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2.
Arch. argent. pediatr ; 118(1): 64-67, 2020-02-00.
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1095682

RESUMO

En los últimos años, se ha observado un incremento significativo en el interés por la prescripción del cannabis medicinal. En el siguiente artículo, se informa acerca de la escasa base científica que avala la prescripción de estos compuestos en un listado amplio y diverso de patologías médicas. Se considera fundamental que cualquier sustancia que vaya a ser utilizada en humanos siga un protocolo de aprobación estricto y científico, que pueda desligarse de modas o de resultados individuales. Es necesario que, antes de la prescripción de una droga en personas, deba tenerse un panorama claro de cuáles son los usos del compuesto en cuestión, pero, sobre todo, de su seguridad, que es prácticamente desconocida en el cannabis medicinal.


In recent years, the interest in medical cannabis prescription has increased significantly. This article provides information about the little scientific basis supporting the prescription of these products for a wide and diverse range of medical conditions. It is critical for any substance to be used in human beings to follow a strict scientific approval protocol, detached from any trend or individual outcome. Before prescribing any drug to human beings, it is necessary to have a clear picture of its uses, especially its safety, which is practically unknown in the case of medical cannabis.


Assuntos
Humanos , Canabidiol/efeitos adversos , Canabidiol/uso terapêutico , Maconha Medicinal/efeitos adversos , Maconha Medicinal/uso terapêutico , Segurança , Dronabinol/uso terapêutico , Canabidiol/farmacologia , Ensaios de Uso Compassivo , Legislação de Medicamentos
3.
Nat Rev Neurol ; 16(1): 9-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31831863

RESUMO

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.


Assuntos
Canabinoides/metabolismo , Endocanabinoides/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Analgésicos/metabolismo , Analgésicos/uso terapêutico , Animais , Canabidiol/metabolismo , Canabidiol/uso terapêutico , Canabinoides/uso terapêutico , Dronabinol/metabolismo , Dronabinol/uso terapêutico , Combinação de Medicamentos , Endocanabinoides/uso terapêutico , Humanos , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo
4.
Drugs Aging ; 36(11): 1035-1045, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31552597

RESUMO

BACKGROUND: Synthetic oral cannabinoids (nabilone and dronabinol) may have adverse respiratory effects. Our purpose was to describe the scope, pattern, and patient characteristics associated with incident off-label synthetic oral cannabinoid use among older adults with chronic obstructive pulmonary disease (COPD) compared to older adults without COPD. METHODS: This was a retrospective, population-based, cohort study using Ontario, Canada, heath administrative data. Individuals aged 66 years or older were included, and physician-diagnosed COPD was identified using a previously validated, highly specific algorithm. Incident off-label oral cannabinoid use was examined between April 1, 2005 and March 31, 2015. Descriptive statistics were used to describe drug use patterns. Multiple logistic regression was used to identify patient characteristics associated with incident drug use. RESULTS: There were 172,282 older adults with COPD and 1,068,256 older adults without COPD identified between April 1, 2005 and March 31, 2015. Incident synthetic oral cannabinoid use during this period occurred with significantly greater (p < 0.001) frequency among older adults with COPD (0.6%) versus older adults without COPD (0.3%). Compared to those without COPD, older adults with COPD used synthetic cannabinoids for significantly longer durations and more frequently at higher doses. CONCLUSIONS: Although incident off-label oral cannabinoid use was relatively low among all older Ontarian adults, this drug class was used with greater frequency and more often in potentially concerning ways among older adults with COPD. These findings raise possible safety concerns, but further research on the respiratory safety of oral cannabinoids among individuals with COPD is needed.


