scholarly journals Evaluation of the reinforcing and subjective effects of heroin in combination with dextromethorphan and quinidine

2017 ◽  
Vol 7 (6) ◽  
pp. 451-461 ◽  
Author(s):  
Suzanne K. Vosburg, PhD ◽  
Maria A. Sullivan, MD, PhD ◽  
Sandra D. Comer, PhD
Keyword(s):  
Maintenance Dose ◽  
Opioid Dependence ◽  
Subjective Effects ◽  
Random Order ◽  
Progressive Ratio ◽  
Subjective Ratings ◽  
Limited Role ◽  
Dose Condition ◽  
Double Blinded ◽  
Modest Reduction

Objective: Studies have suggested that the N-methyl-D-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence.Design: This double-blinded, placebo-controlled inpatient study evaluated the effects of 0, 30, and 60 mg of dextromethorphan and quinidine (DMQ) on the reinforcing and subjective effects of heroin in recently detoxified heroin abusers.Participants: Nine heroin-dependent participants were admitted and then detoxified from heroin over the course of several days.Interventions: Participants were subsequently stabilized on 0, 30, or 60 mg of DMQ. Each dose of DMQ was administered for two consecutive weeks, and the effects of heroin (0, 12.5, and 50 mg) were studied under each DMQ maintenance dose condition. DMQ and heroin dose were administered in random order both within and between participants.Results: Planned comparisons revealed statistically significant increases in progressive ratio breakpoint values and positive subjective ratings as a function of heroin dose. There were no consistent changes in any of the responses as a function of DMQ maintenance dose, other than a modest reduction in craving.Conclusions: In summary, results from this study suggest that maintenance on dextromethorphan in combination with quinidine has a limited role in the treatment of opioid dependence.

scholarly journals Impact of Morphine Dependence and Withdrawal on the Reinforcing Effectiveness of Fentanyl, Cocaine, and Methamphetamine in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Robert W. Seaman Jr ◽  
Gregory T. Collins
Keyword(s):  
Opioid Dependence ◽  
Progressive Ratio ◽  
Morphine Dependence ◽  
Sprague Dawley ◽  
Self Administration ◽  
Stimulant Use ◽  
Concurrent Use ◽  
Reinforcing Effects ◽  
The Individual ◽  
The Impact

Recent estimates suggest increased popularity of the concurrent use of opioids and stimulants, with over 50% of treatment-seeking opioid users reporting regular stimulant use. The goal of the current study was to determine how opioid dependence and withdrawal affect the reinforcing effects of fentanyl, cocaine, and methamphetamine. Male Sprague-Dawley rats were allowed to self-administer fentanyl under a progressive ratio (PR) schedule of reinforcement. Baseline evaluations of reinforcing effectiveness of fentanyl, cocaine, and methamphetamine were determined. Opioid dependence was then established by administering escalating doses of morphine (10–40 mg/kg) twice-daily for four days and subsequently maintained by once-daily injections of 40 mg/kg morphine. To evaluate the impact of opioid dependence and withdrawal on the self-administration of fentanyl, cocaine, and methamphetamine, sessions occurred either 12 or 20 h after the morphine, respectively. During opioid withdrawal, the fentanyl dose-response curve was shifted rightward with an increase in maximal effectiveness, whereas it was shifted rightward with a reduction in maximal effectiveness when evaluated in rats currently dependent on opioids, relative to baseline. The reinforcing effects of cocaine and methamphetamine were unchanged by either condition. The current studies provide direct evidence that the reinforcing effects of fentanyl are increased in opioid-withdrawn rats and reduced in opioid-dependent rats, relative to rats that are not physically dependent on opioids. These findings suggest that motivations to use opioids are dependent on the state of the individual whereas stimulants retain their reinforcing effects regardless of whether the individual is in an opioid-dependent or withdrawn state.

