Category Archives: Noticias

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Vicki & Aubrie Hill and Intractable Epilepsy

Category : Noticias

The story of Aubrey Hill and her mom who moved to California to get reliable access to cannabis oil to treat her intractable epilepsy — with positive results.
A patient story with a happy ending
patient testimony on using cannabis for epilepsy

A few weeks ago I met Vicki and Aubrie at an event here in Northern California. When they found out that I was the medical director for Hawaiian Ethos, Vicki couldn’t wait to talk to me. With courage and persistence over many years, they have figured out what works best for Aubrie’s epilepsy, and were eager to have me tell their tale. There is a wealth of scientific evidence on the use of cannabis in seizure disorders but nothing carries the message as well as a good story with a happy ending.

This is the story of a vibrant young girl and her determined, brave mother. In 2000, at age five, Aubrie got her scheduled MMR booster. Ten days later she developed a low-grade fever that lasted for 24 days. As the fever persisted, she was getting dehydrated and going deeper into what her mother called a ‘deep, strange sleep.’ She lost her ability to speak and her personality changed, with a loss of interest in her surroundings – unusual for this active five year old. After three weeks, her mother insisted she be hospitalized in Huntsville, Alabama where they lived, because she knew something was terribly wrong. Aubrie was seen by neurologists and, along with a myriad of other diagnoses, they assumed she might have multiple sclerosis. After one week in the hospital she experienced her first seizure, had a lumbar puncture, and they found grey matter in her cerebrospinal fluid. She was diagnosed with meningitis, transferred to Birmingham for ICU care and given 21 days of antibiotics, and started on several seizure medications.

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Aubrey Hill

After the 21 days of antibiotics, the doctors realized it was not infectious meningitis at all and gave her steroids for Acute Disseminated Encephalomyelitis (ADEM), a rare side effect of the MMR booster. She improved immediately and was apparently back to normal.

But it turned out she was not normal. For the next two years, unbeknown to her parents, she was having conversations with cartoon characters in her mind. Finally, her mother observed a partial-complex seizure that looked like the original ADEM. They took her to the University of Alabama Children’s Hospital where she was given multiple anti-seizure medications, none of which were effective. At this point, she was getting partial-complex seizures 3-4 times a week and they were increasing in intensity and frequency.

The left temporal lobe appeared to be the source of the seizures, so she was referred to neurosurgeons who recommended surgery for a seizure disorder that was not responsive to any of the medications available. The family finally agreed to this so the surgeons removed a large amount of brain tissue: the left temporal lobe, some of the hippocampus and some of the frontal lobe. Then, in the ICU, right after surgery, she had her first grand mal seizure. She was in 8th grade.

A young girl this age wants to get her driver’s license. Despite medications, she was still having small seizures regularly but was able to hide them from her parents for a while. But when it became evident she was not seizure-free, another surgery was recommended. Aubrie consented. Again, in the ICU after the surgery, she had a large seizure and noticed that she had lost vision on the right side of her visual field. Six years later, the family was finally informed what the doctors already knew: she had had a stroke causing hemianopia (blindness over half her field of vision). There were also cognitive issues, and alexia without apraxia – difficulty seeing words, an inability to read, and difficulty pronouncing the right words for what she meant to say. She was in 9th grade. The trauma for a girl at this age was intense.

Then, when Aubrie was 18, puberty came along. With the onset of puberty, she developed tonic-clonic grand mal seizures, some lasting more than 20 minutes. They were violent and often difficult to stop with any medications at hand. She was tried on 17 different medications and ended up on 2: Vimpat and Depakote – at maximum dosages. The other fifteen drugs had to be abandoned with “unacceptable side-effects.” Still, every time her period would come around, or the full moon, she would have at least one grand mal seizure, often requiring ER visits due to the severity and inability to control with home medications. She would have more than 4 in a 24-hour period during this early-puberty time.