Assuntos
Dronabinol/análogos & derivados , Uso de Medicamentos/estatística & dados numéricos , Prescrição Inadequada/estatística & dados numéricos , Uso Off-Label/estatística & dados numéricos , Medicamentos sob Prescrição/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Algoritmos , Estudos de Coortes , Dronabinol/administração & dosagem , Dronabinol/efeitos adversos , Dronabinol/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Ontário , Medicamentos sob Prescrição/efeitos adversos , Medicamentos sob Prescrição/uso terapêutico , Estudos Retrospectivos
5.
Schmerz ; 33(5): 384-391, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31473816

RESUMO

BACKGROUND: Geriatric patients often suffer from a long history of pain and have a limited life expectancy. Cannabinoid receptor agonists like dronabinol may be an effective, low-risk treatment option for geriatric patients with chronic pain. OBJECTIVES: The effectiveness and side effects of dronabinol therapy in geriatric patients are analyzed. The effects of the approval requirement are presented. METHODS: In our retrospective monocentric cohort study, the study population comprised all geriatric patients over the age of 80 years who were treated in our office since the cannabis law came into effect on 10 March 2017 until 17 July 2018 (evaluation date). Geriatric, nonpalliative pain patients (group A) and geriatric palliative patients (group B) were investigated. The basis of the evaluation was a questionnaire sheet that we use in our office with details of dosages, pain intensity, treatment effects and side effects from dronabinol therapy. RESULTS: By using dronabinol, 21 of the 40 geriatric patients (52.5%) achieved pain relief of more than 30%, 10% of the patients of more than 50%. On average, about four symptoms or side effects related to previous treatment were positively influenced. 26% of patients reported side effects. The rejection rates on the part of the health insurances were 38.7% (group A) and 10.3% (group B). CONCLUSIONS: This study is one of the few analyses of the use of Dronabinol in geriatric patients. We show that cannabis-based drugs (in this case dronabinol) are an effective, low-risk treatment option that should be considered early in therapy. Regarding the indication spectrum, further clinical studies and an approval-free test phase are necessary.


Assuntos
Assistência Ambulatorial , Dronabinol , Dor , Cuidados Paliativos , Idoso , Assistência Ambulatorial/economia , Assistência Ambulatorial/normas , Estudos de Coortes , Dronabinol/uso terapêutico , Humanos , Dor/tratamento farmacológico , Cuidados Paliativos/economia , Cuidados Paliativos/normas , Estudos Retrospectivos
6.
Complement Ther Med ; 46: 123-130, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519268

RESUMO

The prior medical literature offers little guidance as to how pain relief and side effect manifestation may vary across commonly used and commercially available cannabis product types. We used the largest dataset in the United States of real-time responses to and side effect reporting from patient-directed cannabis consumption sessions for the treatment of pain under naturalistic conditions in order to identify how cannabis affects momentary pain intensity levels and which product characteristics are the best predictors of therapeutic pain relief. Between 06/06/2016 and 10/24/2018, 2987 people used the ReleafApp to record 20,513 cannabis administration measuring cannabis' effects on momentary pain intensity levels across five pain categories: musculoskeletal, gastrointestinal, nerve, headache-related, or non-specified pain. The average pain reduction was -3.10 points on a 0-10 visual analogue scale (SD = 2.16, d = 1.55, p < .001). Whole Cannabis flower was associated with greater pain relief than were other types of products, and higher tetrahydrocannabinol (THC) levels were the strongest predictors of analgesia and side effects prevalence across the five pain categories. In contrast, cannabidiol (CBD) levels generally were not associated with pain relief except for a negative association between CBD and relief from gastrointestinal and non-specified pain. These findings suggest benefits from patient-directed, cannabis therapy as a mid-level analgesic treatment; however, effectiveness and side effect manifestation vary with the characteristics of the product used.


Assuntos
Cannabis/química , Maconha Medicinal/uso terapêutico , Dor/tratamento farmacológico , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Canabidiol/efeitos adversos , Canabidiol/uso terapêutico , Cannabis/efeitos adversos , Dronabinol/efeitos adversos , Dronabinol/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Flores/química , Humanos , Maconha Medicinal/efeitos adversos
7.
Schmerz ; 33(5): 392-398, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31444574

RESUMO

This article reports a case of pronounced, chronic lumboischialgia, which was not satisfactorily controlled by conventional analgesic treatment. The level of pain under high-dose dronabinol treatment with oral and inhalative administration as well as the way to reimburse the cost of medicinal cannabis flowers, the treatment success and criteria of the economic prescription procedure are presented.


