“11-nor-Δ9-Tetrahydrocannabinol-9-carboxylic acid glucuronide (THCCOOH-glucuronide) is an 1-β-O-acyl glucuronide which degrades not only to 11-nor-9-carboxy-Δ9-THC (THCCOOH) but, additionally, to an isomer with a currently unknown structure. The present study was carried out to examine whether acyl glucuronide isomers are formed by acyl migration and if they are involved in formation of this isomer. THCCOOH-glucuronide was incubated in phosphate buffer (pH 7.4, 37°C, 7days) and a variety of glucuronide cleavage procedures were performed. Samples of the incubation mixture and of different biological specimens from cannabis users were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). A total of six chromatographically separated isomeric acyl glucuronides were detected during incubation of THCCOOH-glucuronide reference substance. In biological specimens of cannabis users, two additional isomers were found. However, the main glucuronide present in human specimens was different from that of a commercially available reference substance. Both, the commercial and the authentic glucuronide were cleaved by β-glucuronidases, the other formed isomers by alkaline hydrolysis only. Mass spectrometric investigations (i.e. product ion, precursor ion and neutral loss scans) confirmed identity. The THCCOOH isomer was detected in all authentic samples, but not in those after buffer incubation. By analyzing THCCOOH-glucuronide in authentic samples, it has to be taken into account that the authentic glucuronide is different from that of the commercial reference standard. THCCOOH-glucuronide undergoes acyl migration and some isomers occur to minor extents in biological specimens. Acyl migration does not lead to the formation of the THCCOOH isomer.” https://www.ncbi.nlm.nih.gov/pubmed/28892757 http://www.sciencedirect.com/science/article/pii/S0731708517317090?via%3Dihub]]>
Monthly Archives: September 2017
Challenges towards Revitalizing Hemp: A Multifaceted Crop.
“Hemp has been an important crop throughout human history for food, fiber, and medicine. Despite significant progress made by the international research community, the basic biology of hemp plants remains insufficiently understood. Clear objectives are needed to guide future research. As a semi-domesticated plant, hemp has many desirable traits that require improvement, including eliminating seed shattering, enhancing the quantity and quality of stem fiber, and increasing the accumulation of phytocannabinoids. Methods to manipulate the sex of hemp plants will also be important for optimizing yields of seed, fiber, and cannabinoids. Currently, research into trait improvement is hindered by the lack of molecular techniques adapted to hemp. Here we review how addressing these limitations will help advance our knowledge of plant biology and enable us to fully domesticate and maximize the agronomic potential of this promising crop.” https://www.ncbi.nlm.nih.gov/pubmed/28886910 http://www.cell.com/trends/plant-science/fulltext/S1360-1385(17)30177-2?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1360138517301772%3Fshowall%3Dtrue]]>
Physicians-in-training are not prepared to prescribe medical marijuana.
“While medical marijuana use is legal in more than half of U.S. states, evidence is limited about the preparation of physicians-in-training to prescribe medical marijuana. We asked whether current medical school and graduate medical educational training prepare physicians to prescribe medical marijuana.
Our study highlights a fundamental mismatch between the state-level legalization of medical marijuana and the lack of preparation of physicians-in-training to prescribe it. With even more states on the cusp of legalizing medical marijuana, physician training should adapt to encompass this new reality of medical practice.”
https://www.ncbi.nlm.nih.gov/pubmed/28892720 http://www.drugandalcoholdependence.com/article/S0376-8716(17)30441-6/fulltext ]]>Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.
“Nowadays, therapeutic indications for cannabinoids, specifically Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is its composition of materials approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (1:1, 10mg) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has in serving as a standardized oral cannabinoid formulation. Moreover, the concept of improving oral bioavailability described here, can pave the way for other potential lipophilic active compounds requiring enhancement of their oral bioavailability.” https://www.ncbi.nlm.nih.gov/pubmed/28890215 http://www.sciencedirect.com/science/article/pii/S016836591730843X]]>
Association of Cannabis, Stimulant, and Alcohol use with Mortality Prognosis Among HIV-Infected Men.
“Questionnaires over a 9-year study period (2002-2010) were used to characterize cannabis, stimulant, and alcohol use among 3099 HIV-infected men participating in the Veterans Aging Cohort Study (VACS) to determine whether use of these substances is associated with changes in the VACS Index, a validated prognostic indicator for all-cause mortality.
At baseline, 18% of participants reported no substance use in the past year, 24% lower risk alcohol use only, 18% unhealthy alcohol use only, 15% cannabis use (with or without alcohol), and 24% stimulant use (with or without alcohol or cannabis).
In adjusted longitudinal analyses, cannabis use [β = -0.97 (95% CI -1.93, 0.00), p = 0.048] was not associated with mortality risk, while stimulant use [1.08 (0.16, 2.00), p = 0.021] was associated with an increased mortality risk, compared to lower risk alcohol use.
Our findings show no evidence of a negative effect of cannabis use on mortality risk, while stimulant use was associated with increased mortality risk among HIV-infected men. Interventions to reduce stimulant use in this patient population may reduce mortality.”
Tingenone, a pentacyclic triterpene, induces peripheral antinociception due to cannabinoid receptors activation in mice.
“Several works have shown that triterpenes induce peripheral antinociception by activation of cannabinoid receptors and endocannabinoids; besides, several research groups have reported activation of cannabinoid receptors in peripheral antinociception.
The aim of this study was to assess the involvement of the cannabinoid system in the antinociceptive effect induced by tingenone against hyperalgesia evoked by prostaglandin E2 (PGE2) at peripheral level.
The results suggest that tingenone induced a peripheral antinociceptive effect via cannabinoidreceptor activation. Therefore, this study suggests a pharmacological potential for a new analgesic drug.”
https://www.ncbi.nlm.nih.gov/pubmed/28889355
“Spasticity is a common neurologic condition in patients with multiple sclerosis, stroke,