Author Archives: adminoacido

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Cannabis sativa (Hemp) Seeds, Δ(9)-Tetrahydrocannabinol, and Potential Overdose.

Category : Dolor

Related Articles

Cannabis sativa (Hemp) Seeds, Δ(9)-Tetrahydrocannabinol, and Potential Overdose.

Cannabis Cannabinoid Res. 2017;2(1):274-281

Authors: Yang Y, Lewis MM, Bello AM, Wasilewski E, Clarke HA, Kotra LP

Abstract
Introduction:Cannabis sativa (hemp) seeds are popular for their high nutrient content, and strict regulations are in place to limit the amount of potentially harmful phytocannabinoids, especially Δ(9)-tetrahydrocannabinol (Δ(9)-THC). In Canada, this limit is 10 μg of Δ(9)-THC per gram of hemp seeds (10 ppm), and other jurisdictions in the world follow similar guidelines. Materials and Methods: We investigated three different brands of consumer-grade hemp seeds using four different procedures to extract phytocannabinoids, and quantified total Δ(9)-THC and cannabidiol (CBD). Discussion: We discovered that Δ(9)-THC concentrations in these hemp seeds could be as high as 1250% of the legal limit, and the amount of phytocannabinoids depended on the extraction procedure employed, Soxhlet extraction being the most efficient across all three brands of seeds. Δ(9)-THC and CBD exhibited significant variations in their estimated concentrations even from the same brand, reflecting the inhomogeneous nature of seeds and variability due to the extraction method, but almost in all cases, Δ(9)-THC concentrations were higher than the legal limit. These quantities of total Δ(9)-THC may reach as high as 3.8 mg per gram of hemp seeds, if one were consuming a 30-g daily recommended amount of hemp seeds, and is a cause for concern for potential toxicity. It is not clear if these high quantities of Δ(9)-THC are due to contamination of the seeds, or any other reason. Conclusion: Careful consideration of the extraction method is very important for the measurement of cannabinoids in hemp seeds.

PMID: 29098190 [PubMed]

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Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts.

Category : Antiinflamatorio

Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts.

Cannabis Cannabinoid Res. 2017;2(1):167-182

Authors: Nallathambi R, Mazuz M, Ion A, Selvaraj G, Weininger S, Fridlender M, Nasser A, Sagee O, Kumari P, Nemichenizer D, Mendelovitz M, Firstein N, Hanin O, Konikoff F, Kapulnik Y, Naftali T, Koltai H

Abstract
Introduction: Inflammatory bowel diseases (IBDs) include Crohn’s disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models. Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR. Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 (COX2) and metalloproteinase-9 (MMP9) gene expression in both cell culture and colon tissue. Conclusions: It is suggested that the anti-inflammatory activity of Cannabis extracts on colon epithelial cells derives from a fraction of the extract that contains THCA, and is mediated, at least partially, via GPR55 receptor. The cytotoxic activity of the C. sativa extract was increased by combining all fractions at a certain combination of concentrations and was partially affected by CB2 receptor antagonist that increased cell proliferation. It is suggested that in a nonpsychoactive treatment for IBD, THCA should be used rather than CBD.

PMID: 29082314 [PubMed]

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Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain.

Category : Dolor

Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain.

Cannabis Cannabinoid Res. 2017;2(1):210-216

Authors: Ryz NR, Remillard DJ, Russo EB

Abstract
Introduction: The roots of the cannabis plant have a long history of medical use stretching back millennia. However, the therapeutic potential of cannabis roots has been largely ignored in modern times. Discussion: In the first century, Pliny the Elder described in Natural Histories that a decoction of the root in water could be used to relieve stiffness in the joints, gout, and related conditions. By the 17th century, various herbalists were recommending cannabis root to treat inflammation, joint pain, gout, and other conditions. There has been a subsequent paucity of research in this area, with only a few studies examining the composition of cannabis root and its medical potential. Active compounds identified and measured in cannabis roots include triterpenoids, friedelin (12.8 mg/kg) and epifriedelanol (21.3 mg/kg); alkaloids, cannabisativine (2.5 mg/kg) and anhydrocannabisativine (0.3 mg/kg); carvone and dihydrocarvone; N-(p-hydroxy-β-phenylethyl)-p-hydroxy-trans-cinnamamide (1.6 mg/kg); various sterols such as sitosterol (1.5%), campesterol (0.78%), and stigmasterol (0.56%); and other minor compounds, including choline. Of note, cannabis roots are not a significant source of Δ(9)-tetrahydrocannabinol (THC), cannabidiol, or other known phytocannabinoids. Conclusion: The current available data on the pharmacology of cannabis root components provide significant support to the historical and ethnobotanical claims of clinical efficacy. Certainly, this suggests the need for reexamination of whole root preparations on inflammatory and malignant conditions employing modern scientific techniques.

PMID: 29082318 [PubMed]

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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….
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  • 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.
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The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy.

Category : Epilepsia

Related Articles

The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy.

