Tag Archives: Cannabinoids

The therapeutic use of cannabinoids: Forensic aspects.

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“Since 2013 in the Italian market has been introduced the Nabiximols, a drug containing two of the main active cannabinoids: Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This drug has been approved in Italy in the treatment of Multiple Sclerosis (MS). It is an oral spray formulation and each puff of 100μl contains 2.7mg of Δ9-THC and 2.5mg of CBD.

In the present study we analyzed urine and blood samples collected from a group of 20 patients treated with Nabiximols in order to evaluate: blood Δ9-THC concentrations in relation to the dose administered and the duration of treatment and the potentiality of this medication to be used for drug habit.

The study was conducted on a sample group of patients affected by MS, of both sexes, age: 49-61 years, treated with Nabiximols for short (28 days) or long-term.

The results of our study allow affirming that it is unlikely to use this medication for drug habit or to sale it in the black market because of the low blood concentrations available and of its high costs.

These statements were confirmed by: (a) the low Δ9-THC concentrations in the pharmaceutical formulation; (b) the low blood concentrations produced by Nabiximols administration, more than 10 times smaller than the blood concentrations known to produce psychotropic effects; (c) the presence of CBD (Δ9-THC natural antagonist); (d) the route of administration (inhaled, not smoked).”

http://www.ncbi.nlm.nih.gov/pubmed/27038587

No more pain upon Gq-protein-coupled receptor activation: role of endocannabinoids.

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“Marijuana has been used to relieve pain for centuries.

The analgesic mechanism of its constituents, the cannabinoids, was only revealed after the discovery of cannabinoid receptors (CB1 and CB2) two decades ago.”

http://www.ncbi.nlm.nih.gov/pubmed/24494686

Cannabis and cancer: toward a new understanding

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“The treatment of cancer, including the disease itself and the symptoms associated with cancer and its therapy, is one of the most important emerging frontiers in cannabinoid therapeutics.

This Current Oncology supplement brings together the work of some of the leading minds around the world who have dedicated themselves and their laboratories to understanding the role of cannabis and cannabinoids in the pathophysiology and management of cancer.

It is an unfortunate reality of 2016 that many doctors still lack the basic knowledge about cannabis, cannabinoids, and the endocannabinoid system that would enable them to have an informed discussion with their patients, and that the knowledge gap gives rise to stigmatization, alienation, and a fracture of the doctor–patient relationship.

Our patient describes her experience in trying to find answers and assistance, and with the help of her treating oncologist, she succeeds in securing legal access to cannabinoids, with remarkable results. Stories of this kind are occurring too often to be ignored or written off as placebo responses or outliers. As a medical profession, we are duty-bound to follow up on such experiences with critical and balanced investigation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791146/

Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation.

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“∆9-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids derived from the Cannabis sativa plant and is known for its anti-inflammatory properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T helper cells including the classic inflammatory Th1 lineage as well as the more recently discovered Th17 lineage. In the current study, we investigated whether THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH response. THC treatment (20 mg/kg) of C57BL/6 mice with DTH caused decreased swelling and infiltration of immune cells at the site of antigen rechallenge. Additionally, THC treatment decreased lymphocyte activation as well as Th1/Th17 lineage commitment, including reduced lineage-specific transcription factors and cytokines. Interestingly, while DTH caused an overexpression of miR-21, which increases Th17 differentiation via SMAD7 inhibition, and downregulation of miR-29b, an IFN-γ inhibitor, THC treatment reversed this microRNA (miR) dysregulation. Furthermore, when we transfected primary cells from DTH mice with miR-21 inhibitor or miR-29b mimic, as seen with THC treatment, the expression of target gene message was directly impacted increasing SMAD7 and decreasing IFN-γ expression, respectively. In summary, the current study suggests that THC treatment during DTH response can simultaneously inhibit Th1/Th17 activation via regulation of microRNA (miRNA) expression.

KEY MESSAGES:

• THC treatment inhibits simultaneous Th1/Th17 driven inflammation. • THC treatment corrects DTH-mediated microRNA dysregulation. • THC treatment regulates proinflammatory cytokines and transcription factors.”

http://www.ncbi.nlm.nih.gov/pubmed/27038180

Endocannabinoid Signaling Regulates Sleep Stability.

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“Since antiquity cannabinoids have been used as a treatment for insomnia, and the first reports in western medical literature regarding the therapeutic utility and physiological effects of cannabis preparations note their hypnogenic properties.

The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized.

We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system.

Our findings demonstrate that eCB signaling is necessary and sufficient for the control of sleep stability, but this neurotransmitter system is not necessary for sleep homeostasis.

 These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816426/

http://www.thctotalhealthcare.com/category/insomnia/

Therapeutic potential of cannabinoids in trigeminal neuralgia.

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“Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain and continues to be a real therapeutic challenge to the clinicians. While the exact cause and pathology of this disorder is uncertain, it is thought that trigeminal neuralgia caused by irritation of the trigeminal nerve. This irritation results from damage due to the change in the blood vessels, the presence of a tumor or other lesions that cause the compression of the trigeminal root.

The pain of trigeminal neuralgia is characterized by unilateral pain attacks that start abruptly and last for varying periods of time from minutes to hours. The quality of pain is usually sharp, stabbing, lancinating, and burning. The attacks are initiated by mild stimuli such as light touch of the skin, eating, chewing, washing the face, brushing the teeth, and exposure to wind.

Although antiepileptic drug therapy may be beneficial in the treatment of trigeminal neuralgia, up to one-half of the patients become refractory or intolerant to these medications. At present there are few other effective drugs. In cases of lacking effect after pharmacotherapy, surgical options may be considered.

Currently there is growing amount of evidence to suggest that the psychoactive ingredient in cannabis and individual cannabinoids may be effective in alleviating neuropathic pain and hyperalgesia. Evidence suggests that cannabinoids may prove useful in pain modulation by inhibiting neuronal transmission in pain pathways.

Considering the pronounced antinociceptive effects produced by cannabinoids, they may be a promising therapeutic approach for the clinical management of trigeminal neuralgia.”

http://www.ncbi.nlm.nih.gov/pubmed/15578967

Anticancer mechanisms of cannabinoids.

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“In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer.

They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals.

In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy.

Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents.”

http://www.ncbi.nlm.nih.gov/pubmed/27022311

Integrating cannabis into clinical cancer care.

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“Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use.

However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use.

For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression.

Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite.

Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy.

A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia.

Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis.

Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating.

Human studies should be conducted to address critical questions related to the foregoing effects.”

http://www.ncbi.nlm.nih.gov/pubmed/27022315

Use of cannabinoids in cancer care: palliative care

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“Cannabinoid Integrative Medicine In Oncologic Palliative Care.

The opportunities to improve and expand palliative care are many. In this supplement, Current Oncology is presenting a discussion on cannabinoid therapeutics. I believe that, as a therapeutic class, cannabinoids have an important role to play in oncologic palliative care—a role that I predict will only grow with time, as knowledge and acceptance of these agents becomes mainstream once more, as in the 19th and early 20th century in North America and Europe.”

http://www.current-oncology.com/index.php/oncology/article/view/2962/2087

In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma.

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“Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance.

Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects.

We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ(9)-tetrahydrocannabinol (thc) and cannabidiol (cbd)…

Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis. Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts.

 

Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl.”

http://www.ncbi.nlm.nih.gov/pubmed/27022310

“Neuroblastomas are cancers that start in early nerve cells (called neuroblasts) of the sympathetic nervous system, so they can be found anywhere along this system.”  http://www.cancer.org/cancer/neuroblastoma/detailedguide/neuroblastoma-what-is-neuroblastoma