A pharmacological basis of herbal medicines for epilepsy.

“Epilepsy is the most common chronic neurological disease, affecting about 1% of the world’s population during their lifetime. Most people with epilepsy can attain a seizure-free life upon treatment with antiepileptic drugs (AEDs).

Unfortunately, seizures in up to 30% do not respond to treatment. It is estimated that 90% of people with epilepsy live in developing countries, and most of them receive no drug treatment for the disease. This treatment gap has motivated investigations into the effects of plants that have been used by traditional healers all over the world to treat seizures.

Extracts of hundreds of plants have been shown to exhibit anticonvulsant activity in phenotypic screens performed in experimental animals.

Some of those extracts appear to exhibit anticonvulsant efficacy similar to that of synthetic AEDs.

Dozens of plant-derived chemical compounds have similarly been shown to act as anticonvulsants in various in vivo and in vitro assays.

To a significant degree, anticonvulsant effects of plant extracts can be attributed to widely distributed flavonoids, (furano)coumarins, phenylpropanoids, and terpenoids.

Flavonoids and coumarins have been shown to interact with the benzodiazepine site of the GABAA receptor and various voltage-gated ion channels, which are targets of synthetic AEDs.

Modulation of the activity of ligand-gated and voltage-gated ion channels provides an explanatory basis of the anticonvulsant effects of plant secondary metabolites.

Many complex extracts and single plant-derived compounds exhibit antiinflammatory, neuroprotective, and cognition-enhancing activities that may be beneficial in the treatment of epilepsy.

Thus, botanicals provide a base for target-oriented antiepileptic drug discovery and development.

In the future, preclinical work should focus on the characterization of the effects of plant extracts and plant-derived compounds on well-defined targets rather than on phenotypic screening using in vivo animal models of acute seizures. At the same time, available data provide ample justification for clinical studies with selected standardized botanical extracts and plant-derived compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/26074183

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

Issues and promise in clinical studies of botanicals with anticonvulsant potential.

“Botanicals are increasingly used by people with epilepsy worldwide. However, despite abundant preclinical data on the anticonvulsant properties of many herbal remedies, there are very few human studies assessing safety and efficacy of these products in epilepsy.Additionally, the methodology of most of these studies only marginally meets the requirements of evidence-based medicine.

Although the currently available evidence for the use of cannabinoids in epilepsy is similarly lacking, several carefully designed and well controlled industry-sponsored clinical trials of cannabis derivatives are planned to be completed in the next couple of years, providing the needed reliable data for the use of these products.

The choice of the best botanical candidates with anticonvulsant properties and their assessment in well-designed clinical trials may significantly improve our ability to effectively and safely treat patients with epilepsy. ”

http://www.ncbi.nlm.nih.gov/pubmed/26341963

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

(1)H NMR and HPLC/DAD for Cannabis sativa L. chemotype distinction, extract profiling and specification.

“The medicinal use of different chemovars and extracts of Cannabis sativa L. requires standardization beyond ∆9-tetrahydrocannabinol (THC) with complementing methods.

We investigated the suitability of (1)H NMR key signals for distinction of four chemotypes measured in deuterated dimethylsulfoxide together with two new validated HPLC/DAD methods used for identification and extract profiling based on the main pattern of cannabinoids and other phenolics alongside the assayed content of THC, cannabidiol (CBD), cannabigerol (CBG) their acidic counterparts (THCA, CBDA, CBGA), cannabinol (CBN) and cannflavin A and B. Effects on cell viability (MTT assay, HeLa) were tested.

The dominant cannabinoid pairs allowed chemotype recognition via assignment of selective proton signals and via HPLC even in cannabinoid-low extracts from the THC, CBD and CBG type.

Substantial concentrations of cannabinoid acids in non-heated extracts suggest their consideration for total values in chemotype distinction and specifications of herbal drugs and extracts.

