“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: cannabis
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
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.”

The endocannabinoid system: a putative role in neurodegenerative diseases.

“Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases.
The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases
Scientific evidence shows that cannabis can provide symptomatic relief in several neurodegenerative diseases such as multiple sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases, and amyotrophic lateral sclerosis. These findings imply that a hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of these diseases. Moreover, given the abundance of CB1 receptors in areas associated with movement and executive thought, researchers’ interest has often focused on endocannabinoid levels in patients with motor degenerative disorders.
CONCLUSIONS:
The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology.”
Clinical endocannabinoid deficiency (CECD) revisited: Can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?

“Ethan B. Russo’s paper of December 1, 2003 explored the concept of a clinical endocannabinoid deficiency (CECD) underlying the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome and other functional conditions alleviated by clinical cannabis.
Available literature was reviewed, including searches via the National Library of medicine database and other sources.
A review of the literature indicates that significant progress has been made since Dr. Ethan B. Russo’s landmark paper, just ten years ago (February 2, 2004). Investigation at that time suggested that cannabinoids can block spinal, peripheral and gastrointestional mechanisms that promote pain in headache, fibromyalgia, irritable bowel syndrome and muscle spasm.
CONCLUSION:
Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially, clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.” http://www.ncbi.nlm.nih.gov/pubmed/24977967
“Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.” http://www.ncbi.nlm.nih.gov/pubmed/15159679
Cannabis for inflammatory bowel disease.
“The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds.
Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders.In murine colitis, cannabinoids decrease histologic and microscopic inflammation.
In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis.
Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn’s disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications.
In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity.
In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use”
[The cannabinoid system and its importance in the perinatal period].

“The cannabinoid system has been recently described, including the endogenous ligands, mainly arachidonic acid derivatives, and their specific receptors. Endocannabinoids are involved in the modulation of synaptic transmission, through which they exert their psychoactive, motor and antinociceptive effects, among others; they also exert extraneural effects, mainly immunomodulation and vasodilation.
Recent data suggest that the cannabinoid system might play an important role in human ontogeny and could participate in the implantation and early development of the embryo, in fetal brain development, and in the beginning of breast feeding after birth.
In addition, the vasodilatory effect of cannabinoids, together with inhibition of the release of excitotoxic amino acids and cytokines, as well as modulation of oxidative stress and the toxic production of nitric oxide, justify the growing evidence pointing to a possible neuroprotective effect of cannabinoids in perinatal asphyxia.”
Schizophrenic Genes may Increase Cannabis Use, Quantity

“Study results showed that those who were genetically pre-disposed to schizophrenia were more likely to use cannabis and in greater quantities than those who did not possess schizophrenia risk genes.
… a pre-disposition to schizophrenia increases your likelihood of cannabis use,””
Schizophrenia And Marijuana Use May Be Linked By The Same Set Of Genes
“A new study published in Molecular Psychiatry suggests that people who are genetically predisposed to developing schizophrenia may also have the propensity for cannabis use, influenced by the same set of genes. The study is a collaboration between King’s College London and the Queensland Institute of Medical Research in Australia, partly funded by the UK Medical Research Council (MRC).
“We know that cannabis increases the risk of schizophrenia. Our study certainly does not rule this out, but it suggests that there is likely to be an association in the other direction as well – that a pre-disposition to schizophrenia also increases your likelihood of cannabis use,” Power said. “Our study highlights the complex interactions between genes and environments when we talk about cannabis as a risk factor for schizophrenia. Certain environmental risks, such as cannabis use, may be more likely given an individual’s innate behaviour and personality, itself influenced by their genetic make-up.””
http://www.medicaldaily.com/schizophrenia-and-marijuana-use-may-be-linked-same-set-genes-289574