Cannabis – the Israeli perspective

Mechoulam, Raphael

doi:10.1515/jbcpp-2015-0091

Cited by 27 publications

(14 citation statements)

References 37 publications

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“…In countries such as Israel and the Netherlands, herbal cannabis products are being produced for medicinal use. A primary argument for the use of herbal cannabis is to harness what is known as the ‘entourage effect’ by engaging a number of cannabinoid receptors . However, while herbal cannabis can be grown in controlled environments to prevent the amount of pesticides or metals that the cannabis is exposed to, there is less control over the specific compounds that are desired for treatment effects.…”

Section: Discussionmentioning

confidence: 99%

Systematic review and meta‐analysis of cannabinoids in palliative medicine

Mücke

Weier

Carter

et al. 2018

J cachexia sarcopenia muscle

111

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We provide a systematic review and meta‐analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017. Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias. In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD]: 0.2 95% confidence interval [CI]: [−0.66, 1.06] P = 0.65), appetite (SMD: 0.81 95% CI: [−1.14, 2.75]; P = 0.42), nausea/vomiting (SMD: 0.21 [−0.10, 0.52] P = 0.19), >30% decrease in pain (risk differences [RD]: 0.07 95% CI: [−0.01, 0.16]; P = 0.07), or sleep problems (SMD: −0.09 95% CI: [−0.62, 0.43] P = 0.72). In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD: 0.20 [−0.15, 0.54]; P = 0.26). Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [−0.02; 0.08]; P = 0.23) or poor mental health (RD: −0.01 [−0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05). Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer‐associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability. In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.

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Section: Discussionmentioning

confidence: 99%

Systematic review and meta‐analysis of cannabinoids in palliative medicine

Mücke

Weier

Carter

et al. 2018

J cachexia sarcopenia muscle

111

View full text Add to dashboard Cite

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“…Israel serves as a prime example; although MMJ was only legalized in Israel nearly 20 years ago, Israeli scientists have been at the forefront since the 1960s when THC was discovered, and later when the human eCB system was elucidated (Mechoulam, 2015). Since then, researchers in Israel have continued to conduct investigations that help clarify the potential benefits of MJ for various medical conditions (Mechoulam, 2016). Uruguay is also positioned to partner in MJ-related research projects given their recent national legalization.…”

Section: Barriers To Cannabis Researchmentioning

confidence: 99%

Marijuana matters: reviewing the impact of marijuana on cognition, brain structure and function, & exploring policy implications and barriers to research

Sagar

Gruber

2018

International Review of Psychiatry

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The neurobiologic effects of cannabis, commonly referred to as 'marijuana' (MJ), have been studied for decades. The impact of recreational MJ use on cognition and measures of brain function and structure is outlined, and variables influencing study results are discussed, including age of the consumer, patterns of MJ use, variations in MJ potency, and the presence of additional cannabinoids. Although evidence suggests that chronic, heavy recreational MJ use is related to cognitive decrements and neural changes, particularly when use begins in adolescence, findings from studies of recreational MJ users may not be applicable to medical marijuana (MMJ) patients given differences in demographic variables, product selection, and reasons for use. Although additional research is needed to fully understand the impact of MJ and individual cannabinoids on the brain, current findings are beginning to inform public policy, including considerations for age limits, potential limits for some cannabinoids, and guidelines for use. However, barriers continue to impede researchers' ability to conduct studies that will guide policy change and provide vital information to consumers and patients regarding best practices and safest methods for use. The need for information is critical, as legalization of MJ for medical and recreational use is increasingly widespread.

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“…Endocannabinoids and one of the most studied phytocannabinoids, Δ 9 -tetrahydrocannabinol (Δ 9 -THC), are agonists with more or less CB 1 R/CB 2 R selectivity. Furthermore, synthetic cannabinoids mainly act (as agonists or antagonists) by binding to the orthosteric site of receptors ( Mechoulam, 2016 ). Indeed, there is a limited number of molecules, either synthetic or phytocannabinoids, that behave as allosteric modulators of cannabinoid receptor function.…”

Section: Introductionmentioning

confidence: 99%

Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes

et al. 2018

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Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties. The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB1 (CB1R) and CB2 (CB2R) receptors and the effects of the compound on agonist activation of those receptors and of CB1–CB2 heteroreceptor complexes. Using [3H]-CP-55940, CBG competed with low micromolar Ki values the binding to CB1R and CB2R. Homogeneous binding in living cells, which is only technically possible for the CB2R, provided a 152 nM Ki value. Also interesting, CBG competed the binding of [3H]-WIN-55,212-2 to CB2R but not to CB1R (Ki: 2.7 versus >30 μM). The phytocannabinoid modulated signaling mediated by receptors and receptor heteromers even at low concentrations of 0.1–1 μM. cAMP, pERK, β-arrestin recruitment and label-free assays in HEK-293T cells expressing the receptors and treated with endocannabinoids or selective agonists proved that CBG is a partial agonist of CB2R. The action on cells expressing heteromers was similar to that obtained in cells expressing the CB2R. The effect of CBG on CB1R was measurable but the underlying molecular mechanisms remain uncertain. The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling.

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Cannabis – the Israeli perspective

Cited by 27 publications

References 37 publications

Systematic review and meta‐analysis of cannabinoids in palliative medicine

Systematic review and meta‐analysis of cannabinoids in palliative medicine

Marijuana matters: reviewing the impact of marijuana on cognition, brain structure and function, & exploring policy implications and barriers to research

Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes

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