Cannflavin A/B are extracted and detected together with cannabinoids but always subordinated, while other phenolics can be accumulated via fractionation and detected in a wide fingerprint but may equally serve as qualitative marker only.

Cell viability reduction in HeLa was more determined by the total cannabinoid content than by the specific cannabinoid profile.

Therefore the analysis and labeling of total cannabinoids together with the content of THC and 2-4 lead cannabinoids are considered essential.

The suitability of analytical methods and the range of compound groups summarized in group and ratio markers are discussed regarding plant classification and pharmaceutical specification.”

Cannabinoid Modulation of Neuroinflammatory Disorders

Table 1.

Cannabis sativa is a herb belonging to the Cannabaceae family, characterized by palmate leaves and numerous fibers. Its first record as a medicine dates back to 5000 years ago and it was found in China, where cannabis was used for a myriad of purposes and diseases, including malaria, neuropathic pain, nausea, sexual dysfunction and constipation.

The use of cannabis spread from Central Asia and deeply influenced Indian folk medicine. However, sedative and psychotropic effects of cannabis turned it into a recreational drug. This fact resulted in discrimination against the consumption of the cannabis plant and its derivatives, which delayed the scientific findings in this field…

In recent years, a growing interest has been dedicated to the study of the endocannabinoid system. The isolation of Cannabis sativa main psychotropic compound, Δ(9)-tetrahydrocannabinol (THC), has led to the discovery of an atypical neurotransmission system that modulates the release of other neurotransmitters and participates in many biological processes, including the cascade of inflammatory responses.

In this context, cannabinoids have been studied for their possible therapeutic properties in neuroinflammatory diseases. In this review, historic and biochemical aspects of cannabinoids are discussed, as well as their function as modulators of inflammatory processes and therapeutic perspectives for neurodegenerative disorders, particularly, multiple sclerosis.

Cannabinoid compounds may be extracted from the plant (phytocannabinoids) or be artificially obtained (synthetic cannabinoids)…

To date, it is still impossible to prove or rule out all benefits of cannabis described empirically by ancient herbal practitioners. For now, science aims to understand how cannabinoid compounds are associated with neuroinflammation and how cannabis-based medicine can help millions of patients worldwide.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386505/

Therapeutic Potential of Cannabinoids in Schizophrenia.

“Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia.

The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana’s psychoactive principle Δ9-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation.

…antipsychotic compounds which manipulate this system may provide a novel therapeutic target for the treatment of schizophrenia.

The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology.

Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/24605939

Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System

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“The “classic” endocannabinoid (eCB) system… An emerging literature documents the “eCB deficiency syndrome” as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system—ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.

Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants.

Clinical interventions characterized as “complementary and alternative medicine” also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances—alcohol, tobacco, coffee, cannabis) also modulate the eCB system.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951193/#!po=4.79452

 

“Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.”

 http://www.ncbi.nlm.nih.gov/pubmed/18404144

[Ttextual research of Cannabis sativa varieties and medicinal part].

“Cannabis used now is identical with that described in ancient herbal literatures.

People did not make a sharp distinction on medicinal part of C. sativa …unripe fruit, fruit and kernel of seed were all used..,both fruit and kernel can be used as medicinal part.

CONCLUSION:

The plants for Fructus Cannabis described in modern and ancient literatures are identical.

The base of the original plant is the same either in ancient or modern.

And the toxicity of the fruit is more than that of the kernel.

The kernel is the exact medicinal part of C. Sativa.”

http://www.ncbi.nlm.nih.gov/pubmed/20862977

Advances in the management of multiple sclerosis spasticity: experiences from recent studies and everyday clinical practice.

“Herbal (smoked) cannabis has long been recognized as a possible option for relief of spasticity and neuropathic pain… An innovative method of benefiting from the mode of action of cannabinoids while limiting their drawbacks is to reduce peak plasma levels of 9-delta-tetrahydrocannabinol and counteract psychoactivity with higher than naturally occurring proportions of a second cannabinoid, cannabidiol.

