Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: Role of 5-HT1A receptors.

“Cannabidiol (CBD), the main non-psychotomimetic component of marihuana…

…we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression…

In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism.”

http://www.ncbi.nlm.nih.gov/pubmed/26711860

Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN-55,212-2

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“Osteosarcoma is the most frequent primary malignant bone tumor that occurs in children and adolescents. Osteosarcoma is a bone malignancy that predominantly affects children and adolescents, and exhibits high invasion and metastasis rates.

Although adriamycin (ADM) is an effective benchmark agent for the management of osteosarcoma, it also results in harmful side-effects including toxicity and chemoresistance that substantially affect the quality of life of patients. Therefore, novel therapeutic approaches and drugs must be sought for the treatment of osteosarcoma.

Natural products which have potential antitumor activities have become a focus of attention for study in previous years. Cannabinoids, the active components naturally derived from the marijuana plant Cannabis sativa L., have been reported as potential antitumor drugs based on their ability to limit inflammation, cell proliferation and cell survival.

To date, several cannabinoids have been identified and characterized, including Δ(9)-tetrahydrocannabinol (THC), cannabidiol, cannabinol (CBN) and anandamide, as well as synthetic cannabinoids, including WIN-55,212-2, JWH-133 and (R)-methanandamide.

In the early 1970s, THC and CBN were shown to inhibit tumor growth in Lewis lung carcinoma. Subsequently, cannabinoids were found to induce apoptosis and inhibit the proliferation of various cancer cells, including those of glioma and lymphoma, and prostate, breast, skin and pancreatic cancer…

In conclusion, the present study indicated that cannabinoid WIN-55,212-2 is antiproliferative, antimetastatic and antiangiogenic against MG-63 cells in vitro, and presented evidence that cannabinoid WIN-55,212-2 may result in synergistic antitumor action in combination with ADM against osteosarcoma.

These findings may offer a novel strategy for the treatment of osteosarcoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580018/

Long-Term Data of Efficacy, Safety and Tolerability in a Real Life Setting of THC/CBD Oromucosal Spray-Treated Multiple Sclerosis Patients.

“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was approved as add-on therapy for spasticity in patients with Multiple Sclerosis (MS).

We showed our forty-weeks post-marketing experience regarding efficacy and safety of THC/CBD spray in an Italian cohort of 102 MS patients…

In conclusion, treatment with THC/CBD spray appears to be a valid answer to some of the unmet needs in MS patients, such as spasticity and other refractory-to-treatment symptoms. “

http://www.ncbi.nlm.nih.gov/pubmed/26608223

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

A Sativex(®) -like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis.

“Sativex(®) is an oromucosal spray, containing equivalent amounts of Δ(9) -tetrahydrocannabinol (Δ(9) -THC) and cannabidiol (CBD)-botanical drug substance (BDS), which has been approved for the treatment of spasticity and pain associated to multiple sclerosis (MS).

In this study, we investigated whether Sativex may also serve as a disease-modifying agent in the Theiler’s murine encephalomyelitis virus-induced demyelinating disease model of MS.

The data support the therapeutic potential of Sativex to slow MS progression and its relevance in CNS repair.”

http://www.ncbi.nlm.nih.gov/pubmed/25857324

The disease-modifying effects of a Sativex-like combination of phytocannabinoids in mice with experimental autoimmune encephalomyelitis are preferentially due to Δ9-tetrahydrocannabinol acting through CB1 receptors.

“Sativex®, an equimolecular combination of Δ9-tetrahydrocannabinol-botanical drug substance (Δ9-THC-BDS) and cannabidiol-botanical drug substance (CBD-BDS), is a licensed medicine that may be prescribed for alleviating specific symptoms of multiple sclerosis (MS) such as spasticity and pain.

However, further evidence suggest that it could be also active as disease-modifying therapy given the immunomodulatory, anti-inflammatory and cytoprotective properties of their two major components.

In this study, we investigated this potential in the experimental autoimmune encephalitis (EAE) model of MS in mice.

We compared the effect of a Sativex-like combination of Δ9-THC-BDS (10mg/kg) and CBD-BDS (10mg/kg) with Δ9-THC-BDS (20mg/kg) or CBD-BDS (20mg/kg) administered separately by intraperitoneal administration to EAE mice.

Treatments were initiated at the time that symptoms appear and continued up to the first relapse of the disease.

The results show that the treatment with a Sativex-like combination significantly improved the neurological deficits typical of EAE mice, in parallel with a reduction in the number and extent of cell aggregates present in the spinal cord which derived from cell infiltration to the CNS.

These effects were completely reproduced by the treatment with Δ9-THC-BDS alone, but not by CBD-BDS alone which only delayed the onset of the disease without improving disease progression and reducing the cell infiltrates in the spinal cord.

Next, we investigated the potential targets involved in the effects of Δ9-THC-BDS by selectively blocking CB1 or PPAR-γ receptors, and we found a complete reversion of neurological benefits and the reduction in cell aggregates only with rimonabant, a selective CB1 receptor antagonist.

Collectively, our data support the therapeutic potential of Sativex as a phytocannabinoid formulation capable of attenuating EAE progression, and that the active compound was Δ9-THC-BDS acting through CB1 receptors.”

Effectiveness and Tolerability of THC/CBD Oromucosal Spray for Multiple Sclerosis Spasticity in Italy: First Data from a Large Observational Study.

“The prospective, non-interventional Mobility Improvement (MOVE) 2 study was designed to provide real life data on clinical outcomes of patients with treatment-resistant multiple sclerosis (MS) spasticity receiving routine treatment with tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®), subsequent to its approval in European countries.

In everyday clinical practice in Italy, THC:CBD oromucosal spray provided symptomatic relief of MS spasticity with good tolerability in a relevant number of previously resistant patients.”

http://www.ncbi.nlm.nih.gov/pubmed/26571097

Cannabidiol as potential treatment in refractory pediatric epilepsy.

“In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children.

From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile.

In humans, CBD efficacy and safety is not supported by well designed trials and its use has been described by anecdotal reports.

It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other antiepileptic drugs alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.”

http://www.ncbi.nlm.nih.gov/pubmed/26567560

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

Cannabidiol-2′,6′-dimethyl ether stimulates body weight gain in apolipoprotein E-deficient BALB/c. KOR/Stm Slc-Apoe(shl) mice.

“The biological activities of cannabidiol (CBD), a major non-psychotropic constituent of the fiber-type cannabis plant, have been examined in detail (e.g., CBD modulation of body weight in mice and rats).

However, few studies have investigated the biological activities of cannabidiol-2′,6′-dimethyl ether (CBDD), a dimethyl ether derivative of the parent CBD.

We herein focused on the effects of CBDD on body weight changes in mice, and demonstrated that it stimulated body weight gain in apolipoprotein E (ApoE)-deficient BALB/c. KOR/Stm Slc-Apoe(shl) mice, especially between 10 and 20 weeks of age.”

http://www.ncbi.nlm.nih.gov/pubmed/26558454

The neuroprotection of cannabidiol against MPP+-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson’s disease.

“Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases.

Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved.

We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP+ toxicity in PC12 cells…

This is the first study to report the involvement of neuronal proteins and trkA in the neuroprotection of CBD.

Our findings suggest that CBD has a neurorestorative potential independent of NGF that might contribute to its neuroprotection against MPP+, a neurotoxin relevant to Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26556726

Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells.

“Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages.

Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells…

The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD.

DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26540221