Effects of CBD on the Human Pain System

originally by George Bennet, CBDPURUS.COM

Visualization of the Endocannabinoid Signaling System by Leanne Chan
The excellent five minute video to the right Visualization of the Endocannabinoid Signaling System by Leanne Chan in 2011 contains great animations and discussion of how cannabinoids act in the body to reduce pain.  The visuals are remarkably explanatory but the verbal description assumes specialist knowledge that most people viewing the video lack.  In particular an understanding of the complete system by which the body senses and can reduce pain is helpful.  A number of clickable references are included for much more in-depth explanations.

So here is a brief layman’s description and interpretation of how the body’s pain systems work and an explanation of some of the other terms and concepts in the video which will hopefully add clarity to what the video says to the average viewer. 

The video can be divided into a number of sections.  The first section (0:00 – 0:50) explains how pain signals (nociceptive signals) ascend from the spinal cord into the thalamus portion of the brain.  This animation in a great article (www.rnceus.com) on the subject shows some details of the process:

animation of pain signal

The gray area represents a horizontal slice of the spinal cord, which has various columns (or bundles) of nerves which send signals up or down the spinal cord. In this animation pain signals are shown flowing up to the brain.  Peripheral reduction of pain is achieved locally, as with the action of aspirin at the site of the pain to reduce sensitivity, or the use of an anesthetic such as Novocain to block transmission of the pain signal at the site, reduction of inflamation via hydrocortisone or stimulation with a TENS unit.  Interestingly, the TENS unit by stimulating nerves at the site of pain causes a blockage or reduction in the pain signal at the interneuron (see animation) by causing the release of GABA, resulting in a CNS (central nervous system) effect rather than a peripheral nervous system effect.  A very understandable explanation of the body’s pain system is available from the University of Texas Medical School ‘s Neuroscience Online (see chapters 5-8).

The video discusses the effect of endocannabinoids on what is known as the descending pain modulation system, which is just a means by which the ascending pain signals in the spinal cord can be reduced (modulated), resulting in a reduction of pain.  Of course modulation could also act in the reverse fashion to increase pain.  This second figure, also from rnceus.com, illustrates the system from where the pain nerve (primary afferent pain neurons) enters the spinal cord to where it reaches the thalamus area of the brain and back to where the descending pathway interacts with the corresponding inhibitory interneuron.  The enlarged section shows the interaction of the neurons at this junction.  This is the area which the video animates in the second part, starting at 0:50.  The enlarged section also lists some of the substances known to have an inhibitory effect on the transmission of pain but fails to include the cannabinoids, probably due to the more recent discovery of cannabinoid receptors.

As the video enters the second section it says “stimulation of the periaqueductal gray is know to produce an analgesic effect. However this neuroregulatory process is thought to be tonically restricted by GABAergic off-cells.” “Tonically restricted” refers to the firing mode of neurons. Phasic firing is the result of a stimulus while tonic firing is a steady state caused, in this case, by “GABAergic off-cells”. The RVM (rostroventromedial medulla), or lower part of the brain which connects to the spinal cord has been shown to have “on-cells” and “off-cells” (see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964993) which are related to increasing or decreasing pain transmission.  The referenced article at nih.gov gives  a nice overview of other descending pain modulation systems, such as those involving the amygdala, norepinephrine and serotonin.

 

 

Descending Pain Modulation System

From 00:50 to 1:15 the video begins to discuss the actual mechanism of the analgesic action.  In the phrase “Depolarization induced suppression of inhibition” the term “depolarization” refers to how neural synapses work.  A synapse is the minute gap between nerve cells (neurons) through which a signal is propagated via an electro-chemical process.  Every cell in the body is covered by a membrane which is polarized, which means it has a different potential (voltage) on the inside versus the outside.  The typical “resting” potential is about -70 millivolts.  This potential is changed by pumping various chemicals such as potassium and sodium through the cell membrane.  For example pumping positive sodium ions out from the cell results in a negative charge.  An electrolyte imbalance, caused for example by excessive sweating resulting in low sodium, disrupts this signaling scheme with potentially fatal consequences.

There are numerous synaptic feedback mechanisms, re-uptake inhibition mechanisms and the like.  Concentrating on the endocannabinoid system only greatly simplifies matters.

From 1:15 to 1:43 the concept of a synaptic feedback mechanism is introduced.

