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Apr 11 - Cannabidiol Inhibits SARS-CoV-2 Replication & Promotes Innate Immune Response



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LuxG2 
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Apr 11 - Cannabidiol Inhibits SARS-CoV-2 Replication & Promotes Innate Immune Response
 

 
The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARSCoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.

Cannabidiol from the cannabis plant has potential to prevent and inhibit SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), a pandemic that has overtaken the world during the past year. SARS-CoV-2, related to severe acute respiratory syndrome-related coronavirus (SARS-CoV), is the seventh species of coronavirus known to infect people. These coronaviruses, which include SARS-CoV, 229E, NL63, OC43, HKU1, and MERS-CoV cause a range of symptoms from the common cold to more severe pathologies (1). Despite recent vaccine availability, SARS-CoV-2 is still spreading rapidly (2), highlighting the need for alternative treatments, especially for populations with limited access to vaccines. To date, few therapies have been identified that block SARS-CoV-2 replication and viral production.

SARS-CoV-2 is a positive-sense single-stranded RNA (+ssRNA) enveloped virus composed of a lipid bilayer and four structural proteins that drive viral particle formation. The spike (S), membrane (M), and envelope (E) are integral proteins of the virus membrane and serve to drive virion budding, while also recruiting the nucleocapsid (N) protein and the viral genomic RNA into nascent virions. Like SARS-CoV, SARS-CoV-2 primarily enters human cells by the binding of the viral S protein to the angiotensin converting enzyme 2 (ACE2) receptor (3–5), after which the S protein undergoes proteolysis by transmembrane protease, serine 2 (TMPRSS2) or other proteases into two non-covalently bound peptides (S1, S2) that facilitate viral entry into the host cell. The N-terminal S1 binds the ACE2 receptor, and the C-terminal S2 mediates viral-cell membrane fusion following proteolytic cleavage by TMRSS2 or other proteases. Depending upon the cell type, viral entry can also occur after ACE2 binding, independent of proteolytic cleavage (6–8). Following cell entry, the SARS-CoV-2 genome is translated into two large polypeptides that are cleaved by two viral proteases, MPro and PLPro (9, 10), to produce 15 proteins, in addition to the synthesis of subgenomic RNAs that encode another 10 accessory proteins plus the 4 structural proteins. These proteins enable viral replication, a*sembly, and budding. In an effort to suppress infection by the SARS-CoV-2 beta-coronavirus as well as other evolving pathogenic viruses, we tested the antiviral potential of a number of small molecules that target host stress response pathways.

One potential regulator of the host stress and antiviral inflammatory responses is cannabidiol (CBD), a member of the cannabinoid class of natural products (11). CBD is produced by Cannabis sativa (Cannabaceae; marijuana/hemp). Hemp refers to cannabis plants or materials derived thereof that contain 0.3% or less of the psychotropic tetrahydrocannabinol (THC) and typically have relatively high CBD content. By contrast, marijuana refers to C. sativa materials with more than 0.3% THC by dry weight. THC acts through binding to the cannabinoid receptor, and CBD potentiates this interaction (12). Despite numerous studies and many typically unsubstantiated claims related to CBD-containing products, the biology of CBD itself is unclear and specific targets are mostly unknown (11). However, an oral solution of CBD is an FDA-approved drug, largely for the treatment of epilepsy (13). Thus, CBD has drug status, is viable as a therapeutic, and cannot be marketed as a dietary supplement in the United States (11). Although limited, some studies have reported that certain cannabinoids have antiviral effects against hepatitis C virus (HCV) and other viruses (14).

