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BACKGROUND AND AIMS: Early-life adversities are known to alter drug reward processing in rodents. Despite the well-known link between early adversity and the risk of substance use disorder, few studies have measured how childhood adversity affects human drug reward. Here, we assessed the relationship between historical childhood adversities and responses to single doses of methamphetamine, d-amphetamine or buprenorphine in healthy participants. METHODS: Using a secondary analysis approach, we assessed the impact of childhood adversity on drug effects from three randomised, placebo-controlled studies in which healthy volunteers received methamphetamine (20 mg oral; n = 35), d-amphetamine (20 mg oral; n = 54) or buprenorphine (0.2 mg sublingual; n = 35). Ratings of feeling effect, liking, disliking, feeling high and wanting more of the drug were collected 15-210 min post-administration, and heart rate changes were analysed using random-intercept mixed-effect models. The area under the curve from these and previous studies was calculated to visualise the relationship between childhood adversity severity and drug effects. RESULTS: Greater childhood adversity was associated with reduced feel effects (significant three-way interactions b = -0.07, 95% CI [-0.12, -0.02], p = 0.009), like effects (b = -0.07, 95% CI [-0.13, -0.00], p = 0.038) and feel high (b = -0.06, 95% CI [-0.10, -0.01], p = 0.020) towards the stimulant drugs 90-180 min post-administration. CONCLUSIONS: Childhood adversity was not significantly associated with other subjective or heart rate responses to the drugs. Overall, participants with more childhood adversities reported dampened subjective responses to stimulant drugs, but not to buprenorphine. Future studies should examine the generalisability of these relationships, to identify the mechanisms underlying the link between childhood adversity and drug responsiveness.
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The ability to calibrate learning according to new information is a fundamental component of an organism's ability to adapt to changing conditions. Yet, the exact neural mechanisms guiding dynamic learning rate adjustments remain unclear. Catecholamines appear to play a critical role in adjusting the degree to which we use new information over time, but individuals vary widely in the manner in which they adjust to changes. Here, we studied the effects of a low dose of methamphetamine (MA), and individual differences in these effects, on probabilistic reversal learning dynamics in a within-subject, double-blind, randomized design. Participants first completed a reversal learning task during a drug-free baseline session to provide a measure of baseline performance. Then they completed the task during two sessions, one with MA (20 mg oral) and one with placebo (PL). First, we showed that, relative to PL, MA modulates the ability to dynamically adjust learning from prediction errors. Second, this effect was more pronounced in participants who performed poorly at baseline. These results present novel evidence for the involvement of catecholaminergic transmission on learning flexibility and highlights that baseline performance modulates the effect of the drug.
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The 3,4-methylenedioxymethamphetamine (MDMA) has long been used non-medically, and it is currently under investigation for its potential therapeutic benefits. Both uses may be related to its ability to enhance empathy, sociability, emotional processing and its anxiolytic effects. However, the neural mechanisms underlying these effects, and their specificity to MDMA compared to other stimulants, are not yet fully understood. Here, using electroencephalography (EEG), we investigated the effects of MDMA and a prototypic stimulant, methamphetamine (MA), on early visual processing of socio-emotional stimuli in an oddball emotional faces paradigm. Specifically, we examined whether MDMA or MA enhance the processing of facial expressions, compared to placebo, during the early stages of visual perception. MDMA enhanced an event-related component that is sensitive to detecting faces (N170), specifically for happy and angry expressions compared to neutral faces. MA did not affect this measure, and neither drug altered other components of the response to emotional faces. These findings provide novel insights into the neural mechanisms underlying the effects of MDMA on socio-emotional processing and may have implications for the therapeutic use of MDMA in the treatment of social anxiety and other psychiatric disorders.
