A Pilot Study of Loss Aversion for Drug and Non-Drug Commodities in Cocaine Users

Background—Numerous studies in behavioral economics have demonstrated that individuals are more sensitive to the prospect of a loss than a gain (i.e., loss aversion). Although loss aversion has been well described in “healthy” populations, little research exists in individuals with substance use disorders. This gap is notable considering the prominent role that choice and decision-making play in drug use. The purpose of this pilot study was to evaluate loss aversion in active cocaine users. Methods—Current cocaine users (N = 38; 42% female) participated in this within-subjects laboratory pilot study. Subjects completed a battery of tasks designed to assess loss aversion for drug and non-drug commodities under varying risk conditions. Standardized loss aversion coefficients (λ) were compared to theoretically and empirically relevant normative values (i.e., λ = 2). Results—Compared to normative loss aversion coefficient values, a precise and consistent decrease in loss aversion was observed in cocaine users (sample λ ≈ 1). These values were observed across drug and non-drug commodities as well as under certain and risky conditions. Conclusions—These data represent the first systematic study of loss aversion in cocaine-using populations and provide evidence for equal sensitivity to losses and gains or loss equivalence. Futures studies should evaluate the specificity of these effects to a history of cocaine use as well as the impact of manipulations of loss aversion on drug use to determine how this phenomenon may contribute to intervention development efforts

Buspirone Maintenance Does Not Alter the Reinforcing, Subjective, and Cardiovascular Effects of Intranasal Methamphetamine

Background—Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact of buspirone maintenance on the subjective and cardiovascular response to methamphetamine was also determined. Methods—Eight research participants (1 female) reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind protocol in which the pharmacodynamic effects of intranasal methamphetamine (0, 15, and 30 mg) were assessed after at least 6 days of buspirone (0 and 45 mg/day) maintenance. Results—Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like subjective (e.g., increased ratings of Good Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure) effects. These effects of methamphetamine were similar under buspirone and placebo maintenance conditions. Maintenance on buspirone was well tolerated and devoid of effects when administered alone. Conclusions—These data suggest that buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use disorder. Given the central role of monoamines in methamphetamine-use disorder, it is reasonable for future studies to continue to target these systems

A Pilot Investigation of Acute Inhibitory Control Training in Cocaine Users

Background—Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals. Methods—Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using the stop-signal task and visual-probe task with eye tracking, respectively. Results—Training condition groups did not differ on demographics, inhibitory control training performance, response inhibition, or cocaine-cue attentional bias. Response inhibition performance improved as a function of inhibitory control training in both conditions. Cocaine-cue attentional bias was observed, but did not change as a function of inhibitory control training in either condition. Conclusions—Response inhibition in cocaine-using individuals was augmented by acute inhibitory control training, which may improve treatment outcomes through better behavioral inhibition. Future studies should investigate longer-term implementation of inhibitory control training, as well as combining inhibitory control training with other treatment modalities

CMB Anisotropy of Spherical Spaces

The first-year WMAP data taken at their face value hint that the Universe might be slightly positively curved and therefore necessarily finite, since all spherical (Clifford-Klein) space forms M^3 = S^3/Gamma, given by the quotient of S^3 by a group Gamma of covering transformations, possess this property. We examine the anisotropy of the cosmic microwave background (CMB) for all typical groups Gamma corresponding to homogeneous universes. The CMB angular power spectrum and the temperature correlation function are computed for the homogeneous spaces as a function of the total energy density parameter Omega_tot in the large range [1.01, 1.20] and are compared with the WMAP data. We find that out of the infinitely many homogeneous spaces only the three corresponding to the binary dihedral group T*, the binary octahedral group O*, and the binary icosahedral group I* are in agreement with the WMAP observations. Furthermore, if Omega_tot is restricted to the interval [1.00, 1.04], the space described by T* is excluded since it requires a value of Omega_tot which is probably too large being in the range [1.06, 1.07]. We thus conclude that there remain only the two homogeneous spherical spaces S^3/O* and S^3/I* with Omega_tot of about 1.038 and 1.018, respectively, as possible topologies for our Universe.Comment: A version with high resolution sky maps can be obtained at http://www.physik.uni-ulm.de/theo/qc

