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1.
Am J Drug Alcohol Abuse ; 50(1): 42-53, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37921613

RESUMO

Background: Impulsive choice is associated with both cocaine use and relapse. Little is known about the influence of transient states on impulsive choice in people who use cocaine (PWUC).Objective: This study investigated the direct effects of induced boredom on impulsive choice (i.e., temporal discounting) in PWUC relative to well-matched community controls.Methods: Forty-one PWUC (≥1× cocaine use in past 3 months; 7 females) and 38 demographically matched controls (5 females) underwent two experimental conditions in counterbalanced order. Temporal discounting was assessed immediately after a standardized boredom induction task (peg-turning) and a self-selected video watched for the same duration (non-boredom). Subjective mood state and perceived task characteristics were assessed at baseline, during experimental manipulations, and after the choice task.Results: PWUC and controls were well matched on sex, age, and socioeconomic status. Groups were also similar in reported use of drugs other than cocaine, except for recent cigarette and alcohol use (PWUC > controls). As expected, peg-turning increased boredom in the sample overall, with higher boredom reported during peg-turning than the video (p < .001, η2p = .20). Participants overall exhibited greater impulsive choice after boredom than non-boredom (p = .028, η2p = .07), with no preferential effects in PWUC (p > .05, BF01 = 2.9).Conclusion: Experimentally induced boredom increased state impulsivity irrespective of cocaine use status - in PWUC and carefully matched controls - suggesting a broad link between boredom and impulsive choice. This is the first study to show that transient boredom directly increases impulsive choice. Data support a viable laboratory method to further parse the effects of boredom on impulsive choice.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Desvalorização pelo Atraso , Feminino , Humanos , Tédio , Comportamento de Escolha , Cocaína/farmacologia , Comportamento Impulsivo
2.
Psychol Rec ; 73(3): 481-500, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39006304

RESUMO

Identifying the processes by which environmental stimuli can come to influence drug use is important for developing more efficacious interventions. This study investigated derived relational responding and the transfer of differential conditioned effects of environmental stimuli paired with "smoked" cocaine in accordance with the relations of symmetry, transitivity, and equivalence using Heart Rate as the measure of conditioning among 12 adults with significant histories of cocaine use. Match-to-sample (MTS) procedures were used to test for emergent relations among two four-member stimulus groupings. One member of a group was then paired with 25-mg of smoked cocaine and one member of the other group was paired with 0-mg of smoked cocaine. 10 participants completed the MTS protocol: 4 participants demonstrated two four-member equivalence classes, 3 participants demonstrated two three-member equivalence classes and 2 participants demonstrated symmetry only. One participant demonstrated no derived relations. Differential respondent elicited changes in HR was demonstrated in the presence of stimuli paired with smoked cocaine among 4 of the 6 participants completing the conditioning phase; all 4 of the participants demonstrated a bi-directional transfer of these functions in accordance with symmetry. Transfer was not reliably demonstrated in accordance with transitive or equivalence relations. The results suggest that drug respondent elicitation in the context of drug use may be a function of both direct conditioning and relational processes. These findings have implications for studying and understanding the processes by which stimuli in the natural ecology can set the occasion for cocaine use and developing cocaine use disorder.