Assuntos
Dronabinol , Dor Lombar , Maconha Medicinal , Adulto , Doença Crônica , Dronabinol/economia , Dronabinol/uso terapêutico , Flores , Humanos , Seguro Saúde/economia , Dor Lombar/tratamento farmacológico , Maconha Medicinal/economia , Maconha Medicinal/uso terapêutico , Dor/tratamento farmacológico , Resultado do Tratamento
9.
PLoS One ; 14(7): e0219670, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31361750

RESUMO

BACKGROUND: Nabiximols (THC/CBD Oromucosal Spray, Sativex) is used as an add-on therapy to treat moderate to severe spasticity of Multiple Sclerosis (MS). OBJECTIVES: To examine the impact of physiotherapy (PT) programs on effectiveness and persistence of nabiximols treatment in people with MS-related spasticity. METHODS: This is an observational multicenter study with a follow-up period of 12 weeks, conducted in routine care settings in Italy. Patients with moderate to severe MS-related spasticity who started nabiximols were included. Spasticity was evaluated by the patient-rated 0-10 numerical rating scale (NRS). Clinical data were collected at baseline (T0), 4 weeks (T1) and 12 weeks (T2) months after enrollment. RESULTS: A total of 297 MS patients were selected, 290 completed the 3 months follow-up period. Mean NRS scores were 7.6 ± 1.1 at T0, 5.8 ± 1.4 at T1 and 5.5 ± 1.5 at T2. At T1, 77% of patients reached ≥20% improvement (initial response, IR); 22% reached ≥30% improvement (clinically relevant response, CRR). At T1, patients undergoing PT had a higher probability to reach CRR (Odds Ratio = 2.6 95% CI 1.3-5.6, p = 0.01). Nabiximols was discontinued in 30/290 (10.3%) patients at T1 (early discontinuers) and in 71/290 (24.5%) patients at T2 (late discontinuers). The probability of being late discontinuers was reduced in patients undergoing PT (Hazard Ratio = 0.41; 95% CI 0.23-0.69, p = 0.001). CONCLUSIONS: Our real-life study confirms nabiximols' effectiveness in MS-related spasticity and suggests that the association of a PT program may improve overall response and persistence to nabiximols treatment.


Assuntos
Canabidiol/uso terapêutico , Dronabinol/uso terapêutico , Esclerose Múltipla/terapia , Espasticidade Muscular/terapia , Sprays Orais , Modalidades de Fisioterapia , Terapia Combinada , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/complicações , Espasticidade Muscular/tratamento farmacológico , Suspensão de Tratamento
10.
Schmerz ; 33(5): 399-406, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31201550

RESUMO

BACKGROUND: There are uncertainties among physicians with respect to the indications, selection of drugs, effectiveness and safety of cannabis-based medicines for chronic pain. METHODS: All statutory health insurance pain physicians in Saarland were asked to complete a self-developed questionnaire assessing their experiences with cannabis-based medicines, which they prescribed between 10 March 2017 and 30 November 2018 for adult patients with chronic cancer and non-cancer pain. RESULTS: All statutory health insurance pain physicians participated in the survey and 13 out of 20 reported having prescribed cannabis-based medicines. The most frequent reasons for prescriptions in 136 patients (1.9% of the patients of the institutions) were failure of established treatment (73%) and desire of the patient (63%). In 35% of patients the type of pain was nociceptive, in 34% neuropathic, in 29% nociceptive and neuropathic and in 13% nociplastic. Dronabinol was prescribed for 95% of the patients and 71% were responders (clinically relevant reduction of pain or of other symptoms). In 29% of patients treatment was terminated due to either a lack of efficacy or adverse events. CONCLUSION: Statutory health insurance pain physicians in Saarland were reluctant to prescribe cannabis-based medicines. Dronabinol was effective and well-tolerated in the majority of the highly selected patients.


