our community.
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abc, Abel James, able james, apple pie, apple pie recipe, best, coconut sugar, cooking, crumble top, crust, Delicious, fat burning, fat burning man, fat loss, fat-burning guy, Fat-Burning Recipes, Fat-Burning Tips, Featured, gluten free, gluten free crust, glutenfree, grain free, granny smith, Health, healthy, homemade, homemade apple pie, keto, kurt, lattice crust, low carb, low-sugar, melt fat, Men, my diet is better than yours, Paleo, perfect crust, perfect gluten-free crust, pie, real food, recipe, Recipes, slice, spices, tasty, The Wild Diet, tv show, weight, Weight Loss, wild, wild diet
Being shameless pie people, my wife and I have been working to perfect a guilt-free apple pie for years. And, by golly, I think we've finally done it.
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You can enjoy food, holiday traditions, and family while maintaining your fitness goals. Learn how to eat, drink and be merry this holiday season without packing on the pounds.
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abc, Abel James, able james, apple pie, apple pie recipe, best, coconut sugar, cooking, crumble top, crust, Delicious, fat burning, fat burning man, fat loss, fat-burning guy, Fat-Burning Recipes, Fat-Burning Tips, Featured, gluten free, gluten free crust, glutenfree, grain free, granny smith, Health, healthy, homemade, homemade apple pie, keto, kurt, lattice crust, low carb, low-sugar, melt fat, Men, my diet is better than yours, Paleo, perfect crust, perfect gluten-free crust, pie, real food, recipe, Recipes, slice, spices, tasty, The Wild Diet, tv show, weight, Weight Loss, wild, wild diet
If you're pining for the fruity, crispy, warm goodness of a perfectly baked apple pie—just like grandma used to make—you need to try this for yourself.
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Abel James, best, chef, christmas, coconut oil, cookbook, dessert, duck eggs, fat burning, fat burning chef, fat burning man, Fat-Burning Recipes, Fat-Burning Tips, Featured, holiday menu, holidays, low carb, low-sugar, Mens Health, old-fashioned, Paleo, paleo pie, paleo-friendly, perfect, pie, pumpkin pie, real food, Recipes, slice, superfood, superfood crust, thanksgiving, The Wild Diet, wild diet
This pumpkin pie is a staple this time of year. If you're looking for a Wild, paleo-friendly dessert, this pie fits nicely into your fat-burning plan.
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Abel James, almond butter, almond butter cups, artificial flavor, brain fog, candies, candy, cinnamon, costumes, cravings, creepy, dark chocolate, eat, fall, fat burning, fat burning man, Fat-Burning Recipes, flavors, franken-candies, frankenstein, genetically modified, gluten free, gluten free desserts, gmo, goodies, granola, halloween, halloween hacks, Headaches, healthier, healthy, indulge, inflammation, junk, keto, kids, low carb, low-sugar, monster, Paleo, paleo-friendly, pecans, processed, pumpkin, Recipes, reeses, snickers, Sugar, sugar cravings, sweet tooth, The Wild Diet, thrive market, treat, trick, wild diet
If you eat real, fresh, Wild Diet Approved foods for long enough, you might notice that pre-packaged candy starts to taste like plastic. Ditch the Reeses and make these Wild Peanut Butter Cups instead.
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This is an incredible recipe that Alyson put together. They all mysteriously disappeared within 24 hours…
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Aging, bees, butter, Dan Barber, Exercise, farm bill, fat, flu, flu shot, Health, LaCroix, low carb, Monsanto, natural, Roundup, Running, Saturated Fat, science, sick
Welcome to Friday's For The Love of Food, Summer Tomato's weekly link roundup.
This week LaCroix slapped with lawsuit, Roundup linked to bee deaths, and low-carb studies are bunk.
Next week's Mindful Meal Challenge will start again on Monday. Sign up now to join us!
Too busy to read them all? Try this awesome free speed reading app to read at 300+ wpm. So neat!
I also share links on Twitter @summertomato and the Summer Tomato Facebook page. I'm very active on all these sites and would love to connect with you.
Links of the week
- Think You Don't Need A Flu Shot? Here Are 5 Reasons To Change Your Mind – 80,000 people died of the flu last year. I'm definitely making my entire family get a flu shot this time around. (NPR)
- What is the essence of pamplemousse? LaCroix still won't tell us. – Those flavors sure don't taste natural to me, but that doesn't mean they're necessarily bad. (Vox)
- How Dan Barber helped Sweetgreen get a new squash on its menu – Gosh I miss Sweetgreen. I'm not sure I've tried this Robin's Koginut squash, but I've definitely had the honeynut from the same breeder and it is unreal. Yay for flavor! (Fast Company)
- Is Butter a Healthy Fat? – I use it. (Quick and Dirty Tips)
- Study: Roundup Weed Killer Could Be Linked To Widespread Bee Deaths – Another reason to boycott Monsanto and buy organic. (NPR)
- Meta-Analysis Of Low-Carb Meta-Analyses Finds The Ones Most Excited About Low-Carb Diets Are Of "Critically Low Quality" – There's nothing particularly special about low-carb diets, and the healthiest people in the world eat relatively high-carb (but unprocessed) diets. The science for virtually every weight loss diet is underwhelming, so the best path is still to try to eat as natural as you can and figure out what works best for yourself. (Weighty Matters)
- The Farm Bill Expired—Now What? – Gawd I'm sick of politics. Le sigh. (Mother Jones)
- Buying new running shoes? Forget minimalist or maximalist, and try on a bunch. – Some surprisingly practical advice. (Washington Post)
- We Slow as We Age, but May Not Need to Slow Too Much – Very cool. (NY Times)
- Coconut Red Lentil Soup Recipe – Yum yum yum yum yum. These flavors are so wonderful this time of year. (101 Cookbooks)
What inspired you this week?
