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1.
J Pain ; 23(1): 45-54, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214700

RESUMO

Many people with fibromyalgia use cannabidiol (CBD) products despite limited rigorous evidence of benefit. In the current study, we conducted a secondary analysis of a cross-sectional survey of N = 878 people with fibromyalgia to investigate naturalistic decision making around CBD product choices, use patterns, and dosing. We subgrouped participants based on use of high-THC cannabis (HTC) in the past year (yes/no) as previous studies have shown that HTC use influences CBD use patterns. The study population was largely female (93.6%), white (91.5%) and 55.5 years old on average. Participants typically purchased CBD products online or at dispensaries, with purchasing driven by personal research (63%) rather than endorsement from medical professionals (16%). Overall, tinctures and topicals were the most common administration routes endorsed. However, participants in the past-year HTC group used inhalation routes far more frequently than those who did not (39.8% vs 7.1%). Among participants using CBD tinctures or edibles, the average dose per session was 16 mg and 24 to 27 mg per day, although approximately one-third of participants did not know what dose of CBD they used. Participants using both inhalation and non-inhalation administration routes reported greater symptom relief than those using non-inhalation routes alone. However, there was no consistent relationship between CBD dose and reported effects, possibly due to expectancy effects around CBD products or interindividual variability. Our granular investigation reveals variability of CBD product dosing practices for fibromyalgia, and how past-year HTC use influences CBD product use. Future clinical trials should investigate the potential benefits of low-dose (<50mg) botanical CBD products. PERSPECTIVE: This article shows that past-year HTC use strongly influences how people with fibromyalgia choose and use CBD products. Participants typically used <50 mg/d of CBD, and there was no relationship between higher CBD dose and reported therapeutic benefit. Future clinical trials should investigate therapeutic benefits of low dose CBD.


Assuntos
Canabidiol/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Tomada de Decisões , Fibromialgia/tratamento farmacológico , Adulto , Idoso , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde
2.
Pharmacol Res ; 175: 105928, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34800625

RESUMO

To address the inconsistent findings from studies that used different models to explore the role of classical cannabinoid type 1 (CB1) and 2 (CB2) receptors in skeletal remodelling, we searched Medline, Web of Science and Embase for relevant studies from inception to June 23, 2020. We identified 38 in vitro, 34 in vivo and 9 human studies. A meta-analysis of in vitro studies showed that exposure to the inverse-agonists AM251 (mean difference [MD]:-26.75, 95% confidence interval [CI]:-45.36,-8.14, p = 0.005), AM630 (standardised[std.] MD:-3.11, CI:-5.26,-0.97, p = 0.004; SR144528, std.MD:-4.88, CI -7.58,-2.18, p = 0.0004) and CBD (std.MD:-1.39, CI -2.64,-0.14, p = 0.03) is associated with reduced osteoclastogenesis, whereas the endocannabinoid 2-AG (std.MD:2.00, CI:0.11-3.89, p = 0.04) and CB2-selective agonist HU308 (MD:19.38, CI:11.75-27.01, p < 0.00001) were stimulatory. HU308 also enhanced osteoblast differentiation (std.MD:2.22, CI:0.95-3.50, p = 0.0006) and activity (std.MD:2.97, CI:1.22-4.71, p = 0.0008). In models of bone loss, CB1/2 deficiency enhanced peak bone volume (std.MD:3.70, CI:1.77-5.63, p = 0.0002) but reduced bone formation (std.MD:-0.54, CI:-0.90,-0.17, p = 0.004) in female mice. In male rats, CB1/2 deficiency (std.MD:2.31, CI:0.30-4.33, p = 0.02) and AM251 or CBD treatments (std.MD:2.19, CI:0.46-3.93, p = 0.01) enhanced bone volume. CB1/2 deficiency (std.MD:9.78, CI:4.96-14.61, p < 0.0001) and AM251 or AM630 treatments (std.MD:28.19, CI:19.13-37.25, p < 0.0001) were associated with osteoprotection. The CB2-selective agonists JWH133 and 4Q3C enhanced bone volume in arthritic rodents (std.MD:14.45, CI:2.08-26.81, p = 0.02). In human, CB2 SNPs (AA:rs2501431, MD:-0.28, CI:-0.55,-0.01, p = 0.04; CC:rs2501432, MD:-0.29, CI:-0.56,-0.02, p = 0.03) were associated with reduced bone mineral density, however the association of Marijuana use remains unclear. Thus, CB1/2 modulation is associated with altered bone metabolism, however findings are confounded by low study number and heterogenicity of models.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Moduladores de Receptores de Canabinoides/administração & dosagem , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Moduladores de Receptores de Canabinoides/efeitos adversos , Humanos
3.
J Psychopharmacol ; 35(7): 773-785, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33593117

