Category Archives: Noticias

  • -

More FDA Warnings, Mislabeled CBD Products & Police Raids

Category : Noticias

A series of police raids in North Dakota has set the stage for a courtroom showdown regarding the legal status of cannabidiol (CBD), the non-intoxicating cannabis component with significant medical properties. Thus far, it’s not going well for purveyors of the claim that hemp-derived CBD is legal in all 50 U.S. states.
By Martin A. Lee On November 10, 2017

Highlights: 
  • The FDA has issued more warning letters to hemp CBD companies for making unsubstantiated medical claims.
  • A study published in the Journal of the American Medical Association indicated that 69 percent of hemp CBD products tested did not contain the amount of cannabidiol indicated on the label.
  • Sporadic police raids continue to target CBD retailers in several states.
  • A legal battle over the status of hemp-derived CBD looms in federal court.

A series of police raids in North Dakota has set the stage for a courtroom showdown regarding the legal status of cannabidiol (CBD), the non-intoxicating cannabis component with significant medical properties. Thus far, it’s not going well for purveyors of the claim that hemp-derived CBD is legal in all 50 U.S. states.

In October 2017, Northwest District Judge Robin Schmidt refused to dismiss drug trafficking charges against Falesteni Abuhamda, the owner of two North Dakota tobacco stores, which allegedly sold products containing CBD with very little or no psychoactive THC [tetrahydrocannabinol]. Abuhamda’s attorney argued that the CBD products were legal because the CBD oil was extracted from the stalk of industrial hemp.

But a forensic scientist with the state’s crime lab easily debunked this argument by stating the obvious: CBD is not found in any appreciable amount in hemp stalk. Rather it exudes from the resinous flowers and leaves of the cannabis plant. And, therefore, CBD is forbidden under the Controlled Substances Act, according to the Drug Enforcement Administration (DEA).

FDA saber-rattling

The Food and Drug Administration (FDA), which defers to the DEA on cannabis-related matters, considers CBD to be an experimental pharmaceutical undergoing evaluation. In early November, the FDA sent letters to several companies selling hemp-derived CBD products warning that they were violating the Federal Food, Drug and Cosmetic Acts.

This was the third time in recent years that the FDA has issued warnings to CBD manufacturers and retailers, which market hemp-derived CBD products as nutraceuticals or food supplements. The most recent round of FDA warning letters did not involve false statements about the source of the CBD extracts. Instead, the agency objected to unsubstantiated medical claims allegedly made by four CBD oil producers: Greenroads Health, Natural Alchemist, That’s Natural! Marketing and Consulting, and last but not least, the Stanley Brothers.

Some of these unsubstantiated claims, according to the FDA, included patient testimonials and assertions that CBD “may be effective in treating tumors from cancer” and other diseases. Thus far, however, there have been no FDA-approved clinical trials that might validate preclinical studies and anecdotal accounts of CBD’s anti-cancer properties.

Today one can easily purchase unregulated CBD products online and at some supermarkets and storefronts across the nation. For the most part, it’s a crapshoot for consumers: A new study published in the Journal of the American Medical Association disclosed that only 31 percent of 84 lab tested hemp-derived CBD products contained the amount of CBD indicated on the label. And who knows what else was in some of these products.

Sporadic raids

While CBD currently seems to be a low priority for federal law enforcement agencies, in recent months there have been sporadic local police raids against CBD retailers in several states besides North Dakota, including (but not limited to):

Image

Ongoing polics raids
  • Indiana. In April 2017, Governor Eric Holcomb signed a bill allowing people with treatment-resistant epilepsy who register with the state to possess CBD products that contain less than 0.3 percent THC. Shortly thereafter, a law enforcement crackdown on CBD retailers resulted in the seizure of more than 3000 CBD products from about 60 stores throughout the Hoosier State. In August, Indiana’s Alcohol and Tobacco Commission declared a moratorium on CBD raids “unless the products clearly violate Indiana law.” Since the moratorium announcement, Indiana excise police have continued to issue citations to stores selling CBD.
  • Missouri. Vince Sanders, owner of American Shaman, a Kansas City-based wholesaler, supplied CBD products to several stores in Missouri and Kansas. He says his products are legal because they are made from industrial hemp and contain hardly any THC. But Missouri law only allows for low-THC cannabis oil to be sold by manufacturers that are licensed by the state health department, which is not the case for American Shaman.
  • Kansas. Kansas is a zero tolerance state when it comes to THC – hardly any is too much in Kansas. Eddie Smith, owner of Into The Mystic, was surprised when police officers showed up at his alternative medicine store in Mission, Kansas, in May 2017 and confiscated an array of hemp-derived CBD products. During a previous visit, an undercover cop purchased some CBD from Smith’s store. A 22-year-old U.S. Army veteran, Smith protested that he had been told “with 100 percent certainty that [CBD] is totally legal in all 50 states.”
  • Wisconsin. In May 2017, police raided several gas stations in Oshkosh, Wisconsin, which sold CBD products. A month later, police busted two storefronts in Franklin, Wisconsin, for retailing CBD-infused gummies that contained traces of THC. The store owners said that they had been assured by the wholesale CBD vendor that the products were legal to sell and possess. But Wisconsin law stipulates that CBD can only be dispensed by a pharmacist or physician – not a gas station – to a patient who has been certified to possess cannabidiol for treating a specific medical condition.
  • Ohio. In August 2017, police returned 18 bottles of hemp-derived CBD to Poor Boys Smoke Shop in Marysville, Ohio, after a Union County prosecutor declined to press charges stemming from a law enforcement raid two years earlier. Medical marijuana is technically legal in Ohio, but corrupt licensing procedures have stymied patient access to cannabis and CBD-rich products.
  • Nebraska. In September 2017, Nebraska Attorney General Doug Peterson declared that CBD sales in the Cornhusker State are flat-out illegal. But under state law, the University of Nebraska Medical Center has the authority to distribute CBD to certified patients who participate in an experimental research program. CBD commerce outside of the university program is strictly forbidden. “To date no drug products containing CBD have received FDA approval,” Peterson noted.
  • Massachusetts. Two detectives visited Jay’s Smoke Shop in Taunton, MA, to inform the proprietor that it was not okay to sell CBD products at his store, even though residents in the Bay State had voted to legalize cannabis both for medical and adult use. It’s currently legal to possess and use cannabis, including CBD-rich products, in Massachusetts, but not in public or while driving a vehicle. Storefront sales won’t be authorized until 2018 at the earliest.

Complicated laws

Image

Source: Wikipedia “Legality of cannabis by U.S. jurisdiction”

Currently eight states plus the District of Columbia have legalized cannabis for both medical and adult use; twenty-one more states allow the therapeutic use of cannabis to some degree, but not recreational use; and 18 states have legalized CBD, but not the whole plant or cannabis products containing higher levels of THC. Only three states consider every part of the cannabis plant, including CBD, to be illegal.

Does this mean that cannabidiol is actually legal in most of the United States?

Yes, sort of … maybe.

Confusion regarding CBD’s status stems in part from the patchwork of complicated laws that vary from state to state. But the main problem is Uncle Sam’s abject refusal to acknowledge what has been known throughout the world for centuries: cannabis has significant medical value. Cannabis prohibition, a draconian, racist relic, is based on a mountain of lies, and until this anachronistic policy is terminated, attempts to sort out the legal status of CBD will be mired in contradiction and uncertainty.

