cbd olie mod psoriasis

December 15, 2021 By admin Off

Nej, fordi cannabidiol – og endda CBD, der er blevet udvundet af cannabis planter – er et ikke-psykoaktivt stof. Stoffet i cannabis, der typisk forårsager en rus-effekt kaldes tetrahydrocannabinol, eller THC. THC er et kontrolleret stof, der ofte findes i marihuana og i Cannabis olie. De produkter, vi har stillet til rådighed i vores online-butik indeholder næsten intet THC og kan derfor ikke forårsage en rus-effekt. Ydermere er vores produkter er 100% lovlige i næsten hele den Europæiske Union, herunder Holland!

Vores onlinebutik fører en række CBD cremer og CBD salver af høj kvalitet, der er egnede til alle hudtyper. Vi sælger endda en shampoo, der er specielt udviklet til sensitiv og irriteret hud.

Cannabidiol (CBD) er en helt lovlig og sikker cannabinoid, der er blevet udvundet fra hamp; en fætter til marihuana, som ikke indeholder THC og som ikke kan give folk en rus/gøre dem ”høje”. Der er mange underarter af cannabis-slægten, ligesom der er mange forskellige typer af biler, og alle af dem har forskellige egenskaber og kvaliteter. Hampplanten er en del af cannabisfamilien, der har en relativ høj koncentration af CBD og er derfor særligt velegnet til fremstilling af CBD produkter.

De mange anvendelser af CBD har været almindeligt kendt i over 50 år, og det er mere end sandsynligt, at vi vil opdage flere og flere fordele. Vi har givet et kort resumé og overblik over vores produkter nedenfor.

Vores CBD-berigede produkter til personlig pleje er specielt udviklet til at forkæle din hud, dit hår og din krop. Du er velkommen til at kigge nærmere på vores hampfrøolie-produkter, som er rige på nærende antioxidanter og essentielle fedtsyrer såsom omega 3 og 6. Det er vigtigt at bemærke, at hampfrøolie og cannabis er to helt forskellige produkter: Cannabis har visse psykoaktive egenskaber – det har hamp ikke, og det betyder, at vores produkter både er sikre og lovlige.

Vil CBD gøre mig ”høj”?

Helt klart! De medicinske effekter i cannabis planten er ideelle til at behandle hudproblemer, akne og andre udvortes lidelser. Du kan bruge disse salver og cremer fra Hemptouch og Jacob Hooy til dette – De bedste på markedet!

CBD produkterne fra Jacob Hooy og Hemptouch har en gavnlig effekt på huden. Hvorvidt det handler om grundigt at nære den tørre hud eller, f.eks., om at behandle svære lidelser som psoriasis eller akne; med disse produkter er du klar til at møde verden igen.

Hvis du har spørgsmål om CBD, er i tvivl om, hvilket produkt der passer bedst til dine behov, eller ønsker at dele dine erfaringer med os, vil vores CBD eksperter være mere end glade for at høre fra dig.

Hudpleje.

Et lovligt og sikkert cannabis-produkt.

First, we studied the effects of CBD on the ionic currents of SZ95 sebocytes. Using whole-cell patch-clamp configurations, membrane currents were elicited by voltage ramp protocols (Figure ​ (Figure4, 4 , A and B) and then normalized to cell membrane capacitance at two different potentials, i.e., at –90 and +90 mV (Figure ​ (Figure4C). 4 C). CBD (10 μM) induced a mostly outwardly rectifying current and a positive shift in the reversal potential, arguing for the activation of certain cation channels upon CBD application.

Next, we dissected the molecular mechanism(s) that underlie the remarkable lipostatic effects of CBD. As expected, neither CB1- nor CB2-specific antagonists (AM251 and AM630) were able to antagonize the lipid synthesis-inhibitory action of CBD (Supplemental Figure 3); hence, alternative options had to be considered.

