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1.
MMWR Morb Mortal Wkly Rep ; 69(2): 44-49, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31945038

RESUMO

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders continue to investigate a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). EVALI patients in Illinois, Utah, and Wisconsin acquired tetrahydrocannabinol (THC)-containing products primarily from informal sources (2,3). This report updates demographic characteristics and self-reported sources of THC- and nicotine-containing e-cigarette, or vaping, products derived from EVALI patient data reported to CDC by state health departments. As of January 7, 2020, among 1,979 (76%) patients with available data on substance use, a total of 1,620 (82%) reported using any THC-containing products, including 665 (34%) who reported exclusive THC-containing product use. Use of any nicotine-containing products was reported by 1,128 (57%) patients, including 264 (13%) who reported exclusive nicotine-containing product use. Among 809 (50%) patients reporting data on the source of THC-containing products, 131 (16%) reported acquiring their products from only commercial sources (i.e., recreational dispensaries, medical dispensaries, or both; vape or smoke shops; stores; and pop-up shops), 627 (78%) from only informal sources (i.e., friends, family, in-person or online dealers, or other sources), and 51 (6%) from both types of sources. Among 613 (54%) EVALI patients reporting nicotine-containing product use with available data on product source, 421 (69%) reported acquiring their products from only commercial sources, 103 (17%) from only informal sources, and 89 (15%) from both types of sources. Adolescents aged 13-17 years were more likely to acquire both THC- and nicotine-containing products from informal sources than were persons in older age groups. The high prevalence of acquisition of THC-containing products from informal sources by EVALI patients reinforces CDC's recommendation to not use e-cigarette, or vaping, products that contain THC, especially those acquired from informal sources. Although acquisition of nicotine-containing products through informal sources was not common overall, it was common among persons aged <18 years. While the investigation continues, CDC recommends that the best way for persons to ensure that they are not at risk is to consider refraining from the use of all e-cigarette, or vaping, products.


Assuntos
Surtos de Doenças , Hospitalização/estatística & dados numéricos , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dronabinol/efeitos adversos , Sistemas Eletrônicos de Liberação de Nicotina , Feminino , Humanos , Lesão Pulmonar/terapia , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
3.
MMWR Morb Mortal Wkly Rep ; 68(47): 1096-1100, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31774740

RESUMO

During August 9-October 31, 2019, 96 patients were classified as having e-cigarette, or vaping, product use-associated lung injury (EVALI) by the Minnesota Department of Health (MDH); other patients are being investigated for case classification and exposures. Among 58 patients interviewed, 53 (91%) reported obtaining tetrahydrocannabinol (THC)-containing products from informal sources such as friends, family members, or in-person or online dealers. Using gas chromatography-mass spectrometry (GCMS), the MDH Public Health Laboratory (PHL) analyzed 46 THC-containing e-cigarette, or vaping, products obtained from 12 EVALI patients for various potential toxicants, including vitamin E acetate, which has recently been detected in some THC-containing products and in samples of lung fluid from EVALI patients (1-4). To explore whether vitamin E acetate is a recently added component in THC-containing products, MDH tested ten products seized by law enforcement in 2018, before the EVALI outbreak, and 20 products seized in 2019, during the outbreak. Twenty-four products obtained from 11 EVALI patients from 2019 contained vitamin E acetate. Among the seized products tested by MDH, none seized in 2018 contained vitamin E acetate, although all tested THC-containing products seized in 2019 tested positive for vitamin E acetate. These chemical analyses of products obtained from EVALI patients and of products intended for the illicit market both before and during the outbreak support a potential role for vitamin E acetate in the EVALI outbreak; however, the number of products tested was small, and further research is needed to establish a causal link between exposure to inhaled vitamin E acetate and EVALI. Collaboration between public health jurisdictions and law enforcement to characterize THC-containing products circulating before the recognition of the EVALI outbreak and during the outbreak might provide valuable information about a dynamic market. These Minnesota findings highlight concerns about e-cigarette, or vaping, products that contain THC acquired from informal sources. Because local supply chains and policy environments vary, CDC continues to recommend not using e-cigarette, or vaping, products that contain THC or any e-cigarette, or vaping, products obtained from informal sources. E-cigarette, or vaping, products should never be used by youths, young adults, or pregnant women.* Until the relationship between inhaled vitamin E acetate and lung health is better characterized, vitamin E acetate should not be added to e-cigarette, or vaping, products.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Legislação de Medicamentos , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Idoso , Dronabinol/efeitos adversos , Dronabinol/análise , Feminino , Humanos , Aplicação da Lei , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Vitamina E/efeitos adversos , Vitamina E/análise , Adulto Jovem
4.
MMWR Morb Mortal Wkly Rep ; 68(45): 1034-1039, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31725708