Most so-called CBD-only states allow possession of very low or no-THC cannabis products, but do not allow licensed dispensaries, production facilities or home cultivation. In other words, one can possess CBD, but one can’t legally buy it or sell it. Overly restrictive laws in CBD-only states often limit the use of CBD products to children with treatment-resistant seizure disorders.

But even in states with legal protections for CBD users, the substance is still technically forbidden under federal law. Several bills are pending in Congress to extricate CBD from the Controlled Substances Act. Such efforts would not be necessary if CBD was federally legal.

No resin, no THC, no CBD

Undaunted, some CBD proponents believe that cannabidiol is already legal by virtue of a 2004 Ninth Circuit U.S. Appeals Court decision (Hemp Industries Association v. DEA) that struck down the DEA’s attempt to ban hemp food products. But this decision never mentioned CBD and the reasoning behind it undermines the notion that hemp stalk is a viable source of CBD.

Image

No resin, no THC, no CBD

The Ninth Circuit rejected the DEA’s argument because hemp food products aren’t made from the resin-bearing parts of the plant – the flower tops and leaves – that contain THC and other proscribed cannabinoids.

Hemp-derived protein powder and nutritional supplements are made from hempseed, which has no resin, no THC and no CBD; thus hemp food, according to the Ninth Circuit ruling, is exempt from the Controlled Substances Act.

The DEA lacked credibility when it argued that hemp food should be banned because it comes from hempseed (which is resin-deficient). And today’s CBD hemp companies lack credibility when they try to skirt the law by arguing that their CBD comes from hemp stalk (which is resin-deficient).

Image

2014 Farm Bill

The Farm Bill exception

The 2014 Farm Bill also makes no mention of CBD, but it is often cited by domestic hemp producers as the reason why CBD is federally legal. The Farm Bill defines industrial hemp as cannabis that contains 0.3 percent THC or less. Cannabis with more than 0.3 percent THC in any part of the plant is considered marijuana and is therefore illegal under federal law.

Most significantly, the Farm Bill carved out an exception to the Controlled Substances Act for industrial hemp that is cultivated under the auspices of a state-sanctioned agricultural or academic research program. (The Farm Bill doesn’t specify what constitutes “research.”) Thus far, twenty-three states have enacted laws pertaining to industrial hemp. And for the first time since World War II, industrial hemp is being grown – supposedly for research purposes –in many parts of the United States.

The Omnibus Appropriations Act of 2016 gave another boost to the fledgling domestic hemp industry by stipulating that federal funds could not be used “to prohibit the transportation, processing, sale or use of industrial hemp that is grown or cultivated in accordance with [the Farm Bill]” – in other words, neither the DEA nor state law enforcement can prevent interstate commerce involving industrial hemp.

Does this mean that CBD oil extracted from hemp grown in Kentucky or Colorado is legal to process, sell and transport across state lines, as long as it doesn’t have more than 0.3 percent THC?

The Hemp Industries Association says yes. The DEA says no.

Legal battle looming

In December 2016, the DEA issued an administrative tracking code for cannabis oil extracts, including CBD concentrates and isolates derived from hemp biomass as well as from marijuana leaves and flower tops. This tracking code did not ban CBD because CBD has always been illegal under the 1970 Controlled Substances Act, which forbids any preparation made from cannabis resin.  All the phytocannabinoids, including CBD and THC, reside in the resinous trichomes of the cannabis plant.

The Hemp Industries Association (HIA) maintains that the DEA failed to recognize the legal distinction between marijuana and hemp, as defined by the Farm Bill, when it announced the new tracking code for cannabis oil extracts. So in January 2017, the HIA filed a judicial review petition that challenged the DEA’s churlish administrative maneuver.

Until a federal judge weighs in, robust CBD commerce will continue in a confusing legal environment, while sports stars and celebrities sing the praises of CBD and medical patients clamor for quality cannabis oil extracts.

About the Author:

Martin A. Lee is the director of Project CBD and author of Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific.



1 Even though 0.3 percent THC is an arbitrary political number with no scientific basis, it has become the current standard that much of the world uses to distinguish hemp from marijuana. The 0.3 percent legal limit for THC is based on the work of Canadian cannabis researcher Ernst Small, who wrote The Species Problem with Cannabis. In this book, Small acknowledged that there isn’t a natural dividing point at which cannabinoid content could be used to distinguish hemp from other kinds of cannabis. Nevertheless, he chose 0.3 percent THC as where to draw the line on the continuum of cannabis types.
2 The 1970 Controlled Substances Act defines “marihuana” as “all parts of the plant Cannabis sativa L. [sic], whether growing or not; the seeds thereof; the resin extracted from any part of such plant; and every compound, manufacture, salt, derivative, mixture, or preparation of such plant, its seeds or resin. Such term does not include the mature stalks of such plant, fiber produced from such stalks, oil or cake made from the seeds of such plant, any other compound, manufacture, salt, derivative, mixture, or preparation of such mature stalks (except the resin extracted therefrom), fiber, oil or cake, or the sterilized seed of such plant which is incapable of germination.”

Powered by WPeMatico


  • -

CBD as Preventative Medicine

Category : Noticias

An excerpt from CBD: A Patient’s Guide to Medicinal Cannabis by Leonard Leinow & Juliana Birnbaum
By By Leonard Leinow & Juliana Birnbaum On November 07, 2017

A new book discusses seven ways CBD-rich cannabis can be used to prevent disease
Highlights: 
  • CBD has anti-inflammatory properties and studies suggest that it can reduce the risk of cancer, metabolic disorders and neurodegenerative disease
  • Low doses of cannabinoids can stimulate the creation of new nerve cells in animal models, even in aging brains
  • CBD has been shown to block an enzyme that destroys bone-building compounds in the body, reducing the risk of age-related bone diseases like osteoporosis and osteoarthritis
  • When applied topically as an infused lotion, serum, oil, or salve, the antioxidants in CBD (a more powerful antioxidant than vitamins E and C) can repair damaged skin

Cannabinoid therapy is connected to the part of the biological matrix where body and brain meet. Since CBD and other compounds in cannabis are so similar to the chemicals created by our own bodies, they are integrated better than many synthetic drugs. According to Bradley E. Alger, a leading scientist in the study of endocannabinoids with a PhD from Harvard in experimental psychology, “With complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind. By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.”

Reduced Risk of Diabetes and Obesity

Image

Regular cannabis users have a lower BMI.

Several studies have shown that regular cannabis users have a lower body mass index, smaller waist circumferences, and reduced risk of diabetes and obesity. One 2011 report published in the American Journal of Epidemiology, based on a survey of more than fifty-two thousand participants, concluded that rates of obesity are about one-third lower among cannabis users. This is despite the findings that participants tend to consume more calories per day, an activity that is potentially related to THC’s stimulation of ghrelin, a hormone that increases appetite but also increases the metabolism of carbohydrates. CBD on its own was shown in 2006 to lower the incidence of diabetes in lab rats, and in 2015 an Israeli-American biopharmaceutical collective began stage 2 trials related to using CBD to treat diabetes. Research has demonstrated that CBD helps the body convert white fat into weight-reducing brown fat, promoting normal insulin production and sugar metabolism.

In studying over 4,600 test subjects, researchers found that current cannabis users had fasting insulin levels that were up to 16 percent lower than their non-using counterparts, higher levels of HDL cholesterol that protects against diabetes, and 17 percent lower levels of insulin resistance. Respondents who had used cannabis in their lifetime but were not current users showed similar but less pronounced associations, indicating that the protective effect of cannabis fades with time.

