Tag Archives: therapy

Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

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“Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons.

The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD.

Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease. The potential for cannabis to enhance the quality of life of Parkinson’s patients is explored.

Marijuana has been shown to improve nonmotor symptoms of PD such as depression, pain, sleep, and anxiety. Moreover, components of cannabis have been demonstrated to have neuroprotective effect due to their anti-inflammatory, antioxidative, and antiexcitotoxic properties.

Due to combination of the above mentioned beneficial effects, cannabis may provide a viable alternative or addition to the current treatment of Parkinson’s disease.”  https://www.hindawi.com/journals/pd/2016/1279042/

“Marijuana: Could it slow Parkinson’s disease progression? Parkinson’s disease is the second most common neurological illness in the United States, causing tremors, slowness of movement, postural instability, and impaired balance and coordination. But findings from a new review suggest symptoms of the condition could be improved with marijuana.”  http://www.medicalnewstoday.com/articles/314648.php

“Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy.” https://www.ncbi.nlm.nih.gov/pubmed/28050308

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders.

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“Anxiety and trauma-related disorders are psychiatric diseases with a lifetime prevalence of up to 25%. Phobias and post-traumatic stress disorder (PTSD) are characterized by abnormal and persistent memories of fear-related contexts and cues. The effects of psychological treatments such as exposure therapy are often only temporary and medications can be ineffective and have adverse side effects.

Growing evidence from human and animal studies indicates that cannabidiol, the main non-psychotomimetic phytocannabinoid present in Cannabis sativa, alleviates anxiety in paradigms assessing innate fear.

More recently, the effects of cannabidiol on learned fear have been investigated in preclinical studies with translational relevance for phobias and PTSD.

Here we review the findings from these studies, with an emphasis on cannabidiol regulation of contextual fear.

The evidence indicates that cannabidiol reduces learned fear in different ways: (1) cannabidiol decreases fear expression acutely, (2) cannabidiol disrupts memory reconsolidation, leading to sustained fear attenuation upon memory retrieval, and (3) cannabidiol enhances extinction, the psychological process by which exposure therapy inhibits learned fear.

We also present novel data on cannabidiol regulation of learned fear related to explicit cues, which indicates that auditory fear expression is also reduced acutely by cannabidiol.

We conclude by outlining future directions for research to elucidate the neural circuit, psychological, cellular, and molecular mechanisms underlying the regulation of fear memory processing by cannabidiol.

This line of investigation may lead to the development of cannabidiol as a novel therapeutic approach for treating anxiety and trauma-related disorders such as phobias and PTSD in the future.”

 https://www.ncbi.nlm.nih.gov/pubmed/27932983

Cannabidiol Mellows Out Resurgent Sodium Current

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“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

State of the evidence: Cannabinoids and cancer pain-A systematic review.

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“Cannabinoids are widely used to alleviate intractable symptoms such as pain, nausea, and muscle spasticity. The purpose of this review was to ascertain the current state of the science regarding use of cannabinoids for cancer pain.

CONCLUSIONS:

Eight randomized control trials met the inclusion criteria for review. Most trials found analgesic effects from cannabinoids when compared to placebo, although not all associations reached statistical significance. The analgesic effects of cannabinoids were also limited by dose-dependent side effects. Side effects most commonly reported were changes in cognition, sedation, and dizziness.

IMPLICATIONS FOR PRACTICE:

There is evidence that cannabinoids are effective adjuvants for cancer pain not completely relieved by opioid therapy, but there is a dearth of high-quality studies to support a stronger conclusion. Cannabinoids appear to be safe in low and medium doses. Methodological limitations of the trials limited the ability to make sound conclusions. Further research is warranted before efficacy, safety, and utility of cannabinoids for cancer pain can be determined.”

https://www.ncbi.nlm.nih.gov/pubmed/27863159

Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression.

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“Renal cell carcinoma (RCC) is a common urologic tumor with a poor prognosis.

Cannabinoid receptor 1 (CB1), which is a G protein-coupled receptor, has recently been reported to participate in the genesis and development of various cancers.

However, the exact role of CB1 in RCC is unknown. The aim of this study was to determine the role of CB1 in RCC cell lines and RCC prognosis, thus underlying its potential as a therapeutic target.

CB1 expression is functionally associated to cellular proliferation, apoptosis, and invasion ability of RCC.

Our data suggest that CB1 might be a potential target for RCC clinical therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/27757850

[The endocannabinoid system and bone].

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“Recent studies suggest an important role for the skeletal endocannabinoid system in the regulation of bone mass in both physiological and pathological conditions. Both major endocannabinoids (anandamid and 2-arachidonoylglycerol), endocannabinoid receptors – CB1-receptor (CB1R) a CB2-receptor (CB2R) and the endocannabinoid metabolizing enzymes are present or expressed in osteoblasts and osteoclasts. Previous studies identified multiple risk and protective variants of CNR2 gene dealing with the relationship to bone density and/or osteoporosis. Selective CB1R/ CB2R-inverse agonists/antagonists and CB2R-inverse agonists/antagonists are candidates for prevention of bone mass loss and combined antiresorptive and anabolic therapy for osteoporosis.”

https://www.ncbi.nlm.nih.gov/pubmed/27734700

Comparing the effects of endogenous and synthetic cannabinoid receptor agonists on survival of gastric cancer cells.

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“Anti-neoplastic activity induced by cannabinoids has been extensively documented for a number of cancer cell types; however, this topic has been explored in gastric cancer cells only in a limited number of approaches.

SIGNIFICANCE:

Through a comparative approach, our results support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells and open possibilities to use cannabinoids as part of a new gastric cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27640887

Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas.

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“The term “cannabinoids” designates a family of compounds with activity upon cannabinoid receptors.

Cannabinoids are classified in three groups: phytocannabinoids, endocannabinoids, and the synthetic analogues of both groups.

They have become a promising tool in the treatment of cancer disease, not only as palliative agents, but also as antitumor drugs, due to their ability to inhibit the proliferation, adhesion, migration, invasion, and angiogenesis of tumour cells.

Two of the cancers where they have shown high anticancer activity are breast and prostate tumours.

Cannabinoids, in particular the non-psychoactive CBD, may be promising tools in combination therapy for breast and prostate cancer, due to their direct antitumor effects, their ability to improve the efficacy of conventional antitumor drugs and their usefulness as palliative treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/27633508

Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model.

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“Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability.

The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor.

In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects.

In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS.

These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice.

These data further support targeting CB1 receptors as a relevant therapy for FXS.”

http://www.ncbi.nlm.nih.gov/pubmed/27589806

Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance.

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“The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids.

To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB.

Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome.

Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules.

It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared.

This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology.

We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival.

A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27486335