Self-reported Drug Effects Research Articles

Dose of Product or Product Concentration: A Comparison of Change in Heart Rate by THC Concentration for Participants Using Cannabis Daily and Occasionally.

Introduction: Studies show that acute cannabis use significantly increases heart rate (HR) and mildly raises blood pressure in the minutes following smoked or inhaled use of cannabis. However, less is known about how the THC concentration of the product or an individual's frequency of use (i.e., tolerance) may affect the magnitude of the change in HR. It is also relatively unexamined how the physical effects of increased HR after acute cannabis use relate to self-reported drug effects or blood THC levels. Aims: To describe the relationship between THC concentration of product used, self-reported subjective intoxication, THC blood levels, and frequency of cannabis use with the change in HR after acute cannabis use. Materials and Methods: Participants (n = 140) were given 15 min to smoke self-supplied cannabis ad libitum, HR was measured at baseline and an average of 2 min post-cannabis smoking. The ARCI-Marijuana scale and Visual Analog Scales (VAS) were administered, and blood samples were taken at both time points. Participants were asked about their frequency of use. Information about the product used was recorded from the package. Linear regression was used to analyze the relationship between changes in HR (post-pre cannabis use) and post-cannabis use HR, blood THC concentration, THC product concentration, frequency of use, and self-reported drug effect. Results: There was a significantly higher HR among those who smoked cannabis compared to the controls (p < 0.001), which did not significantly differ by frequency of use (p = 0.18). Higher concentration THC (extract) products did not produce a significantly different HR than lower concentration (flower) products (p = 0.096). VAS score was associated with an increase in HR (p < 0.05). Overall, blood THC levels were not significantly related to the change in HR (p = 0.69); however, when probed, there was a slight positive association among the occasional use group only. Discussion: Cardiovascular effects of cannabis consumption may not be as subject to tolerance with daily cannabis use and do not directly increase with THC concentration of the product. This is a departure from other effects (i.e., cognitive, subjective drug effects) where tolerance is well established. These findings also suggest that, at least among those with daily use, higher concentration THC products (>60%) do not necessarily produce cardiovascular physiological effects that are significantly more robust than lower concentration (<20%) products.

A dose-ranging study of the physiological and self-reported effects of repeated, rapid infusion of remifentanil in people with opioid use disorder and physical dependence on fentanyl.

Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans. This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence. An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40min per dose, with infusions administered over 5s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5min. Pupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose. This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.

A crowdsourcing survey study on the subjective effects of delta-8-tetrahydrocannabinol relative to delta-9-tetrahydrocannabinol and cannabidiol.

Delta-8-tetrahydrocannabinol (Δ8-THC) has emerged as a new retail cannabinoid product in the U.S. This study queried Δ8-THC users about product use characteristics and self-reported drug effects. Participants were recruited via a large online crowdsourcing platform (Amazon Mechanical Turk). Adults (N = 252) with past year Δ8-THC use (35% with at least weekly use) completed surveys and open-ended questions related to their reasons for using and past experiences with Δ8-THC-containing retail products. Participants with past year use of Δ9-tetrahydrocannabinol (Δ9-THC) and/or cannabidiol (CBD; 81% and 63%) compared the effects of Δ8-THC to those of Δ9-THC and/or CBD by rating drug effects on a visual analog scale from -50 to + 50 where negative scores indicated Δ8-THC effects are weaker, positive scores indicated Δ8-THC effects are stronger, and a score of 0 indicated equal effects to Δ9-THC or CBD. Compared to Δ9-THC, self-reported ratings for "Drug effect," "Bad effect," "Sick," "Anxiety," "Paranoia," "Irritability," "Restlessness," "Memory Problems," and "Trouble Performing Routine Tasks" were lower for Δ8-THC (d = -0.21 to -0.44). Compared to CBD, ratings for Δ8-THC effects were higher for "Drug effect," "Good effect," "High," "Relaxed," "Sleepy," "Hunger/Have the Munchies," "Memory Problems," "Trouble Performing Routine Tasks," and "Paranoia" (d = 0.27-1.02). Qualitative responses indicated that participants used Δ8-THC because it is perceived as (a) legal, (b) a substitute or similar to Δ9-THC, and/or (c) less intense than Δ9-THC. Δ8-THC is an understudied psychoactive component of cannabis that shares more characteristics with Δ9-THC than CBD and should be characterized further with human laboratory studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Association between ABCB1 rs2235048 Polymorphism and THC Pharmacokinetics and Subjective Effects following Smoked Cannabis in Young Adults