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Abel James, abel james my diet, Alyson Rose, anti-inflammatory, avocado, bacon, Breakfast, breakfast recipe, breakfast sandwich, comfort food, egg, egg sandwich, Fat-Burning Recipes, fat-melting, Featured, low carb, my diet is better than yours, Paleo, plantain starch, recipe, Recipes, Resistant Starch, sandwich, The Wild Diet, wild dessert, wild dessert party
The hearty breakfast sandwich that drips down your arm and is so good you lick every finger when you're done.
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Abel James, acting, actor, beef liver, benefits of fasting, blood sugar, body composition, body fat, bone broth, calorie counting, Carbs, cod liver oil, eating disorder, electrolytes, Episodes, Exercise, fasting, fat adapted, fat burning, fat burning man show, fat loss strategy, Fat-Burning Tips, fatty coffee, Featured, get shredded, glycogen, grocery list, hangry, high fat, inflammation, instagram, intermittent fasting, Interviews, keto, keto flu, ketogenic, Ketogenic Diet, kids choice awards, legumes, lifestyle, low body fat, low carb, Mens Health, mental focus, nickelodeon, nutrient timing, omegas, Paleo, plant based, Podcasts, power ranger, Primal, rapid fat loss, sleep, social media, steak and eggs, Sugar, supplementation, Supplements, The Wild Diet, tv show, vegan, Vegetables, videos, weight training, wheat, william shewfelt, workout, Workouts
What would it be like to get down to 3.8% body fat? Today's guest stars as the red Power Ranger on Nickelodeon's "Power Rangers Ninja Steel" and he's going to tell you exactly how he gets shredded for acting roles.
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Bail Bonds in Falfurrias, TX
YP - The Real Yellow PagesSM - helps you find the right local businesses to meet your specific needs. Search results are sorted by a combination of factors to give you a set of choices in response to your search criteria. These factors are similar to those you might use to determine which business to select from a local Yellow Pages directory, including proximity to where you are searching, expertise in the specific services or products you need, and comprehensive business information to help evaluate a business's suitability for you. "Preferred" listings, or those with featured website buttons, indicate YP advertisers who directly provide information about their businesses to help consumers make more informed buying decisions. YP advertisers receive higher placement in the default ordering of search results and may appear in sponsored listings on the top, side, or bottom of the search results page.
1. Selina's Bail Bonds
123 E Fm 1418Falfurrias, TX 78355
From Business: We are a Nation Wide Bonding Company We Post: State Bonds Federal Bonds Replevy Bonds and all other Court Bonds. Selina's Bail Bonds was established in 1989. We h…
2. Mireles Bail Bonds
215 E Miller StFalfurrias, TX 78355
3. Bravo's Bail Bonds
700 S Caldwell StFalfurrias, TX 78355
4. Falfurrias Bail Bonds
615 Taylor RdFalfurrias, TX 78355
5. Garza Joe H Bail Bonds
Po Box 473Falfurrias, TX 78355
6. Alice USA Bail Bonds
Serving the Falfurrias Area
Great Service. Got my son out in less then an hour.
We found6results


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Mortal Kombat 11 Gets Old Skool Meets New Skool Trailer
Old skool meets new skool in the latest trailer for WB Games and NetherRealm Studios' Mortal Kombat 11.
The trailer, which can be seen below, takes a closer look at the characters from both the past and the present who will meet up as part of the title's time-bending new narrative.
Mortal Kombat 11 – Old Skool vs. New Skool Trailer
Also announced today was the fact that Liu Kang, Kung Lao, and Jax Briggs will be added to the title's roster.
The game will come out for the PlayStation 4, Xbox One, Nintendo Switch, and PC on April 23. Those that pre-order the game can add Shao Kahn to the roster.
in News
Ahead of its release for the PlayStation 4 on April 26, Sony Interactive Entertainment and SIE Bend Studio have released a new video for Days Gone that takes a look at its world
in News
All Might will soon be here to utilize his One for All Quirk in Bandai Namco's anime-based fighter Jump Force
in News
SNK has released a new video for Samurai Showdown that shows newcomer Darli Dagger in action
in News
Ahead of its launch on April 23 for the PlayStation 4, Xbox One, Nintendo Switch, and PC, WB Games and NetherRealm Studio have released a launch trailer for Mortal Kombat 11


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Listings in Restaurant Vietnamese
Stay up to date with Asian and Vietnamese restaurants. Our directory contains favorite Asian and Vietnamese restaurant places to eat.
Malai Kitchen
in Restaurants, Restaurant Asian, Restaurant Vietnamese
A Modern Approach to Thai and Vietnamese Cuisine. With locations in Uptown Dallas, Southlake, and Fort Worth, Malai Kitchen showcases a different side of Southeast Asian cuisine. quality ingredients and preparing as much as possible from scratch
3699 McKinney Ave #319
Dallas, Texas 75204
United States
Review this
La Me Vietnamese Restaurant
in Restaurants, Restaurant Asian, Restaurant Vietnamese
La Me Vietnamese Restaurant offers vietnamese food that is very authentic and delicious.
9780 Walnut St #140
Richardson, Texas 75243
United States
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Asia Wok
in Restaurants, Restaurant Asian, Restaurant Vietnamese, Restaurant Chinese
Asia Wok offers unfussy counter serve offering typical Chinese eats such as Kung Pao chicken & chow mein.
