Tag Archives: plant

Endocannabinoids and immune regulation

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“Cannabinoid pharmacology has made important advances in recent years after the discovery of the cannabinoid receptors.

These discoveries have added to our understanding of exogenous and endogenous cannabinoid signaling along with exploring the various pathways of their biosynthesis, molecular structure, inactivation, and anatomical distribution of their receptors throughout the body.

The endocannabinoid system is involved in immunoregulation and neuroprotection.

The discovery of cannabinoid receptors occurring naturally throughout the vertebrate body and the availability of highly selective and potent canabimimetics led to the identification of a naturally occurring lipid signaling system termed the endocannabinoid system.

Interestingly, the endocannabinoid system dates back very long in the evolution because it exists as an ancient plant signaling system regulating the plant immunity-related genes in response to infection and stress.

The main pharmacological functions of the endocannabinoid system include neuromodulation, controlling motor functions, cognition, emotional responses, homeostasis and motivation. However, in the periphery, this system is an important modulator of autonomic nervous system, the immune system and microcirculation.

There have been a number of recent studies which have demonstrated that the endocannabinoids have both inhibitory effects and stimulatory impact on the immune system and may be actually important in homeostasis or control of the immune reactions.

 The image of endocannabinoid system now appears to be of a modulatory complex which affects the physiological functions in peripheral tissues and can thus be considered as a potential therapeutic target in the future.
Thus, manipulation of endocannabinoids in vivo may constitute a novel treatment modality against inflammatory disorders.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044336/

Integrating cannabis into clinical cancer care.

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“Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use.

However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use.

For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression.

Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite.

Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy.

A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia.

Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis.

Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating.

Human studies should be conducted to address critical questions related to the foregoing effects.”

http://www.ncbi.nlm.nih.gov/pubmed/27022315

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

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“The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia.

Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders.

Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD).

Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders.

Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression.

Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27023732

Cannabis in Pain Treatment: Clinical & Research Considerations.

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“Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. While research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed both to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This paper reviews clinical, research and policy issues related to herbal cannabis in order to support clinicians in thoughtfully advising and caring for patients who use cannabis and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.

PERSPECTIVE:

Herbal cannabis is increasingly available for clinical use in the U.S despite continuing controversies over its efficacy and safety. This paper explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it and to identify needed directions for research.”

http://www.ncbi.nlm.nih.gov/pubmed/26961090

Effects of cannabinoid receptor activation by CP55,940 on normal bladder function and irritation-induced bladder overactivity in non-awake anaesthetised rats.

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“CP55,940 is a synthetic analogue of tetrahydrocannabidiol, which is a psychoactive ingredient of the Cannabis plant.

This study was designed to evaluate the effects of CP55,940 on normal bladder function in vivo and examine whether it suppresses urinary frequency induced by nociceptive stimuli in the bladder.

CP55,940 decreases bladder activity and urinary frequency induced by nociceptive stimuli, probably by suppression of bladder afferent activity. Effects of CP55,940 were abolished by both CBR antagonists. This data implicates a role for the endocannabinoid system in bladder mechanoafferent function in rats. In addition, our results show that CP55,940 reverses urinary frequency exemplified in an overactive bladder model, suggesting it could be an effective treatment for patients with lower urinary tract symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/26942594

Plant-derived, synthetic and endogenous cannabinoids as neuroprotective agents. Non-psychoactive cannabinoids, ‘entourage’ compounds and inhibitors of N-acyl ethanolamine breakdown as therapeutic strategies to avoid pyschotropic effects.

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“There is good evidence that plant-derived and synthetic cannabinoids possess neuroprotective properties.

These compounds, as a result of effects upon CB(1) cannabinoid receptors, reduce the release of glutamate, and in addition reduce the influx of calcium following NMDA receptor activation.

The major obstacle to the therapeutic utilization of such compounds are their psychotropic effects, which are also brought about by actions on CB(1) receptors. However, synthesis of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, which also have neuroprotective properties, are increased under conditions of severe inflammation and ischemia, raising the possibility that compounds that prevent their metabolism may be of therapeutic utility without having the drawback of producing psychotropic effects.

In this review, the evidence indicating neuroprotective actions of plant-derived, synthetic and endogenous cannabinoids is presented. In addition, the pharmacological properties of endogenous anandamide-related compounds that are not active upon cannabinoid receptors, but which are also produced during conditions of severe inflammation and ischemia and may contribute to a neuroprotective action are reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/12505646

Plant-Derived and Endogenous Cannabinoids in Epilepsy.

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“Cannabis is one of the oldest psychotropic drugs and its anticonvulsant properties have been known since the last century.

The aim of this reveiw was to analyze the efficacy of cannabis in the treatment of epilepsy in adults and children. In addition, a description of the involvement of the endocannabinoid system in epilepsy is given in order to provide a biochemical background to the effects of endogenous cannabinoids in our body.

General tolerability and adverse events associated with cannabis treatment are also investigated. Several anecdotal reports and clinical trials suggest that in the human population cannabis has anticonvulsant properties and could be effective in treating partial epilepsies and generalized tonic-clonic seizures, still known as “grand mal.”

They are based, among other factors, on the observation that in individuals who smoke marijuana to treat epilepsy, cessation of cannabis use precipitates the re-emergence of convulsive seizures, whereas resuming consumption of this psychotropic drug controls epilepsy in a reproducible manner.

In conclusion, there is some anecdotal evidence for the potential efficacy of cannabis in treating epilepsy.

Though there has been an increased effort by patients with epilepsy, their caregivers, growers, and legislators to legalize various forms of cannabis, there is still concern about its efficacy, relative potency, availability of medication-grade preparations, dosing, and potential short- and long-term side effects, including those on prenatal and childhood development.”

http://www.ncbi.nlm.nih.gov/pubmed/26892745

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

Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents.

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“Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets.

The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer.

Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration.

Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition.

Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators.

Importantly, the de-orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies.

Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine.”

http://www.ncbi.nlm.nih.gov/pubmed/26890476

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

Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease.

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“The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago.

In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma.

The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss.

Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness.

The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26881135

Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the blood-brain barrier.

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“The cannabinoid (CB) receptors are the main targets of the cannabinoids, which include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the last few years, accumulated evidence has suggested a role of the CB receptors in neuroprotection.

The blood-brain barrier (BBB) is an important brain structure that is essential for neuroprotection. A link between the CB receptors and the BBB is thus likely, but this possible connection has only recently gained attention.

Cannabinoids and the BBB share the same mechanisms of neuroprotection and both protect against excitotoxicity (CB1), cell death (CB1), inflammation (CB2) and oxidative stress (possibly CB independent)-all processes that also damage the BBB.

Several examples of CB-mediated protection of the BBB have been found, such as inhibition of leukocyte influx and induction of amyloid beta efflux across the BBB.

Moreover, the CB receptors were shown to improve BBB integrity, particularly by restoring the tightness of the tight junctions. This review demonstrated that both CB receptors are able to restore the BBB and neuroprotection, but much uncertainty about the underlying signaling cascades still exists and further investigation is needed.”

http://www.ncbi.nlm.nih.gov/pubmed/24929655