Genetic influences on acute responses to psychoactive drugs may contribute to individual variability in addiction risk. ABCB1 is a human gene that encodes P-glycoprotein, an ATP-dependent efflux pump that may influence the pharmacokinetics of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. Using data from 48 young adults (aged 19–25 years) reporting 1–4 days of cannabis use per week who completed a placebo-controlled human laboratory experiment, we tested the hypothesis that the rs2235048 polymorphism of ABCB1 would influence acute responses to smoked cannabis. C-allele carriers reported on average greater frequency of weekly cannabis use compared to the TT genotype carriers (TC/CC mean ± SEM = 2.74 ± 0.14, TT = 1.85 ± 0.24, p = 0.004). After smoking a single cannabis cigarette to their desired high, C-allele carriers had higher area-under-the-curve (AUC) of both THC metabolites (11-OH-THC TC/CC = 7.18 ± 9.64, TT = 3.28 ± 3.40, p = 0.05; THC-COOH TC/CC = 95.21 ± 116.12, TT = 45.92 ± 42.38, p = 0.043), and these results were impact by self-reported ethnicity. There were no significant differences in self-reported subjective drug effects except for a greater AUC of visual analogue scale rating of drug liking (TC/CC = 35,398.33 ± 37,233.72, TT = 15,895.56 ± 13,200.68, p = 0.017). Our preliminary findings suggest that further work in a larger sample should investigate whether human ABCB1 influences cannabis-related phenotypes and plays a role in the risk of developing a cannabis use disorder.

Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction - a prospective observational study.

The β-1 adrenergic receptor blocker metoprolol is primarily metabolized by the polymorphic enzyme cytochrome P 450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Our purpose was to investigate the impact of CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction (MI). We included 136 patients with MI discharged on treatment with metoprolol with a recommendation to the general practitioner (GP) to increase the metoprolol dose up to 200mg/day within 2months if possible. At follow-up, metoprolol dosage after up-titration, metoprolol steady-state trough plasma concentrations, hemodynamic parameters, potential metoprolol-induced adverse drug reactions and number of visits to the GP were measured. CYP2D6 genotyping including the reduced-function variant alleles CYP2D6*9, CYP2D6*10 and CYP2D6*41 was performed after end of follow-up. According to the genotype-defined CYP2D6 phenotypes, 30% of the patients were metoprolol extensive metabolizers (EMs), 55% intermediate metabolizers (IMs) and 13% poor metabolizers (PMs; carriers of non-coding and reduced-function variant included). Dose-adjusted metoprolol trough concentrations were significantly higher in IM (2-fold) and PM (6.2-fold) groups vs. the EM group (p< 0.001). Only 35% of patients in the PM group achieved the primary end point, i.e. reaching at least 85% of the expected maximum heart rate (HR) during exercise, compared with 78% in the EM group (p< 0.01), and maximum observed HR at exercise was significantly lower in the PM group vs. the EM group (129 ± 5 vs. 142 ± 2bpm, p< 0.007). In contrast, metoprolol maintenance dose, blood pressure, exercise capacity, number of visits at the GP and frequency and severity of self-reported potential metoprolol-related adverse drug reactions were not significantly different between the groups. Using a comprehensive CYP2D6 genotyping panel, the present study demonstrates a > 6-fold increase of dose-adjusted plasma metoprolol trough concentration in CYP2D6 PMs vs. EMs with a parallel lower increase in achieved maximum HR during exercise but without association between genotype and frequency or severity of self-reported adverse drug effects. This may indicate that CYP2D6 PMs potentially could benefit of the increased plasma concentration per dose in a naturalistic setting.

