Tag Archives: cannabinoid

Activation of Cortical Type 2 Cannabinoid Receptors Ameliorates Ischemic Brain Injury, Study Suggests

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“A new study published in the March issue of The American Journal of Pathology suggests that cortical type 2 cannabinoid (CB2) receptors might serve as potential therapeutic targets for cerebral ischemia.

Researchers found that the cannabinoid trans-caryophyllene (TC) protected brain cells from the effects of ischemia in both in vivo and in vitro animal models. In rats, post-ischemic treatment with TC decreased cerebral infarct size and edema. In cell cultures composed of rat cortical neurons and glia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R), TC decreased neuronal injury and mitochondrial depolarization, specifically through type 2 cannabinoid receptor (CB2R) pathways.

“To our knowledge, novel data presented in this study provide evidence for the first time supporting a previously unappreciated role of cortical CB2R, especially neuronal CB2Rs, in ischemia,” says lead investigator Won-Ki Kim, PhD, of the Department of Neuroscience, College of Medicine, Korea University in Seoul. “This study suggests that further investigation is warranted to establish the clinical usefulness of TC as a preventative and therapeutic agent for treatment of stroke.””

More: http://www.sciencedaily.com/releases/2013/02/130221141140.htm

GW Pharmaceuticals: Giving New Meaning To ‘High Potential’

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“GW Pharmaceuticals (GWPH) is an UK-based biopharmaceutical company focused on the discovery and development of cannabinoid-based products for a wide range of indications. GW has established a technology platform based on genetically modified cannabis plants and has become a leader in plant-derived cannabinoid therapeutics.

 GW’s lead program is Sativex, a cannabis extract based oromucosal spray whose main actives are the cannabinoids delta-9- tetrahydrocannabinol (THC), and cannabidiol (CBD). It is approved for the treatment of multiple sclerosis (MS) spasticity in 21 countries outside of the U.S and already marketed in seven countries (eight following Italian launch in Q213).

…While MS spasticity has provided proof-of-concept in the worldwide approvability of Sativex, a more meaningful commercial opportunity is in the treatment of opioid-refractory cancer pain. Sativex has been tested in two Phase II trials in cancer pain. The trials have demonstrated that Sativex is safe and effective when used in addition to opioids in patients whose cancer pain is not sufficiently managed by opioids alone. Based on these results, GW has initiated three Phase III trials. The first two are expected to complete during 2014 and support an FDA filing.”

More: http://seekingalpha.com/article/1490392-gw-pharmaceuticals-giving-new-meaning-to-high-potential

A Double-Blind, Placebo-Controlled, Crossover Pilot Trial With Extension Using an Oral Mucosal Cannabinoid Extract for Treatment of Chemotherapy-Induced Neuropathic Pain.

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“Neuropathic pain caused by chemotherapy limits dosing and duration of potentially life-saving anti-cancer treatment and impairs quality of life. Chemotherapeutic neuropathy responds poorly to conventional treatments, and there is an urgent medical need for new treatments. Recent preclinical studies demonstrate that cannabinoid agonists suppress established chemotherapy-evoked neuropathy.

This was a pilot trial to begin to investigate a currently available cannabinoid agent, nabiximols (oral mucosal spray containing cannabinoids), in the treatment of chemotherapy-induced neuropathic pain.

CONCLUSION:

Chemotherapy-induced neuropathic pain is particularly resistant to currently available treatments. This pilot trial found a number needed to treat of five and an average decrease of 2.6 on an 11-point NRS-PI in five “responders” (as compared with a decrease of 0.6 with placebo) and supports that it is worthwhile to study nabiximols in a full randomized, placebo-controlled trial of chemotherapy-induced neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23742737

Study: Cannabinoids Offer Likely Therapeutic Option For Patients With Post-Traumatic Stress

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“Future research targeting cannabinoids and their receptors may lead to evidence-based treatments for patients diagnosed with post-traumatic stress disorder (PTSD), according to clinical trial data published in May in the journal Molecular Psychiatry.

Investigators at the New York University School of Medicine reported that subjects diagnosed with PTSD typically possess elevated quantities of endogenous cannabinoid receptors in regions of the brain associated with fear and anxiety. Investigators also determined that many of these subjects experience a decrease in their natural production of anandamide, an endogenous cannabinoid neurotransmitter, resulting in an imbalanced endocannibinoid regulatory system.

