Effects of Trauma Cue Exposure and Posttraumatic Stress Disorder (PTSD) on Affect and Cannabis Craving in Cannabis Users With Trauma Histories: Use of Expressive Writing as an Online Cue-Reactivity Paradigm: Effets de l'exposition aux signaux traumatiques et du SSPT sur l'affect et le besoin de cannabis chez les consommateurs de cannabis ayant des antécédents de traumatismes : utilisation de l'écriture expressive comme paradigme de réactivité en ligne.

OBJECTIVES: Posttraumatic stress disorder (PTSD) and cannabis use disorder (CUD) commonly co-occur. Conditioned associations between psychological trauma cues, distress, cannabis use, and desired relief outcomes may contribute to the comorbidity. These conditioned associations can be studied experimentally by manipulating trauma cue exposure in a cue-reactivity paradigm (CRP) and examining effects on affective and cognitive outcomes in participants with and without PTSD. However, traditional CRPs take place in-lab limiting recruitment/power. We aimed to examine the effects of CRP condition (trauma and neutral) and PTSD group (likely PTSD+ and PTSD-) on affective and craving outcomes using a stand-alone online expressive writing CRP. METHODS: Participants (n = 202; 43.6% male; Mage = 42.94 years, SD = 14.71) with psychological trauma histories and past-month cannabis use completed a measure of PTSD symptoms (PTSD Checklist-5 for DSM-5 [PCL-5]) and were randomized to complete either a trauma or neutral expressive writing task. Then they completed validated measures of affect (Positive and Negative Affect Schedule-Short Form [PANAS-SF]) and cannabis craving (Marijuana Craving Questionnaire-Short Form [MCQ-SF]). RESULTS: Linear mixed models tested the hypothesized main and interactive effects of CRP condition (trauma and neutral) and PTSD group (likely PTSD+ and PTSD-) on negative and positive affect (PANAS-SF) and cannabis craving dimensions (MCQ-SF). The hypothesized main effects of trauma versus neutral expressive writing were found for negative affect and the expectancy dimension of cannabis craving and of PTSD group for negative affect and all cannabis craving dimensions; no interactions were observed. CONCLUSIONS: Expressive writing appears a useful online CRP. Interventions focused on reducing negative affect and expectancy craving to trauma cues may prevent/treat CUD among cannabis users with PTSD. PLAIN LANGUAGE SUMMARY TITLE: The Use of an Online Expressive Writing as a Trauma Cue Exposure: Effects on Craving and Emotions.

People who have gone through trauma sometimes experience both post-traumatic stress disorder (PTSD) and a tendency to use cannabis excessively (cannabis use disorder or CUD). Researchers believe that there's a connection between traumatic memories, emotional distress, cannabis use, and the relief people feel afterward. These associations can be studied experimentally by using a cue-reactivity paradigm (CRP) to examine effects on craving and affective outcomes in those with and without PTSD. This study included 202 participants who had a history of trauma and reported regular cannabis use. They were randomly assigned to write about a traumatic or neutral personal experience. After, they filled out questionnaires about their PTSD symptoms, emotions (both positive and negative), and cravings for cannabis during the task. We expected that the type of writing task (those assigned to the trauma vs. neutral condition) and PTSD status would be associated with increased cannabis craving, negative emotions, and reduced positive emotions. We found that writing about trauma increased negative feelings and positive expectations about using cannabis for relief, especially for those with PTSD. People with PTSD also seemed to have more ongoing negative feelings and cravings for cannabis. The authors suggest that traditional in-lab experiments might be necessary to fully understand how trauma reminders can influence cravings and emotions in individuals with PTSD-CUD.

The impact of cannabidiol placebo on responses to an acute stressor: A replication and proof of concept study.

