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

Effect of Non-psychotropic Plant-derived Cannabinoids on Bladder Contractility: Focus on Cannabigerol.

“There are anecdotal reports that some Cannabis preparations may be useful for bladder dysfunctions.

Here, we investigated the effect of a number of non- psychotropic phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabichromene (CBC) on mouse bladder contractility in vitro.

CBG, THCV, CBD and CBDV, but not CBC, at concentration ranging from 10(-8) M to 10(-4) M, decreased (with similar potency), the contractions induced by acetylcholine without significantly modifying the contractions induced by electrical stimulation.

The rank order of efficacy was CBG=THCV>CBD>CBDV.

In depth studies on CBG showed that the effect of this phytocannabinoid on acetylcholine-induced contractions was not affected by CB1 or CB2 receptor antagonists.

Additionally, CBG also reduced acetylcholine-induced contractions in the human bladder.”

http://www.ncbi.nlm.nih.gov/pubmed/26197538

Δ9-Tetrahydrocannabinolicacid synthase production in Pichia pastoris enables chemical synthesis of cannabinoids.

“Δ9-tetrahydrocannabinol (THC) is of increasing interest as a pharmaceutical and bioactive compound.

Chemical synthesis of THC uses a laborious procedure and does not satisfy the market demand.

The implementation of biocatalysts for specific synthesis steps might be beneficial for making natural product availability independent from the plant.

Δ9-Tetrahydrocannabinolicacid synthase (THCAS) from C. sativa L. catalyzes the cyclization of cannabigerolic acid (CBGA) to Δ9-tetrahydrocannabinolic acid (THCA), which is non-enzymatically decarboxylated to THC.

In conclusion, production of THCAS in Pichia pastoris MutS KM71 KE1, subsequent isolation, and its application in a two-liquid phase setup enables the synthesis of THCA on a mg scale.”

http://www.ncbi.nlm.nih.gov/pubmed/26197418

Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury

Heart and Circulatory Physiology

“CANNABINOIDS ARE NATURAL and synthetic compounds structurally or pharmacologically related to the constituents of the plant Cannabis sativa or to the endogenous agonists (endocannabinoids) of the cannabinoid CB1 and CB2 receptors.

Cannabidiol (CBD) is a major cannabinoid constituent of Cannabis.

In contrast to tetrahydrocannabinol, CBD binds very weakly to CB1 and CB2 receptors. Contrary to most cannabinoids, CBD does not induce psychoactive or cognitive effects.

CBD has been shown to have anti-inflammatory properties. CBD (together with tetrahydrocannabinol) has been successfully tested in a few preliminary human trials related to autoimmune diseases…

Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling.

Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts.

Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo.

Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia.”

http://ajpheart.physiology.org/content/293/6/H3602

Cannabinoid pharmacology in the cardiovascular system: potential protective mechanisms through lipid signalling.

“Cannabinoids include not only plant-derived compounds (of which delta9-tetrahydrocannabinol is the primary psychoactive ingredient of cannabis), but also synthetic agents and endogenous substances termed endocannabinoids which include anandamide (2-arachidonoylethanolamide) and 2-arachidonoylglycerol.

Cannabinoids act on specific, G-protein-coupled, receptors which are currently divided into two types, CB1 and CB2. Relatively selective agonists and antagonists for these receptors have been developed, although one agent (SR141716A) widely used as an antagonist at CB1 receptors has non-cannabinoid receptor-mediated effects at concentrations which are often used to define the presence of the CB1 receptor.

Both cannabinoid receptors are primarily coupled to Gi/o proteins and act to inhibit adenylyl cyclase. Stimulation of CB1 receptors also modulates the activity of K+ and Ca2+ channels and of protein kinase pathways including protein kinase B (Akt) which might mediate effects on apoptosis. CB, receptors may activate the extracellular signal-regulated kinase cascade through ceramide signalling.

Cannabinoid actions on the cardiovascular system have been widely interpreted as being mediated by CB1 receptors although there are a growing number of observations, particularly in isolated heart and blood vessel preparations, that suggest that other cannabinoid receptors may exist.

Interestingly, the currently identified cannabinoid receptors appear to be related to a wider family of lipid receptor, those for the lysophospholipids, which are also linked to Gi/o protein signalling.

Anandamide also activates vanilloid VR1 receptors on sensory nerves and releases the vasoactive peptide, calcitonin gene-related peptide (CGRP), which brings about vasodilatation through its action on CGRP receptors.

Current evidence suggests that endocannabinoids have important protective roles in pathophysiological conditions such as shock and myocardial infarction.