Given that sebum production is the result of holocrine secretion, the amount of sebum produced is at least as dependent on the proliferative activity of basal layer sebocytes in the sebaceous gland as on the amount of lipogenesis that individual sebocytes engage in (27, 28). Therefore, the novel and significant antiproliferative activity of CBD on human sebocytes in vitro and ex vivo documented here (Figure ​ (Figure2, 2 , A and I) is expected to greatly reduce sebum production in vivo. Moreover, it is also important to emphasize that, clinically, it is highly desirable that basal sebogenesis and viability of sebocytes are unaffected (Figure ​ (Figure1, 1 , A–C, and Figure ​ Figure2, 2 , A–C) by CBD (at least in the noncytotoxic concentrations and after short-term treatments; Supplemental Figure 2, A–E), since a sufficient level of sebum production is a critical factor for maintaining proper function of the epidermal barrier, one of the central components of skin homeostasis (56).

Christos C. Zouboulis.

We found that SZ95 sebocytes express TRPV1, TRPV2, and TRPV4 both at the mRNA and protein levels (Supplemental Figure 4, A–C). Among these TRP channels, TRPV4 showed the highest mRNA levels by far (expression of TRPA1 and TRPM8 was below the detection limit; data not shown).

1 DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 2 Laboratory for Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. 3 Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4 Department of Dermatology, University of Lübeck, Lübeck, Germany. 5 Neurobiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 6 Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy. 7 Departments of Dermatology, Venereology, and Allergology and Immunology, Dessau Medical Center, Dessau, Germany. 8 School of Translational Medicine, University of Manchester, Manchester, United Kingdom.

We also investigated the effects of CBD on the lipidome of SZ95 sebocytes under in vitro conditions that mimicked “acne-like” circumstances (the latter was achieved by using a key “pro-acne” inflammatory mediator, AA) (1, 2, 21, 24–26). Importantly, CBD almost completely normalized the AA-enhanced “pathological” lipogenesis of SZ95 sebocytes (Figure ​ (Figure1G). 1 G). This suggests that CBD may primarily normalize both quantitatively and qualitatively excessive and abnormal lipid production induced by acne-promoting stimuli.

We first assessed the biological effects of CBD (1–10 μM) on the lipogenesis of SZ95 sebocytes. Although eCBs are known to show intense lipogenic actions via the metabotropic CB2 receptors (12), neither semiquantitative Oil Red O nor quantitative Nile Red staining indicated changes in the basal neutral (sebaceous) lipid synthesis of SZ95 sebocytes following 24-hour CBD treatment (Figure ​ (Figure1, 1 , A–C) (or 48-hour CBD treatment; data not shown). Intriguingly, however, CBD markedly inhibited the lipogenic action of the prototypic eCB, AEA, in a dose-dependent manner (1–10 μM; Figure ​ Figure1, 1 , C–E).

1 DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 2 Laboratory for Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. 3 Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4 Department of Dermatology, University of Lübeck, Lübeck, Germany. 5 Neurobiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 6 Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy. 7 Departments of Dermatology, Venereology, and Allergology and Immunology, Dessau Medical Center, Dessau, Germany. 8 School of Translational Medicine, University of Manchester, Manchester, United Kingdom.

Investigation of the cutaneous cannabinoid system seems to be a promising choice when searching for novel therapeutic possibilities (7, 8). Indeed, we have shown previously that the skin ECS regulates cutaneous cell growth and differentiation (9, 10), and it reportedly exerts antiinflammatory effects (11). Of further importance, we have also demonstrated that the ECS plays a key role in the regulation of sebum production (12). According to our recent findings, prototypic eCBs, such as N-arachidonoyl ethanolamide (anandamide [AEA]) and 2-arachidonoylglycerol, are constitutively produced in human sebaceous glands. Moreover, using human immortalized SZ95 sebocytes, we have also demonstrated that these locally produced eCBs (acting through a CB2 cannabinoid receptor→ERK1/2 MAPK→PPAR pathway) induce terminal differentiation of these cells, which is characterized by increased neutral lipid (sebum) production of the sebocytes (12). These findings confirmed unambiguously that human sebocytes have a functionally active ECS; yet, we did not possess data on the potential effect(s) of plant-derived cannabinoids.

