Promoting cannabis products to pharmaceutical drugs

Koltai, Hinanit; Poulin, Patrick; Namdar, Dvory

doi:10.1016/j.ejps.2019.02.027

Cited by 27 publications

(19 citation statements)

References 17 publications

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“…The possible permutations for different combinations of compounds, phytocannabinoids, and terpenoids in a given strain is a challenge for the development of cannabis-based drugs. The specificity in phytocannabinoid–terpenoid correlations and interaction may imply that during pharmaceutical development the inter-entourage effect of its components should be tested for antagonistic, additive, or synergistic results [10,11,18]. Controlling the ratios between terpenoids and phytocannabinoids in a given preparation may substantially improve biological activity, clarifying and improving potential therapies [10].…”

Section: Discussionmentioning

confidence: 99%

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Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity

et al. 2019

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Mixtures of different Cannabis sativa phytocannabinoids are more active biologically than single phytocannabinoids. However, cannabis terpenoids as potential instigators of phytocannabinoid activity have not yet been explored in detail. Terpenoid groups were statistically co-related to certain cannabis strains rich in Δ9-tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA), and their ability to enhance the activity of decarboxylase phytocannabinoids (i.e., THC or CBD) was determined. Analytical HPLC and GC/MS were used to identify and quantify the secondary metabolites in 17 strains of C. sativa, and correlations between cannabinoids and terpenoids in each strain were determined. Column separation was used to separate and collect the compounds, and cell viability assay was used to assess biological activity. We found that in “high THC” or “high CBD” strains, phytocannabinoids are produced alongside certain sets of terpenoids. Only co-related terpenoids enhanced the cytotoxic activity of phytocannabinoids on MDA-MB-231 and HCT-116 cell lines. This was found to be most effective in natural ratios found in extracts of cannabis inflorescence. The correlation in a particular strain between THCA or CBDA and a certain set of terpenoids, and the partial specificity in interaction may have influenced the cultivation of cannabis and may have implications for therapeutic treatments.

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Section: Discussionmentioning

confidence: 99%

“…This phenomenon has been called “the entourage effect” [10] and may originate from synergistic interactions between cannabis compounds. In some cases of synergistic activity, the effect may originate from the activation of more than one signaling pathway [13,18].…”

Section: Introductionmentioning

confidence: 99%

Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity

et al. 2019

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“…Thus, cannabis appliance should be optimized to contain mixtures of these C. sativa -derived combined components. Another possibility is to use the whole extract with all compounds that produce the greatest synergistic activity [ 107 ].…”

Section: The “Entourage Effect” Of Cannabinoids and Terpenes For The mentioning

confidence: 99%

The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

Ferber

Namdar

Hen-Shoval

et al. 2020

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Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.

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“…Identifying the APIs and their specific compositions within a plant extract, followed by the manufacture of a pure and quantifiable compositions, may lead to pharmaceutical drugs inspired by or based on only the beneficial compounds in cannabis for a certain medical condition. Importantly, these might be targeted to specific mechanisms involved with different diseases [ 31 , 33 , 37 ].…”

Section: Taking Advantage Of the “Entourage Effect”mentioning

confidence: 99%

“…As for the future, we appreciate the aspects involved in cannabis-based drug development, such as complex entourage effects and terpene considerations [ 33 , 34 , 35 , 36 , 37 ]. We also acknowledge the current difficulties of the pharma industry to include natural preparations, as discussed above.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Chronological Review and Rational and Future Prospects of Cannabis-Based Drug Development

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Despite the surge in cannabis chemistry research and its biological and medical activity, only a few cannabis-based pharmaceutical-grade drugs have been developed and marketed to date. Not many of these drugs are Food and Drug Administration (FDA)-approved, and some are still going through regulation processes. Active compounds including cannabinergic compounds (i.e., molecules targeted to modulate the endocannabinoid system) or phytocannabinoid analogues (cannabinoids produced by the plant) may be developed into single-molecule drugs. However, since in many cases treatment with whole-plant extract (whether as a solvent extraction, galenic preparation, or crude oil) is preferred over treatment with a single purified molecule, some more recently developed cannabis-derived drugs contain several molecules. Different combinations of active plant ingredients (API) from cannabis with proven synergies may be identified and developed as drugs to treat different medical conditions. However, possible negative effects between cannabis compounds should also be considered, as well as the effect of the cannabis treatment on the endocannabinoid system. FDA registration of single, few, or multiple molecules as drugs is a challenging process, and certain considerations that should be reviewed in this process, including issues of drug–drug interactions, are also discussed here.

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Promoting cannabis products to pharmaceutical drugs

Cited by 27 publications

References 17 publications

Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity

Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity

The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders

Chronological Review and Rational and Future Prospects of Cannabis-Based Drug Development

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