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1.
Talanta ; 236: 122863, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635245

RESUMO

Cannabis is currently one of the most consumed drugs in many countries. Δ9-tetrahydrocannabinol (THC) is the principal psychoactive component of this drug and is present in saliva after consumption. This paper reports a novel biomolecule-free electrochemical approach to detect an ultra-low level of THC in saliva using modified electrodes with molecules of the same analyte (THC) that are detected later via square wave voltammetry. The results from this research revealed that the electrodeposition of THC on the working electrode (sensor analyte) could highly enhance the limit of detection by improving the affinity of the THC molecules present in the sample (sample analyte) to the sensing electrode surface. Detailed descriptions about the optimization of the sensor and its performance in simple media, such as PBS, and complex media, such as simulated and real saliva, are provided. This novel and yet simple electrochemical-based sensing strategy allowed for a low limit of detection of 1.6 ng/mL THC in simulated and real saliva, distinguishing concentrations ranging from 2 to 25 ng/mL, making this technology viable for a real-world application such as roadside testing.


Assuntos
Cannabis , Alucinógenos , Dronabinol , Eletrodos , Saliva
2.
Talanta ; 237: 122905, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736642

RESUMO

Herein we report on the early detection of cannabinoids in urine samples according to their affinity profiles in competitive assays with labelled ghrelin (GHR). We have demonstrated for the first time that cannabidiol (CBD) and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (carboxy-THC) act as extracellular ligands for the growth hormone secretagogue receptor (GHS-R1a), strongly promoting the binding of ghrelin (GHR), the endogenous ligand of GHS-R1a. The affinity profiles of CBD and carboxy-THC are significantly different from the profiles of synthetic GHR mimetics such as CJC-1295 or [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-Substance P peptides, which are the most common interferents; the cannabinoids promoted the GHR/GHS-R1a interaction, while the ghrelin mimetics acted rather as competitive inhibitors. The analysis of 1:4 diluted urine samples proved that the proposed method displays good linearity and sensitivity in the range of 5-30 ng/mL for both CBD and carboxy-THC, whereas GHR mimetics display no interference at concentrations up to 100 ng/mL. The results were validated by comparison with the gas chromatography tandem mass spectrometry reference method. CBD may exert the same promoting effect on the interaction of GHS-R1a with other GHR mimetics listed as performance-enhancing substances.


Assuntos
Canabidiol , Canabinoides , Canabidiol/análise , Canabinoides/análise , Dronabinol/análise , Cromatografia Gasosa-Espectrometria de Massas , Receptores de Grelina
3.
Sci Total Environ ; 805: 150269, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34536871

RESUMO

Evaluating consumption estimates for lipophilic drugs in wastewater has proven to be a challenge. A common feature for these compounds is that they are excreted in faeces and in conjugated form in urine. Limited research with no obvious experimental evidence has been conducted to investigate the degree to which faecal-bound chemical markers contribute towards mass loads in wastewater. Cannabis chemical markers, known as phytocannabinoids, have been suggested in literature to fall into this category. In this study, cannabis users (n = 9) and non-cannabis users (n = 5) were recruited and provided faecal and urine samples after using the substance. The common chemical markers of cannabis consumption, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH), Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), were investigated. An extraction method was developed for the cannabis chemical markers in faecal matter and urine and analysis was performed by liquid chromatography-mass spectrometry. Participant samples were used to establish adsorption and desorption dissolution kinetics models and to assess the equilibrium between faeces and water for these compounds. Equilibration between phases were found to be fast (<5 min). THC-COOH, which is the primary metabolite used in wastewater studies, partitioned ~40% in water while the less polar metabolite and CBD remained largely associated with the particulate fraction. Faecal loads of both cannabis users and non-users affected the total measured amounts of cannabinoids in the aqueous phase. The implications for wastewater monitoring of lipophilic substances are discussed.


Assuntos
Canabinoides , Vigilância Epidemiológica Baseada em Águas Residuárias , Dronabinol , Fezes , Humanos , Detecção do Abuso de Substâncias , Água
4.
Rev. colomb. anestesiol ; 49(4): e302, Oct.-Dec. 2021. tab
Artigo em Inglês | LILACS, COLNAL | ID: biblio-1341241

RESUMO

Abstract Fibromyalgia is a chronic disease of unclear etiology, involving a neural oversensitization and impaired pain modulation, in addition to a clinical deficiency of the endocannabinoid system. Fibromyalgia is associated with a number of somatic and psychological disorders and hence multiple pharmacological approaches have been used, including opioids, antidepressants, antiepileptics, and more recently medical cannabis. This narrative review comprises a review of the current literature on the efficacy of cannabinoids in fibromyalgia. The studies describe a possible influence of cannabis on pain control in patients with fibromyalgia, with positive effects on quality of life and sleep. The use of cannabis seems to be beneficial in patients with fibromyalgia; however, more robust studies are still needed to establish is actual efficacy in pain management, quality of life and improvement of associated symptoms.