Behavioral and Physiological Effects of Remifentanil and Alfentanil in Healthy Volunteers 

1999 ◽  
Vol 90 (3) ◽  
pp. 718-726 ◽  
Author(s):  
Matthew L. Black ◽  
Joanna L. Hill ◽  
James P. Zacny
Keyword(s):  
Healthy Volunteers ◽  
Dose Range ◽  
Subjective Effects ◽  
Cold Pressor Test ◽  
Drug Effects ◽  
Cold Pressor ◽  
Psychomotor Tests ◽  
Potency Ratio ◽  
Psychomotor Effects ◽  
Double Blinded

Background The subjective and psychomotor effects of remifentanil have not been evaluated. Accordingly, the authors used mood inventories and psychomotor tests to characterize the effects of remifentanil in healthy, non-drug-abusing volunteers. Alfentanil was used as a comparator drug. Methods Ten healthy volunteers were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial in which they received an infusion of saline, remifentanil, or alfentanil for 120 min. The age- and weight-adjusted infusions (determined with STANPUMP, a computer modeling software package) were given to achieve three predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests were completed, and miosis was assessed, during and after the infusions. In addition, analgesia was tested at each dose level using a cold-pressor test. Results Remifentanil had prototypic micro-like opioid subjective effects, impaired psychomotor performance, and produced analgesia. Alfentanil at the dose range tested had more mild effects on these measures, and the analgesia data indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may exist between remifentanil and alfentanil. A psychomotor test administered 60 min after the remifentanil infusion was discontinued showed that the volunteers were still impaired, although they reported feeling no drug effects. Conclusions The notion that the pharmacodynamic effects of remifentanil are extremely short-lived after the drug is no longer administered must be questioned given our findings that psychomotor effects were still apparent 1 h after the infusion was discontinued.

scholarly journals Acute effects of inhaled menthol on the rewarding effects of intravenous nicotine in smokers

2018 ◽  
Vol 32 (9) ◽  
pp. 986-994 ◽  
Author(s):  
Gerald W Valentine ◽  
Elise E DeVito ◽  
Peter I Jatlow ◽  
Ralitza Gueorguieva ◽  
Mehmet Sofuoglu
Keyword(s):  
Random Sequence ◽  
Subjective Effects ◽  
Random Order ◽  
Test Session ◽  
Controlled Study ◽  
Nicotine Metabolism ◽  
Double Blind ◽  
Subjective Responses ◽  
Intravenous Nicotine ◽  
Nicotine Deprivation

Objective: This double-blind, placebo controlled study examined whether menthol inhaled from an electronic cigarette (e-cigarette) would change subjective and withdrawal alleviating effects of intravenous nicotine in young adult smokers. Methods: A total of 32 menthol-preferring smokers and 25 non-menthol-preferring smokers participated in the study that consisted of a random sequence of three different inhaled menthol conditions (0.0%, 0.5%, and 3.2%) across three test sessions (a single menthol condition per session). In each test session (performed at least 24 hours apart), a random order of saline, and two different nicotine infusions of 0.25 mg and 0.5 mg/70 kg of bodyweight were administered, one hour apart, concurrent with menthol inhalation. Results: While menthol did not alter the positive subjective effects of nicotine, menthol significantly enhanced aversive effects of nicotine in non-menthol-preferring smokers and reduced smoking urges in menthol-preferring smokers. In addition, menthol-preferring smokers reported blunted positive subjective responses to nicotine and less severe nicotine withdrawal after overnight nicotine deprivation. Finally, compared to non-menthol-preferring smokers, menthol-preferring smokers had a significantly lower baseline nicotine metabolite ratio indicating slower nicotine metabolism within our sample of menthol-preferring smokers. Conclusions: Our findings did not support an enhancement of nicotine’s positive subjective effects from inhaled menthol. However, as compared to non-menthol-preferring smokers, menthol-preferring smokers had blunted positive subjective responses to nicotine and reduced overnight withdrawal severity that may be partly due to inhibition of nicotine metabolism from chronic exposure to inhaled menthol. Collectively, these results reveal a more complex and nuanced role of inhaled menthol in smokers than previously recognized.

