Farmers’ A1manac • Page 58

Ken · Jun 26, 2020

@Mr. Serotonin how's clamming?

Max_123 · Jun 26, 2020

Ken said:

@Mr. Serotonin how's clamming?

Def can't ask that

Max_123 · Jun 26, 2020

I'm gonna have pasta salad for the 3rd day in a row cause I made too much

lati · Jun 26, 2020

Sean Murphy said:

damn your day can only go down from here

Not unless I have another hot dog

jorbjorb · Jun 26, 2020

Ken said:

Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants and accounts for up to 40% of the plant's extract.[9] As of 2019, clinical research on cannabidiol included studies of anxiety, cognition, movement disorders, and pain, but there is insufficient high-quality evidence that it is effective for these conditions.[10][11]

Cannabidiol can be taken into the body in multiple ways, including by inhalation of cannabis smoke or vapor, as an aerosol spray into the cheek,[1][2] and by mouth. It may be supplied as CBD oil containing only CBD as the active ingredient (no included tetrahydrocannabinol (THC) or terpenes), a full-plant CBD-dominant hemp extract oil, capsules, dried cannabis, or as a prescription liquid solution.[4][11] CBD does not have the same psychoactivity as THC,[12][13] and may change the effects of THC on the body if both are present.[9][12][14][15] As of 2018, the mechanism of action for its putative biological effects has not been determined.[12][14]

In the United States, the cannabidiol drug Epidiolex was approved by the Food and Drug Administration in 2018 for the treatment of two epilepsy disorders.[16] Since cannabis is a Schedule I controlled substance in the United States,[17] other CBD formulations remain illegal to prescribe for medical use or to use as an ingredient in foods or dietary supplements.[18]
Medical uses[edit]
Epilepsy[edit]
See also: Charlotte's web (cannabis)
In 2018, CBD was FDA-approved (trade name Epidiolex) for the treatment of two forms of treatment-resistant epilepsy: Dravet syndrome and Lennox-Gastaut syndrome in children with refractory epilepsy.[19][20][21] The recommended daily dose of Epidiolex is 10 mg per kg body weight per day in epileptic children 2–5 years old.[4] While Epidiolex treatment is generally well tolerated, it is associated with minor adverse effects, such as gastrointestinal upset, decreased appetite, sleepiness and lethargy, and poor sleep quality.[19][20][21]

Other uses[edit]
Research on other uses for CBD includes several neurological disorders, but the findings have not been confirmed to establish such uses in clinical practice.[8][10][11][12][22][23][24] In October 2019, the FDA issued an advisory warning that the effects of CBD during pregnancy or breastfeeding are unknown, indicating that the safety, doses, interactions with other drugs or foods, and side effects of CBD are not clinically defined, and may pose a risk to the mother and infant.[25]

Side effects[edit]
Research indicates that cannabidiol may reduce adverse effects of THC, particularly those causing intoxication and sedation, but only at high doses.[26] Safety studies of cannabidiol showed it is well tolerated, but may cause tiredness, diarrhea, or changes in appetite as common adverse effects.[27] Epidiolex documentation lists sleepiness, insomnia and poor quality sleep, decreased appetite, diarrhea, and fatigue.[4]

Potential interactions[edit]
Laboratory evidence indicated that cannabidiol may reduce THC clearance, increasing plasma concentrations which may raise THC availability to receptors and enhance its effect in a dose-dependent manner.[28][29] In vitro, cannabidiol inhibited receptors affecting the activity of voltage-dependent sodium and potassium channels, which may affect neural activity.[30] A small clinical trial reported that CBD partially inhibited the CYP2C-catalyzed hydroxylation of THC to 11-OH-THC.[31] Little is known about potential drug interactions, but CBD mediates a decrease in clobazam metabolism.[32]

Pharmacology[edit]
Pharmacodynamics[edit]
Cannabidiol has low affinity for the cannabinoid CB1 and CB2 receptors,[33][34] although it can act as an antagonist of CB1/CB2 agonists despite this low affinity.[34] Cannabidiol may be an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain.[35] It also may act as an inverse agonist of GPR3, GPR6, and GPR12.[36] CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist.[37] It is an allosteric modulator of the μ- and δ-opioid receptors as well.[38] The pharmacological effects of CBD may involve PPARγ agonism and intracellular calcium release.[9]

Pharmacokinetics[edit]
The oral bioavailability of CBD is approximately 6% in humans, while its bioavailability via inhalation is 11 to 45% (mean 31%).[6][7] The elimination half-life of CBD is 18–32 hours.[8] Cannabidiol is metabolized in the liver as well as in the intestines by the cytochrome P450 enzymes CYP2B6, CYP2C19, CYP2D6, CYP2J2, and CYP3A4, and by the isoenzymes UGT1A7, UGT1A9, and UGT2B7.[39][40][41][4] CBD may have a wide margin in dosing.[23]

