Measures Of Subjective Effects Research Articles

Psychometric Evaluation of the Modified E-cigarette Evaluation Questionnaire for use with High School Adolescents and Young Adults.

The subjective experience of positive and negative effects of e-cigarette use has been shown to relate to e-cigarette use outcomes in adults, but no validated measure of e-cigarette subjective response exists for adolescents and young adults (AYAs). In the current study, the psychometric properties of the Modified E-cigarette Evaluation Questionnaire (MECEQ) were evaluated for use with AYAs. 997 AYAs who endorsed using nicotine e-cigarettes at least 4 days per week completed an anonymous, online survey in 2022 (51.1% male; 17.39 [1.88] years old; 33.9% Hispanic; 68% White). Analyses included factor analysis to determine the latent structure of the MECEQ, internal consistency, measurement invariance, between-group differences, and test-criterion relationships with vaping frequency and dependence. The originally-proposed, five-factor structure and a novel four-factor structure were supported, and each subscale was internally consistent. Both models reached scalar invariance for all participant subgroups tested (e.g., sex, daily vaping status), and several between-groups differences were observed. For instance, compared to less frequent vaping, daily vaping was associated with increased Craving Reduction (5-factor), reduced Stimulant Effects (4-factor), and reduced Aversion (5-factor; 4-factor). Adjusted relationships between both MECEQ versions and vaping frequency and dependence provided evidence of concurrent validity. Similar to adults, a five-factor and four-factor version of the MECEQ were supported and evidenced internal consistency, scalar measurement invariance, and concurrent relationships with vaping frequency and dependence. Moving forward, researchers are encouraged to include the MECEQ in future studies to better understand the importance of subjective response in AYA vaping behavior. The Modified E-cigarette Evaluation Questionnaire (MCEQ), an e-cigarette-adapted version of the Modified Cigarette Evaluation Questionnaire (MCEQ), recently was validated to assess subjective e-cigarette effects among adults. Here, we demonstrate that the MECEQ can be used among adolescents and young adults (AYAs). The MECEQ can be scored using the original, five-factor MCEQ structure or using a novel, four-factor structure. Both versions were internally consistent, reached scalar measurement invariance, and evidenced concurrent relationships with vaping frequency and dependence. In sum, this study provides the field with the first psychometrically-sound measure of subjective effects of e-cigarette use for use with AYAs.

Subjective effects of simultaneous alcohol and cannabis versus alcohol-only use: A qualitative analysis.

Theoretical models of addictive behavior suggest that subjective effects serve as a mechanism through which substance use disorders develop. However, little is known about the subjective effects of simultaneous alcohol and cannabis use, particularly whether simultaneous use (a) heightens specific subjective effects or (b) is related to unique subjective effects relative to single-substance effects. The present study used formative, qualitative data analysis to examine patterns of responses within open-answer text response data on subjective effects of simultaneous use. College students who simultaneously use alcohol and cannabis (N = 443; 68.2% female) were asked to describe how alcohol effects differ on simultaneous alcohol and cannabis use versus alcohol-only use days. Conventional content analysis revealed nine concepts related to simultaneous (vs. alcohol-only) use subjective effects including as follows: (a) increased/decreased impairment, (b) low arousal/relaxation, (c) balancing/replacement effects, (d) "cross-faded" effects, (e) little-to-no differences, (f) altered sensation and perception, (g) increased negative affective states, (h) increased appetite, and (i) increased/decreased negative consequences. Increased impairment (N = 191) and increased relaxation (N = 110) were the most often endorsed subjective effects, followed by decreased impairment (N = 55), balancing/replacement effects (N = 50) and cross-faded/enhancement effects (N = 44). Subjective effects from simultaneous use largely map onto domains of single-substance alcohol and cannabis effects (e.g., relaxation, sociability, cognitive/behavioral impairment), but also include distinct domains related to simultaneous use (e.g., balancing/replacement effects, altered sensation and perception). Future quantitative research is needed to validate measures of subjective effects from simultaneous use and their relations with use behavior. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Using Young Adult Language to Describe the Effects of Simultaneous Alcohol and Marijuana Use: Implications for Assessment

