Therapeutic potential of cannabis-related drugs.

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“In this review, I will consider the dual nature of Cannabis and cannabinoids.

The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the ‘abuse’ of Cannabis outside the clinic.

The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma.

As with every other medicinal drug of course, the ‘trick’ will be to maximise the benefit and minimise the cost.

After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/26216862

COMPARATIVE EFFECTS OF PARATHION AND CHLORPYRIFOS ON ENDOCANNABINOID AND ENDOCANNABINOID-LIKE LIPID METABOLITES IN RAT STRIATUM.

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“Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE).

The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems.

Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications.”

http://www.ncbi.nlm.nih.gov/pubmed/26215119

Cannabidiol is a negative allosteric modulator of the type 1 cannabinoid receptor.

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“Cannabidiol has been reported to act as an antagonist of cannabinoid agonists at type 1 cannabinoid receptors (CB1 ).

We hypothesized that cannabidiol can inhibit cannabinoid agonist activity through negative allosteric modulation of CB1…

Cannabidiol behaved as a non-competitive negative allosteric modulator of CB1 .

Allosteric modulation, in conjunction with non-CB1 effects, may explain the in vivo effects of cannabidiol.

Allosteric modulators of CB1 have the potential to treat central nervous system and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of CB1.”

http://www.ncbi.nlm.nih.gov/pubmed/26218440

Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal model.

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“Cannabinoid pharmacology has proven nettlesome with issues of promiscuity a common theme among both agonists and antagonists.

One recourse is to develop allosteric ligands to modulate cannabinoid receptor signaling.

Cannabinoids have come late to the allosteric table…

In summary, three of the allosteric modulators evaluated function in a manner consistent with allosterism in a neuronal 2-AG-based model of endogenous cannabinoid signaling.”

http://www.ncbi.nlm.nih.gov/pubmed/26211948

Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on neurons and mitochondrial functions.

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“Mitochondrial dysfunction contributes to cell death after cerebral ischemia/reperfusion (I/R) injury.

Cannabinoid CB1 receptor is expressed in neuronal mitochondrial membranes (mtCB1R) and involved in regulating mitochondrial functions under physiological conditions…

In purified neuronal mitochondria, mtCB1R activation attenuated Ca(2+)-induced mitochondrial injury.

In conclusion, mtCB1R is involved in ACEA-induced protective effects on neurons and mitochondrial functions, suggesting mtCB1R may be a potential novel target for the treatment of brain ischemic injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26215450

An Overview of Products and Bias in Research.

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“Cannabis is a genus of annual flowering plant.

Cannabis is often divided into 3 species-Cannabis sativa, Cannabis indica, and Cannabis ruderalis-but there is significant disagreement about this, and some consider them subspecies of the same parent species.

Cannabis sativa can grow to 5-18 feet or more, and often has a few branches.

Cannabis indica typically grows 2-4 feet tall and is compactly branched.

Cannabis ruderalis contains very low levels of Δ-9-tetrahyocannabinol so is rarely grown by itself. Cannabis ruderalis flowers as a result of age, not light conditions, which is called autoflowering. It is principally used in hybrids, to enable the hybrid to have the autoflowering property.

There are > 700 strains of cannabis, often with colorful names.

Some are strains of 1 of the 3 subspecies. Many are crossbred hybrids.

The strains can be named in a variety of ways: smell or lineage are common ways of naming. There are only a few rules about how the strains are named, and most strains’ names do not follow the rules.

There are 4 basic preparations of marijuana: bhang, hasish, oil (or hash oil), and leaves and/or buds.

In medical marijuana trials, subjective outcomes are frequently used but blind breaking can introduce significant bias. Blind breaking occurs when patients figure out if they are in the control or the treatment group. When this occurs, there is significant overestimation of treatment effect.”

http://www.ncbi.nlm.nih.gov/pubmed/26202343

Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect.

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“Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes.

It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain.

Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids.

It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury.

Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist.

This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/15342139

Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice.

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“Combinations of analgesics from different classes are commonly used in the management of chronic pain. The goal is to enhance pain relief together with the reduction of side effects.

The present study was undertaken to examine the anti-allodynic synergy resulting from the combination of WIN 55,212-2, a cannabinoid CB1 receptor agonist, and JTC-801, a nociceptin/orphanin FQ receptor antagonist, on neuropathic pain…

In conclusion, co-administration of acannabinoid with a nociceptin/orphanin FQ receptor antagonist resulted in a synergistic interaction, which may have utility in the pharmacological treatment of neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/21664922

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