To test the effect of CBD on SARS-CoV-2 replication, we pretreated A549 human lung carcinoma cells expressing exogenous human ACE-2 receptor (A549-ACE2) for 2 hours with 0–10 μM CBD prior to infection with SARS-CoV-2. After 48 hours, we monitored cells for expression of the viral spike protein (S). For comparison, we also treated cells over a similar dose range with an MLK inhibitor (URMC-099) previously implicated as an antiviral for HIV (12) and KPT-9274, a PAK4/NAMPT inhibitor (13) that our analysis suggested might reverse many changes in gene expression caused by SARS-CoV-2. All three inhibitors potently inhibited viral replication under non-toxic conditions with EC50s ranging from 0.2–2.1 μM (Fig. 1A). CBD inhibited SARS-CoV-2 replication in Vero E6 monkey kidney epithelial cells as well (fig. S1A). No toxicity was observed at the effective doses (fig. S1B). We also determined that CBD suppressed replication of a related beta-coronavirus, mouse hepatitis virus (MHV), under non-toxic conditions with an EC50 of ~5 μM using A549 cells that express the MHV receptor (A549-MHVR), indicating the potential for more broader viral efficacy (fig. S1C,D).


image

Fig. 1.
Cannabidiol (CBD) is a potent inhibitor of SARS-CoV-2 infection in vitro.
(A) A549 cells with ACE2 overexpression (A549-ACE2) were treated with indicated doses of CBD, KPT-9274, or URMC-099 followed by infection with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. EC50 values are indicated. (B) The 1H qNMR spectra of CBD from a reference material and CBD samples from three different suppliers A, B, and C. (C) A549-ACE2 cells were treated with indicated doses of CBD from three different suppliers followed by infection with SARS-CoV-2 at an MOI of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. EC50 values are indicated.

When isolated from its source plant, natural non-synthetic CBD is typically extracted along with other cannabinoids, representing the unavoidable residual complexity of natural products. To verify that CBD is indeed responsible for the viral inhibition, we analyzed a CBD reference standard as well as CBD from three different sources for purity using 100% quantitative NMR (qNMR). These sources included two chemical vendors (Suppliers A and B) and one commercial vendor that used natural materials (Supplier C). The striking congruence between the experimental 1H NMR and the recently established quantum-mechanical HiFSA (1H Iterative Full Spin Analysis) profiles observed for all materials confirmed that 1) the compounds used were indeed CBD with purities of at least 97% (Fig. 1B) and 2) congeneric cannabinoids were not present at levels above 1.0% (11). Analysis of these different CBD preparations in the viral A549-ACE2 infection a*say showed similar EC50s with a range from 0.6–1.8 μM likely reflecting the intrinsic biological variability of the a*say (Fig. 1C). No toxicity was observed for any of the CBD preparations at the doses used to inhibit viral infection (fig. S1 E–G).

CBD is often consumed as part of a C. sativa extract, particularly in combination with psychoactive THC enriched in marijuana plants. We therefore determined whether congeneric cannabinoids, especially analogues with closely related structures and polarities produced by the hemp plant, are also capable of inhibiting SARS-CoV-2 infection. Remarkably, only CBD was a potent agent, while limited or no antiviral activity was exhibited by the structurally closely related congeners that share biosynthesis pathways and form the biogenetically determined residual complexity of CBD purified from C. sativa: THC, cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabichromene (CBC), or cannabigerol (CBG) (Fig. 2 A–B; see Methods). None of these compounds were toxic to the A549-ACE2 cells in the dose range of interest (fig. S2). Notably, combining CBD with THC (1:1) significantly suppressed CBD efficacy consistent with competitive inhibition by THC.


image

Limited or no inhibition of SARS-CoV-2 infection by Cannabinoids other than CBD.
(A) A549-ACE2 cells were treated with indicated doses of various cannabinoids or a CBD/THC 1:1 mixture followed by infection with SARS-CoV-2 at an MOI of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. All cannabinoids tested were isolated from a hemp extract as described in Methods. (B) Chemical structures of cannabinoids and 7-OH CBD. (C) A549-ACE2 cells were treated with indicated doses of 7-OH CBD followed by infection with the SARS-CoV-2 at an MOI of 0.5. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. Representative data of CBD from Figure 1C (Supplier A) is used for comparison. EC50 values are indicated.

