Tag Archives: therapeutic

The phytocannabinoid, Δ⁹-tetrahydrocannabivarin, can act through 5-HT₁A receptors to produce antipsychotic effects.

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“This study aimed to address the questions of whether Δ(9)-tetrahydrocannabivarin (THCV) can (i) enhance activation of 5-HT1 A receptors in vitro and (ii) induce any apparent 5-HT₁A receptor-mediated antipsychotic effects in vivo…

Our findings suggest that THCV can enhance 5-HT₁A receptor activation, and that some of its apparent antipsychotic effects may depend on this enhancement.

We conclude that THCV has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/25363799

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.

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“Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency.

The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models…:

This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours…

CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/26439367

Targeting the endocannabinoid system to treat anxiety-related disorders.

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“The endocannabinoid system plays an important role in the control of emotions, and its dysregulation has been implicated in several psychiatric disorders.

The most common self-reported reason for using cannabis is rooted in its ability to reduce feelings of stress, tension, and anxiety.

Nevertheless, there are only few studies in controlled clinical settings that confirm that administration of cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD).

There are considerable encouraging preclinical data to suggest that endocannabinoid-targeted therapeutics for anxiety disorders should continue.

In this review, we will describe data supporting a role for the endocannabinoid system in preventing and treating anxiety-like behavior in animal models and PTSD patients.

Cannabinoids have shown beneficial outcomes in rat and mouse models of anxiety and PTSD, but they also may have untoward effects that discourage their chronic usage, including anxiogenic effects.

Hence, clinical and preclinical research on the endocannabinoid system should further study the effects of cannabinoids on anxiety and help determine whether the benefits of using exogenous cannabinoids outweigh the risks.

In general, this review suggests that targeting the endocannabinoid system represents an attractive and novel approach to the treatment of anxiety-related disorders and, in particular, PTSD.”

http://www.ncbi.nlm.nih.gov/pubmed/26426887

Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1.

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“Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis.

Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation.”

http://www.ncbi.nlm.nih.gov/pubmed/26426981

“We report for the first time the involvement of cannabinoid receptor 1 (CB1)-mediated signaling in the onset and progression of radiation-induced pulmonary fibrosis (RIF). We were able to delay the onset of RIF by genetic targeting of CB1 receptors as well as by its pharmacological inhibition. Thus, pharmacological targeting of CB1 receptors with peripherally restricted CB1 antagonists void of central nervous system complications may represent a novel strategy to prevent the development of RIF.

In summary, we provide the first evidence on the key pathological role of CB1 signaling in radiation-induced pulmonary fibrogenesis and show that peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating and untreatable complication of radiotherapy/irradiation. Our results also suggest that targeting CB1 may provide benefits in other lung diseases associated with inflammation and fibrosis.”

http://www.atsjournals.org/doi/10.1165/rcmb.2014-0331OC

Cannabis and Endocannabinoid Signaling in Epilepsy.

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“The antiepileptic potential of Cannabis sativa preparations has been historically recognized.

Recent changes in legal restrictions and new well-documented cases reporting remarkably strong beneficial effects have triggered an upsurge in exploiting medical marijuana in patients with refractory epilepsy.

Parallel research efforts in the last decade have uncovered the fundamental role of the endogenous cannabinoid system in controlling neuronal network excitability raising hopes for cannabinoid-based therapeutic approaches.

However, emerging data show that patient responsiveness varies substantially, and that cannabis administration may sometimes even exacerbate seizures. Qualitative and quantitative chemical variability in cannabis products and personal differences in the etiology of seizures, or in the pathological reorganization of epileptic networks, can all contribute to divergent patient responses.

Thus, the consensus view in the neurologist community is that drugs modifying the activity of the endocannabinoid system should first be tested in clinical trials to establish efficacy, safety, dosing, and proper indication in specific forms of epilepsies.

To support translation from anecdote-based practice to evidence-based therapy, the present review first introduces current preclinical and clinical efforts for cannabinoid- or endocannabinoid-based epilepsy treatments.

Next, recent advances in our knowledge of how endocannabinoid signaling limits abnormal network activity as a central component of the synaptic circuit-breaker system will be reviewed to provide a framework for the underlying neurobiological mechanisms of the beneficial and adverse effects.

Finally, accumulating evidence demonstrating robust synapse-specific pathophysiological plasticity of endocannabinoid signaling in epileptic networks will be summarized to gain better understanding of how and when pharmacological interventions may have therapeutic relevance.”

http://www.ncbi.nlm.nih.gov/pubmed/26408165

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

Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

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“There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS).

These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration.

Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms.

This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS.”

http://www.ncbi.nlm.nih.gov/pubmed/26408162

Cannabinoid receptor activation in the basolateral amygdala blocks the effects of stress on the conditioning and extinction of inhibitory avoidance.

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“The endocannabinoid system has recently emerged as important in the regulation of extinction learning and in the regulation of the hypothalamic-pituitary-adrenal axis.

Here, we aimed to examine the involvement of the cannabinoid CB(1) receptor in the basolateral amygdala (BLA) in inhibitory avoidance (IA) conditioning and extinction and to test whether cannabinoid activation would reverse the effects of stress on these memory processes.

Together, our findings may support a wide therapeutic application for cannabinoids in the treatment of conditions associated with the inappropriate retention of aversive memories and stress-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/19741114

Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress.

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“Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD).

Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD…

…cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders.

…the results extend previous findings to another stress model and to a post-trauma treatment configuration that are more relevant to clinical context and add to the growing body of data pointing to a therapeutic potential of cannabinoids for treatment of PTSD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242307/

http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/

Cannabinoid receptor activation prevents the effects of chronic mild stress on emotional learning and LTP in a rat model of depression.

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“The endocannabinoid (eCB) system has recently emerged as a promising therapeutic target for the treatment of stress-related emotional disorders.

Recent data suggest that the eCB system could represent a new therapeutic target for the treatment of depression.

The findings suggest that enhancing cannabinoid signaling could represent a novel approach to the treatment of cognitive deficits that accompany stress-related depression.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924526/

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

Neural correlates of cannabidiol and Δ9-tetrahydrocannabinol interactions in mice: implications for medical cannabis.

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“It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ9-tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC.

The aim of this study is to investigate whether CBD modulates THC-induced functional effects and c-Fos expression in a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols.

These data re-affirm that CBD modulates the pharmacological actions of THC and provide information regarding brain regions involved in the interaction between CBD and THC.”

http://www.ncbi.nlm.nih.gov/pubmed/26377899