RESUMO

Cannabis has been legalised for medical use in an ever-increasing number of countries. A growing body of scientific evidence supports the use of medical cannabis for a range of therapeutic indications. In parallel with these developments, concerns have been expressed by many prescribers that increased use will lead to patients developing cannabis use disorder. Cannabis use disorder has been widely studied in recreational users, and these findings have often been projected onto patients using medical cannabis. However, studies exploring medical cannabis dependence are scarce and the appropriate methodology to measure this construct is uncertain. This article provides a narrative review of the current research to discern if, how and to what extent, concerns about problems of dependence in recreational cannabis users apply to prescribed medical users. We focus on the main issues related to medical cannabis and dependence, including the importance of dose, potency, cannabinoid content, pharmacokinetics and route of administration, frequency of use, as well as set and setting. Medical and recreational cannabis use differs in significant ways, highlighting the challenges of extrapolating findings from the recreational cannabis literature. There are many questions about the potential for medical cannabis use to lead to dependence. It is therefore imperative to address these questions in order to be able to minimise harms of medical cannabis use. We draw out seven recommendations for increasing the safety of medical cannabis prescribing. We hope that the present review contributes to answering some of the key questions surrounding medical cannabis dependence.


Assuntos
Moduladores de Receptores de Canabinoides/farmacologia , Abuso de Maconha/etiologia , Maconha Medicinal/farmacologia , Moduladores de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/efeitos adversos , Humanos , Maconha Medicinal/administração & dosagem , Maconha Medicinal/efeitos adversos
4.
Parkinsonism Relat Disord ; 83: 37-40, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33465546

RESUMO

Essential tremor (ET) is a common clinical syndrome characterized by action tremors affecting both upper limbs that can compromise manual tasks' execution and impair functional and social performance. The primary pharmacological treatment is symptomatic, but effective medicines are somewhat limited. There is a clear need to find new effective therapies for the treatment of ET. Cannabidiol (CBD) is a modulator of CB1 receptor and CB1 agonists can reduce tremors in experimental models. We hypothesized that a single acute CBD intake would reduce tremors in ET patients. We performed a randomized, controlled, double-blind, crossover study on 19 patients with ET. They were 10 males and 9 females, had mean 63 years of age, and mean 23 years of disease duration and had insufficient control of their tremors with the usual pharmacological treatment. They ingested a single oral dose of CBD (300 mg) or placebo in two experimental sessions performed 2-weeks apart. Patients were evaluated immediately before and after oral ingestion (60 min and 210 min), using the Fahn-Tolosa-Marin clinical scale. There was no carryover effect. There were no significant differences in upper limb tremors score, specific motor task tremor scores (writing and drawing/pouring) or clinical impression of change after treatment with placebo or CBD. In conclusion, a single 300 mg oral dose of CBD had no significant effect on the severity of upper limb tremors of ET patients. Our findings did not exclude the possibility that chronic treatment with CBD could have a symptomatic effect.


Assuntos
Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Tremor Essencial/tratamento farmacológico , Tremor Essencial/fisiopatologia , Extremidade Superior/fisiopatologia , Administração Oral , Idoso , Canabidiol/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
5.
J Psychopharmacol ; 35(7): 864-874, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33427014