Self-reported adverse drug effects and associated factors among H. pylori infected patients on standard triple therapy: Prospective follow up study.

One of the most common reasons for poor medication adherence and associated treatment failure of triple therapy is adverse drug effect (ADEs) of medications. Assessment of ADEs and associated factors during H. pylori eradication therapy. Consented H. pylori positive adult outpatients on standard triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) were involved in this facility based follow up study from May 2016 to April 2018 at Bahir Dar city in Ethiopia. Pre-developed questionnaire and formats were used to collect sociodemographic, medical information, and patient practice data before, during, and after therapy. Bivariate and backward stepwise multivariate logistic regression was used to analyze data. P-value < 0.05 at 95%CI was considered as significant. A total of 421 patients were involved in the study. Almost 80% of the patients were urban residents. Mean (±SD) age and body weight of patients were 30.63 (± 10.74) years and 56.79 (± 10.17) kg, respectively. ADE was reported from 26.1% of the patients and of all the reported ADEs, more than 85% was manifested with gastrointestinal symptoms which include gastrointestinal discomfort(39.1%), nausea (13.6%), constipation(12.7%), diarrhea(12.9%) and anorexia(10%). Determinants of self-reported ADEs among patients in the present study were body mass index above 25 (AOR: 2.55; 95%CI (1.21-5.38), p = 0.014), duration of acid-pepsin disorder more than 3weeks (AOR: 3.57; 95%CI (1.63-7.81), p = 0.001), pain feeling during long interval between meals (AOR: 2.14; 95%CI (1.19-3.84), p = 0.011), and residence in urban area (AOR: 1.95; 95% CI (1.04-3.67), p = 0.038). Significant proportion of patients reported ADEs which commonly manifested with gastrointestinal symptoms. Consideration of patients' body mass index, duration of the disorder, period of the day when patients feel pain, and patients' area of residence could help to reduce ADEs experienced during H. pylori eradication therapy.

Acute and residual effects of smoked cannabis: Impact on driving speed and lateral control, heart rate, and self-reported drug effects

BackgroundAlthough driving under the influence of cannabis is increasingly common among young adults, little is known about residual effects on driver behavior. This study examined acute and residual effects of smoked cannabis on simulated driving performance of young cannabis users. MethodsIn this double-blind, placebo-controlled, parallel-group randomized clinical trial, cannabis users (1–4 days/week) aged 19–25 years were randomized with a 2:1 allocation ratio to receive active (12.5% THC) or placebo (0.009% THC) cannabis in a single 750 mg cigarette. A median split (based on whole-blood THC concentrations at the time of driving) was used to divide the active group into low and high THC groups. Our primary outcome was simulated driving performance, assessed 30 min and 24 and 48 h after smoking. Secondary outcomes included blood THC concentrations, subjective drug effects, and heart rate. ResultsNinety-six participants were randomized, and 91 were included in the final analysis (30 high THC, 31 low THC, 30 placebo). Mean speed (but not lateral control) significantly differed between groups 30 min after smoking cannabis (p ≤ 0.02); low and high THC groups decreased their speed compared to placebo. Heart rate, VAS drug effect and drug high increased significantly immediately after smoking cannabis and declined steadily after that. There was little evidence of residual effects in any of the measures. ConclusionAcutely, cannabis caused decreased speed, increased heart rate, and increases in VAS drug effect and drug high. There was no evidence of residual effects on these measures over the two days following cannabis administration.

Helicobacter pylori eradication rate of standard triple therapy and factors affecting eradication rate at Bahir Dar city administration, Northwest Ethiopia: A prospective follow up study.

