Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics.

“Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications.

Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists.

Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents.

This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV.

Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid.

Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine.”

http://www.ncbi.nlm.nih.gov/pubmed/27274310

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Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway.

“Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes.

Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses.

Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.

SIGNIFICANCE STATEMENT:

The cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia.

However, the mechanisms by which CBD may produce antipsychotic effects are entirely unknown. Using preclinical behavioral procedures combined with molecular analyses and in vivo neuronal electrophysiology, our findings identify a functional role for the nucleus accumbens as a critical brain region whereby CBD can produce effects similar to antipsychotic medications by triggering molecular signaling pathways associated with the effects of classic antipsychotic medications.

Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via a direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/27147666

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

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Blockade of Nicotine and Cannabinoid Reinforcement and Relapse by a Cannabinoid CB1-Receptor Neutral Antagonist AM4113 and Inverse Agonist Rimonabant in Squirrel Monkeys.

“Nicotine, the main psychoactive component of tobacco, and (-)-Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, play major roles in tobacco and marijuana dependence as reinforcers of drug-seeking and drug-taking behavior.

Drugs that act as inverse agonists of cannabinoid CB1 receptors in the brain can attenuate the rewarding and abuse-related effects of nicotine and THC…

Recently-developed CB1-receptor neutral antagonists may provide an alternative therapeutic approach to nicotine and cannabinoid dependence.

These findings point to CB1-receptor neutral antagonists as a new class of medications for treatment of both tobacco dependence and cannabis dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/26888056

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Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

“Cannabis has a long history of medicinal use.

Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes.

Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs).

Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting.”

http://www.ncbi.nlm.nih.gov/pubmed/26561338

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

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Clinical perspectives on medical marijuana (cannabis) for neurologic disorders.

“The American Academy of Neurology published an evidence-based systematic review of randomized controlled trials using marijuana (Cannabis sativa) or cannabinoids in neurologic disorders.

Several cannabinoids showed effectiveness or probable effectiveness for spasticity, central pain, and painful spasms in multiple sclerosis.

The review justifies insurance coverage for dronabinol and nabilone for these indications.

Many insurance companies already cover these medications for other indications.

It is unlikely that the review will alter coverage for herbal marijuana.

Currently, no payers cover the costs of herbal medical marijuana because it is illegal under federal law and in most states.

Cannabinoid preparations currently available by prescription may have a role in other neurologic conditions, but quality scientific evidence is lacking at this time.”

http://www.ncbi.nlm.nih.gov/pubmed/26336632

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Cannabinoids for the Treatment of Movement Disorders.

“Use of cannabinoids as medications has a long history.

Unfortunately, the prohibition of cannabis and its classification in 1970 as a schedule 1 drug has been a major obstacle in studying these agents in a systematic, controlled manner.

The number of class 1 studies (randomized, double-blind, placebo-controlled) in patients with movement disorders is limited. Hence, it is not possible to make recommendations on the use of these cannabinoids as primary treatments for any of the movement disorders at this time.

Fortunately, there is an expanding body of research in animal models of age-dependent and disease-related changes in the endocannabinoid system that is providing new targets for drug development.

Moreover, there is growing evidence of a “cannabinoid entourage effect” in which a combination of cannabinoids derived from the plant are more effective than any single cannabinoid for a number of conditions.

Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective.

As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will expand.”

http://www.ncbi.nlm.nih.gov/pubmed/26206230

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Israeli-American Team Hopes to Cure Diabetes With Cannabis

israel diabetes

“An American-Israeli biotech team is taking cannabis research to the next level by developing novel therapies using cannabis extract to treat diabetes, inflammatory conditions, chronic pain and cardiovascular disease.

ISA Scientific just signed a deal with Yissum, the technology-transfer company of the Hebrew University of Jerusalem, Hadasit, the technology-transfer company of the Hadassah Medical Organization in Jerusalem, and the Kennedy Trust for Rheumatology Research (KIR) in the United Kingdom to help bring the drugs to market.

All the credit for the idea, however, goes to a Hebrew University researcher who has worked on idea for years.

“Raphael Mechoulam deserves all the credit for this,” fellow researcher Chaim Lotan of Hadassah University Medical Center said.

Mechoulam discovered that cannabidiol (CBD) receptors existed not only in the brain but in other tissues found throughout the body.

Knowing this, he then went to work finding a way to alter cannabinoids to work on certain areas of the body.

“He synthesized a whole ‘family’ of cannabinoids, and therefore with some changes in molecular structure you can tailor cannabinoids to different receptors,” Lotan said.

Lotan, a cardiologist, helped work on making a drug for the heart.

“My role was only the cardiac part,” he explained “but we may see effects in other organs as well since we found so many receptors.”

The team is now ready for Phase 2 trials of the drug for diabetes and chronic pain and is hopeful that the drug, which has now psychoactive properties at all, will ultimately provide a solution that may not only manage diabetes but perhaps even cure the widespread disease.

“Unlike insulin and other existing medications for diabetes, CBD may actually suppress, reverse and perhaps cure the disease,” ISA Scientific Chief Executive Officer Mark J. Rosenfeld said. “So, the therapeutic alternatives offered by cannabis chemistry could go far in helping to resolve conditions responsible for a huge public health crisis in China and elsewhere.””

http://www.jspacenews.com/israeli-american-team-hopes-cure-diabetes-cannabis/

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

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Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception.

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“Cannabis has been used for thousands of years as a therapeutic agent for pain relief, as well as for recreational purposes.

Delta-9-Tetrahydrocannabinol (Δ9-THC)… produces antinociceptive effects in a wide range of preclinical assays of pain.

Considerable preclinical research has demonstrated the efficacy of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids.

Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Delta(9)-THC.

These results suggest that various constituents of this plant may interact in a complex manner to modulate pain.

The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model…

Importantly, the antinociceptive effects of Delta(9)-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching.

These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Delta(9)-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Delta(9)-THC.

The results obtained in the present study are consistent with the view that Δ9-THC is the major phytocannabinoid present in marijuana that produces antinociception in the acetic acid abdominal stretching test.

…these results suggest that there is potential to develop medications containing various concentrations of specific phytocannabinoids to optimize therapeutic effects (e.g., antinociception) and minimize psychomimetic effects.

In sum, the results of the present study further support the notion that Δ9-THC is the predominant constituent of marijuana that is responsible for eliciting antinociceptive effects and indicate that CB1 receptors play a predominant role in mediating these effects.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765124/

http://www.thctotalhealthcare.com/category/pain-2/

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Cannabinoid receptor type 2 activation in atherosclerosis and acute cardiovascular diseases.

“In the last decades, the cannabinoid system (comprising synthetic and endogenous cannabinoid agonists and antagonists, their receptors and degrading enzymes) has been shown to induce potent immunomodulatory activities in atherogenesis and acute ischemic complications.

Differently from the other cannabinoid receptors in which controversial results are reported, the selective activation of the cannabinoid receptor type 2 (CB2) has been shown to play anti-inflammatory and protective actions within atherosclerotic vessels and downstream ischemic peripheral organs.

CB2 is a transmembrane receptor that triggers protective intracellular pathways in cardiac, immune and vascular cells in both in human and animal models of atherosclerosis…

medications activating CB2 function in the circulation or peripheral target organs might be a promising approach against atherogenesis.

This review updates evidence from preclinical studies on different CB2-triggered pathways in atherosclerosis and acute ischemic events.”

http://www.ncbi.nlm.nih.gov/pubmed/25245379

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