RESUMO

The United States is experiencing an unprecedented outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). All EVALI patients have used e-cigarette, or vaping, products, and most (≥85%) have reported using products containing tetrahydrocannabinol (THC) (2,3), the principal psychoactive component of cannabis. To examine whether e-cigarette, or vaping, product use behaviors differed between adult EVALI patients and adults who use these products but have not developed lung injury, the Illinois Department of Public Health (IDPH) conducted an online public survey during September-October 2019 targeting e-cigarette, or vaping, product users in Illinois. Among 4,631 survey respondents, 94% reported using any nicotine-containing e-cigarette, or vaping, products in the past 3 months; 21% used any THC-containing products; and 11% used both THC-containing products and nicotine-containing products. Prevalence of THC-containing product use was highest among survey respondents aged 18-24 years (36%) and decreased with increasing age. E-cigarette, or vaping, product use behaviors of 66 EVALI patients aged 18-44 years who were interviewed as part of the ongoing outbreak investigation were compared with a subset of 519 survey respondents aged 18-44 years who reported use of THC-containing e-cigarette, or vaping, products. Compared with these survey respondents, EVALI patients had higher odds of reporting exclusive use of THC-containing products (adjusted odds ratio [aOR] = 2.0, 95% confidence interval [CI] = 1.1-3.6); frequent use (more than five times per day) of these products (aOR = 3.1, 95% CI = 1.6-6.0), and obtaining these products from informal sources, such as a dealer, off the street, or from a friend (aOR = 9.2, 95% CI = 2.2-39.4). The odds of using Dank Vapes, a class of largely counterfeit THC-containing products, was also higher among EVALI patients (aOR = 8.5, 95% CI = 3.8-19.0). These findings reinforce current recommendations not to use e-cigarette, or vaping, products that contain THC and not to use any e-cigarette, or vaping, products obtained from informal sources. In addition, because the specific compound or ingredient causing lung injury is not yet known, CDC continues to recommend that persons consider refraining from use of all e-cigarette, or vaping, products while the outbreak investigation continues (1).


Assuntos
Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Dronabinol/efeitos adversos , Feminino , Humanos , Illinois/epidemiologia , Masculino , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
5.
MMWR Morb Mortal Wkly Rep ; 68(39): 865-869, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31581166

RESUMO

In July 2019, the Illinois Department of Public Health and the Wisconsin Department of Health Services launched a coordinated epidemiologic investigation after receiving reports of several cases of lung injury in previously healthy persons who reported electronic cigarette (e-cigarette) use, or vaping (1). This report describes features of e-cigarette product use by patients in Illinois and Wisconsin. Detailed patient interviews were conducted by telephone, in person, or via the Internet with 86 (68%) of 127 patients. Overall, 75 (87%) of 86 interviewed patients reported using e-cigarette products containing tetrahydrocannabinol (THC), and 61 (71%) reported using nicotine-containing products. Numerous products and brand names were identified by patients. Nearly all (96%) THC-containing products reported were packaged, prefilled cartridges, and 89% were primarily acquired from informal sources (e.g., friends, family members, illicit dealers, or off the street). In contrast, 77% of nicotine-containing products were sold as prefilled cartridges, and 83% were obtained from commercial vendors. The precise source of this outbreak is currently unknown (2); however, the predominant use of prefilled THC-containing cartridges among patients with lung injury associated with e-cigarette use suggests that they play an important role. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. Given the diversity of products reported and frequency of patients using both THC- and nicotine-containing e-cigarette products, additional methods such as product testing and traceback could help identify the specific cause of this outbreak.