3.
Addict Biol ; 27(4): e13183, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35754107

RESUMO

Attenuating enzymatic degradation of endocannabinoids (eCBs) by fatty acid amide hydrolase (FAAH) reduces cannabis withdrawal symptoms in preclinical and clinical studies. In mice, blocking cyclooxygenase-2 (COX-2) activity increases central eCB levels by inhibiting fatty acid degradation. This placebo-controlled study examined the effects of the FDA-approved COX-2 selective inhibitor, celecoxib, on cannabis withdrawal, 'relapse', and circulating eCBs in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (12M, 3F) completed a crossover study comprising two 11-day study phases (separated by >14 days for medication clearance). In each phase, the effects of daily BID placebo (0 mg) or celecoxib (200 mg) on cannabis (5.3% THC) intoxication, withdrawal symptoms (4 days of inactive cannabis self-administration) and 'relapse' (3 days of active cannabis self-administration following abstinence) were assessed. Outcome measures included mood, cannabis self-administration, sleep, food intake, cognitive performance, tobacco cigarette use and circulating eCBs and related lipids. Under placebo maintenance, cannabis abstinence produced characteristic withdrawal symptoms (negative mood, anorexia and dreaming) relative to cannabis administration and was associated with increased OEA (a substrate of FAAH) and oleic acid (metabolite of OEA), with no change in eCB levels. Compared to placebo, celecoxib improved subjective (but not objective) measures of sleep and did not affect mood or plasma levels of eCBs or associated lipids and increased cannabis craving. The overall absence of effects on cannabis withdrawal symptoms, self-administration or circulating eCBs relative to placebo, combined with an increase in cannabis craving, suggests celecoxib does not show promise as a potential pharmacotherapy for CUD.


Assuntos
Cannabis , Abuso de Maconha , Síndrome de Abstinência a Substâncias , Agonistas de Receptores de Canabinoides , Celecoxib/uso terapêutico , Estudos Cross-Over , Ciclo-Oxigenase 2/uso terapêutico , Dronabinol , Endocanabinoides , Humanos , Abuso de Maconha/psicologia , Recidiva , Fumantes , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/psicologia
4.
Addict Biol ; 26(4): e12993, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33389797

RESUMO

There are no FDA-approved treatments for cannabis use disorder (CUD). Preclinical research has shown that the 5HT-2C agonist lorcaserin attenuates cue-induced reinstatement of THC seeking and self-administration. The goal of this placebo-controlled, counterbalanced, within-subject human laboratory study was to examine lorcaserin's effects on cannabis intoxication and self-administration. Lorcaserin (10 mg BID) was administered during one of two 13-day inpatient phases and placebo during the other; each phase was separated by ≥7 days of washout. Inpatient phases comprised (1) standardized cannabis administration (7.0% THC) at no financial cost (intoxication), counterbalanced with (2) the option to self-administer cannabis following either 0 or 3 days of abstinence. Cognitive task performance, food intake, subjective ratings of drug effects, objective/subjective sleep measures, and tobacco cigarette use were also assessed. Fifteen normal-weight, daily cannabis users (4F, 11M) not seeking treatment for CUD completed the study. Lorcaserin significantly reduced cannabis self-administration following 0 and 3 days of cannabis abstinence and also reduced craving for cannabis during abstinence. Lorcaserin produced small but significant increases in positive cannabis ratings and body weight relative to placebo. Lorcaserin also reduced tobacco cigarette smoking on days of cannabis administration relative to placebo. During abstinence, subjective but not objective measures of sleep quality worsened during lorcaserin maintenance. Overall, lorcaserin's ability to decrease drug taking and cannabis craving in nontreatment-seeking cannabis users supports further investigation of 5HT-2C agonists as potential pharmacotherapies for CUD.


Assuntos
Benzazepinas/uso terapêutico , Abuso de Maconha/tratamento farmacológico , Fumar Maconha/tratamento farmacológico , Adulto , Afeto/efeitos dos fármacos , Fissura/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoadministração , Sono/efeitos dos fármacos , Qualidade do Sono , Adulto Jovem
5.
Addict Biol ; 24(4): 707-716, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-29659126

