Delta-9-Tetrahydrocannabinol/Cannabidiol (Sativex®): A Review of Its Use in Patients with Moderate to Severe Spasticity Due to Multiple Sclerosis.

Posted on April 1, 2014 by David

“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex®] is an oromucosal spray formulation that contains principally THC and CBD at an approximately 1:1 fixed ratio, derived from cloned Cannabis sativa L. plants.

The main active substance, THC, acts as a partial agonist at human cannabinoid receptors (CB1 and CB2)…

THC/CBD is approved in a number of countries, including Germany and the UK, as an add-on treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

In the largest multinational clinical trial that evaluated the approved THC/CBD regimen in this population, 12 weeks’ double-blind treatment with THC/CBD significantly reduced spasticity severity (primary endpoint) compared with placebo in patients who achieved a clinically significant improvement in spasticity after 4 weeks’ single-blind THC/CBD treatment, as assessed by a patient-rated numerical rating scale.

A significantly greater proportion of THC/CBD than placebo recipients achieved a ≥30 % reduction (a clinically relevant reduction) in spasticity severity. The efficacy of THC/CBD has been also shown in at least one everyday clinical practice study (MOVE 2). THC/CBD was generally well tolerated in clinical trials. Dizziness and fatigue were reported most frequently during the first 4 weeks of treatment and resolved within a few days even with continued treatment.

Thus, add-on THC/CBD is a useful symptomatic treatment option for its approved indication.”

http://www.ncbi.nlm.nih.gov/pubmed/24671907

Structural requirements for potent direct inhibition of human cytochrome P450 1A1 by cannabidiol: role of pentylresorcinol moiety.

Posted on March 31, 2014 by David

“Our recent work has shown that cannabidiol (CBD) exhibits the most potent direct inhibition of human cytochrome P450 1A1 (CYP1A1)…

These results suggest that the pentylresorcinol structure in CBD may have structurally important roles in direct CYP1A1 inhibition, although the whole structure of CBD is required for overall inhibition.”

http://www.ncbi.nlm.nih.gov/pubmed/23811569

“CYP1A1 regulates breast cancer proliferation and survival. This study supports the notion that CYP1A1 promotes breast cancer proliferation and survival… reduction of CYP1A1 levels is a potential strategy for breast cancer therapeutics.” http://www.ncbi.nlm.nih.gov/pubmed/23576571

The yin and yang of cannabis-induced psychosis: the actions of Δ(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia.

Posted on March 18, 2014 by David

“There is substantial epidemiological evidence showing that cannabis increases the risk of psychosis, whereas other research suggests that schizophrenia patients self-medicate with the substance. These conflicting accounts may at least be partially explained by the two phytocannabinoids cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC) and their opposing actions on schizophrenia-related symptoms.

…propsychotic actions of THC… antipsychotic actions of CBD.

…animal studies… showing that CBD antagonises the neurobehavioural effects of THC, while others show the opposite, that CBD potentiates the actions of THC.

Various mechanisms are put forth to explain these divergent effects such as CBD antagonism at central CB1 receptors…”

…the present study suggests a beneficial property of a direct cannabinoid receptor agonist… and of CBD…”

http://www.ncbi.nlm.nih.gov/pubmed/22716133

http://www.thctotalhealthcare.com/category/schizophrenia/

Can Cannabis Cure Schizophrenia? GWPH Thinks So

Posted on March 18, 2014 by David

“GW Pharmaceuticals (GWPH)… touted the extended breadth of its cannabinoid drugs: beyond treating pediatric epilepsy and cancer pain, GWPH says it has the capabilities to treat Type 2 diabetes and schizophrenia. This would position GWPH as a fantastic pharma stock play,..

“As GW continues to progress its clinical work with cannabinoids, our pipeline has the potential to yield, as it did with Epidiolex, a flow of exciting new product candidates in a wide variety of therapeutic areas,” said Dr. Stephen Wright, GW’s Director of Research and Development.