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Emoções , Expressão Facial , N-Metil-3,4-Metilenodioxianfetamina , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Estimulantes do Sistema Nervoso Central/farmacologia , Eletroencefalografia/métodos , Emoções/efeitos dos fármacos , Emoções/fisiologia , Reconhecimento Facial/efeitos dos fármacos , Reconhecimento Facial/fisiologia , Alucinógenos/farmacologia , Metanfetamina/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Percepção Visual/efeitos dos fármacos , Percepção Visual/fisiologia , Método Duplo-CegoRESUMO
OBJECTIVE: Traumatic brain injury (TBI) is a risk factor for suicide, but questions related to mechanisms remain unanswered. Impulsivity is a risk factor for suicide and is a common sequela of TBI. The authors explored the relationships between TBI and both suicidal ideation and suicide attempts and explored whether impulsivity and comorbid psychiatric diagnoses mediate these relationships. METHODS: This cross-sectional retrospective chart review study included 164 veterans enrolled in a previous study. Sixty-nine veterans had no TBI history, and 95 had a TBI history (mild, N=44; moderate, N=13; severe, N=12; and unclear severity, N=26). To examine the associations between TBI and suicidal ideation or suicide attempts, as well as potential mediators of these relationships, chi-square tests, t tests, and logistic regression models were used. RESULTS: Unadjusted analyses indicated that veterans with TBI were more likely to report suicidal ideation; however, in analyses controlling for mediators, this relationship was no longer significant. Among veterans with TBI, suicidal ideation was related most strongly to high impulsivity (odds ratio=15.35, 95% CI=2.43-96.79), followed by depression (odds ratio=5.73, 95% CI=2.53-12.99) and posttraumatic stress disorder (odds ratio=2.57, 95% CI=1.03-6.42). TBI was not related to suicide attempts, yet suicide attempts were related to high impulsivity (odds ratio=6.95, 95% CI=1.24-38.75) and depression (odds ratio=3.89, 95% CI=1.56-9.40). CONCLUSIONS: These findings suggest that impulsivity, followed by psychiatric diagnoses, most strongly mediate the relationships between TBI and both suicidal ideation and suicide attempts. Impulsivity may be mechanistically related to, and serve as a future treatment target for, suicidality among veterans with TBI.
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Lesões Encefálicas Traumáticas , Veteranos , Humanos , Tentativa de Suicídio/psicologia , Ideação Suicida , Veteranos/psicologia , Estudos Retrospectivos , Estudos Transversais , Comportamento Impulsivo , Fatores de Risco , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/epidemiologiaRESUMO
Neural complexity correlates with one's level of consciousness. During coma, anesthesia, and sleep, complexity is reduced. During altered states, including after lysergic acid diethylamide (LSD), complexity is increased. In the present analysis, we examined whether low doses of LSD (13 and 26 µg) were sufficient to increase neural complexity in the absence of altered states of consciousness. In addition, neural complexity was assessed after doses of two other drugs that significantly altered consciousness and mood: delta-9-tetrahydrocannabinol (THC; 7.5 and 15 mg) and methamphetamine (MA; 10 and 20 mg). In three separate studies (N = 73; 21, LSD; 23, THC; 29, MA), healthy volunteers received placebo or drug in a within-subjects design over three laboratory visits. During anticipated peak drug effects, resting state electroencephalography (EEG) recorded Limpel-Ziv complexity and spectral power. LSD, but not THC or MA, dose-dependently increased neural complexity. LSD also reduced delta and theta power. THC reduced, and MA increased, alpha power, primarily in frontal regions. Neural complexity was not associated with any subjective drug effect; however, LSD-induced reductions in delta and theta were associated with elation, and THC-induced reductions in alpha were associated with altered states. These data inform relationships between neural complexity, spectral power, and subjective states, demonstrating that increased neural complexity is not necessary or sufficient for altered states of consciousness. Future studies should address whether greater complexity after low doses of LSD is related to cognitive, behavioral, or therapeutic outcomes, and further examine the role of alpha desynchronization in mediating altered states of consciousness.
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Relação Dose-Resposta a Droga , Dronabinol , Eletroencefalografia , Dietilamida do Ácido Lisérgico , Metanfetamina , Humanos , Metanfetamina/administração & dosagem , Metanfetamina/farmacologia , Dronabinol/farmacologia , Dronabinol/administração & dosagem , Masculino , Adulto , Dietilamida do Ácido Lisérgico/farmacologia , Dietilamida do Ácido Lisérgico/administração & dosagem , Feminino , Adulto Jovem , Eletroencefalografia/efeitos dos fármacos , Alucinógenos/administração & dosagem , Alucinógenos/farmacologia , Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/administração & dosagemRESUMO
BACKGROUND: The prosocial compound ± 3,4-methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that has shown promise as an adjunct to psychotherapy in the treatment of post-traumatic stress disorder. MDMA increases positive responses to social images, and it has been suggested that the ability of MDMA to positively bias social perception may underlie its therapeutic efficacy as a psychotherapy adjunct. However, the effect of the compound on affective responses to positive or negative social feedback has not been tested. AIMS: In this study, we aimed to test the effects of MDMA compared to placebo and the prototypical stimulant, methamphetamine (MA), on responses to positive and negative social feedback. METHODS: This was a double-blind, placebo-controlled, crossover trial (NCT03790618), comparing the effects of two doses of MDMA (0.75 mg/kg, 1.5 mg/kg) to both placebo and MA (20 mg) on responses to a personalized social feedback task, similar to a dating app, in healthy adult volunteers ages 18-40 (N = 36, 18 women, 18 men). RESULTS/OUTCOMES: The high dose of MDMA increased positive affective responses to social feedback. CONCLUSIONS/INTERPRETATIONS: These findings suggest one process by which MDMA may facilitate social connection. Further work is needed to understand how MDMA affects responses to more generalized types of social feedback and to understand these effects in clinical populations.
