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

The endocannabinoid system and its therapeutic exploitation.

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“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

Medical Marijuana: Sleeping Medicine

“The most frequent comment by those ignorant of the medical properties of cannabis or those believing the U.S. Government’s propaganda, is that marijuana patients use it only to get “high” which incidentally can be somewhat like a Starbucks espresso jolt or maybe two or three martinis.

Anybody who knows anything at all about marijuana knows that it causes euphoria or a feeling of well being. After all, isn’t that why we take medicine when we are sick—to feel better?

At any rate, marijuana users, as medical patients of which there are at least 400,000 with legal permits, or as many as ten million “illegal” users who use it instead of alcohol, tobacco, prescription tranquilizers or antidepressants, have found it beneficial for a wide variety of illnesses and diseases.

It is certain that the euphoria or feeling of comfort is very important for all these conditions. If some ignorant people consider that to be getting high, no users will disagree.

Many medical patients use it only in the evening to enable them to sleep. This is true especially with those in chronic pain, which represents about 70 percent of patients. Pain frequently or even most usually prevents sleep and some patients tell me, “if I can get a decent night’s sleep, I can fight alligators all day”.

Sleeping pills are prescribed mostly for those in pain who cannot sleep without those pills. The crazy thing about this is that many or maybe most sleeping pills are as addicting as heroin. Valium, the most prescribed sleeping pill for many years, produced millions of addicts, and there are many valium-like drugs with similar problems.

In my experience with 4,000 plus patients, I was told by hundreds that by using marijuana they were able to cut down or eliminate completely most prescription sleeping pills.

The U.S. Government purports that marijuana is addicting. This is not so. If a person uses it frequently to relieve or control pain, the patient wants relief. Does that mean he is addicted to relief? If one takes aspirin everyday, is he addicted to aspirin? To me, the comparison is valid.

One of the critical signs of addiction is uncomfortable withdrawal symptoms. Most marijuana users will run out of their medicine once in a while. Do they get withdrawal symptoms? If so, they are very minor, like running out of aspirin.

It is known that very heavy marijuana use (which is uncommon because it costs more than gold) can cause mild withdrawal symptoms, such as disrupted sleep and nervousness (from Merck Manual).

I think the final coup de grace is also given by the Merck Manual “any drug which causes euphoria and diminishes anxiety can cause dependence” (not addiction—my comment).”-

Dr. Phillip Leveque

http://www.salem-news.com/articles/june272007/marijuana_sleep_62707.php

Cannabis for better sleep

“The use of both natural cannabinoids and cannabis extracts are associated with improved sleep in patients with various debilitating illnesses, according to a review of clinical trial data published in the journal Chemistry & Biodiversity.

“Cannabis … has been utilized for [the] treatment of pain and sleep disorders since ancient times,” authors wrote. “Modern clinical trials indicate that patients administered cannabis extracts report experiencing “more restful sleep, [an] increase [in] their daytime level of function, and [a] markedly improve[d] … quality of life.”

According to available data, of the 2,000 subjects that have been administered cannabis extracts in clinical trials, most “demonstrate marked improvement in subjective sleep parameters.”

Trial volunteers have not reported developing tolerance to the drug, even after using it for several years.

Full text of the study, “Cannabis, pain, and sleep: Lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine,” appears in the journal Chemistry & Biodiversity.”

http://azarius.net/news/193/Cannabis_for_better_sleep/

Cannabis ‘helped woman to sleep’

“A YOUNG mother using cannabis to help her sleep has been given the benefit of the probation act at Wexford District Court.

Shelly Donnelly, Moortown Great, Ballmitty, had pleaded guilty to the possession of cannabis at her home on June 11, 2010.

Judge Donnchadh O Buachalla heard that the property at Moortown Great was searched and a small quantity of cannabis herb was found. It was for Donnelly’s own use.

Eva Lalor, for Donnelly, said her client is 24years-old and has a fiveyear-old daughter with her long-term partner.

Ms Lalor said Donnelly was suffering from insomnia following a family bereavement and was using cannabis to help her sleep. Donnelly, who has no previous convictions, is now on medication to help her sleep.

Judge O Buachalla gave her the benefit of the probation act, saying that he hopes she has learnt her lesson from the experience.”

http://www.independent.ie/regionals/wexfordpeople/news/cannabis-helped-woman-to-sleep-27726026.html

Stab victim started taking cannabis to sleep

A YOUNG man started smoking cannabis herb to help him sleep after he was stabbed through the heart and lungs, a court heard. Francis Kelly (23) spent two weeks in intensive care, and started taking the drug after he came out of hospital….

He was in intensive care for two weeks and was on tablets while he was in hospital.

Mr O’Doherty said that Kelly couldn’t sleep when he left hospital and he started taking it to help him relax.”

More: http://www.herald.ie/news/stab-victim-started-taking-cannabis-to-sleep-27997127.html

Cannabis helped night worker sleep

Mark Jackson has escaped without having a conviction recorded for his latest drug offences. 
Mark Jackson has escaped without having a conviction recorded for his latest drug offences.