Sativex® oromucosal spray (1:1 ratio of 9-delta-tetrahydrocannabinol/cannabidiol) has recently been approved in a number of EU countries and elsewhere for use in patients with MS-related spasticity who are resistant to treatment with other antispasticity medications.

In clinical trials, Sativex provided initial relief of spasticity symptoms within the first 4 weeks of treatment (trial period) in up to about half of patients resistant to other available oral antispasticity medications and demonstrated clinically significant improvement in spasticity (30% or higher reduction from baseline) in three-quarters of the initial responders. Adverse events were limited mainly to mild or moderate cases of somnolence and dizziness.

Under everyday clinical practice conditions, Sativex at a mean daily dose of <7 sprays/day, was shown to relieve spasticity in about 70% of patients previously resistant to treatment.

Clear improvements were also noted in associated symptoms such as sleep disturbances, bladder problems, loss of mobility and cramps…

Follow-up studies in Sativex responders support continued benefit without the need to increase doses for at least 1 year.

Sativex appears to be a promising solution for a meaningful proportion of patients with MS-related spasticity who have inadequate response to current antispasticity medications.”

http://www.ncbi.nlm.nih.gov/pubmed/24289844

Medicinal Cannabis Does Not Influence the Clinical Pharmacokinetics of Irinotecan and Docetaxel

“For the past 4,000 years, patients and doctors of each era have resorted to cannabis when conventional treatments were ineffective or lacking. Indeed, in oncology beneficial effects have been reported for cancer-associated anorexia, chemotherapy-induced nausea and vomiting, and palliation…

The only U.S. Food and Drug Administration (FDA)-approved medicinal cannabis products are an oral formulation containing dronabinol (Marinol®)… the synthetic version of delta9-tetrahydrocannabinol (THC), the main pharmacologically active cannabinoid, and capsules containing nabilone, an analog of dronabinol (Cesamet®)…

…many patients claim (subjectively) that a whole or partially purified extract of Cannabis sativa L. offers advantages over a single isolated ingredient…

We anticipated an increased use of medicinal cannabis concurrent with anticancer drugs, and undertook a drug-interaction study to evaluate the effect of concomitant medicinal cannabis on the pharmacokinetics of irinotecan and docetaxel…

Conclusion. Coadministration of medicinal cannabis, as herbal tea, in cancer patients treated with irinotecan or docetaxel does not significantly influence the plasma pharmacokinetics of these drugs. The evaluated variety of medicinal cannabis can be administered concomitantly with both anticancer agents without dose adjustments.”

Full text: http://theoncologist.alphamedpress.org/content/12/3/291.long

Three out of four doctors recommend marijuana in New England Journal of Medicine poll

More than three out of four doctors support medical cannabis for a hypothetical breast cancer patient, New England Journal of Medicine reports“More than three out of four doctors support medical cannabis for a hypothetical breast cancer patient, New England Journal of Medicine reports

In a poll by the well-respected New England Journal of Medicine released today, more than three out of four doctors recommended medical cannabis for a hypothetical late-stage breast cancer patient.

“We were surprised by the outcome of polling and comments, with 76% of all votes in favor of the use of marijuana for medicinal purposes — even though marijuana use is illegal in most countries,” Jonathan N. Adler, M.D., and James A. Colbert, M.D. wrote for the NEJOM May 30th.

Marijuana is a federally illegal – schedule one drug – that the U.S. government claims has no medical value and is more dangerous than heroin or LSD. Yet 19 states have legalized cannabis for medical use, given its 10,000 year history as a safe herbal remedy for nausea, pain and insomnia among other conditions.”

More: http://blog.sfgate.com/smellthetruth/2013/05/30/three-out-of-four-doctors-recommend-marijuana-in-new-england-journal-of-medicine-poll/