At 1:44 an endogenous (generated within the body) cannabinoid is depicted being synthesized by the cell membrane.  The cannabinoids are shown crossing the synaptic cleft and binding with the matching receptors (likely CB1 for CBD products) thereby affecting intracellular signal transduction pathways, reducing the influx of calcium ions into the pre-synaptic neuron causing a decrease in neurotransmitter (GABA) release.  This in turn influences the frequency of post-synaptic firing.  The result of this is, of course, a reduction in pain.

And that is how the endogenous cannabinoid signaling system is part of the descending pain modulation system works (and this sentence should actually mean something to you now).

At 2:42 the discussion changes to how exogenous cannabinoids can be transferred to the appropriate neurons.  Two methods are shown oral, which is slow and subject to detrimental digestive effects and inhaled, which by directly entering the blood is much quicker.

At 3:37 a normal synapse is compared to ones affected by endogenous or exogenous cannabinoids.

At 3:56 the mechanism of action is shown again and the use of cannabinoids for symptoms other than pain, such as anxiety, spasticity, anorexia and nausea.  Many other uses of cannabinoids in medicine are currently being investigated.  Finding other substances which affect the cannabinoid system is mentioned as a worthy goal and an example of one, a re-uptake inhibitor, is shown.  Re-uptake inhibitors of other neurotransmitters such as serotonin are commonly used, as exemplified by Prozac, Celebrex and others.

Hopefully the information in the video as well as the pain system of the human body now makes more sense.  If not study of the above reference links and additional references below should be a help.

Additional references:

https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/v/neuronal-synapses-chemical

http://www.dummies.com/how-to/content/understanding-the-transmission-of-nerve-impulses.html

Descending pain modulation and chronification of pain -http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301419/

By George Bennet, CBDPURUS.COM

ICOMR.org Suggested Cannabidiol (CBD) Dosage

Suggested Dosing Range
The following is a general guideline based on patient response and manufacturers. A patient must find their own efficacy as each person will experience varying degrees of CBD needed to properly coat the Synaptic Clefs.

Pain & Inflammation
(5mg to 10mg daily)

Anxiety & Depression
(10mg to 25mg daily)

Cancers, Chemotherapy Rash, Epilepsy
(50mg to 200mg daily)

Disclaimer – CBD does not cure and may
provide relief from many additional ailments
on a patient by patient basis. The body cures itself. These statements have not been evaluated by the FDA and are not intended to diagnose, treat or cure any disease. Always check with your physician before starting any new supplement program.

Georgia Medical Marijuana Commission to Discuss Cultivation

This past week in downtown Atlanta The Georgia Commission on Medical Cannabis met and held it’s second meeting to discuss the likelihood of having in-state medical cannabis cultivation. There are three more meetings planned for the group before the end of 2015.

The meetings come after the passing of bill HB 1, which legalized the right for patients who are registered with the state of Georgia for certain medical conditions to possess and consume cannabis oil that is high in the cannabinoid cannabidiol (CBD), the compound known for many medical benefits, and low in tetrahydrocannabinol (THC), the compound found in marijuana to have psychoactive effects.

The only problem with the bill passing is that a patient cannot get the healing CBD oil into the state without breaking a few of the federal drug trafficking laws. The Georgia Medical Cannabis Commission is working on a plan for in-state production and distribution of CBD oil to fix this issue.

Four major players in the manufacturing of medical cannabis in other U.S. states consulted with the group, providing information and recommendations on the different ways the state could grow the plant and distribute the oil, showing the state that there are a lot of interested parties who would jump at the chance to be a part of the medical marijuana business in Georgia.

Some others are giving their recommendations as well, including Jason Cranford, the founder of Flowering Hope Foundation and the creator of a strain of cannabis oil that is high in CBD and low in THC called Haleigh’s Hope, which was named after a six year old girl from Georgia.

Jason says that he’s seen issues regarding over-regulation of cannabis, causing many pitfalls for companies who are trying to produce the CBD oil that many Georgia patients need.

Cranford says, “I’ve seen states that attempt to be the sole license holder to cultivate and distribute. This model gives local government control over health care and will not make the citizens very happy. This gives the government too much control over an individual’s health care and the options they choose.”

Cranford also mentions that if the state of Georgia would consider a wider range of cannabinoids, not just CBD, many more people would be able to find relief from medical conditions that cause them to suffer greatly.

Many people who relocate from Georgia to Colorado are looking for seizure medicines that include THCA, another cannabinoid found in cannabis. Because he can’t ship the product, Cranford says that companies like his need to be able to cultivate in Georgia so he doesn’t break any drug trafficking laws that may occur from state to state.

