Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer

Blasco-Benito, Sandra; Seijo-Vila, Marta; Caro-Villalobos, Miriam; Tundidor, Isabel; Andradas, Clara; García-Taboada, Elena; Wade, Jeff; Smith, S.; Guzmán, Manuel; Pérez-Gómez, Eduardo; Gordon, Mara; Sánchez, Cristina

doi:10.1016/j.bcp.2018.06.025

Cited by 144 publications

(128 citation statements)

References 27 publications

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“…Submaximal concentrations of tamoxifen in combination with pure THC and cannabis drug preparation decreased the viability in an additive manner. The additive effects observed between tamoxifen and cannabinoids in cell cultures was not evident in vivo [48]. There are no clinical studies evaluating the effect of cannabinoids on treatment with tamoxifen.…”

Section: Selective Estrogen Receptor Modulatorsmentioning

confidence: 96%

“…Blasco-Benito et al evaluated the antitumor efficacy of pure THC with that of a botanical drug preparation made from fresh cannabis flowers. The botanical drug preparation was more potent than pure THC in producing antitumor responses in cell culture and animal models of different BC subtypes, including the HR+ subtype [48].…”

Section: Cannabinoids and Hormone Receptor-positive Breast Cancer (Prmentioning

confidence: 98%

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Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment

Dobovišek

Krstanović

Borštnar

et al. 2020

Cancers

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Breast cancer (BC) is the most common cancer in women worldwide. Approximately 70-80% of BCs express estrogen receptors (ER), which predict the response to endocrine therapy (ET), and are therefore hormone receptor-positive (HR+). Endogenous cannabinoids together with cannabinoid receptor 1 and 2 (CB1, CB2) constitute the basis of the endocannabinoid system. Interactions of cannabinoids with hypothalamic-pituitary-gonadal axis hormones are well documented, and two studies found a positive correlation between peak plasma endogenous cannabinoid anandamide with peak plasma 17β-estradiol, luteinizing hormone and follicle-stimulating hormone levels at ovulation in healthy premenopausal women. Do cannabinoids have an effect on HR+ BC? In this paper we review known and possible interactions between cannabinoids and specific HR+ BC treatments. In preclinical studies, CB1 and CB2 agonists (i.e., anandamide, THC) have been shown to inhibit the proliferation of ER positive BC cell lines. There is less evidence for antitumor cannabinoid action in HR+ BC in animal models and there are no clinical trials exploring the effects of cannabinoids on HR+ BC treatment outcomes. Two studies have shown that tamoxifen and several other selective estrogen receptor modulators (SERM) can act as inverse agonists on CB1 and CB2, an interaction with possible clinical consequences. In addition, cannabinoid action could interact with other commonly used endocrine and targeted therapies used in the treatment of HR+ BC.

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Section: Selective Estrogen Receptor Modulatorsmentioning

confidence: 96%

Section: Cannabinoids and Hormone Receptor-positive Breast Cancer (Prmentioning

confidence: 98%

Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment

Dobovišek

Krstanović

Borštnar

et al. 2020

Cancers

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“…The hundreds of cannabis chemovars or varieties (commonly referred to as strains) developed over millennia have unique and complex constituent profiles, of which each may provide targeted therapeutic usage due to the unique synergistic combination of plant chemicals. Some pharmaceutical preparations have attempted to isolate the key constituents (there are over 140 phytocannabinoids [17]) to provide standardised formulas that may harness this 'entourage effect' [16,18], while being able to provide batch-to-batch assurance of the medicine.…”

Section: Introductionmentioning

confidence: 99%

Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review

et al. 2020

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Background: Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes. Medicinal cannabis has been reported to have potential efficacy in reducing pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and intractable childhood epilepsy. Yet its potential application in the field of psychiatry is lesser known. Methods: The first clinically-focused systematic review on the emerging medical application of cannabis across all major psychiatric disorders was conducted. Current evidence regarding whole plant formulations and plant-derived cannabinoid isolates in mood, anxiety, sleep, psychotic disorders and attention deficit/hyperactivity disorder (ADHD) is discussed; while also detailing clinical prescription considerations (including pharmacogenomics), occupational and public health elements, and future research recommendations. The systematic review of the literature was conducted during 2019, assessing the data from all case studies and clinical trials involving medicinal cannabis or plant-derived isolates for all major psychiatric disorders (neurological conditions and pain were omitted). Results: The present evidence in the emerging field of cannabinoid therapeutics in psychiatry is nascent, and thereby it is currently premature to recommend cannabinoid-based interventions. Isolated positive studies have, however, revealed tentative support for cannabinoids (namely cannabidiol; CBD) for reducing social anxiety; with mixed (mainly positive) evidence for adjunctive use in schizophrenia. Case studies suggest that medicinal cannabis may be beneficial for improving sleep and post-traumatic stress disorder, however evidence is currently weak. Preliminary research findings indicate no benefit for depression from high delta-9 tetrahydrocannabinol (THC) therapeutics, or for CBD in mania. One isolated study indicates some potential efficacy for an oral cannabinoid/ terpene combination in ADHD. Clinical prescriptive consideration involves caution in the use of high-THC formulations (avoidance in youth, and in people with anxiety or psychotic disorders), gradual titration, regular assessment, and caution in cardiovascular and respiratory disorders, pregnancy and breast-feeding. Conclusions: There is currently encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders. Supportive findings are emerging for some key isolates, however, clinicians need to be mindful of a range of prescriptive and occupational safety considerations, especially if initiating higher dose THC formulas.

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“…In this same context, a recent study reported that a botanical drug preparation (BDP) was more potent than pure THC to produce antitumor responses in cell culture and animal models of breast cancer. While pure THC mainly activated CB2R and generated reactive oxygen species (ROS), the BDP modulated different targets and mechanisms of action [78]. This combined effect, observed with the association of phytocannabinoids and other compounds present in the Cannabis sativa plant, such as terpenoids, is known as the entourage effect [79] (Figure 2).…”

Section: Cannabis Phytocannabinoids: Focus On Tetrahydrocannabinol Anmentioning

confidence: 99%

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

et al. 2020

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Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound—Δ9-tetrahydrocannabinol (Δ9-THC)—as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS). Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa. However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself. In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.

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Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer

Cited by 144 publications

References 27 publications

Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment

Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment

Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

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