#TRPV1. TRPM8 | Explore Tumblr posts and blogs

allcbdblog · 3 years ago

Text

Tetrahydrocannabivarin (THCV)

THCV is a cannabinoid found in marijuana. It has been revealed to have anti-inflammatory and neuroprotective residential properties, along with being an effective therapy for discomfort alleviation Tetrahydrocannabivarin (THCV) is a cannabinoid that is discovered in Cannabis. It is structurally comparable to tetrahydrocannabinol (THC), the main psychoactive compound in Marijuana, however has different pharmacology. THCV has been revealed to minimize food consumption and also body weight and also might serve for the therapy of obesity. Additionally, it shows up to have analgesic impacts without producing psychotropic side effects connected with other cannabinoids such as Delta9-tetrahydrocannabinol( D9-THC) or cannabidiol, which are both present at high degrees guest at Cannabis. Cannabinoids have actually additionally just recently come to be prominent amongst professional athletes that use them to boost their performance by lowering muscle mass exhaustion during exercise. Although these compounds create comparable physiological feedbacks when provided systemically, they act through unique molecular targets within the mind that show up to mediate a few of their activities. The CB1 receptor is a G protein-coupled receptor situated on presynaptic terminals throughout the main nerve system and also peripheral cells. It has been recognized as the primary moderator for cannabinoid-induced alterations in synaptic transmission as well as natural chemical launch at both excitatory and also inhibitory synapses. In contrast, anandamide acts mostly through its cognate receptors, which are members of the short-term potential vanilloid subfamily of ion networks. These consist of TRPV1, TRPA1, and also TRPM8. Anandamide also binds non-cannabinoid related receptors consisting of PPARs, peroxisome proliferators activated receptor; 5HT2A serotonin receptor, as well as adenosine A( 1) receptor.

What is THCV.

Cannaclear THCV item is a cannabinoid located in marijuana. t is structurally similar to THC but has a various psychedelic impact. THCV is thought to have anti-inflammatory and analgesic results. It might additionally have positive impacts on fat burning and diabetes. Extra research study is needed to figure out the full healing potential of THCV. The primary distinction in between THC and THCV is that THCV does not create any kind of euphoria or "high" feeling when taken in. This implies it can be made use of as a choice for individuals that are incapable to endure the high generated by cigarette smoking cannabis. Furthermore, unlike many cannabinoids, THCV shows up to do not have psychotropic homes; nevertheless, some researches recommend that THCV might generate sedation.

What are the results of THCV?

There is some evidence that THCV might work for weight loss. It has actually been shown to increase fat metabolic process in computer mice and rats, as well as lower body mass index in humans. Additionally, it was discovered to have anti-inflammatory homes comparable to CBD. Nevertheless, these findings were only observed at high dosages. There is also initial research suggesting that THCV can assist with rest conditions such as sleeping disorders and also obstructive rest apnea. This effect appears to take place via a mix of its anxiolytic task as well as sedative action on GABA receptors in the brain's limbic system. The results are dose-dependent; greater dosages show up more probable to generate signs related to anxiety or clinical depression.

Just how is THCV made use of?

THCV is available as an oil or powder as well as can be taken in by mouth or smoked. It might likewise be evaporated, however this method calls for a high-powered device to remove the complete effect of the compound. The effects are reported to last for 4-- 6 hrs after consumption. Inhalation takes about thirty minutes before working. As with any other marijuana product, it is essential that you know exactly how your body reacts to THCV so you do not enter trouble. If you have no idea what you're doing, stay with vaping. To find out more on utilizing THCV in various means click on this link.

What are the threats of THCV?

Tetrahydrocannabivarin (THCV) is a cannabinoid discovered in Cannabis. It is a homolog of tetrahydrocannabinol (THC), the key psychedelic compound in Cannabis. THCV has been revealed to be effective in reducing the psychoactive impacts of THC, such as anxiety as well as paranoia, as well as may additionally have various other benefits, such as increasing bone density and also reducing weight gain. Nevertheless, there are presently no researches on its long-lasting safety or effectiveness for any clinical problem. Cannabinoids can communicate with each other when taken with each other, so it's important that you do not take them at the same time. As an example, some people experience sleepiness after taking CBD oil alone; however, this does not imply they will experience sleep problems when taking both CBD and THC items concurrently. Actually, lots of research subjects that took a placebo reported sensations of increased wakefulness while intoxicated of tetrahydrocannabinol.

Conclusion.

Tetrahydrocannabivarin (THCV) is a cannabinoid located in Marijuana. It is a homolog of tetrahydrocannabinol (THC), the main psychoactive compound in Cannabis. THCV has actually been shown to function as a CB1 receptor antagonist, implying that it obstructs the results of THC. This could make THCV a helpful medication for the treatment of addiction to THC or marijuana.

#guest at Cannabis

0 notes

samsaintjames · 3 years ago

Text

Okay, so I weird tangent here considering this post... and I wanted to originally put this in the tags - but my rambling is too long.

BUT warm water is not very effective for that particular purpose. You gotta use cold water.

Here's the physiological reason: Because of TRPM8 channels (yeah look, ion channels are my speciality okay?) - which are cold sensitive (in contrast to like TRPV1 and 2 which are heat sensitive [TRPV1 also responds to capsaicin, which is why chili peppers feel hot]) - and expressed in muscles; relevant here: also in those muscles that control the bladder and there seems to be a connection.

You can thank me later... or not. And I'm absolutely not responsible for what you people do with that knowledge.

And if you don't believe me just saying that: here's the paper where they demonstrate it in rats https://pubmed.ncbi.nlm.nih.gov/25843641/

World of Warcraft tweets

273 notes · View notes

greenkeepery · 5 years ago

Text

The Science Behind the Best Cream for Back Pain Relief

You know the feeling. You’re blazing through your workout when, suddenly, that nagging twinge in your back grabs your attention. Or you worked hard in the yard all weekend, but come Monday morning, your back muscles won’t let you forget it. Most everyone will need relief from back pain and discomfort at some point. In fact, over 80% of adults will experience back pain during their lives.[1] When you need back pain relief, and you’re searching for a back pain cream you can get over-the-counter, you want to be absolutely sure that what you find is the best pain relief cream there is. CBDMEDIC

back pain ointment is what you’re looking for.

Why Is CBDMEDIC Back Pain Cream the Best?

There are dozens of over-the-counter pain-relief creams and ointments out there. But many of them are simply generic “muscle rubs,” and not tailored pain-relief formulas. Some of them contain topical NSAIDs (non-steroidal anti-inflammatory drugs). We’ve all heard about the risks of taking NSAIDs orally, such as liver, kidney, and digestive system damage. Topical NSAID preparations have a much lower risk of side effects; however, some physicians think we should exercise the same precautions about using topical NSAIDs as are necessary with the oral versions.[2]

If you’re looking for the best cream for back pain, one that’s both safe and effective, with the convenience of buying it over-the-counter, then we’ve got your back! CBDMEDIC

Back & Neck Pain Relief Ointment is made from powerful yet gentle plant-based components. Its well-balanced, synergistic formula designed to give you the best topical pain relief there is, without a prescription.

The Topical Cream and Ointment Advantage

You know you want an ointment or cream for back pain relief, but do you know all the benefits of using a high-quality topical product? First, it’s an instinctive response to want to rub where it hurts. Just think back to when you tumbled over as a kid or to any strains and sprains you’ve had as an adult. And the powerful ingredients in CBDMEDIC

back pain cream smell great! The distinctive scent of menthol and camphor (more about them later) are probably familiar to you. The scent in itself can signal a sense of comfort that starts to help your back muscles relax.

Not only is using a cream intuitive and familiar, it’s also a highly efficient mode of administration because it bypasses a process known as first-pass metabolism. When you take something for pain relief by mouth, it has to pass through the liver and the digestive system first, which means you lose a great deal of its effect before it even gets into your bloodstream to address where you actually hurt. This doesn’t happen with a topical cream. Applying a cream directly to your skin, therefore, can make the ingredients more effective as the active ingredients do not need to enter the bloodstream, instead going to work at the point of pain– as long as the cream is formulated right, that is!