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Aubrey hugged by Emerald Pharms director Chelsea Lucich

Aubrie had a boyfriend, and they began to secretly smoke recreational marijuana. She was stealing money from her mother to buy it and telling no one. But her mother noticed that she suddenly changed from a suicidal miserable girl who wouldn’t come out of her room into a happy young woman with an enormous appetite. Asked ‘What gives?’ Aubrie told her about the cannabis. Vicki said no more stealing, but it’s obviously good for you so I’ll get it for you in a safe way. So, Mom took over finding marijuana for her daughter in the prohibitive state of Alabama. It did not seem to affect the seizures, but it did make her happy and helped her gain some weight back. At $400/ounce every month for substandard weed, they would parse it out to last the whole month. It was worth it.

Then Vicki found some oil being made in Santa Barbara, CA. Over an 8-month period, she sold some land she had inherited, and spent $16K for the oil that helped, but still didn’t stop the seizures. She knew she was on the right track.

Through Facebook, she connected with a grower in Tuolumne County, CA and he suggested she take the green herb, crush it, and sprinkle that and the kief over her daughter’s pizza. This increased dosage decreased the severity of the seizures, but she still had grand mals every month around her period time. They decided to move to California, where they could really learn and use this medicine.

Vicki sold her house in Huntsville, and $20K in debt, she, Aubrie, and their Maltese dog landed at an Airbnb in Santa Rosa, CA with no local connections or set plans. Two days after landing in CA, Aubrie had a grand mal and Vicki knew she had to get some cannabis quickly. They drove to Tuolumne County where her new friend provided medicine that was rich in THCA. It helped, but she needed large amounts. The THCA decreased the severity and frequency of the seizures, and she could stop one from coming on if the aura was noticed and the medicine was given under Aubrie’s tongue. For the next year they regularly drove to Tuolumne County (4 hours each way) to get this medicine. They then added THC to the mix and found that this would stop the seizures immediately, but would not prevent them. Plus, Aubrie was stoned all the time, not a great situation. But they knew they were getting closer. As Vicki is quick to point out: “There are worse things than Aubrie stoned. She can function with THC, but she could not function on the maximum doses of Depakote.”

A year ago through Emerald Pharms, they found Care By Design and purified CBD products. Aubrie started taking CBD oil capsules twice a day, each with 30mg of CBD for a total of 60mg a day. She stayed on 200mg of Vimpat twice a day, with no side effects. And she took a single dose of Ativan 0.5mg every night, allowing her to sleep well through the night. The seizures decreased in frequency dramatically.

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Fit &
healthy

Still, during full moons and her period, Aubrie could get grand mals. They had several visits to the local hospital when rectal Diastat would not work for stopping violent seizures. (Diastat, which would knock her out for hours, often causes withdrawal seizures within 24 hours of taking it.)

Earlier this year, they met a physician who specializes in pediatric epilepsy and it was recommended that Aubrie take 300mg each day of CBD, according to her size and weight. So they increased the CBD. She is up to 125mg twice a day and it is holding her nicely. In addition, she is using a concentrated oil-extract that has 8.48mg CBD and 12.65mg THC, taking mom-made capsules in MCT (medium-chain triglyceride) oil twice a day. She has had stretches as long as 2-3 weeks with no seizures which they consider a miracle. If she gets an aura, she takes THC or THCA, which have been successful in stopping the seizure before it starts.

One year after starting the CBD, she is brighter, clearer and more active than she has been in years. She had made friends, will take an Uber to town to play pool, and has recently stated that she is ready to learn again. Aubrie is having a life.

At 22, Aubrie may never live independently, she wears an ID bracelet with her condition and medications listed, and she will never drive a car. But she is finally managing her ‘intractable’ seizure disorder and is happy to be alive.

Stacey Kerr MD is a teacher, physician, and author living and working in Northern California. Dr. Kerr was in private practice until she decided to write and educate full-time. After several years working with the Society of Cannabis Clinicians, and co-developing the first comprehensive online course in cannabinoid medicine, she is now serving as the Medical Director for Hawaiian Ethos, an evidence-based cannabis company on the Big Island of Hawaii.

