A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia.

Posted on November 27, 2016 by David

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“Cognitive impairment is a core symptom domain of schizophrenia, neurological disorders and substance abuse. It is characterised by deficits in learning, memory, attention and executive functioning and can severely impact daily living.

Antipsychotic drugs prescribed to treat schizophrenia provide limited cognitive benefits and novel therapeutic targets are required. Cannabidiol (CBD), a component of the cannabis plant, has anti-inflammatory and antipsychotic-like properties; however, its ability to improve cognitive impairment has not been thoroughly explored. The aim of this systematic review was to evaluate preclinical and clinical literature on the effects of CBD in cognitive domains relevant to schizophrenia.

CBD improves cognition in multiple preclinical models of cognitive impairment, including models of neuropsychiatric (schizophrenia), neurodegenerative (Alzheimer’s disease), neuro-inflammatory (meningitis, sepsis and cerebral malaria) and neurological disorders (hepatic encephalopathy and brain ischemia). To-date, there is one clinical investigation into the effects of CBD on cognition in schizophrenia patients, with negative results for the stroop test. CBD attenuates Δ⁹-THC-induced cognitive deficits.

The efficacy of CBD to improve cognition in schizophrenia cannot be elucidated due to lack of clinical evidence; however, given the ability of CBD to restore cognition in multiple studies of impairment, further investigation into its efficacy in schizophrenia is warranted. Potential mechanisms underlying the efficacy of CBD to improve cognition are discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/27884751

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

Posted on November 25, 2016 by David

“There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds.

The endocannabinoid system has been suggested to represent a potential new target in this indication.

Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys.

After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile.

As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations.

The antipsychotic potential of cannabidiol has been investigated in various behavioral paradigms and different animal models of aspects of schizophrenia.

Although the results were partially inconsistent, they indicate that cannabidiol treatment ameliorates impairments of PPI, social interaction behavior and cognition in rodents and rhesus monkeys.

In addition, individual treatment attempts as well as one randomized, double-blind clinical study, demonstrated the antipsychotic potential of cannabidiol and its superior side effect profile compared to conventional antipsychotics. In addition, a recently conducted clinical trial investigating cannabidiol as an add-on medication showed promising results, although these have not yet been published in a peer reviewed process.

Obviously more clinical trials are needed to substantiate the current findings, and in particular to investigate long-term efficacy and safety in larger cohorts.

However, cannabidiol seems to represent a mechanistically different and less side-effect prone antipsychotic compound for the treatment of schizophrenia, even though the underlying pharmacological mechanisms are still under debate.

Nevertheless, the association between increased anandamide levels and reduced psychotic symptoms in schizophrenic patients treated with cannabidiol, points to a potentially new antipsychotic mechanism of action involving anandamide.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099166/

Cannabidiol Mellows Out Resurgent Sodium Current

Posted on November 22, 2016 by David

“Cannabidiol has received abundant media attention as a potential therapy for intractable epilepsy, based mainly on anecdotal evidence.

These findings suggest that cannabidiol could be exerting its anticonvulsant effects, at least in part, through its actions on voltage-gated sodium channels, and resurgent current may be a promising therapeutic target for the treatment of epilepsy syndromes.”

http://www.epilepsycurrents.org/doi/full/10.5698/1535-7511-16.6.399

Anti-excitotoxic effects of cannabidiol are partly mediated by enhancement of NCX2 and NCX3 expression in animal model of cerebral ischemia.

Posted on November 20, 2016 by David

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“Excitotoxicity and imbalance of sodium and calcium homeostasis trigger pathophysiologic processes in cerebral ischemia which can accelerate neuronal death.

Neuroprotective role of cannabidiol (CBD), one of the main non-psychoactive phytocannabinoids of the cannabis plant, has attracted attention of many researchers in the neurodegenerative diseases studies.

The present investigation was designed to determine whether cannabidiol can alleviate the severity of ischemic damages and if it is able to exert its anti-excitotoxic effects through sodium and calcium regulation.

The present results indicate that administration of cannabidiol (100 and 200 ng/rat) in the MCAO-induced cerebral ischemia caused a remarkable reduction in neurological deficit, infarction, brain edema, and BBB permeability in comparison with the vehicle group. Up-regulation of NCX2 and NCX3 in cannabidiol-received groups was also observed.