Assuntos
Surtos de Doenças , Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Dronabinol/efeitos adversos , Feminino , Humanos , Illinois/epidemiologia , Masculino , Wisconsin/epidemiologia , Adulto Jovem
6.
MMWR Morb Mortal Wkly Rep ; 68(39): 860-864, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31581168

RESUMO

Electronic cigarettes (e-cigarettes), also called vapes, e-hookas, vape pens, tank systems, mods, and electronic nicotine delivery systems (ENDS), are electronic devices that produce an aerosol by heating a liquid typically containing nicotine, flavorings, and other additives; users inhale this aerosol into their lungs (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis (1). Use of e-cigarettes is commonly called vaping. Lung injury associated with e-cigarette use, or vaping, has recently been reported in most states (2-4). CDC, the Food and Drug Administration (FDA), state and local health departments, and others are investigating this outbreak. This report provides data on patterns of the outbreak and characteristics of patients, including sex, age, and selected substances used in e-cigarette, or vaping, products reported to CDC as part of this ongoing multistate investigation. As of September 24, 2019, 46 state health departments and one territorial health department had reported 805 patients with cases of lung injury associated with use of e-cigarette, or vaping, products to CDC. Sixty-nine percent of patients were males, and the median age was 23 years (range = 13-72 years). To date, 12 deaths have been confirmed in 10 states. Among 514 patients with information on substances used in e-cigarettes, or vaping products, in the 30 days preceding symptom onset, 76.9% reported using THC-containing products, and 56.8% reported using nicotine-containing products; 36.0% reported exclusive use of THC-containing products, and 16.0% reported exclusive use of nicotine-containing products. The specific chemical exposure(s) causing the outbreak is currently unknown. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. CDC will continue to work in collaboration with FDA and state and local partners to investigate cases and advise and alert the public on the investigation as additional information becomes available.


Assuntos
Surtos de Doenças , Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Idoso , Dronabinol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
7.
MMWR Morb Mortal Wkly Rep ; 68(42): 953-956, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31647788

RESUMO

In August 2019, the Utah Department of Health (UDOH) received reports from health care providers of several cases of lung injury in persons who reported use of electronic cigarette (e-cigarette), or vaping, products (1,2). To describe the characteristics of medical care, potentially related conditions, and exposures among 83 patients in Utah, detailed medical abstractions were completed for 79 (95%) patients. Among patients receiving chart abstractions, 70 (89%) were hospitalized, 39 (49%) required breathing assistance, and many reported preexisting respiratory and mental health conditions. Interviews were conducted by telephone or in person with 53 (64%) patients or their proxies, and product samples from eight (15%) of the interviewed patients or proxies were tested. Among 53 interviewed patients, all of whom reported using e-cigarette, or vaping, products within 3 months of acute lung injury, 49 (92%) reported using any products containing tetrohydrocannabinol (THC), the principal psychoactive component of cannabis; 35 (66%) reported using any nicotine-containing products, and 32 (60%) reported using both. As reported in Wisconsin and Illinois (1), most THC-containing products were acquired from informal sources such as friends or illicit in-person and online dealers. THC-containing products were most commonly used one to five times per day, whereas nicotine-containing products were most commonly used >25 times per day. Product sample testing at the Utah Public Health Laboratory (UPHL) showed evidence of vitamin E acetate in 17 of 20 (89%) THC-containing cartridges, which were provided by six of 53 interviewed patients. The cause or causes of this outbreak is currently unknown (2); however, the predominant use among patients of e-cigarette, or vaping, products with prefilled THC-containing cartridges suggests that the substances in these products or the way in which they are heated and aerosolized play an important role in the outbreak. At present, persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific cause or causes of lung injury are not yet known and while the investigation continues, persons should consider refraining from use of all e-cigarette, or vaping, products.


