RESUMO
BACKGROUND: In a recent randomized, double-blind, placebo-controlled study, we observed a nonsignificant reduction of attack frequency in cluster headache after pulse administration of psilocybin (10 mg/70 kg, 3 doses, 5 days apart each). We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen. METHODS: Eligible participants returned to receive a psilocybin pulse at least 6 months after their first round of study participation. Participants kept headache diaries starting two weeks before and continuing through eight weeks after the first drug session. Ten participants completed the extension phase and all ten were included in the final analysis. RESULTS: In the three weeks after the start of the pulse, cluster attack frequency was significantly reduced from baseline (18.4 [95% confidence interval 8.4 to 28.4] to 9.8 [4.3 to 15.2] attacks/week; p = 0.013, d' = 0.97). A reduction of approximately 50% was seen regardless of individual response to psilocybin in the first round. Psilocybin was well-tolerated without any unexpected or serious adverse events. DISCUSSION: This study shows a significant reduction in cluster attack frequency in a repeat round of pulse psilocybin administration and suggests that prior response may not predict the effect of repeated treatment. To gauge the full potential of psilocybin as a viable medicine in cluster headache, future work should investigate the safety and therapeutic efficacy in larger, more representative samples over a longer time period, including repeating the treatment. CLINICAL TRIALS REGISTRATION: NCT02981173.
Assuntos
Cefaleia Histamínica , Psilocibina , Humanos , Psilocibina/administração & dosagem , Psilocibina/uso terapêutico , Cefaleia Histamínica/tratamento farmacológico , Masculino , Feminino , Método Duplo-Cego , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Alucinógenos/administração & dosagem , Alucinógenos/uso terapêuticoRESUMO
In the cerebellum, hippocampus, and prefrontal cortex of mature male Wistar rats with trained spatial navigational skill in the Morris water maze, the transcriptional activity the NAPA gene that regulates the transport and secretion of synaptic vesicles, release of neurotransmitters, and protein degradation was determined by real-time PCR. Animals subjected to forced swimming in a time-matched regime (active control) and naïve rats were used as the comparison groups. Suppression of NAPA gene activity was found in the hippocampus and cerebellum of the active control group, while navigation skill training led to a significant increase in gene expression in all brain structures under study. The findings suggest the existence of specific mechanisms regulating NAPA gene activity during the formation of spatial memory and adaptive behavior under stress conditions.
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Encéfalo , Memória Espacial , Animais , Masculino , Ratos , Encéfalo/metabolismo , Expressão Gênica , Hipocampo/metabolismo , Aprendizagem em Labirinto/fisiologia , Ratos Wistar , Memória Espacial/fisiologia , Natação , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/genéticaRESUMO
We studied the effects of chronic intranasal administration of amyloidogenic fibrils of the proinflammatory protein S100A9 alone or in combination with glutamate antibodies on the expression of the neuregulin-1 gene (NRG1), a regulator of various physiological processes, in particular, regulation of neurogenesis and apoptosis, in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of long-term memory disturbances. Under conditions of amnesia induced by S100A9 fibrils, pronounced (>90%) blockade of the expression of the NRG1 gene was found in all cerebral structures. Glutamate antibodies prevented/corrected disturbances in the cerebral expression of the NRG1 gene, thereby maintaining the activity of the NRG1/ErbB molecular signaling system, probably associated with the formation of spatial memory.