Excess insulin promotes the conversion of sugars into stored fat and leads to weight gain and obesity. The research emerging about the interplay between cannabinoids and insulin regulation may lead to some major breakthroughs in the prevention of obesity and type 2 diabetes.

Better Cholesterol Profiles and Lowered Risk of Cardiovascular Disease

Image

Regular cannabis users had increased levels of HDL-C and slightly lower levels of LDL-C.

A 2013 study that measured data from 4,652 participants on the effect of cannabis on metabolic systems compared non-users to current and former users. It found that current users had higher blood levels of high-density lipoprotein (HDL-C) or “good cholesterol.” The same year, an analysis of over seven hundred members of Canada’s Inuit community found that, on average, regular cannabis users had increased levels of HDL-C and slightly lower levels of LDL-C (“bad cholesterol”).

Linked to diet and lifestyle, atherosclerosis is common in developed Western nations and can lead to heart disease or stroke. It is a chronic inflammatory disorder involving the progressive depositing of atherosclerotic plaques (immune cells carrying oxidized LDL or low-density lipoproteins). A growing body of evidence suggests that endocannabinoid signaling plays a critical role in the pathology of atherogenesis. The condition is now understood to be a physical response to injuries in the arterial walls’ lining, caused by high blood pressure, infectious microbes, or excessive presence of an amino acid called homocysteine. Studies have demonstrated that inflammatory molecules stimulate the cycle leading to atherosclerotic lesions. Existing treatments are moderately effective though carry numerous side effects. CB2 receptors triple in response to inflammation, allowing anandamide and 2-AG, the body’s natural cannabinoids, to decrease inflammatory responses. The CB2 receptor is also stimulated by plant-based cannabinoids.

A 2005 animal trial showed that low-dose oral cannabinoids slowed the progression of atherosclerosis. Researchers the following year wrote that the immunomodulatory capacity of cannabinoids was “well established” in science and suggested they had a broad therapeutic potential for a variety of conditions, including atherosclerosis.

A 2007 animal study with CBD showed it had a cardioprotective effect during heart attacks, and more details were published that year about the involvement of the CB1 and CB2 receptors in cardiovascular illness and health.

Reduced Risk of Cancer

Image

Several studies had already shown that THC prevents tumors and reduces them.

Could cannabidiol help prevent tumors and other cancers before they grow? A 2012 study showed that animals treated with CBD were significantly less likely to develop colon cancer after being induced with carcinogens in a laboratory. Several studies had already shown that THC prevents tumors and reduces them, including one in 1996 on animal models that found that it decreased the incidence of both benign and hepatic adenoma tumors. In 2015, scientists analyzed the medical records of over eighty-four thousand male patients in California and found that those who used cannabis, but not tobacco, had a rate of bladder cancer that was 45 percent below the norm. Topical products can be used to treat and prevent skin cancers. Continuing research is focused on the best ratio of CBD to THC and the most effective dose level in cancer prevention and treatment.

Cannabinoids Help Maintain Brain Health and Create Resilience to Trauma and Degeneration

Image

Cannabinoids help maintain and regulate brain health.

Cannabinoids are neuroprotective, meaning that they help maintain and regulate brain health. The effects appear to be related to several actions they have on the brain, including the removal of damaged cells and the improved efficiency of mitochondria. CBD and other antioxidant compounds in cannabis also work to reduce glutamate toxicity. Extra glutamate, which stimulates nerve cells in the brain to fire, causes cells to become over-stimulated, ultimately leading to cell damage or death. Thus, cannabinoids help protect brain cells from damage, keeping the organ healthy and functioning properly. CBD has also been shown to have an anti-inflammatory effect on the brain.

As the brain ages, the creation of new neurons slows down significantly. In order to maintain brain health and prevent degenerative diseases, new cells need to be continuously created. A 2008 study showed that low doses of CBD– and THC-like cannabinoids encouraged the creation of new nerve cells in animal models, even in aging brains. CBD also helps prevent other nerve-related diseases like neuropathy and Alzheimer’s disease.

Protects against Bone Disease and Broken Bones

Image

CBD helps spur the process of new bone-cell formation.

Cannabinoids are facilitative of the process of bone metabolism—the cycle in which old bone material is replaced by new at a rate of about 10 percent per year, crucial to maintaining strong, healthy bones over time. CBD in particular has been shown to block an enzyme that destroys bone-building compounds in the body, reducing the risk of age-related bone diseases like osteoporosis and osteoarthritis. In both of those diseases, the body is no longer creating new bone and cartilage cells. CBD helps spur the process of new bone-cell formation, which is why it has been found to speed the healing of broken bones and, due to a stronger fracture callus, decrease the likelihood of re-fracturing the bone (bones are 35–50 percent stronger than those of non-treated subjects).

Protects and Heals the Skin

Image

CBD can an repair damage from free radicals like UV rays and environmental pollutants.

The skin has the highest amount and concentration of CB2 receptors in the body. When applied topically as an infused lotion, serum, oil, or salve, the antioxidants in CBD (a more powerful antioxidant than vitamins E and C) can repair damage from free radicals like UV rays and environmental pollutants. Cannabinoid receptors can be found in the skin and seem to be connected to the regulation of oil production in the sebaceous glands. Cannabis-based topical products are being developed to treat related issues from acne to psoriasis and can promote faster healing of damaged skin. In fact, historical documents show that cannabis preparations have been used for wound healing in both animals and people in a range of cultures spanning the globe and going back thousands of years. The use of concentrated cannabis oils to treat skin cancer is gaining popularity with a number of well-documented cases of people curing both melanoma and carcinoma-type skin cancers with the topical application of CBD and THC products. Cannabis applied topically is not psychoactive.

Anti-inflammatory

Image

CBD is a known anti-inflamatory.

Cannabinoids have been proven to have an anti-inflammatory effect in numerous studies. CBD engages with the endocannabinoid system in many organs throughout the body, helping to reduce inflammation systemically. The therapeutic potential is impressively wide-ranging, as inflammation is involved in a broad spectrum of diseases.

This article has been adapted from CBD: A Patient’s Guide to Medicinal Cannabis by Leonard Leinow & Juliana Birnbaum (Berkeley, CA: North Atlantic Books, 2017).

Powered by WPeMatico


  • -

From Clone to Concentrate: How CBD Cannabis Oil is Made

Category : Noticias

See how CBD cannabis oil is extracted and produced.
By Project CBD On November 08, 2017

How CBD cannabis oil is made

See how cannabis oil is extracted and produced.

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

Powered by WPeMatico


  • -

Cannabis & Sleep Disturbances

Category : Noticias

Quality sleep is critical to human emotional, mental and physical health, yet it eludes between 50-70 million Americans. In this report, we will explore why sleep matters, the role of the endocannabinoid system in sleep, and how cannabis and its components—in particular, CBD and THC—may benefit those with sleep issues.
By Nishi Whitely On October 29, 2017

A Project CBD Special Report
Highlights: 
  • Sleep disturbances are the most common health problem in America. Those with sleep issues are poorly served by prescription and over-the-counter sleeping pills and other pharmaceuticals, which have serious risks.

  • CBD and other plant cannabinoids show promise for treating insomnia, sleep apnea, narcolepsy, and other sleep-related disorders.