Let’s take a closer look at the science behind these ingredients and what makes CBDMEDIC

back pain cream the best cream for back pain relief.

Menthol

Menthol is an organic, natural compound that is derived from wild mint or peppermint leaves. In fact, it’s what gives plants of the mint family their distinctive smell and taste. Menthol has been used topically for its pain relieving and refreshing properties for a couple of millennia,[3] but it’s only been in the last couple of decades that scientists have discovered how it works.

Menthol is a natural analgesic[4] and anesthetic[5], which means it’s going to be very soothing for your aches and pains. In addition, menthol is what’s known technically as a counterirritant. Menthol interacts with specific receptor sites in our nervous system known as TRPM8 channels (or transient receptor potential melastatin 8). These nerve receptors are involved in our perception of temperature, and because of their famous association with menthol, they even go by the name Cold and Menthol receptors.[6]

When used in a topical cream, menthol produces a cooling sensation on the skin at the source of pain. In reality, menthol doesn’t lower the temperature of your skin. It creates a sensation of cooling by interacting with the TRPM8 nerve receptors. According to Gate Theory, which is a way of understanding how we experience pain,[7] certain non-painful stimuli will cause nerve “gates” to close shut in the presence of painful stimuli, with the result that the sensation of pain is prevented from reaching our brains. This means the cooling sensation of menthol competes with and counteracts pain sensations, resulting in effective topical pain relief.

On top of all these pain-relieving activities, menthol also dilates blood vessels in the skin where it’s applied.[8] This improves blood flow to the area of injury or inflammation, which helps bring relief and supports healing.

Menthol has been widely studied for its pain-relieving properties. Menthol is easily absorbed through the skin. It’s one of the major active ingredients in CBDMEDIC

back pain cream, along with other important ingredients that work together to give you the best topical pain relief you can find.

Camphor

Camphor is another organic, natural compound that can be easily absorbed topically to soothing effect. Camphor is extracted from the bark of the evergreen tree Cinnamonun camphora, or camphor laurel. Like menthol, its cousin in pain relief, camphor has a distinctive aroma as a result of all the powerful plant terpenes it produces.

Camphor has a long history of topical use for many purposes, including its antibacterial and antifungal effects.[9] It also has anti-inflammatory properties,[10] and is approved by the US Food and Drug Administration (FDA) for use as a topical analgesic and anesthetic.[11] One study that looked at camphor and menthol in combination with other natural oils, found they were effective at relieving mild to moderate pain and inflammation when applied to the skin several times a day consistently over time[12] Another study showed that camphor itself was effective at relieving back pain.[13] Camphor has also been shown to have an anti-inflammatory effect in an animal model used to study arthritis.[14] It’s soothing to rub into your muscles and can relax muscle cramps and spasms.[15]

In a similar way to menthol, camphor acts as a counterirritant by producing both cold and warm sensations when applied in a topical cream. This means it competes with and counteracts sensations of pain before they can reach the brain, allowing us to experience the pleasure of pain relief. Camphor also increases blood flow in the skin and to muscles. As with menthol, increasing blood flow to an area of inflammation or injury helps promote pain relief and supports healing.[16]

As well as being a counterirritant, camphor may work its pain-relieving magic by directly interacting with certain receptor sites in our nervous system known as TRPV1 (transient receptor potential vanilloid 1) and TRPA1 (transient receptor potential ankyrin 1). Both TRPV1 (also known as the capsaicin receptor) and TRPA1 are intricately involved in how we experience pain.[17]

Camphor and menthol are tried and true allies to have on your pain-relieving team. Together, they are a sure-fire duo for giving you the best topical pain relief there is. But there’s more! CBDMEDIC

back pain cream also includes other high-performing, natural ingredients which provide additional benefits.

Argan Oil

Argan oil is an edible (but don’t eat our creams!), nutrient-rich oil that comes from the kernels of the Argan tree, which is native to Morocco. It has been used for centuries in topical applications, for culinary purposes, and is known for its cosmetic moisturizing capabilities.

Coconut Oil (MCT Oil)

All-natural coconut oil is an edible oil derived from the meat of fresh coconuts. Coconut oil consists of approximately 60 percent MCTs, which stands for medium-chain triglycerides. The body can use and process MCTs more readily than other types of fats. Coconut oil contains fatty acids and polyphenol compounds that are gentle and nourishing for the skin.

Frankincense Oil

Frankincense comes from the resin of the Boswellia tree, which is found mainly in the mountainous regions of India, Africa and the Middle East. It has been used for thousands of years in Ayurvedic medicine,[18] the traditional medicine of India.

Myrrh Oil

Myrrh is well known for its pleasant fragrance, Frankincense and myrrh are often paired in our imaginations because of their complimentary benefits, and that’s why you’ll find them together in the best topical creams!

Honeysuckle Oil

The honeysuckle plant has been used historically in Traditional Chinese Medicine for a variety of reasons including its soothing and fragrant qualities.

Jojoba Oil

Jojoba oil is what’s known as a carrier oil. It is able to moisturize in a similar way to our skin’s own natural oils without blocking the skin pores. Jojoba oil is readily absorbable, and highly effective at carrying the other topical healing ingredients with it.

Get Back to the Activity of Life

You don’t want to miss out on your favorite pursuits, or even on tackling more yard work! If you’re looking for quick, safe, and effective back pain relief without a prescription, try the most effective cream available with extra strength Camphor and Menthol for back pain and a soothing moisturizing effect. CBDMEDIC has the answer you’re looking for with our science-based best cream for back pain.

Useful Tips

If you don’t feel substantial relief after using this cream three times a day for seven days consult with your health care provider

Review the ingredients before you use CBDMEDIC

back pain cream in case you are sensitive or have an allergy to any of them.

If you’re using CBDMEDIC

back pain cream for the first time, apply it to a small area of your skin to begin with and wait 30 minutes before applying it to a larger area.

Don’t use this cream on any area of your skin that is broken, burnt, or has a rash.

Wash your hands after each application to avoid accidently rubbing your eyes or face, which may lead to irritation.

References

https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Low-Back-Pain-Fact-Sheet

https://www.practicalpainmanagement.com/treatments/topical-nonsteroidal-anti-inflammatory-drugs-nephrotoxicity-there-safer-option?page=0,1

https://www.sciencedirect.com/science/article/abs/pii/S0190962207007554

https://pubmed.ncbi.nlm.nih.gov/11897159/

https://pubmed.ncbi.nlm.nih.gov/18593637/

https://www.ncbi.nlm.nih.gov/books/NBK5238/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009371/

https://pubmed.ncbi.nlm.nih.gov/27131832/

http://www.ijcasereportsandimages.com/archive/2013/002-2013-ijcri/001-02-2013-hamidpour/ijcri-00102201311-hamidpour-full-text.php#ref9

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629446/

https://www.fda.gov/drugs/status-otc-rulemakings/rulemaking-history-otc-camphorated-oil-drug-products

https://pubmed.ncbi.nlm.nih.gov/25553684/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968782/

https://pubmed.ncbi.nlm.nih.gov/20353012/

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.1414

https://pubmed.ncbi.nlm.nih.gov/25451841/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6725586/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309643/

<!– –>

The post The Science Behind the Best Cream for Back Pain Relief appeared first on Greenkeepery.

source https://greenkeepery.com/the-science-behind-the-best-cream-for-back-pain-relief/?utm_source=rss&utm_medium=rss&utm_campaign=the-science-behind-the-best-cream-for-back-pain-relief

0 notes

caalamus · 4 years ago

Link

Caalam.us

#Caalamus #New York #NY #Beats #Drums #Bass #Synthesizer #Synth #Reason #PunkClock #Video #Videography

0 notes

bookpiofficial · 5 years ago

Text

Thermo-TRP Channels in Pain Sensation: An Overview | Chapter 03 | Modern Advances in Pharmaceutical Research Vol. 3

The perception of temperature is a major component of sensory experience of animal and human organisms. A sensitive response of the nervous system to changes in temperature is of predominant importance for homeo-therms to maintain a stable body temperature. Recent investigations in central and peripheral thermosensitivity have emphasized the importance of temperature-activated transient receptor potential (TRP) cation channels and they are being ardently pursued as targets for analgesic drug discovery. They are the largest group of sensory detectors expressed in nerve terminals and pain receptors activated by temperature and provide information about thermal changes in the environment. These temperature sensitive or thermo-TRP channels (TRPA1, TRPM8, TRPV1, TRPV2, TRPV3 and TRPV4) have been characterized to date that exhibit sensitivity to increases or decreases in temperature as well as to chemical substances that elicit similar hot or cold sensations. The thermal thresholds of many thermo-TRP channels are known to be modulated by extracellular mediators, released by tissue damage or inflammation. Antagonists or blockers of these channels are likely as promising targets for new analgesic drugs at the periphery and central levels and thus, controlling the modulation of thermo-TRP channels by inflammatory mediators and ligands may be a useful alternative strategy in developing novel analgesics.