Resumen La fibromialgia es una enfermedad crónica, cuya etiología no es clara, en la que se involucra una sobresensibilización neural y disminución de la modulación del dolor, así como una deficiencia clínica del sistema endocannabinoide. Está asociada a una variedad de trastornos somáticos y psicológicos, por lo cual se han utilizado múltiples abordajes farmacológicos, entre ellos opioides, antidepresivos, antiepilépticos y, recientemente, cannabis medicinal. En esta revisión narrativa se hace una reseña de la literatura actual relacionada con la eficacia de los cannabinoides en la fibromialgia. Los estudios describen una posible influencia del cannabis sobre el control del dolor en pacientes con fibromialgia, con efectos positivos sobre la calidad de vida y el sueño. El uso del cannabis parece tener beneficios en los pacientes con fibromialgia; sin embargo, aún se requieren estudios más robustos para establecer su verdadera eficacia en el manejo del dolor, calidad de vida y mejoría de los síntomas asociados.


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Cannabis , Fibromialgia/terapia , Maconha Medicinal , Dronabinol , Canabinoides , Literatura de Revisão como Assunto , Fibromialgia
5.
Am J Case Rep ; 22: e933488, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762615

RESUMO

BACKGROUND Delta-8 tetrahydrocannabinol (delta-8 THC) is an isomer of delta-9-tetrahydrocannabinol (delta-9 THC), the primary psychoactive cannabinoid in the marijuana plant. Typically found at lower concentrations in marijuana, delta-8 THC exhibits psychoactive properties similar to delta-9 THC. Products containing delta-8 THC are readily available across the US and currently there is a lack of available confirmatory testing specific to delta-8 THC as there is cross-reactivity to other naturally occurring cannabinoids in standard immunoassays. Pediatric exposures to this substance are on the rise. CASE REPORT We present a case with laboratory confirmation of a previously healthy 2-year-old girl ingesting approximately 15 mg/kg of delta-8 THC gummies. The patient arrived minimally responsive and requiring intubation for encephalopathy. Laboratory confirmation of delta-8 THC exposure is not routinely available with common testing modalities. A urine drug screen preformed in the hospital was positive for delta-9 THC. With the collaboration of the Drug Enforcement Administration's Toxicology Testing Program, detection and confirmation of delta-8 THC was performed in the serum and urine using liquid chromatography-quadrupole time-of-flight mass spectrometry. CONCLUSIONS The prevalence of delta-8 THC-containing products in the illicit drug market is increasing rapidly. Delta-8 THC products are now available in gas stations and in headshops. The clinical presentation of delta-8 THC exposure is similar to known effects of delta-9 THC exposure. These similarities limit the clinicians' abilities to determine the specific substance ingested. Symptomatic and supportive care remains an effective treatment for cannabinoid toxicity.


Assuntos
Encefalopatias , Canabinoides , Criança , Pré-Escolar , Dronabinol/análogos & derivados , Ingestão de Alimentos , Feminino , Humanos
6.
Medicina (Kaunas) ; 57(10)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684144

RESUMO

Cannabis products that contain the tetrahydrocannabinol (THC) cannabinoid are emerging as promising therapeutic agents for the treatment of medical conditions such as chronic pain. THC elicits psychoactive effects through modulation of dopaminergic neurons, thereby altering levels of dopamine in the brain. This case report highlights the complexity associated with medicinal cannabis and the health risks associated with its use. A 57-year-old male with Parkinson's disease was experiencing worsening tremors and vivid hallucinations despite therapy optimization attempts. It was discovered that the patient took cannabis for chronic back pain, and a pharmacogenomics (PGx) test indicated the presence of variants for the COMT and HTR2A genes. These variants could increase dopamine levels and predispose patients to visual hallucinations. Once the cannabis was discontinued, the patient's hallucinations began to slowly dissipate. Cannabis use continues to expand as it gains more acceptance legally and medicinally, but cannabis can affect the response to drugs. This patient case suggests that cannabis use in combination with dopamine-promoting drugs, especially in a patient with genetic variants, can increase the risk for vivid hallucinations. These conditions support the importance of considering herb-drug interactions and PGx data when performing a medication safety review.


