E-cigarette Price Impacts legal and Black-Market Cigarette Purchasing Under a Hypothetical Reduced-Nicotine Cigarette Standard.

INTRODUCTION: The Tobacco Control Act gives the U.S. Food and Drug Administration authority to establish a reduced-nicotine content standard in combusted cigarettes. This future potential regulation may pose a significant public health benefit; however, black markets may arise to meet demand for normal-nicotine content cigarettes among smokers unwilling to transition to or use an alternative product. AIMS AND METHODS: We determined the behavioral-economic substitutability of illicit normal-nicotine content cigarettes and e-cigarettes for reduced-nicotine content cigarettes in a hypothetical reduced-nicotine regulatory market. Adult cigarette smokers were recruited online to complete hypothetical cigarette purchasing tasks for usual-brand cigarettes, reduced-nicotine content cigarettes, and illicit normal-nicotine content cigarettes, as well as a cross-commodity task in which reduced-nicotine content cigarettes were available across multiple prices and illicit cigarettes were concurrently available for $12/pack. Participants completed two three-item cross-commodity purchasing tasks in which e-cigarettes were available for $4/pod or $12/pod alongside reduced-nicotine content cigarettes and illicit cigarettes. RESULTS: Usual-brand cigarette purchasing was greater than illicit normal-nicotine content cigarettes and less than reduced-nicotine content cigarettes. In the cross-commodity purchasing tasks, illicit cigarettes and e-cigarettes both served as economic substitutes for reduced-nicotine content cigarettes; however, when e-cigarettes were available for $4/pod, they were purchased at greater levels than illicit cigarettes and resulted in greater reductions in reduced-nicotine content cigarettes purchasing than when available for $12/pod. CONCLUSIONS: These data suggest that some smokers are willing to engage in illicit cigarette purchasing in a reduced-nicotine regulatory environment, but e-cigarette availability at lower prices may reduce black-market engagement and shift behavior away from combusted cigarette use. IMPLICATIONS: E-cigarettes available at low, but not high, prices were stronger substitutes for legal, reduced-nicotine content cigarettes than illegal, normal-nicotine content cigarettes in a hypothetical reduced-nicotine tobacco market. Our findings suggest the availability of relatively inexpensive e-cigarettes may reduce illicit cigarette purchasing and combusted cigarette use under a reduced-nicotine cigarette standard.

Attention-Deficit/Hyperactivity Disorder Symptoms Are Associated with Greater Delay Discounting of Condom-Protected Sex and Money.

Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risk of detrimental life outcomes. Recent research also indicates that ADHD is associated with sexual risk behavior, such as unprotected sex. Some risky sexual behaviors may be driven, in part, by preference for immediate rewards, referred to as delay discounting, which is prominent in etiological models of ADHD. Therefore, the present study examined the effect of delay on preference for both monetary and sexual outcomes in adults with many ADHD symptoms (both on and off medication) and with fewer ADHD symptoms. Online participants (N = 275; n = 161 males, n = 114 females) completed a monetary delay discounting task, assessing preference for smaller sooner versus larger delayed hypothetical money, and the Sexual Delay Discounting Task, assessing preference for condom use in hypothetical casual sex scenarios based on delay until condom availability. Those with greater ADHD symptoms discounted delayed monetary outcomes as well as delayed condom-protected sex (i.e., preferred sooner money rewards and immediate unprotected sex) significantly more than those with fewer symptoms; however, no effect of current medication use was found across monetary or sexual delay discounting among those with greater ADHD symptoms. This study is the first to demonstrate the relation between ADHD symptoms and reduced condom-use likelihood. Increased discounting of delayed condom-protected sex might constitute one mechanism of risky sexual behavior among individuals with ADHD symptoms. Interventions geared toward increasing condom use in situations in which condoms may otherwise be unavailable, may mitigate risky sexual behaviors and their associated harms in this population.

Methylenedioxymethamphetamine-like discriminative stimulus effects of seven cathinones in rats.