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Cérebro , Transtornos da Memória , Neuregulina-1 , Memória Espacial , Animais , Camundongos , Ácido Glutâmico/imunologia , Ácido Glutâmico/metabolismo , Camundongos Endogâmicos C57BL , Neuregulina-1/genética , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Envelhecimento , Proteínas Amiloidogênicas/farmacologia , Calgranulina B/farmacologia , Anticorpos/administração & dosagem , Receptores ErbB/metabolismoRESUMO
OBJECTIVE: Using a patient-informed regimen, we conducted an exploratory randomized, double-blind, placebo-controlled study to systematically investigate the effects of psilocybin in cluster headache. BACKGROUND: Sustained reductions in cluster headache burden after limited quantities of psilocybin-containing mushrooms are anecdotally reported, although to date there are no controlled studies investigating these effects. METHODS: Participants were randomized to receive psilocybin (0.143 mg/kg) or placebo (microcrystalline cellulose) in a pulse of three doses, each ~5 days apart. Participants maintained headache diaries starting 2 weeks before and continuing through 8 weeks after the first drug session. A total of 16 participants were randomized to receive experimental drug and 14 were included in the final analysis. RESULTS: In the 3 weeks after the start of the pulse regimen, the change in cluster attack frequency was 0.03 (95% confidence interval [CI] -2.6 to 2.6) attacks/week with placebo (baseline 8.9 [95% CI 3.8 to 14.0]) and -3.2 (95% CI -8.3 to 1.9) attacks/week with psilocybin (baseline 9.6 [95% CI 5.6 to 13.6]; p = 0.251). Group difference in change from baseline had a moderate effect size (d = 0.69). The effect size was small in episodic participants (d = 0.35) but large in chronic participants (d = 1.25), which remained over the entire 8-week period measured (d = 0.81). Changes in cluster attack frequency were not correlated with the intensity of acute psychotropic effects during psilocybin administration. Psilocybin was well-tolerated without any unexpected or serious adverse events. CONCLUSIONS: Findings from this initial, exploratory study provide valuable information for the development of larger, more definitive studies. Efficacy outcomes were negative, owing in part to the small number of participants. The separation of acute psychotropic effects and lasting therapeutic effects underscores the need for further investigation into the mechanism(s) of action of psilocybin in headache disorders.
Assuntos
Cefaleia Histamínica , Humanos , Cefaleia Histamínica/tratamento farmacológico , Psilocibina/farmacologia , Psilocibina/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego , CefaleiaRESUMO
Proinflammatory S100A9 protein is a promoter of inflammation-linked neurodegeneration and the Tnfrsf1A gene encodes the TNF receptor 1A that binds TNFα to function as a regulator of inflammation. We studied the effects of chronic intranasal administration of in vitro prepared S100A9 fibrils alone or in combination with anti-glutamate antibodies on the expression of the Tnfrsf1A gene in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of impaired spatial memory. A differential cerebral pattern of Tnfrsf1A gene activity and its modification by S100A9 fibrillar structures were observed: inhibition of Tnfrsf1A gene expression in the hippocampus and cerebellum and its activation in the prefrontal cortex. Anti-glutamate antibodies normalized the expression of the Tnfrsf1A gene in the prefrontal cortex by affecting the TNF signaling pathway and preventing the development of inflammation.
Assuntos
Envelhecimento/fisiologia , Amnésia/patologia , Calgranulina B/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/biossíntese , Memória Espacial/fisiologia , Animais , Anticorpos/imunologia , Cerebelo/metabolismo , Ácido Glutâmico/imunologia , Hipocampo/metabolismo , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/metabolismo , Navegação Espacial/fisiologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We analyzed delayed effect of intranasal administration of anti-glutamate antibodies on mnestic function and tissue concentrations of neurotransmitters in the hippocampus and prefrontal cortex in aging C57BL/6 mice. It was found that after 14-day administration of anti-glutamate antibodies, improvement of the passive avoidance conditioning persisted for 7 days after the treatment was discontinued. In 7 days after discontinuation of treatment, increased content of dopamine and its metabolites as well as aspartic acid and taurine was observed in the hippocampus of mice treated with anti-glutamate antibodies. In the prefrontal cortex, administration of anti-glutamate antibodies had no effect on the levels of neurotransmitters, but increased the concentration of glutamate.