GW has started Phase 2a trial using to treat schizophrenia featuring purified CBD as its active ingredient.”

http://www.mainstreet.com/article/family/family-health/can-cannabis-cure-schizophrenia-gwph-thinks-so

A drug discovery case history of ‘delta-9-tetrahydrocannabinol, cannabidiol’.

Posted on March 15, 2014 by David

“…the Cannabis sativa herb has been known for its therapeutic benefit for centuries… interest in the clinical potential of cannabinoid-based drugs escalated after the discovery of the endocannabinoid system… therapeutic applications of cannabinoids (plant-derived or synthetic)… may constitute a useful addition to the pharmacotherapeutic armamentarium in chronic conditions insufficiently alleviated by existing drugs.” http://www.ncbi.nlm.nih.gov/pubmed/22646020

“The endocannabinoid system and its therapeutic exploitation.” http://www.ncbi.nlm.nih.gov/pubmed/15340387

“Cannabinoid receptors as therapeutic targets.” http://www.ncbi.nlm.nih.gov/pubmed/16402900

“Cannabinoids.” http://www.ncbi.nlm.nih.gov/pubmed/16266285

“Plant, synthetic, and endogenous cannabinoids in medicine.” http://www.ncbi.nlm.nih.gov/pubmed/16409166

Cannabidiol-2′,6′-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor.

Posted on March 3, 2014 by David

“Cannabidiol (CBD), one of the major components of marijuana, is known to inhibit LOX activity…

15-LOX is suggested to be involved in development of atherosclerosis, and CBDD may be a useful prototype for producing medicines for atherosclerosis.”

http://dmd.aspetjournals.org/content/37/8/1733.long

“15-lipoxygenase inhibitors as anti-atherosclerosis agents.” http://www.ncbi.nlm.nih.gov/pubmed/18465533

Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice.

Posted on March 1, 2014 by David

“Patients suffering from Alzheimer’s disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces…

The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.

This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model.

Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.”

http://www.ncbi.nlm.nih.gov/pubmed/24577515

Cannabinoid inhibition of adenylate cyclase: relative activity of constituents and metabolites of marihuana.

Posted on February 27, 2014 by David

“delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.”

http://www.ncbi.nlm.nih.gov/pubmed/3601007

Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L.

Posted on February 27, 2014 by David

“Chemical investigation of the pollen grain collected from male plants of Cannabis sativa L. resulted in the isolation for the first time of two flavonol glycosides from the methanol extract, and the identification of 16 cannabinoids in the hexane extract. The two glycosides were identified as kaempferol 3-O-sophoroside and quercetin 3-O-sophoroside by spectroscopic methods including high-field two-dimensional NMR experiments. The characterisation of each cannabinoid was performed by GC-FID and GC-MS analyses and by comparison with both available reference cannabinoids and reported data. The identified cannabinoids were delta9-tetrahydrocannabiorcol, cannabidivarin, cannabicitran, delta9-tetrahydrocannabivarin, cannabicyclol, cannabidiol, cannabichromene, delta9-tetrahydrocannabinol, cannabigerol, cannabinol, dihydrocannabinol, cannabielsoin, 6a, 7, 10a-trihydroxytetrahydrocannabinol, 9, 10-epoxycannabitriol, 10-O-ethylcannabitriol, and 7, 8-dehydro-10-O-ethylcannabitriol.”

http://www.ncbi.nlm.nih.gov/pubmed/15688956

Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation.

Posted on February 27, 2014 by David

“Plant cannabinoids, like Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), activate/desensitize thermosensitive transient receptor potential (TRP) channels of vanilloid type-1 or -2 (TRPV1 or TRPV2). We investigated whether cannabinoids also activate/desensitize two other ‘thermo-TRP’s’, the TRP channels of vanilloid type-3 or -4 (TRPV3 or TRPV4), and if the TRPV-inactive cannabichromene (CBC) modifies the expression of TRPV1-4 channels in the gastrointestinal tract…

CONCLUSIONS:

Cannabinoids can affect both the activity and the expression of TRPV1-4 channels, with various potential therapeutic applications, including in the gastrointestinal tract.”

http://www.ncbi.nlm.nih.gov/pubmed/21726418