Assessment of aerosol deposition and movement in open field conditions

Overall objective of this study was to evaluate the dispersion of aerosol plumes generated by a truck-mounted ultra low-volume (ULV) applicator and a hand-held thermal fogger under open field conditions.  Experiments were also planned to determine the relative capture efficiencies of various sampling techniques in such applications.  The ULV applicator was used at three travel speeds (8.5, 16.8, 24.8 km/h) and the thermal fogger at two release heights (0.6 and 1.1 m above ground) to investigate the effect of speed or release height on deposition at 6, 12, 24, and 48 m downwind.  High volume air sampler (HVS), low volume air samplers (LVS), spinning cotton ribbon (CR) samplers, polypropylene green plastic cards (GC), acetate cards (AC), and water-sensitive papers (WSP) were used to collect deposits.  The ULV applicator was tested with water and oil sprays while the thermal fogger was tested with the latter tracer only.  Using water- and oil-based tracers, all deposition targets were analyzed by fluorometry.  Results showed decreased tracer deposition with increase in sampling distance.  Overall, travel speed affected deposition at the near sample locations only, but in most sample locations, normalized deposits were comparable at all speeds.  Spray release height did not affect deposition of active samplers but had significant effect on deposition of passive samplers at 6 m location only.  Overall, the higher release height resulted in more deposition in most downwind locations.  There were good correlations between depositions on active and passive samplers. The HVS, CR, GC, and AC samplers were effective in sampling aerosol plume dispersion under open field conditions.  The paper includes relationships among capture efficiencies of various samplers.Keywords: ULV applicator, thermal fogger, deposition samplers, Yellow 131SC dye, Pyranine 10G, fluorometr

N-Acetylcysteine Reduces Cocaine-Cue Attentional Bias and Differentially Alters Cocaine Self-Administration Based on Dosing Order

Background—Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. Methods—The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400 mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60 mg). Fourteen individuals (N = 14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Results—Cocaine-cue attentional bias was greatest following administration of 0 mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. Conclusions—These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues

Influence of Pregabalin Maintenance on Cannabis Effects and Related Behaviors in Daily Cannabis Users

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a next-generation VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; EXP 2) mg/day pregabalin in cannabis users who were not seeking treatment or trying to reduce/quit their cannabis use. The protocol consisted of two outpatient maintenance phases (11 days in EXP 1 and 15 days in EXP 2) that concluded with four experimental sessions within each phase. During experimental sessions, maintenance continued, and participants completed two 2-day blocks of sampling and self-administration sessions to determine the reinforcing effects of smoked cannabis (0% and 5.9% delta⁹-tetrahydrocannabinol [THC]), as well as subjective, attentional bias, performance, and physiological responses. In addition, naturalistic cannabis use, side effects, sleep quality, craving, and other self-reported substance use were measured during pregabalin maintenance. Cannabis was self-administered and produced prototypical effects, but pregabalin generally did not impact the effects of cannabis or alter naturalistic use. These human laboratory results in cannabis users not trying to reduce/quit their use do not support the efficacy of pregabalin as a stand-alone pharmacotherapy for CUD

Naltrexone-Bupropion Combinations Do Not Affect Cocaine Self-Administration in Humans

The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 mg) was then determined using a modified progressive ratio and relapse procedure. Subjective and cardiovascular effects were also measured. Cocaine produced prototypical dose-related increases in self-administration, subjective outcomes (e.g., Like Drug ), and cardiovascular indices (e.g., heart rate, blood pressure) during placebo maintenance. Naltrexone and bupropion alone, or in combination, did not significantly decrease self-administration on either procedure. Low doses of bupropion (i.e., 100 mg) blunted the effects of the cocaine on subjective measures of Like Drug and Stimulated . No unexpected adverse effects were observed with naltrexone and bupropion, alone and combined, in conjunction with cocaine. Together, these results do not support the use of these bupropion-naltrexone combinations for the treatment of cocaine use disorder. Future research should determine if novel drug combinations may decrease cocaine self-administration