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

Pro-inflammatory obesity in aged cannabinoid-2 receptor deficient mice.

“Cannabinoid-1 receptor signaling increases the rewarding effects of food intake and promotes the growth of adipocytes, whereas CB2 possibly opposes these pro-obesity effects by silencing the activated immune cells that are key drivers of the metabolic syndrome.

Pro- and anti-orexigenic cannabimimetic signaling may become unbalanced with age because of alterations of the immune and endocannabinoid system…

CB2 agonists may fortify CB2-mediated anti-obesity signaling without the risk of anti-CB1 mediated depression that caused the failure of rimonabant.”

http://www.ncbi.nlm.nih.gov/pubmed/26303348

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/

[Neuroprotective mechanisms of cannabinoids in brain ischemia and neurodegenerative disorders].

“One of the most important causes of morbidity and mortality is neurologic dysfunction; its high incidence has led to an intense research of the mechanisms that protect the central nervous system from hypoxia and ischemia. The mayor challenge is to block the biochemical events leading to neuronal death.

This may be achieved by neuroprotective mechanisms that avoid the metabolic and immunologic cascades that follow a neurological damage. When it occurs, several pathophysiological events develop including cytokine release, oxidative stress and excitotoxicity.

Neuroprotective effects of cannabinoids to all those mechanisms have been reported in animal models of brain ischemia, excitotoxicity, brain trauma and neurodegenerative disorders.

Some endocannabinoid analogs are being tested in clinical studies (I-III phase) for acute disorders involving neuronal death (brain trauma and ischemia).

The study of the cannabinoid system may allow the discovery of effective neuroprotective drugs for the treatment of neurological disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26299059

Cannabinoid receptor type 1 agonist ACEA improves motor recovery and protects neurons in ischemic stroke in mice.

“Brain ischemia produces neuronal cell death and the recruitment of pro-inflammatory cells.

In turn, the search for neuroprotection against this type of insult has rendered results involving a beneficial role of endocannabinoid receptor agonists in the Central Nervous System.

In this work, to further elucidate the mechanisms associated to this neuroprotective effect…

Motor tests showed a progressive deterioration in motor activity in ischemic animals, which only ACEA treatment was able to counteract.

Our results suggest that CB1R may be involved in neuronal survival and in the regulation of neuroprotection during focal cerebral ischemia in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/26296704

http://www.thctotalhealthcare.com/category/stroke-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

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“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/