Category Archives: Nausea/Vomiting

The emerging role of cannabinoid neuromodulators in symptom management.

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Abstract

“INTRODUCTION:

The cannabinoids nabilone (Cesamet) and dronabinol (Marinol) are indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in cancer patients who have failed to respond adequately to conventional antiemetic therapy.

DISCUSSION:

The endocannabinoid (CB) system interacts with numerous other systems and pharmaceutical cannabinoids target ubiquitous CB1 and CB2 receptors in the central nervous system and periphery, relieving nausea and vomiting and pain.

SUMMARY:

The benefits of this novel class of medications in cancer may extend beyond CINV, as indicated by data from preclinical studies and animal models.”

http://www.ncbi.nlm.nih.gov/pubmed/17139494

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/

News about therapeutic use of cannabis and endocannabinoid system.

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“Growing basic research in recent years led to the discovery of the endocannabinoid system with a central role in neurobiology. New evidence suggests a therapeutic potential of cannabinoids in cancer chemotherapy-induced nausea and vomiting as well as in pain, spasticity and other symptoms in multiple sclerosis and movement disorders. Results of large randomized clinical trials of oral and sublingual Cannabis extracts will be known soon and there will be definitive answers to whether Cannabis has any therapeutic potential. Although the immediate future may lie in plant-based medicines, new targets for cannabinoid therapy focuses on the development of endocannabinoid degradation inhibitors which may offer site selectivity not afforded by cannabinoid receptor agonists.”  http://www.ncbi.nlm.nih.gov/pubmed/15033046

http://www.elsevier.es/es-revista-medicina-clinica-2-linkresolver-novedades-sobre-las-potencialidades-terapeuticas-13059327

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

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Philosophical Transactions of the Royal Society B: Biological Sciences: 367 (1607)

“Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive ‘multi-targeting’.”  https://www.ncbi.nlm.nih.gov/pubmed/23108552

“Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities”  http://rstb.royalsocietypublishing.org/content/367/1607/3353.long

Major Health Benefits of Medical Cannabis

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“The benefits of medical marijuana plant are extensive, pervasive, and long-standing. Because of the way the cannabis impacts the Autonomic Nervous System which develops the breath and relaxes the body, prospective for health and curative characteristics are huge. Some of the major health benefits of medical cannabis are explained below:

Treats Migraines

Cannabis healing has been very effective in the treatment of migraine headaches. Migraine headaches are vascular in source and are often preceded by an air characterized by nausea, flashes of light, faintness or photosensitivity.

Slows Down Tumor Growth

Studies have shown that cannabis help in slow down the facsimile and slow down the production of cancer cells in body. It is also a natural antiemetic, which makes it effectual in plummeting the nausea and vomiting related with chemo and radiation therapies. So taking marijuana slows down the tumor growth too.

Relieves Symptoms of Chronic Diseases

Marijuana is one of the best natural pain relievers that can help sufferers of chronic pain live more relaxed lives. The side effects are often much less severe than the other common pain medications.

Prevents Alzheimer’s

Cannabis reduces the occurrence of depression in Alzheimer’s patients, which can help patients to keep up a higher level of brain function. That is a powerful way to keep patients performance for a longer time after the first onset of Alzheimer’s disease.

Treats Glaucoma

Some strains of this medicinal plant have been shown that, they are potentially decreasing the force that glaucoma can place on the optic nerve; thereby the patients can easily cut the critical condition by smoking or taking the marijuana edibles or medicines.

Prevents Seizures

Seizure is a kind of epilepsy which almost affects more than 2 millions of Americans and 30 millions of people worldwide. Epilepsy is a condition when some of the brain cells become abnormally excitable. People using marijuana to control epilepsy should be alert when there is any removal of any tablets which controls seizures may leave you more susceptible to the patient. Marijuana is no exception. Patients with epilepsy are advised to exercise caution when using oral THC because there is no enough sufficient knowledge about the convulsive or anti-convulsive properties of the single compound.

For ADD and ADHD

Many people who endure with ADD and/or ADHD find that medical cannabis recovers their knack to hub and their level of recital with definite tasks. There are no clinical studies on humans but there are some beginner studies have done on animals that point to less hyperactivity and impulsivity with the use of cannabinoids (the active medicines in cannabis).

Relieve PMS

Millions of women have an illness on Premenstrual Syndrome (PMS). PMS includes the symptoms of headaches, abdominal cramps, bloating and fluid retention. Many women report that they have tried several different medications but none as give any significant relief like Medical Marijuana. Cannabis medicine has shown to give symptomatic relief from all the unpleasant symptoms of PMS.

Calm Those With Tourette’s and OCD

Several psychological disorders have been known to be related with the medical benefits of marijuana as well. Taking weed of prescribed amount on regular basis can slow down the tics for those who are suffering from Tourette’s syndrome and Obsessive Compulsive Disorder (OCD). Yes some of the qualities in marijuana plant help the patient to calm themselves when any creation of intrusive thoughts which produces fear, uneasiness and abnormal behaviors.”

http://www.herbalmission.org/major-health-benefits-of-medical-cannabis.php

Medicinal use of cannabis: history and current status.

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Abstract

“OBJECTIVE:

To provide an overview of the history and pharmacology of cannabis in relation to current scientific knowledge concerning actual and potential therapeutic uses of cannabis preparations and pure cannabinoids.

METHODS:

The literature on therapeutic uses of cannabis and cannabinoids was assessed with respect to type of study design, quality and variability of data, independent replications by the same or other investigators, magnitude of effects, comparison with other available treatments and reported adverse effects. The results of this review were also compared with those of major international reviews of this topic in the past five years.

