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Treasure Hunt

Category : Noticias

Nine ways that scientists are targeting the endocannabinoid system with synthetic drugs and isolates
By Martin A. Lee On December 13, 2017

In recent years, cannabis has been at the center of one of the most important developments in modern science, which has significantly advanced our understanding of health and disease.

Research on marijuana’s effects led directly to the discovery of a major biochemical signaling system in the human body – the endocannabinoid system – which plays a pivotal role in regulating a wide range of physiological processes that affect our mood, our blood pressure, our bone density, our metabolism, our intestinal fortitude, our energy level, how we experience pain, stress, hunger, and much more.

“By using a plant that has been around for thousands of years, we discovered a new physiological system of immense importance,” says Israeli scientist Raphael Mechoulam. “We wouldn’t have been able to get there if we had not looked at the plant.”

Described by Mechoulam as “a medicinal treasure trove,” cannabis contains more than 100 unique biologically active compounds known as “cannabinoids,” including tetrahydrocannabinol (THC) and cannabidiol (CBD). THC causes the high that cannabis is famous for, CBD does not; both have important therapeutic attributes.

In addition to phytocannabinoids produced by the plant, there are endogenous cannabinoids – marijuana-like molecules – that occur naturally in the human brain and body. And there are also synthetic cannabinoids created by pharmaceutical researchers, who are developing new medicines that target the endocannabinoid system for therapeutic benefit.

Some of these novel synthetic compounds activate the same cannabinoid receptors – CB1 and CB2 – in the brain and body that respond pharmacologically to THC and other cannabis components.1

Medical scientists are also experimenting with synthetic drugs designed to improve “endocannabinoid tone” without binding directly to cannabinoid receptors.

Here are nine strategies that scientists are currently pursuing in an effort to harness the healing potential of the endocannabinoid system:

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Marinol

1. Single-molecule plant cannabinoids

Dronabinol, marketed in pill form as Marinol, is a single-molecule THC extract combined with sesame oil. It got fast-tracked for approval by the Food and Drug Administration in 1985 in response to rising patient demand for medical marijuana.

Other THC preparations are also on the FDA’s radar, including Syndros, a liquid THC drug produced by Insys. But patented single-molecule THC is a poor substitute for whole plant cannabis.

Even though it is highly psychoactive and potentially dysphoric, pharmaceutical THC is legally accessible in all 50 states as a prescription medication.

Cannabidiol, unlike pure THC, is not yet legal in all 50 states. But CBD will soon become a legal pharmaceutical, as the FDA is poised to approve Epidiolex, a botanically derived anti-seizure medication produced by GW Pharmaceuticals. Epidiolex is pure CBD with a dash of cannabidivarin (CBDV), a “minor” cannabinoid that also has potent anti-epileptic properties.

Along with the imminent advent of pharmaceutical CBD, several R&D firms have begun to harvest single-molecule cannabinoids, such as CBDV, from a yeast substrate. As this biotechnology improves, drug developers and pharmacists will have access to numerous single-molecule cannabis compounds.

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Image Credit: Bryan Satalino

2. Synthetic cannabinoid analogs

Scientists have created synthetic analogs of plant cannabinoids for research purposes and for commercial sale and distribution. Nabilone, a synthetic THC analog, was developed by Eli Lilly and Co. as a treatment for chemotherapy-induced nausea and vomiting.

Marketed under the trade name Cesamet, this synthetic cannabinoid is used as an adjunct therapy for chronic pain management in Canada and other countries. Clinical trials of Nabilone have indicated some effectiveness for fibromyalgia, Parkinson’s, PTSD-related nightmares, irritable bowel disease, and multiple sclerosis.

Researchers are using various synthetic analogs to investigate the biochemical pathways and molecular mechanisms of the endocannabinoid system. Some of these compounds (such as WIN55,212-2 and CP55,940) bind to both cannabinoid receptors – CB1 and CB2 – much like THC. Other experimental drugs target only one type of cannabinoid receptor and not the other. 2

A cannabinoid agonist binds to a cell receptor and causes it to initiate a signaling cascade that modulates various physiological processes and protects neurons against toxic insults. A cannabinoid antagonist binds to a cell receptor and prevents it from signaling.

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Image Credit: Bryan Satalino

3. Synthetic cannabinoid antagonists

Cannabinoid CB1 receptors, which mediate the psychoactive effects of THC, are concentrated in the brain and central nervous system. When THC binds to CB1, it can make a person feel stoned – and hungry. The “munchies,” scientists confirmed, are linked to stimulation of CB1 receptors in areas of the brain that regulate hunger and satiety. If activated, CB1 receptors induce appetite; if blocked, they reduce it.

SR141716,” a synthetic CB1 antagonist developed by the French pharmaceutical giant Sanofi-Aventis, was initially utilized as a research tool: By blocking CB1 and monitoring which functions were altered, scientists advanced their understanding of the endocannabinoid system.

Sanofi strategists believed they had invented the perfect diet pill, and they promoted SR141716 as an appetite suppressant in Europe. But the diet drug, sold as “Rimonabant,” proved to be too blunt an instrument. Before long, the synthetic CB1 antagonist was pulled from circulation because of dangerous side effects – high blood pressure, nausea, vomiting, anxiety, mood swings, depression, headaches, seizures, sleep disorders, and a heightened risk of suicide.

If nothing else, the CB1 antagonist debacle provided vivid evidence that a well-functioning endocannabinoid system is essential for good health.3

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4. Peripherally restricted CB1 agonists

Cannabinoid CB1 receptors, the most prevalent protein receptors in the human brain, influence many neurological functions, including marijuana’s mood-altering effects. CB1 receptors are also expressed in the enteric nervous system (the gut), the liver, kidneys, heart and other peripheral organs.

Stimulating CB1 receptors can deliver significant therapeutic benefits, but THC’s psychoactivity limits its medical utility, according to Big Pharma catechism, which defines the CB1-mediated marijuana “high” as an adverse side effect that drug designers should avoid if they hope to win regulatory approval of their patented synthetic novelties.

So pharmaceutical researchers have created peripherally-restricted CB1 agonists (such as AZ11713908) that only activate CB1 receptors outside the central nervous system, but don’t cross the blood-brain barrier.

A peripherally restricted CB1 agonist won’t cause side effects such as disconcerting dysphoria or useless euphoria. But such a compound has never been approved for therapeutic use by the FDA.