BackgroundEradication of Helicobacter pylori infection with standard triple therapy has been accepted to curb associated risks of chronic gastritis andpeptic ulcer disease.ObjectiveTo assess H. pylori eradication rate of standard triple therapy and patient related factors affecting eradication rate.MethodsA facility based prospective follow up study was conducted in Bahir Dar City Administration, Ethiopia, on consented outpatients presented with gastritis and peptic ulcer disease and positive for H. pylori stool antigen test from May 2016 to April 2018. Eradication was confirmed with stool antigen test made after 4–6 weeks of standard triple therapy, comprising of proton pump inhibitor, clarithromycin and amoxicillin. Pre-developed questionnaire and data collection formats were used to collect variables before and after therapy. Bivariate and backward stepwise multivariate logistic regression was used to analyze data. P-value < 0.05 at 95%CI was considered as significant.ResultsThe overall H. pylori eradication rate was 90.3% (379/421). Almost 80% of the patients were urban residents. Mean (±SD) age and body weight of patients were 30.63 (± 10.74) years and 56.79 (± 10.17) kg, respectively. Self-reported adverse drug effects and area of residence of patients were factors affecting eradication rate significantly. Patients with no self-reported adverse drug effect were 3.85 (AOR: 3.85; 95%CI (1.41–5.26)) times more likely to eradicate H. pylori infection compared to those reported adverse effects. Patients living in rural area were 2.7 (AOR: 2.7; 95%CI (1.19–20.0)) times more likely to achieve eradication compared to urban residents.ConclusionH. pylori eradication rate is within the recommended level for clinical practice, indicating that modifications of the standard triple therapy observed in the different healthcare institutions are not evidence-based. Emphasis should be given to adverse drug effects of medications and tailored counseling based on area of residence could have a contribution in improving eradication rate.

The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial

RationalePrevious research demonstrating that lysergic acid diethylamide (LSD) produces alterations in time perception has implications for its impact on conscious states and a range of psychological functions that necessitate precise interval timing. However, interpretation of this research is hindered by methodological limitations and an inability to dissociate direct neurochemical effects on interval timing from indirect effects attributable to altered states of consciousness.MethodsWe conducted a randomised, double-blind, placebo-controlled study contrasting oral administration of placebo with three microdoses of LSD (5, 10, and 20 μg) in older adults. Subjective drug effects were regularly recorded and interval timing was assessed using a temporal reproduction task spanning subsecond and suprasecond intervals.ResultsLSD conditions were not associated with any robust changes in self-report indices of perception, mentation, or concentration. LSD reliably produced over-reproduction of temporal intervals of 2000 ms and longer with these effects most pronounced in the 10 μg dose condition. Hierarchical regression analyses indicated that LSD-mediated over-reproduction was independent of marginal differences in self-reported drug effects across conditions.ConclusionsThese results suggest that microdose LSD produces temporal dilation of suprasecond intervals in the absence of subjective alterations of consciousness.

A Novel Observational Method for Assessing Acute Responses to Cannabis: Preliminary Validation Using Legal Market Strains.

Background: The development of novel cannabis research methods that are compatible with current federal regulations is imperative to conduct studies of the effects of legal market cannabis. There is very little research on higher strength, higher Δ9-tetrahydrocannabinol (THC), which has become increasingly available since legalization. Research on strains containing cannabidiol (CBD), a second primary, but nonpsychotomimetic, cannabinoid, is very limited.Materials and Methods: Using a novel observational methodology, regular cannabis users were asked to use one of two legal market cannabis strains that they purchased from a local dispensary (one strain containing 8% THC and 16% CBD (THC+CBD) and one containing a 17% THC concentration, but no CBD (THC). After using their suggested cannabis strain as they typically would for a 3-day period, participants returned to the laboratory immediately after their final use. Measures included a blood draw to measure cannabinoid blood levels and circulating cytokines, self-reported subjective drug effects, and verbal recall memory.Results: Analysis of CBD/THC concentration levels in the blood following the 3-day strain manipulation suggests that all, but one participant (n=23/24) followed instructions and used their assigned strain. Individuals in the THC group (n=11) smoked no more than their usual amount, and participants who used the THC+CBD (n=12) strain smoked more than their reported usual amount, but did not have significantly different THC+metabolite blood levels from the THC group. The THC+CBD strain was also associated with less desire to smoke, lower levels of subjective drug effects, and lower levels of circulating cytokines (TNF-α, IL-6, and IL-1β) immediately after use.Conclusions: Initial results support the feasibility of this novel observational methodology involving brief manipulation of strain use. Preliminary findings indicate that participants may self-titrate cannabis use based on cannabinoid concentration and the THC+CBD strain was associated with lower levels of cannabis craving, subjective intoxication, and circulating cytokines.

