Cannabis, cannabidiol, and epilepsy – From receptors to clinical response.

Posted on by

“The use of cannabis for medicinal purposes is becoming more prevalent.

For this purpose, various preparations of cannabis of varying strengths and content are being used.

The recent changes in the legal environment have improved the availability of products with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) concentrations.

There is some anecdotal evidence of their potential efficacy, but the mechanisms of such action are not entirely clear.

Some suspect an existence of synergy or “entourage effect” between CBD and THC.

There is strong evidence that THC acts via the cannabinoid receptor CB1.

The mechanism of action of CBD is less clear but is likely polypharmacological.

The scientific data support the role of the endocannabinoid system in seizure generation, maintenance, and control in animal models of epilepsy.

There are clear data for the negative effects of cannabis on the developing and mature brain though these effects appear to be relatively mild in most cases.

Further data from well-designed studies are needed regarding short- and long-term efficacy and side effects of CBD or high-CBD/low-THC products for the treatment of seizures and epilepsy in children and adults.”

http://www.ncbi.nlm.nih.gov/pubmed/25282526

http://www.thctotalhealthcare.com/category/epilepsy-2/

Type-2 cannabinoid receptor regulates proliferation, apoptosis, differentiation, and OPG/RANKL ratio of MC3T3-E1 cells exposed to Titanium particles.

Posted on by

“The type-2 cannabinoid receptor (CB2) is expressed in osteoblasts and plays a role in bone metabolism through regulation on bone mass and bone turnover, but the functional importance of CB2 in osteoblasts under Titanium (Ti) stimulation is incompletely understood.

This study aimed to investigate the CB2 expression in osteoblasts under Ti stimulation and the effects of CB2 activation on proliferation, apoptosis, differentiation, mineralization, OPG, and RANKL expression of MC3T3-E1 cells exposed to Ti particles…

In conclusion, CB2 activation has a favorable inhibitory effect on Ti-induced reactions in MC3T3-E1 cell through modulating proliferation, apoptosis, differentiation, and RANKL expression.

These findings suggest that activation of CB2 might be an effective therapeutic strategy to promote bone formation and reduce bone dissolution.”

http://www.ncbi.nlm.nih.gov/pubmed/25292314

Intraocular pressure, ocular toxicity and neurotoxicity after administration of cannabinol or cannabigerol.

Posted on by

“Cannabinol or cannabigerol was administered to cats topically in doses of 250, 500 and 1000 micrograms as a single drop or chronically via osmotic minipumps (20 micrograms hr-1) over a period of 9 days. While cannabinol had a modest effect on intraocular pressure after a single dose, it caused a more significant reduction in ocular tension during chronic administration. Cannabigerol had similar effects, but the magnitude of response to its chronic administration was greater. Cannabinol but not cannabigerol caused conjunctival erythema and hyperemia. After systemic administration of cannabinol (20, 40 or 80 mg kg-1) to rats, 8-13 Hz polyspike discharges appeared in the electrocorticogram during wakefulness and during rapid eye movement sleep episodes. Cannabigerol (10, 30 and 100 mg kg-1) lacked this effect.

These results indicate that chronic administration of these cannabinoids lowers ocular tension considerably.

Like marihuana and delta-9-tetrahydrocannabinol, cannabinol produced both ocular toxicity and neurotoxicity. As cannabigerol lacked these toxicities, it appears that the ocular hypotensive effect of this cannabinoid is somewhat dissociable from both the adverse central and ocular effects accompanying marihuana intake.”

http://www.ncbi.nlm.nih.gov/pubmed/6499952

A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol.

Posted on by

“Both delta 9-tetrahydrocannabinol (delta 9-THC) and cannabigerol, two naturally occurring marihuana cannabinoids, produced only a modest fall in intraocular pressure after acute topical application to the eyes of cats.

After chronic administration unilaterally to the cornea via Alzet osmotic minipumps and connecting extraocular cannulas, however, a considerable fall in ocular tension amounting to 4 to 7 mm Hg occurred. After systemic administration of delta 9-THC to rats, polyspike discharges appeared in the cortical electroencephalogram initially during wakefulness and behavioral depression. These polyspikes subsequently became evident within rapid eye movement sleep episodes. Cannabigerol was devoid of this effect. After removal of either sympathetic or parasympathetic input to the eyes of cats, the intraocular pressure lowering effect of delta 9-THC was not changed. Neither delta 9-THC nor cannabigerol altered the rate of formation of aqueous humor. On the other hand, both cannabinoids produced a two-to three-fold increase in aqueous outflow facility.

These results suggest that cannabigerol and related cannabinoids may have therapeutic potential for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pubmed/1965836

Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells.

Posted on by

“Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells.

Abstract

Geraniol (1), olivetol (2), cannabinoids (3 and 4) and 5-fluorouracil (5) were tested for their growth inhibitory effects against human oral epitheloid carcinoma cell lines (KB) and NIH 3T3 fibroblasts using two different 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay.

Cannabigerol (3) exhibited the highest growth-inhibitory activity against the cancer cell lines.”

http://www.ncbi.nlm.nih.gov/pubmed/9875457

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

Antiestrogenic effects of marijuana smoke condensate and cannabinoid compounds.

