Intrahypothalamic injection of cannabidiol increases the extracellular levels of adenosine in nucleus accumbens in rats.

“Cannabidiol (CBD) is a constituent of Cannabis sativa that promotes wakefulness as well as enhances endogenous levels of wake-related neurotransmitters, including dopamine. However, at this date, the effects of CBD on the sleep-inducing molecules, such as adenosine (AD), are unknown. Here, we report that intrahypothalamic injection of CBD (10μg/1μL) increases the extracellular levels of AD collected from nucleus accumbens. Furthermore, the pharmacodynamic of this drug shows that effects on the contents of AD last 2h post-injection. These preliminary findings suggest that CBD promotes the endogenous accumulation of AD.”

http://www.ncbi.nlm.nih.gov/pubmed/24800644

“Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats…Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.”  http://www.ncbi.nlm.nih.gov/pubmed/16844117

“The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent.”  http://www.ncbi.nlm.nih.gov/pubmed/19045957

http://www.thctotalhealthcare.com/category/insomnia/

Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine.

“Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times.

This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex).

Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile.

No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients’ quality of life.”

http://www.ncbi.nlm.nih.gov/pubmed/17712817

Therapeutic benefits of cannabis: a patient survey.

“Clinical research regarding the therapeutic benefits of cannabis (“marijuana”) has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970.

In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai’i. The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0-10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai’i.

No serious adverse effects were reported.

These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety.

Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.”

http://www.ncbi.nlm.nih.gov/pubmed/24765558

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998228/

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