TRIB3 is known to inhibit the NF-κB pathway (50), and, furthermore, CBD has already been reported to exert its antiinflammatory actions via inhibition of the NF-κB signaling (51). Importantly, we found that CBD cotreatment indeed prevented the LPS-induced phosphorylation (hence inactivation) of the inhibitory IκBα and phosphorylation (hence activation) of the p65 (RelA) NF-κB isoform (Figure ​ (Figure8B). 8 B). These data indicate that, irrespective of the investigated cell type, interference with the NF-κB pathway could be an important mechanism in the development of the antiinflammatory actions of CBD. It should also be noted that TRPV4 antagonism exerted only negligible effects on the action of CBD (Figure ​ (Figure8B), 8 B), again confirming that antiinflammatory activity of CBD is a TRPV4-independent process.

Ralf Paus.

CBD has already been shown to activate (e.g., certain TRP channels, α1 and 5-HT1a receptor, etc.), antagonize (e.g., TRPM8 and 5-HT3 receptor as well as “classical” [CB1 and CB2] and “novel” [GPR55] cannabinoid receptors, etc.), or allosterically modulate (e.g., μ- and δ-opioid receptors, etc.) the activity of a plethora of different receptors and, furthermore, to influence various other cellular targets (e.g., cyclooxygenase and lipoxygenase enzymes, fatty acid amide hydrolase, eCB membrane transporter, phospholipase A2, voltage-dependent anion channel 1, etc.) (15, 32–37, 57–60). Therefore, exploration of its exact mechanism of action appeared to be a great challenge. The fact that we have shown previously that activation of TRPV1 can evoke similar lipostatic effects (38) as those found for CBD (Figure ​ (Figure1 1 and Figure ​ Figure2, 2 , D–H), together with our present findings that CBD induced membrane currents on sebocytes (Figure ​ (Figure4), 4 ), prompted us to first investigate the role of TRP channels in mediating the above anti-acne modalities. We discovered that the lipostatic and antiproliferative effects of CBD were mediated by the activation of TRPV4 (and not TRPV1 or TRPV2) ion channels (Figures ​ (Figures5, 5 , C–E, and Figure ​ Figure6A) 6 A) and the concomitant increase in [Ca 2+ ] IC . Actually, the “negative regulation” of lipogenesis by the elevation of [Ca 2+ ] IC is not unprecedented, since it has already been described in sebocytes (38) as well as in adipocytes (61, 62). It is also important to note that, within the confines of another study, we have shown that extracellular Ca 2+ plays an important negative regulatory role in the sebaceous lipogenesis (C.C. Zouboulis et al., unpublished observations). Of further importance, we have also shown that the antiinflammatory activity of CBD is a TRPV4-independent process (Figure ​ (Figure6 6 B).

( A ) IL1B and IL6 mRNA expression following 5 μg/ml LPS treatment with or without 10 μM CBD (24-hour treatments started at the day 2 after the transfection). *** P < 0.001 compared with the corresponding CBD-free treatments. ### P < 0.001 compared with the SCR group receiving the same treatments. “siTRIB3a” and “siTRIB3b” mark 2 different siRNA constructs against TRIB3. ( B ) Western blot analysis of lysates of SZ95 sebocytes treated with 5 μg/ml LPS, 10 μM CBD, and 1 μM HC for 25 minutes. ( C ) Determination of the intracellular cAMP concentration following 1-hour CBD (10 μM) or vehicle treatment. Data are presented as mean ± SEM of 3 independent determinations. One additional experiment yielded similar results. ( D and E ) TRIB3 and TNFA mRNA expression following the indicated treatments (5 μg/ml LPS, 10 μM CBD, and 10 nM ZM). ( A , D , and E ) Data are presented using the ΔΔCT method; PPIA -normalized mRNA expression of the vehicle control was set as 1 (solid line). Data are expressed as mean ± SD of 3 independent determinations. One additional experiment yielded similar results. ( C – E ) ** P < 0.01, *** P < 0.001. ( F ) Western blot analysis of lysates of SZ95 sebocytes treated with 5 μg/ml LPS, 10 μM CBD, and 100 nM ZM for 25 minutes. ( B and F ) Numbers on the OD row indicate the optical density of the P-IκBα and P-P65 bands normalized to the corresponding β-actin signals.