Synthetic cathinone derivatives are commonly considered quasi-legal alternatives for stimulant drugs, such as cocaine and methamphetamine, but some derivatives are increasingly being detected in club drug formulations of Ecstasy or 'Molly' as substitutes for methylenedioxymethamphetamine (±-MDMA). Although several studies have evaluated the psychostimulant-like effects of synthetic cathinones, few cathinone compounds have been assessed for MDMA-like activity. In order to determine their likelihood of interchangeability with entactogenic club drugs, the discriminative stimulus effects of methcathinone, 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone were assessed in Sprague-Dawley rats trained to discriminate 1.5 mg/kg racemic methylenedioxymethamphetamine (±-MDMA) from vehicle. Methamphetamine and the cathinones 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone fully substituted for the discriminative stimulus effects of ±-MDMA. In contrast, methcathinone produced a maximum of only 43% ±-MDMA-appropriate responding and higher doses suppressed responding. Most, but not all of the cathinone compounds tested have discriminative stimulus effects similar to those of MDMA as well as psychostimulant-like effects; however, the potency of MDMA versus psychostimulant substitution varies substantially among the compounds, suggesting that a subset of synthetic cathinones are more MDMA-like than psychostimulant-like. These findings further highlight the highly-variable pharmacology of this class of compounds and suggest that those cathinones with MDMA-like effects may also have increased use as club drugs.

The Hotel Room Purchase Task: Effects of Gender and Partner Desirability on Demand for Hypothetical Sex in Individuals with Disordered Cocaine Use and Controls.

Hypothetical purchase tasks allow for rapid assessment of behavioral economic demand for numerous commodities and are useful in evaluating reinforcer pathologies, such as substance and behavioral addiction. Currently, there is not a task for evaluating demand for sex without requiring implicit engagement in sex work. The current study used a novel purchase task with hotel rooms for sex as the hypothetical commodity to assess demand for sex in individuals with disordered cocaine use, a population that frequently engages in risky sexual behavior. Adults meeting criteria for cocaine abuse or dependence (13 males, ten females) and noncocaine-using controls (eight males, three females) chose hypothetical sexual partners from a series of photographs and endorsed two partners with whom they would most and least like to have sex. Participants then completed the hotel purchase task for both partners, wherein they reported how many nights at a hotel room, at prices from $10 to $1280 per night, they would purchase in a year. Demand intensity was significantly greater and demand elasticity was significantly lower for the most preferred relative to the less preferred partner. Males demonstrated significantly greater intensity and lesser elasticity for sex than females. Demand metrics did not differ between the cocaine and control group. This task may serve as a useful measure of demand for sex without requiring implicit hypothetical engagement in sex work. Future studies exploring the relation between task performance and other characteristics such as sexual dysfunction, in addition to acute substance administration effects, may further determine the task's clinical utility.

Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents.

There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe), and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (≥80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74-78% drug-appropriate responding in DOM-trained and MDMA-trained rats at doses that suppressed responding. 5-MeO-DALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25I-NBOMe, fully substituted for DOM, whereas only 25B-NBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.

Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents.

