Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity.

“The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients.

The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting.


Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.”


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A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease.

“Huntington’s disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD.

We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex®, a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex® and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks.

The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores.

Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p = 0.286), cognitive (p = 0.824), behavioral (p = 1.0) and functional (p = 0.581) scores were detected during treatment with Sativex® as compared to placebo. No significant molecular effects were detected on the biomarker analysis.

Sativex® is safe and well tolerated in patients with HD, with no SAE or clinical worsening.

No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers.

Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations. Clincaltrals.gov identifier: NCT01502046.”


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Evidences for the anti-panic actions of Cannabidiol.

“Panic disorder (PD) is a disabling psychiatry condition that affects approximately 5% of the worldwide population. Currently, long-term selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PD; however, the common side-effect profiles and drug interactions may provoke patients to abandon the treatment, leading to PD symptoms relapse.

Cannabidiol (CBD) is the major non-psychotomimetic constituent of the Cannabis sativa plant with anti-anxiety properties that has been suggested as an alternative for treating anxiety disorders.

In the present chapter, we included both experimental laboratory animal and human studies that have investigated the putative anti-panic properties of CBD.

Taken together, the studies assessed in the present chapter clearly suggest an anxiolytic-like effect of CBD in both animal models and healthy volunteers.

Novel clinical trials involving patients with the PD diagnosis, however, are clearly needed to clarify the specific mechanism of action of CBD and the safe and ideal therapeutic doses of this compound.”


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Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway.

“Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes.

Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses.

Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.


The cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia.

However, the mechanisms by which CBD may produce antipsychotic effects are entirely unknown. Using preclinical behavioral procedures combined with molecular analyses and in vivo neuronal electrophysiology, our findings identify a functional role for the nucleus accumbens as a critical brain region whereby CBD can produce effects similar to antipsychotic medications by triggering molecular signaling pathways associated with the effects of classic antipsychotic medications.

Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via a direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.”



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[Study on the extraction process for cannabinoids in hemp seed oil by orthogonal design].

“OBJECTIVE: To select the optimum extracting procedure for cannabinoids from hemp seed oil.

METHODS: The optimum extracting procedure was selected with the content of cannabinol and delta9-tetrehydrocannabinol from hemp seed oil by orthogonal test design. We have examined three factors that may influence the extraction rate: the time of extraction, the times of extraction and the amount of methanol.

RESULTS: The optimum extraction condition was adding 5 ml, two times amount of methanol into hemp seed oil for 15 min.

CONCLUSION: The above extraction process gave the most rational, stable, feasible and satisfactory results. The method is convenient.”


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Study: Cannabinoids Limit Neuroblastoma Cell Proliferation

Study: Cannabinoids Limit Neuroblastoma Cell Proliferation

“The administration of the cannabinoids THC and CBD limit cancer activity in neuroblastoma cells in culture and in animals, according to preclinical data published in the journal Current Oncology.

Neuroblastoma is an aggressive form of childhood cancer that often goes inadequately addressed by conventional treatment.

Investigators reported that both types of cannabinoids reduced neuroblastoma cell viability, but that CBD demonstrated superior anti-cancer ability. The study is the first to document the anti-cancer properties of CBD in this particular cancerous cell line.

They concluded, “Our findings about the activity of CBD in nbl (neuroblastoma) support and extend previous findings about the anti-tumor activities of CBD in other tumors and suggest that cannabis extracts enriched in CBD and not in THC could be suitable for the development of novel non-psychotropic therapeutic strategies in nbl.”  http://enewspf.com/2016/04/21/study-cannabinoids-limit-neuroblastoma-cell-proliferation/

“In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791143/?report=reader

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Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice.

“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans.

It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson’s patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal disorders.

To investigate this possibility we evaluated if CBD would prevent catalepsy induced by drugs with distinct pharmacological mechanisms.

These findings indicate that CBD can attenuate catalepsy caused by different mechanisms (D2 blockade, NOS inhibition and CB1 agonism) via 5-HT1A receptor activation, suggesting that it could be useful in the treatment of striatal disorders.”


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Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

“Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant.

Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic.

In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol.

Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors.”


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A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.

“Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain.

A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers.

The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed.

Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day.

In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies.”


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Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrheic skin and acne treatment.

“Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands.

We have previously shown that a non-psychotropic phytocannabinoid ((-)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing “pro-acne agents”-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes.

Therefore, in the current study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], (-)-cannabigerol [CBG], (-)-cannabigerovarin [CBGV] and (-)-Δ9 -tetrahydrocannabivarin [THCV]).

Viability and proliferation of human SZ95 sebocytes were investigated by MTT- and CyQUANT-assays; cell death and lipid synthesis were monitored by DilC1 (5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 μM, the phytocannabinoids only negligibly altered viability of the sebocytes, whereas high doses (≥50 μM) induced apoptosis.

Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, CBDV had only minor effects, whereas CBG and CBGV increased it.

Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced “acne-like” lipogenesis.

Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions.

Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents.

Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.”



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