This article was reprinted by Project CBD with permission. It may not be reproduced in any form without approval from the source.

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Statement on Cannabidiol for the FDA

Category : Noticias

Project CBD responds to the Food and Drug Administration’s call for statements on the use of CBD.
By On September 14, 2017

Project CBD's statement to the FDA on cannabidiol

Sept. 13, 2017

The legal and regulatory status of cannabidiol (CBD), a component of the cannabis plant with a huge therapeutic upside, has emerged as a contentious subject in the United States, even though CBD is not intoxicating, has a stellar safety profile, and has no intrinsic abuse liability. When, as expected, CBD becomes an approved pharmaceutical, it will be a matter of enforcement discretion on the FDA’s part as to whether producers of artisanal CBD-rich formulations will be allowed to operate. Accordingly, Project CBD makes the following recommendations to the FDA:

  • Do not make CBD a prescription-only drug. This would only serve the interests of a few pharmaceutical companies while hurting patients who have benefited from CBD-rich food supplements, topicals and other artisanal preparations.
  • Fast track clinical studies designed to compare the efficacy of CBD isolates and whole plant CBD rich extracts. Let’s learn more about the pros and cons of both in order to maximize their benefits and minimize harm.
  • Require safety warnings for CBD isolates regarding drug interactions.
  • While facilitating access to pharmaceutical CBD, don’t impede safe access to artisanal CBD-rich products. We recognize that the FDA is generally not in the business of approving plants as medicine. Nor should the FDA be in the business of undermining plant medicine in general and CBD-rich cannabis therapeutics, in particular.
  • Prohibit the use of toxic thinning agents and flavoring additives in CBD-rich vape oil products. Several additives (propylene glycol and polyethylene glycol, for example) that are commonly found in CBD vape oil cartridges become toxic when heated and inhaled. Most flavoring additives have not been safety tested for inhalation; some are known to be highly toxic when combusted.
  • Publish all FDA test results pertaining to CBD hemp oil products. Artisanal CBD producers have a mixed record thus far with respect to product safety, labeling accuracy, and quality control. The FDA has already documented instances of fraud and product mislabeling when it analyzed the content of several CBD hemp oil items. The bad apples – hemp oil extracts with little or no CBD or excess THC – should not be a pretext for the FDA to prohibit or restrict access to safe, non-pharmaceutical CBD products.
  • Don’t privilege pharmaceutical priorities at the expense of the fledgling, domestic CBD-rich agricultural sector and the CBD food supplement and topical industry. In Denver, Colorado, state law permits wholesale manufacturers of CBD extracts and edibles to source hemp biomass from within and outside Colorado provided that it originates from a farmer who cultivates CBD-rich plants under regulations guided by safe consumption criteria.
  • Implement procedures to harmonize the patchwork of state regulations regarding CBD. Thus far a coherent regulatory framework is lacking. It’s federally illegal to sell food supplements and other products infused with CBD across state lines, but there’s a gap in federal oversight of CBD manufacturing operations.

Here’s why:

Extensive preclinical research has documented the anti-inflammatory properties of single-molecule CBD in animal models of various pathologies, including neuropathic pain, epilepsy, rheumatoid arthritis, irritable bowel syndrome, multiple sclerosis, obesity and diabetes. Scientists are beginning to understand the specific pharmacological mechanisms underlying CBD’s potential as a treatment for cancer, heart disease, addiction, depression and numerous other health disorders. Cannabidiol is a pleiotropic compound that produces many effects through multiple molecular pathways. It taps into how we function biologically on a very deep level: CBD can penetrate the cell membrane and bind to receptors on the nucleus (PPARs), which regulate gene expression and mitochondrial activity.