Assuntos
Ácido Aspártico , Ácido Glutâmico , Envelhecimento , Animais , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test sessions spaced 2 weeks apart. Subjects maintained headache diaries starting 2 weeks before the first session until 2 weeks after the second session. Physiological and psychological drug effects were monitored during sessions and several follow-up contacts with subjects were carried out to assure safety of study procedures. Ten subjects were included in the final analysis. Over the 2-week period measured after single administration, the reduction in weekly migraine days from baseline was significantly greater after psilocybin (mean, - 1.65 (95% CI: - 2.53 to - 0.77) days/week) than after placebo (- 0.15 (- 1.13 to 0.83) days/week; p = 0.003, t(9) = 4.11). Changes in migraine frequency in the 2 weeks after psilocybin were not correlated with the intensity of acute psychotropic effects during drug administration. Psilocybin was well-tolerated; there were no unexpected or serious adverse events or withdrawals due to adverse events. This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin. The separation of acute psychotropic effects and lasting therapeutic effects is an important finding, urging further investigation into the mechanism underlying the clinical effects of select 5-HT2A receptor compounds in migraine, as well as other neuropsychiatric conditions. Clinicaltrials.gov : NCT03341689.
Assuntos
Transtornos de Enxaqueca/prevenção & controle , Psilocibina/uso terapêutico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
RATIONALE: Animal studies and anecdotal human reports suggest that cannabinoids have antinociceptive effects. Controlled human studies have produced mixed results. OBJECTIVES: We sought to reduce existing variability by investigating the effects of intravenous delta-9-tetrahydrocannabinol (THC) in several pain paradigms within the same human subjects, addressing some of the limitations to the published literature. METHODS: In this exploratory randomized, double-blind, placebo-controlled, cross-over study, healthy human subjects received 0.01 mg/kg or 0.03 mg/kg intravenous THC or placebo (ethanol vehicle) infused over 10 min on three test days, each separated by at least 72 h. Capsaicin (250 µg) was injected intradermally to induce chemical pain and hyperalgesia. Four other forms of acute pain were induced: mechanical (von Frey filament), hot and cold (thermode), and electrical (pulse generator). Pain ratings were obtained before drug administration, at peak drug effects, and 2 h after drug administration and included both objective and subjective measures. THC drug effects and vital signs were also collected during experimental sessions. Nonparametric analysis with repeated measures was performed. RESULTS: THC induced euphoria, perceptual and cognitive alterations, and tachycardia in a dose-related manner, but failed to have significant effects in experimentally induced acute chemical, mechanical, thermal, or electrical pain and capsaicin-induced hyperalgesia. CONCLUSIONS: In this exploratory controlled study, intravenous THC lacked significant antinociceptive properties in experimental models of acute pain and capsaicin-induced hyperalgesia in healthy human subjects. Continued study of THC and other cannabinoids through high-quality, controlled studies in both healthy volunteers and patients with pain conditions is warranted to inform the growing demand for the clinical application of cannabinoids in pain management.
Assuntos
Analgésicos/administração & dosagem , Dronabinol/administração & dosagem , Euforia/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Dor/tratamento farmacológico , Psicotrópicos/administração & dosagem , Administração Intravenosa , Adulto , Canabinoides/farmacologia , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Euforia/fisiologia , Feminino , Voluntários Saudáveis/psicologia , Humanos , Masculino , Dor/diagnóstico , Dor/psicologia , Medição da Dor/métodos , Medição da Dor/psicologiaRESUMO
Intranasal administration of antibodies to glutamate in a dose of 250 µg/kg for two weeks facilitated spatial learning and memory formation in the Morris water maze in aging C57BL/6 mice. In animals treated with glutamate antibodies, the content of serotonin and dopamine metabolites 3-MT and HVA in the hippocampus decreased, but no changes in the metabolism of neurotransmitter acids were revealed. In the prefrontal cortex, dopamine level decreased and the content of its metabolite DOPAC increased; in parallel, an increase in excitatory and inhibitory amino acids (aspartic acid, glutamate, glycine, taurine, and GABA) was observed.
