“We identified 16 randomized placebo-controlled trials investigating cannabinoids as symptomatic treatment in multiple sclerosis (MS). There is evidence that nabiximols oromucosal spray may reduce subjective symptoms of spasticity and that dronabinol is effective against neuropathic pain in patients with MS.”
http://www.ncbi.nlm.nih.gov/pubmed/26535431
http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/
“Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors.
Cannabinoids are also involved in remote preconditioning of the heart.
The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart.
The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase.
The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression.
The delayed cardioprotective effect of another cannabinoid, Δ9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory.
The adenosine triphosphate-sensitive K+ channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury.
Cannabinoids inhibit Na+/Ca2+ exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids.
The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia-reperfusion injury in the clinical setting.”
“Chronic diseases are due to deviations of fundamental physiological systems, with different pathologies being characterised by similar malfunctioning biological networks.
The ensuing compensatory mechanisms may weaken the body’s dynamic ability to respond to further insults and reduce the efficacy of conventional single target treatments.
The multitarget, systemic, and prohomeostatic actions emerging for plant cannabinoids exemplify what might be needed for future medicines.
Indeed, two combined cannabis extracts were approved as a single medicine (Sativex®), while pure cannabidiol, a multitarget cannabinoid, is emerging as a treatment for paediatric drug-resistant epilepsy.
Using emerging cannabinoid medicines as an example, we revisit the concept of polypharmacology and describe a new empirical model, the ‘therapeutic handshake’, to predict efficacy/safety of compound combinations of either natural or synthetic origin.”
“Activation of the endocannabinoid system through CB1, CB2 and additional receptor subtypes results in the inhibition of a broad range of cancers.
The endocannabinoid system was discovered through research focusing on the classical cannabinoid agonist, ?9-tetrahydrocannabinol (?9-THC), and other synthetic cannabinoids.
This proposal will focus on the potential treatment of human breast cancer using cannabinoids as selective antitumor agents.
We have found that cannabinoid compounds activating CB1, CB2 and additional receptor subtypes can inhibit breast cancer cell proliferation and invasiveness and we have discovered down-stream targets that potentially link cannabinoid receptor stimulation to these effects.
Furthermore, our preliminary studies provide evidence that endogenous endocannabinoid tone tonically inhibits metastatic breast cancer cell proliferation and invasiveness through the activation of cannabinoid receptors.
Our preliminary data also suggests that cannabinoid compounds possess selective efficacy, having less adverse effects on the normal human cells from which the breast cancers arise.
Since toxicity in healthy tissue limits the efficacy of current cancer treatments, discovering the mechanism behind selective efficacy in human tissues is of clinical importance.
Cannabinoids can inhibit multiple types of tumor growth in vivo…
Testing the hypotheses outlined in the application may lead to the development of effective inhibitors of breast, and perhaps other, cancers.
This research may also elucidate novel mechanisms related to the anticancer activity of cannabinoids, and will serve to develop the career of the candidate in the field of cancer biology.”
“Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic noncancer pain.
The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among subjects with chronic noncancer pain.
A standardized herbal cannabis product (12.5% THC) was dispensed to eligible subjects for a one-year period; controls were subjects with chronic pain from the same clinics who were not cannabis users.
The primary outcome consisted of serious adverse events (SAEs) and non-serious adverse events (AEs). Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver and endocrine function.
Secondary efficacy parameters included pain and other symptoms, mood, and quality of life.
Two hundred and sixteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 215 controls (chronic pain but no current cannabis use) from seven clinics across Canada. The median daily cannabis dose was 2.5g/d.
There was no difference in risk of SAEs between groups.
Medical cannabis users were at increased risk of non-serious AEs; most were mild to moderate. There were no differences in secondary safety assessments.
Quality-controlled herbal cannabis, when used by cannabis-experienced patients as part of a monitored treatment program over one year, appears to have a reasonable safety profile.
This study evaluated the safety of cannabis use by patients with chronic pain over one year. The study found that there was a higher rate of adverse events among cannabis users compared to controls but not for serious adverse events at an average dose of 2.5g herbal cannabis per day.”
“Δ9-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea…
Combined subthreshold doses of THC and CBDA reduced acute nausea.
Higher doses of THC or CBDA alone, as well as these combined doses also reduced acute nausea.
Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.”
“It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ9-tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC.
The aim of this study is to investigate whether CBD modulates THC-induced functional effects and c-Fos expression in a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.
These data re-affirm that CBD modulates the pharmacological actions of THC and provide information regarding brain regions involved in the interaction between CBD and THC.”
“To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study.
There was suggestive evidence for treatment effects of Δ9-THC on some aspects of disability.
There were no major safety concerns.
Overall, patients felt that these drugs were helpful in treating their disease.
These data provide limited evidence for a longer term treatment effect of cannabinoids.”
“Depression and pain are two of the most debilitating disorders worldwide and have an estimated cooccurrence of up to 80%. Comorbidity of these disorders is more difficult to treat, associated with significant disability and impaired health-related quality of life than either condition alone, resulting in enormous social and economic cost.
Several neural substrates have been identified as potential mediators in the association between depression and pain, including neuroanatomical reorganization, monoamine and neurotrophin depletion, dysregulation of the hypothalamo-pituitary-adrenal axis, and neuroinflammation.
However, the past decade has seen mounting evidence supporting a role for the endogenous cannabinoid (endocannabinoid) system in affective and nociceptive processing, and thus, alterations in this system may play a key role in reciprocal interactions between depression and pain.
This review will provide an overview of the preclinical evidence supporting an interaction between depression and pain and the evidence supporting a role for the endocannabinoid system in this interaction.”
http://www.ncbi.nlm.nih.gov/pubmed/26342110
“The plant Cannabis sativa has been used as a medicine throughout the world for several thousand years, with reports of its use in treating painful symptoms appearing as early as 2600 BC. The principal psychoactive ingredient of Cannabis sativa, delta-9-tetrahydrocannabinol (Δ9-THC), was first identified in 1964, and subsequent studies to understand its mechanism of action led to the discovery of the endogenous cannabinoid (endocannabinoid) system… Because of the distribution of the endocannabinoid system throughout spinal and supraspinal regions, it is in a prime position to regulate neurophysiological activities such as affective and nociceptive processing… evidence suggests a prominent role for the endocannabinoid system in the interaction between depression and pain,” http://ijnp.oxfordjournals.org/content/early/2015/09/04/ijnp.pyv095.long
“Cannabinoid compounds include phytocannabinoids, endocannabinoids, and synthetics.
The two primary phytocannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with CB1 receptors in the brain and peripheral tissue and CB2 receptors in the immune and hematopoietic systems.
The route of delivery of cannabis is important as the bioavailability and metabolism are very different for smoking versus oral/sublingual routes.
Gold standard clinical trials are limited; however, some studies have thus far shown evidence to support the use of cannabinoids for some cancer, neuropathic, spasticity, acute pain, and chronic pain conditions.”