BACKGROUND: Our group has previously reported that cannabidiol (CBD) expectancy alone blunts markers of stress, particularly during anticipation, but it is not clear the extent to which such findings were specific to the methods utilized. AIMS: To examine CBD-related placebo effects on stress reactivity and anticipation and to validate a protocol to be used in a neuroimaging study. METHODS: Forty-eight healthy adults (24 female) were randomly assigned to be informed that they ingested a CBD-containing oil or a CBD-free oil despite receiving the same oil (CBD-free). Following oil administration, participants engaged in a laboratory stressor and were then incorrectly informed that they would engage in a second more difficult task following a waiting period. Subjective state (sedation, energy, stress, anxiety) and heart rate were assessed at baseline, post-oil administration, immediately following the first stressor, and while anticipating the second stressor. RESULTS: Subjective stress and anxiety were significantly elevated immediately following the stressor (p-values < 0.001). CBD expectancy was associated with increased subjective sedation (p < 0.01) and tended to be associated with blunted subjective stress (p = 0.053). Post hoc within-condition pairwise compassions suggested a return to pre-stressor levels during the anticipation period in the CBD condition for subjective stress and anxiety (p = 0.784, 0.845), but not the CBD-free condition (p = 0.025, 0.045). CONCLUSION: Results replicate and extend previous findings that CBD expectancy alone can impact stress- and anxiety-relevant responses in the laboratory context.

The Impact of Cannabidiol Expectancy on Cortisol Responsivity in the Context of Acute Stress: Associations with Biological Sex.

Background: Cannabidiol (CBD), a nonpsychoactive cannabinoid found in the cannabis plant, has gained interest for its purported stress- and anxiety-reducing effects. However, the mechanisms underlying these effects remain unclear. Our group previously found that CBD expectancy alone resulted in lower state anxiety (vs. CBD-free expectancy) among those who strongly believed it was helpful for such purposes, in addition to influencing physiological measures (i.e., heart rate variability). Aims: Using data collected as part of this previously published larger study, we aimed to explore the extent to which CBD expectancy alone impacts cortisol in the context of a laboratory stressor. Methods: A sample of 43 healthy adults (23 female) participated in one orientation and two experimental laboratory sessions. They received the same oil (CBD-free) during both experimental sessions but were told they received CBD oil in counterbalanced order in one of their sessions. Participants then engaged in a laboratory stressor (the Maastricht Acute Stress Test; MAST) and salivary cortisol samples were collected throughout [T1: baseline; T2: 90-min postabsorption (PA); T3: poststress (0-PS); T4: 10-min poststress (10-PS); T5: 30-min poststress (30-PS)]. Linear marginal models were used for analyses. Results: Findings indicated that a physiological stress response was elicited in the context of the MAST, which is consistent with what has been reported previously. Interestingly, while cortisol levels were significantly lower in the CBD expectancy condition (vs. CBD-free) immediately following the MAST (0-PS) and 10-min later (10-PS), this effect seems to be largely driven by males, evidenced by a three-way interaction. Cortisol levels did not reliably vary across expectancy conditions at any other time point. Conclusion: Overall, these results suggest that CBD expectancy appears to blunt cortisol in anticipation of a stressor, particularly in males. Findings suggest that it is important to consider the impact of drug-related expectations when assessing CBD-related effects on stress-related processes.

Do we really need two sessions?: The use of a structured interview as a trauma cue reactivity paradigm.

OBJECTIVES: Derived from classical conditioning theory and rooted in motivational mechanisms, cue reactivity paradigms (CRPs) are used in addictions research to measure participants' propensities for substance-relevant responses (e.g., craving) during exposure to substance-relevant cues (e.g., drug paraphernalia). CRPs are also useful in PTSD-addiction comorbidity research, allowing the study of affective and substance-relevant responses to trauma cues. However, studies using traditional CRPs are time-consuming with high attrition rates due to repeat testing. Thus, we sought to test whether a single session semi-structured trauma interview could serve as a CRP in terms of eliciting theorized cue exposure effects on craving and affect measures. METHOD: Fifty regular cannabis users with trauma histories provided detailed descriptions of their most traumatic lifetime experience, and a neutral experience, according to an established interview protocol. Linear mixed models examined the effect of cue type (trauma vs. neutral) on affective and craving responses. RESULTS: As hypothesized, the trauma interview elicited significantly greater cannabis craving (and alcohol craving among the drinkers), and, greater negative affect among those with more severe PTSD symptoms, compared to the neutral interview. CONCLUSION: Results suggest an established semi-structured interview may function effectively as a CRP for use in trauma and addictions research.