Assuntos
Anticorpos/farmacologia , Ácido Glutâmico/imunologia , Memória Espacial/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Envelhecimento/psicologia , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Teste do Labirinto Aquático de MorrisRESUMO
Chronic intranasal administration of antibodies to glutamate to aging C57Bl/6 mice improved passive avoidance conditioning, had no effect on horizontal and vertical locomotor activity, but slowed locomotion in the open-field test. Administration of antibodies to glutamate increased the content of dopamine and its metabolites in mouse hippocampus, but had no effect on the metabolism of neurotransmitter amino acids. In the frontal cortex, antibodies to glutamate did not affect neurotransmitter metabolism, but increased the level of both excitatory and inhibitory amino acids without changing their ratio.
Assuntos
Envelhecimento/fisiologia , Anticorpos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , Memória/efeitos dos fármacos , Administração Intranasal , Animais , Anticorpos/química , Ácido Aspártico/metabolismo , Aprendizagem da Esquiva/fisiologia , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Dopamina/metabolismo , Antagonistas de Aminoácidos Excitatórios/química , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Glicina/metabolismo , Haptenos/química , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Ácido Hidroxi-Indolacético/metabolismo , Imunoconjugados/química , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Coelhos , Serotonina/metabolismo , Soroalbumina Bovina/química , Ácido gama-Aminobutírico/metabolismoRESUMO
One prominent, long-standing view is that individuals with schizophrenia smoke cigarettes more than the general population to "self-medicate" cognitive deficits and other symptoms. This study tested the self-medication hypothesis by examining the effects of smoking abstinence and resumption on cognition in patients with schizophrenia. Nicotine-dependent smokers with schizophrenia (n=26) were trained on a cognitive battery and then hospitalized to achieve and maintain confirmed abstinence from smoking for ~1 week. Cognition was tested while smoking as usual (baseline), one day after smoking cessation (early abstinence), ~1 week later (extended abstinence), and within ~3 weeks of resuming smoking (resumption). The test battery included measures of processing speed, attention, conflict resolution, verbal memory, working memory, verbal fluency, and executive function to evaluate multiple cognitive domains affected by schizophrenia. Positive and negative symptoms of schizophrenia, depressive symptoms, and dyskinesia were also measured at baseline and after prolonged abstinence. There were no significant changes in global cognitive test performance with smoking cessation, abstinence, or resumption. There were small decreases in a measure of processing speed and delayed verbal recall with abstinence, but these findings failed to survive adjustments for multiple comparisons. Surprisingly, in this within subject "On-Off-Off-On" design, there were no significant effects of early or prolonged abstinence from smoking on cognitive and behavioral measures in smokers with schizophrenia. The results of this study challenge the widely held "self-medication" hypothesis of smoking and schizophrenia, question the extent of pro-cognitive effects of smoking and nicotine in schizophrenia, and support encouraging smoking cessation in schizophrenia.