Assuntos
Cannabis , Doença de Parkinson , Cannabis/efeitos adversos , Dopaminérgicos , Dronabinol/efeitos adversos , Alucinações/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico
8.
Development ; 148(19)2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610637

RESUMO

Many developmental disorders are thought to arise from an interaction between genetic and environmental risk factors. The Hedgehog (HH) signaling pathway regulates myriad developmental processes, and pathway inhibition is associated with birth defects, including holoprosencephaly (HPE). Cannabinoids are HH pathway inhibitors, but little is known of their effects on HH-dependent processes in mammalian embryos, and their mechanism of action is unclear. We report that the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) induces two hallmark HH loss-of-function phenotypes (HPE and ventral neural tube patterning defects) in Cdon mutant mice, which have a subthreshold deficit in HH signaling. THC therefore acts as a 'conditional teratogen', dependent on a complementary but insufficient genetic insult. In vitro findings indicate that THC is a direct inhibitor of the essential HH signal transducer smoothened. The canonical THC receptor, cannabinoid receptor-type 1, is not required for THC to inhibit HH signaling. Cannabis consumption during pregnancy may contribute to a combination of risk factors underlying specific developmental disorders. These findings therefore have significant public health relevance.


Assuntos
Padronização Corporal/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/toxicidade , Dronabinol/toxicidade , Holoprosencefalia/induzido quimicamente , Receptor Smoothened/metabolismo , Teratógenos/toxicidade , Animais , Agonistas de Receptores de Canabinoides/farmacologia , Moléculas de Adesão Celular/genética , Células Cultivadas , Dronabinol/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Tubo Neural/efeitos dos fármacos , Tubo Neural/embriologia , Tubo Neural/metabolismo , Transdução de Sinais/efeitos dos fármacos , Teratógenos/farmacologia
10.
Chem Res Toxicol ; 34(10): 2169-2179, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34622654

RESUMO

The outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) has been cause for concern to the medical community, particularly given that this novel illness has coincided with the COVID-19 pandemic, another cause of severe pulmonary illness. Though cannabis e-cigarettes tainted with vitamin E acetate were primarily associated with EVALI, acute lung injuries stemming from cannabis inhalation were reported in the literature prior to 2019, and it has been suggested that cannabis components or additives other than vitamin E acetate may be responsible. Despite these concerning issues, novel cannabis vaporizer ingredients continue to arise, such as Δ8-tetrahydrocannabinol, Δ10-tetrahydrocannabinol, hexahydrocannabinol, and cannabichromene. In order to address cannabis e-cigarette safety and vaping in an effective manner, we provide a comprehensive knowledge of the latest products, delivery modes, and ingredients. This perspective highlights the types of cannabis vaping modalities common to the United States cannabis market, with special attention to cartridge-type cannabis e-cigarette toxicology and their involvement in the EVALI outbreak, in particular, acute lung injurious responses. Novel ingredient chemistry, origins, and legal statuses are reviewed, as well as the toxicology of known cannabis e-cigarette aerosol components.


Assuntos
Cannabis/química , Lesão Pulmonar/etiologia , Fumar Maconha/efeitos adversos , Extratos Vegetais/química , Aerossóis/química , Aerossóis/toxicidade , Cannabis/metabolismo , Dronabinol/química , Dronabinol/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Extratos Vegetais/toxicidade , Vitamina E/química
11.
J Vet Pharmacol Ther ; 44(6): 870-882, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34605042

RESUMO

Medical use of Cannabis (or hemp) began thousands of years ago. In the 20th century, mechanisms of action were demonstrated with the discovery of its active substances, the phytocannabinoids, and its pharmacological targets, the endocannabinoid system. This system is composed of receptors, endogenous substances, and enzymes, and it participates in the modulation of physiological mechanisms in several species, including dogs. Studies indicate that changes in this system may contribute to the genesis of some diseases. Therefore, the use of substances that act on its components may help in the treatment of these diseases. The main phytocannabinoids described are Δ9- tetrahydrocannabinol (THC) and cannabidiol (CBD). In humans, the benefits of using CBD in several diseases have been demonstrated. The popularization of this type of treatment has also reached veterinary medicine, which on one hand was related to an increase in adverse event records, but on the other also allowed reports of anecdotal evidences of its effectiveness and safety in animals. Clinical studies published so far indicate that the use of CBD in dogs can be safe at given doses and can contribute to osteoarthritis and idiopathic epilepsy treatments. Clinical and pre-clinical studies and case reports were reviewed in this report to identify the main characteristics of hemp-based therapies in dogs, including its pharmacokinetics, pharmacodynamics, safety, and efficacy in the treatment of diseases.


