| 1. |
- Mayo, Leah M., 1987-, et al.
(författare)
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Gender differences in the behavioral and subjective effects of methamphetamine in healthy humans
- 2019
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Ingår i: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 236:8, s. 2413-2423
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Tidskriftsartikel (refereegranskat)abstract
- RationaleMethamphetamine (MA) use is steadily increasing and thus constitutes a major public health concern. Women seem to be particularly vulnerable to developing MA use disorder, as they initiate use at a younger age and transition more quickly to problematic use. Initial drug responses may predict subsequent use, but little information exists on potential gender differences in the acute effects of MA prior to dependence.ObjectiveWe examined gender differences in the acute effects of MA on subjective mood and reward-related behavior in healthy, non-dependent humans.MethodsMen (n = 44) and women (n = 29) completed 4 sessions in which they received placebo or MA under double-blind conditions twice each. During peak drug effect, participants completed the monetary incentive delay task to assess reaction times to cues signaling potential monetary losses or gains, in an effort to determine if MA would potentiate reward-motivated behavior. Cardiovascular and subjective drug effects were assessed throughout sessions.ResultsOverall, participants responded more quickly to cues predicting incentivized trials, particularly large-magnitude incentives, than to cues predicting no incentive. MA produced faster reaction times in women, but not in men. MA produced typical stimulant-like subjective and cardiovascular effects in all participants, but subjective ratings of vigor and (reduced) sedation were greater in women than in men.ConclusionsWomen appear to be more sensitive to the psychomotor-related behavioral and subjective effects of MA. These findings provide initial insight into gender differences in acute effects of MA that may contribute to gender differences in problematic MA use.
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| 2. |
- Bershad, Anya K., et al.
(författare)
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Effects of MDMA on attention to positive social cues and pleasantness of affective touch
- 2019
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Ingår i: Neuropsychopharmacology. - : NATURE PUBLISHING GROUP. - 0893-133X .- 1740-634X. ; 44:10, s. 1698-1705
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Tidskriftsartikel (refereegranskat)abstract
- The psychostimulant drug +/- 3,4-methylenedioxymethamphetamine (MDMA) reportedly produces distinctive feelings of empathy and closeness with others. MDMA increases social behavior in animal models and has shown promise in psychiatric disorders, such as autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). How it produces these prosocial effects is not known. This behavioral and psychophysiological study examined the effects of MDMA, compared with the prototypical stimulant methamphetamine (MA), on two measures of social behavior in healthy young adults: (i) responses to socially relevant, "affective" touch, and (ii) visual attention to emotional faces. Men and women (N = 36) attended four sessions in which they received MDMA (0.75 or 1.5 mg/kg), MA (20 mg), or a placebo in randomized order under double-blind conditions. Responses to experienced and observed affective touch (i.e., being touched or watching others being touched) were assessed using facial electromyography (EMG), a proxy of affective state. Responses to emotional faces were assessed using electrooculography (EOG) in a measure of attentional bias. Subjective ratings were also included. We hypothesized that MDMA, but not MA, would enhance the ratings of pleasantness and psychophysiological responses to affective touch and increase attentional bias toward positive facial expressions. Consistent with this, we found that MDMA, but not MA, selectively enhanced ratings of pleasantness of experienced affective touch. Neither drug altered the ratings of pleasantness of observed touch. On the EOG measure of attentional bias, MDMA, but not MA, increased attention toward happy faces. These results provide new evidence that MDMA can enhance the experience of positive social interactions; in this case, pleasantness of physical touch and attentional bias toward positive facial expressions. The findings are consistent with evidence that the prosocial effects are unique to MDMA relative to another stimulant. Understanding the behavioral and neurobiological processes underlying the distinctive social effects of MDMA is a key step to developing the drug for psychiatric disorders.
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| 3. |
- Brewer, Judson, et al.
(författare)
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Interventions and Implications
- 2021
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Ingår i: Intrusive Thinking. - : MIT Press. - 9780262542371 ; , s. 347-377
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Bokkapitel (refereegranskat)
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| 4. |
- Cavallo, Joel S., et al.