CONCLUSIONS:

Pure tetrahydrocannabinol and several analogues have shown significant therapeutic benefits in the relief of nausea and vomiting, and stimulation of appetite in patients with wasting syndrome. Recent evidence clearly demonstrates analgesic and anti-spasticity effects that will probably prove to be clinically useful. Reduction of intraocular pressure in glaucoma and bronchodilation in asthma are not sufficiently strong, long lasting or reliable to provide a valid basis for therapeutic use. The anticonvulsant effect of cannabidiol is sufficiently promising to warrant further properly designed clinical trials. There is still a major lack of long term pharmacokinetic data and information on drug interactions. For all the present and probable future uses, pure cannabinoids, administered orally, rectally or parenterally, have been shown to be effective, and they are free of the risks of chronic inflammatory disease of the airways and upper respiratory cancer that are associated with the smoking of crude cannabis. Smoking might be justified on compassionate grounds in terminally ill patients who are already accustomed to using cannabis in this manner. Future research will probably yield new synthetic analogues with better separation of therapeutic effects from undesired psychoactivity and other side effects, and with solubility properties that may permit topical administration in the eye, or aerosol inhalation for rapid systemic effect without the risks associated with smoke inhalation.”

http://www.ncbi.nlm.nih.gov/pubmed/11854770

[Potential therapeutic usefulness of cannabis and cannabinoids].

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Abstract

“Diseases in which Cannabis and cannabinoids have demonstrated some medicinal putative properties are: nausea and vomiting associated with cancer chemotherapy, muscle spasticity (multiple sclerosis, movement disorders), pain, anorexia, epilepsy, glaucoma, bronchial asthma, neuroegenerative diseases, cancer, etc. Although some of the current data comes from clinical controlled essays, the majority are based on anecdotic reports. Basic pharmacokinetic and pharmacodynamic studies and more extensive controlled clinical essays with higher number of patients and long term studies are necessary to consider these compounds useful since a therapeutical point of view.”

http://www.ncbi.nlm.nih.gov/pubmed/11205042

The Therapeutic Potential of Cannabis and Cannabinoids

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“Background

Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany.”

“Therapeutic potential

Cannabis preparations exert numerous therapeutic effects. They have antispastic, analgesic, antiemetic, neuroprotective, and anti-inflammatory actions, and are effective against certain psychiatric diseases. Currently, however, only one cannabis extract is approved for use. It contains THC and CBD in a 1:1 ratio and was licensed in 2011 for treatment of moderate to severe refractory spasticity in multiple sclerosis (MS). In June 2012 the German Joint Federal Committee (JFC, Gemeinsamer Bundesausschuss) pronounced that the cannabis extract showed a “slight additional benefit” for this indication and granted a temporary license valid up to 2015.”

“The cannabis extract, which goes by the generic name nabiximols, has been approved by regulatory bodies in Germany and elsewhere for use as a sublingual spray. In the USA, dronabinol has been licensed since 1985 for the treatment of nausea and vomiting caused by cytostatic therapy and since 1992 for loss of appetite in HIV/Aids-related cachexia. In Great Britain, nabilone has been sanctioned for treatment of the side effects of chemotherapy in cancer patients.”

Results

“Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting.”

Conclusion

“There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442177/

 

[The mechanism of action of cannabis and cannabinoids].

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Abstract

“The effect of cannabis can be explained on the basis of the function of the cannabinoid receptor system, which consists of CB receptors (CB1, CB2), endoligands to activate these receptors and an enzyme–fatty acid amidohydrolase–to metabolize the endoligands. The endoligands of the cannabinoid receptor system are arachidonic acid-like substances, and are called endocannabinoids. Indications exist that the body also contains arachidonic acid-like substances that inhibit fatty acid amido hydrolase. Various cannabinoids have diverse effects on the receptors, functioning as agonists, antagonists or partial antagonists, as well as affecting the vanilloid receptor. Many known effects of cannabis can be explained on the basis of this mechanism of action as can the use of cannabis in various conditions including multiple sclerosis, Parkinson’s disease, glaucoma, nausea, vomiting and rheumatoid arthritis.”

http://www.ncbi.nlm.nih.gov/pubmed/16463612

Cannabinoid receptors and their ligands.

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Abstract

“There are at least two types of cannabinoid receptors, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors exist primarily on central and peripheral neurons, one of their functions being to modulate neurotransmitter release. CB(2) receptors are present mainly on immune cells. Their roles are proving more difficult to establish but seem to include the modulation of cytokine release. Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol and 2-arachidonyl glyceryl ether. Other endocannabinoids and cannabinoid receptor types may also exist. Although anandamide can act through CB(1) and CB(2) receptors, it is also a vanilloid receptor agonist and some of its metabolites may possess yet other important modes of action. The discovery of the system of cannabinoid receptors and endocannabinoids that constitutes the “endocannabinoid system” has prompted the development of CB(1)- and CB(2)-selective agonists and antagonists/inverse agonists. CB(1)/CB(2) agonists are already used clinically, as anti-emetics or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilation that accompanies advanced cirrhosis, and cancer. Following their release onto cannabinoid receptors, endocannabinoids are removed from the extracellular space by membrane transport and then degraded by intracellular enzymic hydrolysis. Inhibitors of both these processes have been developed. Such inhibitors have therapeutic potential as animal data suggest that released endocannabinoids mediate reductions both in inflammatory pain and in the spasticity and tremor of multiple sclerosis. So too have CB(1) receptor antagonists, for example for the suppression of appetite and the management of cognitive dysfunction or schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/12052030