Category Archives: Nausea/Vomiting

Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans

Posted on by
Reply

Mary Ann Liebert, Inc. publishers

“Cannabidiol (CBD) is a cannabinoid of the cannabis plant devoid of intoxicating effects. It may be of therapeutic value in a large number of diseases, including epilepsy, anxiety disorders, depression, schizophrenic psychosis, inflammatory diseases, dystonia, nausea, and vomiting without causing relevant or severe side effects.

No biosynthetic enzyme or pathway exists in the human body to convert CBD to THC.

This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods.

However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations.

Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.”

https://www.ncbi.nlm.nih.gov/pubmed/28861499

http://online.liebertpub.com/doi/full/10.1089/can.2016.0036

“A Conversion of Oral Cannabidiol to Delta9-Tetrahydrocannabinol Seems Not to Occur in Humans.”  https://www.ncbi.nlm.nih.gov/pubmed/28861507

Medicinal Uses of Marijuana and Cannabinoids

Posted on by
Reply

Publication Cover

“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation 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. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”

http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20

“Review Identifies 140 Controlled Clinical Trials Related to Cannabis”  http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/

Cannabinoid signaling in health and disease.

Posted on by
Reply

Image result for Canadian Journal of Physiology and Pharmacology

“Cannabis sativa has long been used for medicinal purposes.

To improve safety and efficacy, compounds from C. sativa were purified or synthesized and named under an umbrella group as cannabinoids.

Currently, several cannabinoids may be prescribed in Canada for a variety of indications such as nausea and pain.

More recently, an increasing number of reports suggest other salutary effects associated with endogenous cannabinoid signaling including cardioprotection.

The therapeutic potential of cannabinoids is therefore extended; however, evidence is limited and mechanisms remain unclear.

In addition, the use of cannabinoids clinically has been hindered due to pronounced psychoactive side effects.

This review provides an overview on the endocannabinoid system, including known physiological roles, and conditions in which cannabinoid receptor signaling has been implicated.”

 https://www.ncbi.nlm.nih.gov/pubmed/28263083

Concise review of the management of iatrogenic emesis using cannabinoids: emphasis on nabilone for chemotherapy-induced nausea and vomiting.

Posted on by
Reply

Image result for Cancer Chemother Pharmacol.

“Chemotherapy-induced nausea and vomiting (CINV) is a prevalent, distressing, and burdensome side effect of cancer chemotherapy. It is estimated to affect the majority of patients receiving certain anti-cancer drug regimens and can be treatment-limiting, even for life-saving medications. Despite seemingly numerous options, such as antimuscarinic anticholinergics, antihistamines, 5-HT3 receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists, preventative therapies are often inadequately effective, particularly for “delayed CINV”-leaving an important unmet clinical need.

Cannabinoid receptor agonists, by virtue of their unique mechanism of action and efficacy and safety data reported in clinical trials, appear to offer a useful additional option.

The mechanistic value of cannabinoids has been well known for many years, but these agents may have been underutilized in the past because of the notoriety and legal status of marijuana. While botanical marijuana contains nearly 500 components, including the psychoactive tetrahydrocannabinol (THC), nabilone is an established, single-entity synthetic cannabinoid receptor agonist that has become the focus of renewed interest. We review the basic pharmacology and clinical trial data of nabilone for use in prophylaxis and treatment of CINV.”

 https://www.ncbi.nlm.nih.gov/pubmed/28235999

Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry.

Posted on by
Reply

Image result for Clin Chem Lab Med.

“Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting.

The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone.

Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids.

Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions.

As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.”

https://www.ncbi.nlm.nih.gov/pubmed/28207408

Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.

Posted on by
Reply

Image result for Handb Exp Pharmacol.

“Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands’ synthesizing/degrading enzymes.

The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury.

For instance, genetic knockout of cannabinoid receptor 1 leads to inflammation and cancer of the intestines. Derivatives of Δ9-tetrahydrocannabinol, such as nabilone and dronabinol, activate cannabinoid receptors and have been introduced into the clinic to treat chemotherapy-induced emesis and loss of appetite; however, they may cause many psychotropic side effects.