RESUMO

The α2a-adrenergic agonist, lofexidine, reduced cannabis withdrawal-related sleep disruption in the laboratory, but side effects (e.g. fatigue, hypotension) limit its utility as a treatment for cannabis use disorder. This study tested the potential efficacy and tolerability of a daily bedtime administration of the FDA-approved α2a-adrenergic agonist, guanfacine, in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (13M, 2F) completed a within-subject study comprising two 9-day inpatient study phases. Each phase tested the effects of daily placebo or immediate-release guanfacine (2 mg) on cannabis intoxication (5.6 percent THC; 2 days), withdrawal (4 days of abstinence) and subsequent 'relapse' (3 days of cannabis self-administration). Ratings of mood, sleep, cardiovascular effects, food intake, psychomotor performance and cannabis self-administration were assessed. An outpatient phase preceded each inpatient phase for medication clearance or dose induction. Under placebo medication conditions, cannabis abstinence produced significant withdrawal, including irritability, sleep disruption and anorexia. Guanfacine reduced ratings of irritability and improved objective measures of sleep during cannabis withdrawal relative to placebo but did not reduce cannabis self-administration. Guanfacine was well tolerated with little evidence of fatigue and only small decreases in blood pressure: no dose was held due to hypotension. Thus, a single daily administration of guanfacine at bedtime improved sleep and mood during cannabis withdrawal relative to placebo. This positive signal supports further studies varying the guanfacine dose, formulation or frequency of administration, or combining it with other medications to increase the likelihood of having an impact on cannabis use.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Guanfacina/uso terapêutico , Abuso de Maconha , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Afeto , Anorexia/etiologia , Anorexia/fisiopatologia , Pressão Sanguínea , Cannabis/efeitos adversos , Comportamento Alimentar , Feminino , Humanos , Humor Irritável , Masculino , Desempenho Psicomotor , Autoadministração , Sono , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Síndrome de Abstinência a Substâncias/psicologia , Adulto Jovem
6.
Addict Biol ; 24(4): 765-776, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30378231

RESUMO

Tobacco and cannabis co-users (T+CUs) have poor cannabis cessation outcomes, but the mechanisms underlying this are not well understood. This laboratory study examined the effects of (1) the partial nicotinic agonist, varenicline, on tobacco cessation among T+CUs, and (2) varenicline, alone, and when combined with the cannabinoid agonist nabilone, on cannabis withdrawal and a laboratory model of cannabis relapse. Non-treatment-seeking T+CUs were randomized to active-varenicline or placebo-varenicline, and completed a 15-day outpatient phase; varenicline was titrated to 1 mg BID during days 1-8, and participants were instructed to abstain from tobacco during days 9-15. Participants then moved inpatient for 16 days, where they continued their outpatient medication and tobacco abstinence. Inpatient testing included two, 8-day medication periods, where active-nabilone and placebo-nabilone were administered in counterbalanced order, and measures of acute cannabis effects (days 1-2), withdrawal (days 4-5) and 'relapse' (days 6-8) were collected. Participants in the active-varenicline group were more likely to achieve cotinine-verified tobacco abstinence during the outpatient period versus placebo-varenicline group (46 percent versus 24 percent, respectively), and also reported less mood disturbance and cigarette craving while inpatient. Active-nabilone attenuated cannabis withdrawal in both groups but did not affect cannabis relapse. Regression analyses revealed that two tobacco-related variables, i.e. age of first cigarette use, and cigarette craving while inpatient, were independent predictors of cannabis relapse outcomes. Thus, varenicline holds promise in this population, as a tool to examine the effects of tobacco abstinence on cannabis use outcomes, and as a component of smoking cessation treatments targeting T+CUs.


Assuntos
Fumar Cigarros/tratamento farmacológico , Dronabinol/análogos & derivados , Abuso de Maconha/tratamento farmacológico , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Abandono do Hábito de Fumar , Síndrome de Abstinência a Substâncias/fisiopatologia , Vareniclina/uso terapêutico , Adulto , Fumar Cigarros/epidemiologia , Comorbidade , Dronabinol/uso terapêutico , Feminino , Humanos , Masculino , Abuso de Maconha/epidemiologia , Nicotina/efeitos adversos , Agonistas Nicotínicos/efeitos adversos , Síndrome de Abstinência a Substâncias/etiologia , Adulto Jovem
7.
Appetite ; 109: 131-136, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27884761

