Molecular Imaging of the Cannabinoid System in Idiopathic Parkinson’s Disease.

International Review of Neurobiology

“The endocannabinoid system is a modulator of neurotransmitter release and is involved in several physiological functions. Hence, it has been increasingly studied as a potential pharmacologic target of Parkinson’s disease.

Several preclinical and clinical studies evidenced a substantial rearrangement of the endocannabinoid system in the basal ganglia circuit following dopamine depletion. The endocannabinoid system has been additionally implicated in the regulation of neuroinflammation and neuroprotection through the activation of CB2 receptors, suggesting a potential target for disease modifying therapies in Parkinson’s disease.

In this chapter, current pharmacological and physiological knowledge on the role of the endocannabinoid system will be reviewed, focusing on preclinical studies animal models and clinical studies in patients with idiopathic Parkinson’s disease. The main strategies for imaging the brain cannabinoid system will be summarized to finally focus on in vivo imaging of patients with Parkinson’s disease.”

https://www.ncbi.nlm.nih.gov/pubmed/30314601

https://www.sciencedirect.com/science/article/pii/S0074774218300692?via%3Dihub

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Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age.

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“Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana.

The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry.

CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson.

CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.”

https://www.ncbi.nlm.nih.gov/pubmed/30298064

https://www.frontiersin.org/articles/10.3389/fimmu.2018.02009/full

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Cannabinoids in depressive disorders.

 Life Sciences “Cannabis sativa is one of the most popular recreational and medicinal plants. Benefits from use of cannabinoid agents in epilepsy, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and others have been suggested. It seems that the endocannabinoid system is also involved in the pathogenesis and treatment of depression, though its role in this mental disease has not been fully understood yet. Both the pro- and antidepressant activity have been reported after cannabis consumption and a number of pre-clinical studies have demonstrated that both agonist and antagonist of the endocannabinoid receptors act similarly to antidepressants. Responses to the cannabinoid agents are relatively fast, and most probably, the noradrenergic, serotoninergic, glutamatergic neurotransmission, neuroprotective activity, as well as modulation of the hypothalamic-pituitary-adrenal axis are implicated in the observed effects. Based on the published data, the endocannabinoid system evidently gives novel ideas and options in the field of antidepressant treatment, however further studies are needed to determine which group of patients could benefit from this type of therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/30290188

https://www.sciencedirect.com/science/article/pii/S0024320518306040?via%3Dihub

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A systematic review on the neuroprotective perspectives of beta-caryophyllene.

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“Beta (β)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect.

This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords “beta (β)-caryophyllene” and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action.

A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer’s disease.

Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.”

https://www.ncbi.nlm.nih.gov/pubmed/30281175

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

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Cannabinoid 1 Receptor Signaling on Hippocampal GABAergic Neurons Influences Microglial Activity.

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“Microglia, the resident immune cells of the brain, play important roles in defending the brain against pathogens and supporting neuronal circuit plasticity. Chronic or excessive pro-inflammatory responses of microglia damage neurons, therefore their activity is tightly regulated.

Pharmacological and genetic studies revealed that cannabinoid type 1 (CB1) receptor activity influences microglial activity, although microglial CB1 receptor expression is very low and activity-dependent. The CB1 receptor is mainly expressed on neurons in the central nervous system (CNS)-with an especially high level on GABAergic interneurons.

Here, we determined whether CB1 signaling on this neuronal cell type plays a role in regulating microglial activity.

Our result suggests that CB1 receptor agonists can modulate microglial activity indirectly, through CB1 receptors on GABAergic neurons.

Altogether, we demonstrated that GABAergic neurons, despite their relatively low density in the hippocampus, have a specific role in the regulation of microglial activity and cannabinoid signaling plays an important role in this arrangement.”

https://www.ncbi.nlm.nih.gov/pubmed/30210289

https://www.frontiersin.org/articles/10.3389/fnmol.2018.00295/full

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Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload.

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“Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats.

In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction.

Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed.

These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.”

“In summary, we have shown that iron treatment in the neonatal period disrupts the apoptotic intrinsic pathway. This finding may place iron excess as a central component in neurodegenerative processes since many neurodegenerative disorders are accompanied by iron accumulation in brain regions. Moreover, indiscriminate iron supplementation to toddlers and infants, modeled here by iron overload in the neonatal period, has been considered a potential environmental risk factor for the development of neurodegenerative disorders later in life. Our findings also strongly suggest that CBD has neuroprotective effects, at least in part by blocking iron-induced apoptosis even at later stages, following iron overload, which puts CBD as a potential therapeutic agent in the treatment of neurodegenerative diseases.”
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Cannabis cures the spine.

