The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells.

“One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.”

http://www.ncbi.nlm.nih.gov/pubmed/16616335

“Marijuana has been used in medicine for many centuries, and nowadays there is a renaissance in the study of the therapeutic effects of cannabinoids. One of the most active areas of research in the cannabinoid field is the study of the potential antitumoral application of these drugs. Our results unravel the mechanism of cannabinoid antitumoral action by demonstrating the proapoptotic role of the stress protein p8 via its downstream targets ATF-4, CHOP, and TRB3.

The identification of this pathway may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of potential antitumoral therapies with cannabinoids.

Our results also support that cannabinoid treatment does not activate this pathway in nontransformed cells, in line with the belief that cannabinoid proapoptotic action is selective for tumor versus nontumor cells, and that cannabinoids act in a synergic fashion with ER stress inducers as well as with other antitumoral agents.

The identification of the p8-regulated pathway described here may contribute to the design of therapeutic strategies for inhibiting tumor growth. In particular, our findings can help to improve the efficiency and selectivity of a potential cannabinoid-based antitumoral therapy.”

http://www.sciencedirect.com/science/article/pii/S1535610806000857

Medical Marijuana: Reducing Spasticity in Multiple Sclerosis Patients

 

“Medical marijuana is a justifiable treatment for spasticity in patients with MS.

Interviews indicate that many patients choose marijuana over other medicines because they experience minimal side effects and rapid improvements in motor functioning…

Compared to the steroids, tranquilizers, and sedatives usually prescribed for MS patients, marijuana is remarkably safe and benign…

There is a lack of evidence for long-term risks associated with marijuana use. The short-term risks are minimal and short-lived.

Studies verify the positive relationship between medical marijuana use and reduced spasticity.

Voters are realizing the cruelty associated with robbing a terminally or chronically ill patient from the medicine that most relieves their pain.

MS is a chronic disease that can lead to severe pain and disability if untreated. For these reasons, medical marijuana should be available to patients who understand the risks associated with its use.

Until medical research develops an equally effective oral drug, marijuana will remain a reasonable option for patients suffering from MS.”

http://www.vanderbilt.edu/AnS/psychology/health_psychology/medicalmarijuana.htm

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect.

“The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy.

The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg).

The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased.

CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly.

Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA.

Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26309534

“Epilepsy is one of the most common diseases of the brain, affecting at least 50 million people globally… Despite development of a number of new antiepileptic drugs, epilepsy could not be significantly reduced and is a challenge to the clinicians… Many plants, known for their anticonvulsant activity are subjected to phytochemical and pharmacological studies. Cannabidiol (CBD) a constituent of the hemp seed exhibits potent anticonvulsant activity…  The CBD possess anticonvulsive, anti-epileptic, and antimicrobial properties… The present study was performed to examine the anticonvulsive effects of CBD in pentylenetetrazole-induced chronic epilepsy rat models… The present study demonstrates that CBD protects against pentylenetetrazole-induced chronic seizures, decreases astrocytic hyperplasia, decreases neuronal cell loss and selectively suppresses NMDA1 receptor in the hippocampus… Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537971/

The Genetic Structure of Marijuana and Hemp.

“Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history.

Drug types of Cannabis (marijuana), which contain high amounts of the psychoactivecannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug.

Hemp types are grown for the production of seed and fibre, and contain low amounts of THC.

Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants.

Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production.

We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity.

We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.”

http://www.ncbi.nlm.nih.gov/pubmed/26308334

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133292

Pregnenolone can protect the brain from cannabis intoxication.

“Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated.

The administration of the main active principle of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor.

Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC.

This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.

These data indicate that THC increases pregnenolone through activation of the CB1 receptor…

In conclusion, this new understanding of the role of pregnenolone has the potential to generate new therapies for cannabis dependence.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057431/

Enhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be Considered as an Anti-addiction Therapeutic: Hypothesizing Dopaminergic Blockade and Promoting Anti-Reward.

“Pregnenolone considered the inactive precursor of all steroid hormones, has recently been shown to protect the brain from Cannabis intoxication.

The major active ingredient of Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol (THC) enhances Pregnenolone synthesis in the brain via stimulation of the type-1 cannabinoid (CB1) receptor.

This steroid has been shown to inhibit the activity of the CB1 receptor thereby reducing many of the effects of THC.

While this mechanism seems correct, in our opinion, Vallee et al., incorrectly suggest that blocking CB1 receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction.

In this hypothesis, we caution the scientific community that, other CB1 receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1 receptor blockers were rejected by the FDA due to mood changes including suicide ideation.