(författare)
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Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans
- 2016
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:8, s. e0161541-
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Tidskriftsartikel (refereegranskat)abstract
- Environmental stimuli repeatedly paired with drugs of abuse can elicit conditioned responses that are thought to promote future drug seeking. We recently showed that healthy volunteers acquired conditioned responses to auditory and visual stimuli after just two pairings with methamphetamine (MA, 20 mg, oral). This study extended these findings by systematically varying the number of drug-stimuli pairings. We expected that more pairings would result in stronger conditioning. Three groups of healthy adults were randomly assigned to receive 1, 2 or 4 pairings (Groups P1, P2 and P4, Ns = 13, 16, 16, respectively) of an auditory-visual stimulus with MA, and another stimulus with placebo (PBO). Drug-cue pairings were administered in an alternating, counterbalanced order, under double-blind conditions, during 4 hr sessions. MA produced prototypic subjective effects (mood, ratings of drug effects) and alterations in physiology (heart rate, blood pressure). Although subjects did not exhibit increased behavioral preference for, or emotional reactivity to, the MA-paired cue after conditioning, they did exhibit an increase in attentional bias (initial gaze) toward the drug-paired stimulus. Further, subjects who had four pairings reported " liking" the MApaired cue more than the PBO cue after conditioning. Thus, the number of drug-stimulus pairings, varying from one to four, had only modest effects on the strength of conditioned responses. Further studies investigating the parameters under which drug conditioning occurs will help to identify risk factors for developing drug abuse, and provide new treatment strategies.
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| 5. |
- de Wit, Harriet, et al.
(författare)
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Does acute stress play a role in the lasting therapeutic effects of psychedelic drugs?
- 2023
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Ingår i: Neuropsychopharmacology. - : SPRINGERNATURE. - 0893-133X .- 1740-634X. ; 48:10, s. 1422-1424
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Tidskriftsartikel (refereegranskat)abstract
- Psychedelic drugs, when used in the context of psychotherapy, can produce significant and long-lasting memories with enduring beneficial effects. Yet, the behavioral and neurobiological mechanisms that underlie these beneficial effects remain a mystery. Here, we suggest that both the quality and durability of memories of the drug-facilitated therapeutic experience may be mediated, in part, by the acute stress responses induced by the drugs. It is known that high doses of psychedelic drugs activate autonomic and hormonal stress responses. For evolutionarily adaptive reasons, acute stress is known to i) instill meaning to the immediate context in which it is experienced, and ii) lead to the formation of salient and lasting memories of the events surrounding the stress. Thus, the stress-inducing effect of psychedelic drugs may contribute to the reported sense of meaning, as well as the durability of the memory of the drug experience. When used in a therapeutic context these actions may i) enhance the salience of insights gained during the experience and ii) strengthen the memories formed by these experiences. Future empirical studies will help to determine whether acute stress contributes to the emotional significance and lasting effects of psychedelic-assisted psychotherapy.
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| 6. |
- Mayo, Leah M., et al.
(författare)
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Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers
- 2016
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Ingår i: Journal of Studies on Alcohol and Drugs. - Piscataway, NJ, United States : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 77:2, s. 317-326
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study examined the acquisition of conditioning between novel stimuli and single doses of alcohol in social drinkers. Environmental stimuli present during the consumption of alcohol or other drugs come to elicit conditioned responses that subsequently increase drug seeking. However, relatively few studies have examined the process of acquisition of these conditioned drug responses in human subjects. Method: We used a procedure previously developed to study acquisition of conditioned responses to a methamphetamine-associated cue. In the present study we applied the paradigm to alcohol, pairing de novo neutral cues with alcohol in social drinkers (N=36). We obtained measures of self-report, behavioral preference, emotional reactivity (assessed using facial electromyography), and attention to specific cues paired with administration of 0.6 g/kg 95% absolute alcohol or placebo. Results: After conditioning, participants showed an increase in attention toward the alcohol-paired cue, and this increase was associated with ratings of liking the alcohol-containing beverage during the conditioning sessions. In contrast to our previous findings with methamphetamine, the alcohol-paired cue did not elicit changes in emotional reactivity (measured by facial electromyography) or behavioral preference. Conclusions: This study extends our previous findings with a stimulant drug to. alcohol and highlights possible similarities and differences in conditioning with different classes of drugs. Conditioning with alcohol was less robust than with methamphetamine, but in both cases the conditioning that did occur was related to positive subjective drug response.
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| 7. |
- Mayo, Leah M, et al.