( A ) Fluorescent Ca 2+ imaging. Compounds were applied as indicated by the arrow. Fluorescence (measured in relative fluorescence units [RF]) was normalized to the baseline. “Low [Ca 2+ ] EC ” indicates the use of nominally Ca 2+ -free Hank’s solution. Two additional experiments yielded similar results. ( B ) Statistical analysis of the fluorescent Ca 2+ -imaging data. Fluorescence (expressed in RF) was normalized to the baseline. Measured peak values were expressed as the percentage of the baseline (mean ± SEM of 3 independent determinations). The solid line indicates 100%. Two additional experiments yielded similar results. *** P < 0.001 compared with the CBD-treated group. ( C ) Neutral lipid synthesis (Nile Red staining). Data are expressed as the percentage of the vehicle control (mean ± SEM of 4 independent determinations). The solid line indicates 100%. Two additional experiments yielded similar results. “Low [Ca 2+ ] EC ” indicates the use of low-Ca 2+ Sebomed medium. * P < 0.05, ** P < 0.01, *** P < 0.001. ( D and E ) Neutral lipid synthesis (Nile Red staining) following selective gene silencing of TRPV4 channel (24-hour treatments, started at day 3 after the transfection). Data are expressed as the percentage of the untransfected vehicle control (mean ± SEM of 4 independent determinations). The solid line indicates 100%. Two additional experiments yielded similar results. * P < 0.05, *** P < 0.001 compared with the SCR cells. “siV4a” and “siV4b” mark 2 different siRNA constructs against TRPV4. SCR, scrambled control; UC, untransfected vehicle control.

We additionally found that CBD also prevented the “pro-acne” LA-T combination from elevating the expression of TNFA (Figure ​ (Figure3A), 3 A), a key cytokine in the pathogenesis of acne vulgaris (2, 24–30). These data suggested that CBD may exert antiinflammatory actions on human sebocytes (as had already been demonstrated for CBD in several other experimental models, such as diabetes, rheumatoid arthritis, etc.) (31). Therefore, in order to confirm the putative universal antiinflammatory action of the CBD on human sebocytes, we next assessed its effects by modeling both Gram-negative infections (applying the TLR4 activator LPS) and Gram-positive infections (using the TLR2 activator lipoteichoic acid [LTA]). We found that CBD completely prevented the above treatments from elevating TNFA expression (Figure ​ (Figure3). 3 ). Moreover, CBD also normalized LPS-induced IL1B and IL6 expression (Figure ​ (Figure3B) 3 B) (expression of these 2 cytokines was found not to be modulated by 24-hour LA-T or LTA treatment; data not shown). Taken together, these results strongly suggest that CBD’s universal sebostatic action is accompanied by substantial antiinflammatory effects, which would be very much desired in the clinical treatment of acne vulgaris (1, 2, 24–30).

1 DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 2 Laboratory for Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. 3 Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4 Department of Dermatology, University of Lübeck, Lübeck, Germany. 5 Neurobiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 6 Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy. 7 Departments of Dermatology, Venereology, and Allergology and Immunology, Dessau Medical Center, Dessau, Germany. 8 School of Translational Medicine, University of Manchester, Manchester, United Kingdom.

Sebostatic (i.e., lipostatic and antiproliferative), but not antiinflammatory, actions of CBD are mediated by the activation of transient receptor potential vanilloid-4 ion channels.

1 DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 2 Laboratory for Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. 3 Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4 Department of Dermatology, University of Lübeck, Lübeck, Germany. 5 Neurobiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 6 Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy. 7 Departments of Dermatology, Venereology, and Allergology and Immunology, Dessau Medical Center, Dessau, Germany. 8 School of Translational Medicine, University of Manchester, Manchester, United Kingdom.

