Experimental & Clinical Psychopharmacology

Call for evidence-based psychedelic integration.
The use of psychedelics for various purposes was common in different civilizations throughout human history and has been explored scientifically for more than a century. Although the applications of psychedelics show promise in the treatment of various psychiatric and neurological indications, as well as in facilitation of well-being and personal growth, several psychedelic-related risks and challenges have also been identified. Psychedelic integration (PI) refers to various practices that serve to either minimize harms or maximize benefits associated with psychedelic use. PI is also recognized as a substantial part of psychedelic-assisted therapy (PAT), following preparation to and facilitation of the psychedelic experience. In the context of clinical/psychotherapeutic practice, several PI models/methods have already been proposed. However, while a number of these models/methods are theory-driven, or have a history of clinical application, each lack any empirical support and thus cannot be described as evidence based. This is to the disadvantage to countless people who had and who will have their psychedelic experiences in various contexts, as the prevalence of using psychedelics increased in recent years and is expected to grow further. Therefore, consistent with general recommendations for developing and implementing evidence-based mental health practices, this article calls for scientific efforts to the development, examination, and evaluation of psychedelic integration models/methods. This article also briefly summarizes the current literature on psychedelic integration, provides a list of exemplary avenues that research on psychedelic integration might take, as well as anticipates and discusses the limitations and challenges of PI-focused research. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Lumateperone for treatment of psychotic symptoms in Lewy body disease: A case report.
Individuals experiencing Lewy body disease (LBD) are particularly vulnerable to the adverse effects of neuroleptics. This sensitivity has been employed by some authorities as a diagnostic component for this disorder. At present, we do not have any Food and Drug Administration–approved antipsychotic for the management of psychotic symptoms in this condition. We present the first case of an LBD patient, showing favorable response in psychotic symptoms with lumateperone, a novel atypical neuroleptic. Our report revealed improvements in cognition, psychosis, and sleep following the initiation of lumateperone without concurrent emergence of extrapyramidal side effects, autonomic instability, parkinsonian features, or cognitive decline, which are typically seen when treated with available antipsychotic medications. Clinicians may wish to consider potential usefulness of lumateperone when managing patients with this disabling condition. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
The association between exercise and prescription opioid misuse: A scoping review.
Exercise prevents chronic diseases and modulates pain. People experiencing pain often use opioids for relief, increasing the risk of prescription opioid misuse. Nonetheless, exercise may influence prescription opioid misuse through the release of endorphins or induced injury-related pain. We aimed to summarize the existing literature on the association between exercise and prescription opioid misuse. We identified studies published through December 2021 in Cochrane, Embase, Medline, and Pubmed, using search terms like “opioid-related disorders,” “opioid misuse,” “exercise,” and “sports.” Observational and experimental studies with adult samples published in English were included. Exclusion criteria included participants <18 years old, studies including heroin use as the outcome, and studies conducted among pregnant or institutionalized individuals. The risk of bias and quality assessment were conducted independently by two authors using the National Institutes of Health Study Quality Assessment Tools, and decisions were cross-checked with a third author. Our search yielded 10,796 records, of which eight studies were included. These studies were heterogeneous clinically and methodologically. Three were intervention trials, three were cross-sectional, and two were cohort studies. Three studies evaluated yoga, two evaluated exercise, and three evaluated sports. Significant findings showed lower prescription opioid misuse among people who exercise, except for one study that showed greater odds of prescription opioid misuse among college athletes. We conclude that the findings on the association between exercise and prescription opioid misuse vary, even within similar study types and samples. Future researchers should consider large samples, standardized questions, and common outcome measures in research on exercise and prescription opioid misuse. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Xylazine suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats.
Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl “high,” alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 μg/kg/infusion) or withdrawal to our knowledge. We established a rat model of xylazine/fentanyl co-SA and withdrawal and evaluated outcomes as a function of biological sex. When administered alone, chronic xylazine (2.5 mg/kg, intraperitoneal) induced unique sex-specific withdrawal symptomatology, whereby females showed delayed onset of signs and a possible enhancement of sensitivity to the motor-suppressing effects of xylazine. Xylazine reduced fentanyl consumption in both male and female rats regardless of whether it was experimenter-administered or added to the intravenous fentanyl product (0.05, 0.10, and 0.5 mg/kg/infusion) when compared to fentanyl SA alone. Interestingly, this effect was dose-dependent when self-administered intravenously. Naloxone (0.1 mg/kg, subcutaneous injection) did not increase somatic signs of fentanyl withdrawal, regardless of the inclusion of xylazine in the fentanyl infusion in either sex; however, somatic signs of withdrawal were higher across time points in females after xylazine/fentanyl co-SA regardless of naloxone exposure as compared to females following fentanyl SA alone. Together, these results indicate that xylazine/fentanyl co-SA dose-dependently suppressed fentanyl intake in both sexes and induced a unique withdrawal syndrome in females that was not altered by acute naloxone treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.
The present study used a rat choice model to test how cocaine or heroin economically interacted with two different nondrug reinforcers along the substitute-to-complement continuum. In Experiment 1, the nondrug alternative was the negative reinforcer timeout-from-avoidance (TOA)—that is, rats could press a lever to obtain a period of safety from footshock. One group of rats chose between cocaine and TOA and another group chose between heroin and TOA. The relative prices of the reinforcers were manipulated across phases while controlling for potential income effects. When cocaine was the reinforcer, rats reacted to price changes by increasing their allocation of behavior to the more expensive option, thereby maintaining relatively proportional intake of cocaine and TOA reinforcers across prices, suggesting these reinforcers were complements here. In contrast, when heroin became relatively cheap, rats increased allocation of income to heroin and decreased allocation of income to TOA, suggesting that heroin substituted for safety. Additionally, rats were willing to accept more footshocks when heroin was easily available. In Experiment 2, the nondrug alternative was saccharin, a positive reinforcer. Heroin and saccharin were complements, but there was no consistent effect of price changes on the allocation of behavior between cocaine and saccharin. As a model of the processes that could be involved in human drug use, these results show that drug-taking behavior depends on the type of drug, the type of nondrug alternative available, and the prices of both. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
A novel abuse liability assessment of e-cigarettes in young adults ii: Reinforcement enhancement and follow-up assessment.
A double-blind study was performed to test the abuse liability of electronic nicotine delivery systems (ENDS) in young adults; in particular, the influence of nicotine on reward sensitivity was assessed. A total of 53 healthy nonusers participated in experimental sessions during which they played a video game made available on a progressive ratio schedule of reinforcement and self-administered nicotine via ENDS. Participants were randomized into one of three groups. Two groups received either a dedicated concentration of nicotine (6 and 12 mg) or a placebo, and whether they received the placebo or their dedicated nicotine dose was randomly determined on a session-by-session basis to mask the sequencing of drug administration. The third group received only a 0 mg (placebo) vaping device during all sessions. In comparison to all placebo conditions, nicotine-induced reward sensitization was evidenced on behavioral measures of video game reinforcement, but not subjective appraisals of the vaping experience. A 1-month follow-up survey provided evidence that reinforcement enhancement by nicotine predicts increased abuse liability of ENDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Changes in weight among individuals with psychiatric conditions or socioeconomic disadvantage assigned to smoke very low nicotine content cigarettes.