Researchers speculated that an increase in the body’s production of cannabinoids would likely restore subjects’ natural brain chemistry and psychological balance. They affirmed, “[Our] findings substantiate, at least in part, emerging evidence that … plant-derived cannabinoids such as marijuana may possess some benefits in individuals with PTSD by helping relieve haunting nightmares and other symptoms of PTSD.”

Authors concluded: “The data reported herein are the first of which we are aware of to demonstrate the critical role of CB1 (cannabinoid) receptors and endocannabinoids in the etiology of PTSD in humans. As such, they provide a foundation upon which to develop and validate informative biomarkers of PTSD vulnerability, as well as to guide the rational development of the next generation of evidence-based treatments for PTSD.”

More: http://norml.org/news/2013/05/30/study-cannabinoids-offer-likely-therapeutic-option-for-patients-with-post-traumatic-trauma

Cannabinoid (CB)1 receptors are critical for the innate immune response to TLR4 stimulation.

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“Sickness behaviours are host defence adaptations that arise from integrated autonomic outputs in response to activation of the innate immune system. These behaviours include fever, anorexia, and hyperalgesia intended to promote survival of the host when encountering pathogens. Cannabinoid (CB) receptor activation can induce hypothermia and attenuate lipopolysaccharide (LPS)-evoked fever. The aim of the present study was to examine the role of CB1 receptors in the LPS-evoked febrile response. CB1 receptor-deficient (CB1-/-) mice did not display LPS-evoked fever; likewise pharmacological blockade of CB1 receptors in wild-type mice blocked LPS-evoked fever. This unresponsiveness is not limited to thermogenesis, as the animals were not hyperalgesic after LPS administration. A toll-like receptor (TLR)3 agonist and viral mimetic polyinosinic:polycytidylic acid evoked a robust fever in CB1-/- mice suggesting TLR3-mediated responses are functional. LPS-evoked c-Fos activation in areas of the brain associated with the febrile response was evident in wild-type mice but not in CB1-/- mice. Liver and spleen TLR4 mRNA were significantly lower in CB1-/- mice compared to wild-type, and peritoneal macrophages from CB1-/- mice did not release pro-inflammatory cytokines in response to LPS. These data indicate that CB1 receptors play a critical role in LPS-induced febrile responses through inhibiting TLR4-mediated cytokine production.”

http://www.ncbi.nlm.nih.gov/pubmed/23739343

Most Docs OK With Medical Marijuana: Survey – MedlinePlus

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“Majority would give a prescription to an advanced cancer patient in pain.Three-quarters of doctors who responded to a survey about medical marijuana said they would approve the use of the drug to help ease pain in an older woman with advanced breast cancer.

….there are two FDA-approved prescription cannabinoid pills — dronabinol (Marinol) and nabilone (Cesamet) — that don’t begin working as quickly as smoked marijuana, but provide longer symptom relief without the high of marijuana.

 They also don’t appear to have any addictive properties, he said.

What many doctors would like to see, according to the survey, is more evidence on the use of marijuana as medicine, so they could make a better-informed decision one way or the other.”

More: http://www.nlm.nih.gov/medlineplus/news/fullstory_137301.html

Synthetic and Patented Cannabinoids

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“Historically, laboratory synthesis of cannabinoids were often based on the structure of herbal cannabinoids, and a large number of analogs have been produced and tested, especially in a group led by Roger Adams as early as 1941 and later in a group led by Raphael Mechoulam.

Newer compounds are no longer related to natural cannabinoids or are based on the structure of the endogenous cannabinoids.

Synthetic cannabinoids are particularly useful in experiments to determine the relationship between the structure and activity of cannabinoid compounds, by making systematic, incremental modifications of cannabinoid molecules.