Introduction: Prevalence of alcohol and marijuana use is highest in young adulthood and an increasing number of young adults report simultaneous alcohol and marijuana (SAM) use, which is consistently linked with numerous negative consequences. To better understand reasons for engaging in SAM use and to refine measurement of subjective effects of SAM use, this study aimed to identify (1) how young adults describe subjective experiences during a SAM use occasion and (2) how language describing subjective effects changes as a function of level of alcohol and marijuana use. Methods: Using Amazon’s Mechanical Turk (MTurk), 323 participants (53.6% women, 68.4% White, M age = 23.0 years) who reported past-month heavy episodic drinking and past-month SAM use were asked to list words to describe how they feel when using only alcohol, only marijuana, and various combinations of alcohol and marijuana. Results: SAM use language varied as a function of age and substance use behavior but was not associated with sex or race. Large differences in the terms used to describe subjective effects were observed when comparing different combinations of alcohol and marijuana use; most notably the term “cross-faded” appeared primarily when engaging at the heaviest combinations of alcohol and marijuana. Conclusion: Young adults have a wide range of vocabulary for describing subjective effects of SAM use, and subjective effects vary as a function of the level of each substance used. Future research should consider integrating such contemporary language when measuring subjective effects of SAM use.

A randomised, crossover, clinical study to assess nicotine pharmacokinetics and subjective effects of the BIDI® stick ENDS compared with combustible cigarettes and a comparator ENDS in adult smokers

BackgroundNicotine pharmacokinetic assessments of electronic nicotine delivery systems (ENDS) are crucial to understand their ability to provide an alternative to cigarette smoking. Subjective effects data also strongly contribute to this understanding. The BIDI® Stick is a disposable ENDS product which contains 59 mg/ml nicotine benzoate salt and various flavours.MethodsIn this study, we assessed nicotine pharmacokinetics and subjective effects of 6 flavour variants of BIDI® Stick ENDS in adult smokers, compared to cigarettes and a comparator ENDS product. During each of eight study visits, 18 volunteer smoker subjects randomly used one of either their usual brand (UB) of cigarette, a BIDI® Stick ENDS, or a comparator ENDS (JUUL 59 mg/ml nicotine with Virginia Tobacco flavour), during both controlled (10 puffs, 30 s apart) and ad libitum (60 min) puffing sessions. Blood samples were collected at various time points and subjective effects questionnaires were administered.ResultsMean [SD] plasma nicotine Cmax 0–120 was not significantly different between BIDI® Stick ENDS with any flavour (range 15.3 [9.90] ng/ml for BIDI® Stick Winter to 17.6 [9.00] ng/ml for BIDI® Stick Classic) and UB cigarettes (16.2 [9.17] ng/ml). Mean [SD] AUC0-120 (range 569.7 [327.29] to 628.6 [408.99] min*ng/ml for BIDI® Stick ENDS and 747.1 [325.48] min*ng/ml for UB cigarettes) and median Tmax 0–120 (range 5-7 min for all BIDI® Stick ENDS and UB cigarettes) values were also not significantly different between BIDI® Stick ENDS and UB cigarettes, while subjective effects measures were also similar between BIDI® Stick ENDS and UB cigarettes. Mean [SD] plasma nicotine Cmax 0–120, AUC0-120, and median Tmax 0–120 were 6.8 [4.13] ng/ml, 243.6 [179.04] min*ng/ml, and 5 min, respectively, for JUUL ENDS. These values were significantly different compared with those for all BIDI® Stick ENDS and UB cigarettes for both Cmax 0–120 and AUC0-120 but not for Tmax 0–120.ConclusionsBIDI® Stick ENDS delivered nicotine to users comparably to their UB combustible cigarette and higher than JUUL ENDS, and also elicited similar subjective effects such as satisfaction and relief. Thus, the BIDI® Stick ENDS may be a satisfying alternative to cigarettes among current smokers and may support their transitioning away from cigarette smoking.Trial registrationClinicalTrials.gov (identifier number NCT05072925).