Author(s) Details

Merab G. Tsagareli Laboratory of Pain and Analgesia, Beritashvili Center for Experimental Biomedicine, Tbilisi 0160, Georgia.

View Volume: http://bp.bookpi.org/index.php/bpi/catalog/book/133

#Analgesia #antinociception #cold pain #heat pain #hyperalgesia #sensory neurons #nociception

0 notes

beastofeasto-blog · 7 years ago

Text

Delights Part 1

I promised fried food and fried food I have brought.

Tonight, I made doughnuts while my cousin made onion bhaji. We had them with a tomato-based aubergine curry and some lightly spiced spinach and onions that isn’t saag. I also made a raita.

I can’t quite tell you how the onion bhaji was made because my cousin was following her own recipe, but they came out very nicely. They were about a quarter of the size of the behemouths served at our local favourite curry house, and had an excellent ratio of crisp outside and tender/crumbly inside.

I, however, assembled the raita that went alongside them and Let Me Tell You, the key component here, that takes it from just a cucumber and yoghurt slodge into a thing of beauty, is one of my favourite flavours full stop.

To make the raita

1) Toast about 2 tbsp whole cumin seeds. You could do this in a dry pan, but why do that if you’re going to be making onion bhajis also? Just toast them in the frying oil. You’ll want a tea strainer sieve to do this. Just place the spices in, and hold them under the oil until they smell just wonderful.

2)Remove from the oil and put into a mortar and pestle, and grind until quite fine. Now here comes the fu part. Take a whole clove of garlic and bash it in, along with a pinch each salt and sugar. Optionally, add in some chilli. ideally fresh, but dried is good, and dried then toasted along with the cumin is excellent. Mash well until you’ve achieved a paste. This is the stuff of dreams, and can be used in many places, but to my mind the best is on little brochettes of meat, such as lamb or beef, cooked on the grill. Or, brushed onto flatbreads fresh from a tandoor.

3)Anyway. Take your paste and combine with about 3 cups of greek-style yoghurt. Stir well.

4) Now, take an English cucumber, about a foot long is good, then roughly peel it, and cut it into cubes. You can do this by slicing it into three cylinders, then slicing each cylinder into planks rather than discs, and each plank into cubes. Mix in, and add however much mint you like. Fresh leaves, shredded finely. Dried mint actually does work here (and more or less nowhere else outside the teapot) .A good starting measure is a loose handful for the agnostic, two for the addict. (If using dry, then a heaped tablespoon is good).

And you’re done. This yoghurt dip isn’t just great with fried things, it’s also (surprise surprise!) good with curries, especially ones that are on the more fiery end of things. This helps for three key reasons

1) Yoghurt has fat in it, and capsaicin, the compound most associated with the heat in chillis, happily dissolves in fat, but isn’t so ready to dissolve in water.

2) Capsaicin works by interacting with TRPV1 heat receptors that to give a sensation of heat without something at high temperature being nearby. Equally, menthol, a compound found in high concentration in mint, interacts with a different, cooling receptor, TRPM8. This potentially helps ease the discomfort of the heat of the chillis.

3) Menthol is an analgesiac — that is, it numbs pain.

What purpose, one may ask, do the cucumbers have in raita, then? They’re there because they taste good and add textural variance, of course!

#food food chemistry science chillis onion bhaji fried food channukah hannukah raita yoghurt

0 notes

ianmkeenan · 8 years ago

Text

Marijuana and Gastrointestinal Cancers

Marijuana and Gastrointestinal Cancers:

Types of Gastrointestinal Cancers

Anal, Bowel and Small Intestine

Gallbladder Cancer

NETs, GIST & Stomach

Liver Cancer

Esophageal Cancer

Pancreatic Cancer

Medical Studies

Study 1

Study 2

Study 3

What is Gastrointestinal cancer? Also known as GI cancer, it’s a group of cancers that wreak havoc on the digestive system. It’s currently the most common form of cancer today.

There are many types of GI Cancer affecting various parts of the digestive system. Thankfully, science is revealing that marijuana can help with them all. Read below to learn more.

The different types of gastrointestinal cancers

To understand marijuana’s impact on gastrointestinal cancel, you must first understand the different types.

Anal, Bowel and Small Intestine Cancers

Colorectal cancer is another common name for bowel cancer. Within the body’s digestive system, the bowel is the part that connects the anus to the stomach. It consists of both the rectum and the large intestine (large colon).

Anal, Bowel and Small Intestine Cancers – Image powered by Cancer.gov

The diseased growth that tends to develop within the large bowel is known as bowel cancer. Most of these cancers develop from polyps. These are small growths inside the rectum or colon. They resemble small cherries on their stalks or tiny spots on the lining of the bowel.

If these polyps are removed early, the chances of developing bowel cancer are greatly reduced. Colorectal cancer is one of the most common internal cancers. However, anal cancer and small intestine cancer are both relatively rare.

Gallbladder Cancer

Cancer of the biliary tract is known as gallbladder cancer. In Western societies, this form of cancer is quite rare. But, it’s not uncommon at all in Asia-Pacific countries.

By the time most people are diagnosed with cancer of the biliary tract, the cancerous tumor is too big to be surgically removed. In other cases, it’s spread so much throughout other parts of the body, it’s simply too late to stop it from spreading any further.

Gallbladder Cancer – Images powered by Medindia.net

Therefore, only about 10%-30% of all biliary tract cancer sufferers are eligible to try surgery as a possible cure for the disease. And, those who do opt for surgery have a very low survival rate. Only about 18.5% of people with cancer of the biliary tract survive up to five years.

For those who aren’t eligible for possible life-saving surgery, physicians recommend chemotherapy. However, there’s no guarantee this will prolong life.

NETs, GIST & Stomach Cancer

The stomach is responsible for receiving food and storing it as it’s delivered by the esophagus. Once broken down, the stomach, a muscular sack-like organ, passes it along to the small bowel. That’s where the nutrients are absorbed into the body’s bloodstream.

NETs, GIST & Stomach Cancer – Image powered by Cancer.net

Most stomach cancers are rare diseases that develop in the mucosa-lining cells. These forms of cancers are called adenocarcinoma of the stomach. It can take years to notice symptoms of gastric cancer, also known as stomach cancer. It tends to develop slowly.

Liver Cancer

One of the bodies most important key organs in the liver. It’s responsible for producing bile. This is what breaks down food’s fats so the bowel can absorb the contents. The liver also helps to produce proteins and fats, which helps with the clotting of blood.

Liver Cancer – Images powered by Medindia.net

Glycogen is stored in the liver. It’s made out of sugars and helps to fuel the body. The liver is also responsible for helping process poisons, toxins, some medications, and alcohol so they can be removed from the body altogether.

Esophageal Cancer

The body’s esophagus acts as a pipe for food. It carries the food from the mouth down into the stomach. There are three main sections of the esophagus:

Upper esophagus

Middle esophagus

Lower esophagus

Anywhere along the esophagus’ length, esophageal cancer can develop.

Esophageal Cancer – Image powered by Thehealthsite.com

The esophagus wall contains glands which produce mucus. This mucus is what helps food easily slide down during swallowing. Glands can produce adenocarcinoma of the esophagus, producing cancer. In Western countries, cancers of the esophagus are the most common types.

Pancreatic Cancer

Your pancreas is a lumpy, thin gland. It’s positioned between the spine and the stomach. The about 13-centimeter long gland is joined to the small bowels first part (the duodenum) by the pancreatic duct.

