A Sensitive Ultrahigh-Performance Liquid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Analysis of Phytocannabinoids and Endocannabinoids in Plasma and Brain

Ahmed, Faizy; Torrens, Alexa; Mahler, Stephen V.; Ferlenghi, Francesca; Huestis, Marilyn A.; Piomelli, Daniele

doi:10.1089/can.2022.0216

Cited by 8 publications

(8 citation statements)

References 52 publications

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“…Results demonstrate that CBD 1 has high stability in mice plasma. Although there is a lack of information in the literature on its plasma stability ( ex vivo ), however, the presented experimental results can be correlated with the reported stability in plasma (rat/mice) under various storage conditions during bioanalytical method validation of CBD 1 . On the other hand, test prodrugs 3a and 3aa exhibited rapid conversion to their native form (CBD 1) in mice plasma.…”

mentioning

confidence: 57%

“…Although there is a lack of information in the literature on its plasma stability (ex vivo), however, the presented experimental results can be correlated with the reported stability in plasma (rat/mice) under various storage conditions during bioanalytical method validation of CBD 1. 47 On the other hand, test prodrugs 3a and 3aa exhibited rapid conversion to their native form (CBD 1) in mice plasma. Therefore, results indicate that 3a and 3aa act as a prodrug had a higher propensity to release quickly into its native form, i.e., CBD 1.…”

Section: Synthesis Of Heterocyclic Cbd-ester Based Prodrug Candidatementioning

confidence: 99%

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Cannabidiol-Based Prodrugs: Synthesis and Bioevaluation

Singh Cham,

Kotwal,

Sharma

et al. 2024

ACS Med. Chem. Lett.

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Cannabidiol (CBD 1) is a nonpsychotic cannabinoid-based drug approved by the U.S. FDA for treating refractory epilepsy, namely, Lennox−Gastaut and Dravet syndrome. However, its low aqueous solubility and oral bioavailability are compensated by administering high doses, and there is an increased demand for conjugates with improved properties. In this direction, the present work is focused on synthesizing CBDbased prodrugs to address the issue of poor solubility and oral bioavailability. Several CBD-based prodrugs were synthesized and studied in a battery of assays: viz, release kinetic (ex vivo), solubility (in vitro), chemical stability (in vitro), plasma stability (ex vivo), pharmacokinetics (in vivo), and efficacy studies (in vivo). Among the synthesized prodrugs, the morpholinyl CBD-based prodrugs 3a and 3aa showed good release behavior, stability, better solubility, and a plasma profile. Moreover, prodrug candidate 3aa showed better therapeutic efficacy. The present study identifies CBD-based prodrugs with improved physiochemical properties and oral exposure.

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confidence: 57%

Section: Synthesis Of Heterocyclic Cbd-ester Based Prodrug Candidatementioning

confidence: 99%

Cannabidiol-Based Prodrugs: Synthesis and Bioevaluation

Singh Cham,

Kotwal,

Sharma

et al. 2024

ACS Med. Chem. Lett.

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“…The most studied receptors in this system are TRPV1, 5-HT 1A , PPARγ and PPARα, although some studies have assessed the role of two G protein-coupled receptors (GPRs), the orphan G protein-coupled receptor (GPR) 55 and G protein-coupled receptor 18 (GPR18). [75][76][77][78][79][80] TRPV1 is a cation-permeable ion channel activated by heat, acidic pH and capsaicin (the pungent compound in the pepper Capsicum frutescens). It is a vanilloid receptor or "transient receptor potential cationic channel, subfamily V, member 1" 81 located on GABAergic and glutamatergic terminals; other perikarya in some limbic system structures with relevant mnemonic functions, such as the hippocampus; motor system-related structures, such as the basal nuclei and cerebellum; and elsewhere.…”

Section: Additional Pharmacological Targets Involved With Cannabinoid...mentioning

confidence: 99%

“…In addition to CB1 and CB2 receptors, the eCS may include additional ligands, and some cannabinoid drugs, such as CBD, bind directly or indirectly to noncannabinoid receptors. The most studied receptors in this system are TRPV1, 5‐HT 1A , PPARγ and PPARα, although some studies have assessed the role of two G protein‐coupled receptors (GPRs), the orphan G protein‐coupled receptor (GPR) 55 and G protein‐coupled receptor 18 (GPR18) 75–80 …”

Section: Introductionmentioning

confidence: 99%

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders

de Fátima dos Santos Sampaio,

de Paiva,

Sampaio

et al. 2024

Basic Clin Pharma Tox

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Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system‐related receptors and other molecular targets, such as the 5‐HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5‐HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5‐HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.

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“…In rodents, repeated exposure to THC or to the CB1/CB2 receptor agonist (WIN 55,212-2) increase plasma and brain concentrations of AEA in male and female mice [42] but the effects on 2-AG are inconsistent [40,43,44]. Similarly, in humans, studies of circulating concentrations of endocannabinoids and NAEs in regular cannabis users or following acute cannabis administration are limited and conflicting [45].…”

Section: Introductionmentioning

confidence: 99%

Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder—Preliminary Findings

Boachie,

Gaudette,

Bazinet

et al. 2023

Brain Sciences

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Background: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain. Methods: Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography–mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which may affect concentrations of AEA as well as other NAEs (OEA, DHEA). Results: In overnight abstinent CUD, AEA, OEA and DHEA concentrations were significantly higher (31–40%; p < 0.05) and concentrations of the endocannabinoid 2-AG were marginally elevated (55%, p = 0.13) relative to HC. There were no significant correlations between endocannabinoids/NAE concentrations and cannabis analytes, self-reported cannabis use frequency or withdrawal symptoms. DHEA concentration was inversely related with marijuana craving (r = −0.86; p = 0.001). Genotype had no significant effect on plasma endocannabinoids/NAE concentrations. Conclusions: Our preliminary findings, requiring replication, might suggest that activity of the endocannabinoid system is elevated in chronic cannabis users. It is unclear whether this elevation is a compensatory response or a predating state. Studies examining endocannabinoids and NAEs during prolonged abstinence as well as the potential role of DHEA in craving are warranted.

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A Sensitive Ultrahigh-Performance Liquid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Analysis of Phytocannabinoids and Endocannabinoids in Plasma and Brain

Cited by 8 publications

References 52 publications

Cannabidiol-Based Prodrugs: Synthesis and Bioevaluation

Cannabidiol-Based Prodrugs: Synthesis and Bioevaluation

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders

Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder—Preliminary Findings

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