Assuntos
Cognição , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Abandono do Hábito de Fumar , Fumar/psicologia , Adulto , Antipsicóticos/administração & dosagem , Transtornos Cognitivos/complicações , Feminino , Humanos , Masculino , Modelos Teóricos , Testes Neuropsicológicos , Nicotina/administração & dosagem , Escalas de Graduação Psiquiátrica , Esquizofrenia/tratamento farmacológico , AutomedicaçãoRESUMO
INTRODUCTION: Cannabis and agonists of the brain cannabinoid receptor (CB1R) produce acute memory impairments in humans. However, the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans. The objective of this analysis was to determine whether the administration of Δ9-Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, impairs encoding and/or retrieval of verbal information. MATERIALS AND METHODS: Healthy subjects were recruited from the community. Subjects were administered the Rey-Auditory Verbal Learning Test (RAVLT) either before administration of THC (experiment #1) (n=38) or while under the influence of THC (experiment #2) (n=57). Immediate and delayed recall on the RAVLT was compared. Subjects received intravenous THC, in a placebo-controlled, double-blind, randomized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication. RESULTS: Total immediate recall, short delayed recall, and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC (experiment #2) and not when the RAVLT was administered prior. CONCLUSIONS: THC acutely interferes with encoding of verbal memory without interfering with retrieval. These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information. Future studies will be necessary to determine whether THC impairs encoding of non-verbal information, to what extent THC impairs memory consolidation, and the role of other cannabinoids in the memory-impairing effects of cannabis. CLINICAL TRIAL INFORMATION: Cannabinoids, Neural Synchrony, and Information Processing (THC-Gamma) http://clinicaltrials.gov/ct2/show/study/NCT00708994 NCT00708994 Pharmacogenetics of Cannabinoid Response http://clinicaltrials.gov/ct2/show/NCT00678730 NCT00678730.
Assuntos
Dronabinol/farmacologia , Aprendizagem/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Psicotrópicos/farmacologia , Percepção da Fala/efeitos dos fármacos , Administração Intravenosa , Adulto , Método Duplo-Cego , Dronabinol/efeitos adversos , Feminino , Humanos , Masculino , Abuso de Maconha/psicologia , Testes Neuropsicológicos , Psicotrópicos/efeitos adversos , Adulto JovemRESUMO
We study the generation of planar quantum squeezed (PQS) states by quantum nondemolition (QND) measurement of an ensemble of ^{87}Rb atoms with a Poisson distributed atom number. Precise calibration of the QND measurement allows us to infer the conditional covariance matrix describing the F_{y} and F_{z} components of the PQS states, revealing the dual squeezing characteristic of PQS states. PQS states have been proposed for single-shot phase estimation without prior knowledge of the likely values of the phase. We show that for an arbitrary phase, the generated PQS states can give a metrological advantage of at least 3.1 dB relative to classical states. The PQS state also beats, for most phase angles, single-component-squeezed states generated by QND measurement with the same resources and atom number statistics. Using spin squeezing inequalities, we show that spin-spin entanglement is responsible for the metrological advantage.
RESUMO
Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impaired passive avoidance learning in old C57Bl/6 mice. Combined treatment with S100A9 fibrils and antibodies to glutamate was followed by an increase in horizontal locomotor activity of animals in the open-field test and did not disturb spatial memory.
Assuntos
Envelhecimento/fisiologia , Amnésia/tratamento farmacológico , Proteínas Amiloidogênicas/antagonistas & inibidores , Anticorpos/farmacologia , Calgranulina B/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Memória Espacial/efeitos dos fármacos , Amnésia/induzido quimicamente , Amnésia/fisiopatologia , Proteínas Amiloidogênicas/farmacologia , Animais , Anticorpos/isolamento & purificação , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Antagonistas de Aminoácidos Excitatórios/isolamento & purificação , Ácido Glutâmico/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Coelhos , Memória Espacial/fisiologiaRESUMO
BACKGROUND: Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. METHODS: Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. RESULTS: Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. CONCLUSIONS: These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. SIGNIFICANCE: Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the effectiveness potential of a topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the chronic constriction injury-induced neuropathic pain model.