CBD is rapidly metabolized in the liver and gut into two main metabolites, 7-carboxy-cannabidiol (7-COOH-CBD) and 7-hydroxy-cannabidiol (7-OH-CBD). Although the levels of 7-COOH-CBD are 40-fold higher than 7-OH-CBD in human plasma, 7-OHCBD is the active ingredient for the treatment of epilepsy (14). Like CBD but unlike the other cannabinoids, 7-OH-CBD effectively inhibited SARS-CoV-2 replication in A549-ACE2 cells (EC50 3.6 μM; Fig. 2C) and was non-toxic to cells (fig. S2H). Analysis of blood plasma levels in healthy patients taking FDA-approved CBD (Epidiolex®) shows a maximal concentration (Cmax) for CBD in the nM range whereas 7-OH-CBD had a Cmax in the μM range, similar to that observed in cultured cells (15). These results suggest that CBD itself is not present at the levels needed to effectively inhibit SARS-CoV-2 in people. By contrast, the plasma concentrations of its metabolite 7-OH-CBD, whose Cmax can be increased several-fold by co-administration of CBD with a high-fat meal, are sufficient to potentially inhibit SARS-CoV-2 infection in humans (15).

CBD could be acting to block viral entry to host cells or at later steps following infection. As CBD was shown to decrease ACE2 expression in some epithelial cells including A549 (16), we first determined whether CBD suppressed the SARS-CoV-2 receptor in our A549-ACE2 overexpressing cells. No decrease in ACE2 expression was observed (Fig. 3A). Furthermore, analysis of lentiviruses pseudotyped with either the SARS-CoV-2 spike protein or the VSV glycoprotein (17) showed that antibody to the spike protein effectively blocked viral infection of the SARS-CoV-2, but not VSV-G expressing viruses. However, 10 μM CBD only partially inhibited cell entry by spike-expressing virus, suggesting that other mechanisms were largely responsible for its antiviral effects (Fig. 3B, and figs. S3 A and B). By contrast, antibodies to the spike protein effectively blocked viral infection of the SARS-CoV-2 but not VSV-G expressing viruses. Consistent with this, CBD was also effective at inhibiting SARS-CoV-2 spike protein expression in host cells even 2 hours after infection in the presence of antibodies to the spike protein to prevent reinfection during this time period (Fig. 3C,​,D).D). To a*sess whether CBD might be preventing viral protein processing by the viral proteases Mpro or PLpro, we a*sayed their activity in vitro (fig. S4). CBD did not affect the activity of either protease, raising the possibility that CBD targets host cell processes.

Now in the link visit this link https://www.ncbi.nlm.nih. .. es/PMC7987002/
+33   



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Top 10 most propped recently  1 month ago '19        #2
Anomic  topics gone triple plat - Number 1 spot x5
Props total: 69499 69 K  Slaps total: 10723 10 K
@
+28   

 1 month ago '19        #3
MP2019 
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You know damn well half of BX can’t / won’t read all that
+58   

 1 month ago '05        #4
4REAL  topics gone triple plat - Number 1 spot x2
Props total: 33213 33 K  Slaps total: 9425 9 K
That's good to hear, but with the "vaccines" on the marketplace, I doubt the government will ever allow for an alternative like this to be used as a "effective treatment" for the virus. They have banked their bread and butter on the EUA experimental "vaccines."

If there is enough studies to show that Cannabidiol does the job, it will be no more need for an EUA on the "vaccines" and will eliminate it's purpose. It's the same reason why they haven't approved Ivermectin as a treatment for the virus when there are thousands of studies showing that it inhibits the covid virus. At the end of the day, this is still bureaucracy.

The boxden christian covid vaccine cult-hood alliance don't understand that though. They think the experimental "vaccines" being pushed by the system is from the kindness of man with their best interest at heart, who are here to "save lives."
+19   

 1 month ago '15        #5
edub911 
Props total: 5762 5 K  Slaps total: 1068 1 K
Lets gooo
+2   

 1 month ago '11        #6
awww  topics gone triple plat - Number 1 spot x4
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weed cure this weed cure that, the sh*t these people are smoking is not weed!!!!!!!!!!!!!!! its fu*king not weeed!!!!!! its breed to make you high!!!!! its not breed to cure anything. now if it was the regular weed yes but the weed they smoking from the streets and dispensaries no, im just so sick of weed smokers man, yall be happy as fu*k when someone say its curing this and that so yall can justify your fu*king addiction crack head tendencies
-35   