RESUMO

BACKGROUND: Cocaine dependence is an important problem without any effective pharmacological treatment. Some preclinical studies have suggested that cannabidiol (CBD), a component of the Cannabis sativa plant, could be useful for the treatment of cocaine use disorders. AIMS: This work aims to evaluate the ability of CBD to reduce priming- and stress-induced reinstatement of the conditioned place preference (CPP) induced by cocaine. METHODS: Young adult CD-1 male mice were allocated to 10 groups (n = 12/group), conditioned with cocaine (10 mg/kg) and exposed to extinction of CPP (two sessions per week). When extinction was achieved, each group received the corresponding treatment before the reinstatement test. In experiment 1, six groups were used: vehicle+saline (Veh+Sal), 5 mg/kg cocaine alone (Veh+Coc) or with CBD 30 or 60 mg/kg (CBD30+Coc, CBD60+Coc) and CBD alone (CBD30+Sal, CBD60+Sal). In experiment 2, four groups were used: exploration (Veh+Expl), social defeat (Veh+SD) and social defeat with CBD (CBD30+SD and CBD60+SD). Furthermore, the relative gene expression of the dopamine transporter (DAT) in the ventral tegmental area was measured. RESULTS: All mice acquired cocaine CPP and extinguished it after three or four weeks. Only the groups treated with cocaine priming (Veh+Coc) or exposed to social defeat (Veh+SD) showed reinstatement of CPP. Interestingly, CBD itself did not induce reinstatement and blocked the reinstating effects of cocaine priming and social defeat. Furthermore, cocaine priming increased DAT gene expression in the ventral tegmental area and CBD completely reversed this effect. CONCLUSION: These results suggest that CBD could reduce reinstatement to cocaine seeking after a period of abstinence.


Assuntos
Comportamento Animal/efeitos dos fármacos , Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Condicionamento Clássico/efeitos dos fármacos , Derrota Social , Animais , Canabidiol/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Masculino , Camundongos , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo
6.
J Parkinsons Dis ; 11(1): 309-321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33216043

RESUMO

BACKGROUND: Little is known about the patients' view on treatment with medical cannabis (MC) for Parkinson's disease (PD). OBJECTIVE: To assess the PD community's perception of MC and patients' experience with MC. METHODS: Applying a questionnaire-based survey, we evaluated general knowledge and interest in MC as well as the frequency, modalities, efficacy, and tolerability of application. Questionnaires were distributed nationwide via the membership journal of the German Parkinson Association and locally in our clinic to control for report bias. RESULTS: Overall, 1.348 questionnaires (1.123 nationwide, 225 local) were analysed. 51% of participants were aware of the legality of MC application, 28% of various routes of administration (ROA) and 9% of the difference between delta9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). PD-related cannabis use was reported by 8.4% of patients and associated with younger age, living in large cities and better knowledge about the legal and clinical aspects of MC. Reduction of pain and muscle cramps was reported by more than 40% of cannabis users. Stiffness/akinesia, freezing, tremor, depression, anxiety and restless legs syndrome subjectively improved for more than 20% and overall tolerability was good. Improvement of symptoms was reported by 54% of users applying oral CBD and 68% inhaling THC-containing cannabis. Compared to CBD intake, inhalation of THC was more frequently reported to reduce akinesia and stiffness (50.0% vs. 35.4%; p < 0.05). Interest in using MC was reported by 65% of non-users. CONCLUSION: MC is considered as a therapeutic option by many PD patients. Nevertheless, efficacy and different ROA should further be investigated.


Assuntos
Moduladores de Receptores de Canabinoides/farmacologia , Conhecimentos, Atitudes e Prática em Saúde , Maconha Medicinal/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/administração & dosagem , Dronabinol/farmacologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Maconha Medicinal/administração & dosagem , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Preferência do Paciente , População Urbana
7.
J Psychopharmacol ; 34(9): 981-989, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32762272

RESUMO

BACKGROUND: Cannabidiol (CBD) is being investigated as a potential treatment for several medical indications, many of which are characterised by altered memory processing. However, the mechanisms underlying these effects are unclear. AIMS: Our primary aim was to investigate how CBD influences cerebral blood flow (CBF) in regions involved in memory processing. Our secondary aim was to determine if the effects of CBD on CBF were associated with differences in working and episodic memory task performance. METHODS: We used a randomised, crossover, double-blind design in which 15 healthy participants were administered 600 mg oral CBD or placebo on separate days. We measured regional CBF at rest using arterial spin labelling 3 h after drug ingestion. We assessed working memory with the digit span (forward, backward) and n-back (0-back, 1-back, 2-back) tasks, and we used a prose recall task (immediate and delayed) to assess episodic memory. RESULTS: CBD increased CBF in the hippocampus (mean (95% confidence intervals) = 15.00 (5.78-24.21) mL/100 g/min, t14 = 3.489, Cohen's d = 0.75, p = 0.004). There were no differences in memory task performance, but there was a significant correlation whereby greater CBD-induced increases in orbitofrontal CBF were associated with reduced reaction time on the 2-back working memory task ( r= -0.73, p = 0.005). CONCLUSIONS: These findings suggest that CBD increases CBF to key regions involved in memory processing, particularly the hippocampus. These results identify potential mechanisms of CBD for a range of conditions associated with altered memory processing, including Alzheimer's disease, schizophrenia, post-traumatic stress disorder and cannabis-use disorders.