Assuntos
Aminas/uso terapêutico , Analgésicos/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Neuropatia Ciática/tratamento farmacológico , Ácido gama-Aminobutírico/uso terapêutico , Administração Tópica , Aminas/administração & dosagem , Analgésicos/administração & dosagem , Animais , Constrição Patológica , Ácidos Cicloexanocarboxílicos/administração & dosagem , Modelos Animais de Doenças , Gabapentina , Masculino , Atividade Motora/efeitos dos fármacos , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ácido gama-Aminobutírico/administração & dosagemRESUMO
We demonstrate a new technique for detecting the amplitude of arbitrarily chosen components of radio-frequency waveforms based on stroboscopic backaction evading measurements. We combine quantum nondemolition measurements and stroboscopic probing to detect waveform components with magnetic sensitivity beyond the standard quantum limit. Using an ensemble of 1.5×10^{6} cold rubidium atoms, we demonstrate entanglement-enhanced sensing of sinusoidal and linearly chirped waveforms, with 1.0(2) and 0.8(3) dB metrologically relevant noise reduction, respectively. We achieve volume-adjusted sensitivity of δBsqrt[V]≈3.96 fTsqrt[cm^{3}/Hz], comparable to the best rf magnetometers.
RESUMO
We show how a test of macroscopic realism based on Leggett-Garg inequalities (LGIs) can be performed in a macroscopic system. Using a continuous-variable approach, we consider quantum nondemolition (QND) measurements applied to atomic ensembles undergoing magnetically driven coherent oscillation. We identify measurement schemes requiring only Gaussian states as inputs and giving a significant LGI violation with realistic experimental parameters and imperfections. The predicted violation is shown to be due to true quantum effects rather than to a classical invasivity of the measurement. Using QND measurements to tighten the "clumsiness loophole" forces the stubborn macrorealist to recreate quantum backaction in his or her account of measurement.
RESUMO
BACKGROUND: Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. METHODS: Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. RESULTS: Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. CONCLUSIONS: At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Dronabinol/efeitos adversos , Alucinógenos/efeitos adversos , Ruído , Transtornos Psicóticos/etiologia , Adolescente , Adulto , Córtex Cerebral/fisiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletroencefalografia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/patologia , Adulto JovemAssuntos
Transtornos Dissociativos/induzido quimicamente , Dronabinol/farmacologia , Potenciais Evocados P300/efeitos dos fármacos , Transtornos Psicóticos/etiologia , Psicotrópicos/farmacologia , Ácido gama-Aminobutírico/deficiência , Adolescente , Adulto , Mapeamento Encefálico , Método Duplo-Cego , Dronabinol/sangue , Eletroencefalografia , Flumazenil/administração & dosagem , Flumazenil/análogos & derivados , Humanos , Masculino , Medição da Dor , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/fisiopatologia , Adulto JovemRESUMO
Gamma (γ)-band oscillations play a key role in perception, associative learning, and conscious awareness and have been shown to be disrupted by cannabinoids in animal studies. The goal of this study was to determine whether cannabinoids disrupt γ-oscillations in humans and whether these effects relate to their psychosis-relevant behavioral effects. The acute, dose-related effects of Δ-9-tetrahydrocannabinol (Δ(9)-THC) on the auditory steady-state response (ASSR) were studied in humans (n=20) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, 0.015, and 0.03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Electroencephalography (EEG) was recorded while subjects listened to auditory click trains presented at 20, 30, and 40 Hz. Psychosis-relevant effects were measured with the Positive and Negative Syndrome scale (PANSS). Δ(9)-THC (0.03 mg/kg) reduced intertrial coherence (ITC) in the 40 Hz condition compared with 0.015 mg/kg and placebo. No significant effects were detected for 30 and 20 Hz stimulation. Furthermore, there was a negative correlation between 40 Hz ITC and PANSS subscales and total scores under the influence of Δ(9)-THC. Δ(9)-THC (0.03 mg/kg) reduced evoked power during 40 Hz stimulation at a trend level. Recent users of cannabis showed blunted Δ(9)-THC effects on ITC and evoked power. We show for the first time in humans that cannabinoids disrupt γ-band neural oscillations. Furthermore, there is a relationship between disruption of γ-band neural oscillations and psychosis-relevant phenomena induced by cannabinoids. These findings add to a growing literature suggesting some overlap between the acute effects of cannabinoids and the behavioral and psychophysiological alterations observed in psychotic disorders.