Assuntos
Cannabis , Dor Crônica , Maconha Medicinal , Cannabis/química , Dor Crônica/tratamento farmacológico , Dronabinol/normas , Dronabinol/uso terapêutico , Alemanha , Humanos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos
11.
BMC Gastroenterol ; 19(1): 105, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238887

RESUMO

BACKGROUND: Daily cannabis assumption is currently associated with several physical and mental health problems, however in the past it was prescribed for a multitude of symptoms, including vomiting, abdominal pain and diarrhea. Through the years, the endocannabinoid system has been recognized in the homeostatic mechanisms of the gut, as well as in the physiological control of intestinal motility and secretion. Accordingly, cannabinoids may be a promising therapy against several gastrointestinal conditions, such as abdominal pain and motility-related disorders. CASE PRESENTATION: We retrospectively analysed the efficacy and safety of a CB1-receptor agonist administered in six patients with refractory chronic diarrhea, between April 2008 and July 2016. After three months of therapy, oral nabilone improved the health of nearly all patients, with visible improvements in reducing diarrheal symptoms and weight gain. Most of the benefits persisted through the three-month follow-up. Only one patient interrupted the treatment after one month, due to severe fatigue and mental confusion; the symptoms disappeared in the follow-up period. CONCLUSIONS: These findings encourage the study of cannabinoids acting on CB1 receptors in chronic gastrointestinal disorders, especially in refractory chronic diarrhea, offering a chance for a substantial improvement in the quality of life of selected patients, with a reasonable safety profile.


Assuntos
Diarreia/tratamento farmacológico , Dronabinol/análogos & derivados , Fármacos Gastrointestinais/uso terapêutico , Adulto , Idoso , Doença Crônica , Dronabinol/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor CB1 de Canabinoide/agonistas
12.
Exp Clin Psychopharmacol ; 27(4): 338-347, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31120286

RESUMO

Given the use of cannabis as an analgesic by a broadening age range of patients, the aim of this study was to determine whether the antinociceptive effects of Δ9-tetrahydrocannabinol (THC) differ by age. The antinociceptive potency and efficacy of THC (1.0-18 mg/kg ip) was compared in male and female rats aged postnatal day 35-40 (adolescent), 60-70 (young adult), and 291-325 (middle-aged adult), using warm water tail withdrawal and paw pressure tests. Motoric effects of THC were assessed using a locomotor activity test. On the tail withdrawal test, THC was significantly more effective in middle-aged adult than in young adult rats and significantly less effective in adolescent than in young adult rats. Similar but smaller age-related differences were observed on the paw pressure test. Sex differences in THC's antinociceptive effects were consistent across the 3 ages examined, with greater THC effects observed in females than males of each age. Age-related differences in THC's locomotor-suppressing effect were also observed, with the greatest effect in young adult female rats. Serum THC levels were slightly higher in adolescent than in young adult rats, and levels of the active metabolites 11-OH-THC and cannabinol, as well as the inactive metabolite 11-nor-9-carboxy-THC, did not differ between adolescent and young adult rats. These results suggest that the pain-relieving effects of THC may be more limited in adolescents than in adults and that these age-related differences in THC effect are not attributable to differential absorption or metabolism of THC. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Dronabinol/farmacologia , Dor/tratamento farmacológico , Caracteres Sexuais , Analgésicos , Animais , Canabinol/farmacologia , Cannabis , Dronabinol/uso terapêutico , Feminino , Locomoção/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Ratos
13.
Int J Mol Sci ; 20(9)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31052404

RESUMO

Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8+CD103+ T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Dronabinol/uso terapêutico , Hipersensibilidade/complicações , Mastócitos/efeitos dos fármacos , Tato , Vulvodinia/tratamento farmacológico , Analgésicos não Entorpecentes/farmacologia , Animais , Dinitrofluorbenzeno/toxicidade , Dronabinol/farmacologia , Feminino , Imunoglobulina E/sangue , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Mastócitos/imunologia , Camundongos , Vulvodinia/etiologia , Vulvodinia/fisiopatologia
14.
Rev Neurol (Paris) ; 175(5): 298-304, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30948262