In order to better answer questions the Commission was asking, Cranford went on to tell them why Georgia needed to grow marijuana plants with varying THC levels. He goes on to say “If you put a cap on it, you are going to make the producers work twice as hard, with twice as many plants and twice as many employees.”

Suterra, a company based in Atlanta, is in the perfect place to be involved in the medical marijuana industry in Georgia. This company’s product line consists of topical creams that many patients, including those with arthritis, use to manage pain.

Jake Bergmann, the CEO of Suterra, recommended a couple business models that would be perfect for Georgia. The first would give a license to a select few businesses to grow and maintain the plant from seed to sell, and the second would be managed by the state. The state would get a company like Suterra to grow and take care of the plants, only to hand over to the state…who would then own the plants in whatever form they are in. Then the state would deliver the CBD oil to the patients who need it.

Bergmann went on to say that if his company got a license to grow marijuana in Georgia that his company could “begin construction on a facility and have cultivation of plants in six months”. That means the CBD oil that is needed for treatment can be made available to patients sooner.

Another medical marijuana business owner, Mike Bragg, discussed some of his research around medical marijuana. Bragg is the President of CBD Farms and CEO (and founder) of Evolve Therapeutics in California, and like the other the two other men he also hails from Georgia. Bragg has even got involved in some research out in California that resulted in CBD slowing of the spread of aggressive cancers, specifically aggressive breast cancer.

Bragg’s father-in-law was diagnosed with stage III lung cancer so Bragg decided to use cannabis oil in the form of capsules on his father-in-law, and his doctors saw that the tumor started to shrink. They wanted more tests to see why the tumor was shrinking, so Bragg’s father-in-law (who is a resident of Georgia) decided to stop the cannabis treatments so the doctor’s wouldn’t find the drug in his tests.

Paranoia about cannabis runs rampant, but why should the sick be so afraid of something that can cure them? Bragg believes one of the biggest issues surrounding medical marijuana is misinformation. There has been a lot of misinformation spread about marijuana in Georgia and other areas of the south, and many people are fearful of being involved with the plant because of that. Bragg recommended to the Commission that the labs, greenhouses, and warehouses all be close together saying that “one million square feet or 25 acres of land would be enough space to cultivate all the medical marijuana needed to treat 500 patients in Georgia”.

The fourth group that spoke to the Commission was Oregonians for Better Health. Robert Blake, a spokesperson for the company said, “The Oregon program is one hundred percent patient-driven. The patients own the plants, not the grower. There are no corporate entities. Companies contract with individual patients who control all the production. Every product that is sold is tested for pesticides, mold, mildew, and other impurities”.

There are countless of medical conditions that can be treated with medical marijuana, which isn’t allowed by the HB 1 bill. It’s only a matter of time before the state of Georgia gets a handle on the popularity of CBD oil for treatment, making higher levels of THC likely in the future.

CBD-Drug Interactions: The Role of Cytochrome P450

Cannabidiol is a safe, non-intoxicating, and non-addictive cannabis compound with significant therapeutic attributes, but CBD-drug interactions may be problematic in some cases.

CBD and other plant cannabinoids can potentially interact with many pharmaceuticals by inhibiting the activity of cytochrome P450, a family of liver enzymes. This key enzyme group metabolizes most of the drugs we consume, including more than 60 percent of marketed meds.

At sufficient dosages, CBD will temporarily deactivate cytochrome P450 enzymes, thereby altering how we metabolize a wide range of compounds, including tetrahydrocannabinol (THC), which causes the high that cannabis is famous for.

http://www.alternet.org/drugs/cbd-drug-interactions-role-cytochrome-p450

When THC or any other foreign compound enters the body, it is metabolized. This process is generally very complicated. Metabolizing something properly can involve multiple molecular pathways and various enzymes that enable the body to get rid of the compound (often done by adding something to the original compound). Or metabolism can entail breaking down a compound into a more basic molecule that the body then uses.

Products of a drug’s metabolism are called its metabolites. These metabolites can have very different properties than the initial drug. Ethanol, for example, owes some of its effects, including much of the hangover, to its two-step metabolism. The buildup of acetaldehyde in the liver—while ethanol is converted first to acetaldehyde and then to acetic acid—is a major reason for ethanol’s liver toxicity and the nausea and vomiting caused by excessive consumption.