A Semantic Scale Network analysis of the revised Mystical Experiences Questionnaire: A call for collaboration

Abstract Background and aims Multiple laboratories have proposed measures of subjective effects of psychedelics as potential mediators of their therapeutic impact. Other work has identified individual differences that covary with subjective responses in informative ways. The range of potential measures of responses, traits, and outcomes is vast. Ideas for new measures are likely numerous. The field will progress efficiently if proposed new scales can add incremental validity. Semantic Scale Network analyses identify conceptual overlap among scales based on items (rather than participant ratings), which could help laboratories avoid putting effort into measures that are unlikely to account for unique variance. Semantic Scale Network analyses can also reveal links to constructs from disparate research literatures, potentially helping investigators generate novel hypotheses and explain connections among disparate findings. The results of Semantic Scale Network analyses have the potential to improve as more investigators enter their scales into the corpus. Method Example analyses using the revised Mystical Experiences Questionnaire (MEQ) underscore the uniqueness and discriminant validity of the MEQ subscales. Results Findings dovetail with published theorizing and suggest potentially novel links with different therapeutic effects. The MEQ total or subscales overlap with measures of awe, inspiration, regret, dissatisfaction, transcendence, depression, fatigue, and spirituality. Links with measures of stress, alexithymia, and gender identity suggest lines of further work. Conclusions This analytic approach might suggest unique applications for psychedelic-assisted treatments and provide perspectives on phenomena outside the field. As psychedelic researchers enter their scales to the corpus for Semantic Scale Network analyses, the field will benefit.

Assessing subjective cannabis effects in daily life with contemporary young adult language

IntroductionSubjective ratings of cannabis effects are important predictors of use-related consequences. However, psychometric research is fairly limited, particularly for measures to capture variability in daily life when diverse modes of cannabis administration and co-substance use are common. MethodsThis study evaluated the predictive utility of a revised item to assess perceived cannabis effects and examined modes of cannabis administration and alcohol and nicotine co-use as moderators. Participants were 106 young adults (18–25 years; 51% female) who completed up to 14 consecutive daily reports of substance use (n = 1405 person-days). Two measures of subjective effects were examined: a standard item (0–100 rating of “how high do you feel?”) and a revised item that uses four crowd-sourced anchor points ranging from relaxed (0), calm/chill (33), high (67), and stoned/baked (100). The items shared substantial variance (Pseudo-R2 = 59.5%), however, the revised item showed greater within-person variability (77.0% vs. 68.8%) and stronger day-level associations with consumption levels (Pseudo-R2 = 25.0% vs. 16.7%). ResultsThe cannabis consumption-subjective effects link was weaker on blunt-only days compared to vape-only days. Subjective cannabis effects were higher on nicotine co-use days after controlling for cannabis consumption; neither alcohol nor nicotine co-use moderated the cannabis consumption-subjective effects link. DiscussionThe revised subjective cannabis effects item is a viable alternative to the standard item among young adults who engage in simultaneous alcohol and cannabis use. ConclusionsFuture research focused on characterizing the variability in cannabis effects is needed.

Acute Pharmacological Effects and Oral Fluid Concentrations of the Synthetic Cannabinoids JWH-122 and JWH-210 in Humans After Self-Administration: An Observational Study.

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2–3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.

Relationship between level of response to alcohol and acute tolerance.

A low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session. Data were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway. Contrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures. These data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.