RESUMO

Eating disorders are associated with a range of abnormalities in eating behavior. Some individuals consume large amounts of non-caloric artificial sweeteners, suggesting abnormalities in appetitive responding. The current study aimed to quantify hedonic and motivating effects of artificial sweetener in individuals with and without an eating disorder. Two laboratory studies were conducted. Hedonic preference was estimated using the number of artificial sweetener packets (0-10) added to unsweetened cherry flavored Kool-Aid (study 1). Motivation to obtain sweetener was assessed by a progressive ratio (PR) work task (study 2). Ninety-three participants (25 anorexia nervosa restricting type (AN-R), 23 AN binge/purge type (AN-B/P), 20 bulimia nervosa (BN), and 25 normal controls (NC)) completed the study. No significant difference in hedonic preference was found among participant groups. Work completed at the PR task ranged from 0 to 9500 key-board presses. The AN-B/P group had a significantly higher breakpoint and performed significantly more work for sweetener compared to the BN and NC groups. Among AN-B/P and AN-R participants, the preferred number of Equal packets was significantly correlated with the breakpoint and total work. The increased amount of work for sweetener among individuals with AN-B/P supports an enhanced reward value of sweet taste in this population, and suggests that the characteristic food avoidance in AN cannot be accounted for by decreased reward value of all taste-related stimuli. This study also supports the novel application of a PR ratio task to quantify the motivating effect of sweet taste among individuals with an eating disorder.


Assuntos
Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Preferências Alimentares/psicologia , Motivação , Edulcorantes , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Eat Disord ; 24(5): 412-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27348805

RESUMO

The purpose of the current study was to examine the relative reinforcing effect of exercise compared to a non-monetary alternative reinforcer (leisure activity), and to money, before and after weight restoration in an inpatient population with anorexia nervosa (AN). Sixty-two inpatients with AN completed a progressive ratio (PR) task to earn exercise, leisure activities, or cash at low weight and after weight restoration. Measures of pathology and motivation to exercise were completed and post-treatment discharge weights were collected. Patients worked harder for exercise at low weight than after weight restoration (df = 46, t = 5.50, p < .001). PR task performance was weakly associated with a measure of commitment to exercise (low weight: r = 0.31, weight restored: r = 0.36, p < .05), but not with other clinical measures or follow-up weights. Contrary to prior suggestions, measurement of the reinforcing value of exercise among individuals with AN via a PR task does not appear valuable in assessing clinical severity or outcome. Other, simpler, self-report measures of commitment to exercise may have greater value in assessing these outcomes.


Assuntos
Anorexia Nervosa/terapia , Terapia por Exercício/métodos , Avaliação de Resultados em Cuidados de Saúde , Cooperação do Paciente/psicologia , Reforço Psicológico , Adulto , Feminino , Humanos , Motivação , Adulto Jovem
9.
Am J Drug Alcohol Abuse ; 41(2): 161-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25321637

RESUMO

BACKGROUND: Butyrylcholinesterase (BChE) is beginning to attract attention as a possible target for cocaine abuse treatment because of its role in metabolizing cocaine. OBJECTIVE: The purpose of this analysis was to assess whether endogenous BChE levels are associated with the subjective effects of cocaine. METHODS: Data from 28 participants in five inpatient cocaine self-administration studies were included in the present analysis. Four minutes after each smoked cocaine dose, participants rated their drug-related effects from 0-100 using a computerized self-report Visual Analogue Scale (VAS). The main outcome measures were nine change-in-VAS ratings between a baseline placebo dose and a 25-mg smoked cocaine dose. RESULTS: After controlling for age, sex, total years of cocaine use, total milligrams of cocaine administered before the 25-mg dose being analyzed, and baseline diastolic blood pressure, endogenous BChE was not significantly associated with any of the nine change-in-VAS ratings. CONCLUSION: Though BChE appears to be a possible target for cocaine abuse treatment, these data suggest that endogenous levels of BChE may not play a role in modifying the subjective effects of cocaine. Future larger studies of BChE in respect to the subjective effects produced by cocaine are needed to confirm or refute these findings.


