“Sequence variants of THCA- and CBDA-synthases were isolated from different Cannabis sativa L. strains expressing various wild-type and mutant chemical phenotypes (chemotypes). Expressed and complete sequences were obtained from mature inflorescences. Each strain was shown to have a different specificity and/or ability to convert the precursor CBGA into CBDA and/or THCA type products. The comparison of the expressed sequences led to the identification of different mutations, all of them due to SNPs. These SNPs were found to relate to the cannabinoid composition of the inflorescence at maturity and are therefore proposed to have a functional significance. The amount of variation was found to be higher within the CBDAS sequence family than in the THCAS family, suggesting a more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore consider CBDAS as the ancestral type of these synthases.”
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Unfazed or Dazed and Confused: Does Early Adolescent Marijuana Use Cause Sustained Impairments in Attention and Academic Functioning?
“There was no evidence indicating that adolescents who used marijuana experienced lingering attention and academic problems, relative to their pre-onset levels, after abstaining from use for at least a year.
These results suggest that adolescents who engage in low to moderate marijuana use experience an increase in observable attention and academic problems, but these problems appear to be minimal and are eliminated following sustained abstinence.”
Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats.
“The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) are due to activational effects of gonadal hormones…
These results suggest that greater antinociceptive tolerance in females, which occurred despite females receiving 40% less THC than males, is not due to activational effects of gonadal hormones.”
Simultaneous determination of endocannabinoids in murine plasma and brain substructures by surrogate-based LC-MS/MS: Application in tumor-bearing mice.
“The endocannabinoids (eCBs), N-arachidonoylethanolamine (anandamide, AEA) and 2-ararchidonylglycerol (2-AG) have been identified as main endogenous ligands for cannabinoid receptors.
Developing a sensitive and robust method to determine AEA and 2-AG has been shown to be essential to understand their effects in stress regulation and the pathogenesis of affective disorders.
Detection was performed in multiple reaction monitoring (MRM) mode with an electrospray ionization source operated in positive ion mode. The method was applied to assess plasma and brain eCBs in tumor-bearing mice.”
The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.
“Multiple drug resistance (MDR) is one of the principal causes of chemotherapeutic treatment failure in malignant disease…
Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter…
Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates…
Cannabis and cannabinoid preparations are used as therapeutic agents.
One of the many applications of cannabinoids is in the palliation of cancer chemotherapy-induced nausea, vomiting and anorexia. Indeed, the commercial preparations, Marinol and Cesamet, containing the synthetic Δ9-tetrahydrocannabinol (THC) analogue, dronabinol (or nabilone), are approved in some countries for this use.
Interestingly, in the future, cannabinoids might be co-administered with conventional cancer chemotherapies not only in a palliative capacity but also as primary anticancer medications. Accordingly, cannabinoids have demonstrated antiproliferative actions on cancer cells in vitro and in vivo…
To conclude, this is the first study to address the interaction of cannabinoids with the multidrug transporter ABCG2/Abcg2. The results presented here indicate that plant-derived cannabinoids are a novel class of ABCG2/Abcg2 inhibitors. Our results may have important implications for the use of cannabinoid compounds with therapeutic drugs that are substrates for ABCG2.”
The cannabis conundrum: Thinking outside the THC box.
“Developing a solid evidence base regarding the health effects of cannabis is imperative given the momentum for legalization and the demand for sound regulatory practices.”
Screening of cannabinoids in industrial-grade hemp using two-dimensional liquid chromatography coupled with acidic potassium permanganate chemiluminescence detection.
“Widely known for its recreational use, the cannabis plant also has the potential to act as an antibacterial agent in the medicinal field.
The analysis of cannabis plants/products in both pharmacological and forensic studies often requires the separation of compounds of interest and/or accurate identification of the whole cannabinoid profile.
In order to provide a complete separation and detection of cannabinoids, a new two-dimensional liquid chromatography method has been developed using acidic potassium permanganate chemiluminescence detection, which has been shown to be selective for cannabinoids.
This was carried out using a Luna 100 Å CN column and a Poroshell 120 EC-C18 column in the first and second dimension respectively. The method has utilised a large amount of the available separation space with a spreading angle of 48.4° and a correlation of 0.66 allowing the determination of more than 120 constituents and mass spectral identification of ten cannabinoids in a single analytical run.
The method has potential to improve research involved in the characterisation of sensitive, complex matrices. ”
http://www.ncbi.nlm.nih.gov/pubmed/25845561
http://onlinelibrary.wiley.com/doi/10.1002/jssc.201500088/abstract
Major urinary protein 1 interacts with cannabinoid receptor type 1 in fatty acid-induced hepatic insulin resistance in a mouse hepatocyte model.
“Hepatic insulin resistance (HIR) is a metabolic abnormality characterized by increased gluconeogenesis which usually contributes from an elevation of free fatty acids.
Cannabinoid receptor type 1 (CB1R) and major urinary protein 1 (MUP1) are thought to play pivotal roles in mitochondrial dysfunction, liver steatosis and insulin resistance.
The aim of this study was to explore the role of MUP1 in CB1R-mediated HIR through the dysregulation of mitochondrial function in AML12 mouse hepatocytes challenged with high concentration of free fatty acids (HFFA)…
Altogether, these findings suggest that the anti-HIR effect of AM251 via improvement of mitochondrial functions might occur in a MUP1-dependent manner.”
The interactive role of cannabinoid and vanilloid systems in hippocampal synaptic plasticity in rats.
“Long-term potentiation (LTP) has been most thoroughly studied in the hippocampus, which has a key role in learning and memory. Endocannabinoids are one of the endogenous systems that modulate this kind of synaptic plasticity. The activation of the vanillioid system has also been shown to mediate synaptic plasticity in the hippocampus. In addition, immunohistochemical studies have shown that cannabinoid receptor type 1 (CB1) and vanilloid receptor 1 (TRPV1) are closely located in the hippocampus.
It seems that agonists of the vanilloid system modulate cannabinoid outputs that cause an increase in synaptic plastisity, while in contemporary consumption of two agonist, TRPV1 agonist can change production of endocannabinoid, which in turn result to enhancement of LTP induction. These findings suggest that the two systems may interact or share certain common signaling pathways in the hippocampus.”
Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla.
“The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles.
Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like peptides derived from alpha hemoglobin, has been described, with yet unknown origin and function in the CNS. Using monoclonal antibodies we now identified the localization of RVD-hemopressin (pepcan-12) and N-terminally extended peptide endocannabinoids (pepcans) in the CNS and determined their neuronal origin…
These data uncover important areas of peptide endocannabinoid occurrence with exclusive noradrenergic immunohistochemical staining, opening new doors to investigate their potential physiological function in the ECS.”