(författare)
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Conditioned Preference to a Methamphetamine-Associated Contextual Cue in Humans
- 2013
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Ingår i: Neuropsychopharmacology. - : Nature Publishing Group: Open Access Hybrid Model Option A. - 0893-133X .- 1740-634X. ; 38:6, s. 921-929
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Tidskriftsartikel (refereegranskat)abstract
- Classical conditioning is widely used to study motivational properties of addictive drugs in animals, but has rarely been used in humans. We established a procedure suitable for studying the neurobiology and individual determinants of classical conditioning in humans. Healthy volunteers were randomly assigned to four groups that received methamphetamine or placebo in the presence of distinctive environmental cues under paired or unpaired conditions. During each session, subjects performed tasks known to activate the ventral striatum. Tasks were performed in the presence of a distinctive context, consisting of a screen background image of a beach or mountains, accompanied by corresponding sounds. Separate groups of subjects carried out the tasks under high ($35-50) or low ($5-20) reward conditions. Within each of the two reward conditions, one group (paired) received methamphetamine (20 mg, oral) or placebo consistently associated with one of the contexts, while the other (unpaired) received drug or placebo unrelated to context. A fifth group (paired) performed the tasks with contextual cues but in the absence of monetary incentives. Before and after conditioning, participants carried out a series of forced choice tasks for the contextual cues, and change of preference over time was analyzed. All paired groups showed a significant increase in preference for the drug-associated context, with a linear trend for increase across the levels of reward. Preference was unrelated to subjective drug effects, and did not change in the unpaired group. These data support the translational utility of our conditioning procedure for studies of reward mechanisms in humans.
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| 8. |
- Van Hedger, Kathryne, et al.
(författare)
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Effects of Acute Drug Administration on Emotion : a Review of Pharmacological MRI Studies
- 2021
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Ingår i: Current Addiction Reports. - : SPRINGERNATURE. - 2196-2952. ; 8:2, s. 181-193
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Forskningsöversikt (refereegranskat)abstract
- Purpose of Review Many drug users claim to use drugs to cope with negative emotions, which may, in turn, result in persistent emotional blunting or anhedonia even when they are not using drugs. The purpose of this review is to describe the ways acute administration of psychoactive drugs impacts brain regions during emotion-related tasks, as a first step in understanding how drugs influence emotion processing in the brain. Recent Findings Drugs have varying effects on neural responses to emotional stimuli. In general, alcohol, analgesics, and psychedelics reduce neural reactivity to negative emotional stimuli in the amygdala and other brain regions. Other drugs produce mixed effects: Stimulants such as caffeine and modafinil increase brain activation while viewing emotional stimuli, whereas MDMA decreases activation during presentation of negative images. The effects of cannabinoids (cannabidiol and THC) are mixed. There are also inconsistent findings on the associations between neural responses to emotional stimuli and subjective drug effects. Consistent with the notion that individuals might use drugs non-medically to diminish the experience of negative emotions, several drugs of abuse decrease neural responses to negative stimuli in limbic brain regions. These neural actions may underlie the reported "emotional blunting" of drugs, which may contribute to drug-seeking behavior. Future work is needed to examine these limbic responses in relation to self-reports of changes in affect, both during acute administration and after extended drug use.
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| 9. |
- Van Hedger, Kathryne, et al.
(författare)
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Neural responses to cues paired with methamphetamine in healthy volunteers
- 2018
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Ingår i: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 43:8, s. 1732-1737
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Tidskriftsartikel (refereegranskat)abstract
- Drug cues, or conditioned responses to stimuli paired with drugs, are widely believed to promote drug use. The acquisition of these conditioned responses has been well characterized in laboratory animals: neutral stimuli paired with drugs elicit conditioned responses resembling the motivational and incentive properties of the drug itself. However, few studies have examined acquisition of conditioning, or the nature of the conditioned response, in humans. In this study, we used fMRI to examine neural responses to stimuli that had been paired with methamphetamine or placebo in healthy young adults. Participants first underwent four conditioning sessions in which visual-auditory stimuli were paired with either methamphetamine (20 mg, oral) or placebo. Then on a drug-free test day, the stimuli were presented during an fMRI scan to assess neural responses to the stimuli. We hypothesized that the stimuli would elicit drug-like brain activity, especially in regions related to reward. Instead, we found that the methamphetamine-paired stimuli, compared to placebo-paired stimuli, produced greater activation in regions related to visual and auditory processing, consistent with the drugs unconditioned effects on sensory processing. This is the first study to demonstrate conditioned neural responses to drug-paired stimuli after just two pairings of methamphetamine in healthy adults. The study also illustrates that conditioned responses may develop to unexpected components of the drugs effects.
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