Assuntos
Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Memória Episódica , Memória de Curto Prazo/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Canabidiol/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Marcadores de Spin , Adulto Jovem
8.
J Psychopharmacol ; 34(9): 969-980, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32755273

RESUMO

BACKGROUND: Cannabidiol has potential therapeutic benefits for people with psychiatric disorders characterised by reward function impairment. There is existing evidence that cannabidiol may influence some aspects of reward processing. However, it is unknown whether cannabidiol acutely affects brain function underpinning reward anticipation and feedback. HYPOTHESES: We predicted that cannabidiol would augment brain activity associated with reward anticipation and feedback. METHODS: We administered a single 600 mg oral dose of cannabidiol and matched placebo to 23 healthy participants in a double-blind, placebo-controlled, repeated-measures design. We employed the monetary incentive delay task during functional magnetic resonance imaging to assay the neural correlates of reward anticipation and feedback. We conducted whole brain analyses and region-of-interest analyses in pre-specified reward-related brain regions. RESULTS: The monetary incentive delay task elicited expected brain activity during reward anticipation and feedback, including in the insula, caudate, nucleus accumbens, anterior cingulate and orbitofrontal cortex. However, across the whole brain, we did not find any evidence that cannabidiol altered reward-related brain activity. Moreover, our Bayesian analyses showed that activity in our regions-of-interest was similar following cannabidiol and placebo. Additionally, our behavioural measures of motivation for reward did not show a significant difference between cannabidiol and placebo. DISCUSSION: Cannabidiol did not acutely affect the neural correlates of reward anticipation and feedback in healthy participants. Future research should explore the effects of cannabidiol on different components of reward processing, employ different doses and administration regimens, and test its reward-related effects in people with psychiatric disorders.


Assuntos
Antecipação Psicológica/efeitos dos fármacos , Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Córtex Cerebral/efeitos dos fármacos , Desvalorização pelo Atraso/efeitos dos fármacos , Retroalimentação Psicológica/efeitos dos fármacos , Motivação/efeitos dos fármacos , Recompensa , Adulto , Mapeamento Encefálico , Canabidiol/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Córtex Cerebral/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
10.
Epileptic Disord ; 22(1): 1-14, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32096470

RESUMO

The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the therapeutic value of cannabis-based products as an anti-seizure treatment for some time, it is only within the last two years that Class I evidence has been available for a pure form of CBD, based on placebo-controlled RCTs for patients with Lennox-Gastaut syndrome and Dravet syndrome. However, just as we are beginning to understand the significance of CBD as a treatment for epilepsy, in recent years, a broad spectrum of products advertised to contain CBD has emerged on the market. The effects of these products are fundamentally dependent on the purity, preparation, and concentration of CBD and other components, and consensus and standardisation are severely lacking regarding their preparation, composition, usage and effectiveness. This review aims to provide information to neurologists and epileptologists on the therapeutic value of CBD products, principally a purified form, in routine practice for patients with intractable epilepsy.


Assuntos
Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Mioclônicas/tratamento farmacológico , Síndrome de Lennox-Gastaut/tratamento farmacológico , Guias de Prática Clínica como Assunto , Canabidiol/administração & dosagem , Canabidiol/normas , Moduladores de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/normas , Humanos
11.
Mult Scler Relat Disord ; 41: 102009, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32086163

RESUMO

BACKGROUND: Growing evidence supports that cannabinoids relieve MS-related spasticity but little is known about cannabis use among people with MS (PwMS) and spasticity. OBJECTIVE: To characterize cannabis use among PwMS and spasticity. METHODS: As part of baseline data collection for a spasticity intervention trial in Oregon, PwMS and self-reported spasticity answered questions about cannabis use. RESULTS: 54% reported ever using cannabis and 36% currently use. 79% use multiple routes of administration, 58% use at least daily. 79% find cannabis helpful for spasticity and 26% use cannabis and prescribed oral antispasticity medications. CONCLUSIONS: Many PwMS and spasticity use cannabis and report it helps their spasticity.