THC metabolites contribute significantly to the effects of cannabis consumption. Eleven-hydroxy-THC (11-OH-THC), for example, is a THC metabolite that activates the CB1 cannabinoid receptor in the brain and induces a high more potently than THC itself. This means that the body’s metabolism of THC can make it more potent.

Cytochrome P450 enzymes contribute to the metabolism of drugs by oxidizing them, which generally means incorporating an oxygen atom into the drug’s molecular structure. Oxidation will usually make a compound more water soluble and therefore easier for the kidneys to filter out. Both steps in the metabolism of ethanol, mentioned above, and the conversion of THC into 11-OH-THC involve oxidation (though ethanol is not oxidized specifically by cytochrome P450).

Different routes of cannabinoid administration have different effects. Inhaled THC enters capillaries in the lungs, passes into general circulation through the pulmonary arteries, and quickly crosses the blood-brain barrier. When ingested orally, however, THC is absorbed in the small intestine and then carried to the liver, where it is metabolized by subclasses of cytochrome P450 (abbreviated CYP), specifically the CYP2C and CYP3A enzymes.

These liver enzymes also metabolize CBD, converting it into 7-OH-CBD and 6-OH-CBD. But there has been relatively little research into the properties of these CBD metabolites.

http://www.alternet.org/drugs/cbd-drug-interactions-role-cytochrome-p450

The way CBD interacts with cytochrome P450 is pivotal; in essence, they deactivate each other. Preclinical research shows that CBD is metabolized by cytochrome P450 enzymes while functioning as a “competitive inhibitor” of the same liver enzymes. By occupying the site of enzymatic activity, CBD displaces its chemical competitors and prevents cytochrome P450 from metabolizing other compounds.

The extent to which cannabidiol behaves as a competitive inhibitor of cytochrome P450 depends on how tightly CBD binds to the active site of the metabolic enzyme before and after oxidation. This can change greatly, depending on how—and how much—CBD is administered, the unique attributes of the individual taking this medication, and whether isolated CBD or a whole plant remedy is used.

If the dosage of cannabidiol is low enough, it will have no noticeable effect on CYP activity, but CBD may still exert other effects. There is no clearly established cut-off dose, below which CBD does not interact with other drugs. A 2013 report on a clinical trial using GW Pharmaceutical’s Sativex, a whole plant CBD-rich sublingual spray, found no interactions with CYP enzymes when approximately 40mg of CBD were administered. A subsequent clinical trial, however, found that 25mg of orally administered CBD significantly blocked the metabolism of an anti-epileptic drug.

How do CBD-generated changes in cytochrome P450 activity impact the metabolic breakdown of THC? Animal studies indicate that CBD pretreatment increases brain levels of THC. That’s because CBD, functioning as a competitive inhibitor of cytochrome P450, slows down the conversion of THC into its more potent metabolite, 11-OH-THC. Consequently, THC remains active for a longer duration, but the peak of the extended buzz is blunted somewhat under the influence of cannabidiol.

Other factors figure prominently in CBD’s ability to lessen or neutralize the THC high.

http://www.alternet.org/drugs/cbd-drug-interactions-role-cytochrome-p450

Lester Bornheim, a research pharmacologist at the University of California in San Francisco, was among the first scientists to study the metabolism of CBD. In 1987, he was awarded a NIDA grant to investigate the effects of phytocannabinoids on cytochrome P450 enzymes. THC and cannabinol (CBN) also inhibit CYP activity, but CBD, of all the plant cannabinoids studied, is the strongest cytochrome P450 deactivator.

“It’s a very unusual enzyme. Almost all other enzymes are designed to fit a single substrate and carry out a single chemical process resulting in a single product,” Bornheim noted, whereas numerous drugs are substrates for cytochrome P450, which seems to function like a generic breakdown mechanism for a wide range of exogenous and endogenous substances.

In 1999, Bornheim addressed the annual gathering of the International Cannabinoid Research Society (ICRS) and drew attention to the possibility that CBD could interfere with the metabolism of many medications. A year earlier, a team of Canadian scientists identified certain compounds in grapefruit that inhibit the expression of some cytochrome P450 enzymes—which is why physicians often warn patients not to eat grapefruit before taking their meds. CBD, in turns out, is a more potent inhibitor of cytochrome P450 enzymes than the grapefruit compound Bergapten (the strongest of several grapefruit components that inhibit CYPs).