Top 10 most propped recently  1 month ago '19        #7
Anomic  topics gone triple plat - Number 1 spot x5
Props total: 69499 69 K  Slaps total: 10723 10 K
 awww said
weed cure this weed cure that, the sh*t these people are smoking is not weed!!!!!!!!!!!!!!! its fu*king not weeed!!!!!! its breed to make you high!!!!! its not breed to cure anything. now if it was the regular weed yes but the weed they smoking from the streets and dispensaries no, im just so sick of weed smokers man, yall be happy as fu*k when someone say its curing this and that so yall can justify your fu*king addiction crack head tendencies
What if crack cures athletes foot??




Last edited by Anomic; 04-11-2021 at 04:11 PM..
+18   

 1 month ago '06        #8
mrep3 
Props total: 19425 19 K  Slaps total: 2310 2 K
 awww said
weed cure this weed cure that, the sh*t these people are smoking is not weed!!!!!!!!!!!!!!! its fu*king not weeed!!!!!! its breed to make you high!!!!! its not breed to cure anything. now if it was the regular weed yes but the weed they smoking from the streets and dispensaries no, im just so sick of weed smokers man, yall be happy as fu*k when someone say its curing this and that so yall can justify your fu*king addiction crack head tendencies
I know a girl that said she heard that the weed in Jamaica is trash. I had to explain to her that it’s not, it’s actually as pure as you can get she was so used to smoking lab sh*t that when she seen actual weed from yard she didn’t know any better
+28   

 1 month ago '17        #9
xcobr35715 
Props total: 1005 1 K  Slaps total: 309 309
 LuxG2 said
The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARSCoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.

Cannabidiol from the cannabis plant has potential to prevent and inhibit SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), a pandemic that has overtaken the world during the past year. SARS-CoV-2, related to severe acute respiratory syndrome-related coronavirus (SARS-CoV), is the seventh species of coronavirus known to infect people. These coronaviruses, which include SARS-CoV, 229E, NL63, OC43, HKU1, and MERS-CoV cause a range of symptoms from the common cold to more severe pathologies (1). Despite recent vaccine availability, SARS-CoV-2 is still spreading rapidly (2), highlighting the need for alternative treatments, especially for populations with limited access to vaccines. To date, few therapies have been identified that block SARS-CoV-2 replication and viral production.

SARS-CoV-2 is a positive-sense single-stranded RNA (+ssRNA) enveloped virus composed of a lipid bilayer and four structural proteins that drive viral particle formation. The spike (S), membrane (M), and envelope (E) are integral proteins of the virus membrane and serve to drive virion budding, while also recruiting the nucleocapsid (N) protein and the viral genomic RNA into nascent virions. Like SARS-CoV, SARS-CoV-2 primarily enters human cells by the binding of the viral S protein to the angiotensin converting enzyme 2 (ACE2) receptor (3–5), after which the S protein undergoes proteolysis by transmembrane protease, serine 2 (TMPRSS2) or other proteases into two non-covalently bound peptides (S1, S2) that facilitate viral entry into the host cell. The N-terminal S1 binds the ACE2 receptor, and the C-terminal S2 mediates viral-cell membrane fusion following proteolytic cleavage by TMRSS2 or other proteases. Depending upon the cell type, viral entry can also occur after ACE2 binding, independent of proteolytic cleavage (6–8). Following cell entry, the SARS-CoV-2 genome is translated into two large polypeptides that are cleaved by two viral proteases, MPro and PLPro (9, 10), to produce 15 proteins, in addition to the synthesis of subgenomic RNAs that encode another 10 accessory proteins plus the 4 structural proteins. These proteins enable viral replication, a*sembly, and budding. In an effort to suppress infection by the SARS-CoV-2 beta-coronavirus as well as other evolving pathogenic viruses, we tested the antiviral potential of a number of small molecules that target host stress response pathways.

