Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

“∆9 -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases.

Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors…

CONCLUSIONS:

Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors.

This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23889474

Medicinal Cannabis Does Not Influence the Clinical Pharmacokinetics of Irinotecan and Docetaxel

“For the past 4,000 years, patients and doctors of each era have resorted to cannabis when conventional treatments were ineffective or lacking. Indeed, in oncology beneficial effects have been reported for cancer-associated anorexia, chemotherapy-induced nausea and vomiting, and palliation…

The only U.S. Food and Drug Administration (FDA)-approved medicinal cannabis products are an oral formulation containing dronabinol (Marinol®)… the synthetic version of delta9-tetrahydrocannabinol (THC), the main pharmacologically active cannabinoid, and capsules containing nabilone, an analog of dronabinol (Cesamet®)…

…many patients claim (subjectively) that a whole or partially purified extract of Cannabis sativa L. offers advantages over a single isolated ingredient…

We anticipated an increased use of medicinal cannabis concurrent with anticancer drugs, and undertook a drug-interaction study to evaluate the effect of concomitant medicinal cannabis on the pharmacokinetics of irinotecan and docetaxel…

Conclusion. Coadministration of medicinal cannabis, as herbal tea, in cancer patients treated with irinotecan or docetaxel does not significantly influence the plasma pharmacokinetics of these drugs. The evaluated variety of medicinal cannabis can be administered concomitantly with both anticancer agents without dose adjustments.”

Full text: http://theoncologist.alphamedpress.org/content/12/3/291.long

Cannabis based spray approved for MS

“Sativex licensed for spasticity in multiple sclerosis. MS charity calls it a ‘milestone’
.
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

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

Therapeutic Utility of Cannabinoid Receptor Type 2 (CB2) Selective Agonists.

“The cannabinoid receptor type 2 (CB2), is a class A GPCR that was cloned in 1993 while looking for an alternate receptor that could explain the pharmacological properties of 9- tetrahydrocannabinol. CB2 was identified among cDNAs based on its similarity in amino-acid sequence to the CB1 receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.

In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, PNS and GI tract. Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.

Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this perspective, we seek to provide a concise update of progress in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/23865723

Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.

“Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors.

Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation.

Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation.

OBJECTIVE:

We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors.

CONCLUSION:

The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process.

 Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.”

http://www.ncbi.nlm.nih.gov/pubmed/17157480

Cannabis and Δ9-tetrahydrocannabinol (THC) for weight loss?

“Obesity is one of the highest preventable causes of morbidity and mortality in the developed world. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the ‘munchies’). This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome.

This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market.

We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age.

Here, we propose that this effect is directly related to exposure to the Δ(9)-tetrahydrocannabinol (THC) present in cannabis smoke.

We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.”

http://www.ncbi.nlm.nih.gov/pubmed/23410498

Amphiregulin is a factor for resistance of glioma cells to cannabinoid-induced apoptosis.

“Gliomas, one of the most malignant forms of cancer, exhibit high resistance to conventional therapies. Identification of the molecular mechanisms responsible for this resistance is therefore of great interest to improve the efficacy of the treatments against these tumors. Delta9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the ability of these compounds to induce apoptosis of tumor cells.

…we identified the epidermal growth factor receptor ligand amphiregulin as a candidate factor to mediate the resistance of glioma cells to cannabinoid treatment… in vivo silencing of amphiregulin rendered the resistant tumors xenografts sensitive to cannabinoid antitumoral action.

Amphiregulin expression was associated with increased extracellular signal-regulated kinase (ERK) activation, which mediated the resistance to THC by blunting the expression of p8 and TRB3-two genes involved in cannabinoid-induced apoptosis of glioma cells.

 Our findings therefore identify Amphirregulin as a factor for resistance of glioma cells to THC-induced apoptosis and contribute to unraveling the molecular bases underlying the emerging notion that targeted inhibition of the EGFR pathway can improve the efficacy of antitumoral therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/19229996