Medical marijuana laws and adolescent marijuana use in the USA from 1991 to 2014: results from annual, repeated cross-sectional surveys.

The Lancet Psychiatry

“Our findings, consistent with previous evidence, suggest that passage of state medical marijuana laws does not increase adolescent use of marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26303557

http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00217-5/fulltext

Prevalence of marijuana use does not differentially increase among youth after states pass medical marijuana laws: Commentary on and reanalysis of US National Survey on Drug Use in Households data 2002-2011.

“There is considerable interest in the effects of medical marijuana laws (MML) on marijuana use in the USA, particularly among youth. The article by Stolzenberg et al. (2015) “The effect of medical cannabis laws on juvenile cannabis use” concludes that “implementation of medical cannabis laws increase juvenile cannabis use”. This result is opposite to the findings of other studies that analysed the same US National Survey on Drug Use in Households data as well as opposite to studies analysing other national data which show no increase or even a decrease in youth marijuana use after the passage of MML. We provide a replication of the Stolzenberg et al. results and demonstrate how the comparison they are making is actually driven by differences between states with and without MML rather than being driven by pre and post-MML changes within states. We show that Stolzenberg et al. do not properly control for the fact that states that pass MML during 2002-2011 tend to already have higher past-month marijuana use before passing the MML in the first place. We further show that when within-state changes are properly considered and pre-MML prevalence is properly controlled, there is no evidence of a differential increase in past-month marijuana use in youth that can be attributed to state MML.”

http://www.ncbi.nlm.nih.gov/pubmed/26895950

Endocannabinoid system in the brain…and elsewhere.

“The endocannabinoid system is a complex system with endogenous ligands, synthesis and transport processes, specific receptors (CB1 and CB2) and intracellular degrading enzymes.

It is widely distributed in the central nervous system, but also in peripheral organs.

In the brain, endocannabinoids and CB1 receptors are almost ubiquitous and play a role in synaptic plasticity: they modulate, through an inhibitory retrograde action, the release of classical neurotransmitters such as amines, acetylcholine or amino acids.

They may exert a neuroprotective effect, but are also involved in appetite and alcohol/drug dependence.

At the periphery, they are present (and overexpressed in case of abdominal obesity) in various organs involved in energy control and metabolic regulation.

Furthermore, CB2 receptors are also present in the brain, although less numerous than CB1 receptors.

They could attenuate pain and also be neuroprotective.

Selective agonists, antagonists and inverse agonists of CB1 and CB2 receptors are currently developed and open new interesting therapeutic perspectives.”

http://www.ncbi.nlm.nih.gov/pubmed/18669206

Cannabis effects on driving longitudinal control with and without alcohol.

“Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis‘ effects on driving longitudinal control (with and without alcohol, drivers’ most common drug combination) relative to psychoactive ∆9 -tetrahydrocannabinol (THC) blood concentrations.

Current occasional (≥1×/last 3 months, ≤3 days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3 h post-inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42 h) and after (1.4 and 2.3 h) driving.

We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC).

THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not.

Neither was associated with altered longitudinal acceleration.

A less-than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers’ tendency to drive faster with alcohol.

Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate.”

http://www.ncbi.nlm.nih.gov/pubmed/26889769

“Stoned Drivers Safer Than Drunk Drivers”                           http://americanlivewire.com/2015-02-15-stoned-drivers-safer-drunk-drivers/

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

“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

Neuroprotective effects of the synthetic cannabinoid HU-210 in primary cortical neurons are mediated by phosphatidylinositol 3-kinase/AKT signaling.

“Cannabinoids (CBs) are neuroprotective in vivo and in vitro.

…the PI 3-K/AKT signaling pathway mediates the neuroprotective effect of exogenous cannabinoids in primary CNS neurons.”

http://www.ncbi.nlm.nih.gov/pubmed/15607953

Identification of endocannabinoids and cannabinoid CB(1) receptor mRNA in the pituitary gland.

“Most data on effects of natural and synthetic cannabinoids on anterior pituitary hormone secretion point out to a primary impact on the hypothalamus. There is also some evidence, however, of possible direct actions of these compounds on the anterior pituitary, although the presence of cannabinoid receptors in the pituitary has not been documented as yet.

In the present study, we evaluated the presence of cannabinoid CB(1) receptor-mRNA transcripts in the pituitary gland by in situ hybridization.

We observed CB(1) receptor-mRNA transcripts in the anterior pituitary and to a lesser extent in the intermediate lobe whereas they were absent in the neural lobe. We then examined whether CB(1) receptor-mRNA levels in both pituitary lobes responded to chronic activation by a specific agonist, as did receptors located in adjacent hypothalamic nuclei and in other brain regions…

We also checked whether endogenous cannabinoid ligands are present in the anterior pituitary and the hypothalamus.

Although anandamide itself was detected only in trace amounts, concentrations of its precursor N-arachidonoyl-phosphatidyl-ethanolamine and of 2-arachidonoyl-glycerol were found in both tissues, suggesting that endocannabinoids may be synthetized in the anterior pituitary.

In summary, CB(1) receptors and corresponding ligands seem to be expressed in cells of the anterior and intermediate lobes of the pituitary, but the response of CB(1) receptor-mRNA transcripts in the anterior lobe to chronic agonist activation is different than the desensitization observed in hypothalamic nuclei.”

http://www.ncbi.nlm.nih.gov/pubmed/10461028

Cannabis sativa: The Plant of the Thousand and One Molecules.

“Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fiber since the dawn of times.

This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibers.

Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively.

In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenes and phenolic compounds, and their biosynthetic routes.

Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities.

The therapeutic and commercial interests of some terpenes and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data.

Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e., cell suspension and hairy root cultures.

Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories.

Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented.”

http://www.ncbi.nlm.nih.gov/pubmed/26870049

“Known since the ancient times for its medicinal and textile uses, hemp is currently witnessing a revival, because of its rich repertoire of phytochemicals, its fibers and its agricultural features, namely quite good resistance to drought and pests, well-developed root system preventing soil erosion, lower water requirement with respect to other crops, e.g., cotton.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740396/

A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

“The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice.

The eCB system is over-active in human obesity.

Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system.

Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity.

In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.”

http://www.ncbi.nlm.nih.gov/pubmed/26849214

Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products.

“Plants are a sustainable resource for valuable natural chemicals best illustrated by large-scale farming centered on specific products. Here, we review recent discoveries of plant metabolic pathways producing natural products with unconventional biomolecular structures.

Prenylation of polyketides by aromatic prenyltransferases (aPTases) ties together two of the major groups of plant specialized chemicals, terpenoids and polyketides, providing a core modification leading to new bioactivities and downstream metabolic processing. Moreover, PTases that biosynthesize Z-terpenoid precursors for small molecules such as lycosantalene have recently been found in the tomato family.

Gaps in our understanding of how economically important compounds such as cannabinoids are produced are being identified using next-generation ‘omics’ to rapidly advance biochemical breakthroughs at an unprecedented rate. For instance, olivetolic acid cyclase, a polyketide synthase (PKS) co-factor from Cannabis sativa, directs the proper cyclization of a polyketide intermediate.

Elucidations of spatial and temporal arrangements of biosynthetic enzymes into metabolons, such as those used to control the efficient production of natural polymers such as rubber and defensive small molecules such as linamarin and lotaustralin, provide blueprints for engineering streamlined production of plant products.”

http://www.ncbi.nlm.nih.gov/pubmed/26851514