Neurocase. 2017 Oct 24;:1-5

Authors: Warren PP, Bebin EM, Nabors LB, Szaflarski JP

Abstract
Epilepsy, commonly encountered by patients with brain tumors, is often refractory to standard therapies. Our aim was to examine the safety and efficacy of pharmaceutical grade cannabidiol (CBD; Epidiolex, GW Pharmaceuticals) in those patients with epilepsy with concomitant tumors enrolled in The University of Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three patients with refractory seizures and a history of a primary brain tumor, two had improvement in seizure frequency and all three had improvement in seizure severity. These pilot results suggest that CBD should be further studied for the treatment of brain tumor-related epilepsy.

PMID: 29063814 [PubMed – as supplied by publisher]

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A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management.

Category : Epilepsia

Related Articles

A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management.

Am J Med Genet A. 2017 Feb;173(2):324-326

Authors: Ho KS, Wassman ER

Abstract
Complex, and sometimes intractable, seizures affect the quality of life and cognitive development of over 90% of individuals with Wolf-Hirschhorn syndrome (WHS). Fine resolution genotype-phenotype mapping of the WHS locus recently identified a candidate gene whose probable function has led to insights into a mechanism connecting WHS seizures with those of Dravet syndrome, a distinct condition caused by mutations in SCN1A and SCN1B. In addition to this possible molecular mechanistic connection, these disorders’ seizures share a strikingly similar constellation of features, including clinical presentation, seizure types, early age of onset, EEG pattern, and responses to specific anti-epileptic drugs. Based in part on these similarities, we suggest that a highly successful Phase III clinical trial of a formulation of cannabidiol for Dravet syndrome seizures may be directly translatable into possible benefits for WHS individuals with challenging seizure patterns. © 2016 Wiley Periodicals, Inc.

PMID: 28102593 [PubMed – indexed for MEDLINE]

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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.

READ FULL STORY

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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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Cannabinoids in Pain Management and Palliative Medicine.

Category : Dolor

Cannabinoids in Pain Management and Palliative Medicine.

Dtsch Arztebl Int. 2017 Sep 22;114(38):627-634

Authors: Häuser W, Fitzcharles MA, Radbruch L, Petzke F

Abstract
BACKGROUND: There are conflicting interpretations of the evidence regarding the efficacy, tolerability, and safety of cannabinoids in pain management and palliative medicine.
METHODS: We conducted a systematic review (SR) of systematic reviews of randomized controlled trials (RCT) and prospective long-term observational studies of the use of cannabinoids in pain management and palliative medicine. Pertinent publications from January 2009 to January 2017 were retrieved by a selective search in the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and Medline. The methodological quality of the SRs was assessed with the AMSTAR instrument, and the clinical relevance of quantitative data syntheses was assessed according to the standards of the Cochrane Collaboration.
RESULTS: Of the 750 publications identified, 11 SRs met the inclusion criteria; 3 of them were of high and 8 of moderate methodological quality. 2 prospective long-term observational studies with medical cannabis and 1 with tetrahydrocannabinol/cannabidiol spray (THC/CBD spray) were also analyzed. There is limited evidence for a benefit of THC/CBD spray in the treatment of neuropathic pain. There is inadequate evidence for any benefit of cannabinoids (dronabinol, nabilone, medical cannabis, or THC/CBD spray) to treat cancer pain, pain of rheumatic or gastrointestinal origin, or anorexia in cancer or AIDS. Treatment with cannabis-based medicines is associated with central nervous and psychiatric side effects.
CONCLUSION: The public perception of the efficacy, tolerability, and safety of cannabis-based medicines in pain management and palliative medicine conflicts with the findings of systematic reviews and prospective observational studies conducted according to the standards of evidence-based medicine.

PMID: 29017688 [PubMed – in process]

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Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome.

Category : Epilepsia

Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome.

Proc Natl Acad Sci U S A. 2017 Oct 02;:

Authors: Kaplan JS, Stella N, Catterall WA, Westenbroek RE

Abstract
Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV1.1. The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased. Treatment with lower doses of CBD also improved autistic-like social interaction deficits in DS mice. Phenotypic rescue was associated with restoration of the excitability of inhibitory interneurons in the hippocampal dentate gyrus, an important area for seizure propagation. Reduced excitability of dentate granule neurons in response to strong depolarizing stimuli was also observed. The beneficial effects of CBD on inhibitory neurotransmission were mimicked and occluded by an antagonist of GPR55, suggesting that therapeutic effects of CBD are mediated through this lipid-activated G protein-coupled receptor. Our results provide critical preclinical evidence supporting treatment of epilepsy and autistic-like behaviors linked to DS with CBD. We also introduce antagonism of GPR55 as a potential therapeutic approach by illustrating its beneficial effects in DS mice. Our study provides essential preclinical evidence needed to build a sound scientific basis for increased medicinal use of CBD.

PMID: 28973916 [PubMed – as supplied by publisher]

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