  • CBD co-administered with THC improves sleep more efficaciously than single-molecule medications.
  • Chronic, heavy consumption of THC-dominant cannabis can disrupt healthy sleep patterns.
  • Our ability to be awake, fall asleep, stay asleep and wake up feeling rested is part of an internal biological process regulated by circadian rhythms and the endocannabinoid system.
CBD, sleep and cannabis

Shut-eye overview

Although sleep is essential for our health, its biological purpose is not fully understood. Oddly, the seemingly inactive state of sleep is actually a dynamic and critical process that helps us store memories, build immunity, repair tissue, regulate metabolism and blood pressure, control appetite and blood sugar, and process learning, along with a myriad of other physiological processes – all of which are regulated by the endocannabinoid system (ECS).

According to the National Institute of Neurological Disorders and Stroke at the National Institute of Health (NIH), new findings suggest “sleep plays a housekeeping role that removes toxins in your brain that build up while you are awake.”

Poor sleep is the number one reported medical complaint in the Unites States and a serious public health concern. The average adult needs between seven and eight hours of sleep per day. Yet, 10-30 million Americans regularly don’t get enough sleep.

Over 60 percent of American adults report having problems sleeping several nights per week.

Over 40 million Americans suffer from more than 70 different sleep disorders. The most common sleep-related ailments include:

  • Insomnia – when one cannot fall asleep or stay asleep.
  • Sleep apnea – which involves impaired breathing while sleeping.
  • Restless leg syndrome – characterized by tingling, discomfort and even pain in the legs that increases at night and is relieved by movement.
  • Circadian rhythm disorders – when one’s internal clock is off and one’s sleep patterns are disturbed.
  • Parasomnias – which entails abnormal movements and activities while sleeping, including sleep walking and nightmares.
  • Excessive daytime sleepiness – when an individual experiences persistent drowsiness during daylight hours from narcolepsy or another medical condition.

Poor sleep is a risk factor for serious illness. Compared to people who get enough sleep, adults who are short-sleepers (less than 7 hours per 24-hour period) are more likely to experience one or more of 10 chronic health conditions, including obesity, heart disease, diabetes, arthritis, stroke and depression.

Those with chronic illnesses are at greater risk for insomnia, which exacerbates their discomfort. Comorbid medical disorders – including conditions that cause hypoxemia (abnormally low blood oxygen levels) and dyspnea (difficult or labored breathing), gastroesophageal reflux disease, pain, and neurodegenerative diseases – have a 75-95 percent increased risk of insomnia.

Pills that kill

Image

pills for sleep disorders have many side effects

In 2016, according to the industry research firm MarketsandMarkets, Americans spent $3.38 billion on prescription sedatives and hypnotics, over-the-counter (OTC) sleep drugs, and herbal sleep aids. It’s projected that the market for such products will experience about a 4.5 percent growth rate between now and 2021.

The quest for good night’s sleep can be hazardous to one’s health. Daniel F. Kripke, MD, sleep expert and co-founder of Research at Scripps Clinic Vitebri Family Sleep Center, discusses the dangers of sleep aids in his paper “Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit.”

Dr. Kripke reviewed 40 studies conducted on prescription sleeping pills, which include hypnotic drugs such as zolpidem (Ambien, Edlmar, Intermezzo and Zolpimist), temazepam (Restoril), eszopiclone (Lunesta), zaleplon (Sonata), triazolam (Halcion), flurazepam (Dalmane and Dalmadorm), quazepam, and other barbiturates used for sleep. Of these 40 studies, thirty-nine found that consumption of hypnotics is “associated with excess mortality” to the tune of a 4.6 times greater risk of death for hypnotic users.

Grim statistics: 10,000 deaths per year are directly caused by and attributed to hypnotic drugs, based on medical examiner data. However, large epidemiological studies suggest the number of fatalities may actually be closer to 300,000-500,000 per year. The difference can be attributed to underreported use of hypnotics at the time of death and the fact that prescription hypnotics are rarely listed as the cause of death.

Dr. Kripke concludes that even limited use of sleeping pills causes “next day functional impairment,” increases risk of “on-the-road driver-at-fault crashes,” increases falls and accidental injuries especially among seniors, is associated with “2.1 times” as many new depression incidents compared to randomized placebo recipients, and increases the risk of suicide. Furthermore, the use of opioids combined with hypnotics – two known dose-dependent respiratory suppressants – can be extremely dangerous, especially when mixed with alcohol and other drugs.1

Alarming data

Another concern: Data from controlled hypnotics trials resulted in 12 cancers in hypnotic participants compared to zero cancers in the placebo group. (When the FDA conducted the same audit, they found 13 cancers.) But it is unclear if the hypnotics were a causative factor in these cancers or if they were promoting progression of cancer that had previously gone undetected. Animal and in vitro (test tube/petri dish) studies also attest to the pro-cancer potential of hypnotics. To learn more visit Dr. Kripke’s website.

In addition to these risks, meta-data (combined data) from placebo-controlled randomized clinical trials showed participants in the hypnotic groups had a 44 percent higher infection rate than the placebo participants.

Are over-the-counter sleep aids any better? These also have adverse side effects. Most OTC sleeping pills (Benadryl and others) have the antihistamine diphenhydramine as the primary ingredient. It can knock you out, but it’s unlikely to provide truly restful sleep.

In an email exchange with Project CBD, Dr. Kripke writes: “Usage of diphenhydramine is associated with developing Alzheimer’s disease, though which is cause and which is effect is certainly unclear. One well-known aspect of diphenhydramine is that it is anticholinergic [blocks the neurotransmitter acetylcholine], that produces some heart symptoms sometimes as well as digestive symptoms such as constipation. In some patients, also, diphenhydramine at night causes rather a lot of daytime sleepiness.”

A large number of OTC sleep aids also include acetaminophen, a pain reliever that has a narrow therapeutic window – meaning at one dose it’s therapeutic, but the slightest increase can be toxic to the liver. All too often consumers don’t read the warning labels about these drugs and consume them with alcohol and other meds. This can cause liver toxicity and/or fatal respiratory suppression.

OTC sleep aids are intended only for occasional or short-term use – never more than two weeks at one time. Although it is not typically reported in the published literature, those who use OTC and prescription sleep aids find that once they start it’s hard to stop.

The endocannabinoid system and sleep

Given the problems with conventional soporifics, medical scientists have been exploring other ways to improve sleep by targeting the endocannabinoid system (ECS). As the primary homeostatic regulator of human physiology, the ECS plays a major role in the sleep-wake cycle and other circadian processes.

Italian scientist Vicenzo DiMarzo summarized the broad regulatory function of the endocannabinoid system in the phrase “Eat, sleep, relax, protect and forget.”

How we fall asleep, stay asleep, wake up, and remain awake is part of an internal biological process regulated by our circadian rhythms and our endocannabinoid system. Circadian rhythms govern a diverse array of actions in the body, including hormone production, heart rate, metabolism, and when to go to sleep and wake up.

It’s as if we have an internal biochemical timer or clock that keeps track of our need for sleep, guides the body to sleep and then influences the intensity of sleep. This biological mechanism is affected by external forces such as travel, medication, food, drink, environment, stress and more.

Key question: Does the endocannabinoid system regulate our experience of circadian rhythms or vice versa?

Evidence of a strong relationship between the two is observed in the sleep-wake cycle fluctuations of anandamide and 2-AG (the brain’s own marijuana-like molecules), along with the metabolic enzymes that create and break down these endogenous cannabinoid compounds.

Anandamide is present in the brain at higher levels at night and it works with the endogenous neurotransmitters oleamide and adenosine to generate sleep. Conversely, 2AG is higher during the day, suggesting that it is involved in promoting wakefulness.

