The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells.

Posted on April 21, 2014 by David

“…there is considerable interest in therapeutics that can modulate survival signalling pathways and target cancer cells for death. There is emerging evidence that cannabinoids, especially Delta(9)-tetrahydrocannabinol (THC), may represent novel anticancer agents, due to their ability to regulate signalling pathways critical for cell growth and survival.

Here, we report that CB1 and CB2 cannabinoid receptors are expressed in human colorectal adenoma and carcinoma cells, and show for the first time that THC induces apoptosis in colorectal cancer cells…

The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17583570

http://www.thctotalhealthcare.com/category/colon-cancer/

Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells to extracellular matrix proteins.

Posted on April 21, 2014 by David

“The aim of this study was to assess the effect of select cannabinoids on human immunodeficiency virus type 1 (HIV-1) transactivating (Tat) protein-enhanced monocyte-like cell adhesion to proteins of the extracellular matrix (ECM)…

KEY FINDINGS:

THC and CP55,940 inhibited Tat-enhanced attachment of U937 cells to ECM proteins in a mode that was linked to the cannabinoidreceptor type 2 (CB2R). The cannabinoid treatment of Tat-activated U937 cells was associated with altered β1-integrin expression and distribution of polymerized actin, suggesting a modality by which these cannabinoids inhibited adhesion to the ECM.

SIGNIFICANCE:

The blood-brain barrier (BBB) is a complex structure that is composed of cellular elements and an extracellular matrix (ECM). HIV-1 Tat promotes transmigration of monocytes across this barrier, a process that includes interaction with ECM proteins.

The results indicate that cannabinoids that activate the CB2R inhibit the ECM adhesion process. Thus, this receptor has potential to serve as a therapeutic agent for ablating neuroinflammation associated with HIV-elicited influx of monocytes across the BBB.”

http://www.ncbi.nlm.nih.gov/pubmed/24742657

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

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure.

Posted on April 8, 2014 by David

“Recent changes in the legality of cannabis have prompted evaluation of whether blood levels of Δ9-tetrahydrocannabinol (THC) or its metabolites could be used to substantiate impairment, particularly related to behavioral tasks such as driving…

These data indicate that thresholds for blood levels of THC do not provide a consistent index of behavioral impairment across individuals with different patterns of THC exposure.”

http://www.ncbi.nlm.nih.gov/pubmed/24703610

Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences.

Posted on April 7, 2014 by David

“Δ9-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in fat tissue where it can remain for prolonged periods.

Under conditions of increased fat utilisation, blood cannabinoid concentrations can increase.

These results confirm that fasting and exercise can increase plasma cannabinoid levels…”

http://www.ncbi.nlm.nih.gov/pubmed/24696079

The detection of THC, CBD and CBN in the oral fluid of Sativex® patients using two on-site screening tests and LC-MS/MS.

Posted on April 7, 2014 by David

“Sativex® is an oromucosal spray used to treat spasticity in multiple sclerosis sufferers in some European countries, the United Kingdom, Canada and New Zealand. The drug has also recently been registered by the Therapeutic Goods Administration (TGA) in Australia for treatment of multiple sclerosis.

Sativex® contains high concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with the former being the subject of random roadside drug tests across Australia to detect cannabis use.

This pilot study aims to determine whether or not patients taking Sativex® will test positive to THC using these roadside screening tests. Detectable levels of THC, CBD and cannabinol (CBN) in their oral fluid were also confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study was a double-blind, placebo controlled design.

In conclusion, Sativex® users may test positive for THC by roadside drug testing within 2-3h of use. Confirmatory analysis can identify Sativex® treatment through use of THC/CBD ratios, however, these ratios would unlikely be sufficient to differentiate non-medicinal cannabis use from Sativex® use if both are taken concurrently.”

http://www.ncbi.nlm.nih.gov/pubmed/24699310

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

Posted on April 7, 2014 by David

“For centuries Cannabis sativa and cannabis extracts have been used in natural medicine.

Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis.

In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma.

Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications.

The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/19832688

Memory Loss From Marijuana Blocked By Ibuprofen; Drug Duo May Halt Alzheimer’s Progression

Posted on April 7, 2014 by David

marijuanachart

“Marijuana’s primary side-effect as a medicine — memory loss — may soon become all but forgotten.

In a stunningly simple turn, investigators found that a simple over-the-counter painkiller, such as ibuprofen, blocks memory loss from the drug’s active ingredient, delta-9-tetrahydrocannabinol (THC). The drug combination may also prevent neurological damage from Alzheimer’s Disease, opening possibilities too for the treatment of a variety of other diseases and conditions.

Nearly five millennia into the history of medical marijuana, investigators from Louisiana State University Health Sciences Center say they’ve found a way to strip marijuana’s most deleterious side effect. The discovery may prompt U.S. regulators to soon approve marijuana-based treatments for ailments beyond nausea and vomiting in chemotherapy patients.”

http://www.medicaldaily.com/memory-loss-marijuana-blocked-ibuprofen-drug-duo-may-halt-alzheimers-progression-263443

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

Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes.

Posted on March 31, 2014 by David

“Inhibitory effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabidiol (CBD), and cannabinol (CBN), the three major constituents in marijuana, on catalytic activities of human cytochrome P450 (CYP) 1 enzymes were investigated.

These results indicated that CBD and CBN showed CYP1 isoform-selective direct inhibition and that CBD was characterized as a potent mechanism-based inhibitor of human CYP1 enzymes, especially CYP1A1.”

http://www.ncbi.nlm.nih.gov/pubmed/20117100

“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

Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: Report of the Guideline Development Subcommittee of the American Academy of Neurology.

Posted on March 26, 2014 by David

“Clinicians might offer oral cannabis extract for spasticity symptoms and pain (excluding central neuropathic pain) (Level A). Clinicians might offer tetrahydrocannabinol for spasticity symptoms and pain (excluding central neuropathic pain) (Level B). Clinicians should counsel patients that these agents are probably ineffective for objective spasticity (short-term)/tremor (Level B) and possibly effective for spasticity and pain (long-term) (Level C). Clinicians might offer Sativex oromucosal cannabinoid spray (nabiximols) for spasticity symptoms, pain, and urinary frequency (Level B). Clinicians should counsel patients that these agents are probably ineffective for objective spasticity/urinary incontinence (Level B). Clinicians might choose not to offer these agents for tremor (Level C). Clinicians might counsel patients that magnetic therapy is probably effective for fatigue and probably ineffective for depression (Level B); fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life (QOL) (Level B); ginkgo biloba is ineffective for cognition (Level A) and possibly effective for fatigue (Level C); reflexology is possibly effective for paresthesia (Level C); Cari Loder regimen is possibly ineffective for disability, symptoms, depression, and fatigue (Level C); and bee sting therapy is possibly ineffective for relapses, disability, fatigue, lesion burden/volume, and health-related QOL (Level C)…”

http://www.ncbi.nlm.nih.gov/pubmed/24663230