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Researchers studying impact on CB2 receptors in animals

5. Selective CB2 agonists

Scientists have been hot on the trail of another type of synthetic cannabinoid – a “selective CB2 agonist” – that will bypass the brain while acting on the peripheral nervous system, where CB2 receptors are concentrated. CB2 receptors regulate immune function, pain perception, and inflammation.

Tinkering with synthetic compounds (such as HU 308 and JWH 133) that selectively stimulate CB2 receptors raises the prospect of healing without the high because CB2 receptors are localized primarily outside the brain and thus do not induce psychoactivity.

Cannabinoid researchers have their eyes on the ultimate prize, the pharmaceutical Holy Grail – a non-addictive painkiller bereft of adverse side effects. Animal experiments focusing on the CB2 receptor initially showed promise.

Thus far, however, drug companies have not been able to synthesize clinically effective CB2-selective compounds, though not for lack of trying. “If drug discovery is a sea, then CB2 is a rock that is surrounded by shipwrecked-projects,” remarked Italian scientist Giovanni Appendino.

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Nanoemulsions

6. Water-soluble cannabinoids

In their natural form, plant cannabinoids and endocannabinoids are oily, hydrophobic substances that don’t dissolve in water. But these lipid molecules can be structurally altered so that they become water soluble without diminishing their therapeutic attributes.

Scientists have developed several ways of synthesizing water-compatible derivatives of THC and other cannabinoids that are more bioavailable and thus potentially more potent than their oily, naturally-occurring counterparts.

The first water-soluble version of THC was created in 1972. Subsequent research found that water-friendly cannabinoid derivatives can lower intraocular pressure in rabbits. A water-soluble cannabinoid ester, “O-1057,” exhibited stronger analgesic properties than THC in preclinical experimentation.

Internet retailers are claiming to sell water-soluble CBD formulated as a nanoemulsion. Pure CBD delivered via nanotechnology is supposed to provide exceptionally high bioavailability and remedial effect compared to a hydrophobic CBD oil extract.

But a CBD isolate typically requires a much higher dose for therapeutic efficacy than a whole plant CBD-rich concentrate – and this factor may cancel out the alleged advantages of nanoemulsified single-molecule CBD.

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ZCZ011 {Image source Wikipedia}

7. Allosteric cannabinoid receptor modulators

Because direct, full-on stimulation of cannabinoid receptors in the brain may trigger undesirable psychoactive effects, scientists have developed synthetic compounds that change the shape of the CB1 receptor and influence how it signals without causing a THC-like high. These compounds, known as allosteric modulators, can either amplify or decrease a receptor’s ability to transmit a signal.

A “positive allosteric modulator” increases the potency and/or efficacy of CB1 receptor activation by anandamide and 2AG (the two main endogenous cannabinoids), thereby boosting the protective effects of the endocannabinoid system.

Scientists at the University of Aberdeen in Scotland have synthesized a positive allosteric modulator of CB1 to treat pain and neurological disorders. When researchers at Virginia Commonwealth University tested this experimental drug (“ZCZ011”) on mice, it reduced inflammatory pain by magnifying the CB1 receptor’s response to anandamide.

But allosteric effects are rarely consistent across species, which significantly impedes drug development in this area.4

 

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The brain on cannabis

8. Inhibitors of endocannabinoid metabolizing enzymes

Medical scientists are experimenting with synthetic designer drugs to enhance endocannabinoid tone without binding directly (or allosterically) to cannabinoid receptors.

Pharmacological augmentation of endocannabinoid signaling can be achieved by inhibiting fatty acid amide hydrolase (FAAH) and/or monoglycerol lipase (MAGL), the catabolic enzymes that break down the brain’s own marijuana-like molecules, anandamide and 2AG, respectively.

Simply put, less FAAH and MAGL means more anandamide and 2AG, resulting in greater cannabinoid receptor activity throughout the body. Drugs that suppress endocannabinoid-metabolizing enzymes indirectly boost cannabinoid receptor signaling, causing a natural high without the vivid psychoactive effects associated with synthetic and plant-based CB1 agonists.

Preclinical research suggests that indirect modulation of endocannabinoid signaling could become a treatment option for various inflammatory conditions and stress-related disorders. FAAH and MAGL inhibition have been shown to ease pain, anxiety, colitis, hypertension, opiate withdrawal, diarrhea and arthritis in animal models.

While drug developers investigate synthetic FAAH-inhibitors (such as URB597) and MAGL-inhibitors (such as JZL 184), one need look no further than the kitchen spice rack for phytonutrients that regulate endocannabinoid tone by inhibiting the same catabolic enzymes. Nutmeg, one of many culinary spices that interact with the endocannabinoid system, inhibits the breakdown of both anandamide and 2AG, the brain’s own marijuana.

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AM404 {Image source Wikipedia}

9. Endocannabinoid reuptake inhibitors

Another way to augment endocannabinoid tone entails delaying the reuptake of anandamide and 2AG. Scientists have synthesized reuptake inhibitors (such as AM404) that target transport molecules known as fatty acid binding proteins. These membrane-penetrating fatty acid binding proteins facilitate the intracellular transport and reuptake of endogenous cannabinoids.

By blocking access to these critical transport molecules, synthetic reuptake inhibitors increase endocannabinoid levels in the brain’s synapses. This results in heightened cannabinoid receptor signaling and endocannabinoid-induced protective effects.

THC and CBD also inhibit endocannabinoid reuptake. Enhancing endocannabinoid tone via reuptake inhibition may be a key mechanism whereby plant cannabinoids confer protective effects against seizures and neurodegeneration, as well as many other health benefits.

Fool’s gold?

Despite repeated setbacks, the possibility of healing without the high persists as an idée fixe among cannabinoid scientists and pharmaceutical researchers.

The lack of success with selective CB2 agonists, peripherally restricted CB1 agonists, allosteric modulators, CB1 antagonists and other non-euphoric cannabinoids underscores the challenges and limitations of synthetic, monomolecular medicine that targets a single protein receptor while forsaking whole plant synergies.

Synthetic CBD analogs are also in development. By tweaking the mother molecule and removing, adding or editing a molecular side chain, pharmaceutical researchers hope to create a marketable compound that is more potent and more effective than botanical CBD.

But a CBD isolate is not inherently superior to a whole plant CBD-rich extract. Preclinical studies that compare the efficacy of single-molecule CBD and full spectrum CBD-rich oil concentrates indicate that CBD solo is effective only at precise, high doses – whereas whole plant CBD-rich extracts have a much wider and safer therapeutic window and are effective at significantly lower doses. Problematic drug interactions are also much likelier with high dose single-molecule CBD.

