Tag Archives: therapy

An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics.

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  “Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.

OBJECTIVES:

This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.

CONCLUSION:

This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/23141881

Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

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“Hemp, Cannabis sativa, is a coarse bushy annual plant with palmate leaves and clusters of small green flowers that grows wild in regions of mild or tropical weather and can attain a height of 3 metres. The genus name Cannabis is complemented by sativa (which means useful). Cannabis has indeed been used throughout history for a variety of purposes…

 Cannabis has been utilised for centuries throughout the world to alleviate disease. Its derivatives were named “panacea”, or “cure-all”, and were sold as a legal medicine, mainly for pain…

The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/

Cannabinoid 1 (CB1) receptor–pharmacology, role in pain and recent developments in emerging CB1 agonists.

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Abstract

“Cannabinoids are antinociceptive in animal models of acute pain, tissue injury and nerve injury induced nociception and act via their cognate receptors, cannabinoid receptor 1 and 2. This review examines the underlying biology of the endocannabinoids and behavioural, neurophysiological, neuroanatomical evidence supporting the notion of pain modulation by these ligands with a focus on the current evidence encompassing the pharmacological characterization of CB1 agonists in this therapy. Separating the psychotropic effects of CB1 agonists from their therapeutic benefits is the major challenge facing researchers in the field today and with the discovery of peripherally acting agonists there seems to be a ray of hope emerging for the diverse potential therapeutic applications of this class of ligands.”

http://www.ncbi.nlm.nih.gov/pubmed/21631407

Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases.

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Abstract

“Chronic liver injury exposes the patient to liver fibrosis and its end stage, cirrhosis, is a major public health problem worldwide. In western countries, prevailing causes of cirrhosis include chronic alcohol consumption, hepatitis C virus infection and non-alcoholic steatohepatitis. Current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Nevertheless, suppression of the cause of hepatic injury is not always feasible and numerous efforts are directed at the development of liver-specific antifibrotic therapies. Along these lines, the authors recently demonstrated that the endocannabinoid system shows promise as a novel target for antifibrotic therapy during chronic liver injury. Indeed, cannabinoid receptors CB1 and CB2 promote dual pro- and antifibrogenic effects, respectively. Therefore, endocannabinoid-based therapies, combining CB2 agonists and CB1 antagonists may open novel therapeutic perspectives for the treatment of chronic liver diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/17298297

Evaluation of oral cannabinoid-containing medications for the management of interferon and ribavirin-induced anorexia, nausea and weight loss in patients treated for chronic hepatitis C virus

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  “The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown.”

 

“Although formal studies are lacking, there is anecdotal evidence that cannabis may be beneficial by alleviating common side effects associated with interferon-ribavirin, including anorexia, nausea, weight loss and insomnia. Despite the potential benefits of cannabis, concerns related to the long-term medical complications of inhaled cannabis use and the inability to legally obtain this product limit the use of it as a therapeutic intervention.”

“Oral cannabinoid-containing medications (OCs) have multiple potential therapeutic uses due to their analgesic, antiemetic, anticonvulsant, bronchodilatory and anti-inflammatory effects. They have been shown in clinical trials to ameliorate chemotherapy-induced nausea, to benefit those with AIDS wasting syndrome and to reduce spasticity in multiple sclerosis patients.”

“CONCLUSIONS:

The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662895/

Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1.

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Cover image

“Although cannabinoids exhibit a broad variety of anticarcinogenic effects, their potential use in cancer therapy is limited by their psychoactive effects. Here we evaluated the impact of cannabidiol, a plant-derived non-psychoactive cannabinoid, on cancer cell invasion. Using Matrigel invasion assays we found a cannabidiol-driven impaired invasion of human cervical cancer (HeLa, C33A) and human lung cancer cells (A549) that was reversed by antagonists to both CB(1) and CB(2) receptors as well as to transient receptor potential vanilloid 1 (TRPV1). The decrease of invasion by cannabidiol appeared concomitantly with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Knockdown of cannabidiol-induced TIMP-1 expression by siRNA led to a reversal of the cannabidiol-elicited decrease in tumor cell invasiveness, implying a causal link between the TIMP-1-upregulating and anti-invasive action of cannabidiol. P38 and p42/44 mitogen-activated protein kinases were identified as upstream targets conferring TIMP-1 induction and subsequent decreased invasiveness. Additionally, in vivo studies in thymic-aplastic nude mice revealed a significant inhibition of A549 lung metastasis in cannabidiol-treated animals as compared to vehicle-treated controls.