Abuse liability of cigarettes with very low nicotine content in pregnant cigarette smokers

The U.S. Food and Drug Administration has proposed reducing the nicotine content of cigarettes to a minimally-addictive level. To our knowledge, this study is the first to examine how pregnant smokers respond to very low nicotine content (VLNC) cigarettes.In Phase 1, participants blindly sampled two VLNC cigarettes (0.4 and 2.4 mg/g of tobacco) and their usual brand (UB) cigarette in separate sessions, then completed a behavioral economic simulation task and measures of subjective effects, craving/withdrawal, and smoking topography. Phase 2 directly compared the relative reinforcing effects of the cigarettes using concurrent choice testing. All possible dose-pair combinations were tested in separate sessions where puffs were earned ad libitum by clicking the code associated with their preferred cigarette 10 times. Phase 3 tested the 0.4 mg/g-UB dose-pair where UB puffs could be earned with a progressively incremented number of clicks (maximum 8400).Ten pregnant smokers in Burlington, VT and Baltimore, MD participated in 2017–2018. Regarding abuse liability, participants chose the 0.4-mg/g dose less than UB (22% vs. 78%) during concurrent choice testing and the 0.4-mg/g dose sustained less demand than the 2.4-mg/g and UB doses on the simulation task. Positive subjective effects were also lower for both VLNC cigarettes vs. UB. Each cigarette reduced nicotine craving/withdrawal and no significant changes indicative of compensatory smoking were noted.Reducing the nicotine content of cigarettes may decrease their abuse liability in pregnant smokers without causing untoward craving/withdrawal or compensatory smoking. Studies of extended exposure to VLNCs in pregnant women are warranted.

Sex differences in the acute effects of smoked cannabis: evidence from a human laboratory study of young adults.

Animal studies have found robust sex differences in the pharmacokinetics and pharmacodynamics of Δ9-tetrahydrocannabinol (THC). However, the human evidence remains equivocal, despite findings that women may experience more severe consequences of cannabis use than men. The objective of this secondary analysis was to examine sex differences in THC pharmacokinetics and in acute subjective, physiological, and cognitive effects of smoked cannabis in a sample of regular cannabis users (use 1-4days per week) aged 19-25years. Ninety-one healthy young adults were randomized to receive active (12.5% THC; 17 females, 43 males) or placebo (< 0.1% THC; 9 females, 21 males) cannabis using a 2:1 allocation ratio. Blood samples to quantify concentrations of THC, 11-OH-THC, and 11-Nor-carboxy-THC (THC-COOH), as well as measures of subjective drug effects, vital signs, and cognition were collected over a period of 6h following ad libitum smoking of a 750-mg cannabis cigarette. Females smoked less of the cannabis cigarette than males (p = 0.008) and had a lower peak concentration of THC and THC-COOH than males (p ≤ 0.01). Blood THC concentrations remained lower in females even when adjusting for differences in estimated dose of THC inhaled. There was very little evidence of sex differences in visual analog scale (VAS) ratings of subjective drug effects, mood, heart rate, blood pressure, or cognitive effects of cannabis. Females experienced the same acute effects of smoked cannabis as males at a lower observed dose, highlighting the need for more research on sex differences in the pharmacology of THC, especially when administered by routes in which titrating to the desired effect is more difficult (e.g., cannabis edibles).

Effects of methamphetamine on neural responses to visual stimuli.

The behavioral and reward-related effects of stimulant drugs have been studied extensively; yet the effect of stimulants on sensory processing is still relatively unknown. Prior brain imaging studies have shown that single doses of stimulant drugs increase neural function during cognitive and attentional processes. However, it is not clear if stimulant drugs such as methamphetamine (MA) affect neural responses to novel sensory stimuli, and whether these effects depend on the visual features of the stimuli. In this study, we examined the effects of a single dose of MA (20mg oral) on neural activation in response to visual stimuli that varied on "non-straight edges" (NSE), a low-level visual feature that quantifies curved/fragmented edges and is related to perceived image complexity. Healthy adult participants (n = 18) completed two sessions in which they received MA and placebo in counterbalanced order before an fMRI scan where they viewed both high and low NSE images. Participants also completed measures of subjective drug effects throughout both sessions. During both sessions, high NSE images activated primary visual cortex to a greater extent than low NSE images. Further, MA increased activation only for low NSE images in three areas of visual association cortex: left fusiform, right cingulate/precuneus, and posterior right middle temporal gyrus. This interaction was unrelated to subjective drug effects. These findings suggest that stimulant drugs may change the relative sensitivity of higher order sensory processing to increase visual attention when viewing less complex stimuli. Moreover, MA-induced alterations in this type of sensory processing appear to be independent of the drugs' ability to increase feelings of well-being.