Assuntos
Moduladores de Receptores de Canabinoides/farmacologia , Cannabis , Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Preparações de Plantas/farmacologia , Autogestão , Adulto , Idoso , Idoso de 80 Anos ou mais , Moduladores de Receptores de Canabinoides/administração & dosagem , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Espasticidade Muscular/etiologia , Preparações de Plantas/administração & dosagem , Resultado do Tratamento
12.
Psychopharmacology (Berl) ; 237(6): 1643-1655, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32095916

RESUMO

RATIONALE: Prepulse inhibition of the startle reflex (PPI) is disrupted in several psychiatric disorders including schizophrenia. Understanding PPI pharmacology may help elucidate the pathophysiology of these disorders and lead to better treatments. Given the advantages of multi-target approaches for complex mental illnesses treatment, we have investigated the interaction between receptors known to modulate PPI (5-HT1A and 5-HT2A) and the neuromodulatory endocannabinoid system. OBJECTIVES: To investigate serotonin and cannabinoid receptor (CBR) co-modulation in a model of PPI disruption relevant to schizophrenia METHODS: Male Swiss mice were pretreated with WIN 55,212-2 (CBR agonist), rimonabant (CB1R inverse agonist), 8-OH-DPAT (5-HT1A/7 agonist), and volinanserin (5-HT2A antagonist) or with a combination of a cannabinoid and a serotonergic drug. PPI disruption was induced by acute administration of MK-801. RESULTS: WIN 55,212-2 and rimonabant did not change PPI nor block MK-801-induced deficits. 8-OH-DPAT increased PPI in control mice and, in a higher dose, inhibited MK-801-induced impairments. Volinanserin also increased PPI in control and MK-801-treated mice, presenting an inverted U-shaped dose-response curve. Co-administration of either cannabinoid ligand with 8-OH-DPAT did not change PPI; however, the combination of volinanserin with rimonabant increased PPI in both control and MK-801-exposed mice. CONCLUSIONS: WIN 55,212-2 and rimonabant had similar effects in PPI. Moreover, serotonin and cannabinoid receptors interact to modulate PPI. While co-modulation of CBR and 5-HT1A receptors did not change PPI, a beneficial effect of 5-HT2A and CB1R antagonist combination was detected, possibly mediated through potentiation of 5-HT2A blockade effects by concomitant CB1R blockade.


Assuntos
Antagonistas de Receptores de Canabinoides/administração & dosagem , Inibição Pré-Pulso/fisiologia , Receptor 5-HT2A de Serotonina/fisiologia , Receptores de Canabinoides/fisiologia , Esquizofrenia/tratamento farmacológico , Antagonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , 8-Hidroxi-2-(di-n-propilamino)tetralina/administração & dosagem , Animais , Benzoxazinas/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Canabinoides/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Fluorbenzenos/administração & dosagem , Masculino , Camundongos , Morfolinas/administração & dosagem , Naftalenos/administração & dosagem , Piperidinas/administração & dosagem , Inibição Pré-Pulso/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Reflexo de Sobressalto/fisiologia , Agonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Resultado do Tratamento
13.
Behav Brain Res ; 378: 112297, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31626848

RESUMO

Although a lot of information can be found on the specific dual role of the endocannabinoid system in the emotional-related responses, little is known whether stimulation or inhibition of the cannabinoid (CB) receptors may affect the activity of the frequently prescribed antidepressant drugs. Our interests have been particularly focused on the potential influence of the CB2 receptors, as the ones whose central effects are relatively poorly documented when compared to the central effects of the CB1 receptors. Therefore, we evaluated the potential interaction between the CB2 receptor ligands (i.e., JWH133 - CB2 receptor agonist and AM630 - CB2 receptor inverse agonist) and several common antidepressant drugs that influence the monoaminergic system (i.e., imipramine, escitalopram, reboxetine). In order to assess the antidepressant-like effects we used two widely recognized behavioural tests, the mouse forced swim test (FST) and the tail suspension test (TST). Brain concentrations of the tested antidepressants were evaluated by the HPLC method. Intraperitoneal co-administration of per se ineffective doses of JWH133 (0.25 mg/kg) or AM630 (0.25 mg/kg) with imipramine (15 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg) significantly shortened the immobility time of mice in the FST and the TST, whereas it did not disturb their spontaneous locomotor activity. Furthermore, the brain levels of antidepressants were not changed. Summarizing, the results of the present study revealed that both activation and inhibition of the CB2 receptor function have a potential to strengthen the antidepressant activity of drugs targeting the monoaminergic system. Most probably, the described interaction has a pharmacodynamic background.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Moduladores de Receptores de Canabinoides/farmacologia , Locomoção/efeitos dos fármacos , Receptor CB2 de Canabinoide/efeitos dos fármacos , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacocinética , Agonistas de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/farmacocinética , Canabinoides/administração & dosagem , Citalopram/administração & dosagem , Sinergismo Farmacológico , Imipramina/administração & dosagem , Indóis/administração & dosagem , Masculino , Camundongos , Reboxetina/administração & dosagem , Receptor CB2 de Canabinoide/agonistas
14.
J Psychoactive Drugs ; 52(2): 145-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31813342