What does this mean in practical terms for a medical marijuana patient on a CBD-rich treatment regimen who takes a prescription blood-thinner like warfarin, for example? CBD reduces the enzymatic degradation of warfarin, thereby increasing its duration of action and effect. A person taking a CBD-rich product should pay close attention to changes in blood levels of warfarin, and adjust dosage accordingly as instructed by their doctor.

http://www.alternet.org/drugs/cbd-drug-interactions-role-cytochrome-p450

In cancer treatment, the precise dosing of chemotherapy is extremely important; doctors often struggle to find the maximum dose that will not be catastrophically toxic. Many chemotherapy agents are oxidized by CYPs before their inactivation or excretion. This means that for patients using CBD, the same dose of chemotherapy may produce higher blood concentrations. If CBD inhibits the cytochrome-mediated metabolism of the chemotherapy and dosage adjustments aren’t made, the chemotherapy agent could accumulate within the body to highly toxic levels.

By and large, however, there have been few reported adverse cannabinoid-drug interactions among the many cancer patients who use cannabis to cope with the wrenching side effects of chemotherapy. It is possible that whole plant cannabis, with its rich compensatory synergies, interacts differently than the isolated CBD that is administered in most research settings. As well, the cytoprotective effects of the cannabinoids may mitigate some of the chemotherapeutic toxicity.

Some epileptic patients have encountered issues with how CBD interacts with their anti-seizure medication. A small clinical study at Massachusetts General Hospital involving children with refractory epilepsy found that CBD elevated the plasma levels and increased the long-term blood concentrations of clobazam, an anticonvulsant, and norclobazam, an active metabolite of this medication. A majority of these children needed to have their dose of clobazam reduced due to side effects. Given that both clobazam and CBD are metabolized by cytochrome P450 enzymes, a drug-drug interaction is not surprising. Published in May 2015, the study concluded that “CBD is a safe and effective treatment of refractory epilepsy in patients receiving [clobazam].” But the report also emphasized the importance of monitoring blood levels for clobazam and norclobazam in patients using both CBD and clobazam.

Dr. Bonni Goldstein has observed cases in which small doses of high-CBD/low-THC cannabis oil concentrate seemed to aggravate seizure disorders rather than quell them. How could this happen, given CBD’s renown anti-epileptic properties?

A 1992 review by Lester Bornheim and his colleagues indicated that CBD inhibits some cytochrome P450 enzymes at smaller doses than what is required for CBD to exert an anti-epileptic effect. This means that a certain dose of CBD could alter the processing of an anti-epileptic drug taken by the patient, but this amount of CBD might not be enough to provide any anti-epileptic relief itself. The advice some physicians offer in this situation may seem counterintuitive: Increase the dose of CBD—perhaps even add a little more THC (or THCA, the raw, unheated, non-psychoactive version of THC)—and this may be more effective for seizure control.

http://www.alternet.org/drugs/cbd-drug-interactions-role-cytochrome-p450

But why would preventing the breakdown of an anti-epileptic drug reduce its effect? There are a number of possible answers, depending on the drug in question. The active component of the drug (the chemical that exerts an anti-epileptic effect) may be a breakdown product of the actual drug taken. So, by slowing the metabolism of the original drug, CBD would make that drug less active.

Other explanations are conceivable. For example, if the activity of certain CYPs is slowed, the drug may be broken down by another metabolic pathway, the products of which could then interfere with the drug’s activity. Or perhaps the inhibition of CYPs is not the predominant way that CBD interacts with certain anti-epileptic medications.

To complicate matters even further, a presentation by Dr. Kazuhito Watanabe at the 2015 International Cannabinoid Research Society meeting in Nova Scotia disclosed preliminary evidence that cannabidiol may “induce”—meaning amplify the activity of—some cytochrome P450 enzymes. (Induction of a protein involves increasing the transcription of its corresponding mRNA, which leads to greater synthesis of the protein.) This suggests that CBD can either increase or decrease the breakdown of other drugs. Again, it depends on the drug in question and the dosages used.

Any pharmaceutical, nutraceutical or green rush scheme to exploit the therapeutic potential of CBD must reckon with the fact that cannabidiol can both inactivate and enhance various cytochrome P450 enzymes in the liver—and this can potentially impact a wide range of medications. Drug interactions are especially important to consider when using life-saving or sense-saving drugs, drugs with narrow therapeutic windows, or medications with major adverse side effects. In particular, those who utilize high doses of CBD concentrates and isolates should keep this in mind when mixing remedies.

