Encapsulation of cannabinoid drugs in nanostructured lipid carriers.

Posted on March 12, 2016 by David

“This study describes the development and optimization of a method to encapsulate the potent and expensive cannabinoids drugs in nanostructured lipid carriers; namely, URB597, AM251 and rimonabant have been considered. NLC production by melt and ultrasonication protocol has been specifically designed to optimize nanoparticle recovery and drug encapsulation efficiency. Special care has been devoted to the modality of oil and water phase emulsification and the entire production has been studied and discussed. NLC recovery, morphology, dimensional distribution and encapsulation efficiency are presented.”

http://www.ncbi.nlm.nih.gov/pubmed/26952905

Nutritional n-3 PUFA Deficiency Abolishes Endocannabinoid Gating of Hippocampal Long-Term Potentiation.

Posted on March 8, 2016 by David

“Maternal n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, is critical during perinatal brain development. How early postnatal n-3 PUFA deficiency impacts on hippocampal synaptic plasticity is mostly unknown. Here we compared activity-dependent plasticity at excitatory and inhibitory synapses in the CA1 region of the hippocampus in weaned pups whose mothers were fed with an n-3 PUFA-balanced or n-3 PUFA-deficient diet. Normally, endogenous cannabinoids (eCB) produced by the post-synapse dually control network activity by mediating the long-term depression of inhibitory inputs (iLTD) and positively gating NMDAR-dependent long-term potentiation (LTP) of excitatory inputs. We found that both iLTD and LTP were impaired in n-3 PUFA-deficient mice. Pharmacological dissection of the underlying mechanism revealed that impairment of NMDAR-dependent LTP was causally linked to and attributable to the ablation of eCB-mediated iLTD and associated to disinhibitory gating of excitatory synapses. The data shed new light on how n-3 PUFAs shape synaptic activity in the hippocampus and provide a new synaptic substrate to the cognitive impairments associated with perinatal n-3 deficiency.”

http://www.ncbi.nlm.nih.gov/pubmed/26946127

Cannabinoid CB2 receptors are involved in the regulation of fibrogenesis during skin wound repair in mice.

Posted on March 5, 2016 by David

“Studies have shown that cannabinoid CB2 receptors are involved in wound repair, however, its physiological roles in fibrogenesis remain to be elucidated.

In the present study, the capacity of cannabinoid CB2 receptors in the regulation of skin fibrogenesis during skin wound healing was investigated.

These results indicated that cannabinoid CB2 receptors modulate fibrogenesis and the TGF‑β/Smad profibrotic signaling pathway during skin wound repair in the mouse.”

http://www.ncbi.nlm.nih.gov/pubmed/26935001

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.

Posted on February 23, 2016 by David

“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

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

Posted on February 21, 2016 by David

“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.

Posted on February 21, 2016 by David

“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.

Posted on February 20, 2016 by David

“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.

Posted on February 19, 2016 by David

“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.

Posted on February 17, 2016 by David

“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.