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Alucinógenos , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Transtornos de Estresse Pós-Traumáticos , Masculino , Adulto , Humanos , Feminino , Retroalimentação , Metanfetamina/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Anfetamina/uso terapêutico , Método Duplo-CegoRESUMO
Taking regular low doses of psychedelic drugs (microdosing) is a practice that has drawn recent scientific and media attention for its potential psychotherapeutic effects. Yet, controlled studies evaluating this practice have lagged. Here, we review recent evidence focusing on studies that were conducted with rigorous experimental control. Studies conducted under laboratory settings using double-blind placebo-controlled procedures and investigator-supplied drug were compiled. The review includes demographic characteristics of participants and dependent measures such as physiological, behavioral, and subjective effects of the drugs. Review criteria were met by 14 studies, all of which involved acute or repeated low (5-20 µg) doses of lysergic acid diethylamide (LSD). Acute microdoses of LSD dose-dependently altered blood pressure, sleep, neural connectivity, social cognition, mood, and perception of pain and time. Perceptible drug effects were reported at doses of 10 to 20 µg but not 5 µg. No serious adverse effects were reported. Repeated doses of LSD did not alter mood or cognition on any of the measures studied. The findings suggest that low doses of LSD are safe and produce acute behavioral and neural effects in healthy adults. Further studies are warranted to extend these findings to patient samples and to other psychedelic drugs and to investigate microdosing as a potential pharmacological treatment for psychiatric disorders.
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Alucinógenos , Dietilamida do Ácido Lisérgico , Humanos , Alucinógenos/administração & dosagem , Alucinógenos/farmacologia , Dietilamida do Ácido Lisérgico/farmacologia , Dietilamida do Ácido Lisérgico/administração & dosagem , Relação Dose-Resposta a DrogaRESUMO
Recent studies and anecdotal reports suggest that psychedelics can improve mood states, even at low doses. However, few placebo-controlled studies have examined the acute effects of low doses of LSD in individuals with psychiatric symptoms. In the current study, we examined the acute and sub-acute effect of a low dose of LSD (26 µg) on subjective effects and mood in volunteers with mild depressed mood. The study used a randomized, double-blind, crossover design to compare the effects of LSD in two groups of adults: participants who scored high (≥17; n = 20) or low (<17; n = 19) on the Beck Depression-II inventory (BDI) at screening. Participants received a single low dose of LSD (26 µg) and placebo during two 5-h laboratory sessions, separated by at least one week. Subjective, physiological, and mood measures were assessed at regular intervals throughout the sessions, and behavioral measures of creativity and emotion recognition were obtained at expected peak effect. BDI depression scores and mood ratings were assessed 48-h after each session. Relative to placebo, LSD (26 µg) produced expected, mild physiological and subjective effects on several measures in both groups. However, the high BDI group reported significantly greater drug effects on several indices of acute effects, including ratings of vigor, elation, and affectively positive scales of a measure of psychedelic effects (5D-ASC). The high BDI group also reported a greater decline in BDI depression scores 48-h after LSD, compared to placebo. These findings suggest that an acute low dose of LSD (26 µg) elicits more pronounced positive mood and stimulant-like effects, as well as stronger altered states of consciousness in individuals with depressive symptoms, compared to non-depressed individuals.