One potential regulator of the host stress and antiviral inflammatory responses is cannabidiol (CBD), a member of the cannabinoid class of natural products (11). CBD is produced by Cannabis sativa (Cannabaceae; marijuana/hemp). Hemp refers to cannabis plants or materials derived thereof that contain 0.3% or less of the psychotropic tetrahydrocannabinol (THC) and typically have relatively high CBD content. By contrast, marijuana refers to C. sativa materials with more than 0.3% THC by dry weight. THC acts through binding to the cannabinoid receptor, and CBD potentiates this interaction (12). Despite numerous studies and many typically unsubstantiated claims related to CBD-containing products, the biology of CBD itself is unclear and specific targets are mostly unknown (11). However, an oral solution of CBD is an FDA-approved drug, largely for the treatment of epilepsy (13). Thus, CBD has drug status, is viable as a therapeutic, and cannot be marketed as a dietary supplement in the United States (11). Although limited, some studies have reported that certain cannabinoids have antiviral effects against hepatitis C virus (HCV) and other viruses (14).

To test the effect of CBD on SARS-CoV-2 replication, we pretreated A549 human lung carcinoma cells expressing exogenous human ACE-2 receptor (A549-ACE2) for 2 hours with 0–10 μM CBD prior to infection with SARS-CoV-2. After 48 hours, we monitored cells for expression of the viral spike protein (S). For comparison, we also treated cells over a similar dose range with an MLK inhibitor (URMC-099) previously implicated as an antiviral for HIV (12) and KPT-9274, a PAK4/NAMPT inhibitor (13) that our analysis suggested might reverse many changes in gene expression caused by SARS-CoV-2. All three inhibitors potently inhibited viral replication under non-toxic conditions with EC50s ranging from 0.2–2.1 μM (Fig. 1A). CBD inhibited SARS-CoV-2 replication in Vero E6 monkey kidney epithelial cells as well (fig. S1A). No toxicity was observed at the effective doses (fig. S1B). We also determined that CBD suppressed replication of a related beta-coronavirus, mouse hepatitis virus (MHV), under non-toxic conditions with an EC50 of ~5 μM using A549 cells that express the MHV receptor (A549-MHVR), indicating the potential for more broader viral efficacy (fig. S1C,D).





Fig. 1.
Cannabidiol (CBD) is a potent inhibitor of SARS-CoV-2 infection in vitro.
(A) A549 cells with ACE2 overexpression (A549-ACE2) were treated with indicated doses of CBD, KPT-9274, or URMC-099 followed by infection with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. EC50 values are indicated. (B) The 1H qNMR spectra of CBD from a reference material and CBD samples from three different suppliers A, B, and C. (C) A549-ACE2 cells were treated with indicated doses of CBD from three different suppliers followed by infection with SARS-CoV-2 at an MOI of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. EC50 values are indicated.

When isolated from its source plant, natural non-synthetic CBD is typically extracted along with other cannabinoids, representing the unavoidable residual complexity of natural products. To verify that CBD is indeed responsible for the viral inhibition, we analyzed a CBD reference standard as well as CBD from three different sources for purity using 100% quantitative NMR (qNMR). These sources included two chemical vendors (Suppliers A and B) and one commercial vendor that used natural materials (Supplier C). The striking congruence between the experimental 1H NMR and the recently established quantum-mechanical HiFSA (1H Iterative Full Spin Analysis) profiles observed for all materials confirmed that 1) the compounds used were indeed CBD with purities of at least 97% (Fig. 1B) and 2) congeneric cannabinoids were not present at levels above 1.0% (11). Analysis of these different CBD preparations in the viral A549-ACE2 infection a*say showed similar EC50s with a range from 0.6–1.8 μM likely reflecting the intrinsic biological variability of the a*say (Fig. 1C). No toxicity was observed for any of the CBD preparations at the doses used to inhibit viral infection (fig. S1 E–G).