Assuntos
Canabidiol , Cannabis , Animais , Proteínas de Transporte , Cães , Dronabinol
12.
J Chromatogr A ; 1658: 462608, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34666269

RESUMO

Aside from Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), other less common cannabinoids have recently gained an increasing popularity, mostly due to their promising biological potential. However, time-saving and cost-effective methods for their preparative purification are missing. In this study, trapping multiple dual mode (MDM), a flow-reversal liquid-liquid chromatography (LLC) operating mode, was used for the separation of different minor cannabinoids from a hemp extract. Separation task specific biphasic solvent systems were selected for the purification of the target constituents, as follows: n-hexane/methanol/water 10/6.5/3.5 for cannabielsoin (CBE); n-hexane/methanol/water 10/7/3 for cannabidivarin (CBDV) and cannabigerol (CBG); n-hexane/methanol/water 10/8/2 for cannabinol (CBN) and n-hexane/methanol/water 10/9/1 for cannabichromene (CBC) and cannabicylol (CBL). For each separation task, the concentration of the hemp extract in the feed stream and mobile phase flow rate were selected by shake-flask and stationary phase retention experiments, respectively. For the determination of the trapping MDM operating parameters, the short-cut method was implemented and followed by equilibrium-cell model-based simulations. The trapping MDM allowed the separation of the targeted cannabinoids with purities of 93-99%, yields of 73-95%, solvent consumption 2-4-fold lower and productivities almost double than those obtained using batch separation.


Assuntos
Canabinoides , Cannabis , Canabinoides/análise , Cromatografia Líquida , Dronabinol , Extratos Vegetais
13.
Int J Mol Sci ; 22(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502436

RESUMO

Up to 20% of pregnant women ages 18-24 consume cannabis during pregnancy. Moreover, clinical studies indicate that cannabis consumption during pregnancy leads to fetal growth restriction (FGR), which is associated with an increased risk of obesity, type II diabetes (T2D), and cardiovascular disease in the offspring. This is of great concern considering that the concentration of Δ9- tetrahydrocannabinol (Δ9-THC), a major psychoactive component of cannabis, has doubled over the last decade and can readily cross the placenta and enter fetal circulation, with the potential to negatively impact fetal development via the endocannabinoid (eCB) system. Cannabis exposure in utero could also lead to FGR via placental insufficiency. In this review, we aim to examine current pre-clinical and clinical findings on the direct effects of exposure to cannabis and its constituents on fetal development as well as indirect effects, namely placental insufficiency, on postnatal metabolic diseases.


Assuntos
Agonistas de Receptores de Canabinoides/efeitos adversos , Dronabinol/efeitos adversos , Retardo do Crescimento Fetal/induzido quimicamente , Placenta/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Doenças Metabólicas/induzido quimicamente , Gravidez
14.
J Pharm Biomed Anal ; 205: 114344, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34492452

RESUMO

Quality control of CBD oils on the Belgium market showed that the CBD content not always corresponds to the label claim. There is a pressing need to develop new analytical methods specifically developed to the assay of such oily samples. Analytical issues are, however, encountered for routine analyses due to the matrix complexity, high cost of cannabinoid standards and low Δ9-THC concentrations. An oily matrix could cause technical damages to analytical instruments and reduce the lifetime of the chromatographic columns. This paper proposes a procedure combining a sample cleanup by QuEChERS, removing the oily matrix, followed by a validated MRM GC-MS/MS method for the routine analysis of CBD oil samples. Eighteen CBD samples were selected on the Belgium market for analysis. This method allows the quantification of CBD, the legality check for the Δ9-THC content by a CBN standard and the screening of seven other cannabinoids namely CBN, CBDV, CBT, CBC, Δ8-THC, THCV and CBG. The method was validated at three concentration levels (0.5-1-2% (w/v)) for CBD and (0.05-0.1-0.2% (w/v)) for CBN. The detection limits for CBT, CBD, CBC, Δ8-THC, CBN and for the other cannabinoids of interest, were 10 and 14 ng/mL respectively. The accuracy profile values for CBD and CBN showed that the ß-expectation tolerance intervals did not exceed the acceptance limits of ± 20%, meaning that 90% of future measurements will be included within this error range.


