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

GW Pharmaceuticals Announces Results of MS Spasticity Study Confirming Sativex Has No Long-Term Negative Effect on Cognition

“-Provides Further Evidence of Long-term Efficacy-

GW Pharmaceuticals, a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, announces top-line results from a 12 month placebo-controlled study of Sativex in patients with spasticity due to Multiple Sclerosis (MS).

The study results confirm the reassuring safety profile of Sativex and provide further evidence of long-term efficacy.”

More: http://finance.yahoo.com/news/gw-pharmaceuticals-announces-results-ms-060000735.html

Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype.

“Cannabinoids, the Cannabis constituents, are known to possess anti-inflammatory properties but the mechanisms involved are not understood. Here we show that the main psychoactive cannabinoid, Δ-9-tetrahydrocannabinol (THC), and the main nonpsychoactive cannabinoid, cannabidiol (CBD), markedly reduce the Th17 phenotype which is known to be increased in inflammatory autoimmune pathologies such as Multiple Sclerosis…

Pretreatment with CBD also resulted in increased levels of the anti-inflammatory cytokine IL-10. Interestingly, CBD and THC did not affect the levels of TNFα and IFNγ. The downregulation of IL-17 secretion by these cannabinoids does not seem to involve the CB1, CB2, PPARγ, 5-HT1A or TRPV1 receptors…

In conclusion, the results show a unique cannabinoid modulation of the autoimmune cytokine milieu combining suppression of the pathogenic IL-17 and IL-6 cytokines along with boosting the expression of the anti-inflammatory cytokine IL-10.”

http://www.ncbi.nlm.nih.gov/pubmed/23892791

Cannabidiol Normalizes Caspase 3, Synaptophysin, and Mitochondrial Fission Protein DNM1L Expression Levels in Rats with Brain Iron Overload: Implications for Neuroprotection.

“We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats.

 Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson’s and Alzheimer’s, and has been related to cognitive deficits in animals and human subjects.

…we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats.

We found that CBD rescued iron-induced effects…

Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23893294

Cannabis Use, Effect And Potential Therapy For Alzheimer’s, MS and Parkinson’s

“The illegal status and wide-spread use of cannabis made basic and clinical cannabis research difficult in the past decades; on the other hand, it has stimulated efforts to identify the psychoactive constituents of cannabis. As a consequence, the endocannabinoid system was discovered, which was shown to be involved in most physiological systems — the nervous, the cardiovascular, the reproductive, the immune system, to mention a few.

One of the main roles of endocannabinoids is neuroprotection, but over the last decade they have been found to affect a long list of processes, from anxiety, depression, cancer development, vasodilatation to bone formation and even pregnancy.

Cannabinoids and endocannabinoids are supposed to represent a medicinal treasure trove which waits to be discovered…

The endocannabinoid system acts as a guardian against various attacks on the mammalian body.

Conclusion

The above described research concerning the endocannabinoid-system is of importance in both basic science and in therapeutics:

  • The discovery of the cannabis plant active constituent has helped advance our understanding of cannabis use and its effects.
  • The discovery of the endocannabinoids has been of central importance in establishing the existence of a new biochemical system and its physiological roles — in particular in neuroprotection.
  • These discoveries have opened the door for the development of novel types of drugs, such as THC for the treatment of nausea and for enhancing appetite in cachectic patients.
  • The endocannabinoid system is involved in the protective reaction of the mammalian body to a long list of neurological diseases such as multiple sclerosis, Alzheimer’s and Parkinson’s disease which raises hope for novel therapeutic opportunities for these diseases.”

More: http://www.sciencedaily.com/releases/2007/10/071014163644.htm

Cannabis based spray approved for MS

“Sativex licensed for spasticity in multiple sclerosis. MS charity calls it a ‘milestone’
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sad woman
 
“The cannabis-based mouth spray, Sativex, has been approved by the UK medicines regulator, MHRA, as a prescription only treatment for MS related spasticity.

Sativex is designed as an add-on treatment for moderate to severe MS spasms and cramping in people who receive inadequate relief from the standard oral anti-spasticity medicines or have experienced unbearable side effects whilst taking these medicines.

Sativex contains two cannabinoids or active ingredients – THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol).  It is the first cannabinoid medicine derived from whole plant extracts from the cannabis sativa plant…”

More: http://www.webmd.boots.com/news/20100621/cannabis-based-spray-approved-for-ms

Pot smoking may help relieve symptoms of MS – NBC News

“Smoking marijuana may improve some symptoms of multiple sclerosis, a new study suggests.

Patients with multiple sclerosis in the study had less muscle tightness, also called spasticity, and less pain after they smoked marijuana, compared with after they took a placebo…

More research is needed to confirm the findings and to investigate whether lower doses of marijuana may have similar benefits with fewer adverse effects, said study researcher Dr. Jody Corey-Bloom, professor of neurosciences and director of the Multiple Sclerosis Center at the University of California, San Diego.

The study is published today (May 14) in the Canadian Medical Association Journal.