Two major roles are played by the pancreas within the body:

Produce insulin – This is what controls how much sugar is in your blood

Produce enzymes – This helps to digest your food

Pancreatic Cancer – Image powered by Cancer.gov

Pancreatic cancer starts within the pancreatic duct’s lining. From there, it spreads throughout the pancreas’ body, then travels on into the nerves and blood vessel surrounding the pancreas. This obstructs the duct of the bile. Cancer of the pancreas can be spread through the lymphatic system, bloodstream or other body parts.

In some cases, cancerous pancreas tumors can be surgically removed. However, if cancer has already spread to outlying organs and tissues by the time it’s detected, this may not be possible.

Medical Studies on Marijuana and Gastrointestinal Cancers

Numerous studies suggest marijuana has a positive effect on gastrointestinal cancers. Below are three.

Study 1: High-CBD Sativa Extract Inhibits Colon Carcinogenesis

Colon cancer has grown to become a major issue related to public health. Many cancer patients have been able to cope due to useful cannabis-based medicines and treatments. One Romano B et al. Phytomedicine (2014) study, investigates the effects of high-cannabidiol (CBD) containing standardized marijuana sativa extract (CBD BDS) on colorectal cancer cell production and in vivo models of colon cancer experimentations.

The production was also evaluated in healthy colonic cells and colorectal carcinoma (DLD-1 and HCT116) using MTT assay. Binding of CBD BDS was evaluated based on its ability to displace human cannabinoid CB1 and CB2 receptors from [(3)H]CP55940.

Cannabidiol – Image powered by Doctorcbdoil.com

CBD BDS effects were examined in vivo, on the tumors, polyps and preneoplastic lesions induced by azoxymethane (AOM), a carcinogenic agent, and in a xenograft model representing cancer of the colon in lab mice.

Scientists found the CBD and CBD BDS reduced cancer cell production in tumoral cells. However, it didn’t affect the healthy ones. The CBD BDS effects were counteracted by the receptor antagonists CB1 and CB2.

In antagonist manner that’s CB1-sensitive only, pure CBD helped reduce the production of cancer cells. CBD BDS was much more sympathetic in binding assays for both CB1 and CB2 receptors than pure CBD. Yet, in vivo, AOM-induced preneoplastic lesions, polyps, and tumor growth were all reduced in the colon cancer xenograft model using CBD BDS.

Conclusion: High CBD Sativa inhibits the production of colorectal cancer cells and reduces color carcinogenesis via the activation of CB1 and CB2 receptors.

Study 2: CBG Inhibits Colon Carcinogenesis

Cannabigerol (CBG) is a cannabinoid that doesn’t get you high. It engages with specific targets that take part in carcinogenesis. Specifically, it:

Blocks transient receptor potential (TRP) M8 (TRPM8) and 5-hydroxytryptamine receptor 1A (5-HT1A) receptors

Activates TRPA1, TRPV1 and TRPV2 channels

Inhibits endocannabinoids’ re-uptake

In a study conducted by Borrelli F et al. Carcinogenesis (2014), scientists investigated colon tumourigenesis can be stopped with CBG. They evaluated colorectal cancer (CRC) cell growth using:

3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide

3-amino-7-dimethylamino-2-methylphenazine hydrochloride assays

CBG’s in vivo antineoplastic effect was assessed in models of mice with colon cancer. The following was found:

CRC cells expressed CB1, CB2, TRPM8, mRNA, 5-HT1A, TRPA1, TRPV1 and TRPV2

CBG promoted stimulated production of ROS, reduced cell growth in CRC cells, upregulated CHOP mRNA and apoptosis

Cannabigerol – image powered by Greendorphin.com

A CB2 receptor antagonist helped further increased activations of TRPA1, TRPV1 and TRPV2 channels. The effect CBG had on cell growth was completely independent of all of these channel activations. These effects were mimicked by other channel blockers, such as TRPM8. But, 5-HT1A did not mimic these effects.

TRPM8 silenced cells saw reductions in the CBG-affected cell growth and CHOP mRNA expression. Xenograft tumor growth was inhibited in vivo, along with the colon carcinogenesis that was chemically induced.

Conclusion: CBG slows the growth of colon cancer in vivo. It also inhibits colon cancer cell growth selectively, much like that of TRPM8 antagonists. Researches related to this study believe CBG should be used in the prevention and cure of colorectal cancer.

Study 3: Cannabis Use & Upper Aerodigestive Tract Cancers

In the past, some have suggested that cannabis may be a cancer-causing agent. But, these findings, according to researchers, have been very inconsistent. A population based controlled study was conducted, Hashibe M et al. Cancer Epidemiol Biomarkers Prev (2006). It studied the association between the risks of the upper aerodigestive tract and lung cancers in Los Angeles, CA and the use of marijuana.

The controlled study included:

1,212 people with cancer

1,040 people who were cancer-free

The cases were matched by neighborhoods, genders, and ages. Each person was quizzed using a standardized questionnaire. They used joint years to express cumulative cannabis use. In other words, smoking one joint each day was represented by 1 joint-year.

0 notes

stuffxthree-blog · 11 years ago

Text

Cold Keeps You Warm

Biology concepts – thermoregulation, TRPM8, vasoconstriction, brown adipose tissue, agonists/antagonists

Pep-O Mint was the first Lifesaver flavor, invented

in 1912. This was followed quickly by the Lifesaver

car in 1918. Built on a Dodge truck chassis, the

important word was dodge, since the car didn’t have

a windshield and the driver had to stick his head out

the side window to see ahead.

Let’s do a demonstration. Borrow a peppermint lifesaver from a friend (well, not borrow really - you’re not going to give it back). Place it between your teeth, so you can close your lips around it and suck air in through the hole (this will be the control for our experiment).

Now put the candy in your mouth like normal and suck on it for a minute or two – don’t chew it up. Swallow to get the saliva out of your mouth and take out the candy. Now take in a long slow breath of air. How does it feel? Did the room get colder in the last two minutes?

If you are like most people, the air feels colder in your mouth now that you've eaten menthol (peppermint). Just like capsaicin can make hot things seem hotter via TRPV1, the cold sensing channel we talked about last week, TRPM8, can make room temperature air seem colder.

The TRPM8 cold sensing ion channel is important for keeping our body temperature in a normal range. Just like TRPV1 senses when we are too warm and initiates cooling mechanisms, TRPM8 tells us we are cold and institutes procedures to make us warmer. One way is to stimulate vasoconstriction, so less heat is lost from the blood through our skin. I’m sure you have noticed that your skin is paler when you are out in the cold. This is from vasoconstriction limiting the amount of blood moving into the surface vessels.

When your core temperature varies from your skin

temperature by too much, TRPM8 will institute

heat conserving and/or generating mechanisms.

For heat conservation, more of the blood (left

cartoon) that goes the skin can be shunted through

the capillaries before it gets to the surface. This

helps reduce the amount of heat loss via radiation

of the heat in the blood. On the right is the effect of

the arrector pili muscles. When cold, they contract

and raise the hairs, trap air, and therefore trap body

heat against the skin so less heat is loss. The

contraction also mounds up the skin – goosebumps.

TRPM8 can also stimulate shivering and the burning of fat to generate warmth. Through the sensations and reactions of TRPV1 and TRPM8, animals learn to maintain a more or less constant body temperature, seeking out temperatures that are good for physiology and avoiding temperatures that would change their core temperature by too much. This was shown in a series of studies described in a 2013 paper, where mice without temperature sensing receptors TRPV1 and/or TRPM8 would not avoid hot or cold temperatures and were prone to hyperthermia and or hypothermia.

So how does the TRPM8 channel sense cold? We saw that with TRPV1 the heat induced a conformation change that caused the channel to open and calcium to flow in and start a neural action potential. Could cold induce a conformation change as well? Maybe. What was seen in a 2011 study was that TRPM8 neurons started firing when the temperature dropped to 28.4˚C (83 ˚F). As the temperature dropped, the neurons would fire more and more strongly, so it could act as a thermostat.