Assuntos
Surtos de Doenças , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Idoso , Dronabinol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Utah/epidemiologia , Adulto Jovem
8.
Nat Neurosci ; 22(12): 1975-1985, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31611707

RESUMO

The increased legal availability of cannabis has led to a common misconception that it is a safe natural remedy for, among others, pregnancy-related ailments such as morning sickness. Emerging clinical evidence, however, indicates that prenatal cannabis exposure (PCE) predisposes offspring to various neuropsychiatric disorders linked to aberrant dopaminergic function. Yet, our knowledge of how cannabis exposure affects the maturation of this neuromodulatory system remains limited. Here, we show that male, but not female, offspring of Δ9-tetrahydrocannabinol (THC)-exposed dams, a rat PCE model, exhibit extensive molecular and synaptic changes in dopaminergic neurons of the ventral tegmental area, including altered excitatory-to-inhibitory balance and switched polarity of long-term synaptic plasticity. The resulting hyperdopaminergic state leads to increased behavioral sensitivity to acute THC exposure during pre-adolescence. The neurosteroid pregnenolone, a US Food and Drug Administration (FDA) approved drug, rescues synaptic defects and normalizes dopaminergic activity and behavior in PCE offspring, thus suggesting a therapeutic approach for offspring exposed to cannabis during pregnancy.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Dronabinol/efeitos adversos , Dronabinol/farmacologia , Pregnenolona/farmacologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Dronabinol/antagonistas & inibidores , Endofenótipos , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Atividade Motora/efeitos dos fármacos , Inibição Neural/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Gravidez , Inibição Pré-Pulso/efeitos dos fármacos , Inibição Pré-Pulso/fisiologia , Ratos , Assunção de Riscos , Filtro Sensorial/efeitos dos fármacos , Filtro Sensorial/fisiologia , Caracteres Sexuais , Área Tegmentar Ventral/metabolismo
10.
Psychopharmacology (Berl) ; 236(11): 3257-3270, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31165913

RESUMO

RATIONALE: While cannabis-based medicinal products have been shown to be effective for numerous neurological and psychiatric disorders, the evidence base regarding their adverse cognitive effects is poorly understood. The cannabinoid 1 receptor modulates memory performance via intracellular and extracellular mechanisms that alter synaptic transmission and plasticity. While previous literature has consistently shown that chronic cannabis users exhibit marked cognitive impairments, mixed findings have been reported in the context of placebo-controlled experimental trials. It is therefore unclear whether these compounds inherently alter cognitive processes or whether individuals who are genetically predisposed to use cannabis may have underlying cognitive deficits. OBJECTIVE: We conducted a meta-analysis to investigate the effects of full and partial cannabinoid 1 receptor (CB1R) agonists, antagonists, and negative allosteric modulators on non-spatial and spatial memory. METHODS: In accordance with the PRISMA guidelines, the EMBASE, MEDLINE, and PsycINFO databases were systematically searched for studies examining the effects of CB1R agonists, antagonists, and negative allosteric modulators on memory performance. RESULTS: We systematically reviewed 195 studies investigating the effects of cannabinoid compounds on memory. In humans (N = 35 studies, comprising N = 782 subjects), delta-9-tetrahydrocannabinol (THC) (1.5-5 mg/kg) relative to placebo impaired performance on non-spatial memory tests, whereas only high THC doses (67 mg/kg) impaired spatial memory. Similarly, THC (0.2-4 mg/kg) significantly impaired visuospatial memory in monkeys and non-human primates (N = 8 studies, comprising N = 71 subjects). However, acute THC (0.002-10 mg/kg) had no effect on non-spatial (N = 6 studies, comprising 117 subjects; g = 1.72, 95% confidence interval (CI) - 0.18 to 3.63, p = 0.08) or spatial memory (9 studies, comprising 206 subjects; g = 0.75, 95% confidence interval (CI) - 1.09 to 2.58, p = 0.43). However, acute, full CB1R agonists significantly impaired non-spatial memory (N = 23 studies, 519 subjects; g = - 1.39, 95% CI - 2.72 to - 0.06, p = 0.03). By contrast, the chronic administration of CB1R agonists had no effect on non-spatial memory (N = 5 studies, comprising 146 subjects; g = - 0.05, 95% confidence interval (CI) - 1.32 to 1.22, p = 0.94). Moreover, the acute administration of CB1R antagonists had no effect on non-spatial memory in rodents (N = 9 studies, N = 149 subjects; g = 0.40, 95% CI - 0.11 to 0.92, p = 0.12). CONCLUSIONS: The acute administration of THC, partial CB1R agonist, significantly impaired non-spatial memory in humans, monkeys, and non-human primates but not rodents. However, full CB1R agonists significantly impaired non-spatial memory in a dose-dependent manner but CB1R antagonists had no effect on non-spatial memory in rodents. Moreover, chronic THC administration did not significantly impair spatial or non-spatial memory in rodents, and there is inconclusive evidence on this in humans. Our findings highlight species differences in the effects of cannabinoid compounds on memory.