Sources

  1. Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. 1998. Br J Clin Pharmacol. 2004.
  2. Bland TM, Haining RL, Tracy TS, Callery PS. CYP2C-catalyzed delta9-tetrahydrocannabinol metabolism: kinetics, pharmacogenetics and interaction with phenytoin. Biochem Pharmacol. 2005.
  3. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol. 1993.
  4. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015.
  5. Jiang R, Yamaori S, Takeda S, Yamamoto I, Watanabe K. Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci. 2011.
  6. Klein C, Karanges E, Spiro A, Wong A, Spencer J, Huynh T, et al. Cannabidiol potentiates Delta(9)-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology. 2011.
  7. Stott C, White L, Wright S, Wibraham D, Guy G. A phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the phamacokinetics of THC/CBD oromucosal spray in healthy volunteers. SpringerPlus. 2013.
  8. Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007.
  9. Yamaori S, Ebisawa J, Okushima Y, Yamamoto I, Watanabe K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011.
  10. Yamaori S, Kinugasa Y, Takeda S, Yamamoto I, Watanabe K. Cannabidiol induces expression of human cytochrome P450 1A1 that is possibly mediated through aryl hydrocarbon receptor signaling in HepG2 cells. Life Sci. 2015.
  11. Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem Pharmacol. 2010.
  12. Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011.
  13. Yamaori S, Okushima Y, Masuda K, Kushihara M, Katsu T, Narimatsu S, et al. Structural requirements for potent direct inhibition of human cytochrome P450 1A1 by cannabidiol: role of pentylresorcinol moiety. Biol Pharm Bull. 2013.

Source: http://www.alternet.org/drugs/cbd-drug-interactions-role-cytochrome-p4

http://www.alternet.org/drugs/cbd-drug-interactions-role-cytochrome-p450

GWPH: GW Pharma’s Cannabidiol beats placebo in mid-stage schizophrenia study; shares up 11%

GW Pharmaceuticals (GWPH +11.2%) heads north on increased volume in response to its announcement of positive top-line results in a Phase 2a clinical trial assessing Cannabidiol (CBD) in 88 schizophrenia patients who failed to respond adequately to first-line anti-psychotic medications. In the study, participants remained on their anti-psychotic treatments and were randomized to receive CBD or placebo as adjunct therapy.

Compared to placebo, patients in the CBD cohort showed a statistically significant improvement in the PANSS positive sub-scale (p=0.018), the Clinical Global Impression of Severity (p=0.04) and Clinical Global Impression of Improvement (p=0.02). CBD was also better than placebo in the area of cognition, but the results were shy of statistical significance (p=0.07). The trial was a proof-of-concept study so the endpoints were exploratory. There was no single primary efficacy endpoint.

CEO Justin Glover says, “These findings further reinforce the potential role of cannabinoids in the field of neuropsychiatric disease. We believe that the signals of efficacy demonstrated in this trial, together with a notably reassuring safety profile, provide GW with the prospect of a new and distinct cannabinoid neuropsychiatric product pipeline opportunity. Similar to our approach with Epidiolex, we believe that our future research in this area may lie within pediatric orphan neuropsychiatric indications and we intend to explore this as a focus for future trials.”

Source: http://seekingalpha.com/news/2778676-gw-pharmas-cannabidiol-beats-placebo-in-mid-stage-schizophrenia-study-shares-up-11-percent

Pharma-Grade CBD Gel Caps – 5mg, 25mg, and 50mg introduced by CBDZone.com

Boynton Beach, Fl. September 3, 2015

Lisa Cicetti, Psy.D., LMHC, BE, CEO of New Directions LLC, a leader in brain based drug rehabilitation market has announced a new company has been created to distribute professional grade CBD products. CBD zone LLC is a new distributor of the new 5 mg silver, 25mg gold, and 50 mg platinum CBD Gel Caps providing an alternative to tinctures and drops. CBD Zone products contain Pharma Grade CBD Isolate from CBD Pur US, a leading provider of high quality Pure CBD isolate. CBD Pur US goes the extra mile by adding an additional patent pending filtering process to screen out unwanted organic debris. This insures purity and safety.  Over time, hemp oils and organic matter may breed and grow unwanted bacteria. CBD Pur US is certified free of heavy metals and other contaminants. No prescription is required and it’s legal in all 50 states.  CBD Zone products can be purchased over the counter.