Regulatory policy should not privilege single-molecule meds over full spectrum cannabis remedies. Patients are best served by having access to a wide range of cannabinoid-based therapeutic options, including artisanal whole plant preparations and synthetic isolates, if and when they become available.


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


Footnotes

  1. Only four cannabis compounds bind directly to either one or both cannabinoid receptors. THC activates CB1 and CB2. Cannabinol (CBN), a THC breakdown component, activates the CB1 receptor, though with less potency than THC. Tetrahydracannabivarin (THCV), the propyl variant of THC, binds to both cannabinoid receptors, activating CB2 while blocking CB1. And beta caryophyllene, an aromatic terpene found in many cannabis strains, green leafy vegetables, and common kitchen spices, activates CB2. Other cannabinoids, including CBD, interact with the endocannabinoid system indirectly without binding like lock and key to a cannabinoid receptor.
  2. Developed as a research tool to study that endocannabinoid system, JWH-018 is a synthetic cannabinoid compound that activates the CB1 receptor but not CB2. After the formula for this potent CB1 agonist was published in the scientific literature, JWH-018 surfaced as a street drug known as “Spice” or “K2.” Media accounts typically mischaracterize Spice as “synthetic marijuana.”
  3. U.S. government scientists have not given up entirely on Rimonabant. The fact that this compound blocks the euphoric effects of cannabis is a big plus to the National Institute on Drug Abuse, which has sponsored research on utilizing CB1 blockers to treat various addictions, including “cannabis dependence.”
  4. Canadian scientists have identified CBD as a “negative allosteric modulator” of the CB1 receptor based on in vitro research. This means that CBD, when administered in combination with THC, will alter the shape of the CB1 receptor in a way that weakens its binding affinity for THC. As a negative allosteric modulator of CB1, CBD lowers the ceiling on THC’s psychoactivity, which might be why people don’t feel as high when using CBD-rich cannabis as compared to a THC-infused product.

Sources

• Han S, Thatte J, Buzard DJ, Jones RM. Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists. J Med Chem. 2013 Nov 14;56(21):8224-56. PubMed PMID: 23865723.
• Ignatowska-Jankowska BM, Baillie GL, Kinsey S, Crowe M, Ghosh S, et al. A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects. Neuropsychopharmacology. 2015 Dec;40(13):2948-59. PubMed PMID: 26052038; PubMed Central PMCID: PMC4864630.
• Mitjavila J, Yin D, Kulkarni PM, Zanato C, Thakur GA, et al. Enantiomer-specific positive allosteric modulation of CB1 signaling in autaptic hippocampal neurons. Pharmacol Res. 2017 Nov 20;PubMed PMID: 29158048.
O’Hearn S, Diaz P, Wan BA, DeAngelis C, Lao N, et al. Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies. Ann Palliat Med. 2017 Aug 31;PubMed PMID: 29156899.
• Pertwee RG, Gibson TM, Stevenson LA, Ross RA, Banner WK, et al. O-1057, a potent water-soluble cannabinoid receptor agonist with antinociceptive properties. Br J Pharmacol. 2000 Apr;129(8):1577-84. PubMed PMID: 10780961; PubMed Central PMCID: PMC1572002.
• Schindler CW, Scherma M, Redhi GH, Vadivel SK, Makriyannis A, et al. Self-administration of the anandamide transport inhibitor AM404 by squirrel monkeys. Psychopharmacology (Berl). 2016 May;233(10):1867-77. PubMed PMID: 26803499; NIHMSID: NIHMS754451; PubMed Central PMCID: PMC4846479.
• Wasilewski A, Misicka A, Sacharczuk M, Fichna J. Modulation of the endocannabinoid system by the fatty acid amide hydrolase, monoacylglycerol and diacylglycerol lipase inhibitors as an attractive target for secretory diarrhoea therapy. J Physiol Pharmacol. 2017 Aug;68(4):591-596. PubMed PMID: 29151076.
• Yu XH, Cao CQ, Martino G, Puma C, Morinville A, et al. A peripherally restricted cannabinoid receptor agonist produces robust anti-nociceptive effects in rodent models of inflammatory and neuropathic pain. Pain. 2010 Nov;151(2):337-44. PubMed PMID: 20696525.

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The Origins of Reefer Madness [Book Excerpt]

Category : Noticias

On August 11, 1930, Harry Jacob Anslinger became the director of the newly formed Federal Bureau of Narcotics (FBN) in Washington, D.C. The Voldemort of vipers, he would run the FBN with an iron fist through six presidential administrations spanning more than three decades.
By Martin A. Lee On October 15, 2017

The War on Cannabis "Reefer Madness"

Excerpted from Smoke Signals: A Social History of Marijuana—Medical, Recreational and Scientific. Reprinted at FAIR online.

Yellow Journalism and the Anti-Cannabis Crusade

On August 11, 1930, Harry Jacob Anslinger became the director of the newly formed Federal Bureau of Narcotics (FBN) in Washington, D.C. He would run the FBN with an iron fist through six presidential administrations spanning more than three decades.

An imposing, husky, bull-necked figure nearly six feet tall, he looked like a tough law-and-order drug buster. With a large square head, huge ears, a cleft chin, and glowering eyes, Anslinger took great pride in his role as the archnemesis of marijuana smokers. He was the godfather of America’s war on drugs, and his influence on public policy would be felt long after death stiffened his fingers in 1975.

When Anslinger grabbed the reins at the FBN, marijuana had already been banned in 24 U.S. states, but there still was no coordinated federal attempt to outlaw the plant. During its first few years, the FBN issued annual reports that minimized the marijuana problem, which Anslinger believed was best dealt with by state and local officials.

The stuff grows “like dandelions,” he complained. Trying to stamp out a plant that flourished everywhere in the world except Antarctica and the Arctic Circle seemed like a dubious proposition. Anslinger had only 300 G-men on his roster, hardly enough to tackle heroin and cocaine, let alone a common weed.

Anslinger didn’t pay much attention to cannabis until 1934, when the FBN was floundering. Tax revenues plummeted during the Great Depression, the bureau’s budget got slashed, and Harry’s entire department was on the chopping block. Then he saw the light and realized that marijuana just might be the perfect hook to hang his hat on. A savvy operator and an extremely ambitious man, he set out to convince Congress and the American public that a terrible new drug menace was threatening the country, one that required immediate action by a well-funded Federal Bureau of Narcotics.