FAAH variant Pro129Thr modulates subjective effects produced by cocaine administration.

The endogenous cannabinoid anandamide (AEA), an agonist at type-1 cannabinoid (CB1) receptors, is metabolized by fatty acid amide hydrolase (FAAH). The common variant rs324420 C->A within the FAAH gene on chromosome 1 codes for a missense substitution (Pro129Thr), resulting in decreased FAAH activity and increased endocannabinoid potentiation. This FAAH variant has been linked to alterations in mood and stress reactivity, as well as being independently linked to increased risk for addiction. We hypothesized that cocaine use disordered (CUD) participants with the FAAH Pro129 Thr variant would exhibit a distinct profile of cocaine-induced subjective effects in the laboratory. A total of 70 CUD participants received intravenous doses of saline (placebo, 0 mg) and cocaine (20, 40 mg) in a lab-controlled setting and rated 10 subjective effect measures prior to and following saline and cocaine administration, using a Visual Analog Scale (VAS). The variant allele was associated with increased cocaine-induced subjective ratings for "Drug Effect," "High," and "Depressed." The prevalence of the variant allele A and the AA genotypes were greater in our CUD group than in the general population (A allele: 47% vs. 34%; AA genotype: 30% vs. 13%; p < .05). Finally, the reported amount and frequency of tobacco and cocaine use was higher in subjects with the AC/AA allele. These results add to existing evidence that this variant of the FAAH genotype may be over-represented among those who have CUD, and this over-representation may result from greater subjective responses to cocaine administration. (Am J Addict 2018;27:567-573).

Rewarding effects of physical activity predict sensitivity to the acute subjective effects of d-amphetamine in healthy volunteers.

While individual differences in reward sensitivity are believed to generalize across drugs and alternative rewards, this notion has received little empirical attention in human research. Here, we tested whether individual differences in the subjective rewarding effects of physical activity were associated with the subjective response to d-amphetamine administration. Healthy volunteers ( n=95; age 18-35 years) completed questionnaires measuring the self-reported pleasurable effects of physical activity and other covariates, and this was followed by two double-blind counterbalanced sessions during which they received either 20 mg oral d-amphetamine or placebo. Subjective drug effects measures were collected before and repeatedly after drug administration. Subjective d-amphetamine-related effects were then reduced via principal components analysis into latent factors of "positive mood," "arousal," and "drug high." Multiple regression models controlling for placebo-related scores, session order, demographics, body mass index, level of physical activity, and use of other drugs showed that degree of self-reported physical activity reward was positively associated with d-amphetamine-induced positive mood and arousal ( βs≥0.25, ps≤0.04), but was not associated with d-amphetamine-induced changes in drug high ( β=0.13, p=0.24). These results provide novel evidence suggesting that individual differences in reward sensitivity cross over between d-amphetamine reward and physical activity reward in humans.