Medications containing natural or synthetic cannabinoids or cannabinoid analogs:

  • Dronabinol (Marinol), is Δ9-tetrahydrocannabinol (THC), used as an appetite stimulant, anti-emetic, and analgesic
  • Nabilone (Cesamet), a synthetic cannabinoid and an analog of Marinol. It is Schedule II unlike Marinol, which is Schedule III
  • Sativex, a cannabinoid extract oral spray containing THC, CBD, and other cannabinoids used for neuropathic pain and spasticity in Canada and Spain. Sativex develops whole-plant cannabinoid medicines
  • Rimonabant (SR141716), a selective cannabinoid (CB1) receptor antagonist used as an anti-obesity drug under the proprietary name Acomplia. It is also used for smoking cessation

Other notable synthetic cannabinoids include:

  • CP-55940, produced in 1974, this synthetic cannabinoid receptor agonist is many times more potent than THC
  • Dimethylheptylpyran
  • HU-210, about 100 times as potent as THC
  • HU-331 a potential anti-cancer drug derived from cannabidiol that specifically inhibits topoisomerase II.
  • SR144528, a CB2 receptor antagonists
  • WIN 55, a potent cannabinoid receptor agonist
  • JWH-133, a potent selective CB2 receptor agonist
  • Levonantradol (Nantrodolum), an anti-emetic and analgesic but not currently in use in medicine”

http://www.news-medical.net/health/Synthetic-and-Patented-Cannabinoids.aspx

Dysregulation of Cannabinoid CB1 Receptor and Associated Signaling Networks in Brains of Cocaine Addicts and Cocaine-Treated Rodents.

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The endocannabinoid system is implicated in the neurobiology of cocaine addiction. This study evaluated the status of cannabinoid CB1 and CB2 receptors, the endocytic cycle of CB1 receptors, receptor regulatory kinases (GRK), and associated signaling (mTOR and p70S6K) in brain cortex of drug abusers and cocaine- and cannabinoid-treated rodents…

 In long-term cocaine addicts, mTOR and p70S6K activations were not altered when compared with controls, indicating that CB1 receptor signaling was dampened. The dysregulation of CB1 receptor, GRK2/3/5, and mTOR/p70S6K signaling by cocaine may contribute to alterations of neuroplasticity and/or neurotoxicity in brains of cocaine addicts.”

More: http://www.ncbi.nlm.nih.gov/pubmed/23727505

Cannabinoids Attenuate Cancer Pain and Proliferation in a Mouse Model

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“Oral cancer represents 3% of all cancers and its overall survival rate of 50% places it among the worst of all cancers

For many years cannabinoids have been used for medicinal and recreational purposes.

Recently, studies have focused on the therapeutic effects of cannabinoids on different cancers. The current study was the first to investigate the therapeutic effects of synthetic cannabinoids on oral cancer.

We investigated the effects of cannabinoid receptor agonists on (1) oral cancer cell viability in vitro and (2) oral cancer pain and tumor growth in a mouse cancer model.

Here we demonstrate the anti-nociceptive and anti-proliferative effects of systemic administration of cannabinoid receptor agonists on human oral cancer cells.

Our results suggest that systemic administration of cannabinoids decease oral cancer pain.

Our findings suggest a direct role for cannabinoid mechanisms in oral cancer pain and proliferation.

The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer.

The present findings suggest that cannabinoid treatment may be a promising alternative therapy for oral cancer pain management. Furthermore, CBr2 agonism is not only palliative, but it may also be effective in inhibiting oral cancer growth, making the agonist a particularly desirable therapeutic agent.”

Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099480/

Evidence: Cannabinoid Therapy Reduces Breast Cancer Tumors

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“Warning: Many alternative treatments are shams with zero proof. Most alternatives make claims that are not backed up by any evidence or hard empirical medical studies, are are not peer-reviewed. 
 
Peer review means your study and its claims will be vetted by a panel of the best doctors and other medical professionals in that field, for critical review. They will try to find fault in its methodology before publication and its recommendations for possible human treatment.
 
For any cannabis-based study strong enough to stand up to this critical review, and for it to be published in a major journal within such a field as cancer research, is incredible. That’s exactly how strong the evidence for cannabis medicine is starting to become.
 
Imagine that. This plant, this “great friend of humanity” which has helped us survive by giving early humans food, fuel, fiber and medicine, and who ancient healers wrote about in 6000 B.C., more than 8,000 years ago, is now coming back to prove itself and to help save us again.
 
And this time we are starting to find the evidence to back up the claims made for this plant over the centuries…”