Acne vulgaris is the most common human skin disease, affecting quality of life of millions worldwide. In spite of heroic basic and applied research efforts, we still lack indisputably curative anti-acne agents, which target multiple pathogenetic steps of acne (sebum overproduction, unwanted sebocyte proliferation, inflammation) and, moreover, which possess favorable side effect profiles (1, 2). Investigations over the last two decades have confirmed unambiguously that the human body expresses such receptors, which are able to specifically bind and recognize characteristic terpene-phenol compounds of the infamous plant Cannabis sativa , collectively referred to as phytocannabinoids. These receptors, their endogenous ligands (the endocannabinoids [eCBs]), and the enzymes involved in the synthesis and degradation of the eCBs collectively constitute the eCB system (ECS), a complex intercellular signaling network markedly involved in the regulation of various physiological processes (3–6).

Next, we aimed at revealing the signaling pathway of the antiinflammatory actions. Thorough assessment of the microarray data highlighted the putative role of TRIB3, a known inhibitor of proinflammatory NF-κB signaling (50). In addition, inhibition of NF-κB signaling plays a crucial role in the development of CBD-mediated antiinflammatory actions in other systems (51). RNA i -mediated selective gene silencing of TRIB3 in human sebocytes (Supplemental Figure 15, A and B) fully abrogated the ability of CBD to inhibit LPS-induced proinflammatory responses (Figure ​ (Figure8A). 8 A). Although a previous study would have suggested it (63), interestingly, TRIB3 was found not to participate in mediating the lipostatic effects of CBD in sebocytes (Supplemental Figure 15C).

Then, in order to identify target genes and pathways regulated (directly or indirectly) by CBD, genome-wide microarray analyses were performed on 3 independent sets of control and CBD-treated SZ95 sebocytes (10 μM CBD for 24 hours). Gene set enrichment analysis (GSEA) (40–42) of the microarray results revealed that numerous mitosis and cell cycle (e.g., “mitosis,” “G 2 /M transition,” “cell cycle,” etc.), inflammation (e.g., “cytokine production,” “cytokine biosynthetic process,” “TLR9 pathway,” “positive regulation of IκB kinase NF-κB cascade,” etc.), and lipid synthesis–related (“acyltransferase activity,” “lipid biosynthetic process,” “positive regulation of MAPK activity,” etc.) gene sets were identified among the downregulated ones, confirming our previous findings on the complex anti-acne effects of CBD. Moreover, downregulation of some “acne-related” gene sets (e.g., “IGF-1 pathway” and “mTOR pathway”) (2, 43) also argued for the putative in vivo anti-acne efficiency of CBD. Further, upregulation of the “calcium signaling pathway” gene set confirmed the involvement of (TRPV4-dependent) calcium signaling (detailed results of GSEA are available in Supplemental Excel files 1 and 2).

1 DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 2 Laboratory for Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium. 3 Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4 Department of Dermatology, University of Lübeck, Lübeck, Germany. 5 Neurobiology Research Group, Department of Physiology, University of Debrecen, Debrecen, Hungary. 6 Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy. 7 Departments of Dermatology, Venereology, and Allergology and Immunology, Dessau Medical Center, Dessau, Germany. 8 School of Translational Medicine, University of Manchester, Manchester, United Kingdom.

Clinically, the key question is whether the above in vitro observations could be translated into significant sebostatic (i.e., lipostatic and antiproliferative) effects of CBD on human sebaceous glands in situ. To explore this on the preclinical level, the full-thickness hSOC technique (20) was used. These hSOC assays, which mimic the human sebaceous gland function in vivo as closely as this is currently possible on the ex vivo level, clearly demonstrated that application of CBD completely prevented the lipogenic action of AEA in situ and, in line with our long-term in vitro observations (Supplemental Figure 2E), decreased basal lipogenesis as well (Figure ​ (Figure2, 2 , D–H). Likewise, CBD markedly suppressed the expression of the proliferation marker MKI67 (Figure ​ (Figure2I). 2 I). This suggests that CBD may also operate as a potent sebostatic agent in vivo when tested in appropriate clinical trials.

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