The highly complex sleep-wake cycle is driven by a variety of neurochemicals and molecular pathways.2 Both anandamide and 2AG activate CB1 cannabinoid receptors that are concentrated in the central nervous system, including parts of the brain associated with regulating sleep.

CB1 receptors modulate neurotransmitter release in a manner that dials back excessive neuronal activity, thereby reducing anxiety, pain, and inflammation. CB1 receptor expression is thus a key factor in modulating sleep homeostasis.

This is not the case, however, with respect to the CB2, the cannabinoid receptor located primarily in immune cells, the peripheral nervous system, and metabolic tissue. Whereas CB1 receptor expression reflects cyclical circadian rhythms, no such fluctuations have been described for the CB2 receptor.

The challenge of studying and treating sleep disturbances is complicated by the fact that sleep disorders are symptomatic of many chronic illnesses. In many cases, poor sleep results in chronic illness, and chronic illness always involves an underlying imbalance or dysregulation of the endocannabinoid system. Although we still have much to learn about the relationship between the ECS and circadian rhythms, it’s clear that adequate quality sleep is a critical component of restoring and maintaining one’s health.

Cannabis for slumber

Image

cannabis for insomnia

Poor sleep and lack of sleep cause physiological changes in the body after just one night, resulting in slower reaction times, deceased cognitive performance, less energy, aggravated pain and inflammation, and in many cases overeating or cravings for high-fat, high-carbohydrate “comfort” foods.

Cannabinoids have been used for centuries to promote sleepiness and to help people stay asleep. In the acclaimed medical reference Materia Medica, published in the 18th century, cannabis was listed as a ‘narcotica’ and ‘anodyna’ (pain reliever). Its reintroduction to Western medicine by Sir William B. O’Shaughnessy in 1843 led to studies that underscored the remedial properties of “Indian hemp” for sleep disorders.

“Of all anaesthetics ever proposed, Indian hemp is the one which produced a narcotism most closely resembling the natural sleep without causing any extraordinary excitement of the vessels, or any particular suspension of secretions, or without fear of a dangerous reaction, and consecutive paralysis,” German researcher Bernard Fronmueller observed in 1860.

Nine years later Fronmueller reported that in 1000 patients with sleep disturbance, Indian hemp produced cures in 53 percent, partial cure in 21.5 percent, and little or no effects in 25.5 percent.

Sleep-related problems continue to drive a large percentage of people to seek relief with cannabis.

A 2014 study by Babson et al notes that approximately 50 percent of long-term cannabis consumers (over 10 years) report using cannabis as a sleep aid. Among medical marijuana patients, 48 percent report using cannabis to help with insomnia.

Another study revealed that 40 percent of insomniacs also suffer from anxiety and depression or another a psychiatric disorder. (Roth, 2007) Would it surprise you to learn that people with mood disorders who use cannabis have the highest rates of sleep benefit at 93 percent? (Babson & Bonn-Miller, 2014)

“Sorrow can be alleviated by good sleep.” So said Thomas Aquinas.

Image

cannabinoids for sleep

CBD, THC, CBN

What about specific plant cannabinoids for sleep?

Cannabidiol (CBD) is alerting or mildly stimulating in moderate doses, while its psychoactive counterpart delta 9-tetrahydrocannabinol (THC) tends to be sedating. However, the science is somewhat paradoxical.

Research data and anecdotal accounts indicate that CBD and THC have differential effects on sleep – both can be alerting or sedating depending on dosage.

The biphasic dose response triggered by CBD and THC is one of the factors that may contribute to conflicting research results with respect to cannabinoids and sleep.3

The association between low-dose cannabidiol and increased wakefulness underscores CBD’s potential as a treatment for narcolepsy and other variants of excessive daytime sleepiness.

Curiously, CBD can help people fall asleep as well as stay awake. An insomnia study indicated that the administration of 160 mgs of CBD decreased nighttime sleep interruptions and increased total sleep time, suggesting that high-dose CBD therapy can improve the quality and duration of sleep.

In addition to showing promise as a safe and effective alternative to conventional psychiatric treatments for insomnia, cannabidiol can reduce symptoms of REM behavior disorder (RBD), which is characterized by the acting out of vivid, intense, and sometimes violent dreams. A preliminary study examined the efficacy of CBD in patients with both Parkinson’s disease and RBD and the results were encouraging.

Obstructive sleep apnea (OSA) is a prevalent form of sleep disorder breathing that affects nine percent of American adults. Research involving animal models of this condition has shown that THC and the endogenous cannabinoid oleamide are effective in reducing sleep apnea events. (Babson 2017) Human studies indicate that dronabinol, a FDA-approved synthetic version of THC, reduces sleep apnea and is safe and well tolerated.

Additionally, cannabinol (CBN), most commonly associated with aged cannabis, is said to potentiate the sedative properties of THC when these two cannabinoids are used together, although this notion may be more modern-day marijuana folklore than scientific fact.

Pain and sleep

Besides the desire for good sleep, treating pain is another common reason for using cannabis. Chronic pain is a major public health issue that directly affects around 20 percent of U.S. adults, many of whom also suffer from diminished sleep. Sometimes it’s hard to know if the pain is causing sleeplessness or if sleeplessness is triggering the pain.

Patients seeking both pain relief and better sleep may achieve positive results with cannabinoids and other cannabis components.4 In their paper “Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex®, a Cannabis-Based Medicine,” Russo et al summarized 13 studies that examined varying cannabis preparations for pain and sleep.

Of particular interest is a Phase II study, involving 24 patients with intractable multiple sclerosis, which compared three different preparations: Tetranabinex (a high THC product); Nabindolex (high CBD); and Sativex® (an almost a 1:1 THC:CBD sublingual remedy).

Different cannabinoid ratios helped in various ways: “Compared to placebo, the CBD-predominant extract significantly improved pain, the THC-predominant extract yielded significant improvement in pain, muscle spasm, spasticity and appetite, and combined THC:CBD extracts (Sativex®) significantly improved muscle spasm and sleep.”

The authors concluded that a combination of CBD and THC (15 mg of each) “improved sleep synergistically.” Of the thirteen studies profiled in this paper, seven showed improvements in sleep. Six of the seven were conducted with Sativex®, the 1:1 CBD:THC sublingual spray, indicating that balanced a cannabinoid profile facilitates sleep improvements among patients with chronic pain.5

The gift of forgetting

The use of cannabis is prevalent among those who suffer from post-traumatic stress disorder (PTSD). A small open trial conducted in Israel showed that 5 mg of smoked THC twice a day resulted in improved sleep and reduced frequency of nightmares in patients with PTSD. (Mechoulam, 2015) This directly correlates with similar test results involving nabilone, a synthetic THC-like drug.

Memory processing occurs when we are asleep, so it stands to reason that someone suffering from PTSD – especially those who experience nightmares – would benefit by using cannabis or cannabinoids to sleep better.

At first glance, it may appear that cannabis is merely a coping mechanism for PTSD patients; it is sometimes negatively characterized this way in the medical literature. Thus far, the majority of studies involving cannabinoids and PTSD have been conducted from an addiction perspective – will cannabis harm PTSD patients and turn them into addicts? – but that may be changing.

Increasingly researchers are recognizing the limitations of the addiction framework, which overlooks the crucial role that the endocannabinoid system plays in helping us forget painful memories, a normal process that is somehow dysregulated when one experiences PTSD.