RESUMO

Many patients have reported that they decrease their use of opioids after starting medical cannabis (MC) but less is known for alcohol. The objective of this exploratory study was to identify any factors which differentiate alcohol abaters from those that do not modify their alcohol use after starting MC (non-abaters). Comparisons were made to identify any demographic, dosing, or health history characteristics which differentiated alcohol abaters (N = 47) from non-abaters (N = 65). Respondents selected from among a list of 37 diseases/health conditions (e.g. diabetes, sleep disorders). Abaters and non-abaters were indistinguishable in terms of sex, age, or prior drug history. A greater percentage of abaters (59.6%) than non-abaters (40.6%, p < .05) reported using MC two or more times per day. Abaters were more likely to be employed (68.1%) than non-abaters (51.1%, p < .05). Abaters also reported having significantly more health conditions and diseases (3.3 ± 2.0) than non-abaters (2.4 ± 1.4, p < .05). This small study offers some insights into the profile of patients whose self-reported alcohol intake decreased following initiation of MC. Additional prospective or controlled research into the alcohol abatement phenomenon following MC may be warranted.


Assuntos
Consumo de Bebidas Alcoólicas/prevenção & controle , Moduladores de Receptores de Canabinoides/administração & dosagem , Maconha Medicinal/administração & dosagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato
15.
J Neurol ; 267(2): 415-421, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31655890

RESUMO

BACKGROUND: The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report symptoms' relief through consumption of cannabis. METHODS: A combination of cannabidiol and tetrahydrocannabinol (CBD/THC) was prescribed as compassionate use to six patients (four patients with myotonic dystrophy types 1 and 2, and 2 patients with CLCN1-myotonia) with therapy-resistant myotonia and myalgia. CBD/THC oil was administered on a low dose in the first 2 weeks and adjusted to a higher dose in the following 2 weeks. Myotonia behaviour scale (MBS), hand-opening time, visual analogue scales (VAS) for myalgia and myotonia, and fatigue and daytime sleepiness severity scale (FSS, ESS) were performed weekly to monitor treatment response. RESULTS: All patients reported an improvement of myotonia especially in weeks 3 and 4 of treatment: MBS improved of at least 2 points in all patients, the hand-opening time variously improved in 5 out of 6 patients. Chronic myalgia was reported by both DM2 patients at baseline, one of them experienced a significant improvement of myalgia under treatment. Some gastrointestinal complaints, as abdominal pain and diarrhoea, improved in 3 patients; however, 4 out of 6 patients reported new-onset constipation. No other relevant side effect was noticed. CONCLUSIONS: These first empirical results suggest a potentially beneficial role of CBD/THC in alleviating myotonia and should encourage further research in this field including a randomized-controlled trial on larger cohorts.


Assuntos
Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Dronabinol/farmacologia , Distrofias Musculares/tratamento farmacológico , Mialgia/tratamento farmacológico , Miotonia/tratamento farmacológico , Adulto , Idoso , Canabidiol/administração & dosagem , Moduladores de Receptores de Canabinoides/administração & dosagem , Doença Crônica , Estudos de Coortes , Ensaios de Uso Compassivo , Dronabinol/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óleos , Resultado do Tratamento
16.
Child Adolesc Psychiatr Clin N Am ; 29(1): 145-156, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708043

RESUMO

The rapidly changing landscape of cannabis in terms of availability, potency, and routes of administration, as well as the decrease in risk perception and changing norms, have contributed to an increase in the popularity of cannabis. Cannabis use is associated with a poorer recovery from a psychotic disorder, increasing the risk of relapse, rehospitalization, and lower social functioning. Data are mixed regarding cannabis use as a component cause of psychosis in people at risk for psychotic disorder. Care providers, parents, and schools must educate youth and adolescents about the risks of cannabis use.