CBD is often consumed as part of a C. sativa extract, particularly in combination with psychoactive THC enriched in marijuana plants. We therefore determined whether congeneric cannabinoids, especially analogues with closely related structures and polarities produced by the hemp plant, are also capable of inhibiting SARS-CoV-2 infection. Remarkably, only CBD was a potent agent, while limited or no antiviral activity was exhibited by the structurally closely related congeners that share biosynthesis pathways and form the biogenetically determined residual complexity of CBD purified from C. sativa: THC, cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabichromene (CBC), or cannabigerol (CBG) (Fig. 2 A–B; see Methods). None of these compounds were toxic to the A549-ACE2 cells in the dose range of interest (fig. S2). Notably, combining CBD with THC (1:1) significantly suppressed CBD efficacy consistent with competitive inhibition by THC.





Limited or no inhibition of SARS-CoV-2 infection by Cannabinoids other than CBD.
(A) A549-ACE2 cells were treated with indicated doses of various cannabinoids or a CBD/THC 1:1 mixture followed by infection with SARS-CoV-2 at an MOI of 0.5 for 48 hours. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. All cannabinoids tested were isolated from a hemp extract as described in Methods. (B) Chemical structures of cannabinoids and 7-OH CBD. (C) A549-ACE2 cells were treated with indicated doses of 7-OH CBD followed by infection with the SARS-CoV-2 at an MOI of 0.5. The cells were stained for spike protein and the percentage of cells expressing the spike protein in each condition was plotted. Representative data of CBD from Figure 1C (Supplier A) is used for comparison. EC50 values are indicated.

CBD is rapidly metabolized in the liver and gut into two main metabolites, 7-carboxy-cannabidiol (7-COOH-CBD) and 7-hydroxy-cannabidiol (7-OH-CBD). Although the levels of 7-COOH-CBD are 40-fold higher than 7-OH-CBD in human plasma, 7-OHCBD is the active ingredient for the treatment of epilepsy (14). Like CBD but unlike the other cannabinoids, 7-OH-CBD effectively inhibited SARS-CoV-2 replication in A549-ACE2 cells (EC50 3.6 μM; Fig. 2C) and was non-toxic to cells (fig. S2H). Analysis of blood plasma levels in healthy patients taking FDA-approved CBD (Epidiolex®) shows a maximal concentration (Cmax) for CBD in the nM range whereas 7-OH-CBD had a Cmax in the μM range, similar to that observed in cultured cells (15). These results suggest that CBD itself is not present at the levels needed to effectively inhibit SARS-CoV-2 in people. By contrast, the plasma concentrations of its metabolite 7-OH-CBD, whose Cmax can be increased several-fold by co-administration of CBD with a high-fat meal, are sufficient to potentially inhibit SARS-CoV-2 infection in humans (15).

CBD could be acting to block viral entry to host cells or at later steps following infection. As CBD was shown to decrease ACE2 expression in some epithelial cells including A549 (16), we first determined whether CBD suppressed the SARS-CoV-2 receptor in our A549-ACE2 overexpressing cells. No decrease in ACE2 expression was observed (Fig. 3A). Furthermore, analysis of lentiviruses pseudotyped with either the SARS-CoV-2 spike protein or the VSV glycoprotein (17) showed that antibody to the spike protein effectively blocked viral infection of the SARS-CoV-2, but not VSV-G expressing viruses. However, 10 μM CBD only partially inhibited cell entry by spike-expressing virus, suggesting that other mechanisms were largely responsible for its antiviral effects (Fig. 3B, and figs. S3 A and B). By contrast, antibodies to the spike protein effectively blocked viral infection of the SARS-CoV-2 but not VSV-G expressing viruses. Consistent with this, CBD was also effective at inhibiting SARS-CoV-2 spike protein expression in host cells even 2 hours after infection in the presence of antibodies to the spike protein to prevent reinfection during this time period (Fig. 3C,​,D).D). To a*sess whether CBD might be preventing viral protein processing by the viral proteases Mpro or PLpro, we a*sayed their activity in vitro (fig. S4). CBD did not affect the activity of either protease, raising the possibility that CBD targets host cell processes.

