Tag Archives: marijuana

Marijuana as antiemetic medicine: a survey of oncologists’ experiences and attitudes.

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Abstract

“A random-sample, anonymous survey of the members of the American Society of Clinical Oncology (ASCO) was conducted in spring 1990 measuring the attitudes and experiences of American oncologists concerning the antiemetic use of marijuana in cancer chemotherapy patients. The survey was mailed to about one third (N = 2,430) of all United States-based ASCO members and yielded a response rate of 43% (1,035). More than 44% of the respondents report recommending the (illegal) use of marijuana for the control of emesis to at least one cancer chemotherapy patient. Almost one half (48%) would prescribe marijuana to some of their patients if it were legal. As a group, respondents considered smoked marijuana to be somewhat more effective than the legally available oral synthetic dronabinol ([THC] Marinol; Unimed, Somerville, NJ) and roughly as safe. Of the respondents who expressed an opinion, a majority (54%) thought marijuana should be available by prescription. These results bear on the question of whether marijuana has a “currently accepted medical use,” at issue in an ongoing administrative and legal dispute concerning whether marijuana in smoked form should be available by prescription along with synthetic THC in oral form. This survey demonstrates that oncologists’ experience with the medical use of marijuana is more extensive, and their opinions of it are more favorable, than the regulatory authorities appear to have believed.”

http://www.ncbi.nlm.nih.gov/pubmed/2045870

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting

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  “Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV.”

“Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial.”

“A systematic review of 30 clinical trials involving orally administered synthetic cannabinoids (nabilone and dronabinol) showed that they were superior to dopamine receptor antagonists in preventing CINV. Both are approved by the US Food and Drug Administration for use in CINV refractory to conventional anti-emetic therapy, but some authors have questioned the appropriateness of orally administered cannabinoids due to the variability in their gastrointestinal absorption, low bioavailability, long half-lives and the difficulties for an adequate self titration of the dose.”

“Animal studies suggest that the combined administration of different cannabinoids may enhance some of the therapeutic effects of delta-9-tetrahydrocannabinol (THC). This might explain why some patients preferred marihuana to synthetic cannabinoids in clinical trials.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997305/

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

Review of cannabinoids and their antiemetic effectiveness.

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Abstract

“Marijuana has been used for over 2 centuries. Its major psychoactive constituent, delta-9-tetrahydrocannabinol (THC) was isolated in 1964 and first used to control nausea and vomiting during chemotherapy in the 1970s. THC has cardiovascular, pulmonary and endocrinological effects as well as actions on the central nervous system. Alterations in mood, memory, motor coordination, cognitive ability, sensorium, spatial- and self-perception are commonly experienced. The precise antiemetic mechanism is unknown. THC and nabilone act at a number of sites within the central nervous system. Cannabinoids have also been shown to inhibit prostaglandin synthesis in vitro. In controlled clinical trials, THC is superior to placebo and prochlorperazine in antiemetic effectiveness. Effectiveness of THC correlates to a ‘high’ experienced by the patient. A variety of chemotherapy regimens respond to THC including high-dose methotrexate and the doxorubicin, cyclophosphamide, fluorouracil combination. Cisplatin is more resistant. Side effects are generally well tolerated but may limit THC use in the elderly or when high doses are administered. Nabilone, a synthetic cannabinoid, is also an effective antiemetic which is more active than prochlorperazine in preventing chemotherapy-induced emesis, including cisplatin-containing regimens. Side effects are similar to THC and may be dose-limiting. Levonantradol, another synthetic cannabinoid, is an effective antiemetic. It may provide more flexibility in the outpatient setting since it can be administered orally or intramuscularly. Most side effects are mild except for dysphoria which may be dose-limiting.”

http://www.ncbi.nlm.nih.gov/pubmed/6301800

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/

Compound in cannabis may help treat epilepsy, researchers say

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“British researchers have determined that a little-studied chemical in the cannabis plant could lead to effective treatments for epilepsy, with few to no side effects.

The team at Britain’s University of Reading, working with GW Pharmaceuticals and Otsuka Pharmaceuticals, tested cannabidivarin, or CBDV, in rats and mice afflicted with six types of epilepsy and found it “strongly suppressed seizures” without causing the uncontrollable shaking and other side effects of existing anti-epilepsy drugs.

The casual use of marijuana — or cannabis — to control seizures dates back to ancient times. Its most prominent component, THC, is among those shown in animal studies to have strong anti-convulsant properties…”

http://articles.latimes.com/2012/sep/14/news/la-sn-cannabis-cbdv-epilepsy-20120914

Effects of marihuana cannabinoids on seizure activity in cobalt-epileptic rats.