The four-factor personality model and its qualitative correlates among opioid agonist therapy clients.

Background: The Four Factor Personality Vulnerability model identifies four specific personality traits (e.g., sensation seeking [SS], impulsivity [IMP], anxiety sensitivity [AS], and hopelessness [HOP]) as implicated in substance use behaviors, motives for substance use, and co-occurring psychiatric conditions. Although the relationship between these traits and polysubstance use in opioid agonist therapy (OAT) clients has been investigated quantitatively, no study has examined the qualitative expression of each trait using clients' voice. Method: Nineteen Methadone Maintenance Therapy (MMT) clients (68.4% male, 84.2% white, mean age[SD] = 42.71 [10.18]) scoring high on one of the four personality traits measured by the Substance Use Risk Profile Scale [SURPS] completed a semi-structured qualitative interview designed to explore their lived experience of their respective trait. Thematic analysis was used to derive themes, which were further quantified using content analysis. Results: Themes emerging from interviews reflected (1) internalizing and externalizing symptoms, (2) adversity experiences, and (3) polysubstance use. Internalizing symptoms subthemes included symptoms of anxiety, fear, stress, depression, and avoidance coping. Externalizing subthemes included anger, disinhibited cognitions, and anti-social and risk-taking behaviors. Adverse experiences subthemes included poor health, poverty, homelessness, unemployment, trauma, and conflict. Finally, polysubstance use subthemes include substance types, methods of use, and motives. Differences emerged between personality profiles in the relative endorsement of various subthemes, including those pertaining to polysubstance use, that were largely as theoretically expected. Conclusion: Personality is associated with unique cognitive, affective, and behavioral lived experiences, suggesting that personality may be a novel intervention target in adjunctive psychosocial treatment for those undergoing OAT.

Investigating predictors of problematic alcohol, cannabis, and nicotine use among legal users of all three substances.

Background: The three most used substances-alcohol, cannabis, and nicotine-are frequently concurrently. Use of each substance has been connected to an increased probability of use of the other substances, and the problematic use of each substance has been linked to demographic factors, substance use factors, and personality. However, little is known about which risk factors are most important for consumers of all three substances. This study examined the extent to which various factors are associated with dependence on alcohol, cannabis, and/or nicotine in users of all three substances. Methods: 516 Canadian adults with past month use of alcohol, cannabis, and nicotine completed online surveys querying their demographics, personality, substance use history, and levels substance dependence. Hierarchical linear regressions were used to determine which factors best predicted levels of dependence on each substance. Results: Alcohol dependence was associated with levels of cannabis and nicotine dependence, and impulsivity, with 44.9% of variance explained. Cannabis dependence was predicted by alcohol and nicotine dependence levels, impulsivity, and the age of onset of cannabis use, with 47.6% of variance explained. Nicotine dependence was best predicted by alcohol and cannabis dependence levels, impulsivity, and dual use of cigarettes and e-cigarettes, with 19.9% of variance explained. Conclusions: Alcohol dependence, cannabis dependence, and impulsivity were the strongest predictors for dependence on each of the substances. A strong relationship between alcohol and cannabis dependence was evident, warranting further research.

Perceptions about THC and CBD effects among adults with and without prior cannabis experience.