Addiction Potential of Cigarettes With Reduced Nicotine Content in Populations With Psychiatric Disorders and Other Vulnerabilities to Tobacco Addiction

A national policy is under consideration to reduce the nicotine content of cigarettes to lower nicotine addiction potential in the United States. To examine how smokers with psychiatric disorders and other vulnerabilities to tobacco addiction respond to cigarettes with reduced nicotine content. A multisite, double-blind, within-participant assessment of acute response to research cigarettes with nicotine content ranging from levels below a hypothesized addiction threshold to those representative of commercial cigarettes (0.4, 2.3, 5.2, and 15.8 mg/g of tobacco) at 3 academic sites included 169 daily smokers from the following 3 vulnerable populations: individuals with affective disorders (n = 56) or opioid dependence (n = 60) and socioeconomically disadvantaged women (n = 53). Data were collected from March 23, 2015, through April 25, 2016. After a brief smoking abstinence, participants were exposed to the cigarettes with varying nicotine doses across fourteen 2- to 4-hour outpatient sessions. Addiction potential of the cigarettes was assessed using concurrent choice testing, the Cigarette Purchase Task (CPT), and validated measures of subjective effects, such as the Minnesota Nicotine Withdrawal Scale. Among the 169 daily smokers included in the analysis (120 women [71.0%] and 49 men [29.0%]; mean [SD] age, 35.6 [11.4] years), reducing the nicotine content of cigarettes decreased the relative reinforcing effects of smoking in all 3 populations. Across populations, the 0.4-mg/g dose was chosen significantly less than the 15.8-mg/g dose in concurrent choice testing (mean [SEM] 30% [0.04%] vs 70% [0.04%]; Cohen d = 0.40; P < .001) and generated lower demand in the CPT (α = .027 [95% CI, 0.023-0.031] vs α = .019 [95% CI, 0.016-0.022]; Cohen d = 1.17; P < .001). Preference for higher over lower nicotine content cigarettes could be reversed by increasing the response cost necessary to obtain the higher dose (mean [SEM], 61% [0.02%] vs 39% [0.02%]; Cohen d = 0.40; P < .001). All doses reduced Minnesota Nicotine Withdrawal Scale total scores (range of mean decreases, 0.10-0.50; Cohen d range, 0.21-1.05; P < .001 for all), although duration of withdrawal symptoms was greater at higher doses (η2 = 0.008; dose-by-time interaction, P = .002). Reducing the nicotine content of cigarettes may decrease their addiction potential in populations that are highly vulnerable to tobacco addiction. Smokers with psychiatric conditions and socioeconomic disadvantage are more addicted and less likely to quit and experience greater adverse health impacts. Policies to reduce these disparities are needed; reducing the nicotine content in cigarettes should be a policy focus.

Strong preference for mint snus flavor among research participants

IntroductionThe Family Smoking Prevention and Tobacco Control Act of 2009 allows the US FDA to regulate tobacco products, including the banning of characterizing flavors, such as fruit and candy, cigarettes. The availability of mint flavored snus may facilitate the use of the product if consumers find it more palatable with respect to taste, odor, pleasantness, and intensity. MethodsThis study assessed product evaluation (PES), odor identification, odor intensity, and odor hedonics among 151 smokers enrolled in a clinical trial of snus substitution for cigarettes. ResultsFar more participants selected Winterchill (N=110) than Robust (N=41), regardless of their menthol cigarette smoking status. Nicotine dependence was higher among those who selected Winterchill (4 vs 3 on Fagerstrom scale, p=0.017). Those who found Winterchill to be more satisfying, less aversive, and having a more intense, more pleasant odor than Robust were substantially more likely to select Winterchill for their one week trial. ConclusionsFindings indicate that subjective effect measures such as the PES and DEQ are capable of differentiating products in terms of flavor preference, and that smokers express a strong preference for mint flavored snus.

Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes.

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of cannabis. The route of administration is important for interpretation of cannabinoid toxicology.

Pharmacogenetics of stimulant abuse liability: association of CDH13 variant with amphetamine response in a racially-heterogeneous sample of healthy young adults.