In some cases, THC and other plant cannabinoids can provide enough relief so that PTSD sufferers are able to embark upon the task of making sense of their traumatic memories and begin the healing process. None of that can happen without quality sleep.

“If you can’t sleep your world goes to hell in a hand basket real fast,” said Al Byrne, a U.S. Navy veteran and medical marijuana advocate.

Many military veterans and victims of sexual abuse are using cannabis to treat their PTSD-related symptoms. A 2016 case study provided clinical data that validated the use of CBD-rich oil as a safe and effective treatment for reducing anxiety and improving sleep in a young girl with PTSD.

Pharmaceuticals provided minimal relief for a 10-year-old girl who had been sexually abused as a young child. And her meds caused major adverse side effects. But a CBD-rich oil regimen resulted in “a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient’s sleep.”

This is not an isolated example. CBD-rich oil, an increasingly popular treatment for anxiety and sleep problems, has emerged in recent years as a viable alternative to Big Pharma drugs.

Dosing for slumber

Cannabis therapeutics is personalized medicine – and this is certainly true with respect to using the herb and its components to treat sleep disorders. The effectiveness of cannabis as a sleep aid is highly variable, depending on the individual user, how the remedy is administered, its cannabinoid ratio and aromatic terpene profile, the timing and dosage – all these factors come into play and influence different outcomes.

Image

natural remedies for insomnia

Success may rest upon how well one manages the psychoactive qualities of cannabis. As with any medicine, there are some risks involved when consuming cannabis to sleep better. Short-term use of cannabis may decrease sleep onset latency (how long it takes to fall asleep). But this improvement may weaken over time. Tolerance develops with chronic consumption, which can impair long term sleep quality.

Too much of a good thing can be problematic for frequent recreational cannabis users, who may begin to experience a reduction in slow-wave deep sleep, leaving the individual feeling like they are not well rested. Could this be because recreational users tend to prefer large amounts of THC-dominant cannabis varieties?

Sleep disturbance, ironically, is perhaps the most notable withdrawal symptom when a heavy user stops smoking marijuana. Compared to kicking addictive pharmaceuticals, cannabis withdrawal is a minor discomfort with symptoms typically lasting for a few days (sometimes a few weeks) after cessation. And cannabis, unlike prescription and over-the-counter sleep aids, has never killed anyone.

Medical cannabis users often experience better outcomes with lower doses, especially when they are treating something in addition to sleep disturbances, such as pain, spasticity, or post traumatic stress disorder. Based on the available literature reviewed by Project CBD, it appears that a 1:1 CBD:THC preparation will most likely confer restorative sleep. Cannabis-naïve patients may find relief with as little as 2.5 mg of THC and 2.5mg CBD. A somewhat higher dose – 5 to 15 mg each of THC and CBD – may work wonders for experienced cannabis users.

The combination of odiferous terpenes present in a given cannabis strain or product can also significantly impact sleep. Individual terpenes have sedating or stimulating effects, thus affecting the sleep-wake cycle. Terpenes can be therapeutic in their own right. As important modulators of cannabinoids, terpenes contribute significantly to how a given cannabis strain or cultivar makes one feel.

Sedating terpenes include terpinolene, nerolidol, phytol, linalool, and myrcene. In addition to causing the infamous “couch-lock” effect at high levels (+0.5%), myrcene can be mildly stimulating at lower levels. Those trying to address pain and sleep issues should consider cannabis remedies that include beta-caryophyllene, as this terpene is also a strong anti-inflammatory and pain-reliever.

Practical Tips for Improving Sleep

In a study published in the Journal of the American Medical Association, 27 percent of respondents indicated that they used complementary, non-pharmaceutical therapies for fatigue and 26.4 percent for sleep deprivation.

Here are a few simple lifestyle modifications and holistic healing options that may improve your sleep quality.

  1. Create an inviting sleep environment. Having a comfortable bed in a relaxing environment is key to quality sleep. Reduce outside or harsh overhead lighting and maintain a comfortable temperature for sleeping. And, reduce noise. If you are a light sleeper consider using a white noise machine to drown out unwanted sound. Salt lamps may help clean the air by reducing negative ions (and provide enough light to get to the bathroom without intruding on sleep).
  2. Have a sleep routine. Going to bed and waking at the same time seven days a week is optimal. Additionally, it is helpful for some people to have a relaxing bedtime routine that lets the mind know it is time to get sleepy. This may include a small warm cup of milk or green tea 45 minutes to an hour before bed, or a few simple yoga stretches to relax, or an Epsom salt bath.
  3. Avoid overstimulation. It is best not to have a television in the bedroom and not to watch violence shows before bedtime, especially for those with adrenal fatigue. Avoid reading or using your phone, laptop or tablet in bed.
  4. Exercise daily. Regardless if your preference is jogging, weightlifting, gardening, walking or tai chi, do some form of exercise every day. But avoid exercising within two hours of bedtime.
  5. Avoid stimulants after 1PM. Caffeine, alcohol, tobacco, certain herbal supplements and drugs may leave you feeling “hyper” and overstimulated, which can impede the brain’s ability to transition into sleep.
  6. Aromatherapy. Many of the sedating essential oil components present in cannabis can also be found in other plants at your local grocery or natural products store, along with misters that spay the oil into the air. Aromatherapy can be relaxing and very helpful to induce sleep. Lavender essential oil, for example, can be help to manage certain sleep disorders.
  7. Use sleep supporting herbs. It is best to work with a healer or someone knowledgeable about herbs and supplements instead of buying whatever sleep cure is touted on the internet. Herbs that have sleep-promoting properties include Valerian, Kava, German Chamomile, Roman Chamomile, Passion Flower, California Poppy, Hops, Lemon Balm, Linden, Skullcap, and Oats. Visit the American Herbalist Guild to find a qualified practitioner.
  8. Nutritional supplements. Consult your physician about products made with Kava, calming minerals, and taking the right kind of magnesium at night.
  9. Other therapies. In addition to cannabis, safe holistic healing alternatives include cognitive-behavioral therapy for insomnia, and bright light therapy for circadian rhythm disorders.

Footnotes

1 In 2014, there were 47,055 accidental opiate overdose deaths. Dr. Daniel Kripke estimates one third of them also involved various hypnotics as a cause of death. It should be noted that cannabis has been shown to improve safety and effectiveness of opiates making it possible for the patient to take a lower dose, thereby reducing the risk of side-effects including death. In some cases, cannabis can replace both the opiate as an effective painkiller and the hypnotic.

2 Highly complex, the sleep-wake cycle is driven by various neurochemicals and brain pathways. Neuroscientist and sleep researcher Dr. Eric Murillo-Rodriguez, says that “Sleep is generated by sleep-promoting neurons placed in the anterior hypothalamus that utilize GABA to inhibit wake-promoting regions in the hypothalamus and brainstem. Then, the brainstem regions inhibited during wake and slow wave sleep become active during rapid eye movement sleep (REM).”

3 In “The effects of cannabinoid administration on sleep: a systematic review of human studies,” Gates et al scrutinized cannabis-related sleep studies prior to 2012. But they found “little consistency in the results [of] six studies with objective sleep measures. Slow wave sleep was described as increasing for a week in one study, whereas three studies reported a decrease in slow wave sleep, and one study showed no change. Rapid eye movement sleep was reported to increase in one study, decrease in a second study, while four studies showed no effect. Stage two sleep [see sidebar] was reported to increase in two studies, while four studies showed no effect. Sleep latency was reported to increase in one study, decrease on a high THC dose in a second study, while two studies showed no effect and two studies did not measure sleep latency.”