Mephedrone and 3,4-methylenedioxy-methamphetamine: Comparative psychobiological effects as reported by recreational polydrug users

2016 ◽  
Vol 30 (12) ◽  
pp. 1313-1320 ◽  
Author(s):  
Lewis Jones ◽  
Phil Reed ◽  
Andrew Parrott
Keyword(s):  
Social Network ◽  
Subjective Effects ◽  
Recovery Period ◽  
Social Network Sites ◽  
Acute Effects ◽  
Subjective Ratings ◽  
Average Amount ◽  
Online Questionnaire ◽  
Nasal Irritation

Aims: The purpose of this study was to compare the effects of mephedrone and 3,4-methylenedioxy-methamphetamine (MDMA), as reported by young recreational polydrug users. Methods: 152 MDMA users and 81 mephedrone users were recruited through snowballing on social network sites. They completed a standard online questionnaire for either mephedrone or MDMA. The questions covered the average amount taken per session, the longest duration of usage in the last 12-months, subjective effects while on-drug, and recovery effects in the days afterwards. Results: Mephedrone users reported a significantly longer maximum session of use than MDMA users. Mephedrone users also reported a significantly greater average amount used per session. The majority of on-drug subjective ratings did not differ between drugs, with similar increases in entactogenic effects. Although mephedrone users did report significantly more frequent issues with sleeping, anger and anxiety. In relation to recovery, mephedrone users reported more frequent craving, nasal irritation, paranoia, and relationship difficulties. Mephedrone users also rated general recovery effects as more severe over the seven-day period following use, taking more days to feel normal. Conclusions: The acute effects of MDMA and mephedrone were broadly similar. However, the recovery period for mephedrone was more enduring, possibly due to the longer duration of acute session usage.

scholarly journals Assessment of fatigue in personnel during sustained operations using ‘SOAP’ – Sustained Operational Assessment Profile

2020 ◽  
Vol 64 ◽  
pp. 2-7
Author(s):  
MS Butola ◽  
YS Dahiya ◽  
BK Rao
Keyword(s):  
Shift Work ◽  
Air Force ◽  
Repeated Measures ◽  
Administrative Support ◽  
Subjective Effects ◽  
Significant Risk ◽  
Sleep Cycle ◽  
Second Phase ◽  
Subjective Ratings ◽  
Sustained Operation

Introduction: Sustained operations are the future of any advanced Air Force, which involve round the clock flying operations over a prolonged period. Such operations have the potential of disrupting normal sleep cycle and may cause fatigue among aircrew and ground duty personnel. It is well known that fatigue among crew member is a significant risk to aerospace safety. The present study was hence undertaken to quantify the subjective fatigue and its effects, among the personnel involved in a simulated exercise using Sustained Operations Assessment Profile (SOAP). Material and Methods: SOAP questionnaire, a validated tool, was used for data collection. In the first phase, 1521 personnel involved in the exercise, including aircrew as well as ground duty tradesmen completed the SOAP questionnaires twice during the simulated sustained military operation. The subjective ratings were statistically analyzed using the Wilcoxon matched paired test. The two levels of repeated measures being mean SOAP scores on day 2 and that on day 5. In the second phase, to ascertain differences in the subjective ratings of SOAP among different streams of pilots, data were recorded during another simulated sustained operation after 6 months. A total of 140 aircrew responded to the SOAP questionnaire during 6 days of sustained operations. SOAP score was acquired on day 1 and day 6 of the operations in the second phase. Results: A total of 3042 completed SOAP responses were analyzed. There was a significant increase in ratings of the three cardinal dimensions of SOAP among all personnel. The aircrew rated the subjective effects higher than maintenance or administrative support group. Among the aircrew, the fighter pilots rated significantly higher as compared to transport or helicopter aircrew. Conclusion: The study revealed significant changes in the cardinal dimensions of SOAP among the aircrew who were routinely not involved in shift work (especially fighter pilots). Scientifically designed “shift work” may be an effective strategy to mitigate effects of fatigue during sustained operations, hence, needs to be practiced as a routine by combat Air Force units.