Now in the link




Head to Lee/Springfield Mass for official COVID relief package...not dispensaries..reserve a Dr appt @ beastcoastgas
-7   

 1 month ago '07        #10
andros06 
Props total: 1624 1 K  Slaps total: 533 533
 MP2019 said
You know damn well half of BX can’t / won’t read all that
I scrolled directly down to the comments to get the general jist before getting into all that. My god that's too much effort. I wanna be prepped if I'm gonna read all that.
+2   

 1 month ago '17        #11
WHATEVERMAN 
Props total: 14574 14 K  Slaps total: 1439 1 K
 awww said
weed cure this weed cure that, the sh*t these people are smoking is not weed!!!!!!!!!!!!!!! its fu*king not weeed!!!!!! its breed to make you high!!!!! its not breed to cure anything. now if it was the regular weed yes but the weed they smoking from the streets and dispensaries no, im just so sick of weed smokers man, yall be happy as fu*k when someone say its curing this and that so yall can justify your fu*king addiction crack head tendencies
The article was about CBD (one specific cannabinoid extracted from the Marijuana plant). Not one word was spoken about smoking weed.
+9   

 1 month ago '09        #12
messy marv stan  topics gone triple plat - Number 1 spot x62
Props total: 222128 222 K  Slaps total: 24949 24 K
 awww said
weed cure this weed cure that, the sh*t these people are smoking is not weed!!!!!!!!!!!!!!! its fu*king not weeed!!!!!! its breed to make you high!!!!! its not breed to cure anything. now if it was the regular weed yes but the weed they smoking from the streets and dispensaries no, im just so sick of weed smokers man, yall be happy as fu*k when someone say its curing this and that so yall can justify your fu*king addiction crack head tendencies








why dont you protset in front of there on 4/20 not because allegedly you hate weed but because of the prices


smh @ $125 for 7 of lemon skunk
+2   

 1 month ago '19        #13
ZigZag  topics gone triple plat - Number 1 spot x19
Props total: 29958 29 K  Slaps total: 8055 8 K
Subplot: This is why NY legalized the weed
+5   

 1 month ago '16        #14
Onetrubeing816 
Props total: 5467 5 K  Slaps total: 931 931
 4REAL said
That's good to hear, but with the "vaccines" on the marketplace, I doubt the government will ever allow for an alternative like this to be used as a "effective treatment" for the virus. They have banked their bread and butter on the EUA experimental "vaccines."

If there is enough studies to show that Cannabidiol does the job, it will be no more need for an EUA on the "vaccines" and will eliminate it's purpose. It's the same reason why they haven't approved Ivermectin as a treatment for the virus when there are thousands of studies showing that it inhibits the covid virus. At the end of the day, this is still bureaucracy.

The boxden christian covid vaccine cult-hood alliance don't understand that though. They think the experimental "vaccines" being pushed by the system is from the kindness of man with their best interest at heart, who are here to "save lives."
Wasn't their alot of people getting sick from taking that horse medicine ivermectin ...or am I mistaken

 1 month ago '19        #15
ym7171yea  topics gone triple plat - Number 1 spot x2
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+1   

 1 month ago '10        #16
lltreyll 
Props total: 3510 3 K  Slaps total: 1088 1 K
CBD is supposed to be the most medicinal aspect of weed....Goodluck getting much more than a strange buzz from extracted CBD though.

Speaking of getting a buzz or getting high from weed... All plants have a defense to them, and marijuana plants are no different..I've long believed that the consumption of weed and the effects of THC was intended to keep animals and whatever from not fu*kin around with weed plants...because the euphoric affect wasnt meant to be enjoyable...Meanwhile millions of people are addicted to consuming weed. Its strange.
-6   

 1 month ago '19        #17
zzxxccvvbb 
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This article is a preprint.
Preprints have not been peer reviewed.
To learn more about preprints in PMC see: NIH Preprint Pilot.

I'll react once it's reviewed
+2   

 1 month ago '19        #18
MP2019 
Props total: 9879 9 K  Slaps total: 1053 1 K
 andros06 said
i scrolled directly down to the comments to get the general jist before getting into all that. My god that's too much effort. I wanna be prepped if i'm gonna read all that.
100

 1 month ago '06        #19
Bilal  topics gone triple plat - Number 1 spot x10
Props total: 145870 145 K  Slaps total: 15174 15 K
Smoke just as much cbd as I do thc everyday.