4A 2014 article by Babson & Bonn-Miller indicated that over 83 percent of surveyed patients taking cannabis for pain said they experienced improved sleep.

5Nicholson et al had similar results in a double-blind placebo-controlled with a 4-way crossover design study evaluating the effect of cannabis extracts on nocturnal sleep, early-morning performance, memory, and sleepiness in eight subjects ages 21-34 years old. A cross-over design is one where each group of participants take two or more interventions; in this case four different preparations were tested, including THC (15 mg) alone; THC and CBD together (5 mg each and 15 mg each); and a placebo. They scientists found that “although impaired memory was observed the next day when 15 mg THC was given alone overnight, there were no effects on memory when 15 mg THC was ingested with 15 mg CBD.” They also found that the effects of THC and CBD appeared to be dose dependent as evidenced by the fact that 7.5 mg of THC did not impair memory, but 15 mg did.

Sources

  • Americal Sleep Association. (2017, July 7). Sleep Statistics. Retrieved from American Sleep Associaton: https://www.sleepassociation.org/sleep/sleep-statistics/
  • Babson, Kim A., Bonn-Miller, Marcel O. (2014). Sleep Disturbances: Implications for Cannabis Use, Cananbis Use Cessation, and Cananbis Use Treatment. Current Addiction Reports, 109-114.
  • Babson, Kimberly A. and James Sottile, Danielle Morabito. 2017. “Cannabis, Cannabinoids, and Sleep: Review of the Literature.” Current Psychiatry Report.
  • Centers for Disease Control and Prevention. (2017, May 2). Sleep & Sleep Disorders. Retrieved from Centers for Disease Control and Prevention: https://www.cdc.gov/sleep/data_statistics.html
  • Ferguson, G. and Ware, M.A. (2015). Review Article: Sleep, Pain and Cananbis. Journal of Sleep Disorders & Therapy, https://www.omicsgroup.org/journals/review-article-sleep-pain-and-cannab….
  • Gates, Peter J and Lucy Albertella, Jan Copeland (2014). The effects of cannabinoid administration on sleep: a systemc review of human studies. Sleep Medicine Reviews, https://www.researchgate.net/profile/Peter_Gates/publication/260604558_T….
  • Gyllenhaal, Charlotte, et al. Efficacy and safety of herbal stimulants and sedatives in sleep disorders. Sleep Medicine, Vol. 4, No. 3, pp 229-251, 2000.
  • Kripke, D. (2016). Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit [version 1;. F1000 Research, https://mechanism.ucsd.edu/teaching/f16/cogs200/Kripke%202016%20F1000Res….
  • Lee, Martin A. Smoke Signals: A Social History of Marijuana – Medical, Recreational and Scientific. New York: Scribner, 2013.
  • Mechoulam, R. (2015). Cannabis – The Israeli perspective. Basic Clinical Physiology Pharmacology, https://www.researchgate.net/profile/Raphael_Mechoulam2/publication/2823….
  • Mechoulam, Raphael and L.A. Parker (2013). The Endocannaboind System and the Brain. The Annual Review of Psychology, 21-47.
  • Murillo-Rodriquez, Eric and Jose Carlos Pastrana-Trejo, Mireille Salas-Crisostomo, and Miriel de-la-Cruz (2016). The Endocannabinoids System Modulating Levels of Consciousness, Emotions and Likely Dream Contents. CNS & Neurological Disorders – Drug Targets, 370-379.
  • Murillo-Rodriguez, E. (2008). The role of the CB1 receptor in the regulation of sleep. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 1420-1427.
  • National Institute of Health. (2017). Brain Basics: Understanding Sleep. Retrieved from National Institute of Health: National Institute of Neurological Disorders and Stroke: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understa…
  • National Institute of Neurological Disorders & Stroke. (2017, July 23). Brain Basics; Understanding Sleep. Retrieved from National Institute of Neurological Disorders and Stroke: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Understa…
  • Nicholson, A. N., Turner, C., Stone, B. M., & Robson, P. J. (2004). Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. Journal of Clinical Pharmacology, 305-313.
  • Pava, Matthew J., Alexandros Makriyannis, David M. Lovinger (2016). Endocannabinoids Signaling Regulates Sleep Stability. PLoSOne, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152473.
  • Pava, Matthew J. et al (2014). Endocannabinoid Modulation of Cortical Up-States and NREM Sleep. PLoSONE, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088672.
  • Prospero-Garcia, Oscar et al (2016). Endocannabinoids and sleep. Neuroscience and Beobehavioral Reviews, 671-679.
  • Russo, Ethan B. (2007). Cannabis, Pain and Sleep: Lessons from Therapeutic Clinical Trials of Sativex, a Cannabis-Based Medicine. Chemistry & Biodiversity, 1729-1743.
  • Russo, E. B. (2001). Handbook of Psychotropic Herbs. Bringhamptom: The Hawthorne Press, Inc.
  • Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effect. British Journal of Pharmacology, 1344-1364.
  • Roth, T. (2007). Insomnia: Definition, Prevalence, Etiology, and Consequences. Journal of Clinical Sleep Medicine, S7S10.
  • Shannon, Scott and Janet Opila-Lehman. (2016) Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Permanente Journal. Fall 2016.
  • Scheet, F. A. (2016). Hungry for Sleep: A Role for Endocannabinoids. Sleep, 495-496.

Powered by WPeMatico


  • -

Red Cross Meets Green Cross

Category : Noticias

A major legal medical marijuana factory in Northern California has become the headquarters of the American Red Cross’ relief efforts for tens of thousands of displaced evacuees fleeing the state’s historic series of wildfires.
By David Downs On October 17, 2017

CannaCraft, Red Cross

From Greenstate.com

A major legal medical marijuana factory in Northern California has become the headquarters of the American Red Cross’ relief efforts for tens of thousands of displaced evacuees fleeing the state’s historic series of wildfires.

The 140-employee company CannaCraft in Santa Rosa is feeding and hosting 200 Red Cross staff for the next five weeks, said Kial Long, spokeswoman at the company. CannaCraft is providing 12,000 square-feet of office space to be used as the American Red Cross Regional Headquarters for Northern California fire relief.

Cannabis remains a federally banned controlled substance considered as dangerous as heroin. But eight states and Washington D.C. have legalized its over the counter use by adults 21 and over. Twenty-nine states have medical cannabis laws. Some 61 percent of U.S. voters support cannabis legalization and 91 percent support medical access to the pain-relieving botanical drug.

Hosting the Red Cross came out of company discussions about ways to help. After surveying available space and equipment, CannaCraft leaders reached out to the Red Cross and offered office space. The Red Cross sent a project leader over to evaluate the space.

READ FULL STORY

Powered by WPeMatico


  • -

Fire, Brimstone & Dioxin

Category : Noticias

Heavy smoke has blanketed the skies in the nine-county San Francisco Bay Area, poisoning the air to an unprecedented degree and prompting air quality alerts and health advisories throughout the region.
By Adrian Devitt-Lee On October 16, 2017

Toxic Smoke Threatens Cannabis Crop and Public Health
Highlights: 
  • Smoke from major fires will contaminate crops in Northern California’s prime cannabis-growing region.
  • Cannabis, a bioaccumulator, will uptake heavy metals from the soil that have deposited on the ground.
  • Analytical labs should test cannabis products for an array of fire-related heavy metals, aromatic hydrocarbons, and dioxins, even those that are not mandated by regulations.
Fire and cannabis

The October firestorms raging in Northern California have incinerated nearly a quarter million acres and displaced more than 100,000 residents. Heavy smoke has blanketed the skies in the nine-county San Francisco Bay Area, poisoning the air to an unprecedented degree and prompting air quality alerts and health advisories throughout the region.