901 Main St # C122
Dallas, Texas 75202
United States
Review this


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DescriptionJust like the traditional toys that we grew up with. Give your dog a little nostalgia in his play time. (from Multipet)Origin
Multipet Sock Pals Monkey Dog Toy with Squeaker
Like That? You'll Love This.
- Blue BuffaloWilderness Trail Treats Natural Crunchy Dog Treats, Duck Recipe10oz$6.49/ea($10.38/lb)
- HartzMaximum Protection Dog Pads with Flash-Dry Technology50ct$15.99/ea($0.32/ct)
7%Bocce's BakeryAll Natural Dog Biscuits, PB + Banana14oz$8.99/eaAny 3 Dog Biscuits for $24.99($10.27/lb)
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- Blue BuffaloSizzlers Bacon-Style Dog Treats, Original15oz$9.99/ea($10.66/lb)
- SmokehouseDog Treats, Pepperoni Stix8oz$7.99/ea($15.98/lb)


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$319,900 0.62 acres 3 Beds | 2 Baths | 1 ½ Bath | 1694 sqft 6801 OLD SOLOMONS ISLAND ROAD, Friendship, MD 20758 - Anne Arundel County
0.62 acres Friendship, MD
This home is a gem! Recently updated with that farm house style and charm. 3 nice size bedrooms, 1 1/2 baths. wood burning stove with blower that heats most of the home. Large renovated kitchen with center island, mud room / pantry off kitchen that leads to relaxing screened in porch. Outdoor entertaining is endless. large fenced in yard with tiki bar. Detached garage/work shop with play house loft. Yard is fully fenced in. Fresh paint and carpet. Located in the town of Friendship, walk to Antique and gift shops, or walk to the cafe for lunch. Take a look!


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Not what you are looking for? Ask the experts!
Re: Icon needed on top of phone to confirm status
Posted: 25-Nov-2017 | 7:35PM • Permalink
Go to your Norton Mobile Security settings. Tap the 3 bars at the top left and tap on App Settings. Scroll down to the Scans section and ensure that the Ongoing Notifications is checked. If it is, uncheck it and restart your device. Then go back and reset the Notifications setting.
Things happen. Export/Backup your Norton Password Manager data.


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Stuff I Wrote on Bacefook ('cause I can't use that other word)
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I told my husband I was going to publish a book that included all the stuff I had posted on Facebook over the years. He said: "So you're publishing a book that's... More > about...nothing?" Yes...yes I guess I am. So dear readers this is a book about nothing. It took me fifteen years to write this nothing book but still it's about something - I'm just not certain what. However this nothing book contains words about me and my random, though very occasionally orderly, ravings when I'm red-eyed at two AM! Hopefully it's also funny.< Less
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In terms of recent scientific investigations on the topic, in 2011 a group of researchers conducted a study that revolutionized the thoughts about CBD and anxiety. They took 10 people with social anxiety who had never had any treatment for this disorder and divided them into two groups. One group was given 400mg of CBD and the other a placebo. The results showed that those who had received the CBD oil had successfully improved their anxiety symptoms compared to the placebo.
To access CBD oil, a solvent extraction process is required, which returns roughly 3-5 grams of oil per ounce of flower product used. Using grain or isopropyl alcohol as a solvent, you can strain the result of the mixture, leaving CBD oil behind. It is a lengthy process, and in countries where cannabis is legal, there are many places to access high-quality CBD oil.
I first encountered CBD while on sabbatical a few years back. As I drove up the Oregon Coast Highway, it was hard to miss all the cannabis shops along the Pacific. I stopped in one, perused the menu, and selected two marijuana specials — Nine-Pound Hammer and Trainwreck — and some CBD gummy bears. The cannabis was, well, as advertised, and the CBD candy, as far as I could tell, was a fruit-flavored placebo.
At this point, I could basically write a book about the best (and worst) ways to biohack your anxiety, so I was more than willing to give CBD oil a shot. For this story, I tried eight different varieties of CBD oil over the course of eight days and recorded how I felt. Each day, I took the CBD oil around the same time—always depositing the same dosage under my tongue and waiting 60 seconds before swallowing—and went about my day. Here are my favorites, how they worked (OK, and tasted), and which you should consider buying.
Devinsky puts more weight behind the scientific advancements: In June, the FDA approved an epilepsy drug called Epidiolex, which contains a purified form of CBD oil. In controlled clinical trials, the drug was proven to reduce seizures in people with Dravet syndrome and Lennox-Gastaut syndrome — and it didn't produce as many of the unpleasant side-effects that come with other epilepsy medications.
Our hemp oil is cold pressed and cold filtered with no added preservatives or dyes. Each 15-millilitre serving (1 tablespoon) contains 10 grams of omega-3 and omega-6. The light, nutty taste is perfect drizzled over veggies, on pasta, or even on your popcorn for movie night. You can also add it to salad dressings, sauces, dips, and shakes. Use this light green oil as a substitute for other oils in recipes that aren't heated above 300 °F (150 °C). Not recommended for frying.
Depending on which hormone is stimulated, cannabis can boost or suppress appetite. For this reason, cannabis oil can help patients with eating disorders or be a natural way to treat obesity. This manipulation of the cannabinoid system is becoming popular, and more research is being done to determine its efficacy for patients with weight concerns. (6)
In order to remove unwanted elements such as fats or waxes, CBD oil is subjected to a process called 'Winterization'. Refined cannabidiol oil is stirred with alcohol and deep-frozen overnight. A Butcher funnel or a piece of paper is then used to filter the fats out. Finally, the extracted oil is heated to the boiling point of alcohol so the alcohol evaporates.