5,6-Methylenedioxy-2-aminoindane (MDAI) has become a common substitute for (±)-3,4-methylenedioxymethamphetamine (MDMA) in Ecstasy. MDAI is known to produce MDMA-like discriminative stimulus effects, but it is not known whether MDAI has psychostimulant or hallucinogen-like effects. MDAI was tested for locomotor stimulant effects in mice and subsequently for discriminative stimulus effects in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally), methamphetamine (1 mg/kg, intraperitoneally), ±MDMA (1.5 mg/kg, intraperitoneally), or (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (0.5 mg/kg, intraperitoneally) from saline. The ability of MDAI to produce conditioned place preference was also tested in mice. MDAI (3 to 30 mg/kg) depressed locomotor activity from 10 to 60 min. A rebound stimulant effect was observed at 1 to 3.5 h following 30 mg/kg. Lethality occurred in 8/8 mice following 100 mg/kg MDAI. Similarly, MDMA depressed locomotor activity immediately following the administration of 0.25 mg/kg and stimulant effects were observed 50-70 min following the administration of 0.5 and 1 mg/kg. MDAI fully substituted for the discriminative stimulus effects of MDMA (2.5 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (5 mg/kg), and cocaine (7.5 mg/kg), but produced only 73% methamphetamine-appropriate responding at a dose that suppressed responding (7.5 mg/kg). MDAI produced tremors at 10 mg/kg in one methamphetamine-trained rat. MDAI produced conditioned place preference from 0.3 to 10 mg/kg. The effects of MDAI on locomotor activity and drug discrimination were similar to those produced by MDMA, having both psychostimulant-like and hallucinogen-like effects; thus, MDAI may have similar abuse potential as MDMA.

Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic Cathinone Derivatives.

Synthetic cathinones, often sold as "bath salts," are a popular class of recreational drugs used as quasi-legal alternatives to cocaine, methamphetamine, and methylenedioxymethamphetamine. The increased prevalence and health consequences of synthetic cathinone use has prompted regulatory agencies to control a number of these compounds; however, a broad class of analogous compounds known as the second-generation cathinones has been brought to the market to take the place of the banned synthetic cathinone derivatives. The current study aims to characterize the behavioral pharmacology of three pyrrolidinylated second-generation cathinones: 4-methyl-α-pyrrolidinopropiophenone (4'-MePPP), α-pyrrolidinopropiobutiophenone (α-PBP), and α-pyrrolidinopentiophenone (α-PVP). Locomotor activity was tested in mice over an 8-hour period. The discriminative stimulus effects of these compounds were tested in rats trained to discriminate either cocaine or methamphetamine. The rewarding effects of these drugs were assessed in mice using conditioned place preference. Both α-PBP and α-PVP produced long-lasting increases in locomotor activity across a wide range of doses, whereas 4'-MePPP produced locomotor stimulation only at 30 mg/kg. Both α-PBP and α-PVP fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine, whereas 4'-MePPP substituted fully for the discriminative stimulus effects of methamphetamine only. Both α-PBP and α-PVP produced conditioned place preference in an inverted U-shaped dose effect, whereas 4'-MePPP did not produce conditioned place preference. These findings suggest that α-PBP and α-PVP are likely to be recreationally used and have potential for addiction and abuse, but 4'-MePPP may not.

Behavioral economic interactions between cannabis and alcohol purchasing: Associations with disordered use.

As cannabis policy changes, there is an urgent need to understand interactions between cannabis and alcohol couse. An online sample of 711 adult past-month cannabis and alcohol users completed both single-item hypothetical purchasing tasks for cannabis and alcohol and cross-commodity purchasing tasks assessing adjusting-price cannabis with concurrently available, fixed-price alcohol, and vice versa. Participants provided information about cannabis and alcohol use patterns, and completed the Alcohol and Cannabis Use Disorder Identification Tests (AUDIT and CUDIT, respectively). Group data showed that cannabis and alcohol served as complements (as the price of the adjusting-price commodity increased, consumption of both commodities decreased). However, individual data showed substantial variability with nontrivial proportions showing patterns of complementarity, substitution, and independence. More negative slopes (greater complementarity) for fixed-price cannabis and alcohol were both associated with greater self-reported drug consumption and CUDIT and AUDIT scores. The negative relation between cross-price slope and CUDIT/AUDIT score indicates that individuals who treat cannabis and alcohol more as complements are more likely to experience disordered use. Based on these cross-commodity purchasing data, when both cannabis and alcohol are concurrently available at low prices, both may be used at high levels, whereas limiting consumption of one commodity (e.g., through increased price) may reduce consumption of the other. These data show the importance of examining individual participant analyses of behavioral economic drug interactions and suggest that manipulation of cost (e.g., through taxes) or cosale restrictions are potential public health regulatory mechanisms for reducing alcohol and cannabis use and couse behaviors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects.