Pharmaceutical preparations[edit]
Nabiximols (brand name Sativex), a patented medicine containing CBD and THC in equal proportions, was approved by Health Canada in 2005 to treat central neuropathic pain in multiple sclerosis, and in 2007 for cancer-related pain.[42] In New Zealand, Sativex is "approved for use as an add-on treatment for symptom improvement in people with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication."[43]

Epidiolex is an orally administered cannabidiol solution. It was approved in 2018 by the US Food and Drug Administration (FDA) for treatment of two rare forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome.[16][18]

Chemistry[edit]
At room temperature, it is a colorless crystalline solid.[44] In strongly basic media and the presence of air, it is oxidized to a quinone.[45] Under acidic conditions it cyclizes to THC,[46] which also occurs during pyrolysis (smoking).[47] The synthesis of cannabidiol has been accomplished by several research groups.[48][49][50]

Biosynthesis[edit]

Cannabidiol and THC biosynthesis[51]
Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the next to last step, where CBDA synthase performs catalysis instead of THCA synthase.[52]

Isomerism[edit]
See also: Tetrahydrocannabinol § Isomerism, and Abnormal cannabidiol

Cannabidiol's 7 double bond isomers and their 30 stereoisomers edit][/paste:font]
Efforts to isolate the active ingredients in cannabis were made in the 19th century.[53] CBD was studied in 1940 from Minnesota wild hemp[53][53] and Egyptian Cannabis indica resin.[54][55] The chemical formula of CBD was proposed from a method for isolating it from wild hemp.[53] Its structure and stereochemistry were determined in 1963.[56]

Society and culture[edit]
Names[edit]
Cannabidiol is the generic name of the drug and its INN.[57]

Food and beverage[edit]

An example of beverages claiming to contain CBD in a Los Angeles grocery.
Food and beverage products containing CBD were introduced in the United States in 2017.[dubious – discuss][58] Hemp seed ingredients which do not naturally contain THC or CBD (but which may be contaminated with trace amounts on the outside during harvesting) were declared by the US Food and Drug Administration (FDA) as Generally recognized as safe (GRAS) in December 2018. CBD itself has not been declared GRAS, and under U.S. federal law is illegal to sell as a food, dietary supplement, or animal feed.[18] State laws vary considerably as non-medical cannabis and derived products have been legalized in some jurisdictions in the 2010s.

Similar to energy drinks and protein bars which may contain vitamin or herbal additives, food and beverage items can be infused with CBD as an alternative means of ingesting the substance.[59] In the United States, numerous products are marketed as containing CBD, but in reality contain little or none.[18][60] Some companies marketing CBD-infused food products with claims that are similar to the effects of prescription drugs have received warning letters from the Food and Drug Administration for making unsubstantiated health claims.[18][61] In February 2019, the New York City Department of Health announced plans to fine restaurants that sell food or drinks containing CBD, beginning in October 2019.[62]

Plant sources[edit]
Selective breeding of cannabis plants has expanded and diversified as commercial and therapeutic markets develop.[18] Some growers in the US succeeded in lowering the proportion of CBD-to-THC to accommodate customers who preferred varietals that were more mind-altering due to the higher THC and lower CBD content.[63] In the US, hemp is classified by the federal government as cannabis containing no more than 0.3% THC by dry weight. This classification was established in the 2018 Farm Bill and was refined to include hemp-sourced extracts, cannabinoids, and derivatives in the definition of hemp.[64]

Non-psychoactivity[edit]
CBD does not appear to have any psychotropic ("high") effects such as those caused by ∆9-THC in marijuana, but is under preliminary research for its possible anti-anxiety and anti-psychotic effects.[10][11][13] As the legal landscape and understanding about the differences in medical cannabinoids unfolds, experts are working to distinguish "medical marijuana" (with varying degrees of psychotropic effects and deficits in executive function) from "medical CBD therapies", which would commonly present as having a reduced or non-psychoactive side-effect profile.[11][13][65]

Various strains of "medical marijuana" are found to have a significant variation in the ratios of CBD-to-THC and are known to contain other non-psychotropic cannabinoids.[66] Any psychoactive marijuana, regardless of its CBD content, is derived from the flower (or bud) of the genus Cannabis. As defined by US federal law, non-psychoactive hemp (also commonly termed "industrial hemp"), regardless of its CBD content, is any part of the cannabis plant, whether growing or not, containing a ∆9-tetrahydrocannabinol concentration of no more than 0.3% on a dry-weight basis.[67] Certain standards are required for legal growing, cultivating, and producing the hemp plant. The Colorado Industrial Hemp Program registers growers of industrial hemp and samples crops to verify that the dry-weight THC concentration does not exceed 0.3%.[67]

I need to be high to read this.