Altogether, these findings provide a novel mechanism underlying the anti-invasive action of cannabidiol and imply its use as a therapeutic option for the treatment of highly invasive cancers.”  http://www.ncbi.nlm.nih.gov/pubmed/19914218

http://www.sciencedirect.com/science/article/pii/S000629520900971X

Substitution profile of the cannabinoid agonist nabilone in human subjects discriminating δ9-tetrahydrocannabinol.

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Abstract

“OBJECTIVES:

The central effects of Δ-tetrahydrocannabinol (Δ-THC), the primary active constituent of cannabis, are attributed to cannabinoid CB1 receptor activity, although clinical evidence is limited. Drug discrimination has proven useful for examining the neuropharmacology of drugs, as data are concordant with the actions of a drug at the receptor level. The aim of this study was to determine the profile of behavioral and physiological effects of the cannabinoid agonist nabilone in humans trained to discriminate Δ-THC.

METHODS:

Six cannabis users learned to identify when they received oral Δ-THC (25 mg) or placebo and then received a range of doses of the cannabinoid agonists nabilone (1, 2, 3, and 5 mg) and Δ-THC (5, 10, 15, and 25 mg). The dopamine reuptake inhibitor methylphenidate (5, 10, 20, and 30 mg) was included as a negative control. Subjects completed the Multiple-Choice Procedure, and self-report, task performance, and physiological measures were collected.

RESULTS:

Nabilone shared discriminative-stimulus effects with the training dose of Δ-THC, produced subject-rated drug effects that were comparable to those of Δ-THC, and increased heart rate. Methylphenidate did not engender Δ-THC-like discriminative-stimulus effects.

CONCLUSIONS:

These data demonstrate that the interoceptive effects of nabilone are similar to Δ-THC in cannabis users. The overlap in their behavioral effects is likely due to their shared mechanism as CB1 receptor agonists. Given the relative success of agonist replacement therapy to manage opioid, tobacco, and stimulant dependence, these results also support the evaluation of nabilone as a potential medication for cannabis-use disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/20838217

Nabilone. A preliminary review of its pharmacological properties and therapeutic use.

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Abstract

“Nabilone is a new orally active cannabinoid for the treatment of severe gastrointestinal toxicity associated with cancer chemotherapy. The pharmacological profile of nabilone suggests that it acts primarily by preventing emesis controlled by the medulla oblongata, although its secondary mild anxiolytic activity may contribute to the overall efficacy. Nabilone 2mg twice daily starting 12 hours prior to, and continued for the duration of, chemotherapy produces significant reduction in the severity and duration of nausea and the frequency of vomiting in about 50 to 70% of patients with severe symptoms refractory to conventional therapy. Nabilone has proven to be more effective in controlling symptoms and preferred by more patients than prochlorperazine 10mg 2 to 4 times daily in a limited number of studies, despite a higher incidence of side effects. Comparative trials against other new antiemetic agents, such as high dose metoclopramide, and use of nabilone in combination with other antiemetics remain to be undertaken. The incidence of side effects is high with nabilone; drowsiness, dizziness and/or vertigo occur in 60 to 70% of patients, but rarely lead to drug withdrawal, although more troublesome effects, such as postural hypotension, ataxia, vision disturbance and toxic psychoses, may cause discontinuation of therapy. Thus, nabilone offers an effective alternative to the treatment options available in a difficult therapeutic area – those patients with severe gastrointestinal side effects from cancer chemotherapy who are refractory to conventional therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/2863127

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT(1A) receptor activation.

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“BACKGROUND AND PURPOSE:

To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT(1A) receptor activation in animal models.”

“CONCLUSIONS AND IMPLICATIONS:

Compared to cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT(1A) receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.”

http://www.ncbi.nlm.nih.gov/pubmed/23121618

Levonantradol for the treatment of chemotherapy-induced nausea and vomiting.

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Abstract

“Twenty patients with cancer previously unresponsive to antiemetic treatment of chemotherapy-induced nausea and vomiting were treated with the new tetrahydrocannabinoid Levonantradol. 15 patients experienced substantial relief and 10 of them preferred the drug for further courses. These observations suggest that Levonantradol can be beneficial to patients refractory to conventional antiemetic therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/6350696