When the temperature dropped severely (to 10˚C) the core temperature changed little, but skin temperature dropped considerably. The TRPM8 thermostat was targeted to keeping the organs and brain warm, not the skin. It accomplishes this by diverting heat via the blood away from the skin. A 2012 study showed that TRPM8 antagonists brought a systemic hypothermia, but repeated use of the antagonist reduced the magnitude of the temperature drop – so unlike most TRPV1antagonists (that bring bad hyperthermia), TRPM8 antagonists might be helpful in medicine.

We don’t yet know how cold activates TRPM8. In

warmth, the channel is closed. With cooler

temperature or menthol (M), the channel is open,

but we don’t know if cold achieves this by a

conformation change. If really cold, the regulatory

proteins break away and the channel can’t work.

So TRPM8 is active in a range of temperatures.

But this still doesn’t answer the questions as to how TRPM8 can detect cool temperatures. It may or may not be a conformation change, but what does occur is an alteration in the apparenttemperature threshold of the neuron. The cold temperature should inhibit firing (cold slows metabolism and chemical activity), but here it increases the metabolism and biochemical activities. TRPM8 makes the neuron seem warmer so that the firing is easier, and this transfers information that the area is in fact colder! That’s an exception.

However it manages the feat, TRPM8 is important for keeping mammals warm. It might even help you lose weight. Chronic cold stimulates TRPM8 all the time, and this ramps up your heat production. A 2012 study showed that for mice, chronic cold could actually prevent them from becoming obese.

Heat production takes energy, and burning more energy helps you lose weight. But there is an important balancing act at work here. Our fat also protects us against losing too much heat in the cold. Look at whales, they have a layer of blubber all over their body to insulate them from the cold water. It has been shown that people with an even layer of fat all over their body make good cold weather swimmers, like Lynne Cox, who swam from her perfectly good boat to the shores of Antarctica and across the Bering Strait in 4˚C (40˚F) water.

On the other hand, bactrian camels keep their fat limited to two humps (one for dromedaries) in order to prevent against having too much insulation in their desert environment. Camels need to be able to dissipate lots of heat. And no, the humps aren’t for storing water! Remember we said that one of the great things about fat is that you can store lots of energy in a small space precisely because can be stored without water.

In brown adipose tissue, there are ATP synthase

proteins (for making ATP) and uncoupling proteins

(for generating heat) in the inner mitochondrial

membrane. When cold, the number of UCP proteins is

increased, as is the number of mitochondria. About

65% of the energy of the proto gradient formed by the

respiratory chain can be converted to ATP by the ATP

synthase. But using the UCP to allow protons back in

means that 100% of the energy is changed to

heat, no ATP is made.

It seems that TRPM8 can stimulate the burning of fat to produce heat. We talked about this before with capsaicin as well. Brown adipose tissue has more mitochondria and more of a protein called UCP1 (uncoupling protein). UCP separates mitochondrial energy burning from ATP production; all the energy goes to making heat.

A 2014 study showed that chronic cold makes brown fat AND white fat upregulate UCP and generate more mitochondria. It makes white fat more like brown fat and this means that more fat is burned. In mice, this chronic cold is enough to keep them from becoming obese, even on a high glucose diet. So if you want to stay skinny, turn your thermostat way down all year round.

The study that showed that chronic cold kept mice from getting fat wasn’t as cruel as it may sound. They didn’t keep the mice at cold temperature all the time, they used a chemical that could mimic the cold and make the TRPM8 channels fire all the time. What did they use? Menthol.

This is a good place to point out the similar exception for TRPV1 and TRPM8. They are both proteins that can be activated by both environmental factors and by chemicals. We saw that TRPV1 is activated by capsaicin and other chemicals. The opening of the channel and firing of the neurons in response to these chemicals was interpreted exactly the same as if the neurons were exposed to damaging heat.

There are many agonists for TRPM8, similar to TRPV1.

In fact, some things that activate TRPM8 also activate

TRPV1. An interesting one is the synthetic agonist called

icilin. It is thousands of time more active on TRPM8 than

cool temperatures. However, it binds to TRPM8 in a

completely different way as compared to menthol and

cool temperatures.

With TRPM8, menthol (in mints) and some other chemicals open the ion channels just as cool/cold temperatures would, and our brains trick us into thinking the mouth or skin is colder than it really is. That’s what is behind our lifesaver trick at the beginning of the post. The air wasn’t any colder; your brain makes you think it was.

Menthol is a terpene alkaloid contained in plants of the genus Mentha (mint, from the Greek mintha). This genus includes 25 species of aromatic herbs, such as peppermint, spearmint, and pennyroyals. Most mints can be and are used in making foods and drinks, but the pennyroyals also contain toxic compounds that will induce liver failure and kill you.

At low concentrations in the mouth or on skin, menthol produces a pleasant cooling sensation, but higher concentrations produce burning, irritation and pain (this has to do with how it activates TRPV1, TRPV3, TRPM8, and TRPA1, depending on the concentration).

In the oral cavity, a small amount of menthol actually desensitizes TRPV1 activation by heat and capsaicin, so chili peppers might not seem so spicy. Biochemical evidence shows that menthol sparks a release of glutamate from neurons. But an increase in glutamate neurotransmitter can actually stop the type C nociceptive neurons from firing (an inhibitory neurotransmitter in this case).

Pennyroyal is a member of the mentha genus (left). It, like

many plants (right image is orange mint), has been used in

medicine. It can be ground and drunk with water to settle a

sick tummy or to induce perspiration. However, pennyroyal

has to be used carefully. In addition to menthol, it contains a

chemical called pulegone. Too much pulegone and here

come the seizures, organ failure and death. Don’t confuse

the two mints.

At this same time, menthol (or other TRPM8 agonists) will sensitize TRPM8 receptors, the combination of these two results means that sucking in air after a wintergreen or peppermint candy will make the air seem colder, but might also make a hot cup of coffee seem cold as well.

I think the only way to resolve these ideas is to start a controlled experiment. What do you predict would happen if you froze a chili pepper and then took a bite? How about eating peppermint laced with capsaicin, or a strong peppermint flavored tea that has been heated to near boiling? Who will win out, TRPM8 or TRPV1?

It may not be so easy to figure out. The agonists and antagonists of the TRPs can have effects on multiple receptors and the effects can be different at different concentrations. Menthol sensitizes TRPM8, but if the temperature is above 37˚ C (98˚ F) it actually makes TRPV3, a heat sensor, more active (2006).

Camphor comes from some species of laurel trees (left), as well as

from some herbs of the mint family, like camphor basil (right).

Dried rosemary leaves are up to 20% camphor. Camphor has

been used for many things, including as a flavoring in asian

sweets, an analgesic, an insect repellent, and a rust proofing

agent. I find it hard to rectify those uses with one another.

Take oil of wintergreen in BenGay for example. We showed that it was a TRPV1 agonist, so it could induce analgesia by counter irritation. But it is also a TRPM8 agonist. In the oral cavity at lower concentrations than used in BenGay, it activates TRPM8 and desensitizes TRPV1. The lifesaver trick will work with peppermint, spearmint, and wintergreen flavors; they all activate TRPM8.

And then there’s camphor. Like menthol, camphor is terpenoid chemical. Camphor can make things seem cool (by activating and sensitizing TRPM8), but it’s more complicated. It actually potentiates both heat and cold sensations. A 2013 study shows that it can sensitize or potentiate TRPV1 (painful hot) and TRPM8 (non-painful cool). Camphor can even activate the noxious cold sensor TRPA1 that we will talk about in a couple of posts. This means that it can be analgesic or painful, warming and cooling.

It becomes even more confusing when you realize that camphor activates TRPM8, just like menthol, but can inhibit the activation of TRPM8 by menthol. Weird, right? Well, consider this – Vick's VapoRub contains menthol and camphor as its active ingredients. Next week, we'll investigate how they can work together to open your nose and make you feel both warm and fuzzy while they cool and invigorate you at the same time.

