“The requirements for an acceptable cannabis assay have changed dramatically over the years resulting in a large number of laboratories using a diverse array of analytical methodologies that have not been properly validated. Due to the lack of sufficiently validated methods, we conducted a single- laboratory validation study for the determination of cannabinoids and terpenes in a variety of commonly occurring cultivars. The procedure involves high- throughput homogenization to prepare sample extract, which is then profiled for cannabinoids and terpenes by HPLC-diode array detector and GC-flame ionization detector, respectively. Spike recovery studies for terpenes in the range of 0.03-1.5% were carried out with analytical standards, while recovery studies for Δ9 -tetrahydrocannabinolic acid, cannabidiolic acid, Δ9 -tetrahydrocannabivarinic acid, and cannabigerolic acid and their neutral counterparts in the range of 0.3-35% were carried out using cannabis extracts. In general, accuracy at all levels was within 5%, and RSDs were less than 3%. The interday and intraday repeatabilities of the procedure were evaluated with five different cultivars of varying chemotype, again resulting in acceptable RSDs. As an example of the application of this assay, it was used to illustrate the variability seen in cannabis coming from very advanced indoor cultivation operations.”
Tag Archives: Cannabinoids
Effects of marijuana smoking on the lung.
“…habitual use of marijuana alone does not appear to lead to significant abnormalities in lung function, except for possible increases in lung volumes… no clear link to chronic obstructive pulmonary disease has been established… findings from a limited number of well-designed epidemiological studies do not suggest an increased risk for the development of either lung or upper airway cancer from light or moderate use… In summary, the accumulated weight of evidence implies far lower risks for pulmonary complications of even regular heavy use of marijuana compared with the grave pulmonary consequences of tobacco.” http://www.ncbi.nlm.nih.gov/pubmed/23802821
Therapy with a Selective Cannabinoid Receptor Type 2 Agonist Limits Albuminuria and Renal Injury in Mice with Type 2 Diabetic Nephropathy.
“A critical involvement of the endocannabinoid/cannabinoid receptor system in diabetes and its complications has been recognized.
Experimental evidence suggested that activation of the cannabinoid receptor type 2 (CB2), which is expressed in the kidney by podocytes and inflammatory cells, had a protective role in early streptozotocin-induced type 1 diabetes in mice.
In this study, we investigated the effects of a CB2 agonist given at a phase of overt disease on renal functional and structural changes in BTBR ob/ob mice, a model of type 2 diabetic nephropathy.
These results suggest that CB2 agonism is a potential option to be added to the available therapeutic armamentarium for type 2 diabetic nephropathy.”
The Use of Medicinal Marijuana for Posttraumatic Stress Disorder: A Review of the Current Literature.
“This study seeks to understand the current literature regarding the use of medicinal marijuana in the treatment of posttraumatic stress disorder (PTSD).
Analysis revealed that most reports are correlational and observational in basis with a notable lack of randomized, controlled studies.
Many of the published studies suggest a decrease in PTSD symptoms with marijuana use… there is a growing amount of neurobiological evidence and animal studies suggesting potential neurologically based reasons for the reported efficacy.
CONCLUSIONS:
Posttraumatic stress disorder is 1 of the approved conditions for medicinal marijuana in some states. While the literature to date is suggestive of a potential decrease in PTSD symptomatology with the use of medicinal marijuana, there is a notable lack of large-scale trials, making any final conclusions difficult to confirm at this time.”
http://www.ncbi.nlm.nih.gov/pubmed/26644963
http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/
Endocannabinoid Regulation of Neuroendocrine Systems.
“The hypothalamus is a part of the brain that is critical for sustaining life through its homeostatic control and integrative regulation of the autonomic nervous system and neuroendocrine systems. Neuroendocrine function in mammals is mediated mainly through the control of pituitary hormone secretion by diverse neuroendocrine cell groups in the hypothalamus.
Cannabinoid receptors are expressed throughout the hypothalamus, and endocannabinoids have been found to exert pronounced regulatory effects on neuroendocrine function via modulation of the outputs of several neuroendocrine systems.
Here, we review the physiological regulation of neuroendocrine function by endocannabinoids, focusing on the role of endocannabinoids in the neuroendocrine regulation of the stress response, food intake, fluid homeostasis, and reproductive function.
Cannabis sativa (marijuana) has a long history of recreational and/or medicinal use dating back to ancient times. It was used as an analgesic, anesthetic, and antianxiety herb as early as 2600 B.C.
The hedonic, anxiolytic, and mood-elevating properties of cannabis have also been cited in ancient records from different cultures. However, it was not until 1964 that the psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol, was isolated and its chemical structure determined (Gaoni & Mechoulam, 1964).”
Endocannabinoid Mechanisms Influencing Nausea.
“One of the first recognized medical uses of Δ(9)-tetrahydrocannabinol was treatment of chemotherapy-induced nausea and vomiting.
Although vomiting is well controlled with the currently available non-cannabinoid antiemetics, nausea continues to be a distressing side effect of chemotherapy and other disorders.
Indeed, when nausea becomes conditionally elicited by the cues associated with chemotherapy treatment, known as anticipatory nausea (AN), currently available antiemetics are largely ineffective.
Considerable evidence demonstrates that the endocannabinoid system regulates nausea in humans and other animals.
In this review, we describe recent evidence suggesting that cannabinoids and manipulations that enhance the functioning of the natural endocannabinoid system are promising treatments for both acute nausea and AN.”
The Endocannabinoid System and Its Role in Regulating the Intrinsic Neural Circuitry of the Gastrointestinal Tract.
“Endocannabinoids are important neuromodulators in the central nervous system.
They regulate central transmission through pre- and postsynaptic actions on neurons and indirectly through effects on glial cells.
Cannabinoids (CBs) also regulate neurotransmission in the enteric nervous system (ENS) of the gastrointestinal (GI) tract.
The ENS consists of intrinsic primary afferent neurons, interneurons, and motor neurons arranged in two ganglionated plexuses which control all the functions of the gut.
Increasing evidence suggests that endocannabinoids are potent neuromodulators in the ENS.
In this review, we will highlight key observations on the localization of CB receptors and molecules involved in the synthesis and degradation of endocannabinoids in the ENS.
We will discuss endocannabinoid signaling mechanisms, endocannabinoid tone and concepts of CB receptor metaplasticity in the ENS. We will also touch on some examples of enteric neural signaling in relation neuromuscular, secretomotor, and enteroendocrine transmission in the ENS. Finally, we will briefly discuss some key future directions.”
Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants.
“Cannabis and analogs of Δ9-tetrahydrocannabinol have been used for therapeutic purposes…
Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD).
Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD.
Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors).
In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors’ therapeutic potential.
MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2.
In the hypothalamic-pituitary-adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted.”
CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord
“Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents.
In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas.
Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region.
We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents.
Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.”
Computational Prediction and Biochemical Analyses of New Inverse Agonists for the CB1 Receptor.
“Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity.
The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 are used here to predict the binding sites for known CB1-selective inverse agonists including rimonabant and its seven known derivatives.
This binding pocket, which differs significantly from previously published models, is used to identify 16 novel compounds expected to be CB1 inverse agonists by exploiting potential new interactions.
We show experimentally that two of these compounds exhibit inverse agonist properties including inhibition of basal and agonist-induced G-protein coupling activity, as well as an enhanced level of CB1 cell surface localization.
This demonstrates the utility of using the predicted binding sites for an ensemble of CB1 receptor structures for designing new CB1 inverse agonists.”