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Alucinógenos , Dietilamida do Ácido Lisérgico , Adulto , Humanos , Afeto , Estado de Consciência , Método Duplo-Cego , Alucinógenos/farmacologia , Voluntários Saudáveis , Dietilamida do Ácido Lisérgico/farmacologia , Estudos Cross-OverRESUMO
Despite distinct classes of psychoactive drugs producing putatively unique states of consciousness, there is surprising overlap in terms of their effects on episodic memory and cognition more generally. Episodic memory is supported by multiple subprocesses that have been mostly overlooked in psychopharmacology and could differentiate drug classes. Here, we reanalyzed episodic memory confidence ratings from 10 previously published data sets (28 drug conditions total) using signal detection models to estimate two conscious states involved in episodic memory and one consciously controlled metacognitive process of memory: autonoetic retrieval of specific details (recollection), noetic recognition absent of retrieved details (familiarity), and retrospective introspection of memory decisions (metamemory). Sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on whether they impacted encoding, consolidation, or retrieval (the formation, stabilization, and access to memory traces, respectively). Sedatives at encoding reliably impaired both recollection and familiarity but at consolidation enhanced recollection. Dissociatives and cannabinoids at encoding impaired recollection but less reliably impaired familiarity, and cannabinoids at retrieval increased false recollections. These drug-induced encoding impairments occasionally came with metamemory enhancements, perhaps because of less interstimulus interference. Psychedelics at encoding impaired recollection but tended to enhance familiarity and did not impact metamemory. Stimulants at encoding enhanced metamemory, at consolidation impaired metamemory, and at retrieval enhanced familiarity and metamemory. These findings allude to mechanisms underlying the idiosyncratic phenomena of drugs, such as blackouts from sedatives and presque vu from psychedelics. Finally, these findings converge on a model in which memory quantity and stability influence metamemory. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Canabinoides , Alucinógenos , Memória Episódica , Metacognição , Humanos , Rememoração Mental , Alucinógenos/farmacologia , Hipnóticos e Sedativos/farmacologia , Canabinoides/farmacologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Stimulant drugs are thought to alter processing of rewarding stimuli. However, the mechanisms by which they do this are not fully understood. METHOD: In this study we used EEG to assess effects of single doses of methamphetamine (MA) on neural responses during anticipation and receipt of reward in healthy volunteers. Healthy young men and women (N = 28) completed three sessions in which they received placebo, a low MA dose (10 mg) or a higher MA dose (20 mg) under double blind conditions. Subjective and cardiovascular measures were obtained, and EEG was used to assess brain activity during an electrophysiological version of the Monetary Incentive Delay (eMID) task. RESULTS: EEG measures showed expected patterns during anticipation and receipt of reward, and MA produced its expected effects on mood and cardiovascular function. However, MA did not affect EEG responses during either anticipation or receipt of rewards. CONCLUSIONS: These findings suggest that the effects of MA on EEG signals of reward processing are subtle, and not related to the drug's effects on subjective feelings of well-being. The findings contribute to our understanding of the neural effects of MA during behaviors related to reward.
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Metanfetamina , Masculino , Adulto , Humanos , Feminino , Metanfetamina/farmacologia , Emoções , Recompensa , Motivação , Encéfalo , Imageamento por Ressonância Magnética , Antecipação PsicológicaRESUMO
MDMA is a stimulant-like drug with distinctive empathogenic effects. Its pro-social effects, such as feelings of connectedness, may contribute to both its popularity as a recreational drug and its apparent value as an adjunct to psychotherapy. However, little is known about the behavioral processes by which MDMA affects social interactions. This investigation examined the effects of MDMA (100 mg versus placebo; N = 18) on feelings of connectedness with an unfamiliar partner during a semi-structured casual conversation. A separate study examined the effects of a prototypic stimulant methamphetamine (MA; 20 mg versus placebo; N = 19) to determine the pharmacological specificity of effects. Oxytocin levels were obtained in both studies. Compared to placebo, both MDMA and MA increased feelings of connection with the conversation partners. Both MDMA and MA increased oxytocin levels, but oxytocin levels were correlated with feeling closer to the partner only after MDMA. These findings demonstrate an important new dimension of the pro-social effects of MDMA, its ability to increase feelings of connectedness during casual conversations between two individuals. Surprisingly, MA had a similar effect. The findings extend our knowledge of the social effects of these drugs, and illustrate a sensitive method for assessing pro-social effects during in-person dyadic encounters.
