Tag Archives: anxiolytic

Cannabidiol Prevents Cerebral Infarction Via a Serotonergic 5-Hydroxytryptamine1A Receptor–Dependent Mechanism

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“Cannabis contains ≈80 different cannabinoids, including the psychoactive component Δ9-tetrahydrocannabinol, and nonpsychoactive components, which include cannabidiol, cannabinol, and cannabigerol.

In those components, cannabidiol, a nonpsychoactive constituent of cannabis, was found to be an anticonvulsant in animal models of epilepsy and in humans with epilepsy. Moreover, cannabidiol has been shown to have antispasmodic, anxiolytic, antinausea, and antirheumatoid arthritic properties. In addition, cannabidiol has been shown to be protective against global and focal ischemic injury.

Cannabidiol has been reported to be a neuroprotectant, but the neuroprotective mechanism of cannabidiol remains unclear. We studied the neuroprotective mechanism of cannabidiol in 4-hour middle cerebral artery (MCA) occlusion mice.

Cannabidiol significantly reduced the infarct volume induced by MCA occlusion in a bell-shaped curve. Similarly, abnormal cannabidiol but not anandamide or methanandamide reduced the infarct volume.

Cannabidiol and abnormal cannabidiol reduced the infarct volume.

These results suggested that the neuroprotective effect of cannabidiol may be related to the increase in CBF through the serotonergic 5-HT1A receptor.”

http://stroke.ahajournals.org/content/36/5/1071

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

Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

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“Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury.

In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line.

This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

Cannabidiol (CBD) is a nonpsychoactive cannabinoid derived from Cannabis sativa and a weak CB1 and CB2 cannabinoid receptor antagonist, with very low toxicity for humans. It has recently been demonstrated in vivo and in vitro that CBD has a variety of therapeutic properties, exerting antidepressant, anxiolytic, anti-inflammatory, immunomodulatory, and neuroprotective effects.  Our results provide novel insight into the neuroprotective properties of CBD, which involves the regulation of the mitochondrial bioenergetics and the glucose metabolism of hippocampal neurons during OGD/R injury.

In summary, our results suggest that CBD exerts a potent neuroprotective effect against ischemia/reperfusion injury by attenuating intracellular oxidative stress, enhancing mitochondrial bioenergetics, and optimizing glucose metabolism via the pentose-phosphate pathway, thus strengthening the antioxidant defenses and preserving the energy homeostasis of neurons. More in-depth studies are required to investigate the precise mechanism underlying the success of CBD treatment and to determine the actual role of CBD in cerebral ischemia.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247568/

“Cannabidiol may soon be used in the emergency room to fight effects of stroke and cardiac emergencies” http://www.naturalnews.com/2017-02-21-cannabidiol-may-soon-be-used-in-the-emergency-room-to-fight-effects-of-stroke-cardiac-emergencies.html

Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction

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“Cannabidiol (CBD) is the major non-psychotropic constituent of the Cannabis plant and has anxiolytic therapeutic potential.

Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression.

We showed that under conditions of strong fear conditioning, CBD reduced contextual fear memory expression both acutely during the extinction session as well as later at a fear retention test.

This pattern of results is consistent with CBD enhancing contextual fear memory extinction when the initial conditioning is strong, but impairing extinction when conditioning is weak. This bidirectional effect of CBD may be related to stress levels induced by conditioning and evoked at retrieval during extinction, rather than the strength of the memory per se.

 In summary, CBD had bidirectional effects on the extinction of contextual fear conditioning, depending on the nature of the initial fear conditioning. Nevertheless, in the more translationally-relevant stronger conditioning setting, CBD both acutely inhibited fear expression and enhanced extinction to produce longer lasting reductions in fear.
These observations provide further support for the potential translational use of CBD in conditions such as posttraumatic stress disorder and specific phobias.”

http://journal.frontiersin.org/article/10.3389/fphar.2016.00493/full?utm_source=S-TWT&utm_medium=SNET&utm_campaign=ECO_FPHAR_XXXXXXXX_auto-dlvrit%0A

Therapeutic potential of fatty acid amide hydrolase, monoacylglycerol lipase, and N-acylethanolamine acid amidase inhibitors.

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“Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation.

FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2).

Over the last decades, increasing the concentration of FAEs and ECs through the inhibition of degrading enzymes has been considered to be a viable therapeutic approach to enhance their anti-nociceptive and anti-inflammatory effects, as well as protecting the nervous system.”

 https://www.ncbi.nlm.nih.gov/pubmed/27766867

Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats.

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“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects.

In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life.

Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease.

The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats.

Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.”

https://www.ncbi.nlm.nih.gov/pubmed/27733830

Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential.

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“Bipolar affective disorder is often poorly controlled by prescribed drugs.

Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression.

We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition.

No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabis relieves symptoms of mania and/or depression.