Assuntos
Butirilcolinesterase/sangue , Transtornos Relacionados ao Uso de Cocaína/sangue , Cocaína/administração & dosagem , Administração por Inalação , Adulto , Pressão Sanguínea/efeitos dos fármacos , Usuários de Drogas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Horm Behav ; 63(1): 105-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23098805

RESUMO

Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cocaína/administração & dosagem , Ciclo Menstrual/fisiologia , Animais , Transtornos Relacionados ao Uso de Cocaína/sangue , Relação Dose-Resposta a Droga , Estradiol/sangue , Feminino , Macaca mulatta , Ciclo Menstrual/sangue , Progesterona/sangue , Reforço Psicológico , Autoadministração
11.
Int J Eat Disord ; 46(7): 737-46, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23853140

RESUMO

OBJECTIVE: Activity-based anorexia is a translational rodent model that results in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of our investigation was to identify vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats. METHOD: Sprague-Dawley rats were maintained under conditions of restricted access to food (N = 64; or unlimited access, N = 16) until experimental exit, predefined as a target weight loss of 30-35% or meeting predefined criteria for animal health. Nonlinear mixed effects statistical modeling was used to describe wheel running behavior, time to event analysis was used to assess experimental exit, and a regressive partitioning algorithm was used to classify phenotypes. RESULTS: Objective criteria were identified for distinguishing novel phenotypes of activity-based anorexia, including a vulnerable phenotype that conferred maximal hyperactivity, minimal food intake, and the shortest time to experimental exit, and a resistant phenotype that conferred minimal activity and the longest time to experimental exit. DISCUSSION: The identification of objective criteria for defining vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats provides an important framework for studying the neural mechanisms that promote vulnerability to or protection against the development of self-starvation and hyperactivity during adolescence. Ultimately, future studies using these novel phenotypes may provide important translational insights into the mechanisms that promote these maladaptive behaviors characteristic of anorexia nervosa.


Assuntos
Anorexia/fisiopatologia , Atividade Motora , Animais , Anorexia Nervosa , Comportamento Animal , Peso Corporal , Modelos Animais de Doenças , Ingestão de Alimentos , Feminino , Humanos , Fenótipo , Ratos , Ratos Sprague-Dawley , Inanição , Redução de Peso
12.
Addict Biol ; 18(6): 993-1002, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22741619

RESUMO

Marijuana withdrawal contributes to the high relapse rates in individuals seeking treatment for marijuana-use disorders. Quetiapine, an atypical antipsychotic, reduces characteristic symptoms of marijuana withdrawal in a variety of psychiatric conditions, including mood lability, sleep disruption and anorexia. This human laboratory study investigated the effectiveness of quetiapine to decrease marijuana withdrawal and relapse to marijuana use in non-treatment-seeking marijuana smokers. Volunteers were maintained on placebo or quetiapine (200 mg/day) in this double-blind, counter-balanced, within-subject study consisting of two 15-day medication phases, the last 8 days of which were in-patient. On the first in-patient day, active marijuana [6.2% delta (9)-tetrahydrocannabinol (THC)] was repeatedly smoked under controlled conditions. For the next 3 days, inactive marijuana (0.0% THC) was available for self-administration (withdrawal). On the subsequent 4 days, active marijuana (6.2% THC) was available for self-administration (relapse). Volunteers (n = 14) who smoked an average of 10 marijuana cigarettes/day, 7 days/week, completed the study. Under placebo, withdrawal was marked by increased subjective ratings of negative mood, decreased sleep quality, and decreased caloric intake and weight loss. Compared with placebo, quetiapine improved sleep quality, increased caloric intake and decreased weight loss. However, quetiapine increased marijuana craving and marijuana self-administration during the relapse phase. These data do not suggest that quetiapine shows promise as a potential treatment for marijuana dependence.


Assuntos
Anorexia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Dronabinol/efeitos adversos , Transtornos do Sono-Vigília/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Afeto/efeitos dos fármacos , Análise de Variância , Anorexia/induzido quimicamente , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacologia , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Abuso de Maconha/tratamento farmacológico , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Placebos , Desempenho Psicomotor/efeitos dos fármacos , Fumarato de Quetiapina , Prevenção Secundária , Autoadministração/estatística & dados numéricos , Transtornos do Sono-Vigília/induzido quimicamente , Redução de Peso/efeitos dos fármacos , Adulto Jovem
13.
Appetite ; 62: 70-5, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23178173

