“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.
Tag Archives: cannabis
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.”
Cannabidiol, a novel inverse agonist for GPR12.
“GPR12 is a constitutively active, Gs protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay. Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Thus, GPR12 is a novel molecular target for CBD. CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter viscoelasticity of metastatic cancer cells. Since we have demonstrated that CBD is an inverse agonist for GPR12, this provides novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.” https://www.ncbi.nlm.nih.gov/pubmed/28888984 http://www.sciencedirect.com/science/article/pii/S0006291X1731759X]]>
Medical Marijuana Helps Kids With Cerebral Palsy, Israeli Study Finds
“Medical marijuana significantly improved the condition of children suffering from cerebral palsy, a study by Wolfson Medical Center near Tel Aviv has found. According to the interim findings, treatment with cannabis oil reduced the disorder’s symptoms and improved the children’s motor skills. It also improved the kids’ sleep quality, bowel movements and general mood. “The THC’s effect is especially relevant to motor function, whether it’s Parkinson’s disease or other motor symptoms,” says Bar-Lev Schleider. “But the THC is also responsible for the psycho-active effect, so we picked a variety that also has a lot of CBD, which moderates the euphoric effect.” One group of children was treated with oil with a 1:6 ratio of THC to CBD, while for another group the ratio was 1:20. “According to the interim findings both oils are effective,” says Bar-Lev Schleider.” http://www.haaretz.com/israel-news/.premium-1.811010]]>
Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.
“Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a non-euphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine if CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. The therapeutic and prophylactic effects of peripheral CBD (100-300μg) were assessed. In end stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (p<0.0001; n=8). Acute, transient joint inflammation was reduced by local CBD treatment (p<0.0001; n=6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (p<0.0001; n=8), and was also found to be neuroprotective (p<0.05; n=6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.” https://www.ncbi.nlm.nih.gov/pubmed/28885454 https://insights.ovid.com/crossref?an=00006396-900000000-99152]]>
Cannabis constituent synergy in a mouse neuropathic pain model.
“Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects.
We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy and sedation. CBD produced a lesser dose-dependent reduction in allodynia, but did not produce the cannabinoid side-effects. When co-administered in a fixed ratio, THC and CBD produced a biphasic dose-dependent reduction in allodynia. At low doses, the THC:CBD combination displayed a 200-fold increase in anti-allodynic potency, but had lower efficacy compared to that predicted for an additive drug interaction. By contrast, high THC:CBD doses had lower potency, but greater anti-allodynic efficacy compared to that predicted for an additive interaction. Only the high dose THC:CBD anti-allodynia was associated with cannabinoid side-effects and these were similar to those of THC alone. Unlike THC, the low dose THC:CBD anti-allodynia was not cannabinoid receptor mediated.
These findings demonstrate that CBD synergistically enhances the pain relieving actions of THC in an animal neuropathic pain model, but has little impact on the THC-induced side-effects. This suggests that low dose THC:CBD combination treatment has potential in the treatment of neuropathic pain.”