The Journal of Thoracic and Cardiovascular Surgery Home

“Cannabis cures the spine.” https://www.ncbi.nlm.nih.gov/pubmed/30172587

“Huo and colleagues elegantly demonstrate that the endogenous cannabinoid system can be modulated to provide neuroprotection in ischemic injury of the spine.

Modulation of the endocannabinoid system attenuates ischemic spinal cord injury through CB2-mediated inhibition of the GAPDH/Siah1 signaling cascade, positively influencing neuron survival and function.” https://www.jtcvs.org/article/S0022-5223(18)32080-4/fulltext

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Anticonvulsant and Neuroprotective Effects of Cannabidiol During the Juvenile Period.

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“Anticonvulsant effects of cannabidiol (CBD), a nonpsychoactive cannabinoid, have not been investigated in the juvenile brain. We hypothesized that CBD would attenuate epileptiform activity at an age when the brain first becomes vulnerable to neurotoxicity and social/cognitive impairments.

To induce seizures, kainic acid (KA) was injected either into the hippocampus (KAih) or systemically (KAip) on postnatal (P) day 20. CBD was coadministered (KA + CBDih, KA + CBDip) or injected 30 minutes postseizure onset (KA/CBDih, KA/CBDip).

Hyperactivity, clonic convulsions, and electroencephalogram rhythmic oscillations were attenuated or absent after KA + CBDih and reduced after KA + CBDip. NeuN immunohistochemistry revealed neuroprotection.

Augmented reactive glia number and expression were reversed in CA1 but persisted deep within the dentate hilus. Parvalbumin-positive (PV+) interneurons were reduced in both models, whereas immunolabeling was dramatically increased within ipsilateral and contralateral dendritic/neuropilar fields following KA + CBDih. Cannabinoid receptor 1 (CB1) expression was minimally affected after KAih contrasting elevations observed after KAip.

Intracranial coadministration data suggest that CBD has higher efficacy in epilepsy with hippocampal focus rather than when extrahippocampal amygdala/cortical structures are triggered by systemic treatments. Inhibition of surviving PV+ and CB1+ interneurons may be facilitated by CBD implying a protective role in regulating hippocampal seizures and neurotoxicity at juvenile ages.”

https://www.ncbi.nlm.nih.gov/pubmed/30169677

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Variability of Multiple Sclerosis Spasticity Symptoms in Response to THC:CBD Oromucosal Spray: Tracking Cases through Clinical Scales and Video Recordings.

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“Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune demyelinating disease of the central nervous system. Patients exhibit heterogeneous patterns of disabling symptoms, including spasticity. In the majority of patients with MS spasticity, it and its associated symptoms contribute to disability, interfere with performance of everyday activities, and impair quality of life. Even under treatment with oral antispasticity drugs, about a third of patients continue to experience spasticity of moderate to severe intensity, underscoring the need for additional treatment options.

The efficacy of tetrahydrocannabinol: cannabidiol (THC:CBD) oromucosal spray as add-on therapy in patients with refractory MS spasticity has been demonstrated in clinical trials and observational studies.

To gain insight into patients’ response to treatment at the individual level, in-depth changes from baseline in various clinical scales and video-assessed parameters were evaluated in patients with resistant MS spasticity before and after 1 month of treatment with THC:CBD oromucosal spray. All 6 patients showed ≥20% improvement in the spasticity Numerical Rating Scale (i.e., were initial responders to treatment), but displayed individual variability in other spasticity-related parameters.

Improved Modified Ashworth Scale scores were observed in 5 cases, with a reduction of -2/-3 points in lower limb scores for 1 patient who also showed benefit in terms of a more stable gait but modest improvement in the timed 10-meter walk test (10MWT). Improvement in the 10MWT (or 25-foot walk test) was noted in 4 of the 6 cases. THC:CBD oromucosal spray also improved upper limb function as indicated by faster 9-Hole Peg Test results.”

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Traditional Uses of Cannabinoids and New Perspectives in the Treatment of Multiple Sclerosis.

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“Recent findings highlight the emerging role of the endocannabinoid system in the control of symptoms and disease progression in multiple sclerosis (MS). MS is a chronic, immune-mediated, demyelinating disorder of the central nervous system with no cure so far. It is widely reported in the literature that cannabinoids might be used to control MS symptoms and that they also might exert neuroprotective effects and slow down disease progression. This review aims to give an overview of the principal cannabinoids(synthetic and endogenous) used for the symptomatic amelioration of MS and their beneficial outcomes, providing new potentially possible perspectives for the treatment of this disease.”

https://www.ncbi.nlm.nih.gov/pubmed/30111755

http://www.mdpi.com/2305-6320/5/3/91

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