RESUMO

Binge eating is a core clinical feature of bulimia nervosa (BN). Enhanced reinforcing value of food may play a role in this behavioral disturbance, but a systematic behavioral assessment of objective measures of the rewarding value of binge eating is lacking. The purpose of this study was to quantify the reinforcing value of food in BN patients as compared with normal controls. A progressive ratio (PR) computerized work task was completed under binge and non-binge instruction. The task consisted of 12 trials. The first trial required 50 keyboard taps to earn one portion of yogurt shake, and subsequent trials required progressive work increments of 200 taps for each additional portion. Completion of all 12 trials required 13,800 taps to earn 2100ml of shake. The breakpoint, defined as the largest ratio completed before a participant stopped working, was the measure of reinforcing efficacy. Ten patients and 10 controls completed the experiment. Under binge instruction, patients completed more trials and taps, and had a higher breakpoint than controls. The non-binge instruction yielded opposite findings; compared to controls, patients completed fewer trials and taps, and had a lower breakpoint. These results support the feasibility and potential utility of a PR task to quantify the reinforcing value of food in patients with BN.


Assuntos
Transtorno da Compulsão Alimentar/psicologia , Bulimia Nervosa/psicologia , Bulimia/psicologia , Dieta , Recompensa , Trabalho , Adulto , Estudos de Avaliação como Assunto , Feminino , Humanos , Iogurte , Adulto Jovem
14.
Drug Alcohol Depend ; 243: 109757, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36608482

RESUMO

BACKGROUND: Despite the high prevalence of polysubstance use, outcomes and potential risks associated with common drug combinations are not well characterized. Many individuals who use cocaine also use cannabis, yet little is known about how interactions between the two drugs might contribute to continued co-use. METHODS: The aim of this double-blind, placebo-controlled study was to determine the physiological and subjective effects of smoked cannabis with smoked cocaine, to identify variables that may contribute to the continued use of this drug combination. Healthy, non-treatment seeking volunteers who reported smoking both cocaine and cannabis (N = 9, all males) completed a 13-day inpatient protocol. On session days, cannabis [0.0 or 5.6 % tetrahydrocannabinol (THC)] was administered 28 min prior to cocaine (0, 12, or 25 mg). Dependent measures included pharmacokinetic assessment of THC and cocaine and their respective metabolites, in addition to subjective and cardiovascular effects. RESULTS: Active cannabis (5.6 % THC) increased plasma levels of THC and the metabolite 11-nor-9-carboxy-Δ9-THC (THCCOOH), as well as subjective ratings of cannabis effects and heart rate relative to inactive cannabis. Cocaine dose-dependently increased plasma cocaine and metabolites and subjective ratings of cocaine effects. Active cannabis pre-treatment decreased plasma levels of cocaine and metabolites. Furthermore, active cannabis attenuated cocaine-related reductions in 'Hunger' and 'Calm.' CONCLUSIONS: Cannabis pre-treatment altered the subjective experience of smoked cocaine and reduced peak plasma levels of cocaine. Future studies should explore additional doses of each drug and whether these changes also impact cocaine's reinforcing effects.


Assuntos
Cannabis , Alucinógenos , Fumar Maconha , Masculino , Humanos , Dronabinol/farmacologia , Fumar , Método Duplo-Cego , Agonistas de Receptores de Canabinoides
15.
Nat Med ; 29(6): 1487-1499, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37291212

RESUMO

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis' positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.ClinicalTrials.gov identifiers: NCT03325595 , NCT03443895 and NCT03717272 .


Assuntos
Cannabis , Alucinógenos , Abuso de Maconha , Síndrome de Abstinência a Substâncias , Animais , Camundongos , Método Duplo-Cego , Dronabinol/efeitos adversos , Alucinógenos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome de Abstinência a Substâncias/tratamento farmacológico
16.
Behav Pharmacol ; 23(5-6): 461-77, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22772334