3 zips bought





Last edited by Bilal; 04-11-2021 at 08:32 PM..
+2   

 1 month ago '04        #20
Houston2k3 
Props total: 541 541  Slaps total: 78 78
However, several issues require close examination before CBD can be considered or even explored as a therapeutic for COVID-19 (11). Although many CBD formulations are available on the market, they vary vastly in quality, the amount of CBD, and their pharmacokinetic properties after oral administration, which are mostly unknown. CBD is quite hydrophobic and forms large micellar structures that are trapped and broken down in the liver, thereby limiting the amount of drug available to other tissues after oral administration. The inactive carriers have a significant impact on clinically obtainable concentrations. As CBD is widely sold as a preparation in an edible oil, we analyzed flavored commercial hemp oils and found a CBD content of only 0.30% in a representative sample (fig. S12). The purity of CBD and, in particular, the composition of the materials labelled as CBD are also important, especially in light of our findings suggesting that other cannabinoids such as THC might act to counter CBD antiviral efficacy. This essentially eliminates the feasibility of marijuana serving as an effective source of antiviral CBD, in addition to issues related to its legal status.
+1   

 1 month ago '04        #21
d.c. supreme  topics gone triple plat - Number 1 spot x1
Props total: 28387 28 K  Slaps total: 1397 1 K
 ZigZag said
Subplot: This is why NY legalized the weed
cuomo just trying to save his job is all he ain't slick
+1   

 1 month ago '20        #22
RockyII 
Props total: 9030 9 K  Slaps total: 1201 1 K
 lltreyll said
CBD is supposed to be the most medicinal aspect of weed....Goodluck getting much more than a strange buzz from extracted CBD though.

Speaking of getting a buzz or getting high from weed... All plants have a defense to them, and marijuana plants are no different..I've long believed that the consumption of weed and the effects of THC was intended to keep animals and whatever from not fu*kin around with weed plants...because the euphoric affect wasnt meant to be enjoyable...Meanwhile millions of people are addicted to consuming weed. Its strange.
I actually prefer CBD (hemp) over actual THC... that THC gives you that high but for me, the CBD gives me more of a calming effect.. shuts my my brain up so I can sleep too. I smoke the weed THC at times, but I prefer the actual CBD hemp over the weed. But that’s just me... you experience may vary
+3   

 1 month ago '19        #23
Number5  topics gone triple plat - Number 1 spot x2
Props total: 12528 12 K  Slaps total: 6018 6 K
 ym7171yea said







+2   

Top 10 most propped recently  1 month ago '19        #24
Anomic  topics gone triple plat - Number 1 spot x5
Props total: 69499 69 K  Slaps total: 10723 10 K
 lltreyll said
CBD is supposed to be the most medicinal aspect of weed....Goodluck getting much more than a strange buzz from extracted CBD though.

Speaking of getting a buzz or getting high from weed... All plants have a defense to them, and marijuana plants are no different..I've long believed that the consumption of weed and the effects of THC was intended to keep animals and whatever from not fu*kin around with weed plants...because the euphoric affect wasnt meant to be enjoyable...Meanwhile millions of people are addicted to consuming weed. Its strange.
The same was said about Peyote. It's the only cactus with no kinda defense mechanism(no spikes on it). The psychedelic effect was meant to ward off predators like how chili peppers(and other hot peppers) used their hotness as a deterrent

But since we humans we can enjoy that sh*t like it's natural
+5   

 1 month ago '05        #25
Dun Language  topics gone triple plat - Number 1 spot x12
Props total: 94204 94 K  Slaps total: 25804 25 K
 mrep3 said
I know a girl that said she heard that the weed in Jamaica is trash. I had to explain to her that it’s not, it’s actually as pure as you can get she was so used to smoking lab sh*t that when she seen actual weed from yard she didn’t know any better
The weed in jamaica was good
It was nice and real dark green like spinach

The high was Nice and mello

bi*ch must be wanted some sour diesel
+1   



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