Pogorzala LA, Mishra SK, & Hoon MA (2013). The cellular code for mammalian thermosensation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33 (13), 5533-41 PMID: 23536068

Rossato M, Granzotto M, Macchi V, Porzionato A, Petrelli L, Calcagno A, Vencato J, De Stefani D, Silvestrin V, Rizzuto R, Bassetto F, De Caro R, & Vettor R (2014). Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production. Molecular and cellular endocrinology, 383 (1-2), 137-46 PMID: 24342393

Ma S, Yu H, Zhao Z, Luo Z, Chen J, Ni Y, Jin R, Ma L, Wang P, Zhu Z, Li L, Zhong J, Liu D, Nilius B, & Zhu Z (2012). Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity. Journal of molecular cell biology, 4 (2), 88-96 PMID: 22241835

Selescu T, Ciobanu AC, Dobre C, Reid G, & Babes A (2013). Camphor activates and sensitizes transient receptor potential melastatin 8 (TRPM8) to cooling and icilin. Chemical senses, 38 (7), 563-75 PMID: 23828908

For more information or classroom activities, see:

Thermoregulation –

http://beyondcoldwaterbootcamp.com/en/thermo-regulation

http://www.unm.edu/~lkravitz/Article%20folder/thermoregulation.html

http://dwb.unl.edu/teacher/nsf/c01/c01links/www.science.mcmaster.ca/biology/4s03/thermoregulation.html

https://worldofbiology.wikispaces.com/biol+2+classroom+presentations

http://www.pbslearningmedia.org/resource/lsps07.sci.life.reg.heatexchange/blood-flow-and-thermoregulation/

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&ved=0CDwQFjAE&url=http%3A%2F%2Fbio.classes.ucsc.edu%2Fbio131%2FThometz%2520Website%2F9%2520-%2520Thermoregulation%2520Lab%25202012.pdf&ei=zSIzU6SuFqPEyQGZ4oD4CA&usg=AFQjCNERS9ye-sPF7qZM-dJHUsFPQ031Tw&sig2=xLwl_fcQ3rIxKcZiLictmw

http://www.life.umd.edu/classroom/bsci338m/Lectures/Temperature.html

https://www.khanacademy.org/science/mcat/organ-systems/muscular-system/v/thermoregulation-by-muscles

https://www.youtube.com/watch?v=kg7QdpOug2Y

http://www.nsta.org/publications/news/story.aspx?id=53687

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=16&ved=0CEgQFjAFOAo&url=http%3A%2F%2Fwww.tarleton.edu%2F~jblevins%2Fexercise%2520physiology%2FSpring%252009%2Fpowers7_ppt_Chap12%2520%255BRead-Only%255D%2520%255BCompatibility%2520Mode%255D.pdf&ei=HSMzU-ToHaSHygGerwE&usg=AFQjCNHxnlMTdNoOKd1p9lJrSyv6yew6Jg&sig2=fsvfEpvq9j0LTxOVaSYQwQ

http://www.studyblue.com/notes/note/n/ch-40-hwpdf/file/9213703

http://vce-unit1and2biology.wikispaces.com/thermoregulation

http://en.wikioffuture.org/Dissertation_Research:_Olfactory_Modulation_of_Thermoregulation_and_Flight_in_Moths

http://hyperphysics.phy-astr.gsu.edu/hbase/thermo/heatreg.html

https://www.youtube.com/watch?v=TSUCdLkI474

http://people.seas.harvard.edu/~jones/cscie129/pages/health/thermreg.htm

https://www.stanford.edu/group/stanfordbirds/text/essays/Temperature_Regulation.html

https://www.mdc-berlin.de/26954638/de/research/research_teams/temperature_detection_and_thermoregulation/Research?cntx=40550329

#zoology #TRPV1. TRPM8 #thermoregulation #obesity #menthol #exception #camphor #brown adipose tissue #animal

0 notes

bookpiofficial · 5 years ago

Text

TRP Channels in Physiological Nociception and Pain | Chapter 01 | Modern Advances in Pharmaceutical Research Vol. 3

The Transient Receptor Potential (TRP) channel superfamily is comprised of a large group of cation-permeable channels, which display an extraordinary diversity of functions from sensory signaling to animal behaviors. These channels are ‘cellular sensors’ that respond to changes in the cellular environment, including temperature, stretch/pressure, chemicals, oxidation/reduction, osmolarity and pH, and of spices, venoms and toxins. The role of TRPs will be further elucidated in complex diseases of the nervous, intestinal, renal, urogenital, respiratory and cardiovascular systems. Although the physiological functions of most TRP channels are not well known, their wide distribution in cellular membranes indicates that the biological functions and activation mechanisms for these channels are diverse and important. In this paper we review our recent findings of activation different TRP channels evoked by chemical irritants such as cinnamon aldehyde and mustard oil for TRPA1, menthol for TRPM8 and capsaicin for TRPV1 by a battery of behavioral tests.

Author(s) Details

Ivliane Nozadze Laboratory of Pain and Analgesia, Beritashvili Center for Experimental Biomedicine, 0160 Tbilisi, Georgia.

Merab G. Tsagareli Laboratory of Pain and Analgesia, Beritashvili Center for Experimental Biomedicine, 0160 Tbilisi, Georgia.

View Volume: http://bp.bookpi.org/index.php/bpi/catalog/book/133

#Allodynia #analgesia #antinociception #cold pain #heat pain #hyperalgesia #sensory neurons

0 notes

ianmkeenan · 8 years ago

Text

Why raw cannabis is the ultimate superfood

Let’s take a step back in time to a world where hemp and cannabis freely abounded. Just one hundred years ago hemp (cannabis sativa with only trace levels of THC) was a common agricultural crop whose seeds and fibre were used for our own nutrition, that of the animals we consumed, and to make everything from clothing, to rope and paper.

Without realising it, our ancestors were receiving a daily boost of vital nutrients, antioxidants, essential fatty acids, vitamins and healthy protein. It’s also possible, if they consumed the hemp leaves or flowers containing cannabinoids, they were giving their own endocannabinoid system a healthy boost.

Of course, back then, people didn’t know they had an endocannabinoid system, let alone that it could be maintained through their diet. Despite the ancient wisdom of Hippocrates, “let food be thy medicine and medicine be thy food,” the idea that consuming vitamins and minerals found in food can prevent illness is a fairly modern one.

Are We Cannabis Deficient?

Fast forward to the present day and the ubiquitous presence of hemp in our lives is a distant memory, pushed out into the nutritional hinterlands by opposing economic and political interests. But could it be that our health has suffered as a result?

Ours is a society plagued ever more by illness and disease, many of which are ailments rarely encountered in the past. Autoimmune disease, degenerative neurological disorders, autism and growing levels of cancer are just some of the conditions dogging our developed nations. As with anything, no one factor can be pinpointed, but amongst the obvious suspects such as stress, pollution and side effects of medication, a deficiency in the nutrients found in hemp might also play a part.

This theory gathers weight when we consider the theory of Clinical Endocannabinoid Deficiency. Humans and all other vertebrates have an endocannabinoid system – a complex network of receptors and cannabis-like chemical compounds called endocannabinoids that interact to bring balance or homeostasis to our bodies and minds. Everything from our immune system, sleep, appetite, bone growth, reproduction, pain, and mood are modulated by the endocannabinoid system.

But according to the theory developed by Neurologist and Researcher Dr Ethan Russo, this fine tuning system can become deficient, resulting in a host of malaises many of which could be considered modern day conditions. These include IBS, fibromyalgia, migraines, MS and potentially many more. Russo also suggests that supplementing our bodies with nutrients found in the cannabis plant can help to boost the endocannabinoid system and in turn alleviate the symptoms associated with the deficiency. He is specifically referring to the special molecules in cannabis called cannabinoids, in particular THC and CBD, which in their own unique ways stimulate the endocannabinoid system.

Raw Hemp and Cannabis Are Dietary Essentials, Says Doctor

But what if consuming hemp and cannabis on a regular basis were just like taking any other health supplement? And why not take it a step further – shouldn’t we consider the cannabis plant as just another fruit, vegetable or herb that promotes balanced health?

That’s just what Dr William Courtney, one of the world’s most vocal advocates of juicing raw cannabis, believes. While an undoubted fan of the cannabis plant in general, Dr Courtney suggests that the health giving benefits are enhanced by eating the leaves and flowers in their unheated, natural state. That’s because freshly picked cannabis contains the acid precursors of the cannabinoids we know so well, THC and CBD.

Why does this matter? For anyone taking THC for health reasons, the psychoactive effect that comes from being heated can be hard to handle, whereas THCa has no psychoactive effect and can as a result be consumed in much higher doses. The non-psychoactive question doesn’t apply to CBD and CBDa as neither cause a high, but Dr Courtney believes that refraining from heating either compound preserves more of their therapeutic benefits.

He says he has observed health improvements in many of his patients, including his own wife Kristen who had a litany of health problems ranging from lupus, childhood rheumatoid arthritis, interstitial cystitis, and endometriosis. At one point Kristen had been on a cocktail of 40 different medications each day, none of which had managed to control her debilitating symptoms. Under Dr Courtney’s guidance she began juicing cannabis, which she says has saved her life. Not only that, after being told she was infertile, she is now the proud mother of three healthy children, having juiced cannabis throughout her pregnancies.

youtube

Despite Dr Courtney and Kristen’s apparent successes, scientifically much less is known about the pharmacological effects of THCa and CBDa. Scientists do know that they do not bind with the endocannabinoid receptors, perhaps eliciting their effects on the body through other mechanisms such as the TRPA1, TRPV1, TRPM8, and GPR55 receptors.

CBDa in particular has been seen to interact with the 5–HT1A serotonin receptor, possibly explaining why it reduces nausea, as well as inhibiting the pro-inflammatory COX-2 (ciclooxigenase-2) enzyme. Preclinical studies on rodents have also found CBDa to have antitumoral activity in breast cancer cells.

Dr Courtney has staked his reputation on the importance of including these acid cannabinoids in the food we eat saying, “there is no doubt that these cannabinoid acids are probably the most important critical essential element in our diet.” He recommends juicing the leaves and flowers from one plant a day, an amount far in excess of that available to the common consumer.

Want to go raw, but not sure what to do next?

This leaves most of us unable to access these potentially valuable sources of health giving nutrients. That’s where Raw Hemp Oil extracts comes in. As more people become interested in consuming raw cannabis, raw hemp and raw food in general, a growing number of companies are offering cannabis extracts containing the raw plant material alone or in combination with the heated cannabinoids. In the end, it’s a matter of choice, trial and error. At Endoca we find that some of our clients prefer our Raw Hemp range, while others prefer our standard CBD oil extracts that have been through the heat process.

But if you are lucky enough to live in a part of the world where cultivation for personal use is legal – why not get planting and enjoy the natural wonders of raw cannabis and hemp in your juices, smoothies and salads.

We’d love to hear about your experiences. Do you juice raw cannabis or hemp? Have you tried Endoca’s Raw Hemp Oil range? Tell us your thoughts in the comments section below.

The post Why raw cannabis is the ultimate superfood appeared first on ENDOCA.

0 notes

ianmkeenan · 8 years ago

Text

Why raw cannabis is the ulimate superfood

Are We Cannabis Deficient?

Raw Hemp and Cannabis Are Dietary Essentials, Says Doctor

youtube

Want to go raw, but not sure what to do next?

We’d love to hear about your experiences. Do you juice raw cannabis or hemp? Have you tried Endoca’s Raw Hemp Oil range? Tell us your thoughts in the comments section below.

The post Why raw cannabis is the ulimate superfood appeared first on ENDOCA.

0 notes

stuffxthree-blog · 11 years ago

Text

Everybody Wants To Be Cool

Biology concepts – TRPM8 cold sensor, menthol, evolution, cold pleasure

The old ads for menthol cigarettes are fascinating, from a biology point of view. The “cool” and the “refreshing” aspects were reflected by using spring and summer outdoor pictures, most often with lots of cool water. At the end of today’s post, we see why this was so. We also see an African American, since menthol cigarettes were targeted much more strongly urban African Americans. They were newer smokers and in typically hotter environments, so the coldness and soothing abilities of the menthol were great selling points.

In 1924, Lloyd “Spud” Hughes patented the menthol cigarette. Not a big deal in the beginning, Hughes sold his patent to a cigarette manufacturer who marketed them as Spud cigarettes in 1927. They became the fifth largest seller, although there still wasn’t much in the way of profit. Kool cigarettes came along in 1933 and advertised the menthol casket nails as “soothing to the throat” and claimed they were actually medicinal.

The menthol cooled the feel of the smoke in the mouth and throat (much more next week on hos menthol feels cool). Menthol made it feel as though you weren’t sucking hot smoke into your lungs. And menthol deadened the discomfort that cigarettes could generate by irritating the lining of the throat and lungs.

These days, almost 90% of cigarettes contain some menthol, even if they don’t advertise themselves as menthol cigarettes. Why? The “cool” factor lends itself to novice smokers, while the throat analgesia appeals to the seasoned addict. But that may not be the main reason. A study from 2004 showed that menthol slows the metabolism of nicotine.

Slowing the metabolism of nicotine, menthol results in nicotine staying in the system longer and at greater concentrations - just perfect for developing a physical addiction. This, combined with the ability to comfortably smoke more cigarettes because of the slight throat numbing and apparent cooling of hot smoke would encourage more consumption, more addiction, and therefore more profit.

There is now (2013-2014) a push by the US Food and Drug Administration to ban or regulate menthol cigarettes. Did you know that menthol addition to shampoo is federally regulated but its addition to cigarettes is not? Let’s look at some of the reasons a change is being considered.

The tobacco plant has supplied cells that are used to show the danger of menthol cigarettes. I just love that. But tobacco has been involved in science in other ways as well. New efforts are underway to have genetically modified tobacco produce medicines or biodisel. And the tobacco mosaic disease actually led to the discovery of viruses and the coining of the word “virus.” This same virus was instrumental in establishing the fields of virology, plant virology and all of molecular biology.

A 2013 series of experiments showed that menthol-containing cigarette smoke is more toxic to cells than non-mentholated cigarette smoke. Menthol alone had no toxic effect on the cells, so it is the combination of menthol and cigarette smoke that kills cells at a higher rate. In the most delicious irony imaginable, the two cell types that the researchers used to monitor cell death after smoke exposure were human lung cells and tobacco plant cells!!!

Additional recent evidence suggests that menthol interacts with the nicotine receptor in the brain. Brody and his co-workers showed that menthol cigarette smoke up regulates the number of nicotine receptors in the brain more than regular cigarette smoke. This might explain why it is harder for menthol cigarette smokers to quit smoking and why more of them fail in their efforts to quit.

Another 2013 study showed that menthol decreased the activity of the nicotine receptor, so that more nicotine was necessary to reach the same level of activation. Once again, this would contribute to a physical addiction. Just a bit of information if you are considering taking up the habit - the “cool” factor and refreshing cold of mentholated smoke just may contribute to your death.

So sensing cool or cold has its place in biology and in society. Chili peppers are sensed as burning hot because they just happen to bind to and activate the TRPV1 heat sensing ion channel – it’s the biological joke being played on us that we have talked about before. TRPV1 a receptor that reacts to both environmental (temperature, pH) conditions and food substances.

On the other end of the scale is the sense of cold. Do organisms sense cold like they sense heat? Isn’t cold just a lack of heat, so that a feeling of cold is just a lack of activation of TRPV receptors? Nope. There are receptors specifically designed to sense cool or cold. Are there exceptions in cold sensing like there were for heat? You should know that answer by now.

Melastatin was the first TRPM protein discovered. The name comes from melanin (the pigment in skin and hair cells) and statin, which means to stop. It was important because it could stop the invasion of tumors of melanin producing cells. We call this maliganant melanoma, one of the deadliest cancers. Tumors with more melastatin were less aggressive and invasive, while those with little melastatin killed patients much sooner.

We learned recently that there are six different TRPV cation channels, and at least four of them are important for sensing different ranges of temperatures. In some cases, like with TRPV1, noxious heat (or capsaicin) results in a sensation of pain and burning, and the body’s mechanisms for cooling are turned on.

Another TRP family member, TRPM8, turns out to be the receptor channel that senses cool temperatures, from about 28˚C (82 ˚F) down to about 10˚C (50 ˚F) or even lower. The M stands for melastatin, a name for the first TRPM, before they knew it was a family of proteins. Now there are eight known members of the TRPM subfamily of TRP ion channels.