The cannabinoids Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects.

Pure synthetic cannabinoids, such as dronabinol and nabilone and specific plant extracts containing THC, CBD, or a mixture of the two in known concentrations, are available and can be delivered sublingually.

Controlled trials of these cannabinoids as adjunctive medication in bipolar disorder are now indicated.”

http://www.ncbi.nlm.nih.gov/pubmed/15888515

Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor.

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“Cognitive and motor disturbances are serious consequences of tremor induced by motor disorders. Despite a lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor.

In the current study, the effects of WIN55, 212-2 (WIN), a cannabinoid receptor (CBR) agonist, on harmaline-induced motor and cognitive impairments was studied.

The neuroprotective and anxiolytic effects of WIN demonstrated in the current study can be offered cannabinoid receptor (CBR) agonism as a potential neuroprotective agent in the treatment of patients with tremor that manifest mental dysfunctions.”

http://www.ncbi.nlm.nih.gov/pubmed/27317835

Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents.

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“There is growing pressure for states and the federal government to legalize the use of cannabis products for medical purposes in the United States.

Sixteen states have legalized (or decriminalized possession of) products high in cannabidiol (CBD) and with restricted Δ9 -tetrahydrocannabinol (Δ9 -THC) content. In most of these states, the intent is for use in refractory epileptic seizures in children, but in a few states, the indications are broader.

The objectives of this review are to provide an overview of the pharmacology and toxicology of CBD; to summarize some of the regulatory, safety, and cultural issues relevant to the further exploitation of its antiepileptic or other pharmacologic activities; and to assess the current status and prospects for clinical development of CBD and CBD-rich preparations for medical use in the United States.

Unlike Δ9 -THC, CBD elicits its pharmacologic effects without exerting any significant intrinsic activity on the cannabinoid receptors (CB1 and CB2 ), whose activation results in the psychotropic effects characteristic of Δ9 -THC, and CBD possesses several pharmacologic activities that give it a high potential for therapeutic use.

CBD exhibits antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties.

In combination with Δ9 -THC, CBD has received regulatory approvals in several European countries and is currently under study in U.S. Food and Drug Administration-registered trials in the United States.

A number of states have passed legislation to allow for the use of CBD-rich, limited Δ9 -THC-content preparations of cannabis for certain pathologic conditions. CBD is currently being studied in several clinical trials and is at different stages of clinical development for various medical indications.

Judging from clinical findings reported so far, CBD and CBD-enriched preparations have great potential utility, but uncertainties regarding sourcing, long-term safety, abuse potential, and regulatory dilemmas remain.”

http://www.ncbi.nlm.nih.gov/pubmed/27285147

Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze.

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“Previous studies have shown that cannabinoidergic system is involved in anxiety.

The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat.

It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system.

It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.”

http://www.ncbi.nlm.nih.gov/pubmed/26904171

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

A systematic review of plant-derived natural compounds for anxiety disorders.

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“Anxiety disorders are the most common mental illnesses affecting human beings. They range from panic to generalized anxiety disorders upsetting the well-being and psychosocial performance of patients. Several conventional anxiolytic drugs are being used which in turn result in several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being conducted by researchers.

The aim of the present study is to comprehensively review phytochemical compounds with well-established anxiolytic activities and their structure-activity relationships as well as neuropsychopharmacological aspects. Results showed that phytochemicals like; alkaloids, flavonoids, phenolic acids, lignans, cinnamates, terpenes and saponins possess anxiolytic effects in a wide range of animal models of anxiety.

The involved mechanisms include interaction with γ-aminobutyric acid (GABA)A receptors at benzodiazepine (BZD) and non-BZD sites with various affinity to different subunits, serotonergic 5-hydrodytryptamine (5-HT)1A and 5-HT2A/C receptors, noradrenergic and dopaminergic systems, glycine and glutamate receptors, and κ-opioid receptor as well as cannabinoid (CB)1 and CB2 receptors.

Phytochemicals also modulate the hypothalamo-pituitary-adrenal (HPA) axis, the levels of pro-inflammatory cytokines like interleukin (IL)-2, IL-6, IL-1β and tumor necrosis factor (TNF)-α, and improve brain derived neurotrophic factor (BDNF) levels. Transient receptor potential cation channel subfamily V (TRPV)3, nitric oxide cyclic guanosine monophosphate (NO-cGMP) pathway and monoamine oxidase enzymes are other targets of phytochemicals with anxiolytic activity.

Taking together, these phytochemicals may be considered as supplements to conventional anxiolytic therapies in order to improve efficacy and reduce adverse effects.

Further preclinical and clinical studies are still needed in order to recognize the structure-activity relationships, metabolism, absorption, and neuropsychopharmacological mechanisms of plant-derived natural agents.”

http://www.ncbi.nlm.nih.gov/pubmed/26845556