Tag Archives: cannabis

Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice.

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“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans.

It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson’s patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal disorders.

To investigate this possibility we evaluated if CBD would prevent catalepsy induced by drugs with distinct pharmacological mechanisms.

These findings indicate that CBD can attenuate catalepsy caused by different mechanisms (D2 blockade, NOS inhibition and CB1 agonism) via 5-HT1A receptor activation, suggesting that it could be useful in the treatment of striatal disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23791616

Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

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“Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant.

Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic.

In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol.

Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27131780

A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.

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“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain.

A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers.

The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed.

Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day.

In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies.”

http://www.ncbi.nlm.nih.gov/pubmed/27121791

Marijuana is medicine, Journal of the American Medical Association concludes

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“Marijuana is one hundred percent a form of medicine, researchers conclude in a bombshell series of reports released by the Journal of the American Medical Association. Cannabis has been used medicinally for thousands of years” http://blog.sfgate.com/smellthetruth/2015/06/23/marijuana-is-medicine-journal-of-the-american-medical-association-concludes/

http://blog.sfgate.com/smellthetruth/2015/06/23/marijuana-is-medicine-journal-of-the-american-medical-association-concludes/

“Cannabinoids for Medical Use. A Systematic Review and Meta-analysis.”  http://jama.jamanetwork.com/article.aspx?articleid=2338251

Cannabimovone, a Cannabinoid with a Rearranged Terpenoid Skeleton from Hemp

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“An investigation of the polar fractions from a nonpsychotropic variety of hemp (Cannabis sativa L.) afforded cannabimovone, a polar cannabinoid with a rearranged 2(34) abeo-terpenoid skeleton, biogenetically originating from the intramolecular aldolization of a 2′,3′-seco-menthanyl precursor.

The structure of cannabimovone was elucidated by spectroscopic analysis, whereas attempts to mimic its biogenetic derivation from cannabidiol gave only anhydrocannabimovone, the intramolecular oxy-Michael adduct of the crotonized version of the elusive natural products.

Biological evaluation of cannabimovone against metabotropic (CB1, CB2) and ionotropic (TRPs) cannabinoid receptors showed a significant activity only for ionotropic receptors, especially TRPV1, whereas anhydrocannabimovone exhibited strong activity at both ionotropic and metabotropic cannabinoid receptors.

Overall, the biological profile of anhydrocannabimovone was somewhat similar to that of THC, suggesting a remarkable tolerance to constitutional and configurational changes.”

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.200901464/abstract

Synthesis of (-)-Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)-Catalyzed Cycloisomerization.

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“The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of a highly stereoselective gold(I)-catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone.”

http://www.ncbi.nlm.nih.gov/pubmed/27119910

The Endocannabinoid System: An Osteopathic Perspective

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“A person is the product of dynamic interaction between body, mind, and spirit—This holistic principle is exemplified by cannabinoid receptors, which span the field of psychoneuroimmunology. Taken together, CB1, CB2, and their endocannabinoid ligands represent a microcosm of mind-body medicine. The primary purpose of the current article is to review the expanding endocannabinoid literature beginning with exogenous compounds—Cannabis and plant cannabinoids—and then shift to the endogenous system, highlighting embryology and development, neuroprotection, autonomics and immunity, inflammation, apoptosis, hunger and feeding, and nociception and pain.” http://jaoa.org/article.aspx?articleid=2093607

In Vitro Propagation of Cannabis sativa L. and Evaluation of Regenerated Plants for Genetic Fidelity and Cannabinoids Content for Quality Assurance.

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“Cannabis sativa L. (Marijuana; Cannabaceae), one of the oldest medicinal plants in the world, has been used throughout history for fiber, food, as well as for its psychoactive properties.

The dioecious and allogamous nature of C. sativa is the major constraint to maintain the consistency in chemical profile and overall efficacy if grown from seed. Therefore, the present optimized in vitro propagation protocol of the selected elite germplasm via direct organogenesis and quality assurance protocols using genetic and chemical profiling provide an ideal pathway for ensuring the efficacy of micropropagated Cannabis sativa germplasm.

A high frequency shoot organogenesis of C. sativa was obtained from nodal segments in 0.5 μM thidiazuron medium and 95 % in vitro rhizogenesis is obtained on half-strength MS medium supplemented with 500 mg/L activated charcoal and 2.5 μM indole-3-butyric acid. Inter Simple Sequence Repeats (ISSR) and Gas Chromatography-Flame Ionization Detection (GC-FID) are successfully used to monitor the genetic stability in micropropagated plants up to 30 passages in culture and hardened in soil for 8 months.”

http://www.ncbi.nlm.nih.gov/pubmed/27108324

Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability.

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“Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models.

Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure.

Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability.

Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and “drug likeness”, while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group.

Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations.

Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.”

http://www.ncbi.nlm.nih.gov/pubmed/27096053

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601