Determined to criminalize the herb and build his bureaucratic fiefdom, America’s top narc promoted all the hoary myths about marijuana-induced mayhem and sexual depravity—stories of pot-crazed axe murderers, playground pushers, sordid drug dens and buxom reefer babes whose lives were ruined by the drug.

“If the hideous monster Frankenstein came face-to-face with the hideous monster Marihuana, he would drop dead of fright,” declared the FBN chief (Washington Herald, 4/1⅔7). Anslinger pulled no punches as he orchestrated a nationwide campaign against marijuana, “the most violence-causing drug in the history of mankind.”

In the world according to Anslinger, cannabis was a deadly, addictive drug that enslaved its users and turned them into deranged criminal freaks. He fed titillating tidbits to reporters, who wrote articles that the FBN chief would then cite in making the case that society was in imminent danger of moral collapse because of marijuana.

Anslinger whipped up enthusiasm for the cause in speeches to temperance organizations, religious groups and civic clubs around the country. His anti-cannabis confabulations were given credence by hellfire-and-brimstone preachers who castigated hemp smokers as fallen sinners. A plant that provided the paper on which Gutenberg first printed the Bible was denounced as “the Devil’s weed.”

Perhaps it was the constant pressure from waging war against a figment of his imagination, or maybe his job was simply too demanding, but on April 1, 1935, an angst-ridden Anslinger checked into the U.S. Marine hospital in Norfolk, Virginia. The FBN chief complained of exhaustion and insomnia—he woke up too early and couldn’t get back to sleep, a condition, ironically, which was treatable with cannabis.

While Anslinger convalesced, others picked up the slack. The FBN chief had a strong ally in the press baron William Randolph Hearst, a megalomaniac obsessed with marijuana, whose newspaper chain stretched across the nation. With an instinc-tual grasp of mass psychology, Hearst used his media empire to influence public policy (as when he pushed the U.S. government into war with Spain in 1898). His contempt for facts, his penchant for fabricated stories and doctored photos, and the hysterical tone of his newspapers gave rise to the pejorative expression “yellow journalism.”

Hearst launched a smear campaign against Mexican migrants and their herb of choice. “Murder Weed Found Up and Down Coast—Deadly Marihuana Dope Plant Ready for Harvest That Means Enslavement of California Children,” the Los Angeles Examiner (1⅕/33) screeched in 1933.

By stigmatizing marijuana and the “foreigners” who smoked it, Hearst succeeded in exacerbating anti-Mexican sentiment during the Great Depression, when many Anglos felt they were competing with brown-skinned migrants for scarce jobs. More than 2 million Mexicans, who had been welcomed while the U.S. economy boomed in the 1920s, were deported when it faltered in the 1930s—a policy of ethnic cleansing vociferously championed by the Hearst conglomerate.

Hearst also cheered the rise of fascist forces in Europe. “Mussolini Leads Way in Crushing Dope Evil” was the headline of a Hearst press screed (3/9/28) that combined two of the owner’s pet passions—his support for fascism and the war on narcotics. Hearst Sunday papers published columns by German Nazi leaders, who conveyed Hitler’s point of view to 30 million readers without space for rebuttal.

During the Third Reich, the verminization of religious and ethnic minorities went hand in hand with Rauschgiftbekämpfung, the “combating of drugs” to promote racial hygiene. Nazi racialist policies and the demonization of marijuana by Anslinger and Hearst were parallel historical phenomena—both exploited fear and hatred of the Other.

The FBN commissioner understood that the likelihood of prohibitory legislation increased if the substance in question was associated with ethnic minorities. Thus Anslinger disclosed in 1936 that 50 percent of violent crimes committed in districts occupied by “Mexicans, Greeks, Turks, Filipinos, Spaniards, Latin Americans and Negroes may be traced to the use of marihuana.” The headlines and the plotlines were antidrug and anticrime, but the subtext was always about race.

Anslinger brandished the non-English term like a truncheon to emphasize the weed’s connection to alien elements that crept over the Mexican border into the United States. Popularized during the Depression, the new name marihuana was, in effect, the evil twin of cannabis, a word familiar to Americans as a medicinal ingredient.

Anslinger eschewed references to benign-sounding cannabis and hemp, while calling for a federal ban on marihuana. Very few Americans knew that marijuana, the weed that some blacks and Chicanos were smoking, was merely a weaker version of the concentrated cannabis medicines that everyone had been taking since childhood.

To gain public support for his crusade, Anslinger depicted marijuana as a sinister substance that made Mexican and African-American men lust after white women. One of the worst things about marijuana, according to the FBN chief, was that it promoted sexual contact across color lines. “Marijuana causes white women to seek sexual relations with Negroes,” Anslinger frothed. He rang alarm bells in segregated America, warning that blacks and whites were dancing cheek-to-cheek in tea houses and nightclubs, where pot-maddened jazz bands performed what the Hearst papers called “voodoo-satanic music.”

In addition to hexing blacks and Mexicans, Anslinger’s antimarijuana diatribes served as a not-so-subtle reminder to white women, who had only recently won the right to vote, that they still needed strong men to protect them from the “degenerate races.” He never tired of telling new versions of the same morality tale, which featured a vulnerable young white woman whose tragic downfall is triggered by smoking marijuana with dark-skinned rogues.

During the run-up to federal legislation that banned cannabis, Anslinger pounded home the message: White women are in mortal peril because of marijuana—and so are American children. That was the upshot of a July 1937 American Magazine article by Anslinger, entitled “Assassin of Youth,” which led with the usual purple prose:

“How many murders, suicides, robberies, criminal assaults, holdups, burglaries and deeds of maniacal insanity it causes each year, especially among the young, can only be conjectured,” the FBN chief warned.

With Anslinger pitching script ideas, cannabis was demonized in several low-budget exploitation flicks, some of which were financed by major distilling companies that stood to lose sizable sums if marijuana were a legal competitor.

The film Marijuana! (1935) featured the lurid tagline “Weird orgies! Wild parties! Unleashed passions!” But when it came to ridiculous anti-marijuana propaganda, nothing could top Hot Fingers Pirelli, the bug-eyed piano player who pounds out jazz tunes in Tell Your Children (1936), better known by its later title Reefer Madness.

A perverted pot addict, Pirelli sneaks into a closet and fires up the Devil’s doob, prompting frightful facial twitches as he morphs into an insane killer. Drug-policy critic Jacob Sullum (Saying Yes) calls it “voodoo pharmacology”—the idea that certain substances are molecularly program-med to compel weird, immoral behavior.