HOSPITALITY manager Mark Jackson has been fined for possessing marijuana, which he smoked after night work to help him get some sleep.

Jackson has a history of drug use dating back to 2000, when the Supreme Court gave him a suspended jail sentence for supplying drugs.

However, his last drug-related offence was in 2005.

Jackson, a 48-year-old who supports four dependents, pleaded guilty in Mackay Magistrate’s Court yesterday to the unlawful possession of a small amount of marijuana and a pipe last October 20.

Police executed a search warrant at his Andergrove home at 12.45am and Jackson was the sole occupant, prosecutor Constable Janelle Young said.

Asked if he had anything to declare, he said he had a bong beside his bed.

A homemade pipe and a small amount of marijuana were found.

He told police he had smoked some marijuana that morning, after night work, because it helped him to sleep.

The items were seized and he was issued with a property receipt.

Duty lawyer John Aberdeen said Jackson “holds a managerial position in hospitality” and did mostly night work.

His previous convictions in 2000 and 2005 were acknowledged but the new offences involved only a small amount of drugs for personal use, Mr Aberdeen said.

Mr Aberdeen asked for no conviction to be recorded because of the length of time that had elapsed since the last offence.

Magistrate Damien Dwyer imposed a fine of $600 and ordered that no conviction be recorded.”

http://www.dailymercury.com.au/news/marijuana-helped-night-worker-get-some-sleep/1228013/

The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent.

“Cannabidiol (CBD) is a constituent of Cannabis sativa that induces nonpsychotropic effects, and some of its biological actions in sleep have been described by the authors’ group.

 Here, the authors report that when administered 10 or 20 microg/1 microl during the lights-on period directly into either lateral hypothalamus (LH) or dorsal raphe nuclei (DRN), which are wake-inducing brain areas, CBD enhanced wakefulness and decreased slow wave sleep and REM sleep. Furthermore, CBD increased alpha and theta power spectra but diminished delta power spectra. Additionally, CBD increased c-Fos expression in LH or DRN.

These findings suggest that this cannabinoid is a wake-inducing compound that presumably activates neurons in LH and DRN.”

http://www.ncbi.nlm.nih.gov/pubmed/19045957

Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats.

“Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Delta(9)-THC modulates sleep, but no clear evidence on the role of CBD is available.

In order to determine the effects of CBD on sleep, it was administered intracerebroventricular (icv) in a dose of 10 microg/5 microl at the beginning of either the lights-on or the lights-off period. We found that CBD administered during the lights-on period increased wakefulness (W) and decreased rapid eye movement sleep (REMS). No changes on sleep were observed during the dark phase. Icv injections of CBD (10 microg/5microl) induced an enhancement of c-Fos expression in waking-related brain areas such as hypothalamus and dorsal raphe nucleus (DRD). Microdialysis in unanesthetized rats was carried out to characterize the effects of icv administration of CBD (10 microg/5 microl) on extracellular levels of dopamine (DA) within the nucleus accumbens. CBD induced an increase in DA release. Finally, in order to test if the waking properties of CBD could be blocked by the sleep-inducing endocannabinoid anandamide (ANA), animals received ANA (10 microg/2.5 microl, icv) followed 15 min later by CBD (10 microg/2.5 microl). Results showed that the waking properties of CBD were not blocked by ANA.

 In conclusion, we found that CBD modulates waking via activation of neurons in the hypothalamus and DRD. Both regions are apparently involved in the generation of alertness. Also, CBD increases DA levels as measured by microdialysis and HPLC procedures.

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 modulatory role of endocannabinoids in sleep].

“The endogenous cannabinoid, or endocannabinoid, system is present in the central nervous system (CNS) of rodents and humans. This system includes receptors, endogenous ligands and enzymes. The presence of cannabinoid receptors, called CB1, in the CNS has been reported in the cerebral cortex, the hippocampus, the cerebellum and the brain stem. This neuroanatomical location suggests that this receptor could modify several physiological functions, such as the consolidation of memory, motor control and the generation of sleep.

 

Recent reports have described the presence of lipids in the CNS that bind to the CB1 receptor. Administration of said molecules induces cannabimimetic effects, and hence it has been suggested that these lipids are endogenous cannabinoids or endocannabinoids. Anandamide, 2-arachidonylglycerol, virodhamine, noladin ether and N-arachidonyldopamine are molecules that belong to the endocannabinoid family. Anandamide has received more attention from researchers because it was the first endocannabinoid to be reported. Pharmacological experiments have shown that this endocannabinoid induces several different intracellular and behavioural changes.

CONCLUSIONS:

In this study, we review the most important pharmacological aspects of exogenous cannabinoids and the neurobiological role played by the endocannabinoid system, including endogenous and exogenous ligands and receptors. We also examine their pharmacological effects on different behaviours, with particular attention given to the modulation of sleep.”

http://www.ncbi.nlm.nih.gov/pubmed/18297624