A 1998 study sponsored by the National Institutes of Health is the basis for a U.S. government patent on the antioxidant and neuroprotective qualities of plant cannabinoids, specifically CBD and psychoactive THC (tetrahydrocannabinol). CBD and THC were found to limit “neurological damage following ischemic insults, such as stroke and trauma.” Both compounds are described as having “particular application … in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia.”

But double blind, randomized clinical trials that could “prove” CBD’s efficacy as a medical treatment have gotten short shrift in the United States because of marijuana prohibition. The few clinical studies involving single-molecule CBD that are underway pale in comparison to the enormous amount of anecdotal data already generated by cannabis clinicians and numerous patients in states where the therapeutic use of cannabis is legal.

Since the rediscovery of CBD-rich cannabis in Northern California in 2009, a growing number of physicians have been recommending CBD-infused oil extracts and concentrates for patients – often with good, and sometimes with jaw-dropping, results in difficult-to-treat cases. Until recently, however, single-molecule CBD formulations were not part of the grassroots medical marijuana experience. While scientists focused on the pharmacology of CBD isolates and other single-molecule cannabinoids, medical marijuana product-makers and providers have been dispensing an array of whole plant CBD-rich options – tinctures, sublingual sprays, gel caps, topicals, edibles, and raw herb – to a wide demographic of patients, many of whom turn to cannabis therapy as a last resort.

In addition to whole plant CBD-rich products sold by medical marijuana dispensaries, CBD isolates derived from industrial hemp are currently available via unregulated online storefronts and delivery services. If, as expected, GW Pharmaceuticals wins FDA approval of Epidiolex, an almost-pure CBD anti-seizure medication, in the near future, it will become available on a prescription basis at a hefty price. Millions of uninsured families in the United States won’t be able to afford it.

The pharmaceutical development of cannabinoid compounds is based upon controlled experimentation with molecular isolates in keeping with the assumption that sick people benefit most from predictable, reproducible medicine that never varies. While isolates can facilitate precision dosage and confidence in the chemical make-up of a drug, monomolecular medicine also has serious drawbacks.

Several scientific studies report that pure, single-molecule CBD, while possibly effective at high doses in preclinical tests, has a much tighter therapeutic window and is much less potent compared to a whole plant CBD-rich concentrate. Moreover, whether synthesized in a lab or heavily refined from industrial hemp paste, pure CBD isolates lack the full array of phytocannabinoids and medicinal terpenes found in whole plant CBD-rich cannabis, which includes hundreds of biologically active components. These constituents interact with CBD and THC to create what scientists refer to as an “entourage” or “ensemble” effect, so that the therapeutic impact of the whole plant is greater than the sum of its parts.

It’s not that single-molecule CBD won’t work — pure CBD can be helpful in certain cases, as clinical trials with epidiolex have shown. But whole plant CBD-rich oil has a much wider therapeutic window than a CBD isolate. This was demonstrated in a 2015 preclinical experiment by Israeli scientists who found that single-molecule CBD required a much higher dose to be effective as an anti-inflammatory and an analgesic compared to a whole plant CBD-rich oil extract. Moreover, if one missed the mark slightly, either too low or too high, then the CBD isolate had little impact on pain and inflammation — unlike the full spectrum CBD-rich oil, which was effective at a much lower, and broader, dosage range. “The therapeutic synergy observed with plant extracts results in the requirement for a lower amount of active components, with consequent reduced adverse effects,” the Israeli researchers concluded.

Other scientists and clinicians have reported similar findings. A 2016 study by Italian researchers found that a whole plant CBD-rich oil extract attenuated inflammation and hypermotility in an animal model of colitis, whereas “pure CBD did not ameliorate colitis” symptoms. “These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD [as a] botanical drug substance for irritable bowel disease treatment.”

