Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.

“Cannabinoid type 1 (CB1) receptors are highly expressed in the brain… Endogenous cannabinoid signaling is modulated by high-fat diet (HFD).

We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD) and HFD.

CB1 cannabinoid receptor knock-out (KO) and wild-type (WT) mice were fed SD or HFD for 4 months .

The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/24586776

Endocannabinoid Modulation of Cortical Up-States and NREM Sleep.

“We hypothesized that the endocannabinoid (EC) system, a neuromodulatory system intrinsic to the cortical microcircuitry, is an important regulator of up-states and sleep…

Overall, these findings demonstrate that the EC system actively regulates cortical up-states and important features of NREM sleep such as its duration and low frequency cortical oscillations.”

http://www.ncbi.nlm.nih.gov/pubmed/24520411

Using cannabis to help you sleep: Heightened frequency of medical cannabis use among those with PTSD.

“The use of cannabis for medical purposes is proliferating in the U.S., and PTSD is an explicitly approved condition for accessing medical cannabis in 5 states. Prior research suggests that people with PTSD often use cannabis to help cope with their condition…

Those with high PTSD scores were more likely to use cannabis to improve sleep, and for coping reasons more generally, compared with those with low PTSD scores. Cannabis use frequency was greater among those with high PTSD scores who used for sleep promoting purposes compared with those with low PTSD scores or those who did not use for sleep promoting purposes.

Consistent with prior research, this study found increased rates of coping-oriented use of cannabis and greater frequency of cannabis use among medical users with high PTSD scores compared with low PTSD scores. In addition, sleep improvement appears to be a primary motivator for coping-oriented use…”

http://www.ncbi.nlm.nih.gov/pubmed/24412475

Cannabidiol in Humans-The Quest for Therapeutic Targets.

“Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties.

However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients.

A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study).

Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects.

Finally, preliminary clinical trials suggest that high-dose oral CBD  may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/24281562

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers.

“Δ9-tetrahydrocannabinol (THC) promotes sleep in animals; clinical use of THC is associated with somnolence (sleepiness)…

These findings suggest that tolerance to the somnolent effects of THC may have occurred…

Somnolence from oral THC may dissipate with chronic, high-dose use.

This has implications for patients who may take chronic oral THC for medicinal purposes, including cannabis dependence treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/23952899

[From cannabis to selective CB2R agonists: molecules with numerous therapeutical virtues].

“Originally used in Asia for the treatment of pain, spasms, nausea and insomnia, marijuana is the most consumed psychotropic drug worldwide. The interest of medical cannabis has been reconsidered recently, leading to many scientific researches and commercialization of these drugs.

Natural and synthetic cannabinoids display beneficial antiemetic, anti-inflammatory and analgesic effects in numerous diseases, however accompanied with undesirable effects due to the CB1 receptor. Present researches focus on the design of therapeutical molecules targeting the CB2 receptors, and thus avoiding central side effects and therefore psychotropic effects caused by the CB1 receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/23732102

Marijuana first plants cultivated by man for medication (Update)

“Marijuana (Cannabis sativa L.) is one of the first plants cultivated by man. Shrouded in controversy, the intriguing history of cannabis as a medication dates back thousands of years before the era of Christianity.

Scientists believe the hemp plant originated in Asia. In 2737 B.C., Emperor Shen Neng of China prescribed tea brewed from marijuana leaves as a remedy for muscle injuries, rheumatism, gout, malaria, and memory loss. During the Bronze Age in 1400 B.C., cannabis was used throughout the eastern Mediterranean to ease the pain of childbirth and menstrual maladies.

More than 800 years before the birth of Christ, hemp was extensively cultivated in India for both its fiber and healing medicinal properties. William Brooke O’Shaughnessy, an Irish physician famous for his investigative research in pharmacology, is credited with introducing the therapeutic, healing properties of cannabis to Western medicine. During the 1830’s Dr. O’Shaughnessy, working for the British in India, conducted extensive experiments on lab animals. Encouraged by his results, Dr. O’Shaughnessy commenced patient treatment with marijuana for pain and muscle spasms. Further experiments indicated that marijuana was beneficial in the treatment of stomach cramps, migraine headaches, insomnia and nausea. Marijuana was also proven to be an effective anticonvulsant.

From the 1840s to the 1890s, hashish and marijuana extracts were among the most widely prescribed medications in the United States The 1850 United States Census records 8,327 marijuana plantations, each larger than 2000 acres. Recreational use of marijuana was not evident until early in the 20th century. Marijuana cigarettes became popular, introduced by migrants workers that brought marijuana with them from Mexico. With the onset of Prohibition, recreational use of marijuana skyrocketed. During the early 1930s, hash bars could be found all across the United States.

Although protested by the American Medical Association, the 1937 Marijuana Tax Act banned the cultivation and use of cannabis by federal law. Under the law, cultivation, distribution and consumption of cannabis products for medicinal, practical or recreational was criminalized and harsh penalties were implemented.”

More: http://guardianlv.com/2013/06/marijuana-first-plants-cultivated-by-man-for-medication/

marijuana

Marijuana May Help Fight Brain Damage

“Marijuana may actually help protect the brain against injury, a new study suggests.”

marijuana, cannabis, drug, addiction, weed

“While marijuana is most commonly known as a recreational drug, an increasingly number of studies show that the plant has many therapeutic qualities like relieving pain, insomnia, lack of appetite and other symptoms associated with conditions like cancer and PTSD.

Now a new study reveals that very low doses of Tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, may protect the brain from long-term cognitive damage in the wake of injury from hypoxia, seizures or toxic drugs.”

More: http://www.counselheal.com/articles/5586/20130530/marijuana-help-fight-brain-damage.htm

The endocannabinoid system and its therapeutic exploitation.

Image result for Nat Rev Drug Discov.

“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html