BACKGROUND: Mescaline is a naturally occurring psychoactive phenethylamine found in several cacti and historically used ceremonially by Indigenous and Latin American populations. Broader recognition of its possible therapeutic value in Western science began in the 1950s; however, knowledge of the safety profile of mescaline and the extent of its use remains limited. The primary aim of this study is to examine the epidemiology of mescaline use among English-speaking adults. METHODS: About 452 respondents completed a web-based survey designed to assess their previous experience with mescaline (subjective effects, outcome measures, and mescaline type used). RESULTS: Most respondents reported that they had consumed mescaline infrequently (⩽once/year), for spiritual exploration or to connect with nature (74%). A small number of respondents reported drug craving/desire (9%), whereas very few reported legal (1%), or psychological problems (1%) related to its use, and none reported seeking any medical attention. Overall, respondents rated the acute mystical-type effects as "moderate," ego-dissolution and psychological insight effects as "slight," and challenging effects as "very slight." Most respondents reported that they used Peyote and San Pedro in their most memorable mescaline experience. Overall, the intensity of acute mescaline effects did not differ between mescaline types. About 50% of the sample reported having a psychiatric condition (i.e. depression, anxiety, etc.), and most (>67%) reported improvements in these conditions following their most memorable experience with mescaline. CONCLUSION: Findings indicate that the mescaline in any form may produce a psychedelic experience that is associated with the spiritual significance and improvements in the mental health with low potential for abuse.

Use patterns, beliefs, experiences, and behavioral economic demand of indica and sativa cannabis: A cross-sectional survey of cannabis users.

Cannabis products available for retail purchase are often marketed based on purported plant species (e.g., "indica" or "sativa"). The cannabis industry frequently claims that indica versus sativa cannabis elicits unique effects and/or is useful for different therapeutic indications. Few studies have evaluated use patterns, beliefs, subjective experiences, and situations in which individuals use indica versus sativa. A convenience sample of cannabis users (n = 179) was surveyed via Amazon Mechanical Turk (mTurk). Participants were asked about their prior use of, subjective experiences with, and opinions on indica versus sativa cannabis and completed hypothetical purchasing tasks for both cannabis subtypes. Participants reported a greater preference to use indica in the evening and sativa in the morning and afternoon. Participants were more likely to perceive feeling "sleepy/tired" or "relaxed" after using indica and "alert," "energized," and "motivated" after using sativa. Respondents were more likely to endorse wanting to use indica if they were going to sleep soon but more likely to use sativa at a party. Hypothetical purchasing patterns (i.e., grams of cannabis purchased as a function of escalating price) did not differ between indica and sativa, suggesting that demand was similar. Taken together, cannabis users retrospectively report feeling different effects from indica and sativa; however, demand generally did not differ between cannabis subtypes, suggesting situational factors could influence whether someone uses indica or sativa. Placebo-controlled, blinded studies are needed to characterize the pharmacodynamics and chemical composition of indica and sativa cannabis and to determine whether user expectancies contribute to differences in perceived indica/sativa effects. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The discounting of death: Probability discounting of heroin use by fatal overdose likelihood and drug purity.