Problematic drug interactions are much more likely with high doses of single-molecule CBD, which can inhibit the metabolism of 60 percent of marketed pharmaceuticals. At high doses, CBD will deactivate certain cytochrome P450 enzymes in the liver, thereby altering how we metabolize a wide range of medications, including clobazam, an anti-epileptic drug. This was evident in GW’s epidiolex trials, when children with intractable seizure disorders were given CBD dosages ranging from 5 to 50 mg per kg of body weight. Doctors had to adjust the amount of clobazam the children were taking because of potentially dangerous interactions with epidiolex. Compare the high dose regimen employed by GW Pharmaceuticals to 1 mg per kg of artisanal whole plant CBD-rich oil that cannabis clinicians in California and elsewhere recommend as an initial dosage for treating pediatric epilepsy.

In cancer treatment, the precise dosing of chemotherapy is extremely important; it can be a challenge for doctors to find the maximum effective dose that will not be catastrophically toxic. Many chemotherapy drugs are oxidized by cytochrome P450 enzymes before their inactivation or excretion. This means that for patients also using CBD, the same dose of chemotherapy may produce higher blood concentrations. If CBD inhibits the metabolism of chemotherapy drugs and dosage adjustments aren’t made, the chemotherapy agent could accumulate within the body to highly toxic levels.

There is no clearly established cut-off dose below which CBD does not interact with other drugs. Any pharmaceutical or nutraceutical scheme to exploit the health benefits of cannabidiol must reckon with the fact that therapeutically relevant doses of CBD isolates 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. By and large, however, there have been few problems reported by cancer patients and others who medicate with artisanal CBD-rich cannabis products. The same can’t be said for CBD isolates.

We recognize there is therapeutic value in CBD isolates as well as in whole plant CBD-rich remedies. The FDA should not ordain pharmaceutical CBD as the only legitimate medical option. Single-molecule medicine is the predominant corporate way, the Big Pharma way, but there’s ample evidence that it’s not always the best way to benefit from cannabis therapeutics. Pure CBD is a molecule, not a miracle, and it doesn’t work for everyone. No-THC and low-THC cannabis oil products represent a small slice of the cannabis therapy spectrum. Patients of all ages and economic means should have access to a range of cannabis-based therapeutic options with different concentrations and ratios of CBD and THC, along with other whole plant components.

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Gut Check: Does CBD change to THC in the stomach?

Category : Noticias

Project CBD exposes fraud and financial interests behind misleading report suggesting that CBD converts to THC in the stomach.
By Project CBD On February 14, 2017

CBD does not convert to THC in the stomach

In 2016, a new journal Cannabis and Cannabinoid Research published a paper suggesting that non-psychoactive cannabidiol (CBD) converts to psychoactive tetrahydrocannabinol (THC) in the stomach. The controversial paper was coauthored by several scientists employed by Zynerba Pharmaceuticals in Devin, Pennsylvania. It was not the first time that researchers addressed this issue.

In considering whether CBD converts to THC in the stomach, there are three major kinds of data that scientists examine:

  • The first involves blood samples and physiological tests of humans who have ingested CBD, which demonstrates if they are actually exposed to THC and if they experience THC-like effects after CBD administration.
  • The second kind of data involves studies that examine excreted metabolites after ingestion of CBD. Excretion studies may not prove that a particular metabolite is physiologically relevant, but they could prove if these breakdown metabolites are formed.
  • And the third and least significant type of data derives from experimental organ models—such as artificial gastric fluid or extracted liver microsomes—that might demonstrate the possibility of a CBD-to-THC conversion, but does not necessarily translate into human experience.

The recent article by John Merrick et. al. (2016) that sparked renewed interest in CBD’s potential conversion to THC falls into the third category. It raised concerns among patients, physicians and policymakers about possible adverse side effects that might limit CBD’s otherwise formidable therapeutic utility and market potential. Misinformation regarding the consequences of oral CBD administration could skew public policy and regulatory decisions at a time when cannabinoid therapies are gaining favor among health professionals and the general public.