scholarly journals A Novel Prebiotic Supplement Increases Bifidobacteria Abundance in Participants Consuming Low-Fiber Diets

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1163-1163
Author(s):  
Jea Woo Kang ◽  
Xinyu Tang ◽  
Angela Zivkovic
Keyword(s):  
Relative Abundance ◽  
Lactate Production ◽  
Random Order ◽  
Daily Basis ◽  
Metagenomic Sequencing ◽  
Funding Sources ◽  
Diet Records ◽  
Stool Samples ◽  
Double Blinded ◽  
Usual Diet

Abstract Objectives The objective of this study was to determine whether a novel fiber supplement consumed by healthy individuals with a habitual diet low in fiber (<15 g/day) increases the proportion of saccharolytic gut microbiota which is associated with the increase in the production of SCFA and their related genes in stool without changing their usual diet. Methods Twenty individuals were enrolled in this double-blinded, randomized order, placebo-controlled, cross-over study. Participants were young, healthy, normal to overweight (BMI 23.0–32.0) and consumed < 15 g/day of fiber. All participants consumed a fiber and placebo supplement for a period of 4 weeks each, with a 4-week washout between intervention arms in random order. Participants recorded their diet for 3 days using 24-hour diet record at each 2-week segment. The diet was patternized each week (i.e., participants were asked to consume the same meals and foods for the 3 days prior to each test day) without significantly changing the participants’ usual diet. The fiber packets contained 12 g/serving per day as a powder containing resistant starch, fructooligosaccharide, sugarcane fiber, and inulin while the placebo packets contained 12 g/serving per day of a powder that matched the fiber supplement in taste and appearance. The powder packet was mixed with water for consumption. Stool samples were collected every 2 weeks throughout the study, and metagenomic sequencing and SCFA analysis was performed. Results The concentration of SCFA measured in the stool sample did not change after the intervention. However, the relative abundance of one of the well known saccharolytic bacteria, Bifidobacterium, increased after the fiber supplementation. Genes related to acetate and lactate production, poxB (P = 0.04) and ldh (P = 0.07) respectively, showed tendency to increase which aligns with the increase in the relative abundance of Bifidobacterium in stool samples. No significant changes and correlations were found with anthropometrics and diet records. Conclusions A small amount of fiber supplemented on a daily basis to individuals consuming low fiber diets resulted in an increase in the relative abundance of the beneficial gut microbial genus, Bifidobacterium. Funding Sources I would like to acknowledge Usana Health Sciences, Inc. for the support in this research.

Abstract 19: Single-Dose Extended-Release Niacin Acutely Attenuates HDL Reduction in the Setting of Experimental Oral Fat Challenge: A Possible Role of ANGPTL-3 and CETP Modulation

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
M Haris U Usman ◽  
Kazuhiro Nakaya ◽  
Arman Qamar ◽  
Prabhjot Nijjar ◽  
Ramprasad Gadi ◽  
...  
Keyword(s):  
Single Dose ◽  
Area Under The Curve ◽  
Density Lipoprotein ◽  
Study Drug ◽  
Random Order ◽  
Open Label ◽  
Transfer Protein ◽  
Drug Naïve ◽  
Double Blinded ◽  
Oral Fat Load