BACKGROUND: Cannabis is associated with a range of therapeutic and non-therapeutic, positive and negative effects. While some benefits and harms may be specific to individual cannabinoid constituents (THC, CBD), individual expectancies may also play a role. OBJECTIVES: Evaluate the extent to which individuals hold expectancies about the effects of CBD, THC, and THC & CBD combined, and whether this differs with prior cannabis experience. METHODS: Canadian adults (N = 345; n = 58 no prior cannabis use, n = 287 prior cannabis use) completed a Qualtrics survey. Participants provided information regarding their expectancies about the effects of cannabinoids (THC, CBD, THC & CBD combined) via a 15-item questionnaire, which included various therapeutic (e.g., helps with pain) and non-therapeutic positive (e.g., enhances positive feelings) and negative (e.g., risk for addiction) effects. They recorded their perceptions about the effects of each cannabinoid on a scale (0="definitely not true", 10="definitely true"). Data was analyzed using linear mixed models. RESULTS: For most therapeutic effects, CBD-containing products (CBD, THC & CBD) were rated higher than THC. For most positive and negative non-therapeutic effects, THC-containing products (THC, THC & CBD) were rated higher than CBD. Those with prior cannabis use (vs no prior use) rated all cannabinoids higher regarding their association with many therapeutic and positive effects, while endorsing weaker expectancies about their role in some negative effects. CONCLUSIONS: Adults endorsed stronger expectancies that CBD-containing products are responsible for producing a rage of therapeutic effects. Those with prior cannabis use experience tended to emphasize the benefits and minimize potential harmful effects of cannabinoids.

Dual users' perceptions of the addictive properties of cigarettes versus E-cigarettes.

INTRODUCTION: Electronic cigarettes ("e-cigarettes") are commonly promoted as a less-harmful alternative to combustible cigarettes, yet many individuals concurrently use both products ("dual users"). Little is known about the extent to which dual users' perceptions of the addictive properties of these products differ, or to what extent there are differences in the factors that elicit craving for each product. METHODS: An online survey evaluated beliefs about the addictive properties of cigarettes vs e-cigarettes and the situational and affective precipitants of product craving, on a scale from 1 to 10, in a sample of Canadian adults that reported past-month use of combustible and e-cigarettes (N = 175; 79 female). RESULTS: Participants rated cigarettes as more addictive than e-cigarettes, and on average reported higher levels of dependence on combustible cigarettes. While the addictive properties of both combustible and e-cigarettes were largely attributed to nicotine, non-nicotine factors (e.g. flavouring, other non-nicotine ingredients) were believed to make a relatively stronger contribution to the addictive properties of e-cigarettes, particularly among women. Participants reported greater increases in craving for combustible cigarettes in response to negative affective states and situational factors, and these effects were strongest among participants that displayed greater dependence on combustible tobacco relative to e-cigarettes. CONCLUSIONS: Dual users perceived cigarettes to be more addictive than e-cigarettes and attributed the addictive properties of each product to different factors. Further, cravings for combustible cigarettes were more strongly linked to certain negative affective states and situational factors relative to e-cigarettes. Findings suggest that there may be limited substitutability between combustible and e-cigarettes.

1-(Hex-5-en-1-yl)-4-{[3-methyl-2,3-di-hydro-1,3-benzo-thia-zol-2-yl-idene]meth-yl}quinolin-1-ium iodide monohydrate.

The title thia-zole orange derivative, bearing an alkene substituent, crystallized as a monohydrate of its iodide salt, namely, (Z)-1-(hex-5-en-1-yl)-4-{[3-methyl-2,3-di-hydro-1,3-benzo-thia-zol-2-yl-idene]meth-yl}quinolin-1-ium iodide monohydrate, C24H25N2S+·I-·H2O. The packing features aromatic π-stacking and van der Waals inter-actions. The water mol-ecule of crystallization inter-acts with the cation and anion via O-H⋯N and O-H⋯I hydrogen bonds, respectively.

The impacts of caffeine administration, expectancies, and related stimuli on coffee craving, withdrawal, and self-administration.