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Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Humanos , Metanfetamina/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Ocitocina , Comunicação , EmoçõesRESUMO
RATIONALE: Stimulant drugs like methamphetamine (MA) activate brain reward circuitry, which is linked to the development of problematic drug use. It is not clear how drugs like MA alter neural response to a non-drug reward. OBJECTIVES: We examined how acute MA impacts neural response to receipt of a monetary reward relative to a loss in healthy adults. We hypothesized that MA (vs. placebo) would increase mesolimbic neural activation to reward, relative to loss. METHODS: In a within-subject, randomized, cross-over, double-blind, placebo-controlled design, 41 healthy adults completed the Doors monetary reward task during fMRI after ingestion of placebo or 20 mg MA. We examined drug effects on neural response to reward receipt (Win vs. Loss) using a priori anatomical striatal regions of interest (nucleus accumbens (NAcc), caudate, putamen). RESULTS: MA decreased NAcc BOLD activation to reward vs loss compared to placebo (p=.007) without altering caudate or putamen BOLD activation. Similar effects for reward vs. loss were obtained using whole brain analysis. Additional exploratory ROI analysis comparing reward and loss activation relative to a neutral "fixation" period indicated that MA increased NAcc BOLD activation during loss trials, without decreasing activation during win trials. CONCLUSIONS: This preliminary evidence suggests that MA increases NAcc neural response to the receipt of monetary loss. Additional studies are needed to replicate our findings and clarify the mechanisms contributing to altered mesolimbic neural response to reward and loss receipt during stimulant intoxication.
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Metanfetamina , Núcleo Accumbens , Humanos , Adulto Jovem , Metanfetamina/efeitos adversos , Motivação , Recompensa , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Stimulants like methamphetamine (MA) affect motivated behaviors via actions on circuits mediating mood, attention, and reward. Few studies examined the effects of single doses of stimulants on reward circuits during anticipation and receipt of rewards and losses. Here, we examined the effects of MA (20 mg) or placebo in a within-subject, double-blind study with healthy adults (n = 43). During 2 fMRI sessions, participants completed the monetary incentive delay task. Primary outcome measures were BOLD activation in selected regions of interest during anticipation and receipt of monetary rewards and losses. Secondary analyses included behavioral measures, whole brain analysis, and arterial spin labeling. MA produced its expected behavioral effects and increased neural activation in the ventral striatum and anterior insula during anticipation of monetary loss versus non-loss. MA did not affect activation during anticipation of gains, or during receipt of wins or losses. MA significantly reduced cerebral blood flow in the striatum and insula. The present finding that a stimulant enhances the responses of striatal and insular regions to upcoming loss suggests that this system may be sensitive to the salience of upcoming events. The finding adds to a complex body of evidence regarding the effects of stimulant drugs on neural processes during motivated behaviors.
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BACKGROUND AND HYPOTHESIS: Diminished social motivation is a negative symptom of schizophrenia and leads to severe functional consequences for many patients suffering from the illness. However, there are no effective medications available to treat this symptom. Despite the lack of approved treatments for patients, there is a growing body of literature on the effects of several classes of drugs on social motivation in healthy volunteers that may be relevant to patients. The aim of this review is to synthesize these results in an effort to identify novel directions for the development of medications to treat reduced social motivation in schizophrenia. STUDY DESIGN: In this article, we review pharmacologic challenge studies addressing the acute effects of psychoactive drugs on social motivation in healthy volunteers and consider how these findings may be applied to deficits in social motivation in schizophrenia. We include studies testing amphetamines and 3,4-methylenedioxymethamphetamine (MDMA), opioids, cannabis, serotonergic psychedelics, antidepressants, benzodiazepines, and neuropeptides. STUDY RESULTS: We report that amphetamines, MDMA, and some opioid medications enhance social motivation in healthy adults and may represent promising avenues of investigation in schizophrenia. CONCLUSIONS: Given the acute effects of these drugs on behavioral and performance-based measures of social motivation in healthy volunteers, they may be particularly beneficial as an adjunct to psychosocial training programs in patient populations. It remains to be determined how these medications affect patients with deficits in social motivation, and in which contexts they may be most effectively administered.
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Apatia , N-Metil-3,4-Metilenodioxianfetamina , Psicofarmacologia , Esquizofrenia , Adulto , Humanos , Motivação , N-Metil-3,4-Metilenodioxianfetamina/uso terapêuticoRESUMO
Individual differences in subjective, stimulant-like effects of alcohol are associated with the risk of developing alcohol use disorder. Specifically, individuals who experience more pronounced stimulant-like effects from alcohol are more likely to continue and escalate their usage. The neural basis for these individual differences in subjective response is not yet known. Using a within-subject design, 27 healthy male social drinkers completed three fMRI scans after ingesting a placebo, 0.4 and 0.8 g/kg alcohol, in a randomized order under double-blind conditions. Subjective stimulant effects of alcohol were assessed at regular intervals during each session. Seed-based and regional homogeneity analyses were conducted to evaluate changes in resting-state functional connectivity in relation to the stimulant effect of alcohol. Results indicated that 0.4 g/kg alcohol increased the connectivity to thalamus, and 0.8 g/kg alcohol decreased the connectivity to ventral anterior insula, primarily from the superior parietal lobule. Both doses reduced regional homogeneity in the superior parietal lobule but without an exact overlap with clusters showing connectivity changes in the seed-based analyses. The self-reported stimulant effect of alcohol was not significantly related to changes in seed-based connectivity or regional homogeneity. These findings suggest that alcohol-induced stimulation effects are not related to these indices of neural activity.