Assuntos
Canabidiol , Espectrometria de Massas em Tandem , Bélgica , Canabidiol/análise , Dronabinol/análise , Cromatografia Gasosa-Espectrometria de Massas , Óleos Vegetais , Controle de Qualidade
15.
BMJ Open ; 11(9): e050831, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493521

RESUMO

OBJECTIVE: To explore values and preferences towards medical cannabis among people living with chronic pain. DESIGN: Mixed-methods systematic review. DATA SOURCES: We searched MEDLINE, EMBASE and PsycINFO from inception to 17 March 2020. STUDY SELECTION: Pairs of reviewers independently screened search results and included quantitative, qualitative and mixed-methods studies reporting values and preferences towards medical cannabis among people living with chronic pain. REVIEW METHODS: We analysed data using meta-narrative synthesis (quantitative findings were qualitised) and tabulated review findings according to identified themes. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess certainty of evidence. RESULTS: Of 1838 initial records, 15 studies proved eligible for review. High to moderate certainty evidence showed that patient's use of medical cannabis for chronic pain was influenced by both positive (eg, support from friends and family) and negative social factors (eg, stigma surrounding cannabis use). Most patients using medical cannabis favoured products with balanced ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD), or high levels of CBD, but not high THC preparations. Many valued the effectiveness of medical cannabis for symptom management even when experiencing adverse events related to concentration, memory or fatigue. Reducing use of prescription medication was a motivating factor for use of medical cannabis, and concerns regarding addiction, losing control or acting strangely were disincentives. Out-of-pocket costs were a barrier, whereas legalisation of medical cannabis improved access and incentivised use.Low to very low certainty evidence suggested highly variable values towards medical cannabis among people living with chronic pain. Individuals with pain related to life-limiting disease were more willing to use medical cannabis, and preferred oral over inhaled administration. CONCLUSIONS: Our findings highlight factors that clinicians should consider when discussing medical cannabis. The variability of patients' values and preferences emphasise the need for shared decision making when considering medical cannabis for chronic pain.


Assuntos
Canabidiol , Cannabis , Dor Crônica , Maconha Medicinal , Dor Crônica/tratamento farmacológico , Dronabinol , Humanos , Maconha Medicinal/uso terapêutico
16.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500787

RESUMO

The cannabis-derived molecules, ∆9 tetrahydrocannabinol (THC) and cannabidiol (CBD), are both of considerable therapeutic interest for a variety of purposes, including to reduce pain and anxiety and increase sleep. In addition to their other pharmacological targets, both THC and CBD are competitive inhibitors of the equilibrative nucleoside transporter-1 (ENT-1), a primary inactivation mechanism for adenosine, and thereby increase adenosine signaling. The goal of this study was to examine the role of adenosine A2A receptor activation in the effects of intraperitoneally administered THC alone and in combination with CBD or PECS-101, a 4'-fluorinated derivative of CBD, in the cannabinoid tetrad, elevated plus maze (EPM) and marble bury assays. Comparisons between wild-type (WT) and A2AR knock out (A2AR-KO) mice were made. The cataleptic effects of THC were diminished in A2AR-KO; no other THC behaviors were affected by A2AR deletion. CBD (5 mg/kg) potentiated the cataleptic response to THC (5 mg/kg) in WT but not A2AR-KO. Neither CBD nor THC alone affected EPM behavior; their combination produced a significant increase in open/closed arm time in WT but not A2AR-KO. Both THC and CBD reduced the number of marbles buried in A2AR-KO but not WT mice. Like CBD, PECS-101 potentiated the cataleptic response to THC in WT but not A2AR-KO mice. PECS-101 also reduced exploratory behavior in the EPM in both genotypes. These results support the hypothesis that CBD and PECS-101 can potentiate the cataleptic effects of THC in a manner consistent with increased endogenous adenosine signaling.