Blocking CB1 receptors would result in reduced neuronal release of Dopamine by disinhibition of GABA signaling.

Long-term blockade of cannabinoid receptors could occur with raising Pregnenolone brain levels…”

http://www.ncbi.nlm.nih.gov/pubmed/26306328

Marijuana Use in Epilepsy: The Myth and the Reality.

“Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia.

Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts.

This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD).

Then, we explore the safety data from animal and human studies. Lastly, we attempt to reconcile the controversy regarding physicians’ and patients’ opinions about whether the available evidence is sufficient to recommend the use of marijuana to treat epilepsy.”

http://www.ncbi.nlm.nih.gov/pubmed/26299273

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

“WILD CANNABIS”: A REVIEW OF THE TRADITIONAL USE AND PHYTOCHEMISTRY OF LEONOTIS LEONURUS.

“Leonotis leonurus, locally commonly known as “wilde dagga” (=wild cannabis), is traditionally used as a decoction, both topically and orally, in the treatment of a wide variety of conditions such as haemorrhoids, eczema, skin rashes, boils, itching, muscular cramps, headache, epilepsy, chest infections, constipation, spider and snake bites. The dried leaves and flowers are also smoked to relieve epilepsy. The leaves and flowers are reported to produce a mild euphoric effect when smoked and have been said to have a similar, although less potent, psychoactive effect to cannabis.

The phytochemistry of particularly the non-volatile constituents of Leonotis leonurus has been comprehensively investigated due to interest generated as a result of the wide variety of biological effects reported for this plant. More than 50 compounds have been isolated and characterised. Leonotis leonurus contains mainly terpenoids, particularly labdane diterpenes, the major diterpene reported is marrubiin. Various other compounds have been reported by some authors to have been isolated from the plant, including, in the popular literature only, the mildly psychoactive alkaloid, leonurine. Leonurine has however, never been reported by any scientific analysis of the extracts of L. leonurus.

Despite the publication of various papers on L. leonurus, there is still, however, the need for definitive research and clarification of other compounds, including alkaloids and essential oils from L. leonurus, as well as from other plant parts, such as the roots which are extensively used in traditional medicine. The traditional use by smoking also requires further investigation as to how the chemistry and activity are affected by this form of administration. Research has proven the psychoactive effects of the crude extract of L. leonurus, but confirmation of the presence of psychoactive compounds, as well as isolation and characterisation, is still required. Deliberate adulteration of L. leonurus with synthetic cannabinoids has been reported recently, in an attempt to facilitate the marketing of these illegal substances, highlighting the necessity for refinement of appropriate quality control processes to ensure safety and quality. Much work is therefore still required on the aspect of quality control to ensure safety, quality and efficacy of the product supplied to patients, as this plant is widely used in South Africa as a traditional medicine. Commercially available plant sources provide a viable option for phytochemical research, particularly with regard to the appropriate validation of the plant material (taxonomy) in order to identify and delimit closely related species such as L. leonurus and L. nepetifolia which are very similar in habit.”

http://www.ncbi.nlm.nih.gov/pubmed/26292023

METABOLIC EFFECTS OF MARIJUANA USE AMONG BLACKS

Logo of nihpa

“Given the paucity of data on metabolic significance of marijuana use, particularly among the black population, the objective of the study was to investigate the potential effects of marijuana on metabolic risk factors and body weight among black patients…

Current marijuana use is associated with significantly lower waist circumference, compared to former users and never users.

Except for diastolic BP that was significantly lower among current users, other metabolic parameters showed tendency towards favorable profile…

Our study on the cardio-metabolic effects on marijuana use among black population from an inner city institution showed consistent results on the association of marijuana use with lower waist circumference that has been demonstrated previously among populations that are largely white.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523241/

 

Sativex® and clinical-neurophysiological measures of spasticity in progressive multiple sclerosis.

“Despite the proven efficacy of Sativex® (9-delta-tetrahydrocannabinol plus cannabidiol) oromucosal spray in reducing spasticity symptoms in multiple sclerosis (MS), little is known about the neurophysiological correlates of such effects.

The aim of the study was to investigate the effects of Sativex on neurophysiological measures of spasticity (H/M ratio) and corticospinal excitability in patients with progressive MS.

This was a randomized, double-blind, placebo-controlled, crossover study…

Our findings confirm the clinical benefit of Sativex on MS spasticity.”

http://www.ncbi.nlm.nih.gov/pubmed/26289497