Background: High density lipoprotein (HDL-c) levels are inversely correlated with the development of atherosclerosis and are reduced postprandially. Niacin is the most potent elevator of fasting HDL-c but the mechanisms are not fully elucidated, and its effects on postprandial HDL-c are largely unknown. Aim: Our aim was to determine whether a single dose ER niacin before a fat challenge acutely attenuates the postprandial drop in HDL-c compared to placebo, and to determine whether angiopoeitin like protein 3 (ANGPTL3) and cholesterol ester transfer protein (CETP) contribute to increased postprandial HDL-c by niacin. Method: We conducted 2 postprandial studies in healthy volunteers: 1. a double-blinded, placebo-controlled, random-order crossover experiment comparing 2 grams of ER niacin to matching placebo, and 2. open-label administration of 1 gram of ER niacin compared to a fat load without niacin. Study drug was administered 1 hour prior to an oral fat load of heavy cream followed by serial plasma sampling for triglyceride (TG), apolipoprotein A-1 (Apo A-1), ANGPTL3, and CETP mass and activity, and HDL-c over 12 hours. Data are expressed as means (95% CI) for incremental (iAUC) or total (tAUC) area under the curve. Results: Study 1 involved 304 fat challenges in 152 subjects. As expected HDL-c dropped after the fat load alone, with an iAUC of -71.9 mg/dL*h (-65.1 to -78.6),whereas 1 gram ER niacin reduced the drop to -32.5 mg/dL*h (-25.6 to -39.3) a 55% difference (p<0.00001). In Study 2, 2 grams ER-Niacin mitigated the drop in HDLc more effectively: the iAUC was -19.0 (-35.7 to -2.3) on placebo vs. -2.1 (-18.8 to +14.6) mg/dL*h on niacin, an 89% difference ( p=0.047). ANGPTL3 iAUC was +2206 ng/mL*h (+1811 to +2602) on placebo vs. +2560 ng/mL*h (+2165 to +2955) on ER-niacin, a 16% rise (p=0.001). CETP activity decreased from an iAUC of +118.2 nmol/L*h (95%CI +90.5 to +146) to -15.7 nmol/L*h (95%CI -36.4 to +5.1) on niacin, so that the usual postprandial increase in CETP activity was abolished by niacin (p<0.00001). Postprandial TG tAUC was strongly inversely correlated with HDL tAUC (Spearman’s rho -0.62, p<0.00005). Conclusions: HDL-c decreases significantly in the setting of an experimental oral fat load. We found that one-time dosing with either 1 or 2 grams of ER-Niacin mitigated this decline in drug-naive subjects. Acute pharmacodynamic effects of ER-niacin including TG lowering, ANGPTL3 elevation and CETP suppression may play a mechanistic role in this process.

scholarly journals Acu-TENS Reduces Breathlessness during Exercise in People with Chronic Obstructive Pulmonary Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Shirley P. C. Ngai ◽  
Lissa M. Spencer ◽  
Alice Y. M. Jones ◽  
Jennifer A. Alison
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Transcutaneous Electrical Nerve Stimulation ◽  
Random Order ◽  
Group Differences ◽  
Chronic Obstructive ◽  
Exertional Dyspnoea ◽  
Obstructive Pulmonary Disease ◽  
Electrical Nerve Stimulation ◽  
Double Blinded

Background. Exertional dyspnoea limits level of physical activity in people with Chronic Obstructive Pulmonary Disease (COPD). This randomized, double-blinded, crossover study evaluated the effect of Acu-TENS, application of Transcutaneous Electrical Nerve Stimulation on acupoints, on breathlessness during exercise in people with COPD. Methods. Twenty-one participants, mean% predicted FEV1  50±21%, attended assessment followed by two intervention days, one week apart. On each intervention day, participants performed two endurance shuttle walk tests (ESWT) (Walk 1 and Walk 2). Walk 1 was performed without intervention and Walk 2 was performed with either Acu-TENS or Sham-TENS, in random order, for 45 minutes before and during Walk 2. Duration of each ESWT and dyspnoea score at isotime of Walk 1 and Walk 2 on each intervention day were compared. Between-group differences in ESWT duration and isotime dyspnoea were also compared. Results. At isotime of Walk 1 and Walk 2, Acu-TENS showed significant reduction in dyspnoea of −0.8 point (95% CI −0.2 to −1.4) but not in Sham-TENS [0.1 point (95% CI −0.4 to 0.6)]. Compared to Sham-TENS, Acu-TENS showed significant reduction in dyspnoea of −0.9 point (95% CI −0.2 to −1.6) while no between-group significance was found in ESWT duration. Conclusion. Acu-TENS alleviated dyspnoea during walking in people with COPD but did not increase walking duration.

