Tag Archives: treatment

Separate and combined effects of the cannabinoid agonists nabilone and Δ9-THC in humans discriminating Δ9-THC

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“Background

Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ9-tetrahydrocannabinol (Δ9-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ9-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment.”

“Conclusions

These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089804/

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

An efficient new cannabinoid antiemetic in pediatric oncology.

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Abstract

“Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9-THC), was administered (18 mg/m2 in edible oil, p.o.) to eight children, aged 3-13 years with various hematologic cancers, treated with different antineoplastic drugs for up to 8 months. The total number of treatments with delta-8-THC so far is 480. The THC treatment started two hours before each antineoplastic treatment and was continued every 6 hrs for 24 hours. Vomiting was completely prevented. The side effects observed were negligible.”

http://www.ncbi.nlm.nih.gov/pubmed/7776837

Efficacy of Crude Marijuana and Synthetic Delta-9-Tetrahydrocannabinol as Treatment for Chemotherapy-Induced Nausea and Vomiting: A Systematic Literature Review.

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Abstract

“Purpose/Objectives: To synthesize the research to determine whether oral delta-9-tetrahydrocannabinol (THC) and smoked marijuana are effective treatments for chemotherapy-induced nausea and vomiting (CINV) and to evaluate side effects and patient preference of these treatments.Data Sources: Original research, review articles, and other published articles in CINAHL(R), MEDLINE(R), and Cochrane Library databases.Data Synthesis: Cannabinoids are effective in controlling CINV, and oral THC and smoked marijuana have similar efficacy. However, smoked marijuana may not be accessible or safe for all patients with cancer. Also, these drugs have a unique side-effect profile that may include alterations in motor control, dizziness, dysphoria, and decreased concentration.Conclusions: This synthesis shows that cannabinoids are more effective than placebo and comparable to antiemetics such as prochlorperazine and ondansetron for CINV.Implications for Nursing: Nurses should feel supported by the literature to recommend oral synthetic THC as a treatment for CINV to their patients and physician colleagues. Nurses should be cognizant of the side-effect profile for this medication and provide appropriate patient education.”

http://www.ncbi.nlm.nih.gov/pubmed/19596652

Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: beyond prevention of acute emesis.

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Abstract

“Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem in the care of cancer patients. Although the use of serotonin (5-HT3) receptor antagonists, as well as neurokinin-1 inhibitors, has reduced rates of acute emesis, many patients still experience acute vomiting; moreover, these agents have reduced efficacy in preventing nausea, delayed CINV, and breakthrough CINV. Nausea, in particular, continues to have a major–and often overlooked–impact on patients’ quality of life. Optimizing the treatment for CINV likely will involve combinations of agents that inhibit the numerous neurotransmitter systems involved in nausea and vomiting reflexes. Cannabinoids are active in many of these systems, and two oral formulations, dronabinol (Marinol) and nabilone (Cesamet), are approved by the US Food and Drug Administration for use in CINV refractory to conventional antiemetic therapy. Agents in this class have shown superiority to dopamine receptor antagonists in preventing CINV, and there is some evidence that the combination of a dopamine antagonist and cannabinoid is superior to either alone and is particularly effective in preventing nausea. The presence of side effects from the cannabinoids may have slowed their adoption into clinical practice, but in a number of comparative clinical trials, patients have expressed a clear preference for the cannabinoid, choosing its efficacy over any undesired effects. Improvement in antiemetic therapy across the entire spectrum of CINV will involve the use of agents with different mechanisms of action in concurrent or sequential combinations, and the best such combinations should be identified. In this effort, the utility of the cannabinoids should not be overlooked.”

http://www.ncbi.nlm.nih.gov/pubmed/17566383

Regulation of nausea and vomiting by cannabinoids.

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“Anti-emetic effects of cannabinoids in human clinical trials”

  “Considerable evidence demonstrates that manipulation of the endocannabinoid system regulates nausea and vomiting in humans and other animals. The anti-emetic effect of cannabinoids has been shown across a wide variety of animals that are capable of vomiting in response to a toxic challenge. CB1 agonism suppresses vomiting, which is reversed by CB1 antagonism, and CB1 inverse agonism promotes vomiting. Recently, evidence from animal experiments suggests that cannabinoids may be especially useful in treating the more difficult to control symptoms of nausea and anticipatory nausea in chemotherapy patients, which are less well controlled by the currently available conventional pharmaceutical agents. Although rats and mice are incapable of vomiting, they display a distinctive conditioned gaping response when re-exposed to cues (flavours or contexts) paired with a nauseating treatment. Cannabinoid agonists (Δ9-THC, HU-210) and the fatty acid amide hydrolase (FAAH) inhibitor, URB-597, suppress conditioned gaping reactions (nausea) in rats as they suppress vomiting in emetic species. Inverse agonists, but not neutral antagonists, of the CB1 receptor promote nausea, and at subthreshold doses potentiate nausea produced by other toxins (LiCl). The primary non-psychoactive compound in cannabis, cannabidiol (CBD), also suppresses nausea and vomiting within a limited dose range. The anti-nausea/anti-emetic effects of CBD may be mediated by indirect activation of somatodendritic 5-HT1A receptors in the dorsal raphe nucleus; activation of these autoreceptors reduces the release of 5-HT in terminal forebrain regions. Preclinical research indicates that cannabinioids, including CBD, may be effective clinically for treating both nausea and vomiting produced by chemotherapy or other therapeutic treatments.”