RESUMO

Comparatively few studies over the past 30 years have used pharmacological manipulations as a means of understanding processes underlying feeding behavior of nonhuman primates. In the 1970s and early 1980s, four laboratories provided data on the anorexigenic effects of a range of drugs on rhesus monkeys and baboons, and a fifth laboratory studied the effects of neuropeptides on feeding behavior of baboons. There were differences in the way anorexigenic drugs altered eating topography, and those that increased dopamine levels had greater abuse liability than those that increased serotonin levels. Studies in the 1980s and 1990s used foraging models and principles of behavioral economics to understand food-drug interactions. Experimenter-given anorexigenic drugs did not function as economic substitutes for food. Recent studies have examined the effects of a range of drugs on consumption of highly palatable food and model diet-induced obesity. Although some drugs, including stimulants, N-methyl-D-aspartate antagonists, and a cannabinoid antagonist increased the latency to standard food consumption, there was little evidence for a selective effect of any drug on highly palatable food consumption. Results obtained in nonhuman primates did not always confirm those observed in rodents. Future studies looking at sex differences and social factors may provide insight into factors related to human obesity.


Assuntos
Experimentação Animal/história , Depressores do Apetite/farmacologia , Modelos Animais de Doenças , Comportamento Alimentar/efeitos dos fármacos , Transtornos da Alimentação e da Ingestão de Alimentos/tratamento farmacológico , Obesidade/tratamento farmacológico , Primatas , Animais , Depressores do Apetite/efeitos adversos , Depressores do Apetite/uso terapêutico , Preferências Alimentares , História do Século XX , História do Século XXI , Humanos , Obesidade/prevenção & controle , Primatas/classificação
17.
Behav Pharmacol ; 23(3): 271-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22495183

RESUMO

Tolerance to the analgesic effects of opioids has been demonstrated in laboratory animals after repeated drug administration; yet, this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine whether tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone (0, 5, and 20 mg/70 kg, orally) were compared, using a within-session cumulative dosing procedure, on the first and fifth days of the 'daily' dosing phase to assess for tolerance; active oxycodone was administered on the second and fourth days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the first and the fifth day of a 5-day 'intermittent' dosing phase; placebo medication was administered on the second and fourth days of the intermittent dosing phase. A 9-day 'washout' period occurred between phases during which no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the cold pressor test, pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the first and the fifth days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the fifth compared with the first day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the first and the fifth days of either dosing phase were detected. Although obtained under limited experimental conditions, these findings suggest that tolerance may not develop to the analgesic effects of therapeutic doses of oxycodone under short-term daily dosing conditions, even though some of its subjective effects may decrease. These data also suggest that intermittent administration may enhance the analgesic effects of oxycodone, while also increasing some of the drug's positive subjective effects related to abuse liability.


Assuntos
Analgésicos Opioides/farmacologia , Oxicodona/farmacologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miose/induzido quimicamente , Medição da Dor , Tempo de Reação/efeitos dos fármacos , Inquéritos e Questionários
18.
Am J Drug Alcohol Abuse ; 38(6): 530-4, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22812932

RESUMO

BACKGROUND: Little is known about whether the duration of cocaine use or an individual's age may influence the acute effects of cocaine, patterns of use, and specific treatment needs. OBJECTIVES: This post hoc analysis determined whether the duration of cocaine use or current age influenced the acute subjective response to cocaine. Data from four smoked cocaine self-administration laboratory studies were combined and analyzed to determine whether the subjective effects of a 25-mg smoked cocaine dose varied as a function of years of cocaine use or current age. METHODS: Thirty-six nontreatment-seeking healthy cocaine users (ages 32-49) were admitted to studies lasting from 12 to 105 days. Participants rated the subjective effects of each cocaine dose from 0 to 100 by completing a computerized self-report visual analogue scale (VAS). The main outcome measures were the change in VAS ratings between a baseline placebo dose and the first 25-mg dose of smoked cocaine. RESULTS: No significant relationship was found between the subjective effects of cocaine and years of cocaine use (mean 20.9, range 5-30) or current age (mean 41.1, range 32-49). CONCLUSION: Among long-term cocaine users between the ages of 32 and 49, the acute subjective effects of cocaine did not vary as a function of years of cocaine use or current age. SCIENTIFIC SIGNIFICANCE: These data fail to support the incentive sensitization theory for addiction by Robinson and Berridge, as cocaine "liking" and "wanting" remained the same regardless of age or years of cocaine use.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Teoria Psicológica , Adulto , Fatores Etários , Transtornos Relacionados ao Uso de Cocaína/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Fatores de Tempo
19.
Drug Alcohol Depend ; 239: 109599, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35963210