It states in U.S. Government patent #6,630,507 on cannabidiol, that CBD has properties as a neuro-protectant, anti-epileptic/anti-seizure, antioxidant, protects the brain from ischemic damage, protects cells of the nervous system, brain and nerves, protects against cellular damage, and has an anti-anxiety effect.  And further we know that CBD can have positive effects on the endocannabinoid system and endocannabinoid deficiency.

A study was conducted this year by New Directions, LLC of Boynton Beach, Fl, one of the nations’ leading biofeedback neuro-recovery center. New Directions is owned by neuropsychologist Dr. Lisa Cicetti, Psy.D. LMHC, BE, http://www.ndbraintherapy.com.  The facility specializes in addiction recovery and brain trauma recovery. To their credit, and staffing 6 PhD’s, each an expert in their own field, they produced a White Paper pilot study on the effects of CBD on the brain.

The following “Cicetti Brain Mapping” illustration is a collective brain map of the effects of CBD on the brain after 2-4 weeks of taking CBD. This image shows the collective change of all the participants. A significant finding was an increase in “relaxing” slow wave surface amplitudes in the posterior section of the brain; a pattern commonly associated with increased relaxation and emotional composure.

brain-map-img

View the white paper pilot study at cannabidiol industry website: www.ICOMR.org. For more information, contact CBD ZONE Director of Marketing, Tina Reine at 877-CBD-1922 or visit www.cbdzone.com.

CBD Pur US Becomes First Cannabidiol (CBD) Company to Obtain Pharma-Grade Certification for Pure CBD Isolate

HILTON HEAD ISLAND, S.C.–After three months of extensive laboratory testing and scientific research by many notable sources, David Mouser, CEO, announced the company has discovered and developed a forth extraction process performed on CBD Pur US Isolate bringing the product to PHARMA GRADE purity. Patents have been initiated to protect the intellectual property pertaining to the 4th critical extraction now used by CBD Pur US. All unwanted plant wax and potentially toxic humic acid have been removed in the process.

“Responsible companies now have an alternative to avoid potential liability, costly litigation, and loss of market reputation…”

CBD Isolate, paste, and oil products all contain humic acid and plant cuticle wax. Humic acid is a natural fertilizer sold for gardening. Consequently, all CBD hemp extractions are subject to growing things. Contamination long range becomes a serious issue regarding “shelf life”. CBD Pur US Isolate PHARMA GRADE now guarantees the industry an unequaled purity for CBD product manufacturers by eliminating these potentially harmful product liability issues (see ProjectCBD, Oct. Page 17-18).

David Mouser, CEO stated, “Responsible companies now have an alternative to avoid potential liability, costly litigation, and loss of market reputation regarding the inherent humic acid issues. CBD Pur PHARMA GRADE is a breakthrough for the CBD industry worldwide. We have now applied the identical 4th extraction process to our new SDP Water Soluable Isolate as well. Oregon Analytical Services confirmed the 99.9% PHARMA GRADE in accordance with ColumbiaBiological.org certification of CBD Pur US. CBD Pur US Isolate is not a synthetic.”

CBD Pur US is the first CBD manufacturer of PHARMA GRADE CBD Isolate distributing worldwide. “We have set an industry standard for all CBD isolate manufacturers, seriously undertaking a leadership role with a passion to maintain accountability to the CBD market space. Look for the CBD Pur US logo on all CBD products. It is your guarantee of PHARMA GRADE CBD. It just makes good sense,” Mouser said.

CBD Pur US main office is in Hilton Head Island, South Carolina with satellite offices in the United Kingdom and Jamaica for export to European, Caribbean, and Latin American manufacturers.
Contacts

CBD Pur US
Mr. John Hamilton, 843-422-1200
Director of Marketing
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Could CBD company be teaming up with Hollywood and NFL with the movie “Concussion” starring Will Smith?

This Christmas CBD may finally get recognized in Hollywood for it’s incredible healing powers in “Concussion”, a movie starring Will Smith as Dr. Bennet Omalu: the man who changed football forever. The film highlights the disease Chronic Traumatic Encephalopathy (CTE), which was literally discovered, and named, by Dr. Omalu. Funny enough, Dr. Omalu has a background in Forensic Pathology with a focus on neuropathology, which means he studies the brains of the deceased. The movie stars big Hollywood names like Alec Baldwin, Luke Wilson, and Albert Brooks as characters surrounding the National Football League (NFL).