Although it bombed at the box office, Reefer Madness was destined to become a cult humor classic among American college students in later years. A vivid example of the national frenzy that set the stage for federal pot prohibition, this film epitomized the synchronicity among Washington, Hollywood and mainstream media in the war against cannabis.

In April 1937, Rep. Robert L. Doughton of North Carolina introduced House Bill 6385, which sought to prohibit the use of marijuana by imposing an exorbitant tax on the drug. When he testified before the House Ways and Means Committee, Harry Anslinger trotted out examples from the “Gore File,” his infamous scrapbook full of Hearst press editorials, racial slurs and anecdotal accounts of horrific murders falsely attributed to marijuana smokers. Bereft of actual scientific data to back up his reefer madness claims, the FBN director presented no evidence of a statistical correlation between marijuana use and criminal behavior.

Members of Congress held only two one-hour hearings to consider the Marihuana Tax Act. The final witness and lone voice of dissent was Dr. William Woodward, the legislative counsel for the American Medical Association, who challenged Anslinger’s claim that cannabis was a dangerous drug with no therapeutic value. AMA doctors, Woodward asserted, were wholly unaware that the “killer weed from Mexico” was actually cannabis. He accurately predicted that federal legislation banning marijuana would strangle any medical use of the plant.

Just four years after relegalizing the consumption of liquor, Congress overwhelmingly passed the Marihuana Tax Act by a voice vote without a recorded tally. Signed by President Franklin D. Roosevelt without fanfare, the law went into effect on October 1, 1937. It was a day of infamy for pot smokers everywhere. Yellow journalism, racial bias and political opportunism had triumphed over medical science and common sense.

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Bugs, Mold and Excrement

Category : Noticias

Welcome to the Brave New World of California Cannabis
By Adrian Devitt-Lee On November 26, 2017

Project CBD critiques the new regulations for America’s largest marijuana market

On November 16, 2017, California officials released a new set of regulations for cannabis manufacturing, testing, and growing. In many respects, these updates are a significant improvement to the initial draft regulations, however, some major problems remain. 

Two important issues pertain to regulations on mold and foreign filth, which are absurdly loose. And unlike the initial proposal, no statement as to the rationale behind the new regulations has been released.

Safety requirements

Allowable limits for contaminants including pesticides, solvents, and microbes are described in sections 5718-5723 of the new regulations. These regulations have fixed a major issue in the initial draft where two different units were confused – parts per million by weight (µg/g) and parts per million by volume. Now solvent and pesticide limits are given in µg/g.

Other significant changes:

  • Solvent limits are largely improved. Certain class 2 solvents have been banned, as Project CBD had previously suggested.
  • Pesticide limits have swung from being very strict to being overly lax. The environmental concerns related to pesticide overuse appear more problematic than the health effects for consumers.
  • Many pesticide safety limits are still based on regulations for tobacco, which is entirely inappropriate.
  • Required tests for microbial contamination are minimal.
  • Limits on mold – one of the most common contaminants of cannabis – are nearly nonexistent. A product is deemed to pass regulations if less than 1/4th of it is covered in mold.

Solvents – §5718

Solvents are broken into two categories for the purpose of regulations. Category 1 solvents are banned and are not permissible at any detectable levels in cannabis products. Category 2 solvents are allowed up to set action limits that depend on the solvent in question and whether the product is inhaled or not. Action limits for non-inhaled products were appropriate in the initial draft proposal and have not changed.

The initial proposed regulations allowed for the use of highly dangerous solvents, including benzene, which Project CBD suggested be banned from use in cannabis manufacturing. We also suggested that regulators consider banning “class 2” solvents such as chloroform, since they are unnecessary for producing most kinds of cannabis extracts.The new regulations now ban the use of benzene and some class 2 solvents like chloroform, but allow other class 2 solvents, including hexane. (Hexane is rarely used to extract oil from cannabis, but is sometimes used to clean the oil of pesticides or other adulterants.) Although Project CBD hopes that cannabis manufacturers avoid using hexane to extract or clean oil, we believe these regulations are appropriate.

Each permissible solvent has a maximum allowable concentration in inhaled cannabis products (e.g. vape cartridges). In the initial draft proposal, these limits were based on safety data from California’s Occupational Health and Safety Administration (OSHA), although the limits were improperly calculated due to confusion with units. (“Parts per million” can have multiple meanings, as mentioned above. See the previous Project CBD statement for more detail.) The new limits are particularly stringent for some class 2 solvents and are overly lenient for ethanol residues.2   On the whole, the new limits are sensible.

 

Pesticides – §5719

Similar to solvents, pesticides are broken into banned pesticides, which are not allowed at any detectable concentration, and allowed pesticides. The action limits for permitted pesticides depend on whether the product is inhaled or not.

The regulations were released with only 5 days for public comments – including the weekend – and were not accompanied by any statement of reasons explaining how new safety limits were determined. As such, Project CBD’s comments on the new pesticide regulations point out potential problems without necessarily suggesting how these issues could be fixed or their extent.

In the new regulations, the list of banned pesticides has shrunk dramatically, from 42 to 21. One of these now-allowed pesticides is a neonicotinoid (acetamiprid) and four others have “high acute toxicity” to humans, according to the initial statement of reasons (bifenthrin, cyfluthrin, naled, and abamectin). Most of the rest of the now-allowed pesticides were banned in the original proposal due to environmental concerns, including myclobutanil (often sold Eagle-20).

The initial set of draft regulations on pesticides were very strict in some regards. The limit of detection (LOD) – which is the lowest concentration of a compound that can be detected reliably – was arbitrarily set at 0.01 – 0.02 µg/g. This is lower than the actual LOD of pesticides in cannabis for most labs. This has changed – now labs will determine their LODs scientifically and list these LODs on lab reports.3 This is an important fix.

To reiterate: because no statement of reasons has been released, we do not know the rationale behind the limits for pesticides on non-inhaled products. But we can say with some certainty that it is not based on the relative safety of these pesticides.

Safe limits for pesticide ingestion are given as the acceptable daily intake (ADI) or acute reference dose (ARfD), and are reported by the World Health Organization. The ADI indicates a level of pesticide ingestion that is considered safe for chronic daily use, which makes sense for food or medicine. Converting the ADI into a limit for a pesticide in cannabis products depends on the amount of product that is consumed. If the limits were based on safe ingestion limits, the ratio of the ADI to the action limit would be constant. In the current proposal, this ratio varies from 2.5 to 750, a 300-fold difference. Pesticides like trifloxystrobin, bifenazate, and permethrin have very high action limits compared to their toxicity when ingested.