In sport, THC has a reporting threshold of 150ng/mL, which means that if the WADA-accredited laboratories detect THC below that level in the urine, it won't be considered a positive test. Other cannabinoids on the WADA Prohibited List don't have a reporting threshold, meaning that the detection of even the tiniest amount in your urine will be considered a positive test.
CBD oil may be of some benefit to those with addiction, suggests a review published in the journal Substance Abuse in 2015. In their analysis of 14 previously published studies, scientists determined that CBD may have therapeutic effects in people with opioid, cocaine, and/or psychostimulant addiction. They also found that CBD may be beneficial in the treatment of cannabis and tobacco addiction. There is some evidence that CBD may block or reduce the effects of THC on the mind.
CBD oil contains CBD (and often other active compounds) in a carrier oil. There are a number of forms of CBD oil, including softgel capsules, tinctures, and under-the-tongue sprays. Some forms of CBD oil can also be applied directly to the skin, in the form of products like creams and salves. The concentration of CBD varies from product to product.
While CBD can be extracted from non-hemp varieties of the plant, hemp-derived CBD is less restricted by the government because of its inherently low levels of THC. CBD from hemp is legal for sale in most US states, while CBD products derived from non-hemp varieties can contain noticeable amounts of THC, and are therefore subject to stricter laws and regulations.
What makes these plants of interest to scientists, healers, and those in need of treatment is cannabidiol, or CBD. CBD is present in both hemp and marijuana, but what makes marijuana psychoactive — giving you the 'high' sensation — is tetrahydrocannabinol (THC). Hemp contains only trace amounts of THC, and studies have shown that CBD is not psychoactive like THC.
Helps a bit with nuropatthy. Helps also with my 8 spinal surgeries. I will buy it again. I was taking both hydrocodone and morapine sulfate 3 times aday for 15 years. They stopped helping so I got Dr to take me off all opioid use. I thought I would just die from the pain. Actually I did. This does really seem to work some. Make pain a bit more manageable. I would recommend it to a friend indeed.
This oil is derived from the Cannabis sativa plant that can contain both CBD and THC in varying concentrations. The clear drawback of cannabis oil is that it cannot be purchased outside of a state that has not legalized the sale of cannabis. Cannabis oil can also contain higher amounts of THC, which could be problematic for those not looking for the psychoactive effects of cannabis oil.
For example, 1 mL of our Canna Oil 20|0 contains 20 mg of THC. The State of Colorado now limits the amount of THC in edibles to 10 mg per piece, so 1 mL of this oil would be equivalent to two (2) edibles. Similarly, a 0.5 gram "joint" of 10% THC contains 50 mg of THC, but more than half of this THC is lost during the combustion process, resulting in a dose of 20-25 mg THC.
@lalyfa In 2010 I went off a cocktail of psychotropics including antidepressants, antianxiety and antipsychotics cold turkey. The meds were wrong for me and the withdrawal was severe and I rarely slept, had RLS, neuropathy and cranky beyond words. Some of these meds took 9+ months to clear my system. Be sure to follow doctor's advice. I did not have a doctor at the time and would not go to the ER knowing it would have resulted in more abuse. Not an intelligent thing to do and not sorry I made the choice even though the experience was horrific and would not reccomend anyone go this route. As to how long the withdrawal lasts the best thing is to discuss this with a pharmacist as this is where their training is and they understand much better and be of help. Wishing you the best.
Thank you for reaching out to us. You could most definitely try our premium hemp oil drops or soft gels. Our premium hemp oil products are great for assisting with a lot of different things such as pain, inflammation, stress, anxiety, mood and sleep. I would start out with our 3x strength option that we have available, and the best method is the drops. You take the recommended amount of drops listed on the bottle, under your tongue. You let the drops sit there for 30 seconds. After the 30 seconds, you swallow the remaining oil in your mouth. Buy doing so this will enter your bloodstream to deliver faster results. Although, I would recommend talking to a doctor before going off any prescribed medicine.
A CNN program that featured Charlotte's Web cannabis in 2013 brought increased attention to the use of CBD in the treatment of seizure disorders.[67][68] Since then, 16 states have passed laws to allow the use of CBD products with a doctor's recommendation (instead of a prescription) for treatment of certain medical conditions.[69] This is in addition to the 30 states that have passed comprehensive medical cannabis laws, which allow for the use of cannabis products with no restrictions on THC content.[69] Of these 30 states, eight have legalized the use and sale of cannabis products without requirement for a doctor's recommendation.[69]
Throughout recent years, cannabis oil has been utilized as a viable treatment for anxiety and depression. Moreover, it is continually being looked into by researchers. Truth be told, the impacts of CBD on anxiety is at present thought to be a standout amongst the most captivating and well-funded sectors of current cannabis research; if development proceeds in the way that it has in the course of the past years, at that point we will unquestionably expand exceptionally compelling means by which oils for anxiety and depression can be utilized as a viable treatment.
As noted in the previous section, CBD oil prices vary significantly by brand. The best practice for most is to determine a per-milligram budget for CBD oil, as well as a maximum price for the entire bottle. For example, you might decide that 10 cents per milligram or less is a reasonable budget; and that $45 (for a 450-mg concentration, based on the budget) is a maximum bottle price. Also, if ordering online, be sure to include potential shipping costs.
Until 2017, products containing cannabidiol marketed for medical purposes were classed as medicines by the UK regulatory body, the Medicines and Healthcare products Regulatory Agency (MHRA) and could not be marketed without regulatory approval for the medical claims.[90] As of 2018, cannabis oil is legal to possess, buy, and sell in the UK, providing the product does not contain more than 0.2% THC and is not advertised as providing a medicinal benefit.[91]
That leaves those touting CBD's effectiveness pointing primarily to research in mice and petri dishes. There, CBD (sometimes combined with small amounts of THC) has shown promise for helping pain, neurological conditions like anxiety and PTSD, and the immune system—and therefore potentially arthritis, diabetes, multiple sclerosis, cancer, and more.