The movie is based off of the GQ article Game Brain, which opened the world’s eyes to what was happening to football players to make them go insane. Omalu, a doctor who is from Nigeria, was tasked with doing the autopsy on football legend Mike Webster (of Steelers fame). Once Omalu began the autopsy of Webster’s brain he couldn’t see any symptoms of anything that Webster was diagnosed with during his life. There wasn’t a single sign of anything wrong…but how could it be? Omalu became obsessed with this and continued studying the brain.

dr-bennetBefore Webster died he was suffering from many different symptoms including massive memory loss, depression, and pain. Lots of pain, so much that Webster couldn’t live a normal life. He lived out of his truck and couldn’t remember if he was ever married or not, despite divorcing from his wife. Webster decided to go get a lawyer, who helped him get disability from the NFL for his disabilities from his career. Omalu became aware of this and, after studying the brain for quite some time, ordered slides of Webster’s brain to be stained a special way.

As soon as Omalu put the slides under his microscope to be shocked at what he saw. There it was, exactly what he had been looking for. Omalu found what caused Webster to go crazy, and it was all over the place. Tau proteins. These proteins appeared to be brown and red splotches on the slides, slowly destroying Webster’s brain. After Omalu did some more studying, he posted his work in medical journals thinking the NFL would be happy about his findings.

Well, the NFL wasn’t happy. In fact, they were kind of pissed that this got out and completely discredited Omalu. Omalu persisted, and something incredible happened: He got a second brain. He continued his studying and wrote another article in the same medical journal he wrote in before…and the NFL got even more pissed and continued to discredit Omalu. And then Omalu got more and more brains…only proving that CTE is real and affects many of the football players that Americans call heroes.

The saddest part is that the NFL denied this for so long, saying Omalu was wrong. But he’s not. Omalu discovered CTE and now we can begin treating these heroes so they don’t suffer like those before them. Like Mike Webster.

brainThe timing on this film is particularly interesting because New Directions Behavioral Health has announced that they will begin treating NFL players for numerous conditions, including addiction and traumatic brain injury. Looks like the NFL has come around, acknowledging Omalu’s research and finally setting up guidelines around traumatic brain injuries.

So, what do the movie “Concussion” and New Directions have in common?

Two words: Kannalife Sciences.

Kannalife is a canna-pharmaceutical company that recently developed and patented a very potent CBD-like compound that is absorbed by the brain more effectively. This patent, KLS-13019, has the ability to help many people who suffer from, oddly enough, neurological conditions. Neurological conditions like CTE, which Dr. Omalu found when studying the brain of deceased football player Mike Webster. And it just so happens that Dr. Omalu is one of Kannalife’s key scientists, specifically in treating CTE.

This got us thinking…could Kannalife be teaming up with Hollywood and NFL with the movie “Concussion” to tell the world about Kannalife’s new CBD-like patented drug? Omalu’s research made such an impact on the NFL that the League was completely against the idea that the sport was responsible for CTE, saying that Omalu’s research was “flawed”. With the news about the NFL offering treatment for athletes combined with their loosening grip on rules pertaining to cannabis, it just can’t be a coincidence that this can all be tied back to CBD and what Dr. Omalu is finding while researching at Kannalife. Movies have predicted many different events in the world and it seems more than coincidental that Hollywood is putting out a blockbuster predicted movie on Christmas Day, right before the Playoffs begin.

It’s becoming increasingly evident that CBD is on the brink of becoming recognized not only by the medical community, but also by the government to be a very powerful medicine. CBD helps treat many neurological conditions and symptoms like PTSD, memory loss, depression, anxiety, and more. CBD can do this because of the special ways the cannabinoid receptors in the brain work with CBD.

All this leaves us wondering what’s coming next in the medical field for CBD. If Hollywood and major sports industries like the NFL are willing to be tied to someone who suggests CBD-like compounds to treat patients, what does that mean for the safe and legal CBD that is available now? CBD is scientifically proven to help heal and nourish the brain, it’s time America sees this. And Hollywood knows it. Why else have Will Smith play Omalu? This movie is destined to be an eye-opener in more ways than one.

Check out the trailer for “Concussion” below:

See related pages about “Concussion” and Kannalife:
IMBD: “Concussion”
Kannalife Patents Pharmaceutical Grade CBD

This article brought to you by International Cannabidiol Organization of Manufacturers and Research (ICOMR) for more CBD research and news, visit www.icomr.org.