New drugs that interfere with endocannabinoid degradation to raise endocannabinoid levels circumvent this obstacle and could be used in the future to treat emesis, intestinal inflammation, and functional disorders associated with visceral hyperalgesia.”

https://www.ncbi.nlm.nih.gov/pubmed/28161834

Therapeutic potential of cannabinoids in counteracting chemotherapy-induced adverse effects: an exploratory review.

Posted on by
Reply

Image result for Phytother Res.

“Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/25504799

Tolerability of dronabinol alone, ondansetron alone and the combination of dronabinol plus ondansetron in delayed chemotherapy-induced nausea and vomiting.

Posted on by
Reply

Image result for J Clin Oncol.

“Dronabinol (Marinol), the synthetic version of tetrahydrocannabinol, is used to treat nausea and vomiting following cancer chemotherapy (CINV).

It has a unique mechanism of action (cannabinoid receptor binding) compared to the more frequently used serotonin receptor antagonists. Tolerability of dronabinol versus ondansetron and the combination of dronabinol plus ondansetron was explored in subjects with delayed CINV.

Dronabinol was well tolerated and resulted in few terminations due to adverse events. The low rate of CNS-related adverse events following D treatment may make it a suitable alternative to serotonin antagonist therapy for delayed CINV.”

https://www.ncbi.nlm.nih.gov/pubmed/27946950

Dronabinol treatment of delayed chemotherapy-induced nausea and vomiting (CINV).

Posted on by
Reply

Image result for J Clin Oncol.

“Dronabinol (MARINOL), synthetic tetrahydrocannabinol, binds to cannabinoid receptors and has antiemetic activity. To explore if this novel mechanism would be of benefit in delayed CINV, dronabinol was added to the prophylactic regimen for acute CINV and continued after chemotherapy.

Efficacy at Endpoint (LOCF) Conclusions: Dronabinol (D) was comparable to ondansetron (O) in total response and but was more effective in reducing nausea intensity and vomiting/retching. Results for the combination of DO were similar to either agent alone.

These results support conducting a larger study since D could become an attractive alternative to serotonin receptor antagonists in treating delayed CINV.”

https://www.ncbi.nlm.nih.gov/pubmed/27946578

Central Aspects of Nausea and Vomiting in GI Disorders.

Posted on by
Reply

Image result for Curr Treat Options Gastroenterol.

“Nausea and vomiting result from continuous interactions among gastrointestinal, central nervous system, and autonomic nervous system. Despite being closely associated, central pathways of nausea and vomiting appear to be at least partly different and nausea is no longer considered only a penultimate step of vomiting. Although our understanding of central pathways of nausea has improved over the last one decade, it is still very basic.

Afferent pathways from gastrointestinal tract via vagus, vestibular system, and chemoreceptor trigger zone project to nucleus tractus solitarius which, in turn, relays the signal to central pattern generator initiating multiple downstream pathways. This central nausea pathway appears to be under constant modulation by autonomic nervous system and cerebral cortex.

There is also some evidence that central pathway of chronic nausea is different from that of acute nausea and closely resembles that of neuropathic pain. This improved understanding has modified the way we can approach the treatment of acute and chronic nausea.

While conventional therapies such as antiemetics (antiserotoninergic, antihistaminic, antidopaminergic) and prokinetics are commonly used to manage acute nausea, they are not as effective in improving chronic nausea.

Recently, neuromodulators such as tricyclic antidepressants, gabapentin, olanzapine, benzodiazepines, and cannabinoids have been shown to have antinausea effect.

There is a need to study the utility of these drugs in managing chronic functional nausea. Improving our understanding of central and peripheral circuitry of nausea will allow us to better utilize the currently available drugs and develop new therapeutic options.”

https://www.ncbi.nlm.nih.gov/pubmed/27734216