RESUMO

OBJECTIVES: To investigate prescription practices for dronabinol, a pure extract of delta-9-tetrahydrocannabinol, prescribed for refractory chronic pain in France since 2004. DESIGN: A descriptive study based on answers to a questionnaire sent to dronabinol prescribers throughout metropolitan France between June and July 2017. MAIN OUTCOMES MEASURES: We assessed the type of prescribers including place of work (hospital, clinic or private practice) and their specialty. We also collected information about the patient profiles, diseases or symptoms initiating dronabinol prescription, its efficacy and side effects. RESULTS: We received completed questionnaires from 26 prescribers in 17 different areas throughout 12 regions. This represented a total of 191 patients of the 377 indexed since 1st January 2006: the sex ratio was 1:1, with an average age of 51 years for men and of 45 for women. The reason for dronabinol prescription was: multiple sclerosis (49.7%); central neuropathic pain from other causes (36.6%); peripheral neuropathic pain (8%); Parkinson's disease (2.9%); and other causes (around 1%). The duration of dronabinol treatment ranged from 1 month to 6 years and the dose from 2.5mg to 30mg per day (in one or several intakes). 59% of the patients declared experiencing a 30 to 50% reduction in pain. CONCLUSION: This first investigation into dronabinol in France underlines the need to further investigate prescription practices and efficacy so as to define conditions of good use and the place of dronabinol in pain management.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Dronabinol/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Dor Intratável/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Feminino , França , Pesquisas sobre Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
16.
Int J Mol Sci ; 20(3)2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720730

RESUMO

Cannabinoids, the biologically active constituents of Cannabis, have potent neuronal and immunological effects. However, the basic and medical research dedicated to medical cannabis and cannabinoids is limited. The influence of these treatments on hematologic reconstitution and on the development of graft versus host disease (GVHD) after bone marrow transplantation (BMT) is largely unknown. In this research, we compared the influence of D9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on lymphocyte activation in vitro and in murine BMT models. Our in vitro results demonstrate that these treatments decrease activated lymphocyte proliferation and affect cytokine secretion. We also discovered that CBD and THC utilize different receptors to mediate these effects. In vivo, in a syngeneic transplantation model, we demonstrate that all treatments inhibit lymphocyte reconstitution and show the inhibitory role of the cannabinoid receptor type 2 (CB2) on lymphocyte recovery. Although pure cannabinoids exhibited a superior effect in vitro, in an allogeneic (C57BL/6 to BALB/c) BMT mouse model, THC-high and CBD-high cannabis extracts treatment reduced the severity of GVHD and improved survival significantly better than the pure cannabinoids. Our results highlights the complexity of using cannabinoids-based treatments and the need for additional comparative scientific results.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Canabidiol/farmacologia , Dronabinol/farmacologia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Inflamação/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Animais , Canabidiol/uso terapêutico , Modelos Animais de Doenças , Dronabinol/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Inflamação/etiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Resultado do Tratamento
17.
Cochrane Database Syst Rev ; 1: CD008940, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30687936

RESUMO

BACKGROUND: Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014. OBJECTIVES: To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. SEARCH METHODS: We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.Abstinence at end of treatment was no more likely with Δ9-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness. AUTHORS' CONCLUSIONS: There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.


Assuntos
Abuso de Maconha/tratamento farmacológico , Acetilcisteína/efeitos adversos , Acetilcisteína/uso terapêutico , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Buspirona/efeitos adversos , Buspirona/uso terapêutico , Dronabinol/efeitos adversos , Dronabinol/uso terapêutico , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Agonistas do Receptor de Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Adulto Jovem
18.
Exp Eye Res ; 180: 192-199, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30605663

RESUMO

Ocular pathologies and blindness have been linked to circadian disorders. In previous studies, our group has demonstrated that retinitis pigmentosa is associated with degenerative changes in the melanopsin system and weaker circadian patterns. We have also shown that cannabinoids preserve retinal structure and function in dystrophic P23H rats. This study is consequently aimed at examining whether the morphologic and functional rescue of retinal degeneration by cannabinoids is associated with amelioration of circadian parameters. The synthetic cannabinoid HU210 (100 µg/kg, i.p.) or vehicle were administered to transgenic P23H rats three times per week, from postnatal day 24-90. Sprague-Dawley rats were used as a healthy control group. Locomotor activity and scotopic electroretinograms were recorded, and the retinal structure was analyzed at the end of the experiment. The ERG a- and b-wave amplitudes and photoreceptor cell number were more deteriorated in vehicle-administered P23H rats as compared to P23H rats treated with HU210. In cannabinoid-administered P23H rats, the locomotor activity circadian rhythms showed less disturbance than that observed in vehicle-administered P23H rats, the latter showing lower values for mesor, amplitude, acrophase, percentage of variance and non-parametric variables. A positive linear correlation was found between retinal values and circadian parameters of locomotor activity from P23H rats. This study thus provides evidence of a positive correlation between cannabinoid-mediated rescue of retinal structure and function and improvement of circadian rhythmicity.