A previous genome-wide association study (GWAS) in a predominately Caucasian sample of healthy young adults linked greater amphetamine-induced rewarding effects with the rs3784943 G allele of the cadherin 13 (CDH13; i.e., a cell adhesion molecule implicated in neuronal connectivity) gene. This association has not been subsequently examined, nor has it been studied in Asian populations, which may have greater frequencies of the risk allele. The objective of this study was to examine the association of rs3784943 with amphetamine response in a racially heterogeneous sample (37% Asian) of healthy young adults. Participants (N=84; 18-35years old) genotyped for rs3784943 completed counterbalanced sessions involving 20mg oral d-amphetamine or placebo administration. At both sessions, cardiovascular and subjective drug effects measures were collected. In the combined racially heterogeneous sample, amphetamine (vs. placebo) effects were significantly greater on "Feel Drug" ratings (p<0.05) and marginally greater on "Feel High" ratings and systolic blood pressure (p<0.10) in G/A + G/G genotypes than A/A genotypes. The G allele was more common among Asian than other racial groups. Among the subsample of Asian participants (N=31), drug effects were significantly greater on Feel Drug (p<0.05) and marginally greater on Feel High and heart rate (p<0.10) among Asians with G/A + G/G (vs. A/A) genotypes. In concert with a previous GWAS result, this candidate gene study provides convergent evidence implicating CDH13 rs3784943 variant in d-amphetamine's drug effect profile and suggests generalization to Asian populations. CDH13 and genes coding for other cell adhesion molecules may be worthy of study in the biology of psychostimulant abuse liability.

Acute effects of cannabis on young drivers’ performance of driving-related skills

Impaired driving is a major source of preventable death in Canada, especially among young adults. Although the effects of alcohol on driving are well known, the impact of driving under the influence of cannabis has not been studied as thoroughly. This human laboratory study examines the impact of an acute dose of smoked cannabis on driving-related skills among young drivers who use cannabis regularly. Participants were weekly smokers between the ages of 19 and 25 years who have had an Ontario class G or G2 license for at least twelve months. Measures of driving simulator performance, cognition, mood, and motor skills were collected before and after a single dose of smoked cannabis containing 12.5% a 9- tetrahydrocannabinol (a 9-THC). Although the data presented are based on an interim analysis of an ongoing study, some measures of subjective drug effects, objective physical measures, and driving simulator performance were found to be significantly altered after drug administration.%%%%M.Sc.

Subjective Effects of Ethanol, Morphine, Δ(9)-Tetrahydrocannabinol, and Ketamine Following a Pharmacological Challenge Are Related to Functional Brain Connectivity.

This analysis examines the neuronal foundation of drug-induced psychomimetic symptoms by relating the severity of these symptoms to changes in functional connectivity for a range of different psychoactive compounds with varying degrees of psychomimetic effects. The repeated measures design included 323 resting-state functional magnetic resonance imaging time series and measures of subjective effects in 36 healthy male volunteers. Four different pharmacological challenges with ethanol, morphine, Δ(9)-tetrahydrocannabinol, and ketamine (12 subjects per drug) were applied. A set of 10 "template" resting-state networks was used to determine individual connectivity maps. Linear regression was used for each individual subject to relate these connectivity maps to three clusters of drug-induced subjective psychomimetic effects ("perception," "relaxation," and "dysphoria") as measured with visual analogue scales. Group analysis showed that the subjective effects of perception correlated significantly across drugs with the connectivity of the posterior cingulate cortex and precentral gyrus with the sensorimotor network (p < 0.005, corrected). No significant correlations were found for relaxation or dysphoria. The posterior cingulate cortex has a role in visuospatial evaluation and the precentral gyrus has been associated with auditory hallucinations. Both the posterior cingulate cortex and the precentral gyrus show changes in activation in patients with schizophrenia, which can be related to the severity of positive symptoms (i.e., hallucinations and delusions), and have previously been related to changes induced by psychoactive drugs. The similarity of functional connectivity changes for drug-induced psychomimetic effects and symptoms of psychosis provides further support for the use of pharmacological challenges with psychomimetic drugs as models for psychosis.

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking.