Exciting Promise of Role of CBD in Alzheimer’s Neuro-inflammation - Dr. David Hepburn

Article Recommended by Dr. David Hepburn:

"GPR55 is a receptor that is getting a lot of attention in medical research. 40% of drugs are meant to target this receptor due to it’s role in conditions ranging from colon cancer to dementia to MS. THC activates this receptor while CBD does the exact opposite, further underscoring the complicated relationship of the various cannabinoids and showing that “cannabis is not cannabis, it’s cannabis.” The CBD blockage of this receptor is showing promise in addressing certain disease states such as Alzheimers disease, as this recent rat research reveals."

-Dr. Dave Hepburn

Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells

Abstract

Background

Neuroinflammation plays a vital role in Alzheimer’s disease and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system, and they play essential roles in the maintenance of homeostasis and responses to neuroinflammation. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia. However, its effects on neuroinflammation, mainly on the production of members of the arachidonic acid pathway in activated microglia, have not been elucidated in detail.

Methods

In this present study, a series of coumarin derivatives, that exhibit GPR55 antagonism properties, were designed. The effects of these compounds on members of the arachidonic acid cascade were studied in lipopolysaccharide (LPS)-treated primary rat microglia using Western blot, qPCR, and ELISA.

Results

We demonstrate here that the various compounds with GPR55 antagonistic activities significantly inhibited the release of PGE2 in primary microglia. The inhibition of LPS-induced PGE2 release by the most potent candidate KIT 17 was partially dependent on reduced protein synthesis of mPGES-1 and COX-2. KIT 17 did not affect any key enzyme involved on the endocannabinoid system. We furthermore show that microglia expressed GPR55 and that a synthetic antagonist of the GPR receptor (ML193) demonstrated the same effect of the KIT 17 on the inhibition of PGE2.

Conclusions

Our results suggest that KIT 17 is acting as an inverse agonist on GPR55 independent of the endocannabinoid system. Targeting GPR55 might be a new therapeutic option to treat neurodegenerative diseases with a neuroinflammatory background such as Alzheimer’s disease, Parkinson, and multiple sclerosis (MS).

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240959/ 

Dr. Dave Hepburn website:https://doctordavidhepburn.com

Sexually Activity in Rats Increased by Cannabinoid 1 Receptor Activation

Article recommend by Dr. Dave Hepburn:

"Men and rats have been closely compared (primarily by women); hence this study is pertinent. The activation of CB1 receptors (the same receptors acted on by plant THC) by the endogenous cannabinoid, anandamide, transforms boring non copulating rats into sexually active animals." 

Dr. Dave Hepburn

Sexual interaction is essential for the transformation of non-copulating rats into sexually active animals by the endocannabinoid anandamide.

Abstract

The endocannabinoid anandamide (AEA) transforms half of the population of previously non-copulating (NC) rats into sexually active animals in a long-lasting manner. The aim of this work was to explore the nature of this transformation.

We identified the dose range in which AEA induces mating behavior in previously NC rats, which evidenced a dose-based, biphasic profile for AEA to induce the transformation of NC rats. We demonstrate that the sexual interaction with a receptive female, involving at least an intromission, is essential for AEA to induce the transformation of NC rats.

This AEA-induced conversion is centrally mediated and involves the activation of CB1 receptors. Results indicate that the sexual impairment of this population of NC rats relies on their incapacity to initiate sexual activity and that an unidentified brain inhibitory influence on sexual behavior expression is removed by AEA treatment, allowing previously NC rats to show copulatory behavior in a long-lasting manner.

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30439451

Dr. David Hepburn website:
doctordavidhepburn.com

Move Over Epidiolex...Already! - Dr. Dave Hepburn

Article recommend by Dr. Dave Hepburn:

A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome.

Abstract

INTRODUCTION: 

Both Tetrahydrocannabidiol (THC) and cannabidiol (CBD) components of cannabis, have been shown to have anticonvulsant effects. Cannabis oils are used to treat seizures in drug-resistant epilepsy (DRE). Recent trials provide data on dosing, side effects, and efficacy of CBD, yet there is a paucity of information on THC in epilepsy. Primary objective was to establish dosing and tolerability of TIL-TC150 - a cannabis plant extract produced by Tilray®, containing 100 mg/mL CBD and 2 mg/mL THC- in children with Dravet syndrome. Secondary objectives were to assess impact of therapy on seizures, electroencephalogram (EEG) and quality of life. 

METHODS: 

Twenty children received add-on therapy with TIL-TC150. The dose ranged from 2 to 16 mg/kg/day of CBD and 0.04 to 0.32 mg/kg/day of THC. Patients were monitored for tolerability and adverse events, and secondary objectives. 

RESULTS: 

Nineteen participants completed the 20-week intervention. Mean dose achieved was 13.3 mg/kg/day of CBD (range 7-16 mg/kg/day) and 0.27 mg/kg/day of THC (range 0.14-0.32 mg/kg/day). Adverse events, common during titration included somnolence, anorexia, and diarrhea. Abnormalities of liver transaminases and platelets were observed with concomitant valproic acid therapy. There was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%, with 50% responder rate of 63%. 

CONCLUSIONS: 

TIL-TC150 was safe and well tolerated in our subjects. TIL-TC150 treatment resulted in a reduction in seizure counts, spike index on EEG, and improved quality of life measures. This study provides safety and dosing information for THC-containing cannabinoid preparations.

“A new and improved treatment that includes a touch of THC (which children handle much better than adults). The uptight FDA/DEA/US government would rather not allow any THC due to adherence to tired, old, uneducated biases. It’s a shame for American children that their government remains so willfully ignorant.”

Dr. Dave Hepburn

To read the full article please visit:
https://www.ncbi.nlm.nih.gov/pubmed/30250864

Dr. David Hepburn website:
doctordavidhepburn.com

Impressive New Ways that CBD Works - Dr. Dave Hepburn

Article recommend by Dr. David Hepburn:

Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor.

Abstract

Cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, exhibits therapeutic potential for various human diseases, including chronic neurodegenerative diseases, such as Alzheimer's and Parkinson's, ischemic stroke, epilepsy and other convulsive syndromes, neuropsychiatric disorders, neuropathic allodynia and certain types of cancer. CBD does not bind directly to endocannabinoid receptors 1 and 2, and despite research efforts, its specific targets remain to be fully identified. Notably, sigma 1 receptor (σ1R) antagonists inhibit glutamate N-methyl-D-aspartate acid receptor (NMDAR) activity and display positive effects on most of the aforesaid diseases. Thus, we investigated the effects of CBD on three animal models in which NMDAR overactivity plays a critical role: opioid analgesia attenuation, NMDA-induced convulsive syndrome and ischemic stroke. In an in vitro assay, CBD disrupted the regulatory association of σ1R with the NR1 subunit of NMDAR, an effect shared by σ1R antagonists, such as BD1063 and progesterone, and prevented by σ1R agonists, such as 4-IBP, PPCC and PRE084. The in vivo administration of CBD or BD1063 enhanced morphine-evoked supraspinal antinociception, alleviated NMDA-induced convulsive syndrome, and reduced the infarct size caused by permanent unilateral middle cerebral artery occlusion. These positive effects of CBD were reduced by the σ1R agonists PRE084 and PPCC, and absent in σ1R-/- mice. Thus, CBD displays antagonist-like activity toward σ1R to reduce the negative effects of NMDAR overactivity in the abovementioned experimental situations.

"As the mystery of how CBD actually works is unveiled, many receptors OTHER than cannabinoid receptors are involved. This mechanism/receptors help explain why CBD works for seizures and make morphine more effective (thus requiring a smaller dose)"

Dr. Dave Hepburn

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pubmed/30223868

Dr. David Hepburn website:
doctordavidhepburn.com

Yet Another Cannabinoid Shows Remarkable Promise - Dr. David Hepburn

Article recommend by Dr. David Hepburn:

Effect of cannabidiolic acid and -tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain.

Abstract

RATIONALE:

Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ9-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties.

OBJECTIVES:

The present study evaluates the anti-inflammatory and anti-hyperalgesia effects of CBD's potent acidic precursor, cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute inflammation in the rat hind paw, when administered systemically (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition, we assess the effects of oral administration of THC or CBDA, their mechanism of action, and the efficacy of combined ineffective doses of THC and CBDA in this model. Finally, we compare the efficacy of CBD and CBDA.

RESULTS:

CBDA given i.p. 60 min prior to carrageenan (but not 60 min after carrageenan) produced dose-dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or CBDA given by oral gavage 60 min prior to carrageenan produced anti-hyperalgesia effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA's effects were blocked by AMG9810 (a transient receptor potential cation channel subfamily V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this indication. Interestingly, when ineffective doses of CBDA or THC alone were combined, this combination produced an anti-hyperalgesia effect and reduced inflammation.

CONCLUSION:

CBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.

“CBDA is the precursor of CBD and is the raw form of cannabis. Already considered 100x more powerful than CBD as an anti-nauseant (anti emetic) and may have a role in the reduction of breast cancer metastasis PLUS anxiety. Stay tuned to see how interesting a molecule this non psychoactive little gem might be.”

Dr. David Hepburn

To read the full article please visit: 

https://www.ncbi.nlm.nih.gov/pubmed/30225659

Dr. David Hepburn website: 

doctordavidhepburn.com

New study: Autism and Cannabis - Dr. David Hepburn

Article recommend by Dr. David Hepburn:

Military Funds Research of Cannabis-based Autism Treatment for Kids

Study: The trial aims to study the effectiveness of cannabidivarin (CBDV) on irritability and repetitive behaviors in children with ASD. 

Raising a child with autism spectrum disorder (ASD) can be an overwhelming experience for parents and have far-reaching effects on the entire family. According to CDC estimates, one in every 68 children has ASD and many exhibit aggressive, self-injurious and repetitive behaviors.

The hope is that CBDV can be an effective treatment for these behaviors without the significant side effects present in current treatments, according to Hollander.

“The remarkable thing to me about this study is, not that it only involves CBDV, but that it is being sponsored by the US Department of Defence. Clearly, we have progressed.”

Dr. David Hepburn

To read the full article please visit:
https://www.childrenshospitals.org/newsroom/childrens-hospitals-today/articles/2018/03/military-funds-research-of-cannabis-based-autism-treatment-for-kids

Dr. Dave Hepburn website:

doctordavidhepburn.com

CANNABIS EFFECTIVE AND SAFE FOR DOGS WITH JOINT ISSUES

Article recommended by Dr. David Hepburn:

Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs

Abstract

Abstract: 

• Objectives: The objectives of this study were to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA).

• Methods: Single-dose pharmacokinetics was performed using two different doses of CBD enriched (2 and 8 mg/kg) oil. Thereafter, a randomized placebo-controlled, veterinarian, and owner blinded, cross-over study was conducted. Dogs received each of two treatments: CBD oil (2 mg/kg) or placebo oil every 12 h. Each treatment lasted for 4 weeks with a 2-week washout period. Baseline veterinary assessment and owner questionnaires were completed before initiating each treatment and at weeks 2 and 4. Hematology, serum chemistry and physical examinations were performed at each visit. A mixed model analysis, analyzing the change from enrollment baseline for all other time points was utilized for all variables of interest, with a p ≤ 0.05 defined as significant.

• Results: Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01).

• Clinical significance: This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.

• Keywords: cannabidiol, CBD oil, hemp, canine, osteoarthritis, pharmacokinetic 

"This comes as no surprise as, for years, pet owners have noticed the beneficial effects of CBD in many aspects of their pet’s well being" 

Dr. David Hepburn 

To read the full article please visit:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065210/

Dr. David Hepburn: Change how family doctors view medical cannabis (second part)

Continuing with our previous post, here you can find the rest of the interview to Dr. David Hepburn. In this part, Dr. Hepburn will talk about the different methods to consume cannabis, the ethical dilemmas about medical cannabis etc.

Interview (part two)

Is it right for commercial cannabis growers to pay for educating doctors who are the gatekeepers to the clients that buy their products?

That goes on all the time with Big Pharma, they're the ones who sponsor all the big events. This is virtually how we do 90 percent of our education. Routinely on a week-to-week basis, we probably get invitations through the week to two, three, four dinners put on by a specialist and sponsored by a drug company. It's nothing untoward, so to speak. There are other avenues for education – reading journals – but the journals are all supported by pharmaceutical companies, right?

What do you think about clinics specializing in pot prescriptions which say they are charging patients fees because they are helping them navigate the confusing federal medical marijuana regulations?

It's all smoke and mirrors, jiggery- pokery is being done. Personally I think it's unethical, so I charge patients nothing. What I do is I give them the options. I say, 'Here's the list of Health Canada's licensed producers, you can select one based on anything you find interesting on their Web page. Be it the fact that some of [them] offer certain deals with respect to a vaporizer and some require less amount purchased at one time.' Different LPs have different advantages and that is what the patients like.

Are cannabis oils more dangerous than vaporizing the drug?

There are those advantages to it, you can encapsulate them, however there are some disadvantages to them as well. And this is where it's very important to caution people to the appropriate uses of oral or edible or ingestible cannabinoids, and that there is a high variability to absorption rates. 

One of the things I heard down in Colorado is people were coming in and they were taking more and more derivatives of one sort or another. Next thing you know it all kicks in because it can take an hour or two to really take effect. People ask me the dose and I say, 'Just a little bit. Start low and go slow.'

There has been a lot of talk recently about the dangers of 'edibles.' What happens when someone is sent to hospital with an overdose?

They might give them IV, saline, tell them to go home and they'd be fine. It's not toxic. In fact, it's incredibly nontoxic, however it gives them an unpleasant experience that may sabotage the use of it. I probably would never start people on an oil, but what I like about the vaporizers is that you can titrate the dosage easily. You know in 95 seconds if it's going to work and it doesn't last very long.

You know the actual best form of cannabinoids to me is, believe it or not, suppositories? They are far and away the best delivery mechanism over all.

Why?

They go through a different absorption system, you know within 15 minutes you have it absorbed in there and it's actually done through the intestinal mucosa. You get a longer lasting effect than you would get for the vaporizer, but you also get a quicker response than you would get from the ingestible.

In sum up as we can see Dr. David Frederick Hepburn keeps trying to educate the medical sector about the use of medical cannabis.

You can be following his work in the following links:

http://davidfrederickhepburn.com

http://doctordavidhepburn.com

Conditions Cannabis is prescribed for - By Dr. David Hepburn

In listing ten common conditions that doctors use cannabis to treat, it is important to appreciate that some conditions respond better to different types or different combinations of cannabinoids. For example, migraines, will respond to THC dominant medications. Joint inflammation conditions prefer CBD dominant strains while others still, like chronic pain, usually settle on a 1:1 CBD:THC combination. Not only are the type and ratio of cannabinoids used important, but so is the dose. For example, a low dose of THC (micro-dosing) can help with anxiety and some types of pain. A higher dose of THC can do the exact opposite and actually exacerbate anxiety and worsen pain. While cannabis is being used for treatment in dozens of conditions ranging from Acne to Tourette’s to Asthma (yes that asthma), here are some of the more common conditions where cannabinoid medicine plays a role. 

Arthritis.

For those with either osteoarthritis or rheumatoid arthritis, their joints are just smoking, which is why many turn to smoking joints. However the ingested route of medical oils are more effective for longer periods of time compared to the relatively quick but short acting relief of an inhalation method such as a vaporizing (always preferred over smoking). Much safer than most medications used to treat arthritis, cannabis has no risk of causing stomach bleeds, constipation and even death that opiates or anti-inflammatory medications (NSAIDS) could cause. In fact, NOBODY dies of cannabis.....ever. This is because, unlike opiates that claim numerous lives every day, there are no cannabinoid receptors in the brainstem, that vital part of the brain that controls our respiratory and cardiovascular systems. 

Stress.

Cannabis acts to harness our own endocannabinoid system (ECS), which includes our naturally produced cannabinoids, anandamide and 2AG. These endocannabinoids are made throughout our body and are made in response to imbalances in multiple systems, usually involving hormones and neurotransmitters. When we make too much cortisol, the stress hormone, our ECS kicks in and we make anandamide that works to shut down cortisol production. When our own natural cannabinoids aren’t enough, then the addition of plant cannabinoids can be very helpful.

Epilepsy.

It has become headline news, of late, that CBD dominant cannabis can significantly reduce seizures in many children (and adults) in some of the more difficult type of seizure disorders. Noting the powerful effect cannabinoids have on children with terrible seizures, many key opinion leaders in the worlds of medicine and government have changed their minds about cannabis. Some families will even relocate to places where there is a more compassionate government that allows children to be treated for seizures with cannabis oil.

Migraineheadaches

William Osler, the founder of modern medicine, stated that “cannabis is the single best treatment for migraines.” This is one of the few conditions where vaporized cannabis is more effective than ingested, as those who get struck by a migraine (often with nausea) don’t want to wait an hour before the ingested oils kick in.

Irritable bowel syndrome

Twitchiness involving nerves and spasm are areas where cannabinoids tend to excel in. This also defines the cause of IBS, a very common condition that may be fraught with constipation, diarrhea or both. The bowel has many cannabinoid receptors (CB2R) that, when activated by cannabis medicine, can reduce gut spasm and cramping.

In the next post we will see another five conditionswhich cannabis can help

• Conditions Cannabis is prescribed for – Dr. David Hepburn. for https://plena-global.com/news-desk/conditions-cannabis-is-prescribed-for/

• http://davidfrederickhepburn.com/

• https://doctordavidhepburn.blogspot.com/