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Consumo de Bebidas Alcoólicas , Alcoolismo , Humanos , Masculino , Etanol/farmacologia , Individualidade , Lobo Parietal , Imageamento por Ressonância Magnética/métodosRESUMO
Psychoactive drugs modulate learning and emotional processes in ways that could impact their recreational and medical use. Recent work has revealed how drugs impact different stages of processing emotional episodic memories, specifically encoding (forming memories), consolidation (stabilizing memories), and retrieval (accessing memories). Drugs administered before encoding may preferentially impair (e.g., GABAA sedatives including alcohol and benzodiazepines, Δ9-tetrahydrocannabinol or THC, ketamine), enhance (e.g., dextroamphetamine and dextromethamphetamine), or both impair and enhance (i.e., ± 3,4-methylenedioxymethylamphetamine or MDMA) emotionally negative and positive compared to neutral memories. GABAA sedatives administered immediately post-encoding (during consolidation) can preferentially enhance emotional memories, though this selectivity may decline or even reverse (i.e., preferential enhancement of neutral memories) as the delay between encoding and retrieval increases. Finally, retrieving memories under the effects of THC, dextroamphetamine, MDMA, and perhaps GABAA sedatives distorts memory, with potentially greater selectively for emotional (especially positive) memories. We review these effects, propose neural mechanisms, discuss methodological considerations for future work, and speculate how drug effects on emotional episodic memory may contribute to drug use and abuse.
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Consolidação da Memória , Memória Episódica , N-Metil-3,4-Metilenodioxianfetamina , Humanos , Psicotrópicos/farmacologia , Emoções , Hipnóticos e Sedativos/farmacologia , Dextroanfetamina/farmacologia , Ácido gama-Aminobutírico , Rememoração MentalRESUMO
Cannabis and its main psychoactive constituent, delta-9-tetrahydrocannabinol (THC), impair cognitive processes, including the ability to inhibit inappropriate responses. However, responses to cannabinoid drugs vary widely, and little is known about the factors that influence the risk for adverse effects. One potential source of variation in response to cannabinoids in women is circulating ovarian hormones such as estradiol and progesterone. Whereas there is some evidence that estradiol affects responses to cannabinoids in rodents, little is known about such interactions in humans. Here, we investigate whether variations in estradiol levels across the follicular phase of the menstrual cycle modulate the effect of THC on inhibitory control in healthy women. Healthy female occasional cannabis users (N = 60) received THC (7.5 mg and 15 mg, oral) and placebo during either the early follicular phase, when estradiol levels are low, or the late follicular phase, when estradiol levels are higher. They completed a Go/No Go (GNG) task at the time of peak drug effect. We hypothesized that the effects of THC on GNG performance would be greater when estradiol levels were elevated. As expected, THC impaired GNG task performance: it increased response time and errors of commission/false alarms and decreased accuracy, relative to placebo. However, these impairments were not related to estradiol levels. These results suggest that THC-induced impairments in inhibitory control are not affected by cycle-related fluctuations in estradiol levels.
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Canabinoides , Cannabis , Alucinógenos , Feminino , Humanos , Agonistas de Receptores de Canabinoides , Canabinoides/farmacologia , Dronabinol/efeitos adversos , Estradiol , Alucinógenos/farmacologiaRESUMO
RATIONALE: Translational research, especially research that bridges studies with humans and nonhuman species, is critical to advancing our understanding of human disorders such as addiction. This advancement requires reliable and rigorous models to study the underlying constructs contributing to the maladaptive behavior. OBJECTIVE: In this commentary, we address some of the challenges of conducting translational research by examining a single procedure, place conditioning. Place conditioning is commonly used with laboratory animals to study the conditioned rewarding effects of drugs, and recent studies indicate that a similar procedure can be used in humans. RESULTS: We discuss the opportunities and challenges of making the procedure comparable across species, as well as discuss the benefits of more systematically applying the procedure to humans. CONCLUSION: We argue that the capacity of humans to report verbally on their internal experiences (perceptions, affective states, likes and dislikes) add an important dimension to the understanding of the procedures used in laboratory animals.