TRPM5 is particularly interesting for our recent discussion of taste, since it works to change the mechanical energy of taste particles + taste receptors into an electrical signal that is sent to the brain. Once again, we see the close relationship between the ion channels, like TRPV1 for capsaicin, and the taste sense. Maybe cold and TRPM8 also influence taste. We shall see.

Less is known about TRPM8 as compared to TRPV1 although they were discovered about the same time (early 2000’s). The pain associated with capsaicin and noxious heat aspects of TRPV1 made it sexier to study. I think we will see that TRPM8 and TRPA1 can be quite interesting in their own right.

Here’s a quick overview of the thermosensing by TRPs. We will talk about it more next week. The TRPVs are generally for warm temperatures, while TRPM8 is for cool temp.s. TRPA1 will be our focus in a few weeks; it senses painful cold. But notice, the garlic and wasabi pictured with TYRPA1 also activate TRPV1, and the camphor shown for TRPV1 also activates TRPM8 (next week). These are related and complex systems.

First of all, TRPM8 is involved in thermoregulation, just as is TRPV1. In humans and other mammals (the naked mole rat excepted), when TRPV1 is activated, the body automatically thinks it is too hot and initiates cooling mechanisms. With TRPM8, the effect is the opposite. Stimulation of this ion channel tells the body that it is too cold, and mechanisms are initiated to increase the core temperature. We will talk about how TRPM8 helps to regulate body temperature next week.

The big question is why it’s important to sense cold as well as heat. For some reason, we sense cool/cold with some distinct proteins and heat with different proteins. Remember, evolution doesn’t follow a plan to make things complex, functional and efficient. Sometimes the functions occur at separate times and come from different pathways; there is no evolutionary goal or roadmap to a destination. It’s all chance.

A 2013 review has an interesting hypothesis as to why sensing cold/cold is so important, aside from just alerting us to the chance we might freeze to death. Based on mouse study results from as early as the 1970’s, and on the answers that human subjects give, it seems that coolness is an evolutionary plus. No- I don’t mean that The Fonz from Happy Days was an evolutionary leap into the future, I mean that cool sensations somehow help us survive and propagate.

We typically heat food because it increases aroma, increases taste, and reduces the work in digestion. These are all important for getting us the nutrients and the calories we need. Taste, as we said several weeks ago, is nature’s way of getting us to eat those things we need and avoid those foods that might harm us.

So why would cool foods or sensations be helpful? Cooling would decrease aroma and taste, so it must be something other than taste. The obvious reason for drinking something cold would be that it cools off our body – but it doesn’t work that way. As soon as you drink a cold drink, your body reacts to the cold by constricting the blood vessels near the cold surface so that heat is not lost. TRPM8 also invokes heating mechanisms after it is activated by the cold water or soda. So in truth, cold drinks don’t cool you off.

On the left is a mint julep, famous in Kentucky and the Deep South during the hot summers. It contains Kentucky bourbon, which is why it is brownish. On the right is the mojito, also good on hot days, but uses rum, so it is popular in the Caribbean and Florida, where the rum is. The connection? They both use mint (menthol) to increase the coolness and refreshing characteristics of the drinks. TRPM8 hard at work to make your Saturday evening a success.

Yet they still feel refreshing on a hot day – what gives? Refreshing may be the key word here. People use many words that together make up “refreshing.” They say that cold drinks revive them, restore their energy, arouse them, reduce stress. All these feelings would promote survival behaviors in a hot environment. But we might also drink a cold drink on a cold day and deem it pleasant. In this case, pleasant can be equated to useful – and useful means promoting survival.

The 1970’s experiments showed that mice would lick a cold piece of metal when they were thirsty, showing that cold helps satisfy thirst. The more amazing thing was that the mice would lick the cold metal even if they could drink all they wanted. This meant that cold drinks were a reward; they activate a pleasure center in the brain. Many studies and experiments have shown these results to be true for humans as well.

So a cold drink on a cold day might be seen as unpleasant, while a cold drink on a hot day is very pleasant (useful). But more important, a cold drink on a cold day when you are thirsty is seen as pleasant and satisfying. It’s our brain helping us to garner the things we need; if cold water is all that’s available to a cold caveman, he better want to drink it. It works the same on skin, cold applied to the skin on a hot day – such as jumping into the pool on a warm day is seen as pleasant, even if it doesn’t cool the body all that much (see above). But the same cannonball on New Years day with the Polar Bear Club, is completely unpleasant.

Comedian and late night talk show host Jimmy Fallon took the Polar Bear Plunge in Chicago this past New Years. Basically, 3000 people jump into a 34˚F (1˚C) Lake Michigan to support Special Olympics. Some do it for the charity, some for the thrill, some because they are unbalanced. For those with a heart condition, it can kill you.

The brain is an amazing organ, it works with our body to get us what we need, and tricks us into doing it – that’s basically what pleasurable things are, evolutionary tricks. But remember – too much of a good thing can be bad in an environment where we can manipulate nature. Unfortunately, evolution doesn’t look into the future, it only worries about what keeps us alive at this moment. This explains the danger of menthol in cigarettes – we find it pleasant even if it is bad for us in the long run.

We will talk more about the TRPM8 next week, about how menthol seems to cool you down, how TRPM8 is a lot like TRPV1, and how it may save your life.

Eccles R, Du-Plessis L, Dommels Y, & Wilkinson JE (2013). Cold pleasure. Why we like ice drinks, ice-lollies and ice cream. Appetite, 71, 357-60 PMID: 24060271

Noriyasu A, Konishi T, Mochizuki S, Sakurai K, Tanaike Y, Matsuyama K, Uezu K, & Kawano T (2013). Menthol-enhanced cytotoxicity of cigarette smoke demonstrated in two bioassay models. Tobacco induced diseases, 11 (1) PMID: 24001273

Brody AL, Mukhin AG, La Charite J, Ta K, Farahi J, Sugar CA, Mamoun MS, Vellios E, Archie M, Kozman M, Phuong J, Arlorio F, & Mandelkern MA (2013). Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 16 (5), 957-66 PMID: 23171716

Ashoor A, Nordman JC, Veltri D, Yang KH, Al Kury L, Shuba Y, Mahgoub M, Howarth FC, Sadek B, Shehu A, Kabbani N, & Oz M (2013). Menthol binding and inhibition of α7-nicotinic acetylcholine receptors. PloS one, 8 (7) PMID: 23935840

For more information or classroom activities, see: Menthol in cigarettes – http://smokefree.gov/menthol-cigarettes http://www.cancer.org/cancer/news/expertvoices/post/2013/08/28/menthol-cigarettes-whats-the-big-deal.aspx http://www.npr.org/2014/01/01/258671720/fda-weighs-restrictions-possible-ban-on-menthol-cigarettes http://www.huffingtonpost.com/2013/11/22/latino-smokers-menthol-cigarettes_n_4326094.html http://www.forbes.com/sites/robwaters/2013/11/20/menthol-an-unequal-opportunity-killer-why-hasnt-the-fda-banned-it/ http://www.webmd.com/smoking-cessation/news/20110323/are-menthol-cigarettes-riskier-than-non-mentholhttp://www.theguardian.com/society/2013/oct/08/menthol-cigarettes-to-be-banned-eu http://www.fool.com/investing/general/2013/12/14/judgement-day-for-menthol-cigarettes-is-getting-cl.aspx

http://www.dw.de/european-parliament-approves-stricter-tobacco-regulations/a-17458107 In lieu of additional web sources, I suggest investigating the National Center for Biotechnology Information site (http://www.ncbi.nlm.nih.gov/) from the National library of Medicine. This site has many resources, from looking at the amino acid or nucleotide sequences from any protein or gene you can imagine (GenBank, http://www.ncbi.nlm.nih.gov/genbank/) to scientific journal articles that may or may not be available to you. Look at PubMed Central (PMC, http://www.ncbi.nlm.nih.gov/pmc/) where all articles are available free to the public.

#zoology #TRPV1. TRPM8 #thermoregulation #exception #cool sensing #animal

0 notes