“The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches.
Effects of exercise on experimentally manipulated craving for cannabis: A preliminary study.
“Cannabis is the most commonly used illicit drug in the United States, and craving for cannabis is related to cannabis use.
Exercise has been demonstrated to reduce craving for substances.
The findings suggest that moderate exercise may be useful for reducing craving, particularly among those who use larger quantities of cannabis.”
https://www.ncbi.nlm.nih.gov/pubmed/29792472
“Exercise activates the endocannabinoid system.” https://www.ncbi.nlm.nih.gov/pubmed/14625449
“Aerobic exercise training reduces cannabis craving and use in non-treatment seeking cannabis-dependent adults.” https://www.ncbi.nlm.nih.gov/pubmed/21408154
Sativex® as Add-on therapy Vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial.
“Purpose/aim: To evaluate the efficacy of tetrahydrocannabinol [THC]:cannabidiol [CBD] oromucosal spray (Sativex®) as add-on therapy to optimized standard antispasticity treatment in patients with moderate to severe multiple sclerosis (MS) spasticity.
RESULTS:
Of 191 patients who entered Phase A, 106 were randomised in Phase B to receive add-on THC:CBD spray (n = 53) or placebo (n = 53). The proportion of clinically-relevant responders after 12 weeks (≥ 30% NRS improvement; primary efficacy endpoint) was significantly greater with THC:CBD spray than placebo (77.4 vs 32.1%; P < 0.0001). Compared with placebo, THC:CBD spray also significantly improved key secondary endpoints: changes in mean spasticity NRS (P < 0.0001), mean pain NRS (P = 0.0013), and mean modified Ashworth’s scale (P = 0.0007) scores from Phase B baseline to week 12. Adverse events, when present, were mild/moderate and without new safety concerns.CONCLUSIONS:
Add-on THC:CBD oromucosal spray provided better and clinically relevant improvement of resistant MS spasticity compared with adjusting first-line antispasticity medication alone.” https://www.ncbi.nlm.nih.gov/pubmed/29792372 https://www.tandfonline.com/doi/abs/10.1080/00207454.2018.1481066]]>Endocannabinoid system and pathophysiology of adipogenesis: current management of obesity.
“The endocannabinoids are now known as novel and important regulators of energy metabolism and homeostasis.
The endocrine functions of white adipose are chiefly involved in the control of whole-body metabolism, insulin sensitivity and food intake. Adipocytes produce hormones, such as leptin and adiponectin, that can improve insulin resistance or peptides, such as TNF-α, that elicit insulin resistance. Adipocytes express specific receptors, such as peroxisome proliferator-activated receptor (PPAR)-γ, which serve as adipocyte targets for insulin sensitizers such as thiazolidinediones.
Recently, endocannabinoids and related compounds were identified in human fat cells.
The endocannabinoid system consists primarily of two receptors, cannabinoid (CB)1 and CB2, their endogenous ligands termed endocannabinoids and the enzymes responsible for ligand biosynthesis and degradation.
The endocannabinoids 2-arachidonylglycerol and anandamide or N-arachidonoylethanolamine increase food intake and promote weight gain in animals. Rimonabant, a selective CB1 blocker, reduces food intake and body weight in animals and humans.”
“The anti-tumor properties of 
“Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid.
The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids.
We show that cholesterol behaves as a binding partner for anandamide, and that following an initial interaction mediated by the establishment of a hydrogen bond, anandamide is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu.
The complex is then directed to the anandamide cannabinoid receptor (CB1) which displays a high affinity binding pocket for anandamide. We propose that cholesterol may regulate the entry and exit of anandamide in and out of CB1 by interacting with low affinity cholesterol recognition sites (CARC and CRAC) located in transmembrane helices.
The mirror topology of cholesterol binding sites in the seventh transmembrane domain is consistent with the delivery, extraction and flip-flop of anandamide through a coordinated cholesterol-dependent mechanism. The binding of anandamide to ceramide illustrates another key function of membrane lipids which may occur independently of protein receptors.
Interestingly, ceramide forms a tight complex with anandamide which blocks the degradation pathway of both lipids and could be exploited for anti-cancer therapies.”