As fatal overdoses from synthetic opioids continue to rise, we need to understand decision-making processes underlying heroin and synthetic opioid use. This study evaluated the influence of sample impurity and fatal overdose risk on hypothetical heroin use. Individuals who currently use heroin (n = 69) were recruited online. Participants completed two probability-discounting tasks evaluating the likelihood of using a sample of heroin based on the likelihood of sample impurity and likelihood of fatal overdose, where greater discounting represented reduced use likelihood. Prior to completing the probability-discounting tasks, participants were randomized to read one of four prompts varying by the presence of information on heroin effects and active (e.g., fentanyl) or inert impurities. Influence of prompts on discounting processes and associations among probability-discounting measures, opioid use behaviors, and dependence severity were evaluated. Heroin use likelihood decreased with increased impurity or overdose risk and in a generally orderly fashion. Discounting was greater (i.e., reduced heroin use likelihood) when overdose risk, compared to sample impurity, was manipulated. Less discounting was associated with more severe opioid dependence. Discounting did not differ among prompts for either task. Individuals might adjust their heroin-use behavior to reduce harm with risk-related information. Greater discounting elicited by overdose relative to impurity risk suggests that equating adulteration and overdose risk is essential for harm reduction. Expanded access to drug checking services, which inform impurity and overdose risk, can reduce fatal overdoses. Due to fear of legal sanctions for these services, legislation and judicial decisions should explicitly protect these services. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Influence of Episodic Future Thinking and Graphic Warning Labels on Delay Discounting and Cigarette Demand.

Delay discounting and operant demand are two behavioral economic constructs that tend to covary, by degree, with cigarette smoking status. Given historically robust associations between adverse health outcomes of smoking, a strong preference for immediate reinforcement (measured with delay discounting), and excessive motivation to smoke cigarettes (measured with operant demand), researchers have made numerous attempts to attenuate the extent to which behaviors corresponding to these constructs acutely appear in smokers. One approach is episodic future thinking, which can reportedly increase the impact of future events on present decision making as well as reduce the reinforcing value of cigarettes. Graphic cigarette pack warning labels may also reduce smoking by increased future orientation. Experiment 1 evaluated the combined effects of episodic future thinking and graphic warning labels on delay discounting; Experiment 2 evaluated solely the effects of episodic future thinking on delay discounting and operant demand. We observed no statistically significant effects of episodic future thinking when combined with graphic warning labels or when assessed on its own. These results serve as a call for further research on the boundary conditions of experimental techniques reported to alter behaviors associated with cigarette smoking.

Sexual discounting: A systematic review of discounting processes and sexual behavior.

Behavioral processes underlying sexual behavior are important for understanding normal human functioning and risk behavior leading to sexually transmitted infections (STIs). This systematic review examines delay and probability discounting in human sexual behavior through synthesis of 50 peer-reviewed, original research articles. Sixteen studies focusing exclusively on monetary delay discounting found small effect size positive correlations with sexual risk behaviors. Eleven studies examined delay or probability discounting of sexual behavior itself using tasks that varied duration, frequency, or quality of sex to determine value. Results show delay and uncertainty of sex causes systematic decreases in value. These studies also show consistent medium effect size relationships between sexual discounting measures and sexual health and substance use, supporting utility above and beyond monetary discounting. Twenty-three studies have modeled clinically relevant decision-making, examining effects of delay until condom availability and STI contraction probability on condom use. Observational and experimental designs found condom-use discounting is elevated in high-risk substance use populations, is sensitive to context (e.g., partner desirability), and is more robustly related to sexual risk compared with monetary discounting or condom use decisions when no delay/uncertainty was involved. Administering cocaine, alcohol, and, for some participants, methamphetamine increased condom-use discounting with minimal effect on monetary discounting or condom use when no delay/uncertainty was involved. Reviewed studies robustly support that sexual behavior is highly dependent on delay and probability discounting, and that these processes strongly contribute to sexual risk. Future research should exploit these systematic relationships to design behavioral and pharmacological approaches to decrease sexual risk behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The drug purity discounting task: Ecstasy use likelihood is reduced by probabilistic impurity according to harmfulness of adulterants.