Nicotine abstinence leads to weight gain, which could be an unintended consequence of a nicotine reduction policy. This secondary analysis used weekly assessments of weight and ratings of “increased appetite/hunger/weight gain” collected in three 12-week, randomized controlled trials evaluating the effects of cigarettes differing in nicotine dose (15.8, 2.4, or 0.4 mg/g) among individuals with affective disorders, opioid use disorder (OUD), and socioeconomically disadvantaged women. Linear mixed models tested differences by dose and time. Analyses first collapsed across populations and then separated out individuals with OUD because biomarkers suggested they used substantially more noncombusted nicotine. Across populations, weight increased significantly over time, averaging 1.03 kg (p <.001), but did not vary by dose nor was there any interaction of dose/time. “Increased appetite/hunger/weight gain” ratings increased significantly as a function of dose, with differences between low and high doses (1.95 and 1.73, respectively, p = .01), but not by time nor any interaction. In the combined group of individuals with affective disorders and socioeconomically disadvantaged women, weight and “increased appetite/hunger/weight gain” ratings increased significantly by dose, with differences between low and high doses (1.43 vs. 0.73 kg, p = .003 and 2.00 vs. 1.76, p = .02, respectively). Among individuals with OUD, there were no significant effects of any kind on either outcome. Individuals with affective disorders and socioeconomically disadvantaged women gained weight and reported more subjective appetite/weight gain when given 0.4, but not 2.4 mg/g cigarettes, despite comparable decreases in nicotine exposure. However, neither change was clinically significant, suggesting minimal short-term adverse consequences of a nicotine reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Loss aversion predicts cigarette smoking status across levels of sociodemographic characteristics.
Loss aversion (LA) is a tendency to be more sensitive to potential losses relative to similar gains. Low LA is associated with increased risk for cigarette smoking and use of other substances. Previous studies of LA and smoking risk controlled for potentially confounding influences of sociodemographic characteristics associated with smoking risk. The present study replicates these earlier observations while also examining the generality of the association between low LA and smoking risk within different levels of each of the five sociodemographic risk factors for smoking (age, educational attainment, gender, income, race/ethnicity). Parallel analyses were conducted using delay discounting (DD) as a positive control; DD is a decision-making bias regarding the rate at which rewards lose value with increasing delay to receipt. Participants were recruited using standard crowdsourcing methods and completed a sociodemographics questionnaire, a hypothetical gamble task measure of LA, and a monetary choice measure of DD. Low LA was associated with increased risk of cigarette smoking after accounting for the influence of sociodemographic characteristics and DD. Similarly, high DD was associated with increased risk of cigarette smoking after accounting for the influence of sociodemographic characteristics and LA. Further analyses showed that associations of LA with smoking risk or DD with smoking risk generally although not always remained significant within varying levels of the sociodemographic characteristics of interest. These results provide support for low LA as a reliable risk factor for smoking that has generality within and across sociodemographic characteristics and closely parallels associations observed with DD and smoking risk. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Combustible cigarette smokers versus e-cigarette dual users among Latinx individuals: Differences in alcohol and drug use severity.
The Latinx population in the United States (U.S.) experiences significant tobacco and other substance use-related health disparities. Yet, little is known about the couse of combustible cigarettes and e-cigarettes (dual use) in relation to substance use behavior among Latinx smokers. The present investigation compared English-speaking Latinx adults living in the United States who exclusively smoke combustible cigarettes versus dual users in terms of alcohol use and other drug use problem severity. Participants were 297 Hispanic/Latinx daily cigarette smokers (36.4% female, Mage = 35.9 years, SD = 8.87) recruited nationally across the United States using Qualtrics Panels to complete self-report measures of behavioral health outcomes. Five analysis of covariance models were conducted to evaluate differences in overall alcohol consumption, dependence, related problems, hazardous drinking, and drug use problem severity between exclusive combustible cigarette smokers (N = 205) and dual users (N = 92). Results indicated that dual users evinced greater levels of alcohol consumption, dependence, alcohol-related problems, and hazardous drinking compared to exclusive combustible cigarette smokers (ps <.001). Dual users also reported greater levels of drug use problems relative to exclusive combustible cigarette smokers (p <.001). The current findings are among the first to document that dual cigarette and e-cigarette use status (compared to exclusive combustible cigarette smoking) may serve as a clinically relevant risk indicator for a range of deleterious substance use problems among Latinx individuals. Future research is needed to corroborate these findings and examine dual-use status as a longitudinal predictor of alcohol and other substance-related problems. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Menstrual Phase Identification Questionnaire (MPIQ): Development and validation of a cross-sectional survey to identify follicular and luteal phases.