It appears that the limits were not based on environmental concerns either: Of the seven least regulated pesticides (i.e. those with the highest allowable limits), five were originally banned due to potential ground water contamination.

For inhaled products, the limits still appear to be based on tobacco, as described in the initial statement of reasons. This may be because very little is known about the effects of heating or burning pesticides (an information vacuum attributable to lobbying from the tobacco industry). Some pesticides will, in fact, become safer when burned, while many others will break down to much more toxic compounds.

The EPA has previously stated that it need not study the health effects of burning pesticides at concentrations below 0.1 µg/g in cigarettes because those individuals are already smoking tobacco. After all, nicotine is the insecticide upon which neonicotinoids are based.

It may be true that inhaling less than 0.1 µg/g of most pesticides is safe. But regulations need to be based on scientific data. If safety data on burning and inhaling pesticides is not available, then the law should include provisions to be updated as new data emerges.

The outcomes of the tobacco industry’s war against science should never be used as the basis of safety regulations for another industry. Tobacco is the leading cause of preventable deaths in the United States, killing roughly half a million people every year. This is precisely because the tobacco industry lobbied to ensure that scientific data on health and safety was not used to inform laws or regulations. That should not be the starting point for any aspect of the emerging cannabis industry.

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A sample could pass with one rodent hair

Foreign material – §5722

The foreign material testing, described in §5722, is beyond the pale. §5722(e) states that:

A sample shall be deemed to have passed the foreign material testing if the presence of foreign material does not exceed:
(1) 1/4 of the total sample area covered by sand, soil, cinders, or dirt;
(2) 1/4 of the total sample area covered by mold;
(3) 1 insect fragment, 1 rodent hair, or 1 count mammalian excreta per 3.0 grams; or
(4) 1/4 of the total sample area covered by an
imbedded foreign material.

A small piece of chocolate weighs about 3.5 grams. Under the new regulations, a 16-piece chocolate bar would be considered acceptable if four pieces were covered in dirt, four more were covered in mold, and each of the 16 pieces had an insect part or rat poop on it.

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Labs are not required to test for mold

Microbes – §5720

 

There is an unprecedented change in regulations on microbial contamination. Cannabis is not required to be free of mold nor are labs required to test for mold. The only limit on mold is given in (2) of the foreign filth section quoted above, which states that up to 1/4th of a product can be covered in mold.

Under the new proposal, products only need to be screened for three microbes: pathogenic E. coli, salmonella, and in the case of inhaled products, aspergillus. Since no statement of reasons were released with the regulations, it is not clear why California is so loose with microbes. Giving regulators the benefit of the doubt, it may be that they are trying not to restrict the use of beneficial microbes, an organic growing practice that uses non-harmful microbes as an alternative to pesticides. But mold is one of the most common contaminants on cannabis. It is absolutely essential to test for mold on cannabis, particularly when grown indoors.

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Testing will be phased in over the course of a year

Phase in of safety testing – §5715

The regulations have been released with just over a month before they will be implemented. To ease the burden on labs, testing will be phased in over the course of a year. This gives labs time to develop and validate methods for each kind of product and each kind of test.

On January 1, 2018, all legal products must be tested for cannabinoids, allowed solvents, banned pesticides, microbes, and product homogeneity.4  On July 1, 2018, three additional tests will be required: banned solvents, allowed pesticides, and foreign material. On January 1, 2019, heavy metals, mycotoxins, and possibly terpenes will also be tested before sales.

Project CBD hopes that terpene testing will become more commonplace, as this will help to illuminate the therapeutic properties of these important plant components.

Other regulations

There are many important aspects of the new regulations that address issues beyond consumer safety. Here are some key points:

  • There is effectively no longer a limit on the size of grows. Each license allows a group or individual to grow up to one acre of cannabis, but there is no limit on the number of licenses a group can get. Project CBD shares the concerns of farmers who are worried that this will allow large-scale agriculture to push out smaller, more sustainable gardens. Privileging wealthy out-of-state investors and big players at the expense of family farmers is bad policy with unhealthy long-term implications for California’s economy and environment.
  • Law enforcement are allowed to copy the materials, records, and books of any employee of any licensed cannabis business. See §5800(a)(4).
  • Recreational products can’t be given away for free. Medical patients can be given free products through a compassionate care program, but this program must be run by a local jurisdiction, not a cannabis business. Moreover, only licensed retailers (e.g. a legal dispensary), not product manufacturers, can provide free products to patients. See §5411.
  • Medical patients under the age of 18 cannot be served at a dispensary. Their caregiver must buy product for them. See §5400(b).
  • Edibles are required to contain no more than 10 mg THC per serving and 100 mg THC per package. Other products must contain less than 1000 mg or 2000 mg THC per package, depending if the product is recreational or medical. See §40306.
  • Edibles cannot contain any other addictive substances, including caffeine, alcohol, and nicotine. Exceptions are made for cannabis chocolate, tea, and coffee. See §40300(b).
  • Labs are required to be certified by one of two groups (the International Standard Oganization or International Electrotechnical Commission). This will help ensure the accuracy and consistency of lab tests, which has been problematic in the past.
  • It is now much easier to get a license to do ethanol extraction, since it is considered a “nonvolatile solvent.” See the definition of “nonvolatile solvent” in §40100.

Adrian Devitt-Lee, a Project CBD contributing writer, is a research associate at CannaCraft, Inc., a Northern California-based medical marijuana company.

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


1 Solvents are classified into one of three groups by the FDA. Class 1 solvents like benzene are either very toxic or environmental hazards and should be avoided in manufacturing if at all possible. Class 3 solvents like ethanol and butane are fairly safe at low concentrations. Class 2 solvents like chloroform and dichloromethane are less dangerous than class 1 solvents, but should be avoided if the use of a class 3 solvent is possible.
2 This is not to say that the allowable limits are wrong. But compared to safety data from OSHA, limits are disproportionately lax for ethanol and strict for class 2 solvents.
3 A second number to be listed on lab reports is the limit of quantification (LOQ), which is at least as large as the LOD. The LOQ is the limit at which the concentration of a chemical can be accurately discerned. The range between the LOD and the LOQ is the range of concentrations where a test can show that a chemical is present, but cannot determine its exact concentration.
4 Products with multiple servings (e.g. a chocolate bar) will be tested every 6 months to ensure that every piece has roughly the same amount of cannabinoids in it. Specifically, the relative standard deviation must be less than 10% of the mean amount of each cannabinoid.