Assuntos
Cognição/efeitos dos fármacos , Cognição/fisiologia , Dronabinol/farmacologia , Memória/efeitos dos fármacos , Memória/fisiologia , Receptor CB1 de Canabinoide/fisiologia , Animais , Canabinoides/efeitos adversos , Canabinoides/farmacologia , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/diagnóstico , Dronabinol/efeitos adversos , Humanos , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Especificidade da Espécie , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia
11.
Psychopharmacology (Berl) ; 236(9): 2713-2724, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31044290

RESUMO

BACKGROUND: The main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), can impair driving performance. Cannabidiol (CBD), a non-intoxicating cannabis component, is thought to mitigate certain adverse effects of THC. It is possible then that cannabis containing equivalent CBD and THC will differentially affect driving and cognition relative to THC-dominant cannabis. AIMS: The present study investigated and compared the effects of THC-dominant and THC/CBD equivalent cannabis on simulated driving and cognitive performance. METHODS: In a randomized, double-blind, within-subjects crossover design, healthy volunteers (n = 14) with a history of light cannabis use attended three outpatient experimental test sessions in which simulated driving and cognitive performance were assessed at two timepoints (20-60 min and 200-240 min) following vaporization of 125 mg THC-dominant (11% THC; < 1% CBD), THC/CBD equivalent (11% THC, 11% CBD), or placebo (< 1% THC/CBD) cannabis. RESULTS/OUTCOMES: Both active cannabis types increased lane weaving during a car-following task but had little effect on other driving performance measures. Active cannabis types impaired performance on the Digit Symbol Substitution Task (DSST), Divided Attention Task (DAT) and Paced Auditory Serial Addition Task (PASAT) with impairment on the latter two tasks worse with THC/CBD equivalent cannabis. Subjective drug effects (e.g., "stoned") and confidence in driving ability did not vary with CBD content. Peak plasma THC concentrations were higher following THC/CBD equivalent cannabis relative to THC-dominant cannabis, suggesting a possible pharmacokinetic interaction. CONCLUSIONS/INTERPRETATION: Cannabis containing equivalent concentrations of CBD and THC appears no less impairing than THC-dominant cannabis, and in some circumstances, CBD may actually exacerbate THC-induced impairment.


Assuntos
Condução de Veículo , Canabidiol/efeitos adversos , Cognição/efeitos dos fármacos , Dronabinol/efeitos adversos , Fumar Maconha/efeitos adversos , Vaping/efeitos adversos , Adulto , Condução de Veículo/psicologia , Canabidiol/administração & dosagem , Cognição/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Dronabinol/administração & dosagem , Feminino , Alucinógenos/administração & dosagem , Alucinógenos/efeitos adversos , Humanos , Masculino , Fumar Maconha/psicologia , Psicotrópicos/efeitos adversos , Vaping/psicologia , Adulto Jovem
12.
Psychopharmacology (Berl) ; 236(9): 2773-2784, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31044291