Evidence continues to accumulate on the influence of the menstrual phase on several biobehavioral outcomes (e.g., substance misuse). Expansion of this knowledge is limited due to the burdensomeness of accurate menstrual phase assessment. Thus, we sought to create and validate a questionnaire that can be used as a stand-alone item within low-resource settings and numerous study designs (e.g., cross-sectional) to accurately identify both the follicular phase (FP) and the luteal phase (LP). Participants completed the self-administered four-item Menstrual Phase Identification Questionnaire (MPIQ) in two recently completed clinical trials. We assessed the accuracy of two MPIQ scoring criteria (less restrictive and more restrictive), as compared to self-report of onset of menses alone, with progesterone confirmation via dried blood spots. Participants (n = 59) were, on average, 33.7 (standard deviation [SD]: ± 4.3) years old and provided a total of 83 responses. Assessing FP and LP using the self-reported onset of menses alone classified 65.1% of the responses with an overall phase identification accuracy of 60.2%. While the more restrictive MPIQ scoring classified 100% of the responses, it yielded a similar accuracy (68.4%). In contrast, the less restrictive MPIQ scoring classified 100% of the responses and also significantly improved phase identification accuracy to 92.1% (p <.001). The MPIQ, as a stand-alone item, allows all cross-sectional responses to be classified with a high level of accuracy. This low-burden questionnaire can be used alone to identify FP and LP in studies that may be otherwise limited by study design, finances, and/or participant burden. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Novel methods for the remote investigation of emerging substances: Application to kratom.
The botanical product commonly called “kratom” is still relatively novel to the United States. Like other natural products marketed as supplements, kratom is highly variable, both in terms of the alkaloids naturally occurring in kratom leaves and in terms of processing and formulation. Kratom products sold in the United States are not well-characterized, nor are daily use patterns among regular users. Surveys and case reports have comprised most of the literature on kratom use among humans. To advance our understanding of real-world kratom use, we developed a protocol for the remote study of regular kratom-using adults in the United States. Our study had three aspects implemented in one pool of participants nationwide: an in-depth online survey, 15 days of ecological momentary assessment (EMA) via smartphone app, and the collection and assay of the kratom products used by participants during EMA. Here, we describe these methods, which can be used to investigate myriad drugs or supplements. Recruiting, screening, and data collection occurred between July 20, 2022 and October 18, 2022. During this time, we demonstrated that these methods, while challenging from a logistical and staffing standpoint, are feasible and can produce high-quality data. The study achieved high rates of enrollment, compliance, and completion. Substances that are emerging or novel, but still largely legal, can be productively studied via nationwide EMA combined with assays of shipped product samples from participants. We discuss challenges and lessons learned so other investigators can adapt these methods. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Expectancy of alcohol analgesia moderates perception of pain relief following acute alcohol intake.
