“To conduct a systematic review and meta-analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past-month marijuana use prevalence among adolescents.
Exogenous Cannabinoid Efficacy: Merely a Pharmacokinetic Interaction?
“Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics relatively well ascertained. Further, the cannabinoid receptors are now molecularly and pharmacologically characterised and the cell processes involved in endocannabinoid transcription, synthesis, post-translational modification and protein expression are reported. Endogenous cannabinoids have been shown to have key roles in immune and pain pathways and neuro-behavioural signalling including appetite regulation. Significant recent interest has thus been shown in understanding these pathways to guide the development of agents that inhibit the natural catabolism of endogenous cannabinoids to modify pain and appetite, and to synthesise antagonists for the treatment of disease such as obesity. This research is concurrent with the renewed clinical interest in exogenous cannabinoids and their use in disease. However, the complex pharmacology and physiological effects of exogenous cannabinoids, either as individual components or in combination, as extracts or via administration of the whole plant in humans, are less well known. Yet as with all other therapeutics, including those derived from plants, knowledge of the pharmacokinetics and dynamics of the complete plant, the individual chemical molecules and their synthetic versions, including formulations and excipients is a standard part of drug development. This article covers the key pharmacological knowledge required to guide further exploration of the toxicity and efficacy of different cannabinoids and their formulations in blinded placebo-controlled studies.” https://www.ncbi.nlm.nih.gov/pubmed/28921125 https://link.springer.com/article/10.1007%2Fs40262-017-0599-0]]>
Cannabidiol Regulates Long Term Potentiation Following Status Epilepticus: Mediation by Calcium Stores and Serotonin.
“Epilepsy is a devastating disease, with cognitive and emotional consequences that are not curable.
In recent years, it became apparent that cannabinoids help patients to cope with epilepsy.
We have studied the effects of cannabidiol (CBD) on the ability to produce long term potentiation (LTP) in stratum radiatum of CA1 region of the mouse hippocampus.
Exposure to seizure-producing pilocarpine reduced the ability to generate LTP in the slice.
Pre-exposure to CBD prevented this effect of pilocarpine.
Furthermore, CBD caused a marked increase in ability to generate LTP, an effect that was blocked by calcium store antagonists as well as by a reduction in serotonin tone. Serotonin, possibly acting at a 5HT1A receptor, or fenfluramine (FFA), which causes release of serotonin from its native terminals, mimicked the effect of CBD.
It is proposed that CBD enhances non-NMDA LTP in the slice by facilitating release of serotonin from terminals, consequently ameliorating the detrimental effects of pilocarpine.”
Time-dependent effect of phytocannabinoid treatments in fat cells.
“The objectives of this paper is to investigate, demonstrate, and compare the mechanism of action of phytocannabinoids as antidiabetic and anti-obesity agents in preadipocytes and adipocytes, relative to rosiglitazone and metformin. Briefly, cannabis extract, Δ9 -tetrahydrocannabinol and cannabidiol (in very low dosages) were shown to promote glucose uptake higher or to equivalent levels, reduce fat accumulation, and reverse the insulin-resistant state of 3T3-L1 cells more effectively, relative to rosiglitazone and metformin. The phytocannabinoids had a more pronounced effect in preadipocytes undifferentiated model rather than the differentiated model. They induced a protective effect at the mitochondrial level by preventing overactivity of the succinate dehydrogenase pathway (p < .01), unlike rosiglitazone, through activation of the glycerol-3-phosphate dehydrogenase shuttling system. An increase in oxygen consumption and an increased expression of beta to alpha adrenoceptors (p < .05) in treated cells were noted. These findings contribute toward understanding the mechanism of action of phytocannabinoids in fat cells and highlight the antidiabetic and anti-obesity properties of various phytocannabinoids that could potentially support the treatment of obesity-related insulin resistance.” https://www.ncbi.nlm.nih.gov/pubmed/29464872]]>
Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability.
“Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals.
Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability.
This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability.
Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis’s abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.”
“Endocannabinoid system plays an important role in pathophysiologic processes such as immune functions and impacts on disease severity.
Our previous study showed that 
“Emerging evidence suggest an impaired endocannabinoid activity in the pathophysiology of binge eating disorder (BED). Herein, we investigated whether endocannabinoid tone could be modified as a consequence of dietary-induced binge eating in female rats.
For this purpose, brain levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), as well as two endocannabinoid-like lipids, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), were assessed in different brain areas involved in the hedonic feeding (i.e., prefrontal cortex, nucleus accumbens, amygdala, hippocampus, and hypothalamus).
The brain density of