Alcohol-induced place conditioning in moderate social drinkers.

To test whether non-dependent drinkers show place preference for a location paired with alcohol, and to test if the amount of time spent in the alcohol-paired location is related to self-reported subjective alcohol effects experienced in that environment. Two groups of subjects completed six conditioning sessions: three with alcohol (0.8g/kg) and three without alcohol. Individuals were assigned randomly to two groups, paired and unpaired, in a 2:1 ratio. The paired group (n=78) received alcohol in one testing room and no-alcohol in another testing room (biased assignment). The unpaired group (n=30) received alcohol and no-alcohol in each testing room. Human Behavioral Pharmacology Laboratory, University of Chicago, Chicago, IL, USA (single site). Healthy male and female social drinkers (n=108) aged 21-40years participated in the study (consisting of 10 separate laboratory visits) between March 2012 and August 2014 (an average of 36 separate subject visits per month). The primary outcome measure was the pre- to post-conditioning change in the percentage of time spent in the least preferred room (obtained during drug-free exploration tests conducted at separate visits before and after the six conditioning sessions were completed). Secondary measures included self-reported subjective mood and drug effects obtained during the conditioning sessions. The groups differed in the change in the percentage of time spent in the initially least preferred room, from pre- to post-conditioning; paired group =11.0%, unpaired group =-1.4%, mean difference=12.4%, 95% confidence interval=1.9-23.0, P=0.02. The change in the percentage of time spent in the least-preferred room was related to the self-reported sedative effects of alcohol during conditioning sessions among paired group participants only. Non-dependent consumers of alcohol appear to develop a behavioral preference for locations paired with alcohol consumption, more so for those who experience sedative effects from alcohol in those locations.

Non-smoker exposure to secondhand cannabis smoke II: Effect of room ventilation on the physiological, subjective, and behavioral/cognitive effects

IntroductionCannabis is the most widely used illicit drug. Many individuals are incidentally exposed to secondhand cannabis smoke, but little is known about the effects of this exposure. This report examines the physiological, subjective, and behavioral/cognitive effects of secondhand cannabis exposure, and the influence of room ventilation on these effects. MethodsNon-cannabis-using individuals were exposed to secondhand cannabis smoke from six individuals smoking cannabis (11.3% THC) ad libitum in a specially constructed chamber for 1h. Chamber ventilation was experimentally manipulated so that participants were exposed under unventilated conditions or with ventilation at a rate of 11 air exchanges/h. Physiological, subjective and behavioral/cognitive measures of cannabis exposure assessed after exposure sessions were compared to baseline measures. ResultsExposure to secondhand cannabis smoke under unventilated conditions produced detectable cannabinoid levels in blood and urine, minor increases in heart rate, mild to moderate self-reported sedative drug effects, and impaired performance on the digit symbol substitution task (DSST). One urine specimen tested positive at using a 50ng/ml cut-off and several specimens were positive at 20ng/ml. Exposure under ventilated conditions resulted in much lower blood cannabinoid levels, and did not produce sedative drug effects, impairments in performance, or positive urine screen results. ConclusionsRoom ventilation has a pronounced effect on exposure to secondhand cannabis smoke. Under extreme, unventilated conditions, secondhand cannabis smoke exposure can produce detectable levels of THC in blood and urine, minor physiological and subjective drug effects, and minor impairment on a task requiring psychomotor ability and working memory.