Inconsistent Findings

There have been extensive clinical trials demonstrating that ingested CBD—even doses above 600 mg—does not cause THC-like effects.1 The lack of THC-like effects was discussed in detail by Grotenhermen et. al. (2017) in a response to Merrick’s publication. The lack of such effects strongly suggests that CBD does not trigger significant CB1 receptor activity in the brain, which would cause a THC-like “high.” One clinical study examined the blood concentration of THC and its active metabolites after 16 men ingested 600 mg of CBD; the resulting change in the concentration of THC metabolites was statistically meaningless. To the extent that THC is formed from orally ingested CBD, it is physiologically insignificant.

There are a few human studies indicating that very small amounts of THC are excreted in urine after someone ingests CBD. Less than 1% of the total CBD is excreted as ∆9-THC, and between 1-2% is excreted as ∆8-THC. These studies demonstrate that a small amount of ingested CBD does isomerize to THC, but this in and of itself has no practical significance. The clinical evidence demonstrating that CBD does not cause THC-like effects subsumes any imagined physiological consequences associated with this data.

Two studies have explored the conversion of CBD to THC in artificial gastric fluid: One performed by Watanabe et. al. (2007) and the recent publication by Merrick and colleagues. Although Merrick cites Watanabe’s work to build the case for CBD-to-THC conversion in the stomach, Merrick’s experiment is strikingly inconsistent with Watanabe’s data. In Watanabe’s simulated gastric fluid study, 15.4% of the CBD was converted into four compounds: ∆9-THC, CBN, 8-OH-iso-HHC, and 9a-OHHHC. (The major product, 8-OH-iso-HHC, is approximately 15 times less potent than THC). Less than 3% of the CBD was actually converted to THC in this experiment, which lasted 20 hours—much longer than CBD remains in the stomach. Yet the article by Merrick proposed that 85% of CBD will break down in a single hour. In other words, the reaction that occurred in Merrick’s study was over 200 times faster than the reaction in Watanabe’s study.2 This discrepancy may be due to different stomach fluid models, and it raises questions about the validity of both models. Moreover, it should be noted that Watanabe explicitly states: “In biological systems, there have been no reports on the conversion of CBD to ∆9-THC itself.”

In Merrick et. al. the discussion following the presentation of test data far outpaces the minor implications of their work. They propose an equation to estimate “THC exposure” after CBD ingestion. What does this equation do for the reader? It provides the reader with information that is at best wildly speculative, and at worst totally wrong. But what does it do for the authors? It inflates the minimal significance of their simulated gastric fluid experiment and conveys a misleading impression that they have discovered something truly important about the use of oral cannabinoid medicine.

From Bad to Worse

The weakest aspect of Merrick’s research is found in the authors’ response (Bonn-Miller et. al. 2017) to cogent criticism about their methodology and conclusion. Published in the same journal, Bonn-Miller’s response is replete with subtle distortions and demonstrable falsehoods, including misrepresentation of the studies they reference to back up their initial report.

In one particularly egregious example, the authors state that “studies documented… poor motor and cognitive performance after administration of oral CBD,” citing an article by Consroe (1979). The actual study by Consroe states that “alcohol and alcohol + CBD, but not CBD given singly, produce decrements of motor and cognitive responses [emphasis added].”

In an attempt to discredit one of the two human studies demonstrating that ingested CBD does not convert to THC to a significant degree, Merrick and his coauthors assert that a chart included in a paper by Martín-Santos et. al. (2012) shows an increase in THC metabolites after CBD administration. But the trend shown in the chart is not only statistically insignificant, it is so minuscule as to be clinically irrelevant.

Other claims in the article, while not outright falsehoods, misrepresent the work of other authors. The conversion of CBD to THC, previously documented by Gaoni and Mechoulam (1968), did not occur in simulated gastric conditions, but rather was performed in a highly unnatural setting with CBD dissolved in sulfuric acid and methanol. This reaction is entirely valid in the realm of chemical synthesis, but it has little to do with real-life human experience.