Assuntos
Canabidiol/farmacologia , Dronabinol/farmacologia , Receptor A2A de Adenosina/metabolismo , Animais , Canabidiol/análogos & derivados , Dronabinol/administração & dosagem , Comportamento Exploratório/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptor A2A de Adenosina/deficiência
17.
Biochemistry ; 60(37): 2749-2760, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34491040

RESUMO

Cytochrome P450 2D6 (CYP2D6) is primarily expressed in the liver and in the central nervous system. It is known to be highly polymorphic in nature. It metabolizes several endogenous substrates such as anandamide (AEA). Concomitantly, it is involved in phase 1 metabolism of several antidepressants, antipsychotics, and other drugs. Research in the field of phytocannabinoids (pCBs) has recently accelerated owing to their legalization and increasing medicinal use for pain and inflammation. The primary component of cannabis is THC, which is well-known for its psychotropic effects. Since CYP2D6 is an important brain and liver P450 and is known to be inhibited by CBD, we investigated the interactions of four important highly prevalent CYP2D6 polymorphisms with selected phytocannabinoids (CBD, THC, CBDV, THCV, CBN, CBG, CBC, ß-carophyllene) that are rapidly gaining popularity. We show that there is differential binding of CYP2D6*17 to pCBs as compared to WT CYP2D6. We also perform a more detailed comparison of WT and *17 CYP2D6, which reveals the possible regulation of AEA metabolism by CBD. Furthermore, we use molecular dynamics to delineate the mechanism of this binding, inhibition, and regulation. Taken together, we have found that the interactions of CYP2D6 with pCBs vary by polymorphism and by specific pCB class.


Assuntos
Canabinoides/metabolismo , Canabinoides/farmacologia , Citocromo P-450 CYP2D6/genética , Canabidiol/metabolismo , Canabidiol/farmacologia , Canabinol/metabolismo , Canabinol/farmacologia , Cannabis/química , Cannabis/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Dronabinol/metabolismo , Dronabinol/farmacologia , Humanos , Simulação de Dinâmica Molecular , Compostos Fitoquímicos/metabolismo , Polimorfismo Genético/efeitos dos fármacos
19.
J Psychiatr Res ; 143: 327-333, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34536664

RESUMO

Cannabis contains a multitude of different compounds. One of them, cannabidiol - a non-psychoactive substance - might counteract negative effects of Δ-9-Tetrahydrocannabinol on hippocampus-dependent memory impairment. The aim of the present study was to investigate the effect of vaping cannabidiol on verbal episodic memory in healthy young subjects. We used a double-blind, placebo-controlled, randomized crossover trial in 39 healthy young subjects. Participants received once a single dose of cannabidiol e-liquid (0.25 ml, 5% cannabidiol, 12.5 mg cannabidiol) and once placebo for vaping after learning 15 unrelated nouns. The primary outcome measure was the short delay verbal memory performance (number of correctly free recalled nouns) 20 min after learning. 34 participants (mean age: 22.26 [3.04]) completed all visits and entered analyses (17 received cannabidiol and 17 received placebo first). Cannabidiol enhanced verbal episodic memory performance (placebo: 7.03 [2.34]; cannabidiol 7.71 [2.48]; adjusted group difference 0.68, 95% CI 0.01 to 1.35; R2ß = .028, p = .048). Importantly, we did not detect medication effects on secondary outcome measures attention or working memory performance, suggesting that CBD has no negative impact on these basic cognitive functions. The results are in line with the idea that vaping cannabidiol interacts with the central endocannabinoid system and is capable to modulate memory processes, a phenomenon with possible therapeutic potential. Further studies are needed to investigate optimal dose-response and time-response relationships.


Assuntos
Canabidiol , Memória Episódica , Adulto , Canabidiol/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Dronabinol/farmacologia , Humanos , Adulto Jovem
20.
Int J Mol Sci ; 22(18)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34575932

RESUMO

(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the Cannabis Sativa and Indica plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of Cannabis extracts (Bedrocan, FM2) or selected cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy. (3) Results: Incubation with the Bedrocan extract or THC exacerbated, whereas incubation with the FM2 extract or cannabidiol attenuated CA1 injury induced by OGD. Δ9-THC toxicity was prevented by CB1 receptor antagonists, the neuroprotective effect of cannabidiol was blocked by TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD, but not THC, had a significant protective effect toward neuronal damage and tissue disorganization caused by OGD in organotypic hippocampal slices. (4) Conclusions: Our results suggest that cannabinoids play different roles in the mechanisms of post-ischemic neuronal death. In particular, appropriate concentrations of CBD or CBD/THC ratios may represent a valid therapeutic intervention in the treatment of post-ischemic neuronal death.


Assuntos
Canabidiol/farmacologia , Dronabinol/farmacologia , Glucose/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Animais , Cannabis/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos
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