“Conventional drugs have only a limited impact on spasticity associated with multiple sclerosis and are rarely satisfactory. A solution for oral transmucosal delivery (spray) containing a mixture of cannabis extracts (2.7 mg of delta-9-tetrahydrocannabinol + 2.5 mg of cannabidiol per spray) has been granted marketing authorisation in France for patients who are inadequately relieved by standard treatments. Three double-blind, placebo-controlled trials in a total of about 300 patients tested this combination, in addition to ongoing treatment, for periods of 6 to 14 weeks. Individually, none of these trials showed any tangible anti-spastic efficacy, but two combined analyses showed “response rates” of about 35% with the mixture versus about 25% with placebo. In a trial with 572 patients, the 241 patients who “responded” after 4 weeks of treatment were randomised to either continue using the cannabis extract or receive placebo. Twelve weeks later, 75% of patients using the extract were still “responders”, versus 51% of patients switched to placebo. The principal adverse effects of the cannabis extracts consist of neuropsychiatric disorders that resolve on treatment withdrawal. The potential for abuse increases with the dose and is tangible from 16 sprays per day. Pharmacokinetic interactions due to P-glycoprotein inhibition are likely. Treatment during pregnancy may lead to neonatal withdrawal symptoms. In practice, about 10% of patients in whom standard anti-spastic medications are unsatisfactory benefit from a specific effect of the cannabis extracts contained in this oral spray.”
Tag Archives: Cannabinoids
The Pharmacokinetics, Efficacy, Safety, and Ease of Use of a Novel Portable Metered-Dose Cannabis Inhaler in Patients With Chronic Neuropathic Pain: A Phase 1a Study.
“Chronic neuropathic pain is often refractory to standard pharmacological treatments.
Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a “main stream” pharmacological treatment for neuropathic pain.
The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis…
This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ9-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs.”
http://www.ncbi.nlm.nih.gov/pubmed/25118789
http://www.thctotalhealthcare.com/category/neuropathic-pain/
Cannabinoids as therapeutic agents in cancer: current status and future implications
“Cannabinoids… active compounds of the Cannabis sativa plant… cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents.
They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models…” http://www.ncbi.nlm.nih.gov/pubmed/25115386
“Cannabinoids… the active compounds of the Cannabis sativa plant… anti-cancer agents… anti-proliferative… anti-angiogenic… anti-migratory and anti-invasive… The administration of single cannabinoids might produce limited relief compared to the administration of crude extract of plant containing multiple cannabinoids, terpenes and flavanoids.” Full-text: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B0%5D=2233&path%5B1%5D=3664
CANNABINOIDS INCREASE LUNG CANCER CELL LYSIS BY LYMPHOKINE-ACTIVATED KILLER CELLS VIA UPREGULATION OF ICAM-1.
“Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action…
Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody…
ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ9-tetrahydrocannabinol (THC) and R(+)-methanandamide, a stable endocannabinoid analogue…
Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell susceptibility to LAK cell-mediated cytolysis.
These findings provide proof for a novel antitumorigenic mechanism of cannabinoids.”
Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling.
“To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology…
Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1…
…our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death.
CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions (e.g., acne vulgaris, seborrhea, dry skin).”
Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
“Acne vulgaris is the most common human skin disease, affecting quality of life of millions worldwide…
Investigation of the cutaneous cannabinoid system seems to be a promising choice when searching for novel therapeutic possibilities…
“Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris…
These data, together with our current findings, point to a promising, cost-effective, and, likely, well-tolerated new strategy for treating acne vulgaris, the most common human skin disease…
…given the extensively documented accumulation of phytocannabinoids from smoked marijuana in the pilosebaceous unit (where they become incorporated into the hair shaft), it is very likely that CBD can reach the sebaceous glands as well, can accumulate, and may well reach “therapeutically sufficient” concentrations there.
Moreover, it is very important to note that, besides the systemic application, one should keep in mind the possibility of the topical administration.”
http://www.jci.org/articles/view/64628
“Schematic overview of the cellular “anti-acne trinity” of CBD and its proposed mechanism of action.”
[A role for the endocannabinoid system in hepatic steatosis].
“The endocannabinoid system (SEC) is an important modulator of several metabolic functions.
This system is composed by cannabinoid receptors type 1 and 2 (RCB1 and RCB2), their endogenous ligands, known as endocannabinoids, and the enzymes involved in their synthesis and degradation. A deregulated SEC originates metabolic alterations in several tissues, resulting in the typical manifestations of the metabolic syndrome…
In this review we discuss the proposed mechanisms by which SEC is involved in the etiology of hepatic steatosis, as well as the therapeutic possibilities involving peripheral RCB1/RCB2 antagonism/agonism, for the treatment of this condition.”
http://www.ncbi.nlm.nih.gov/pubmed/25052273
http://www.thctotalhealthcare.com/category/hepatic-steatosis/
Endocannabinoid CB1 antagonists inhibit hepatitis C virus production, providing a novel class of antiviral host targeting agents.
“Direct acting antivirals have significantly improved treatment outcomes in chronic hepatitis C (CHC), but side effects, drug resistance and cost mean that better treatments are still needed.
Lipid metabolism is closely linked with hepatitis C virus (HCV) replication and endocannabinoids are major regulators of lipid homeostasis.
The cannabinoid 1 (CB1) receptor mediates these effects in the liver.
Here we investigated whether CB1 blockade inhibits HCV replication.
The antiviral effect of a CB1 antagonist, AM251 was examined…
Treatment with AM251 strongly inhibited HCV RNA (~70%), viral protein (~80%), the production of new virus particles (~70%), and virus infectivity (~90%)…
We suggest that CB1 antagonists may represent an entirely new class of drugs with activity against HCV.
Anti-Cancer Effects In Active Component Of Marijuana
“Guillermo Velasco and colleagues, at Complutense University, Spain, have provided evidence that suggests that cannabinoids such as the main active component of marijuana (THC) have anticancer effects on human brain cancer cells.
In the study, THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy. Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy.
As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.”
http://www.medicalnewstoday.com/releases/144770.php
“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/
The non-psychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability.
“Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy.
Since the two non-psychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity.
These data suggest that CBDV anti-epileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.”