Merrick and his cohorts also suggest that a recent review by István Ujváry and Lumir Hanuš (2016) “highlighted” the “consistent findings of CBD conversion to THC.” But only a single sentence in this review mentions the conversion of CBD to THC, and this sentence was accompanied by a figure caption indicating that ∆9-THC was a “minor (<1%) urinary metabolite.” Ujváry and Hanuš also note the presence of a small amount of ∆8-THC, which is less psychoactive than ∆9-THC.

It is unclear if the journal Cannabis and Cannabinoid Research peer-reviewed the response to criticism of Merrick’s article, as the response does not appear to meet the standards of scientific reporting. The purpose of peer-review is for scientists to confirm the validity of a paper before publication so that others can read it without questioning the accuracy of its contents. In publishing this response by Bonn-Miller et. al., Cannabis and Cannabinoid Research seems to have failed that goal.3

But the authors may have succeeded in advancing the agenda of Zynerba Pharmaceuticals, the company that funded their research. Zynerba disclosed in a press release (April 12, 2016) that it was developing a transdermal delivery system that “avoids the gastrointestinal tract and potential stomach acid degradation of CBD into THC (associated with psychoactive effects).” In other words, Zynerba has a financial interest in depicting oral CBD, which is well tolerated in clinical research, as potentially harmful.

While purporting to solve a problem that doesn’t actually exist may not amount to much scientifically, Zynerba isn’t the only company making erroneous claims about CBD converting to THC in the stomach. Ananda Scientific, a privately-held Delaware corporation, tried to one-up its competitors by asserting that its hemp-derived CBD formulation is “protected from being transformed, after it is ingested, into THC which is a risk factor in other existing [hemp CBD] products.”

Copyright, Project CBD. May not be reprinted without permission.

Footnotes

1 There are, of course, many effects common to both THC and CBD. The “tetrad” test that is used to assay CB1 receptor activity involves measuring catalepsy, hypothermia, hypomotility, and analgesia. Ingested CBD consistently evokes analgesia, but is inactive on other measures of the tetrad.

2 The rate constant from Merrick’s study was -3.1 * 10^-2 per min, while it was -1.4 * 10^-4 per min in Watanabe’s study. The rate constant for Watanabe’s experiment can be calculated as follows. If we assume first-order kinetics – which makes sense for the degradation of a molecule – then [CBD] / [initial CBD] = exp(-k * t), where k is the rate constant, and […] indicates we are considering concentrations. Since 15.4% of the CBD had degraded at 20 hours (1200 min), the left side of the equation is 1-0.154 = 0.846 when ‘t’ on the right side is 1200 min. Solving for k, we see that k = -ln(0.846)/1200 min ≈ -1.4 * 10^-4/min. If we then compare these rate constants, we see that k_Merrick/k_Watanabe = 222, meaning that CBD degraded 222 times faster in Merrick’s experiment than in Watanabe’s.

3 A coauthor of Grotenhermen’s article told Project CBD that their critical commentary was peer-reviewed before publication. But when asked by Project CBD, the editor of Cannabis and Cannabinoid Research did not comment on whether or not Bonn-Miller (2017) was peer-reviewed. Dr. Bonn-Miller, who was the first author of the response to criticism but was not an author on Merrick’s initial publication, is on the editorial board of Cannabis and Cannabinoid Research.


Sources

Bergamaschi MM, Queiroz RHC, Zuardi AW, Crippa JAS. Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent. Current Drug Safety. 2011, 6:237-249.

Bonn-Miller M, Banks SL, Sebree T. Conversion of Cannabidiol Following Oral Administration: Authors’ Response to Grotenhermen et al. Cannabis and Cannabinoid Research. January 2017, 2(1): 5-7.

Consroe P, Carlini EA, Zwicker AP, Lacerda LA. Interaction of Cannabidiol and Alcohol in Humans. Psychopharmacology. 1979, 66:45-50.

Gaoni Y and Mechoulam R. The iso-tetrahydrocannabinols. Israeli Journal of Chemistry. 1968, 6:679-690.

Grotenhermen F, Russo E, Zuardi AW. Even High Doses of Oral Cannabidiol do not Cause THC-like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research. January 2017, 2(1): 1-4.