Although laboratory studies indicate alcohol reduces pain intensity and increases pain threshold, these effects likely do not completely explain perceived pain relief from alcohol intake. In this study, we tested expectancy of alcohol analgesia (EAA) as a moderator of subjective pain relief following oral alcohol challenge in individuals with and without chronic orofacial pain. Social drinkers (N = 48; 19 chronic pain; 29 pain-free controls) completed two testing sessions: alcohol administration (BrAC: 0.08 g/dL) and placebo. Alcohol expectancy (AE) was assessed using the EAA questionnaire and two 100-mm Visual Analogue Scales (VASs) regarding strength of belief that alcohol provides pain relief (AE VAS 1) or reduces pain sensitivity (AE VAS 2). Participants completed quantitative sensory testing (QST) involving application of pressure to the masseter insertion. Pain threshold (lbf; three repetitions) and pain intensity (4, 5, and 6 lbf; three repetitions each; 100-mm VAS) were collected. After each stimulus, participants rated perceived pain relief due to consumption of the study beverage (0–100 VAS). Higher EAA and AE VAS 1 ratings were associated with stronger perceived relief in the alcohol, but not placebo, condition. However, expectancy specifically related to reduction in pain sensitivity (AE VAS 2) was not associated with relief. Additionally, changes in pain threshold and intensity were not significantly correlated with perceived relief. Taken together, results suggest expectancy that alcohol provides pain relief is an important determinant of its negative reinforcing effects. Future studies should investigate challenging these expectancies as a means of reducing alcohol-related risk in people with pain. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Stereotype threat contributes to poorer recall performance among undergraduate students with problematic drinking patterns.
Stereotype threat occurs when individuals from stigmatized groups feel they are expected to conform to a negative stereotype associated with their group. Studies show that activating stereotype threat can impair performance on cognitive tasks in various marginalized groups. Individuals with problematic alcohol use are subject to stigmatized views related to cognitive abilities and socialization skills; thus, we examine for the first time whether eliciting stereotype threat impairs performance on a memory and a theory of mind task in undergraduate students with varying drinking patterns. We randomized 205 students to a neutral or a stereotype threat condition, which informed participants that the purpose of the study was to assess memory performance and theory of mind skills in relation to different patterns of alcohol consumption. In the stereotype threat group, individuals with problematic drinking patterns demonstrated significantly worse memory performance than nonproblematic drinkers and nondrinkers. The same was not true in the neutral condition, where memory recall did not differ significantly as a function of drinking status. Experimental group and drinking status failed to reveal significant effects on cognitive and affective theory of mind performance. Problematic alcohol use patterns were only associated with poorer memory when stereotype threat was elicited, which indicates that assessments of neurocognitive profiles may be biased, at least for memory performance, if stereotype threat is inadvertently elicited in substance users. Broader implications support the imperative to avoid stigmatization of problematic substance use in scientific communication and clinical settings. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Signal processing and machine learning with transdermal alcohol concentration to predict natural environment alcohol consumption.
Wrist-worn alcohol biosensors continuously and discreetly record transdermal alcohol concentration (TAC) and may allow alcohol researchers to monitor alcohol consumption in participants’ natural environments. However, the field lacks established methods for signal processing and detecting alcohol events using these devices. We developed software that streamlines analysis of raw data (TAC, temperature, and motion) from a wrist-worn alcohol biosensor (BACtrack Skyn) through a signal processing and machine learning pipeline: biologically implausible skin surface temperature readings (< 28°C) were screened for potential device removal and TAC artifacts were corrected, features that describe TAC (e.g., rise duration) were calculated and used to train models (random forest and logistic regression) that predict self-reported alcohol consumption, and model performances were measured and summarized in autogenerated reports. The software was tested using 60 Skyn data sets recorded during 30 alcohol drinking episodes and 30 nonalcohol drinking episodes. Participants (N = 36; 13 with alcohol use disorder) wore the Skyn during one alcohol drinking episode and one nonalcohol drinking episode in their natural environment. In terms of distinguishing alcohol from nonalcohol drinking, correcting artifacts in the data resulted in 10% improvement in model accuracy relative to using raw data. Random forest and logistic regression models were both accurate, correctly predicting 97% (58/60; AUC-ROCs = 0.98, 0.96) of episodes. Area under TAC curve, rise duration of TAC curve, and peak TAC were the most important features for predictive accuracy. With promising model performance, this protocol will enhance the efficiency and reliability of TAC sensors for future alcohol monitoring research. (PsycInfo Database Record (c) 2024 APA, all rights reserved)

Experimental and Clinical Psychopharmacology - Vol 32, Iss 2