“The cannabis plant has been used for several centuries for a number of therapeutic applications, including the attenuation of nausea and vomiting. Ineffective treatment of chemotherapy-induced nausea and vomiting prompted oncologists to investigate the anti-emetic properties of cannabinoids in the late 1970s and early 1980s, before the discovery of the 5-HT3 antagonists. The first cannabinoid agonist, nabilone (Cesamet), which is a synthetic analogue of Δ9-THC was specifically licensed for the suppression of nausea and vomiting produced by chemotherapy. Furthermore, synthetic Δ9-THC, dronabinol, entered the clinic as Marinol in 1985 as an anti-emetic and in 1992 as an appetite stimulant. In these early studies, several clinical trials compared the effectiveness of Δ9-THC with placebo or other anti-emetic drugs. Comparisons of oral Δ9-THC with existing anti-emetic agents generally indicated that Δ9-THC was at least as effective as the dopamine antagonists, such as prochlorperazine.”

“There is some evidence that cannabis-based medicines may be effective in treating the more difficult to control symptoms of nausea and delayed nausea and vomiting in children. Abrahamov et al. (1995) evaluated the anti-emetic effectiveness of Δ8-THC, a close but less psychoactive relative of Δ9-THC, in children receiving chemotherapy treatment. Two hours before the start of each cancer treatment and every six hours thereafter for 24 h, the children were given Δ8-THC as oil drops on the tongue or in a bite of food. After a total of 480 treatments, the only side effects reported were slight irritability in two of the youngest children (3.5 and 4 years old); both acute and delayed nausea and vomiting were controlled.”

“Chemotherapy-induced vomiting is well controlled in most patients by conventionally available drugs, nausea (acute, delayed and anticipatory) continues to be a challenge. Nausea is often reported as more distressing than vomiting, because it is a continuous sensation. Indeed, this distressing symptom of chemotherapy treatment (even when vomiting is pharmacologically controlled) can become so severe that as many as 20% of patients discontinue the treatment. Both preclinical and human clinical research suggests that cannabinoid compounds may have promise in treating nausea in chemotherapy patients.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165951/

Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain.

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Image result for The Journal of Supportive Oncology

“Many patients with life-threatening diseases such as cancer experience severe symptoms that compromise their health status and deny them quality of life. Patients with cancer often experience cachexia, pain, and depression,which translate into an unacceptable quality of life. The discovery of the endocannabinoid system has led to a renewed interest in the use of cannabinoids for the management of nausea, vomiting, and weight loss arising either from cancer or the agents used to treat cancer. The endocannabinoid system has been found to be a key modulator of systems involved in pain perception, emesis, and reward pathways. As such, it represents a target for development of new medications for controlling the symptoms associated with cancer. Although the cannabinoid receptor agonist tetrahydrocannabinol and one of its analogs are currently the only agents approved for clinical use, efforts are under way to devise other strategies for activating the endocannabinoid system for therapeutic uses.”

http://www.ncbi.nlm.nih.gov/pubmed/15357514

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

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Abstract

  “The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.”

Summary

“The discovery of an endocannabinoid signaling system has opened new possibilities for research into understanding the mechanisms of marijuana actions, the role of the endocannabinoid system in homeostasis, and the development of treatment approaches based either on the phytocannabinoids or novel molecules. CB1 agonists may have roles in the treatment of neuropathic pain, spasticity, nausea and emesis, cachexia, and potentially neuroprotection after stroke or head injury. Agonists and antagonists of peripheral CB receptors may be useful in the treatment of inflammatory and autoimmune disorders, as well as hypertension and other cardiovascular diseases. CB1 antagonists may find utility in management of obesity and drug craving. Other novel agents that may not be active at CB receptor sites, but might otherwise modify cannabinoid transport or metabolism, may also have a role in therapeutic modification of the endocannabinoid system. While the short and long term toxicities of the newer compounds are not known, one must expect that at least some of the acute effects (psychotropic effects; hypotension) may be shared by CB agonists. While there are few, long-term serious toxicities attributable to marijuana, extrapolation to newer and more potent agonists, antagonists, and cannabinoid system modulators cannot be assumed. CB1 agonists have the potential in animal models to produce drug preference and drug seeking behaviors as well as tolerance and abstinence phenomena similar to, though not generally as severe as those of other drugs of addiction. There is increasing evidence from human observations that withdrawal from the phytocannabinoids can produce an abstinence syndrome characterized primarily by irritability, sleep disturbance, mood disturbance, and appetite disturbance in chronic heavy users, therefore, such possible effects will need to be considered in the evaluation of newer shorter acting and more potent agonists.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2544377/