St John’s wort greatly decreases the plasma concentrations of oral S‐ketamine

Ketamine is an intravenous anaesthetic and analgesic agent but it can also be used orally as an adjuvant in the treatment of chronic pain. This study investigated the effect of the herbal antidepressant St John's wort, an inducer of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of oral S-ketamine. In a randomized cross-over study with two phases, 12 healthy subjects were pretreated with oral St John's wort or placebo for 14 days. On day 14, they were given an oral dose of 0.3 mg/kg of S-ketamine. Plasma concentrations of ketamine and norketamine were measured for 24 h and pharmacodynamic variables for 12 h. St John's wort decreased the mean area under the plasma concentration-time curve (AUC(0-∞)) of ketamine by 58% (P < 0.001) and decreased the peak plasma concentration (C(max)) of ketamine by 66% (P < 0.001) when compared with placebo. Mean C(max) of norketamine (the major metabolite of ketamine) was decreased by 23% (P = 0.002) and mean AUC(0-∞) of norketamine by 18% (P < 0.001) by St John's wort. There was a statistically significant linear correlation between the self-reported drug effect and C(max) of ketamine (r = 0.55; P < 0.01). St John's wort greatly decreased the exposure to oral S-ketamine in healthy volunteers. Although this decrease was not associated with significant changes in the analgesic or behavioural effects of ketamine in the present study, usual doses of S-ketamine may become ineffective if used concomitantly with St John's wort.

Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir

this study aimed to investigate the effect of antivirals ritonavir and lopinavir/ritonavir on the pharmacokinetics and pharmacodynamics of oral oxycodone, a widely used opioid receptor agonist used in the treatment of moderate to severe pain. a randomized crossover study design with three phases at intervals of 4 weeks was conducted in 12 healthy volunteers. Ritonavir 300 mg, lopinavir/ritonavir 400/100 mg, or placebo b.i.d. for 4 days was given to the subjects. On day 3, 10 mg oxycodone hydrochloride was administered orally. Plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were determined for 48 h. Pharmacokinetic parameters were calculated with standard noncompartmental methods. Behavioral effects and experimental cold pain analgesia were assessed for 12 h. ANOVA for repeated measures was used for statistical analysis. ritonavir and lopinavir/ritonavir increased the area under the plasma concentration-time curve of oral oxycodone by 3.0-fold (range 1.9- to 4.3-fold; P <0.001) and 2.6-fold (range 1.9- to 3.3-fold; P <0.001). The mean (± SD) elimination half-life increased after ritonavir and lopinavir/ritonavir from 3.6 ± 0.6 to 5.6 ± 0.9 h (P <0.001) and 5.7 ± 0.9 h (P <0.001), respectively. Both ritonavir (P <0.001) and lopinavir/ritonavir (P <0.05) increased the self-reported drug effect of oxycodone. ritonavir and lopinavir/ritonavir greatly increase the plasma concentrations of oral oxycodone in healthy volunteers and enhance its effect. When oxycodone is used clinically in patients during ritonavir and lopinavir/ritonavir treatment, reductions in oxycodone dose may be needed to avoid opioid-related adverse effects.

Breastfeeding and Prolactin Levels in Lactating Women With a Family History of Alcoholism

Many motivated new mothers fail to reach public health goals for breastfeeding, highlighting the need to identify risk factors. Because having a family history of alcoholism is associated with blunted prolactin responses to an alcohol challenge in nonlactating individuals, this study aimed to identify associations in family history of alcoholism, prolactin, and breastfeeding behaviors in lactating women. This was a 2-day experimental study that used within-subject alcohol or control beverage consumption and between-subject family history of alcoholism factors. The participants were non-alcohol-dependent lactating women; 7 were family history-positive (FHP) for alcohol dependence, and 21 were family history-negative (FHN). Consumption of 0.4 g/kg alcohol or nonalcoholic beverage occurred in separate randomized sessions, followed by use of a breast pump. Basal and suckling-induced prolactin, blood alcohol concentrations, milk yield, self-reported drug effects, neophobia, and breastfeeding patterning were measured. Although no group differences in alcohol pharmacokinetics were detected, FHP women exhibited blunted prolactin to breast stimulation after drinking the control and alcohol beverage and felt more of the stimulant-like effects of alcohol than did FHN women. FHP women reported more frequent daily breastfeeding than did FHN women. This is the first evidence that family history of alcoholism is associated with a blunted magnitude, rapidity, and duration of the prolactin response to breast stimulation and an alcohol challenge in lactating women. More frequent breastfeeding by FHP women suggests behavioral compensation for perceived and/or actual poor lactation. Alcohol did not enhance lactational performance, further disputing the lore that alcohol is a galactagogue.