Improved symptoms

Previous studies have suggested marijuana use may have benefits for MS patients, but most have investigated oral forms of the drug, including mouth sprays and capsules. In addition, most studies have asked patients to report changes in their symptoms, rather than having a researcher objectively assess them…

Participants were randomly assigned to receive treatment with a marijuana cigarette or a placebo cigarette, which did not contain delta-9-tetrahydrocannabinol (THC), the active ingredient of marijuana. Participants smoked a marijuana cigarette once a day for three consecutive days under the supervision of a researcher. Eleven days later, participants repeated the procedure, but this time, they switched treatment groups so that everyone received the marijuana cigarette and placebo at some point in the study. On average, participants smoked four puffs of their cigarettes at each session.

Shortly after each treatment session, the researchers assessed participants with a test specifically designed to measure spasticity.

After smoking marijuana, participants experienced a 30 percent reduction in spasticity, compared with when they smoked the placebo cigarette, Corey-Bloom said.”

More: http://www.nbcnews.com/health/pot-smoking-may-help-relieve-symptoms-ms-771076

Cannabis eases multiple sclerosis (MS) stiffness per study published in neurology journal

“The trial, led by John Peter Zajicek of Britain’s Clinical Neurology Research Group, says standardized doses of cannabis extract can be useful in easing pain and spasms in this disease.”


	Use of cannabis extract helps ease painful muscle stiffness among patients with multiple sclerosis (MS), according to a large new trial.

“Use of cannabis extract helps ease painful muscle stiffness among patients with multiple sclerosis (MS), according to a large trial published on Tuesday in the Journal of Neurology, Neurosurgery and Psychiatry…”

http://www.nydailynews.com/life-style/health/cannabis-eases-multiple-sclerosis-ms-stiffness-study-article-1.1179450

 

Aylsham multiple sclerosis sufferer says cannabis-based drug ‘changed my life’

“A new cannabis-based licensed drug has transformed the life of multiple sclerosis (MS) sufferer Teresa Pointer from Aylsham.”

Teresa Pointer, from Aylsham, whose MS has been helped by using a new drug based on cannabis plant extracts.
PHOTO: ANTONY KELLY

“Mrs Pointer, 42, spotted an advertisement in the EDP eight years ago, asking people to take part in treatment trials at the James Paget University Hospital, Gorleston, and she has not looked back.

Today, thanks to two daily sprays of Sativex into her mouth, Mrs Pointer can sleep at night, walk for longer – and she has got her sense of humour back.

“I got in touch with Dr Willy Notcutt at the James Paget and then started on a clinical trial of Sativex. It was the best decision I’ve ever made and it’s done so much for me. It really has given me my life back,” said Mrs Pointer, who lives with her husband and two daughters in Hungate Street.

She was diagnosed in 2004 with MS, a disease which affects nerves in the brain and spinal cord.

An increase in muscle tone, or “spasticity”, is a common symptom, causing involuntary muscle spasms, immobility, disturbed sleep, and pain.

Although MS is incurable, treatments and specialists can help sufferers manage their symptoms.

Within two weeks of starting the trial, Mrs Pointer, whose health problems forced her to retire from her job as an assistant cook at Aylsham’s Bure Valley School, began to notice an improvement.

“It doesn’t take any of the symptoms away but it relieves them,” she said. The drug relaxed her muscles, easing the pain, discomfort and spasms when her legs would “try and jump off the bed”, which stopped her sleeping.

“I had been getting so tetchy through lack of sleep. I was snappy and angry all the time. But, because it helped me sleep, I could laugh and smile again. I found the funnier side of life which I thought I’d lost forever.”

At a later point in the double-blind trial, which involved 18 local patients, Mrs Pointer, without her knowledge or that of the medical team, was given a placebo instead of Sativex. Her symptoms soon returned and she could not sleep.

After discussions with specialists, she was put back on the drug. “That night I slept like a baby again. The contrast was so stark,” she said.

Mrs Pointer said she had no previous experience of cannabis but Sativex only relaxed muscles, it did not generate the “high” sought by recreational drug users.

She also believes that, without the drug, she would be using her wheelchair far more often than she does at present as it relaxes her leg muscles enough to allow her to walk greater distances.

Dr Notcutt, research and development director at the James Paget, said Mrs Pointer’s participation in the trial had been invaluable.

He added: “The results of these studies are being used all across the world as doctors and others look at the potential value of this medicine. Teresa and others like her locally have been pioneers in a therapy that has a huge potential in many different areas. Without more volunteers to help us explore, medical research will only make very slow progress.”

■ Around 100,000 people in the UK have MS. It is normally diagnosed in people between the ages of 20 and 40, and affects almost three times as many women as men.

■ Sativex, in the form of a mouth spray, contains the principal extracts delta-9-tetrahydrocannabinol and cannabidiol – found in the leaf and flower of the cannabis plant, and is the first cannabinoid preparation to be licensed in the UK for use in the treatment of muscle spasms in MS.”

http://www.eveningnews24.co.uk/mobile/news/aylsham_multiple_sclerosis_sufferer_says_cannabis_based_drug_changed_my_life_1_2276182

[Marihuana and cannobinoids as medicaments].

“Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen.

Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting.

Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease.

Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells.

Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications.

In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin.

Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.”

http://www.ncbi.nlm.nih.gov/pubmed/23421098