RESUMO

RATIONALE: Cannabis use is common among adolescents and some research suggests that adolescent cannabis use increases the risk for depression, anxiety, and cognitive impairments in adulthood. In human studies, however, confounds may affect the association between cannabis use and the development of brain disorders. OBJECTIVES: These experiments investigated the effects of adolescent exposure to either cannabis smoke or THC on anxiety- and depressive-like behavior and cognitive performance in adulthood in Long-Evans rats. METHODS: Adolescent rats of both sexes were exposed to either cannabis smoke from postnatal days (P) 29-49 or ascending doses of THC from P35-45. When the rats reached adulthood (P70), anxiety-like behavior was investigated in the large open field and elevated plus maze, depressive-like behavior in the sucrose preference and forced swim tests, and cognitive function in the novel object recognition test. RESULTS: Despite sex differences on some measures in the open field, elevated plus maze, forced swim, and novel object recognition tests, there were no effects of either adolescent cannabis smoke or THC exposure, and only relatively subtle interactions between exposure conditions and sex, such that sex differences on some performance measures were slightly attenuated. CONCLUSION: Neither cannabis smoke nor THC exposure during adolescence produced robust alterations in adult behavior after a period of abstinence, suggesting that adverse effects associated with adolescent cannabis use might be due to non-cannabinoid concomitants of cannabis use.


Assuntos
Cognição/efeitos dos fármacos , Dronabinol/efeitos adversos , Emoções/efeitos dos fármacos , Fumar Maconha/efeitos adversos , Fumar Maconha/psicologia , Fatores Etários , Animais , Cannabis/efeitos adversos , Cognição/fisiologia , Dronabinol/administração & dosagem , Emoções/fisiologia , Feminino , Exposição por Inalação/efeitos adversos , Masculino , Ratos , Ratos Long-Evans , Caracteres Sexuais
13.
Neuroimage ; 197: 575-585, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31075393

RESUMO

The primary psychoactive compound in cannabis, Δ9-tetrahydrocannabinol (THC), binds to cannabinoid receptors (CB1) present in high concentrations in the prefrontal cortex (PFC). It is unknown whether the PFC hemodynamic response changes with THC intoxication. We conducted the first double-blind, placebo-controlled, cross-over study of the effect of THC intoxication on functional near infrared spectroscopy (fNIRS) measures of PFC activation. Fifty-four adult, regular (at least weekly) cannabis users received a single oral dose of synthetic THC (dronabinol; 5-50 mg, dose individually tailored to produce intoxication) and identical placebo on two visits at least one week apart. fNIRS recordings were obtained during a working memory task (N-Back) at three timepoints: before THC/placebo, at 100 min (when peak effects were expected), and at 200 min after THC/placebo administration. Functional data were collected using a continuous-wave NIRS device, with 8 sources and 7 detectors arrayed over the forehead, resulting in 20 channels covering PFC regions. Participants also completed frequent heart rate measures and subjective ratings of intoxication. Approximately half of participants reported significant intoxication. Intoxication ratings were not correlated with dose of THC. Increases in heart rate significantly correlated with intoxication ratings after THC dosing. Results indicated that 100 min after THC administration, oxygenated hemoglobin (HbO) response significantly increased from pre-dose HbO levels throughout the PFC in participants who reported significant intoxication. Changes in HbO response significantly correlated with self-reported intoxication at 100 min after THC administration. Among those who reported intoxication, HbO response decreased at 200 min after THC, when intoxication had largely resolved, compared to the peak THC time point. This study demonstrates that THC intoxication causes increased PFC activity, and fNIRS of the PFC can measure this effect. Increased neural activation in PFC represents a potential biomarker for cannabis intoxication.


Assuntos
Dronabinol/efeitos adversos , Abuso de Maconha/diagnóstico , Córtex Pré-Frontal/efeitos dos fármacos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino
14.
Evid. actual. práct. ambul ; 22(1): e001119, abr. 2019. ilus, tab.
Artigo em Espanhol | LILACS | ID: biblio-1014994

RESUMO

Esta revisión analiza la situación actual de la utilización del como herramienta terapéutica dentro del ámbito de la salud en Argentina, haciendo referencia a los distintos actores involucrados y dilemas futuros que pueden presentarse. Paracomprender en su totalidad el marco social, cultural e histórico, se desarrollan distintos aspectos, como la descripción química y biológica del , evolución del consumo a través de la historia, las repercusiones del consumo y las distintas aplicaciones que tiene en el campo de la medicina. También se describen las diferentes realidades que hay en el mundo, así como las legislaciones de otros países y la comparación de estas con la que tenemos en nuestro país. Finalmente se mencionan los desafíos pendientes y sus posibles abordajes.(AU)