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Epilepsy, Endocannabinoids and Phytocannabinoids

Category : Noticias

Cannabidiol and several other cannabis components can help patients with seizure disorders, and sometimes it’s best to combine CBD with conventional anti-epileptic meds.
By Stacey Kerr, M.D. On November 25, 2017

Highlights: 

• More than 5 million Americans suffer from epilepsy.
CBD is helping many patients, including children with seizure disorders.
THCA, the unheated form of THC, and linalool, an aromatic terpene present in many varieties of cannabis, are potent anticonvulsant compounds.
• Oftentimes, patients must experiment with different cannabis products to find the best remedy for their condition.

“David,” a 10 year old boy, had his first seizure at 2 months of age. The convulsions were photosensitive generalized tonic-clonic seizures that occurred 1-4 times each day. These events were occurring daily, even though he was being treated with two anti-seizure medications – lamotrigine (Lamictal) and valproic acid. But they had already tried carbamazepine, phenobarbital, zonisamide and levetiracetam (Keppra) without success.

On the recommendation of his physician, THCA was added to his medication at 0.05mg/kg/day and his parents immediately noticed a reduction in seizure frequency. They then increased the THCA dosage to 2.2mg/kg/day, and even though there was no benefit noted to this increased dosage, the parents continued at this higher amount. After three months of THCA treatment, his parents reported to his physician a 40% reduction in seizure activity, shorter seizures, and the ability to discontinue the anti-seizure medication Diastat, which they had been using for seizure rescue.  Hoping for even more control, they began a formula that contained THC at a THCA:THC ratio of 4:1. This caused transient side effects of somnolence but did nothing to improve the frequency of seizures.

Even if it did not completely resolve his seizure disorder, the phytocannabinoid THCA was able to make a significant difference in David’s quality of life. He is not alone. Cannabis holds hope for many, like David, who suffer from seizure disorders.

Epilepsy is a complex medical, economic, and social issue that affects at least 5.1 million of the US population by 2013 population reports. In Hawaii, there are an estimated 15,000 patients with seizure disorders. The total indirect and direct cost of epilepsy in the United States is estimated to be $15.5 billion yearly. 1, 2 For the individuals and families of those patients with seizure disorders, life can be limited and extremely complicated depending on the type and frequency of seizures and on the effects of anti-seizure medications, both therapeutic and undesirable.

Seizures occur when a part of the brain becomes overly excited or when nerves in the brain begin to fire in an abnormal way. An abrupt imbalance between the triggers of excitatory signals and inhibitory signals causes the excitatory forces to take over. This excitation then spreads to surrounding cells which all start firing in the same abnormal way. Increased excitation of nerve cells, or decreased inhibition of nerve cells due to a variety of potential insults can lead to a seizure. Balance, or homeostasis, is disrupted.

Most epileptics have no known cause for their seizures. The minority have numerous identified causes that include trauma, infections, inborn metabolic errors, drugs (or withdrawal from drugs), and inherited conditions.

Conventional treatment

There are no treatments for the underlying causes of seizures, and no treatments to reliably prevent the development of seizures after head traumas. There are only medications to limit the seizure intensity or frequency, and these medications are not always effective. In fact, a third of epileptic patients fail to become seizure free even after trying and tolerating two or more appropriately prescribed anti-epileptic drugs (AEDs).3

More than 20 new seizure medications have been developed over the past few decades, but the percentage of patients with uncontrolled seizures has not changed as much as we would hope or expect. Patients who are resistant to AEDs have a higher risk of complications and sudden death due to epilepsy.  The need for multiple AEDs also increases the occurrence of significant side effects. The need for better, safer, and more effective treatment is clear.

Safety profile

Cannabis is a safe medication with no incidence of fatalities due to the lack of cannabinoid receptors in the brainstem. The most common side effects reported among patients using cannabis for seizure control are fatigue, decreased appetite, and somnolence, all of which resolve when cannabis is discontinued. AEDs can have significant side effects, and contrary to cannabis some of these can be fatal.

It is important to note that there are some drug-drug interactions when using cannabis with AEDs because cannabinoids are primarily metabolized by the Cytochrome P-450 system in the liver. Competition for these enzymes can affect the serum levels of AEDs, so patients using cannabis in addition to prescribed AEDs should be monitored, and dosage adjustments may be needed.

Image

The endocannabinoid system in epilepsy

The job of the endocannabinoid system is to maintain homeostasis, so it is no surprise that cannabis has been used to help control seizures for centuries. Well-designed studies on rats have shown that the endocannabinoid system is a significant part of the brain’s response to seizure disorders.

We know that cannabinoid receptors are particularly dense in the central nervous system, and while we do not yet completely understand all the mechanisms that explain the anti-seizure effects of cannabis, we do have theories.

There are cannabinoid receptors in the hippocampus, that part of the brain that handles emotions and memory encoding. Abnormal changes in cells in the hippocampus are a cause of medial temporal lobe epilepsy, which is one of the most common forms. In this type of epilepsy, hippocampal cells create an excitatory feedback loop that causes seizures. Animal and human studies show that cannabinoids seem to be protective of the normal hippocampal cells, and may make the abnormal cells less active.4

In acutely seizing animals, the endocannabinoid 2-AG was significantly increased compared to controls. By testing the levels of both anandamide and 2-AG we have seen that both are synthesized on demand when seizures occur, thus activating the CB1 receptors. It also appears that there is a significant increase in CB1 receptor expression in epileptic animals, a receptor increase that is prolonged and probably permanent.

In studies done on rats with refractory seizures, it was noted that THC completely terminated those seizures without causing sedation, while maximal levels of phenobarbital or phenytoin were unable to do the same. This indicates that phytocannabinoids may offer advantages in treating refractory seizures compared to currently prescribed anti-convulsants.5

In more recent years research on animal models and human clinical observations have rekindled interest in using cannabis to control epilepsy. Cannabinoids decrease glutamate synthesis throughout the central nervous system, which in turn decreases inflammation and seizure activity.6 Regardless of the mechanism, human clinical observations are promising for the use of cannabis as an anti-epileptic medication, either alone or as adjunctive therapy.

