Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers

Paudel, Kalpana S.; Hammell, Dana C.; Agu, Remigius U.; Valiveti, Satyanarayana; Stinchcomb, Audra L.

doi:10.3109/03639041003657295

Cited by 106 publications

(98 citation statements)

References 35 publications

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“…Furthermore, transdermal delivery of other medications, such as naltrexone and acamprosate, could enhance the utility of pharmacotherapy based treatments for alcohol dependence in general. Transdermal delivery is a controllable extended release formulation (Paudel et al , 2010), therefore improves patient compliance because medications can be administered less frequently. Additionally, transdermal products are non-invasive which promotes patient friendly usage, in contrast to injectable formulations.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 250 μL of blood was collected and placed into silanized microcentrifuge tubes containing heparin, centrifuged at 10,000 × g for 3 min and plasma was stored at −70°C until quantification by LC-MS. CBD was extracted according to previously described methods (Paudel et al , 2010). Briefly, CBD was extracted from 50 μL of plasma using 500 μL of acetonitrile (ACN):ethyl acetate (1:1, v/v).…”

Section: Methodsmentioning

confidence: 99%

“…Estimated oral bioavailability of CBD is roughly 6% (Agurell et al , 1981; Ohlsson et al , 1986); therefore, it is difficult and expensive to achieve suitable plasma levels for clinical efficacy. These drug delivery obstacles may be circumvented by alternative delivery routes, such as transdermal delivery (Paudel et al , 2010). Additionally, transdermal delivery is advantageous because it promotes patient compliance, as this route of administration is non-invasive and pain free compared to injectable formulations, which is especially important in the alcohol dependent population (Swift et al , 2011).…”

Section: Introductionmentioning

confidence: 99%

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Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder

Liput

Hammell²,

Stinchcomb

et al. 2013

Pharmacology Biochemistry and Behavior

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Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism. Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration. In experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance (p = 0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation. Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/d). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex by 56.1% (p < 0.05), while IP CBD resulted in a 50.6% (p < 0.05) reduction in FJB+ cells. These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder

Liput

Hammell²,

Stinchcomb

et al. 2013

Pharmacology Biochemistry and Behavior

Self Cite

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“…This selective targeting of KSHV-induced neoplasia suggests that CBD may have a desirable therapeutic index when used to treat cancer. Moreover, a recent study demonstrated that CBD can be delivered effectively by nasal and transdermal routes, 46 which may be particularly valuable for the treatment of Kaposi sarcoma oral or skin lesions. 47 The molecular mechanisms by which CBD exerts its therapeutic effects are not fully understood, although CBD has been shown to act as an inverse agonist of the cannabinoid receptors CB1 and CB2.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Inhibits Growth and Induces Programmed Cell Death in Kaposi Sarcoma-Associated Herpesvirus-Infected Endothelium

Maor

Kuzontkoski

et al. 2012

Genes & Cancer

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Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma-associated herpesvirus (KSHV). It is prevalent among the elderly in the Mediterranean, inhabitants of sub-Saharan Africa, and immunocompromised individuals such as organ transplant recipients and AIDS patients. Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host. When the host's immune system weakens, KSHV begins to replicate again, and active tumor growth ensues. New therapeutic approaches are needed. Cannabidiol (CBD), a plant-derived cannabinoid, exhibits promising antitumor effects without inducing psychoactive side effects. CBD is emerging as a novel therapeutic for various disorders, including cancer. In this study, we investigated the effects of CBD both on the infection of endothelial cells (ECs) by KSHV and on the growth and apoptosis of KSHV-infected ECs, an in vitro model for the transformation of normal endothelium to Kaposi sarcoma. While CBD did not affect the efficiency with which KSHV infected ECs, it reduced proliferation and induced apoptosis in those infected by the virus. CBD inhibited the expression of KSHV viral G protein-coupled receptor (vGPCR), its agonist, the chemokine growth-regulated protein α (GRO-α), vascular endothelial growth factor receptor 3 (VEGFR-3), and the VEGFR-3 ligand, vascular endothelial growth factor C (VEGF-C). This suggests a potential mechanism by which CBD exerts its effects on KSHV-infected endothelium and supports the further examination of CBD as a novel targeted agent for the treatment of Kaposi sarcoma.

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“…Cannabis typically has a moderate analgesic effect, and may function best when used synergistically with opioids for pain control . Paudel showed CBD delivery for chronic, extended use could be done via transdermal methods, whereas CBD use for breakthrough pain could be achieved using an intranasal method, allowing for a more rapid onset of approximately 10 minutes . The mortality and morbidity associated with narcotic use for pain control continues to be a serious concern for physicians.…”

Section: Potential Therapies For the Otolaryngic Patientmentioning

confidence: 99%

Therapeutic Cannabis and Endocannabinoid Signaling System Modulator Use in Otolaryngology Patients

Bryant

Daniels

Cognetti

et al. 2018

Laryngoscope Investig Oto

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Objectives1) review benefits and risks of cannabis use, with emphasis on otolaryngic disease processes; 2) define and review the endocannabinoid signaling system (ESS); and 3) review state and federal regulations for the use and research of cannabis and ESS modulators.MethodsThis manuscript is a review of the current literature relevant to the stated objectives.ResultsCannabis (marijuana) use is increasing. It is the most widely used illicit substance in the world. There is increasing interest in its therapeutic potential due to changing perceptions, new research, and legislation changes controlling its use. The legal classification of cannabis is complicated due to varied and conflicting state and federal laws. There are currently two synthetic cannabinoid drugs that are FDA approved. Current indications for use include chemotherapy‐related nausea and vomiting, cachexia, and appetite loss. Research has demonstrated potential benefit for use in many other pathologies including pain, inflammatory states, and malignancy. Data exists demonstrating potential antineoplastic benefit in oral, thyroid, and skin cancers.ConclusionsESS modulators may play both a causal and therapeutic role in several disorders seen in otolaryngology patients. The use of cannabis and cannabinoids is not without risk. There is a need for further research to better understand both the adverse and therapeutic effects of cannabis use. With increasing rates of consumption, elevated public awareness, and rapidly changing legislation, it is helpful for the otolaryngologist to be aware of both the adverse manifestations of use and the potential therapeutic benefits when talking with patients.

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Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers

Abstract: The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.

Cited by 106 publications

References 35 publications

Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder

Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder

Cannabidiol Inhibits Growth and Induces Programmed Cell Death in Kaposi Sarcoma-Associated Herpesvirus-Infected Endothelium

Therapeutic Cannabis and Endocannabinoid Signaling System Modulator Use in Otolaryngology Patients

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