This review analyzes the current situation of the use of cannabis as a therapeutic tool in the field of health in Argentina,referring to the different actors involved and future dilemmas that may arise. To fully understand the social, cultural andhistorical framework, different aspects can be defined, such as the chemical and biological description of cannabis, theevolution of consumption throughout history, the repercussions of recreational consumption and the different applicationsthat it has on the medical field. It also describes the different realities that exist in the world, as well as the laws of othercountries and the comparison of these with the one we have in our country. Finally, the pending challenges and theirpossible approaches, are mentioned.(AU)


Assuntos
Humanos , Masculino , Feminino , História Medieval , História do Século XX , Maconha Medicinal/uso terapêutico , Uso da Maconha/legislação & jurisprudência , Uso da Maconha/tendências , Argentina , Dronabinol/efeitos adversos , Dronabinol/farmacologia , Canabidiol/efeitos adversos , Canabidiol/farmacologia , Canabinoides/classificação , Cannabis/classificação , Cannabis/química , Drogas Ilícitas , Saúde Pública/tendências , Uso da Maconha/história , Uso da Maconha/terapia
16.
PLoS One ; 14(3): e0209947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30861005

RESUMO

Cannabis withdrawal upon discontinuation of long-term, heavy Cannabis use is reported in humans; however, methods to establish the nature and intensity of cannabinoid withdrawal, especially directly observable signs, have not been widely established. This study quantified activity in the home cage of rhesus monkeys and examined the extent to which activity can be used to quantify tolerance to and dependence on Δ9-tetrahydrocannabinol (Δ9-THC). Home-cage activity was measured in one group that received Δ9-THC (1 mg/kg s.c.) every 12 h (i.e., chronic Δ9-THC), and a second group that received Δ9-THC (0.1 mg/kg i.v.) once every 3 days (i.e., intermittent Δ9-THC). Treatment was temporarily discontinued in the chronic Δ9-THC group and the effects of rimonabant and Δ9-THC were examined in both groups. Activity counts were highest during the day (lights on 0600-2000 h) and were lower at night. Rimonabant (0.1-3.2 mg/kg i.v.) dose-dependently increased activity (maximum 20-fold) in the chronic Δ9-THC group but did not significantly alter activity in the intermittent Δ9-THC group. Δ9-THC (0.32-3.2 mg/kg i.v.) dose-dependently decreased activity counts (maximum 4-fold) in both groups but was somewhat more potent in the intermittent as compared with the Δ9-THC group. Discontinuation of Δ9-THC treatment resulted in an immediate (i.e., within 24 h) and time-related increase in activity. The time-related increase in home-cage activity upon abrupt discontinuation of chronic Δ9-THC treatment, as well as the effects of rimonabant to increase activity in monkeys receiving chronic, but not intermittent, Δ9-THC treatment, are consistent with signs of physical dependence on Δ9-THC in primates.


Assuntos
Dronabinol/efeitos adversos , Tolerância a Medicamentos , Alucinógenos/efeitos adversos , Atividade Motora/efeitos dos fármacos , Rimonabanto/administração & dosagem , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Administração Intravenosa , Animais , Modelos Animais de Doenças , Feminino , Alucinógenos/farmacologia , Humanos , Macaca mulatta , Masculino , Rimonabanto/farmacologia
17.
Eur Arch Psychiatry Clin Neurosci ; 269(1): 87-105, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30706168

RESUMO

We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders. Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a  meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists. THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.


