Cannabis and cannabinoid drug development: evaluating botanical versus single molecule approaches

Bonn‐Miller, Marcel O.; ElSohly, Mahmoud A.; Loflin, Mallory; Chandra, Suman; Vandrey, Ryan G.

doi:10.1080/09540261.2018.1474730

Cited by 54 publications

(66 citation statements)

References 32 publications

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“…Alternatively, CBD is gaining popularity for medical uses due to its different mechanism of action from that of THC and its safety profile [2]. Current cannabinoid drug development is characterized by two distinctive paths with one path focused on the direct use of CBD oils and the other path focused on the use of natural or synthetic CBD [8]. On the one hand, the pursuit of purified CBD for drug development follows established guidelines for drug discovery with regard to quality, safety, and efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Most worryingly, CBD oil adulteration, such as dilution, blending, and rectification are legally permissible. Adulteration of CBD oils most likely diminishes the benefits associated with the entourage effects of the natural constituents [5][6][7][8]. Furthermore, acute poisoning due to the addition of a synthetic cannabinoid to CBD products has been reported by a growing number of users [9].…”

Section: Introductionmentioning

confidence: 99%

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Potency Assessment of CBD Oils by Their Effects on Cell Signaling Pathways

Urasaki

Beaumont²,

Workman³

et al. 2020

Nutrients

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This study used nanofluidic protein posttranslational modification (PTM) profiling to measure the effects of six cannabidiol (CBD) oils and isolated CBD on the signaling pathways of a cultured SH-SY5Y neuronal cell line. Chemical composition analysis revealed that all CBD oils met the label claims and legal regulatory limit regarding the CBD and tetrahydrocannabinol (THC) contents, respectively. Isolated CBD was cytotoxic, with an effective concentration (EC50) of 40 µM. In contrast, the CBD oils had no effect on cell viability at CBD concentrations exceeding 1.2 mM. Interestingly, only an unadulterated CBD oil had strong and statistically significant suppressive effects on the pI3K/Akt/mTOR signaling pathway with an EC50 value of 143 µM and a slow-acting timescale requiring hours. Systematic profiling of twenty-six proteins, which served as biomarkers for nine signaling pathways, revealed that the unadulterated CBD oil downregulated seven signaling pathways but had no measurable effect on the other two signaling pathways. The remaining CBD oils, which were adulterated, and isolated CBD had weak, variable, or undetectable effects on neuronal signaling pathways. Our data clearly showed that adulteration diminished the biological activities of CBD oils. In addition, nanofluidic protein PTM profiling provided a robust means for potency assessment of CBD oils.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Potency Assessment of CBD Oils by Their Effects on Cell Signaling Pathways

Urasaki

Beaumont²,

Workman³

et al. 2020

Nutrients

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“…In almost all prospective open label studies with larger cohorts purified plant derived CBD has been used. Since pharmaceuticalgrade synthetically derived cannabidiol is chemically identical to the cannabidiol found naturally in the cannabis plant, we did not expect any relevant differences in efficacy and tolerance (10). Nevertheless, this study is the first to report efficacy and tolerance of synthetic cannabidiol in epilepsy treatment to be comparable to plant derived CBD.…”

Section: Discussionmentioning

confidence: 84%

“…Recently, the first pharmaceutical formulation of highly purified, plant derived CBD has been approved by the US Food and Drug Administration (9). Single molecule cannabinoid drug development is a different approach where pharmaceuticalgrade synthetically derived substances are used (10). Easier quality control, unlimited production possibilities and reduced environmental impact are advantages of synthetically derived cannabinoids and support further investigations of its therapeutic use.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

et al. 2019

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Objective: Controlled and open label trials have demonstrated efficacy of cannabidiol for certain epileptic encephalopathies. However, plant derived cannabidiol products have been used almost exclusively. Efficacy of synthetically derived cannabidiol has not been studied before. The objective of this study was to evaluate tolerability and efficacy of synthetic cannabidiol in patients with pharmacoresistant epilepsy. Methods: In this prospective, open-label study (DRKS00013177), patients with pharmacoresistant epilepsy received synthetic cannabidiol in addition to their previously stable anticonvulsive treatment. Starting dose was 5 mg/kg/day, up-titrated to a maximum of 50 mg/kg/day. Primary efficacy endpoint was monthly frequency of motor seizures at 3 months. Results: Between April 2017 and May 2019, 35 patients were enrolled in the study. Mean age was 19.7 years (SD 14.6). Median motor seizure frequency decreased from 21.8 (IQR 7.5-52.5) seizures per month at baseline to 8.5 (IQR 3.7-28.3, p < 0.001) at 3 months, effect not influenced by AED changes and drop-outs. Adjusted percentage reduction was 40.0% (IQR 18.2-58.5). Adverse events (AE) were reported in 25 patients (71.4%), most frequently somnolence (40%), diarrhea (34.3), and loss of appetite (20%). Two patients (5.7%) discontinued treatment due to AE. Median (range) of treatment duration was 321 days (range 36-824). With ongoing treatment up to date in 21 patients (60%). Conclusion: Efficacy and tolerance in our study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD. Regarding economic and ecological aspects, synthetic cannabidiol might be a reasonable alternative to plant derived cannabidiol.

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“…Indeed, federal regulation and pharmaceutical drug development of cannabis, hemp, and cannabinoid products is an often complex and poorly understood issue. 6,7 The current state and federal cannabinoid and medical cannabis laws are surely overdue for an overhaul, as cannabis is shackled by its Schedule I status in the United…”

Section: New Hope For An Old Medicinementioning

confidence: 99%

The legalization of cannabinoid products and standardizing cannabis-drug development in the United States: a brief report

Marcu

2020

Dialogues in Clinical Neuroscience

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This brief report covers recent advances in cannabis and cannabinoid regulation and drug approval. The popularity of cannabis and cannabinoid products continues to rise, and these products are available for the majority of the population in the United States to purchase as easily as alcohol. Although many states have approved programs and research licenses, these activities and products all remain federally illegal. The solution may be for the United States to offer multiple pathways for product approval that adapt to the diversity of the products and the needs of the consumer. Multiple pathways for market approval would protect public health, whether the public is using cannabis and cannabinoids as a medicine, a wellness product, or as a recreational substance.

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Cannabis and cannabinoid drug development: evaluating botanical versus single molecule approaches

Cited by 54 publications

References 32 publications

Potency Assessment of CBD Oils by Their Effects on Cell Signaling Pathways

Potency Assessment of CBD Oils by Their Effects on Cell Signaling Pathways

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

The legalization of cannabinoid products and standardizing cannabis-drug development in the United States: a brief report

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