Ken · Jun 26, 2020

alina said:

Not unless I have another hot dog

Renee · Jun 26, 2020

can anyone read the first company under "hosting"?
first project i've had in 3 months and off to a great start

https://iot-analytics.com/wp/wp-content/uploads/2019/01/I4.0-Vendor-Landscape-v4.5.jpg

iCarly Rae Jepsen · Jun 26, 2020

Renee said:

can anyone read the first company under "hosting"?
first project i've had in 3 months and off to a great start
View attachment 54123
https://iot-analytics.com/wp/wp-content/uploads/2019/01/I4.0-Vendor-Landscape-v4.5.jpg

alibaba

Ken · Jun 26, 2020

Yeah, I agree with Ian.

Renee · Jun 26, 2020

iCarly Rae Jepsen said:

alibaba

Dirty Sanchez · Jun 26, 2020

AMD not in microchips there smh.

Ken · Jun 26, 2020

Dirty Sanchez said:

AMD not in microchips there smh.

Renee · Jun 26, 2020

Dirty Sanchez said:

AMD not in microchips there smh.

my job is to just get the names into excel. i didn't make the picture

but do you work for them? i'm gonna need the name of Dir of Marketing soon and all contact info

Ken · Jun 26, 2020

Renee said:

my job is to just get the names into excel. i didn't make the picture

but do you work for them? i'm gonna need the name of Dir of Marketing soon and all contact info

https://www.linkedin.com/in/john-m-... was named Chief,sales teams to drive success.

Dirty Sanchez · Jun 26, 2020

Ken said:

Intel can eat s**+!

Sean Murphy · Jun 26, 2020

alina said:

Not unless I have another hot dog

Ken · Jun 26, 2020

ComedownMachine said:

This is A1

Renee · Jun 26, 2020

Ken said:

https://www.linkedin.com/in/john-m-taylor-cmo#:~:text=John Taylor was named Chief,sales teams to drive success.

damn, got logged out of my boss' account.

K0ta · Jun 26, 2020

ComedownMachine said:

This is A1

Sean Murphy · Jun 26, 2020

CLOSE the goddamn bars jfc

Borat 2: Vengeance · Jun 26, 2020

Sean Murphy said:

CLOSE the goddamn bars jfc

Seriously what’s a bar that can’t serve alcohol

Sean Murphy · Jun 26, 2020

Borat 2: Vengeance said:

Seriously what’s a bar that can’t serve alcohol

I assume what they mean is things will be outdoor or to-go which is still encouraging all the same people to still visit.

iCarly Rae Jepsen · Jun 26, 2020

Borat 2: Vengeance said:

Seriously what’s a bar that can’t serve alcohol

Nothing tastes better than a good glass of water

Sean Murphy · Jun 26, 2020

iCarly Rae Jepsen said:

Nothing tastes better than a good glass of water

there are times when this is very true

Borat 2: Vengeance · Jun 26, 2020

iCarly Rae Jepsen said:

Nothing tastes better than a good glass of water

Rhetorical question buddy

Log in or Sign up

Farmers’ A1manac • Page 58

entrusted Supporter

Nope. Supporter

Nope. Supporter

formerly spaghettti Supporter

7 rings Prestigious

entrusted Supporter

dry clean only Prestigious

run away with me Platinum

entrusted Supporter

dry clean only Prestigious

Prestigious Prestigious

entrusted Supporter

dry clean only Prestigious

entrusted Supporter

Prestigious Prestigious

merry crisis Platinum

entrusted Supporter

dry clean only Prestigious

wrap yourself in petals for armor.

merry crisis Platinum

Fan of senior hounds Prestigious

merry crisis Platinum

run away with me Platinum

merry crisis Platinum

Fan of senior hounds Prestigious

Log in or Sign up

Farmers’ A1manac • Page 58

Useful Searches

entrusted Supporter

Nope. Supporter

Nope. Supporter

formerly spaghettti Supporter

7 rings Prestigious

entrusted Supporter

dry clean only Prestigious

run away with me Platinum

entrusted Supporter

dry clean only Prestigious

Prestigious Prestigious

entrusted Supporter

dry clean only Prestigious

entrusted Supporter

Prestigious Prestigious

merry crisis Platinum

entrusted Supporter

dry clean only Prestigious

wrap yourself in petals for armor.

merry crisis Platinum

Fan of senior hounds Prestigious

merry crisis Platinum

run away with me Platinum

merry crisis Platinum

Fan of senior hounds Prestigious