BACKGROUND: Ecstasy typically contains adulterants in addition to, or in lieu of, MDMA which may pose a greater risk to users than MDMA itself. The current study aimed to evaluate the effectiveness of adulterant-related informational prompts in reducing Ecstasy use using a novel probability discounting task. METHODS: An online sample of past-month Ecstasy users (N = 278) were randomized to one of four different framing prompt conditions: no prompt; a prompt describing MDMA's effects; a prompt describing adulterants as inert "filler"; or a prompt describing adulterants as pharmacologically-active, potentially-harmful compounds. Each prompt contained general, potential public-health information that was not specifically related to subsequent behavioral tasks. All participants then completed an identical Drug Purity Discounting Task, in which they indicated the likelihood of using a sample of Ecstasy across different probabilities of the sample being impure, and then completed a hypothetical Ecstasy purchasing task. RESULTS: Likelihood of Ecstasy use decreased as impurity probability increased across conditions. Ecstasy use likelihood was highest in the "inert" prompt condition, whereas pharmacologically-active adulterant or adulterant-nonspecific prompts resulted in comparably low likelihood of use. Ecstasy-use likelihood did not differ among conditions when the likelihood of sample impurity was 0. Ecstasy purchasing did not differ among groups. Inelastic purchasing was associated with greater likelihood of using potentially-impure Ecstasy. CONCLUSIONS: Altogether, these data highlight the necessity of education regarding pharmacologically-active, rather than inert, adulterants in Ecstasy, and suggest that increased access to drug checking kits and services may mitigate some of the harms associated with Ecstasy use.

Delay and probability discounting in cocaine use disorder: Comprehensive examination of money, cocaine, and health outcomes using gains and losses at multiple magnitudes.

Understanding factors associated with cocaine use disorder is important given its public health impact. One factor is delay discounting (devaluation of future consequences). Cocaine users have shown greater delay discounting of money rewards than non-cocaine users. But underexamined are factors known to affect discounting, such as the sign (reward vs. loss), magnitude (e.g., $10 vs. $1,000), and commodity (e.g., money vs. health) of the consequence. Also underexamined is probability discounting (devaluation of uncertain consequences). We conducted a comprehensive group-comparison study of discounting processes by comparing sign, magnitude, and commodity effects between demographically matched cocaine users (n = 23) and never users (n = 24) for delay discounting and sign and magnitude effects for probability discounting. Participants completed delay and probability discounting tasks spanning rewards and losses; money, cocaine, and health outcomes; and magnitudes of $10, $100, and $1,000. Four primary findings emerged when controlling for other drug use. First, cocaine users pervasively discounted delayed consequences more than never users regardless of sign, magnitude, or commodity, with the possible exception of delay discounting of $1,000 health equivalences. Second, both groups discounted delayed rewards more than losses, with a similar trend for probability discounting. Third, magnitude effects in cocaine users for delayed and probabilistic outcomes were similar to those previously observed in never users and other-drug users. Fourth, cocaine users discounted cocaine-related outcomes more than money and health, with variable results comparing money and health. These data suggest that the behavioral processes of delay and probability discounting are qualitatively similar for cocaine users and never users. However, quantitatively, cocaine users generally showed greater delay discounting and similar probability discounting compared with never users. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Potential for limited reinforcing and abuse-related subjective effects of intranasal oxytocin.

BACKGROUND: There has been growing interest in using oxytocin as a pharmacotherapy for psychiatric disorders, including substance use disorder. Limited data exist regarding oxytocin's reinforcing efficacy, which is a necessary consideration for novel pharmacotherapies, especially in substance-using populations. AIMS: This study aimed to determine the potential reinforcing effects of intranasally administered oxytocin by assessing behavioral economic demand and subjective effects. METHODS: Healthy adults (n = 23) participated in a double-blind, repeated-measures, laboratory study wherein they received intranasal oxytocin (40 IU) or placebo in a randomized order across two sessions. Participants completed drug purchasing tasks at the conclusion of both sessions. Throughout both sessions, subjective and physiological effects were assessed. RESULTS: Demand-curve analysis of purchasing tasks revealed greater median purchasing for oxytocin relative to placebo. Physiological and subjective effects did not significantly differ between oxytocin and placebo. However, a nonsignificant trend was observed for moderately greater drug liking for oxytocin relative to placebo. There was a significant, positive correlation between the difference in drug liking (between oxytocin and placebo) and the difference in lowest-price purchasing (between oxytocin and placebo). CONCLUSIONS: These data suggest the potential for limited reinforcing and abuse-related subjective effects of intranasal oxytocin. Given the small sample, the greater drug liking of oxytocin compared to placebo, and the positive relation between demand and drug liking, it is possible that oxytocin may produce reinforcing effects in some participants. Therefore, additional studies of oxytocin reinforcement are warranted.