Therefore, their cardiovascular effects and the receptors mediating them are the subject of increasing investigative interest.”

http://www.ncbi.nlm.nih.gov/pubmed/15005177

No smoke, no fire: What the initial literature suggests regarding vapourized cannabis and respiratory risk

“Given current limitations in developing an inhalant alternative for delivering cannabis medication, smoked marijuana remains the most readily accessible form of cannabis among medicinal users…

Cannabis actually served as an asthma treatment in the 1800s and, perhaps, in ancient times…

Informed health care professionals may consider making recommendations to their medicinal cannabis patients for vapourization of the plant, particularly for those who want the rapid relief that oral administration fails to provide.

It is not our intention to encourage inappropriate use of the plant, but to increase safety for those who choose to use it.

Vapourization of cannabis is likely less harmful than smoking.

Preliminary findings do support the idea that vapourization is an improvement over smoking.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456813/

Medical Marijuana in Pediatric Neurological Disorders.

“Marijuana and marijuana-based products have been used to treat medical disease.

Recently, derivatives of the plant have been separated or synthesized to treat various neurological disorders, many of them affecting children.

Unfortunately, data are sparse in regard to treating children with neurologic illness. Therefore, formal conclusions about the potential efficacy, benefit, and adverse effects for these products cannot be made at this time.

Further robust research using strong scientific methodology is desperately needed to formally evaluate the role of these products in children.”

http://www.ncbi.nlm.nih.gov/pubmed/26060306

“The endocannabinoid-CB receptor system: Importance for development and in pediatric disease.”  http://www.ncbi.nlm.nih.gov/pubmed/15159678

Marijuana kills brain cancer, new study confirms

“The active molecules in cannabis kill brain cancer — another study has revealed.”

“Scientists using an extract of whole-plant marijuana rich in pot’s main psychoactive ingredient THC as well as cannabidiol (CBD) showed “dramatic reductions in tumor volumes” of a type of brain cancer.”  http://blog.sfgate.com/smellthetruth/2014/11/18/marijuana-kills-brain-cancer-new-study-confirms/

“Marijuana kills brain cancer, new study confirms. The active molecules in cannabis kill brain cancer — another study has revealed.” http://blog.seattlepi.com/marijuana/2014/11/18/marijuana-kills-brain-cancer-new-study-confirms/#13130101=0

“Marijuana Kills Brain Cancer Cells. Researchers have found that the THC in marijuana causes brain cancer cells to die in both mice and humans.”  http://www.nbcphiladelphia.com/news/health/Marijuana_Kills_Brain_Cancer_Cells_All__National_.html

“Marijuana Kills Brain Cancer, New Study Confirms” http://cancerguide.byethost8.com/marijuana-kills-brain-cancer-new-study-confirms-sfgate-blog/

http://www.thctotalhealthcare.com/category/brain-cancer/

Photosynthetic response of Cannabis sativa L., an important medicinal plant, to elevated levels of CO2

“Cannabis sativa L. (Cannabaceae) is a widely distributed plant around the world. It has a long history of medicinal use as far back as the 6th century B.C. Cannabis sativa is the natural source of the cannabinoids, a unique group of terpeno-phenolic compounds that accumulate in the glandular trichomes of the plant.

Δ9-Tetrahydrocannabinolic acid (Δ9-THCA) is the major cannabinoid which upon decarboxylation with age or heating gives rise to Δ9-THC, the primary psychoactive agent. The pharmacologic and therapeutic potency of Cannabis preparations and Δ9-THC have been extensively reviewed.

Despite of its medicinal importance and widespread occurrence, to the best of our knowledge, no information is available on the consequences of rising atmospheric CO2 concentration on its photosynthesis and growth performance.

This study describes the short term effect of elevated CO2 on photosynthetic characteristics and stomatal response in four different high Δ9-THC yielding varieties of Cannabis sativa.

The higher water use efficiency (WUE) under elevated CO2 conditions in Cannabis sativa, primarily because of decreased stomatal conductance and subsequently the transpiration rate, may enable this species to survive under expected harsh greenhouse effects including elevated CO2 concentration and drought conditions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550578/

Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes.

“Cannabis sativa L. is an important medicinal plant.

In order to develop cannabis plant material as a medicinal product quality control and clear chemotaxonomic discrimination between varieties is a necessity.

Therefore in this study 11 cannabis varieties were grown under the same environmental conditions. Chemical analysis of cannabis plant material used a gas chromatography flame ionization detection method that was validated for quantitative analysis of cannabis monoterpenoids, sesquiterpenoids, and cannabinoids. Quantitative data was analyzed using principal component analysis to determine which compounds are most important in discriminating cannabis varieties.

In total 36 compounds were identified and quantified in the 11 varieties. Using principal component analysis each cannabis variety could be chemically discriminated. This methodology is useful for both chemotaxonomic discrimination of cannabis varieties and quality control of plant material.”

http://www.ncbi.nlm.nih.gov/pubmed/21040939