The resurgence of interest in using psychedelic drugs, including lysergic acid diethylamide (LSD), in psychiatry has drawn attention to the medically unsupervised practice of 'microdosing'. Thousands of users claim that very low doses of LSD, taken at 3-4-day intervals, improve mood and cognitive function., However, few controlled studies have described the effects of the drug when taken in this way. Here, in a double-blind controlled study, we studied the effects of four repeated doses of LSD tartrate (13 or 26 μg) or placebo, administered to healthy adults at 3-4 day intervals, on mood, cognitive performance and responses to emotional tasks. Participants were randomly assigned to one of three drug conditions: placebo (N = 18), 13 μg LSD (N = 19), or 26 μg LSD (N = 19). They attended four 5-hour drug-administration sessions separated by 3-4 days, followed by a drug-free follow-up session 3-4 days after the last session. LSD (26 μg) produced modest subjective effects including increased ratings of 'feeling a drug effect' and both stimulant-like and LSD-like effects, but the drug did not improve mood or affect performance on psychomotor or most emotional tasks. No residual effects were detected on mood or task performance on the drugfree follow-up session. We conclude that within the context of a controlled setting and a limited number of administrations, repeated low doses of LSD are safe, but produce negligible changes in mood or cognition in healthy volunteers.
Rational Smoking typically begins during adolescence or early adulthood in a social context, yet the role of social context in animal models is poorly understood. Objectives The present study examined the effect of social context on acquisition of nicotine self-administration. Methods Sixty day-old male and female Sprague-Dawley rats were trained to press a lever for nicotine (0.015 mg/kg, IV) or saline infusions (males only) on a fixed-ratio (FR1) schedule of reinforcement across 9 sessions in duplex chambers that were conjoined with either a solid wall or a wall containing wire mesh creating a social context between rat dyads (social visual, auditory, and olfactory cues). In a subsequent experiment, sex differences and dose-dependent effects of nicotine [0 (saline), 0.015 or 0.03 mg/kg, IV] were directly compared in rats trained in the isolated or social context on a schedule progressing from FR1 to FR3. These rats were given 20 sessions followed by 3 extinction sessions. Results We consistently found transient social facilitation of low dose nicotine self-administration in males during the first session. However, across training overall we found social suppression of nicotine intake that was most prominent in females during later sessions. Conclusions Collectively, these findings suggest that at the age of transition from adolescence to adulthood, a social context enhances the initial reinforcing effects of nicotine in males, but protects against nicotine intake during later sessions especially in females. These findings highlight the importance of sex and social context in studying neural mechanisms involved in initiation of nicotine use.
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 two 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 vs. 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 this system may be sensitive to 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.
Social isolation, such as that experienced during the pandemic, is associated with reduced feelings of connectedness with others. Researchers have developed simple conversational procedures to enhance feelings of connectedness, even between strangers. In the present controlled study, we used such a procedure to demonstrate that participants report greater feelings of closeness to another individual after a 45-min conversation about “deep” compared to “shallow” topics. Healthy young adults (N=37) were paired with a same-sex stranger on two sessions separated by at least 2 days. In one session, they were given “deep talk” topics to discuss, and in the other session, the topics were “small talk.” At the end of each session and again 1 week later, participants rated their partners and their experiences, including how much they liked their partners, their feelings of closeness, and feeling understood. Participants reported liking their deep talk partner more than their small talk partner. They described the deep conversation as being more meaningful and reported feeling closer to their deep talk partner. These effects were evident immediately after the session and remained robust a week later. This study shows that the conversational procedure can be used to assess the two conversations within the same subjects, and that the effects are lasting. Future studies, in both therapeutic and laboratory settings, may shed light on the processes that mediate these feelings of connection.
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