RESUMO

BACKGROUND: Due to the poor oral bioavailability of buprenorphine, an oral formulation has not been thought possible. Lyndra Therapeutics is developing a once-weekly long-acting oral product containing buprenorphine. We evaluated the efficacy of this formulation in reducing intravenous (i.v.) fentanyl self-administration by three male and three female rhesus monkeys. METHODS: Buprenorphine HCl and naloxone HCl were co-formulated using an 11:1 ratio of buprenorphine:naloxone in a controlled-release gastric residence formulation administered in an oral capsule (LYN-013). Naloxone was included to determine the feasibility of combining naloxone with buprenorphine in the formulation as an abuse deterrent. Complete fentanyl dose-response functions were determined during each session. The efficacy of single doses of 56/5, 112/10 and 168/15 mg buprenorphine/naloxone in reducing fentanyl self-administration was examined over 13 days. RESULTS: LYN-013 significantly decreased the rate of responding for fentanyl for 3 days and significantly reduced total intake of fentanyl for 8 days. Time to maximal buprenorphine levels (Tmax) ranged between 56 and 68 h for all 3 doses. The maximal buprenorphine level (Cmax) following 168 mg was 2.3 ng/ml which was significantly greater that those observed for 56 mg (1.22 ng/ml) and 112 mg (1.35 ng/ml). Finally, the area-under-curves (AUCtau) were buprenorphine dose-dependently increased from 88 to 127-265 h*ng/ml. There were no signs of non-specific changes in behavior. CONCLUSIONS: A once-weekly oral buprenorphine/naloxone formulation produced sustained suppression of fentanyl self-administration in monkeys suggesting that oral delivery of buprenorphine with this formulation could provide a new opportunity to treat opioid use disorders (OUD).


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Animais , Buprenorfina/uso terapêutico , Combinação Buprenorfina e Naloxona/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Feminino , Fentanila/uso terapêutico , Macaca mulatta , Masculino , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
20.
Horm Behav ; 59(2): 227-35, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21192940

RESUMO

There are currently no FDA-approved pharmacotherapies for cocaine abuse. Converging preclinical and clinical evidence indicates that progesterone may have potential as a treatment for cocaine-abusing women, who represent a growing portion of cocaine users. We have previously shown that oral progesterone reduced the positive subjective effects of cocaine in female cocaine users during the follicular phase of the menstrual cycle, when endogenous progesterone levels were low. To extend these findings, the present study assessed the effects of oral progesterone (150 mg BID) administered during the follicular phase on smoked cocaine self-administration in women relative to the normal follicular and luteal phases. Healthy, non-treatment seeking female cocaine smokers (N=10) underwent three 4-day inpatient stays, during: 1) a normal follicular phase; 2) a normal luteal phase; and 3) a follicular phase when oral progesterone was administered. During each stay, participants completed 4 self-administration sessions in which they first smoked a "sample" dose of cocaine (0, 12, 25 or 50 mg) and then had 5 opportunities at 14-minute intervals to self-administer that dose at a cost of $5 per dose. Expected cocaine dose effects on self-administration, subjective effects, and cardiovascular effects were observed. However, there was no effect of oral progesterone administration or menstrual cycle phase on cocaine self-administration. Thus, oral progesterone was not effective in reducing cocaine use in women under the current conditions. However, based on previous literature, further research assessing the role of oral progesterone for the treatment of cocaine dependence in women is warranted.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína/administração & dosagem , Progesterona/administração & dosagem , Progesterona/farmacologia , Fumar , Administração por Inalação , Administração Oral , Adulto , Transtornos Relacionados ao Uso de Cocaína/sangue , Formas de Dosagem , Relação Dose-Resposta a Droga , Feminino , Hormônios/sangue , Humanos , Progesterona/química , Autoadministração
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