St John’s wort greatly reduces the concentrations of oral oxycodone

Background Chronic pain is associated with depression. Self-treatment of depression with herbal over-the-counter medicine St John’s wort makes pain patients prone to drug interactions. Aims The aim of this study was to assess the potential of St John’s wort to alter the CYP3A-mediated metabolism of a μ-opioid receptor agonist, oxycodone. Methods The study design was placebo-controlled, randomized, cross-over with two phases at intervals of 4 weeks and was conducted with 12 healthy participants. St John’s wort (Jarsin®) or placebo was administered t.i.d. for 15 days and oral oxycodone hydrochloride 15 mg on day 14. Oxycodone pharmacokinetics and pharmacodynamics were compared after St John’s wort or placebo. Behavioural and analgesic effects were assessed with subjective visual analogue scales and cold pressor test. Plasma drug concentrations were measured from 0 to 48 h, behavioural and analgesic effects from 0 to 12 h. Results Following St John’s wort administration the oxycodone AUC decreased 50% ( p < 0.001). Oxycodone elimination half-life shortened from a mean ± SD 3.8 ± 0.7 to 3.0 ± 0.4 h ( p < 0.001). The self-reported drug effect of oxycodone as measured by AUEC 0–12 decreased significantly ( p = 0.004). Differences between St John’s wort and placebo phases in cold pain threshold and intensity AUEC 0–12 were not observed. Conclusions St John’s wort greatly reduced the plasma concentrations of oral oxycodone. The self-reported drug effect of oxycodone decreased significantly. This interaction may potentially be of some clinical significance when treating patients with chronic pain.

Inappropriate Medication Use as a Risk Factor for Self‐Reported Adverse Drug Effects in Older Adults

To determine the association between inappropriate medication use and self-reported adverse drug effects (ADEs). Prospective cohort study with three annual mailed surveys. Population-based sample of Iowa Medicare beneficiaries. Cohort members (n5626) with established mobility disability and complete pharmacy dispensing records, continuous Medicare eligibility, and survey data. The number of unique drug ingredients dispensed and inappropriate use were assessed for the year before the ADE survey. Inappropriate medication use was defined according to published criteria: contraindicated drugs for elderly people, drug-disease interactions (constructed from linked Medicare claims), drug-drug interactions, and therapeutic duplications. An ADE was defined from the following question: "In the past 12 months, have you experienced an unwanted effect or side effect of a medication?" Of respondents to the ADE survey, 22.0% reported having experienced an ADE in the past year, and 322 (51.4%) received at least one potential inappropriate medication. Factors associated univariately with ADE self-report were number of medications, number of mobility limitations, any inappropriate medication use, and each of the individual domain appropriateness indicators, as well as number of different domains of inappropriate use. The adjusted odds ratio for developing an ADE was 2.14 (95% confidence interval=1.26-3.65) for those with inappropriate use versus no inappropriate use. Efforts to reduce ADEs by reducing medication inappropriateness should be encouraged as a complement to efforts focused on reducing the number of medications prescribed.

Acute alcohol consumption disrupts the hormonal milieu of lactating women.