Evaluating the co-use of opioids and cannabis for pain among current users using hypothetical purchase tasks.

BACKGROUND: Cannabinoids may potentiate opioid analgesia and therefore could be used to reduce reliance on opioids for analgesia. AIMS: The current study evaluated whether the concurrent availability of cannabis influences opioid consumption using a behavioral economic demand framework. METHODS: An online survey assessed cannabis and opioid use frequency and dependence measures, pain severity, and demand for both cannabis and opioids alone and when concurrently available using hypothetical purchase tasks. Adults reporting current use of opioids for pain management and past 30-day cannabis exposure (N=155) completed two hypothetical purchase tasks in which only grams of cannabis or units of participants' index opioids were available for purchase, and two hypothetical tasks in which both were concurrently available and the price of one drug increased whereas the other was kept constant. Paired-sample t-tests compared the demand of each drug alone with when it was available concurrently with an alternative. RESULTS: Demand intensity was significantly reduced and demand elasticity was significantly increased for both cannabis and opioids when the alternate commodity was available, although the reductions in cannabis consumption were more pronounced than they were for opioid consumption in the presence of the alternate commodity. CONCLUSIONS: These data provide behavioral economic evidence that cannabis access may modestly reduce demand for opioids in persons who have pain. Additional clinical studies that evaluate the analgesic effects of cannabis and cannabis-opioid effects on pain are warranted.

Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats.

BACKGROUND: The development of novel synthetic psychoactive substances continues to accelerate. There are little or no data on the pharmacological mechanisms, behavioral effects, or abuse liability of many of the newer compounds, despite increasing reports of severe adverse effects in recreational users. METHODS: The current study investigated the discriminative stimulus and locomotor stimulant effects of a group of synthetic cathinone analogs: N-ethylpentylone, dimethylone, dibutylone, clephedrone, 3',4'-tetramethylene-α-pyrrolidinovalerophenone (TH-PVP). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine, methamphetamine or MDMA from vehicle. RESULTS: N-Ethylpentylone, dimethylone, dibutylone and clephedrone increased locomotor activity. Maximal effects were similar among the test compounds. Relative potencies were: methamphetamine > N-ethylpentylone > clephedrone > dimethylone > MDMA > cocaine > dibutylone. TH-PVP dose-dependently depressed locomotor activity. N-Ethylpentylone, dimethylone, dibutylone and clephedrone substituted fully for the discriminative stimulus effects of methamphetamine. N-Ethylpentylone, dibutylone and clephedrone fully substituted for cocaine, whereas dimethylone produced a maximum of 67% drug-appropriate responding. Dimethylone, dibutylone and clephedrone fully substituted for MDMA, whereas N-ethylpentylone produced only 50% drug-appropriate responding. TH-PVP produced a maximum of 38% methamphetamine-appropriate responding, 50% cocaine-appropriate responding, and less than 1% MDMA-appropriate responding. CONCLUSIONS: These data provide initial evidence that the novel psychoactive substances N-ethylpentylone, dimethylone, dibutylone, and clephedrone demonstrate potential for abuse as psychostimulants and/or club drugs, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of methamphetamine, cocaine and/or MDMA. TH-PVP has minimal activity in the assays tested and may have little or no abuse liability.

"Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA.

This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in "Ecstasy" formulations, these data indicate that adulterated "Ecstasy" formulations may drive more compulsive drug use than those containing only MDMA.

Impure but not inactive: Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis.

BACKGROUND: Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit "party pills" or "ecstasy" formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP. AIMS: The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP. METHODS: DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM). RESULTS: Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested. CONCLUSIONS: These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.