Assuntos
Canabinoides/uso terapêutico , Ritmo Circadiano/efeitos dos fármacos , Dronabinol/análogos & derivados , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Degeneração Retiniana/tratamento farmacológico , Animais , Ritmo Circadiano/fisiologia , Dronabinol/uso terapêutico , Eletrorretinografia , Masculino , Atividade Motora/fisiologia , Visão Noturna/fisiologia , Células Fotorreceptoras de Vertebrados/fisiologia , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Retina/fisiopatologia , Degeneração Retiniana/fisiopatologia
19.
J Crohns Colitis ; 13(4): 525-535, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30418525

RESUMO

Cannabis sativa and its extracts have been used for centuries, both medicinally and recreationally. There is accumulating evidence that exogenous cannabis and related cannabinoids improve symptoms associated with inflammatory bowel disease [IBD], such as pain, loss of appetite, and diarrhoea. In vivo, exocannabinoids have been demonstrated to improve colitis, mainly in chemical models. Exocannabinoids signal through the endocannabinoid system, an increasingly understood network of endogenous lipid ligands and their receptors, together with a number of synthetic and degradative enzymes and the resulting products. Modulating the endocannabinoid system using pharmacological receptor agonists, genetic knockout models, or inhibition of degradative enzymes have largely shown improvements in colitis in vivo. Despite these promising experimental results, this has not translated into meaningful benefits for human IBD in the few clinical trials which have been conducted to date, the largest study being limited by poor medication tolerance due to the Δ9-tetrahydrocannabinol component. This review article synthesises the current literature surrounding the modulation of the endocannabinoid system and administration of exocannabinoids in experimental and human IBD. Findings of clinical surveys and studies of cannabis use in IBD are summarised. Discrepancies in the literature are highlighted together with identifying novel areas of interest.


Assuntos
Canabinoides/uso terapêutico , Cannabis , Endocanabinoides/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fitoterapia , Receptores de Canabinoides/metabolismo , Administração por Inalação , Analgésicos não Entorpecentes/uso terapêutico , Animais , Dronabinol/uso terapêutico , Endocanabinoides/genética , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Extratos Vegetais/uso terapêutico , Polimorfismo de Nucleotídeo Único , Receptores de Canabinoides/genética
20.
Urology ; 123: 120-125, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30142408

RESUMO

OBJECTIVE: To further define the relationship between tetrahydrocannabinol (THC) and lower urinary tract symptoms (LUTS), specifically how THC use associates with the frequency of LUTS in young community-dwelling men in the United States. MATERIALS AND METHODS: The National Health and Nutrition Examination Survey database was queried (2005-2008). Men ages 20-59 who completed the urinary and substance abuse questionnaires were included. The presence of LUTS was defined as having ≥2 of the following: nocturia (≥2), hesitancy, incomplete emptying, or incontinence. THC use was self-reported, and participants were considered regular smokers if they endorsed smoking at least once per month. Multivariable logistic regression was performed to analyze the relationship between THC and LUTS. RESULTS: Among 3,037 men who met inclusion criteria, 14.4% (n = 477) of subjects reported THC use. In multivariable analyses, adjusting for clinical variables, regular THC users remained significantly less likely to report LUTS (odds ratio of 0.55; confidence interval 95% 0.408-0.751, P <.01) compared to nonusers. CONCLUSION: Obesity, diabetes, and multiple comorbidities are well-established risk factors for LUTS within the National Health and Nutrition Examination Survey. Regular THC use, however, appears to be protective from LUTS in young community-dwelling men.


Assuntos
Agonistas de Receptores de Canabinoides/uso terapêutico , Dronabinol/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Adulto , Estudos Transversais , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
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