Despite the lack of scientific evidence to support the claim that alcohol is a galactagogue, lactating women have been advised to drink alcohol as an aid to lactation for centuries. To test the hypothesis that alcohol consumption affects the hormonal response in lactating women, we conducted a within-subjects design study in which 17 women consumed a 0.4 g/kg dose of alcohol in orange juice during one test session and an equal volume of orange juice during the other. Changes in plasma prolactin, oxytocin, and cortisol levels during and after breast stimulation, lactational performance, and mood states were compared under the two experimental conditions. Oxytocin levels significantly decreased, whereas prolactin levels and measures of sedation, dysphoria, and drunkenness significantly increased, during the immediate hours after alcohol consumption. Changes in oxytocin were related to measures of lactational performance such as milk yield and ejection latencies, whereas changes in prolactin were related to self-reported measures of drunkenness. Although alcohol consumption resulted in significantly higher cortisol when compared with the control condition, cortisol levels were not significantly correlated with any of the indices of lactational performance or self-reported drug effects. Moreover, cortisol levels steadily decreased on the control day, indicating that the procedures were not stressful to the subjects. In conclusion, recommending alcohol as an aid to lactation may be counterproductive. In the short term, mothers may be more relaxed, but the hormonal milieu underlying lactational performance is disrupted, and, in turn, the infant's milk supply is diminished.

Sensitivity to acute methadone dose changes in maintenance patients

This study assessed whether methadone patients can identify acute dose changes in their maintenance dose, and explored the relationships between self-reported drug effects and real or perceived dose changes. Four times each week patients (N = 10) unpredictably received either 80%, 90%, 100%, 110% or 120% of their usual daily dose (50–100 mg). Approximately 24 hr later they indicated which dose they had received on the previous day, and rated the previous day's dose in terms of good effects, bad effects, and change in medication taste. Correct estimation of the doses received was always at the levels expected by chance alone. Furthermore, this sample of patients could not detect dose-related changes in medication taste. However, self-reports of good effects were significantly higher when patients believed that they had received a dose increment, and ratings of bad effects were higher when patients believed that they had received a dose decrement.

Individual Differences in Responses to Ethanol and d‐Amphetamine: A Within‐Subject Study

In some individuals, ethanol (EtOH) produces marked stimulant-like subjective effects resembling those of stimulant drugs, like d-amphetamine (AMP). In this study, we examined the neurochemical basis of these individual differences by examining the same subjects' responses to both EtOH and AMP. A positive correlation between subjects' responses to the two drugs may suggest that AMP and EtOH produce their stimulant-like subjective effects by a shared mechanism. Twenty-seven volunteers (17 male, 10 female), aged 21-35, received beverages or capsules containing EtOH 0.8 g/kg, AMP 10 or 20 mg, or placebo on four separate sessions in random order and under double-blind conditions. Various self-reported and objective drug effects were measured, including measures sensitive to subjective and cognitive stimulant-like effects. EtOH and AMP produced their prototypical subjective and behavioral effects, including increased ratings of stimulant-like subjective effects, increased heart rate and blood pressure, and improved vigilance performance after AMP and increased ratings of sedative-like subjective effects, increased heart rate and blood pressure, and impaired vigilance performance after EtOH. Consistent with previous reports, there was substantial intersubject variability in subjective responses to EtOH: some subjects reported primarily stimulant-like effects, whereas others reported primarily sedative-like effects. To examine the relationship between these responses to EtOH and subjects' responses to AMP, correlations were examined between effects of EtOH and AMP. For all subjects together, there was a significant positive correlation between responses to EtOH and 20 mg AMP on the ARCI A scale (a measure of stimulant-like subjective effects; r = 0.41, p < 0.05). Among only those subjects who reported primarily stimulant-like effects from EtOH, the correlation between EtOH and AMP was 0.64 (p < 0.05). Subjects who experience pronounced stimulant-like effects from EtOH also report greater stimulant effects from AMP, suggesting that these effects may be mediated through similar mechanisms. These correlations between the drugs' effects were not observed on other measures, such as DSST or vigilance task performance or heart rate. This may indicate that these other effects are mediated by separate mechanisms. The study illustrates a novel approach to studying the neurochemical basis of drug effects.