Assuntos
Canabidiol/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Dronabinol/farmacologia , Maconha Medicinal/farmacologia , Transtornos Mentais/tratamento farmacológico , Canabidiol/efeitos adversos , Moduladores de Receptores de Canabinoides/efeitos adversos , Dronabinol/efeitos adversos , Humanos , Maconha Medicinal/efeitos adversos
18.
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
19.
J Anal Toxicol ; 43(4): 233-258, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30615181

RESUMO

Currently, an unprecedented number of individuals can legally access cannabis. Vaporization is increasingly popular as a method to self-administer cannabis, partly due to perception of reduced harm compared with smoking. Few controlled laboratory studies of cannabis have used vaporization as a delivery method or evaluated the acute effects of cannabis among infrequent cannabis users. This study compared the concentrations of cannabinoids in whole blood and oral fluid after administration of smoked and vaporized cannabis in healthy adults who were infrequent users of cannabis. Seventeen healthy adults, with no past-month cannabis use, self-administered smoked or vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10 and 25 mg in six double-blind outpatient sessions. Whole blood and oral fluid specimens were obtained at baseline and for 8 h after cannabis administration. Cannabinoid concentrations were assessed with enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods. Sensitivity, specificity and agreement between ELISA and LC-MS-MS results were assessed. Subjective, cognitive performance and cardiovascular effects were assessed. The highest concentrations of cannabinoids in both whole blood and oral fluid were typically observed at the first time point (+10 min) after drug administration. In blood, THC, 11-OH-THC, THCCOOH and THCCOOH-glucuronide concentrations were dose-dependent for both methods of administration, but higher following vaporization compared with smoking. THC was detected longer in oral fluid compared to blood and THCCOOH detection in oral fluid was rare and highly erratic. For whole blood, greater detection sensitivity for ELISA testing was observed in vaporized conditions. Conversely, for oral fluid, greater sensitivity was observed in smoked sessions. Blood and/or oral fluid cannabinoid concentrations were weakly to moderately correlated with pharmacodynamic outcomes. Cannabis pharmacokinetics vary by method of inhalation and biological matrix being tested. Vaporization appears to be a more efficient method of delivery compared with smoking.


Assuntos
Dronabinol/sangue , Dronabinol/farmacocinética , Fumar Maconha/sangue , Psicotrópicos/sangue , Psicotrópicos/farmacocinética , Saliva/química , Detecção do Abuso de Substâncias/métodos , Volatilização , Adulto , Cannabis/química , Cromatografia Líquida , Método Duplo-Cego , Dronabinol/administração & dosagem , Dronabinol/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Feminino , Alucinações/etiologia , Humanos , Masculino , Fumar Maconha/efeitos adversos , Fumar Maconha/legislação & jurisprudência , Concentração Osmolar , Psicotrópicos/administração & dosagem , Psicotrópicos/efeitos adversos , Sensibilidade e Especificidade , Fatores Sexuais , Espectrometria de Massas em Tandem , Vômito/etiologia , Adulto Jovem
20.
Cerebellum ; 18(3): 593-604, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30610540

RESUMO

Cannabis is the third most used psychoactive drug worldwide. Despite being legally scheduled as a drug with high harm potential and no therapeutic utility in countries like the USA, evidence shows otherwise and legislative changes and reinterpretations of existing ambiguous laws make this drug increasingly available by legal means. Nevertheless, this substance is able to generate clear addiction syndromes in some individuals who use it, which are accompanied by brain alterations resembling those caused by other addictive drugs. Moreover, there is no available pharmacological treatment for this disorder. This fact motivates a deep study and comprehension of the neural basis of addiction-relevant cannabinoid effects. Interestingly, the cerebellum, a hindbrain structure which involvement in functions not related to motor control and planning is being increasingly recognized in the last decades, seems to be involved in the effects of addictive drugs and addiction-related processes and also presents a high density of cannabinoid receptors. Preclinical research on the involvement of the cerebellum in cannabis' effects has focused in the drug's motor incoordinating actions, potentially underestimating its participation in addiction. Therefore, this review addresses the studies reporting cerebellar involvement in cannabis effects both in experimental animals and human subjects and the possible relevance of these changes for addiction. Additionally, future experimental approaches will be proposed and hopefully this work will stimulate research on the cerebellum in cannabis addiction and help recognizing it as an important part of the neural circuitry affected in cannabis-related disorders.


Assuntos
Cannabis/efeitos adversos , Cerebelo/efeitos dos fármacos , Dronabinol/efeitos adversos , Abuso de Maconha/fisiopatologia , Animais , Humanos
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