Assuntos
Moduladores de Receptores de Canabinoides , Uso da Maconha , Transtornos Psicóticos , Esquizofrenia , Adolescente , Moduladores de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/efeitos adversos , Moduladores de Receptores de Canabinoides/química , Moduladores de Receptores de Canabinoides/provisão & distribuição , Criança , Humanos , Uso da Maconha/efeitos adversos , Uso da Maconha/epidemiologia , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etiologia , Esquizofrenia/epidemiologia , Esquizofrenia/etiologia
17.
J Neurodev Disord ; 11(1): 16, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31370779

RESUMO

BACKGROUND: Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. METHODS: Twenty children and adolescents (aged 6-17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL™), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale-Severity (CGI-S) and Improvement (CGI-I). RESULTS: The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-CFXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. CONCLUSIONS: ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. TRIAL REGISTRATION: ANZCTR, ACTRN12617000150347 Registered 27 January 2017.


Assuntos
Sintomas Comportamentais/tratamento farmacológico , Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Síndrome do Cromossomo X Frágil/tratamento farmacológico , Administração Cutânea , Adolescente , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Sintomas Comportamentais/etiologia , Canabidiol/administração & dosagem , Canabidiol/efeitos adversos , Moduladores de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/efeitos adversos , Criança , Feminino , Síndrome do Cromossomo X Frágil/complicações , Géis , Humanos , Masculino , Resultado do Tratamento
19.
J Psychiatr Res ; 111: 134-139, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30738930

RESUMO

Cannabis is commonly used recreationally for its euphoric and relaxing effects, while its medical use is permitted in several jurisdictions. With only low-quality evidence suggesting anxiolytic effects of cannabis and strong public sentiment surrounding such purported effects, the purpose of this study was to examine the prevalence of cannabis for medicinal purposes (CMP) use for anxiety symptoms. An online survey was disseminated to CMP users registered with a Canadian licensed producer. Respondents completed demographic and validated self-report questionnaires (GAD-7, PHQ-9, MINI-SPIN, and panic disorder/agoraphobia DSM-5 criteria). Cannabis use behaviors were also discussed. Overall, 2032 completed responses with a verified user number were collected. Of the total sample, 888 (43.7%) reported CMP authorization to treat anxiety symptoms and completed all psychometric screening instruments. Rates of probable disorders were high (Generalized Anxiety Disorder: 45.6%, Social Anxiety Disorder: 42.4%, Major Depressive Disorder: 25.7%, Panic Disorder/Agoraphobia: 25.7%); 63.4% met screening criteria for ≥1 disorder. Most (92%) reported that cannabis improved their symptoms, despite continuing to endorse moderate-level severity. Nearly half (49%) reported replacing a non-psychiatric (53.7%) or psychiatric medication (46.3%) prescribed to them by their physician with CMP. Respondents endorsed daily CMP use and severity of anxiety (GAD-7, p < 0.001) and depressive (PHQ-9, p < 0.001) symptoms were positively associated with the amount of cannabis used/day. The vast majority perceived symptom improvement with CMP use and did not believe CMP use was associated with impairment or an inability to control use. Nevertheless, the possibility of cannabis use disorder cannot be ruled out as well as the possibility that improvements in non-psychiatric conditions were attributed to improvements in anxiety. These results highlight the need to systematically evaluate CMP use for mental illness.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Ansiedade/tratamento farmacológico , Moduladores de Receptores de Canabinoides/farmacologia , Uso da Maconha , Maconha Medicinal/farmacologia , Avaliação de Resultados da Assistência ao Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Canadá/epidemiologia , Moduladores de Receptores de Canabinoides/administração & dosagem , Moduladores de Receptores de Canabinoides/efeitos adversos , Depressão/tratamento farmacológico , Depressão/epidemiologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Uso da Maconha/epidemiologia , Maconha Medicinal/administração & dosagem , Maconha Medicinal/efeitos adversos , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
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