scholarly journals Influence of Cannabinoid Receptor 1 Genetic Variants on the Subjective Effects of Smoked Cannabis

2021 ◽  
Vol 22 (14) ◽  
pp. 7388
Author(s):  
Thomas Murphy ◽  
Justin Matheson ◽  
Robert E. Mann ◽  
Bruna Brands ◽  
Christine M. Wickens ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Subjective Effects ◽  
Area Under The Curve ◽  
Controlled Clinical Trial ◽  
Cannabinoid Receptor 1 ◽  
Maximum Value ◽  
Global Trend ◽  
The World ◽  
Double Blinded ◽  
The Impact

As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need to explore the possible genetic differences underlying the subjective effects of cannabis. This pilot study investigated specific genetic variations within the cannabinoid receptor 1 (CNR1) gene for association with the subjective effects of smoked cannabis. Data were obtained from a double-blinded, placebo-controlled clinical trial studying the impact of cannabis intoxication on driving performance. Participants randomized to the active cannabis group who consented to secondary genetic analysis (n = 52) were genotyped at the CNR1 rs1049353 and rs2023239 polymorphic areas. Maximum value and area under the curve (AUC) analyses were performed on subjective measures data. Analysis of subjective effects by genotype uncovered a global trend towards greater subjective effects for rs1049353 T-allele- and rs2023239 C-allele-carrying subjects. However, significant differences attributed to allelic identity were only documented for a subset of subjective effects. Our findings suggest that rs1049353 and rs2023239 minor allele carriers experience augmented subjective effects during acute cannabis intoxication.

scholarly journals Potential Moderating Effects of Sex/Gender on the Acute Relative Reinforcing and Subjective Effects of Reduced Nicotine Content Cigarettes in Vulnerable Populations

2019 ◽  
Vol 22 (6) ◽  
pp. 878-884
Author(s):  
Joanna M Streck ◽  
Danielle R Davis ◽  
Raina D Pang ◽  
Stacey C Sigmon ◽  
Janice Y Bunn ◽  
...  
Keyword(s):  
Sex Differences ◽  
Vulnerable Populations ◽  
Subjective Effects ◽  
Secondary Analysis ◽  
Nicotine Content ◽  
Smoking Addiction ◽  
Psychiatric Conditions ◽  
Reinforcing Effects ◽  
Double Blinded ◽  
Gender Interactions

Abstract Introduction Reports in relatively healthy smokers suggest men are more sensitive than women to the subjective effects of reduced nicotine content cigarettes (RNCCs). We know of no reports examining sex differences in the relative reinforcing effects of RNCCs, an important outcome in assessing smoking’s addiction potential. The aim of the present study is to address this gap by examining sex/gender differences on reinforcing effects while examining whether sex differences in subjective effects are discernible in vulnerable populations. Methods Secondary analysis of a within-subject, double-blinded experiment examining acute effects of cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among 169 adult smokers with psychiatric conditions or socioeconomic disadvantage. Effects of dose, sex, and their interaction were examined on reinforcing (concurrent-choice and Cigarette Purchase Task [CPT] testing), and subjective effects (Cigarette Evaluation Questionnaire [CEQ] and craving/withdrawal ratings). Results Reducing nicotine content decreased the relative reinforcing effects of smoking in concurrent-choice and CPT testing (p’s &lt; .05) with no significant effects of sex nor dose × sex/gender interactions. Reducing nicotine content decreased CEQ ratings with only a single significant effect of sex (higher Psychological Reward scores among women than men, p = .02) and no significant dose × sex/gender interactions. Results on craving/withdrawal paralleled those on the CEQ. Conclusions Reducing nicotine content decreases the addiction potential of smoking independent of sex in populations highly vulnerable to smoking and addiction, with no indication that women are less sensitive to subjective effects of RNCCs or would benefit less from a policy reducing the nicotine content of cigarettes. Implications A policy reducing the nicotine content of cigarettes has the potential to reduce the addiction potential of smoking across men and women who are especially vulnerable to smoking, addiction, and tobacco-related adverse health impacts.

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