Posted on by

“The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, ie., delta9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated…

The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity.

This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use.”

http://www.ncbi.nlm.nih.gov/pubmed/16392670

“Antiestrogen treatment of breast cancer: an overview.”  http://www.ncbi.nlm.nih.gov/pubmed/7044524

“Newly Found Estrogen Pathway Suggests Novel Breast Cancer Targets”   http://www.genengnews.com/gen-news-highlights/newly-found-estrogen-pathway-suggests-novel-breast-cancer-targets/81250405/

“New Estrogen Mechanism Holds Novel Cancer Treatment Promise”
http://www.counselheal.com/articles/11565/20140929/new-estrogen-mechanism-holds-novel-cancer-treatment-promise.htm

“CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen.”  http://www.ncbi.nlm.nih.gov/pubmed/24148245

“Scientists discover new role estrogen plays in cancer growth”  http://www.nydailynews.com/life-style/health/scientists-discover-new-role-estrogen-plays-cancer-growth-article-1.1957877

“Antiestrogen-induced remissions in stage IV breast cancer.”  http://www.ncbi.nlm.nih.gov/pubmed/1021225

“Antiestrogenic effects of marijuana smoke condensate and cannabinoid compounds.”  http://www.ncbi.nlm.nih.gov/pubmed/16392670

“New estrogen-related breast cancer mechanism detected”   http://www.medicalnewstoday.com/articles/283168.php

“Δ(9)-tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action… Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects).”  http://www.ncbi.nlm.nih.gov/pubmed/25177025

“Anti-Estrogen Drugs to Treat Breast Cancer”  http://www.fccc.edu/cancer/types/breast/treatment/hormonal/anti-estrogen.html

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

 

Advances in the Management of MS Spasticity: Recent Observational Studies.

Posted on by

“Clinical trials demonstrate the efficacy and tolerability of an intervention under experimental conditions, but information on use under daily practice conditions is required to confirm the effectiveness and safety of new management options.

Clinical outcomes for THC:CBD oromucosal spray (Sativex®) in patients with treatment-resistant MS spasticity have been collected in post-marketing safety registries from the UK and Germany, a safety study from Spain and two observational studies from Germany, including one investigating its effects on driving ability.

Collectively, findings from daily practice support the long-term effectiveness and safety of THC:CBD oromucosal spray.

There was no evidence of abuse/misuse or other adverse events of special interest with a cannabis-based medicine and no impairment of driving ability.

Observational data and real world experience reinforce the efficacy and safety of THC:CBD oromucosal spray as reported in phase III clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/25278118

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Advances in the management of multiple sclerosis spasticity: recent clinical trials.

Posted on by

“Most patients with multiple sclerosis (MS) experience spasticity as the clinical course evolves. Associated symptoms include (often painful) spasms, urinary dysfunction and sleep disturbances. THC:CBD oromucosal spray (Sativex®) is approved for symptom improvement in adult patients with moderate to severe MS-related spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

SUMMARY:

In pivotal clinical trials of THC:CBD oromucosal spray, a meaningful proportion of patients with treatment-resistant MS spasticity achieved clinically relevant improvement with active treatment versus placebo. The utility of a 4-week trial of therapy to identify patients who respond to treatment was demonstrated in an enriched-design study.

THC:CBD oromucosal spray was well tolerated in these studies, with no evidence of effects typically associated with recreational cannabis use.

In a subsequent post approval clinical trial, THC:CBD oromucosal spray had no statistically significant effect on cognition and mood compared with placebo.

Moreover, after 50 weeks’ treatment, approximately two-thirds of patients, physicians and caregivers reported improvement from baseline in spasticity based on global impressions of change.

In phase III clinical trials, approximately one-third of MS patients with treatment-resistant spasticity had a clinically relevant and statistically significant response to THC:CBD oromucosal spray.

In addition to a reduction in spasticity, responders experienced meaningful relief from associated symptoms.

THC:CBD oromucosal spray was generally well tolerated and efficacy was maintained over the longer term.

A post-approval clinical trial indicated no effect of THC:CBD oromucosal spray on cognition or mood after 50 weeks of use.”

http://www.ncbi.nlm.nih.gov/pubmed/25278117

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity nervous pathways.

Posted on by

“Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS…

Evidence indicates that the antispasticity effects of THC:CBD oromucosal spray (Sativex®) are associated with enhanced cortical long-term potentiation.

CB1 receptors, which are associated with movement, postural control, and pain and sensory perception, influence glutamatergic pathways.

THC:CBD oromucosal spray was shown to reverse motor cortex plasticity from long-term depression through long-term potentiation of synaptic transmission, thereby restoring, at least in part, effective corticospinal inputs to spinal circuits.”

http://www.ncbi.nlm.nih.gov/pubmed/25278116

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabinoids Alleviate Experimentally Induced Intestinal Inflammation by Acting at Central and Peripheral Receptors.

Posted on by

“… an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases…

CONCLUSIONS:

This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis.

Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.”

http://www.ncbi.nlm.nih.gov/pubmed/25275313