These findings support the view that the reduction of ischemic injuries elicited by cannabidiol can be at least partly due to the enhancement of NCX protein expression and its cerebro-protective role in those cerebral territories supplied by MCA.”

https://www.ncbi.nlm.nih.gov/pubmed/27856160

Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice.

Posted on November 11, 2016 by David

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“Tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) is an add-on therapy for moderate-to-severe multiple sclerosis (MS)-related drug-resistant spasticity (MSS).

In everyday clinical practice, THC:CBD oromucosal spray provided symptomatic relief of MSS and related troublesome symptoms.”

https://www.ncbi.nlm.nih.gov/pubmed/27732980

Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

Posted on November 10, 2016 by David

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“Evidence suggests that the non-psychotropic cannabis-derived compound, cannabidiol (CBD), has anti-neoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM).

DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM.

Here we studied the anti-proliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures.

This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system (CNS) toxicity.

We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells.

Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells.

Co-treatment regiments combining CBD and DNA-damaging agents produced synergistic anti-proliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs.

Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells.

Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little-to-no therapeutic window when considering NPCs.”

https://www.ncbi.nlm.nih.gov/pubmed/27821713

“Definition of antineoplastic: inhibiting or preventing the growth and spread of tumors or malignant cells” http://www.merriam-webster.com/dictionary/antineoplastic

Targeting the Endocannabinoid System in Psychiatric Illness.

Posted on November 5, 2016 by David

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“Prevalence of psychiatric disorders continues to rise globally, yet remission rates and patient outcome remain less than ideal. As a result, novel treatment approaches for these disorders are necessary to decrease societal economic burden, as well as increase individual functioning.

The recent discovery of the endocannabinoid system has provided an outlet for further research into its role in psychiatric disorders, because efficacy of targeted treatments have been demonstrated in medical illnesses, including cancers, neuropathic pain, and multiple sclerosis.

The present review will investigate the role of the endocannabinoid system in psychiatric disorders, specifically schizophrenia, depressive, anxiety, and posttraumatic stress disorders, as well as attention-deficit hyperactivity disorder.

Controversy remains in prescribing medicinal cannabinoid treatments due to the fear of adverse effects. However, one must consider all potential limitations when determining the safety and tolerability of cannabinoid products, specifically cannabinoid content (ie, Δ-tetrahydrocannabinol vs cannabidiol) as well as study design.

The potential efficacy of cannabinoid treatments in the psychiatric population is an emerging topic of interest that provides potential value going forward in medicine.”

https://www.ncbi.nlm.nih.gov/pubmed/27811555

Cannabinoids, inflammation, and fibrosis.

Posted on November 3, 2016 by David

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“Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs).

As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis.

A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ⁹-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented.

The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed.

The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances.

Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents.

Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.”

https://www.ncbi.nlm.nih.gov/pubmed/27435265

Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis.

Posted on October 29, 2016 by David

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“Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine.

Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects.

Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation.

Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.

The results of the present study correlate and expand the findings suggesting CBD as a potent compound that is able to modulate experimental gut inflammation.

In this study we demonstrate that during intestinal inflammation, CBD is able to control the inflammatory scenario and the subsequent intestinal apoptosis through the restoration of the altered glia-immune homeostasis.

CBD is therefore regarded as a promising therapeutic agent that modulates the neuro-immune axis, which can be recognised as a new target in the treatment of inflammatory bowel disorders.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190/

Cortical and spinal excitability in patients with multiple sclerosis and spasticity after oromucosal cannabinoid spray.

Posted on October 25, 2016 by David

“Delta-9-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) has been recently approved for the management of treatment-resistant multiple sclerosis (MS) spasticity.

Although the symptomatic relief of Sativex® on MS-spasticity has been consistently demonstrated, the pathogenetic implications remain unclear and the few electrophysiological studies performed to address this topic yielded controversial results.

We therefore aimed to investigate the mechanisms underpinning the modulation of spastic hypertonia by Sativex®, at both central and spinal levels, through an extensive neurophysiological battery in patients with MS.

Our results confirm the clinical benefit of Sativex® on spastic hypertonia and demonstrate that it might modulate both cortical and spinal circuits, arguably in terms of both excitation and inhibition.

We suggest that the clinical benefit was likely related to a net increase of inhibition at cortical level that, in turn, might have influenced spinal excitability.”

https://www.ncbi.nlm.nih.gov/pubmed/27772772

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