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Abstract

“Rats rendered chronically epileptic by bilateral implantation of cobalt into frontal cortices were simultaneously prepared with permanent electrodes for longitudinal recording of the electroencephalogram (EEG) and electromyogram (EMG). Delta-8-tetrahydrocannabinol (delta-8-THC; 10 mg/kg), delta-9-tetrahydrocannabinol (delta-9-THC; 10 mg/kg), cannabidiol (CBD; 60 mg/kg), or polyvinylpyrrolidone (PVP) vehicle (2 ml/kg) was administered IP twice daily from day 7 through 10 after cobalt implantation, at which time generalized seizure activity in non-treated cobalt-epileptic rats was maximal. Relative to PVP-treated controls, CBD did not alter the frequency of appearance of seizures during the course of repeated administration. In contrast, both delta-8-THC and delta-9-THC markedly reduced the incidence of seizures on the first and second days of administration. Interictal spiking during this period, on the other hand, was actually enhanced. On the third and fourth days, tolerance to the effect on seizures was evident, with a return of seizure frequency of THC-treated rats to values not significantly different from those of controls. Unlike the effect on seizures, no tolerance developed to the marked suppression of rapid eye movement (REM) sleep induces by delta-8-THC and delta-9-THC. REM sleep remained reduced in the treated animals during the first 2 days after termination of THC administration. In contrast, REM sleep time was unaffected by repeated administration of CBD. These results suggest that delta-8-THC and delta-9-THC exert their initial anticonvulsant effect by limiting the spread of epileptogenic activity originating from the cobalt focus.”

http://www.ncbi.nlm.nih.gov/pubmed/6280204

Marijuana use and epilepsy: prevalance in patients of a tertiary care epilepsy center.

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Abstract

“The authors sought to determine the prevalence of marijuana use in patients with epilepsy by performing a telephone survey in a tertiary care epilepsy center. Twenty-one percent of subjects had used marijuana in the past year with the majority of active users reporting beneficial effects on seizures. Twenty-four percent of all subjects believed marijuana was an effective therapy for epilepsy. Despite limited evidence of efficacy, many patients with epilepsy believe marijuana is an effective therapy for epilepsy and are actively using it.”

http://www.ncbi.nlm.nih.gov/pubmed/15184622

Endocannabinoids and Their Implications for Epilepsy

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“This review covers the main features of a newly discovered intercellular signaling system in which endogenous ligands of the brain’s cannabinoid receptors, or endocannabinoids, serve as retrograde messengers that enable a cell to control the strength of its own synaptic inputs. Endocannabinoids are released by bursts of action potentials, including events resembling interictal spikes, and probably by seizures as well. Activation of cannabinoid receptors has been implicated in neuroprotection against excitotoxicity and can help explain the anticonvulsant properties of cannabinoids that have been known since antiquity.”

“Cannabis in its various forms, including marijuana and hashish, is produced from the flowers and leaves of the hemp plant, Cannabis sativa. Through their primary psychoactive ingredient, Δ9-tetrahydrocannabinol (THC), these drugs affect the central nervous system by activating specific membrane-bound receptors. The primary brain receptors, cannabinoid receptors type 1 (CB1), are G protein–coupled, seven-transmembrane domain proteins that share numerous similarities with heterotrimeric G protein–coupled receptors for conventional neurotransmitters such as γ-aminobutyric acid (GABA) and glutamate. The CB1s bind THC with a high degree of selectivity and are heterogeneously distributed throughout the brain. Inasmuch as THC is a plant-derived compound not produced in mammals, endogenous ligands must exist for the cannabinoid receptor, that is, endocannabinoids. Indeed, several endogenous ligands for CB1 have been discovered, with anandamide being the first. Anandamide and 2-arachidonoyl glycerol (2-AG), are thought to be the major brain endocannabinoids, with regional differences in which one or the other predominates. Endocannabinoids have been strongly implicated in a growing variety of physiologic phenomena, including regulation of eating, anxiety, pain, extinction of aversive memories, and neuroprotection. Potent agonists and antagonists for CB1 exist and may serve as the foundation of new therapeutic strategies for treating pathologies. The voluminous work summarized here has been extensively covered in recent reviews on cannabinoid neurochemistry and pharmacology as well as neurophysiology. This review focuses on the neurophysiology of the endocannabinoid systems.”

“Conclusion

From what is known about their synthesis and release, endocannabinoids should be produced under many conditions of increased neuronal excitability and specific intercellular signaling. For example, an epileptic seizure, with its large swings in transmembrane voltage, increases in intracellular calcium, and marked release of neurotransmitters, such as acetylcholine and glutamate, should prominently release endocannabinoids. Indeed, seizures induced by kainic acid (a glutamate agonist) increase hippocampal levels of anandamide in normal and wild-type mice. Intriguingly, CB1 knockout mice and normal mice treated with a CB1 antagonist had more pronounced seizures and more severe excitotoxic cell death than untreated normal mice. Although the detailed mechanisms of neuroprotection have not been worked out, the rapid increases in expression of the immediate early genes, c-fos and zipf268, and subsequent increase in brain-derived neurotrophic factor (BDNF) normally induced by kainic acid, were absent in the CB1 knockout mice. The results complement previous evidence that exogenous cannabinoids can be neuroprotective and show that CB1 activation by seizure-induced release of endocannabinoids also is normally neuroprotective.”

“The important new directions being opened by investigations of endocannabinoids underscore the prescient opinion of Robert Christison, who, in 1848, noting its various beneficial effects, argued that cannabis “is a remedy which deserves a more extensive inquiry…””

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1176361/