“We have never recorded higher levels of air pollution in the Bay Area,” said air district spokeswoman Kristine Roselius.

While a limited number of deaths have been reported thus far, the public health impacts of this disaster will be felt for many months to come. This is not a typical wildfire; in Santa Rosa, flames have melted gas pipes, power lines, even a cellphone tower. The blaze has scorched thousands of homes and cars, releasing metals into the air. Rubber, fibreglass, paint, and electrical equipment burn to uncommon and highly dangerous toxins, such as dioxins and other biphenyl compounds.

Poisons contained in the smoke will slowly fall from the air and be absorbed by plants and the watershed, contaminating agricultural crops, including those in the Emerald Triangle, America’s cannabis breadbasket. The timing couldn’t have been worse for cannabis farmers as these fires came at the start of harvest season. Cannabis producers and consumers need to be cautious about the chemicals that could accumulate.

There are three common ways that toxins and carcinogens in smoke can be removed from the atmosphere:

  • Volatile chemicals like formaldehyde and carbon monoxide will dissipate by reacting with trace gasses in the air, perturbing the concentration of ozone and other gasses. When carbon monoxide reacts with oxygen radicals, for example, it converts to carbon dioxide.
  • Hardier chemicals may be removed from the sky by wet deposition, whereby rain pulls pollution out of the atmosphere. But that requires precipitation. And if it rains, highly toxic run-off will pollute the watershed.
  • Other chemicals will simply fall from the sky and deposit onto plants, soil, and other solid surfaces. These compounds include benzene, polycyclic aromatic hydrocarbons, and dioxins. The chemicals that settle on cannabis or nearby water and soil can be absorbed by the plant and passed on to the consumer. Cannabis, a bioaccumulator, will uptake heavy metals from the soil that have deposited on the ground.

While these toxins can pose serious health hazards, it is important not to exaggerate harms. Cannabis smoke (even from untainted, organically grown cannabis) also contains carcinogens, but smoking marijuana does not increase the risk of oral and lung cancers—possibly because THC, CBD, and other plant cannabinoids exert a direct anti-tumor action against oral and lung cancer.

Another factor that may mitigate harm from inhaled cannabis smoke is the inhibition of a group of enzymes called CYP1A. Polycyclic aromatic hydrocarbons become more carcinogenic when metabolized by CYP1A enzymes in the body: By inhibiting CYP1A in the lungs, cannabinoids could reduce the activation of these carcinogens.

In cannabis smoke, roughly 0.5% of the plant material converts to polycyclic aromatic hydrocarbons. That is 5000 parts per million by weight (ppm). Carcinogenicity of aromatic hydrocarbons is usually discussed at concentrations on the order of 10 ppm.1 It remains to be seen if toxins deposited by the fires will be greater than the concentrations normally found in cannabis smoke. If not, then this cannabis is likely safe to consume (though it may require a warning under prop 65). To reduce further toxicity, it would be best for people to avoid smoking cannabis tainted by the wildfires: vaporization and ingestion are alternatives.

But consumers should also be aware that extraction processes (including butane, ethanol, and CO2) may concentrate these unwanted chemicals, though this is not precisely known. Cannabis producers and consumers should make sure, if possible, that any lab tests apply to the final product, not just the plant material that was used for extraction.

Accurate testing is paramount. Unfortunately, some cannabis labs have a record of providing results before they have validated their methods and can be certain that their numbers are correct. (Validation involves spiking precise amounts of contaminants into clean cannabis samples to ensure that accurate results are obtained.)

Several fire-generated toxins that may be deposited on cannabis crops—including benzene and toluene—are on the list of regulated solvents that California labs will likely have to quantify in cannabis products as of 2018. In preparation for the upcoming regulations, analytical labs may have already validated methods for detecting these compounds.

But other, less common toxins, such as benzopyrenes and polychlorinated dibenzo dioxins (PCDDs; sometimes simply called dioxins), are not included in the new regulations. Dioxins are particularly important: they are formed when chlorinated plastics burn, such as PVC pipes. One kind of dioxin, which is called TCDD, disrupts endocrine, immune, and reproductive systems as well as fetal development. It is also a carcinogen at larger concentrations. (TCDD was also a contaminant in Agent Orange, a chemical weapon created by Monsanto and used in the Vietnam war.)2

Whether mandated by state regulations or not, cannabis labs should also test for these compounds.3 Thus far, however, cannabis labs have not validated testing procedures for these compounds.

Another concern: helicopters and planes have been dumping tons of fire-repellant in an effort to contain the fires. The fire-repellant used, another Monsanto-designed product called Phos-Chek, may also have adverse health consequences. One of the main constituents of Phos-Chek is ammonium salt. Ammonium is a fertilizer: If absorbed through the plant, it is unlikely to be toxic, but smoking or vaporizing ammonium stuck on cannabis resin should be avoided.4

Project CBD hopes that some lab in California will validate methods and offer tests to detect the major contaminants that result from the wildfires. We expect these will include benzene, toluene, benzopyrenes, and heavy metals, as well as some dioxins and polychlorinated biphenyls.

Adrian Devitt-Lee, a Project CBD contributing writer, is a senior research associate with CannaCraft.

Footnotes:

  1. Parts per million is a unit that can cause some confusion. It can mean concentration by weight (ppmw) or by volume (ppmv). When discussing cannabis and lab tests, parts per million is measured in weight: ppmw means microgram of contaminant per gram of cannabis. (A microgram, written µg, is one millionth of a gram.) But when talking about safety data, especially for inhaled compounds, parts per million is usually micrograms of contaminant per liter of air. This makes it much easier to determine the concentration of contaminants in a person’s lung. Since an adult human’s lungs contain about 4-6 liters and a joint weighs about half a gram, ppmv is roughly 10 times larger than ppmw. In other words, the lab test for a contaminant should be no more than 10 times larger than the safety parameter for inhaling that contaminant. This is a rule of thumb, not a definitive statement. See the report in footnote 4 for more information on safety data.
  2. TCDD is pervasive in the environment. It can be found at low concentrations in milk and meat, with beef being the worst offender. This is partly because dioxins are extremely durable compounds—the half life of TCDD is close to 10 years. The average human body has roughly 1-5 parts per trillion dioxin in their fat tissue (that is, 1-5 picograms of dioxin per gram of fat). These levels have been declining greatly since the 1970s.
  3. This list is not finalized. The proposed regulations were repealed after the public comment period by the trailer bill, the bill that merged recreation and medical cannabis regulations. The new regulations have not yet been released.
  4. Inhaling ammonia in cannabis at concentrations below 100 ppm is likely safe. 100 ppm means 100 µg ammonia per g cannabis product. The number is based on the equation described Appendix A of this report by Project CBD. Using the terminology from that document, the STEL for ammonia is 27 µg/L. It is reasonable to assume that children use less than 0.25 grams of cannabis and that adults use less than 1 gram of cannabis in a 15 minute period. This increases the estimates in the document by a factor of four.

Sources

Powered by WPeMatico


  • -

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.

Image

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.

Image

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.

Image

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.

Powered by WPeMatico


  • -

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.

Powered by WPeMatico


  • -

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.

Powered by WPeMatico


  • -

Translate »