It's also important to select CBD oil products based on your concentration preferences. Some forms of CBD oil – such as vapors and tinctures – normally have higher-than-average concentrations, whereas sprays and topicals tend to have lower concentrations. Remember: higher concentration means more pronounced effects, but not necessarily mean higher quality.
There is currently one FDA-approved prescription CBD product, called Epidiolex, for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. There is also an oral spray called Sativex, which is a combination of THC and CBD used to treat pain related to multiple sclerosis, but it is not approved in the United States.
While we don't normally think of anxiety as desirable, it's actually a critical adaptive response that can help us cope with threats to our (or a loved one's) safety and welfare. These responses help us recognize and avert potential threats; they can also help motivate us to take action to better our situation (work harder, pay bills, improve relationships, etc.). However, when we don't manage these natural responses effectively, they can become maladaptive and impact our work and relationships. This can lead to clinically diagnosable anxiety-related disorders. We've all heard the saying, "stress kills." It's true!
There is no scientific evidence or research on CBD as an effective treatment for migraine—in large part because it has not been formally studied. However, it may still be a viable topical option for some patients with joint and muscle pain associated with migraine. "If you have a lot of neck pain or soreness, it is perfectly reasonable to use CBD oil. It may even prevent nausea and vomiting," Dr. Silberstein says.
Hemp Oil Complex™ is a combination of well-balanced polyunsaturated fatty acids (PUFAs, omega-3 oil) delivering essential fatty acids needed for the formation of specialized lipid mediators for a healthy immune response. Hemp oil and omega-3 oil may support the resolution phase of the inflammatory process by providing PUFAs which are known to be precursors to endocannabinoids. Additionally, Brassica (TrueBroc®) is an important phytonutrient providing antioxidant support by activating the Nrf2/ARE pathways.
What makes these plants of interest to scientists, healers, and those in need of treatment is cannabidiol, or CBD. CBD is present in both hemp and marijuana, but what makes marijuana psychoactive — giving you the 'high' sensation — is tetrahydrocannabinol (THC). Hemp contains only trace amounts of THC, and studies have shown that CBD is not psychoactive like THC.
A. The FDA is aware that several states have either passed laws that remove state restrictions on the medical use of marijuana and its derivatives or are considering doing so. It is important to conduct medical research into the safety and effectiveness of marijuana products through adequate and well-controlled clinical trials. We welcome the opportunity to talk with states who are considering support for medical research of marijuana and its derivatives to provide information on Federal and scientific standards.
Avoid using hemp oil for frying. It should be used in cold and warm dishes that are never heated above 121 degrees F. High heat breaks down polyunsaturated fats into harmful peroxides. Use Hemp Seed Oil as a flavor-enhancer in many recipes. Do not use as a substitute for frying oils. Keep bottles tightly sealed after opening and store in the refrigerator or freezer.
CBD's action within the brain and body is quite complicated. To date, scientists have discovered more than a dozen different mechanisms of action, or ways that CBD affect us. It's very likely that the beneficial effects of CBD are a result of the total of its activation of all of these biological pathways, not a single one in particular. Much more research is needed to fully understand the mechanisms by which CBD relieves ailments such as anxiety and seizures.
Anxiety disorders are the most common mental health concern in the United States. An estimated 30 percent of adults in the United States (that's 66 million people) and an estimated 25 percent of teenagers and preteens are affected by anxiety. As a functional medicine practitioner, I see many people who struggle with anxiety and panic attacks, and from these statistics, it should be no surprise. But just because something is common doesn't make it normal. Fortunately, new insights into the cause of anxiety may help with the development of more effective treatment options.
After seasonal harvests of specific cultivars, these high-CBD hemp crops are put through a specialized solvent-free extraction process to yield a hemp oil that is naturally high in cannabidiol. This pure hemp extract is then tested for safety, quality, and cannabinoid content before being exported to our processing facilities in the United States. Importing any cannabis or hemp product into the United States is a complicated and serious task, so we leave nothing to chance before our high-CBD hemp oil makes its journey across the Atlantic Ocean.
Early preclinical findings also suggest that CBD may have therapeutic value as a treatment of substance use disorders. CBD reduced the rewarding effects of morphinexxxviii and reduced cue-induced heroin seekingxxxix in animal models. A few small clinical trials have examined CBD and/or nabiximols (THC/CBD) for the treatment of substance use disorders; however, the available data are not sufficient to draw conclusions. NIDA is supporting multiple ongoing clinical trials in this area.
There is a lot of excitement about hemp oil these days. There is also a lot of confusion. While many people have heard of hemp oil, they aren't exactly sure what it does. Or whether or not it contains THC, the psychoactive ingredient in marijuana. Will hemp oil make you "high"? If you use a hemp oil supplement are you breaking any laws? The following are answers to some of the most frequently asked questions about hemp oil.
Helps a bit with nuropatthy. Helps also with my 8 spinal surgeries. I will buy it again. I was taking both hydrocodone and morapine sulfate 3 times aday for 15 years. They stopped helping so I got Dr to take me off all opioid use. I thought I would just die from the pain. Actually I did. This does really seem to work some. Make pain a bit more manageable. I would recommend it to a friend indeed.
Chronic stress can kill your quality of life, so stressed-out folks are always looking for proven ways to change this reality. Cannabis oil has the ability to both release pleasure hormones and relax the mind. It reduces stress and allows a calming and peaceful feeling to take over the body. Chemical components of cannabis, called cannabinoids, activate specific receptors found throughout the body to produce pharmacologic effects, particularly in the central nervous system and the immune system.
Cannabidiol is POSSIBLY SAFE when taken by mouth or sprayed under the tongue appropriately. Cannabidiol in doses of up to 300 mg daily have been taken by mouth safely for up to 6 months. Higher doses of 1200-1500 mg daily have been taken by mouth safely for up to 4 weeks. A prescription cannabidiol product (Epidiolex) is approved to be taken by mouth in doses of up to 10-20 mg/kg daily. Cannabidiol sprays that are applied under the tongue have been used in doses of 2.5 mg for up to 2 weeks.
Our Editor's Pick is the tincture from CBDistillery. This tincture is available in five strengths ranging from 250mg to 5,000mg, which accommodates a wide range of THC preferences, as well as 15 and 30 milliliter containers. The tincture has a price-point that is slightly below average, making it a good option for value seekers. The tincture, which is non-flavored, routinely undergoes third-party testing to ensure safety and high quality; the testing results are available on CBDistillery's product pages.
In fact, the U.S. Food and Drug Administration (FDA) approved Epidiolex (a drug made with a purified form of CBD oil) in June 2018 for the treatment of seizures associated with two rare and severe forms of epilepsy in patients 2 years of age and older. These two epilepsy forms are known as Lennox-Gastaut syndrome and Dravet syndrome. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana.
The base of so many great cannabis products starts with great cannabis oil. At Caliva, we invest in innovation and utilize cutting-edge oil extraction and refinement technology to to produce high purity cannabis oil. Our team of cultivators, scientists, and artisan formulators work together to produce the perfect oil blend to fit your product development needs. From vape cartridges, to specialty topicals, edibles and tincture, our oil formulations serve as the basis for high quality cannabis products. All Caliva oils are tested to 2018 California state standards. Our oil is sold by the kilo only and shipped in laboratory grade glass.
We're proud to be present at Cannabis Europa; 'the foremost arena to share knowledge and shape the future of medicinal cannabis in Europe'. Together with Nastasia Bach (Pivot Regulatory), Alex Hearn (Senzer), Jason Moscovici (ROBIC) and pharmaceutical consultant Sofia Sanz our Founder and CEO Tjalling Erkelens discusses ways to find common ground between the pharma world and the medicinal cannabis industry. ... See MoreSee Less
These statements have not been evaluated by the Food and Drug Administration (FDA). These products are not meant to diagnose, treat or cure any disease or medical condition. Please consult your doctor before starting any exercise or nutritional supplement program or before using these or any product during pregnancy or if you have a serious medical condition.
There have been a number of studies investigating the conceivable part of CBD oil in vanquishing pain of all proportions, be it menstrual cramps or pain of a chronic magnitude. The Journal of Experimental medicine speaks about the utilization of CBD oil for suppressing neuropathic pain in rodents. In spite of the fact that such studies are yet to be replicated with human beings, CBD oil is a good tolerance-builder, an agent that enhances the physique's ability to cope with and be resilient to pain.
How do you know if you're having a panic or anxiety attack? Panic attacks and anxiety attacks share some symptoms, but they differ in intensity, duration, and whether or not there is a trigger. Some treatments are similar and include therapy, stress management, and breathing exercises. Learn more about the differences between a panic attack and an anxiety attack here. Read now
Cannatonic: A potent pain-reliever, Cannatonic hails from Spain and stands as one of the earliest cultivars to be bred for its high CBD content. This cultivar is a cross between MK Ultra and G13 Haze, and it helps relieves anxiety, muscle spasms, pain, and migraines while providing uplifting energy. Cannatonic tends to relax and loosen muscles without locking users to their couches.
Our family has been making healthy oils and supplements in the Pacific Northwest for nearly 30 years. As a leader in the natural foods industry, we stake our reputation on innovating and creating the quality products our customers have come to expect. And like all of our products, our Ideal CBD Hemp Oil meets the very highest standards of excellence.
On the other hand, ingestion of cannabis oil can take up to 2 hours (or longer) for onset of effects. The effects themselves may last for up to 10 hours, depending on the potency and amount (volume) of cannabis oil taken, and the mechanism of delivery (drops placed under the tongue vs. ingested with food). Clients with chronic disorders may prefer this method of consumption.
Hash oil is consumed usually by smoking, ingestion, or vaporization.[10] Smoking or vaporizing hash oil is known colloquially as "dabbing",[10] from the English verb to daub (Dutch dabben, French dauber), "to smear with something adhesive".[16] Dabbing devices include special kinds of water pipes ("oil rigs"), and vaporizers similar in design to electronic cigarettes.[10] Oil rigs include a glass water pipe and a hollow tube (called a "nail"), with an indentation on the side which is sometimes covered with a dome.[10] The pipe is often heated with a blowtorch rather than a cigarette lighter.[10]
MADE IN USA WITH 24/7 SUPPORT: All of our supplements are manufactured, tested and bottled in San Diego, CA in a FDA registered facility for quality and consistency. We also offer email support 24/7 and back every purchase with a 30-day, 100% satisfaction guarantee. If for any reason you are not satisfied with the results simply email us and we can refund you or get you the right product for your needs.
Chronic pain: The body's ECS plays a role in alleviating and managing pain, so CBD oil can work as a supplement for individuals with medical conditions that cause chronic pain, such as arthritis and multiple sclerosis. CBD oil also increases levels of adenosine in the brain; adenosine is a neurotransmitter that aids cardiovascular function and eases painful inflammation.
I like this product. At first I didn't like it because of the Stevia. That is the reason for the four stars instead of five. But with that said , I like the product . I find it taste great and it is relaxing and helps with my anxiety and depression . I also mix it with some other CBD things and this helps to make everything last longer . 5000 mg is a big plus too . So many others are 750 or 1000 and once you get above that , the price increases dramatically . This price is good for this product. I find that if I just take the CBD oil I have without this product that the effect is not good . My mother said it helps her with the arthritis pains and she also gave a little to her dog and she felt it helped him too . Great product and I will be ordering more.
In a study whose findings have not yet been published, he and a colleague, Daniel Friedman, found that patients receiving CBD in addition to their usual medicines had 39 percent fewer convulsive seizures than patients who remained on their normal drug regimen. Given that the study included only the most treatment-resistant patients, this is an "excellent response," Devinsky says.
Now 13, Jackson — whose diagnosis is undetermined — continues to use marijuana every day. (Like many patients, he ingests it in droplet form, which allows for more precise dosing and avoids lung problems.) He still has seizures, but they are less severe and they occur once every week or two, down from around 200 a month before he started using cannabis. He is back in school full time and is well enough to go on hikes and bike rides with his family.
A: Our Hemp Oil is regulated to contain no levels of THC as per the legal limits of the State of Idaho. Our CBD Oil is also tested and contains no levels of THC. Our Hemp Oil and CBD Oil are both 100% from the Cannabis plant (save the Peppermint Essential Oil Flavoring and Stevia in our Peppermint option). We do not dilute or use any fillers such as Medium Chain Triglycerides (MCT), Vegetable Glycerin, or other fillers. We do offer our CBD Oil in a variety of strengths to suit everyones needs starting at Regular Strength, 3X Strength, & 5X Strength. Click the below image to see more specific to Zatural CBD Oil and Hemp Oil.
It's important to note that each state has its own individual laws on possession limits. Many states now have their own laws on the books for CBD oil specifically. Tennessee, for example, has made cannabis oil legal if it's derived from hemp rather than marijuana. As Professor Elliot Altman of the Botanical Medical Research Center at Middle Tennessee State University, explains, "The legal definition is hemp is less than point three percent THC which is the psychotropic agent. Marijuana is point three percent or greater." (14)
Reality: Hemp oil is an increasingly popular product, used for an expanding variety of purposes. The washed hemp seed contains no THC at all. The tiny amounts of THC contained in industrial hemp are in the glands of the plant itself. Sometimes, in the manufacturing process, some THC- and CBD-containing resin sticks to the seed, resulting in traces of THC in the oil that is produced. The concentration of these cannabinoids in the oil is infinitesimal. No one can get high from using hemp oil.
There is currently one FDA-approved prescription CBD product, called Epidiolex, for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. There is also an oral spray called Sativex, which is a combination of THC and CBD used to treat pain related to multiple sclerosis, but it is not approved in the United States.
A. We understand that parents are trying to find treatments for their children's medical conditions. However, the use of untested drugs can have unpredictable and unintended consequences. Caregivers and patients can be confident that FDA-approved drugs have been carefully evaluated for safety, efficacy, and quality, and are monitored by the FDA once they are on the market. The FDA continues to support sound, scientifically-based research into the medicinal uses of drug products containing marijuana or marijuana constituents, and will continue to work with companies interested in bringing safe, effective, and quality products to market.
Receptra Naturals CBD products are derived from proprietary CBD rich hemp, grown on family owned and operated farms in Colorado using 100% organic farming practices on select organic soils without the use of pesticides or fungicides. I got to know the folks at Receptra while dealing with Charlotte's Web Botanicals years back and continued to stay in contact when they left CW to form Receptra Naturals.
THC oil is created by extracting the THC compound from marijuana. THC is the compound responsible for producing a "high" feeling in its users, as well as other medicinal effects. This oil is highly regulated in the US and across the world. THC oil is not legal by federal law, but it is legal in states that allow for recreational or medicinal use of cannabis with a doctor's prescription.
The active ingredients in cannabis may be extracted and separated in a number of ways, including water, CO2, alcohol, and organic solvents, such as butane. At Canna Farms, we like to keep things simple! We use a proprietary solvent-less extraction process to obtain a pure, natural, concentrated whole-plant cannabis resin. This resin is rich in THC, CBD, and other cannabinoids and terpenes. This process does NOT use any harsh or dangerous solvents, which ensures safety for our clients as well as our staff.
The fatty acids in hemp oil offer certain health benefits. For example, the oil contains sitosterol, which can help lower cholesterol. It also contains tocopherols, which have antioxidant properties to help prevent your cells from damage, and anticancer agents, according to the "Journal of Nutraceuticals, Functional and Medicinal Foods." Hemp oil also contains a 3-to-1 ratio of omega-3 fatty acids to omega-6 fatty acids, which can help lower your risk of cancer, inflammation and blood clots, the "Journal of Nutraceuticals, Functional and Medicinal Foods" reports. Fatty acids also promote normal brain function.
Years passed, and more studies rolled out with medically beneficial findings regarding cannabis until 2009 when Steep Hill Laboratory in Oakland, California, tested cannabis samples provided by Harborside Health Center to discover that a handful of cultivars contained more CBD than THC. This discovery kicked other labs into gear. They wanted to study medical cannabis to understand and potentially calibrate their cannabinoid ratios. Soon thereafter, laboratories uncovered CBD-dominant strains boasting 20:1 CBD to THC ratios, which opened up the cannabis market for a panoply of CBD products.
NIDA provides research-grade marijuana for scientific study. The agency is responsible for overseeing the cultivation of marijuana for medical research and has contracted with the University of Mississippi to grow marijuana for research at a secure facility. Marijuana of varying potencies and compositions is available. DEA also may allow additional growers to register with the DEA to produce and distribute marijuana for research purposes.
Hemp oil is an abundant source of alpha-linolenic acid. Alpha-linolenic acid is an omega-3 fatty acid that is essential to proper organ function. It is similar to the omega-3 fatty acids found in fish oil, and can help prevent heart disease, arthritis and depression, according to the University of Maryland Medical Center. It can also help reduce low density lipoprotein cholesterol, the "bad" cholesterol that clogs arteries.
Hemp oil can be used for the treatment of minor health ailments and as a dietary supplement for the promotion of general good health. Hemp oil is considered one of the most useful natural supplements for the body due to its ability to provide essential fatty acids to humans that we would not be able to manufacture on our own. However, you should also be aware of potential side effects associated with hemp oil. As such, be sure to speak to a medical professional for more information on hemp oil effects.
A: Mamun, Our Full spectrum CBD oil is great for assisting with pain, inflammation, sleep, anxiety and stress. Depending on the severity of the pain you are experiencing you will want to choose an oil that is stronger or weaker. 5x strength is the strongest option we have available. https://zatural.com/products/cannabis-sativa-hemp-oil-drops?variant=14337796210730
Designed to provide the optimum absorption of CBD into the blood stream by employing a patented slow release delivery system. It's well accepted that CBD is most effective when taken sublingualy, however most oils when taken in this way are swallowed and broken down by your body. The Gel-Tab™. is placed under the tongue and the CBD is slowly absorbed resulting in higher rates of CBD being absorbed than what would be achieved with a normal oil
It's important to know that although THC and CBD are the most studied components of cannabis, there are many more chemical compounds found within the plant, such as cannabigerol (CBG), cannabichromene (CBC), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), terpenes, and flavonoids. While there is still much to learn about these other chemicals, researchers in Israel have discovered that whole-plant cannabis extracts that contain these other chemicals are more beneficial than isolated extracts that contain just CBD or THC.
Word of Caution: Although this list clearly shows that cannabis essential oil can be an effective remedy for many common health conditions, it is still a potent chemical substance extracted from a plant with psychotropic substances. Therefore, you should always be very careful while using such an essential oil, including the amount you use and the conditions under which you use it. Speak to a professional about mixing essential oils and present medications before adding any new elements to your health regimen. Also, the use of cannabis is restricted/banned in many countries, so consult a local health specialist before use.
Technically speaking, its THC—the cannabinoid that gets you high—which is illicit. When you take a drug test, the aim is to detect THC in your body, not "cannabis." If you possessed weed without any THC in it, technically you wouldn't be in violation of the law. Because "weed" without THC has a different name: hemp. And the rules governing hemp are quite different from the restrictions placed on cannabis.
The carrier oils used to create our products will solidify and go cloudy in cold temperatures. It is important to remember that this will not change the quality of the oil or alter its effects. If your oil has turned solid or gone cloudy, place the sealed bottle in a container of hot water until it melts and then mix thoroughly by inverting the bottle 5-10 times.
CBD Essence company unquestionably understands some facts about hemp oil. The proprietor Don has genuinely been around the pharmaceutical business for many years, and subsequently, he knows how to convey a quality and successful item. Every one of their oils is made utilizing CO2 extraction techniques. They maintain a strategic distance from CBD isolates, and they generally uncover lab test results to guarantee there is no substantial metals or contaminants in the oil.
There are certifications and regulations that testify to the quality of the hemp used. These certifications are important because they're essentially the brand's credentials. You must research the brand you use. I chose Ananda hemp because they had every certification possible, and they're affiliated with a higher learning institution to do further research.
The product was shipped as I expected, packed well, and delivered on time. The cost factor is also appealing. After researching products, I have found something more affordable than I have come across so far. That will help to keep me loyal to the product. It is a very saturated, competitive field out there for this product, so if it works, and the price is affordable, I will buy it over other products, who wouldn't? I hope as laws change, the cost will come down even more. And if you are wondering for yourself about using this kind of product for your anxiety, I would tell you to give it a try. Start off with a low type dose, and see what works for you.
I have been using Purekana for 13 months to help with my chronic anxiety. Before discovering this brand I had smoked cannabis but found it made my symptoms much worse and I had several panic attacks. Purekana's CBD oil tastes good, works fast and lasts long without the paranoia effects. I can't thank this company enough for helping me turn my life around.
John Staughton is a traveling writer, editor, and publisher who earned his English and Integrative Biology degrees from the University of Illinois in Champaign, Urbana (USA). He is the co-founder of a literary journal, Sheriff Nottingham, and calls the most beautiful places in the world his office. On a perpetual journey towards the idea of home, he uses words to educate, inspire, uplift and evolve.
My skin started clearing up after a week and a half (I am under lot of stress, so- pimples, acne- it WAS a problem). It is a very nutty product, I added it to my coffee and put it in the blender. Makes it nice and smooth, rich and creamy. My dog has had some kind of skin condition, I was using coconut oil she had a good coat but still had the skin problem - her hair has now grown back after two and a half weeks, and she looks forward to getting the oil in her food every morning.
Cannabis sales have been illegal since the 1970 Controlled Substances Act was passed, with the only exceptions being the products made from the "mature stalk" and "sterilized seed" of the hemp plant, which could still be sold since they contained little to no psychoactive components. Even today, federal law has not changed its stance on cannabis. On the state level, however, things have changed dramatically. As of this writing, there are 30 states that have legalized the sale of cannabis in some form, whether that be medicinally or recreationally. Because federal law continues to outlaw the production and sales of cannabis aside from the CBD oil and hemp seed oil from hemp plants, it is illegal for states that have legalized cannabis to sell products across state borders.