Martín-Santos R, Crippa JA, Batalla A, Bhattacharyya S, Atakan Z, Borgwardt S, Allen P, Seal M, Langohr K, Farré M, Zuardi AW, McGuire PK. Acute Effects of a Single, Oral Dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers. Current Pharmaceutical Design. 2012, 18:4966-4979.

Merrick J, Lane B, Sebree T, Yaksh T, O’Neill C, and Banks SL. Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid. Cannabis and Cannabinoid Research. April 2016, 1(1): 102-112.

Ujváry I and Hanuš L. Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy. Cannabis and Cannabinoid Research. March 2016, 1(1): 90-101.

Watanabe K, Itokawa Y, Yamaori S, Funahashi T, Kimura T, Kaji T, Usami N, Yamamoto I. Conversion of cannabidiol to ∆9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice. Forensic Toxicology. 2007 25:16-21.

See also:

Solomon, Shoshanna, “Israeli cannabis-based nanotech droplets start US sales,” The Times of Israel, Dec. 5, 2016.

Zynerba Pharmaceuticals, Inc., “Cannabis and Cannabinoid Research Publishes Data Demonstrating the Degradation of Cannabidiol to Psychoactive Cannabinoids when Exposed to Simulated Gastric Fluid,” press release, April 12, 2016.

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Cannabis Use During Pregnancy: Is it Safe?

Category : Noticias

is using cannabis during pregnancy safe?

Pamela is newly pregnant with her third child. She and her husband think this is going to be their last one because she is having a dreadful time with nausea – morning sickness that lasts all day long. She knows all the tricks. Saltines by her bedside, taking Vitamin B6 and B12, and eating frequently even though her stomach is queasy. She tried ginger. She tried acupuncture. She considered hypnosis. None of it is working, and the added stress of two little ones who still need her attention is making her pregnancy a miserable experience.

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CBD for Fibromyalgia and Opioid Withdrawal

Category : Noticias

patient testimony: CBD to wean off opiates for fibromyalgia

I wanted to relay the experience I’m having with CBD aiding opiate withdrawal. I am a 72-year-old woman. A doctor put me on fentanyl patches about 10 years ago, after trying various painkillers for my intense fibromyalgia pain. They did not notify me how difficult, if not impossible, it would be to get off of them. I use the generic Mylan brand, which can be cut down without deleterious effects. Several times over the years I have attempted to taper down, but even cutting off the tiniest sliver of the patch resulted in intense withdrawal symptoms, so I gave up.

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ICRS 2017: Report from Montreal

Category : Noticias

Dr. Paula Dall’Stella at ICRS conference in Montreal, June 2017

During the last week of June, more than 400 scientists from 25 countries met in Montreal for the 27th annual symposium of the International Cannabinoid Research Society (ICRS). Several presentations and posters showcased new findings about cannabidiol (CBD), the non-euphoric component of the cannabis plant that is transforming the medical marijuana landscape.

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CBD and Parkinson’s Disease

Category : Noticias

How cannabinoid therpay may help Parkinson's disease

Scientists at the University of Louisville School of Medicine in Kentucky have identified a previously unknown molecular target of cannabidiol (CBD), which may have significant therapeutic implications for Parkinson’s Disease (PD).

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Marijuana for the Masses

Category : Noticias

How cannabis helped to ease the pain of changing times

It’s been 50 years since the fabled “Summer of Love” in San Francisco. The City by the Bay was the epicenter of a countercultural uprising fueled by cannabis and LSD, which happened so vividly and with such intensity that it generated worldwide attention.

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Project CBD Responds to California’s Proposed Testing Requirements

Category : Noticias

Project CBD response to California cannabis testing regulations

Our organization outlines our concerns with the State of California’s proposed regulations for cannabis testing regarding pesticides, heavy metals, and solvents and our recommendations for amending them. We believe the following recommendations will benefit patients, recreational users, and people working in the industry.

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