Monthly Archives: July 2015

Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice.

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“Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy.

Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective…

Overall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.”

Cannabinoids for the Treatment of Movement Disorders.

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“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

The endocannabinoid anandamide affects the synthesis of human syncytiotrophoblast-related proteins.

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“The human syncytiotrophoblast (hST) has a major role in the production of important placental hormones.

Several molecules regulate hST endocrine function but the role of endocannabinoids in this process is still unknown.

Here, we report that the endocannabinoid anandamide (AEA) decreased cAMP levels, impaired human chorionic gonadotropin secretion, placental alkaline phosphatase activity and decreased aromatase mRNA levels and protein expression, through cannabinoid (CB) receptor activation.

AEA also downregulated leptin and placental protein 13 transcription, though via a CB receptor-independent mechanism.

All this evidence suggests AEA is a novel modulator of hormone synthesis by the syncytiotrophoblast, supporting the importance of the endocannabinoid signalling in placental function.”

http://www.ncbi.nlm.nih.gov/pubmed/26202891

Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys.

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“Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects limit their use. Therapeutic utility might be improved by combining opioids with other drugs to enhance analgesic effects, but only if adverse effects are not similarly changed.

Cannabinoids have been shown to enhance the antinociceptive potency of opioids without increasing other effects; this study examined whether the effectiveness of cannabinoids is altered in morphine-dependent monkeys.

Tolerance developed to the antinociceptive effects of morphine and cross-tolerance developed to cannabinoids under conditions that produced modest physical dependence.

Compared with the doses examined in this study, much smaller doses of opioids have antinociceptive effects when given with cannabinoids; it is possible that tolerance will not develop to chronic treatment with opioid/cannabinoid mixtures.”

http://www.ncbi.nlm.nih.gov/pubmed/26202613

Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury.

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“Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts.

Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury.

Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana.

In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults.

CONCLUSION:

A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury.

THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.”

http://www.ncbi.nlm.nih.gov/pubmed/26202357

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

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“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.

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“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

Lack of presynaptic interaction between glucocorticoid and CB1 cannabinoid receptors in GABA- and glutamatergic terminals in the frontal cortex of laboratory rodents.

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“Corticosteroid and endocannabinoid actions converge on prefrontocortical circuits associated with neuropsychiatric illnesses. Corticosteroids can also modulate forebrain synapses by using endocannabinoid effector systems…

Altogether, corticosteroids are unlikely to exert direct non-genomic presynaptic neuromodulation in the frontal cortex, but they may do so indirectly, via the stimulation of trans-synaptic endocannabinoid signaling.”

http://www.ncbi.nlm.nih.gov/pubmed/26196379

Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist.

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“Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease.

Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury.

We have previously reported the receptor affinity of 3′,5′-dichloro-2,6-dihydroxy-biphenyl-4-yl)-phenyl-methanone (SMM-189) and the characterization of the beneficial effects of SMM-189 in the mouse model of mild traumatic brain injury.

Herein, we report the further characterization of SMM-189 as a potent and selective CB2 inverse agonist, which acts as a noncompetitive inhibitor of CP 55,940.

The ability of SMM-189 to regulate microglial activation, in terms of chemokine expression and cell morphology, has been determined.

Finally, we have determined that SMM-189 possesses acceptable biopharmaceutical properties indicating that the triaryl class of CB2 inverse agonists are viable compounds for continued preclinical development for the treatment of neurodegenerative disorders and traumatic brain injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26196013

Use and effects of cannabinoids in military veterans with posttraumatic stress disorder.

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“Published evidence regarding the use of cannabis and cannabis derivatives by military veterans with posttraumatic stress disorder (PTSD) is reviewed.

SUMMARY:

When inhaled or delivered orally or transdermally, cannabinoids (the psychoactive components of unrefined marijuana and various derivative products) activate endogenous cannabinoid receptors, modulating neurotransmitter release and producing a wide range of central nervous system effects, including increased pleasure and alteration of memory processes. Those effects provide a pharmacologic rationale for the use of cannabinoids to manage the three core PTSD symptom clusters: reexperiencing, avoidance and numbing, and hyperarousal.

Cross-sectional studies have found a direct correlation between more severe PTSD symptomatology and increased motivation to use cannabis for coping purposes, especially among patients with difficulties in emotional regulation or stress tolerance. Data from 4 small studies suggested that cannabinoid use was associated with global improvements in PTSD symptoms or amelioration of specific PTSD symptoms such as insomnia and nightmares.

CONCLUSION:

While further research into cannabinoid treatment effects on PTSD symptoms is required, the evaluated evidence indicates that substantial numbers of military veterans with PTSD use cannabis or derivative products to control PTSD symptoms, with some patients reporting benefits in terms of reduced anxiety and insomnia and improved coping ability.”

http://www.ncbi.nlm.nih.gov/pubmed/26195653