Specific cannabinoids as medicine

The evidence continues to indicate that whole-plant usage is more effective than any single isolated constituent, perhaps due to the entourage effect. Cannabis contains many cannabinoids, THC and CBD being only two of over 80 possibles. In addition, the plant contains terpenes which are medically active chemicals that give the plant its fragrance. Combining these constituents can decrease side effects from any single cannabinoid and together, and may be more effective in controlling seizures. 7 We do not yet know what the best combination is for any specific type of seizure but the evidence is strong enough to encourage more research efforts for answers.

CBD: Is CBD the primary cannabinoid that treats seizure disorders? It seems so if you consider the recent reports of use in severely affected children. CBD is certainly a major player, but not the only one. CBD has been clinically proven as an anticonvulsant for many and at worst, for a minority of patients with epilepsy, it gave no benefit. Its anti-convulsive effects are probably due to a combination of beneficial activities. CBD blocks NMDA receptors (similar to the AED Felbamate) and enhances GABA receptors (similar to phenobarbital and Depakote). It stabilizes ion channels (similar to Dilantin and Keppra), acts as an anti-inflammatory, and also as a neuroprotectant.8

THC: In some study models, THC reduced seizure frequency and intensity, but in others there was no effect. Some patients treated with THC had increased seizure activity.6

THCA: THCA, the acidic raw form of THC is non-psychoactive and also appears to have anti-seizure qualities.9

CBDV: Cannabidivarin or CBDV, is a non-intoxicating cannabinoid that also has significant anti-convulsant properties which were even more effective when combined with CBD.6,10

Alpha-linalool: The terpene alpha-linalool has been shown to have anti-seizure activity in pre-clinical models, especially when combined with cannabinoids.7,9

Dosing

Cannabis has a biphasic dose-response, meaning that more is not always better or more effective. This is more prevalent in THC than in CBD but patients and clinicians are cautioned to avoid the assumption that if a dose is not working, it should be increased. It very well may need to be decreased, especially if THC is part of the preparation.

Dosing for adults has been noted at amounts as small as .02 mg cannabinoids/kg/day, but the clinical trials done on Epidiolex (a purified CBD product made by GW Pharmaceuticals) tested a range of 2-50mg/kg/day. While dosing cannabis for seizures is still an evolving science, an experienced physician treating children for intractable seizures shares the following guidelines. First, an EEG is recorded prior to starting CBD oil and then repeated at 1-3 months if the child is showing improvement. Oral or sublingual dosing of a quality-controlled, lab-analyzed CBD oil with a ratio of at least 10:1 CBD:THC is started at 1mg/kg/day divided into every 8 hour doses. These doses are increased every 1-2 weeks depending on the child’s results. She notes that the therapeutic range for many patients appears to be between 4-9 mg/kg/day. As the seizures decrease in frequency, it is possible that the AEDs can be slowly weaned.10

The latest publication on the use of cannabis for the treatment of epilepsy comes from three physicians with experience in the states of Maine, Washington, and California. Of their 272 combined patients, fourteen percent found cannabis to be ineffective at reducing seizures, fifteen percent experienced a 1-25% reduction in seizures, twenty-eight percent experienced a 76-99% reduction, and ten percent had a complete clinical response.

CBD made the difference

When Sam was 4, he had his first myoclonic seizure, and those progressed to myoclonic absence seizures. Sam did not fall to the floor and twitch. Instead, sometimes 100 times a day, he lost consciousness for 20-30 seconds at a time. He stopped, stared vacantly, his head bobbed rhythmically and then it would all be over. He didn’t even notice these seizures, only that when he would come to, everything around him had shifted slightly. But it kept him from a normal life: having full conversations, from learning in school, and from participating in sports.

Sam had tried almost two-dozen treatments including intravenous immunoglobulin and a ketogenic diet. Few of these were effective, and those that were either had worrisome side effects (hand tremors, hives, zombie consciousness, etc.) or they quit working after a short while. By the time he was 11, he was on massive doses of corticosteroids – the only thing they’d found that made any difference – but the side effects were devastating. He’d been hospitalized twice and seen six neurologists in three states.

Then, as a last resort, his parents decided to try CBD. The effects were profound, but the road was “not a straight line,” to quote his father. CBD had immediately helped – dropping the seizure rate from 68 on a Thursday to 6 on the following Monday. A few years after starting the CBD, Sam was down to between 0 and 5 seizures a day on 1000mg of CBD and taking no other seizure medications. Then, he had his first-ever generalized tonic-clonic seizure. Three weeks later he had another, so Depakote was added to his regimen. The Depakote worked.

Sam is now 15 years old and has had 15 months without a seizure. To his parents, this is a relief and a miracle. He is taking 875mg of Depakote a day, and 250mg of CBD twice a day. Now active in sports, fly fishing and rock climbing, Sam gets to be a normal boy.

Clearly, there is promise in the use of cannabis to manage epilepsy and still much to learn.

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.


1.     (cdc.gov/epilepsy)

2.     (http://www.epilepsy.com/hawaii)

3.     Kwan P. Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342(5):314-9

4.     Gloss, Vickrey. Cannabinoids for Epilepsy. The Cochrane Library, 2012

5.     Wallace M.J. et al. The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy, Journal of Pharmacology and Experimental Therapeutics, Vol. 307:129–137, 2003

6.     Devinsky et al. Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia, 55(6):791–802, 2014

7.     Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and epilepsy. Neurotherapeutics. 2015;12:747–768

8.     Jones NA, et al. 2010. Cannabidiol displays anti-epileptiform and anti-seizure properties in vitro and in vivo. Journal of Pharmacology and Experimental Therapeutics 332(2):569-577

9.     Sulak D, et al. The current status of artisanal cannabis for the treatment of epilepsy in the United States, Epilepsy Behav (2017), http://dx.doi.org/10.1016/j.yebeh.2016.12.032

10.  Hill et al, Cannabidivarin is Anticonvulsant in Mouse and Rat, Br J Pharmacol. 2012 Dec;167(8):1629-42. doi: 10.1111/j.1476-5381.2012.02207.x.

11.  Elisabetsky E, Brum LS, Souza DO. Anticonvulsant properties of linalool in glutamate related seizure models. Phytomedicine 1999;6(2):107-13

12.  Bonnie Goldstein MD. https://www.theroc.us/goldstein.pdf

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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):

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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).

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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.”

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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

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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

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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

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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

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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

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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

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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

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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).

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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.

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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

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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

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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.

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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.

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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.

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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.

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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

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