BACKGROUND: Caffeine is the most commonly consumed psychoactive substance, yet its potential reinforcing properties have been understudied. AIMS: This study examined the impact of caffeine administration and expectancy on coffee-related craving, withdrawal, and cue reactivity via a balanced-placebo design. METHODS: Following 18-h caffeine abstinence, 65 daily coffee consumers (54% male) received either caffeine-containing (100 mg) or placebo gum, along with either accurate or inaccurate information regarding the gum's caffeine content. Participants were exposed to neutral and coffee-related stimuli using different sensory modalities (visual and combined auditory/olfactory). Craving, withdrawal, and heart rate were assessed at baseline and after each cue presentation. Following the cue-reactivity assessments, participants were provided with an opportunity to self-administer units of coffee. RESULTS: Caffeine expectancy was associated with reduced subjective withdrawal 30 min following the gum administration but was not significantly impacted by actual caffeine administration. The presentation of coffee-related cues was found to increase self-reported craving and heart rate, regardless of the expectation that caffeine had been administered. Visual, but not auditory/olfactory, cue reactivity appeared blunted when participants received a prior dose of caffeine. Prior caffeine ingestion also reduced the probability of subsequent coffee self-administration. CONCLUSION: To our knowledge, this is the first examination of the impact of caffeine administration and expectancy on cue-elicited coffee craving and coffee consumption. Although there was some evidence that caffeine expectancy and administration were found to impact subjective withdrawal and self-administration respectively, neither was found to exert strong consistent effects on cue reactivity.

Craving and emotional responses to trauma and cannabis cues in trauma-exposed cannabis users: Influence of PTSD symptom severity.

Conditioned craving to trauma cues and avoidance learning have both been implicated in the high concurrence of trauma-related distress and substance misuse. Using a cue-exposure paradigm involving personalized trauma, cannabis, and neutral cues, we examined if conditioned craving and/or elevated negative affect to trauma cues are mechanisms linking PTSD and cannabis use disorder. Fifty-one trauma-exposed cannabis users were randomly presented the three cue types. Craving and emotional responses were evaluated after each cue using the Marijuana Craving Questionnaire-Short Form (Heishman et al., 2001) and the Positive and Negative Affect Schedule (Watson et al., 1988). Relief cannabis craving (compulsivity and emotionality) was significantly higher after trauma than cannabis and neutral cues (p's < 0.001) and was also higher among those with more severe PTSD symptoms (p's < 0.05). The relationship between PTSD symptom severity and cannabis craving was stronger after trauma than cannabis cues for the compulsivity component of craving (p < .05). Relief craving was also higher after the cannabis cue than after the neutral cue (expectancy and purposefulness; p < .001). Negative affect was significantly higher: after trauma than cannabis and neutral cues (p's < 0.001); and among those with more severe PTSD symptoms (p < . 005). Positive affect was significantly lower after trauma than cannabis cues (p < .05). Trauma cue exposure might promote cannabis misuse through conditioned craving as well as the desire to relieve negative affect. Conditioned cannabis craving involving an uncontrollable compulsion to use cannabis in response to trauma reminders appears particularly likely among cannabis users with more severe PTSD symptoms.

Posttraumatic Stress Disorder Symptoms and Coping Motives are Independently Associated with Cannabis Craving Elicited by Trauma Cues.

Cannabis use is common among individuals with posttraumatic stress disorder (PTSD), although its use can ultimately worsen PTSD outcomes. Cannabis-use coping motives may help explain the PTSD-cannabis relationship. Frequent pairing of trauma cues with substance use to cope with negative affect can lead to conditioned substance craving. For the present cue-reactivity study, we examined if PTSD symptoms were associated with cannabis craving elicited by a personalized trauma cue and explored whether coping motives mediated this hypothesized relationship; enhancement motives were included as a comparison mediator. Participants (N = 51) were trauma-exposed cannabis users who completed validated assessments on PTSD symptom severity and cannabis use motives. They were then exposed to a personalized audiovisual cue based on their own traumatic experience after which they responded to questions on a standardized measure regarding their cannabis craving. The results demonstrated that PTSD symptoms were associated with increased cannabis craving following trauma cue exposure, B = 0.43, p = .004, 95% CI [0.14, 0.72]. However, the results did not support our hypothesis of an indirect effect through general coping motives, indirect effect = .03, SE = .08, 95% CI [-.10, .21]. We found an independent main effect of general coping motives on trauma cue-elicited cannabis craving, B = 1.86, p = .002, 95% CI [0.72, 3.01]. These findings have important clinical implications suggesting that clinicians should target both PTSD symptoms and general coping motives to prevent the development of conditioned cannabis craving to trauma reminders in trauma-exposed cannabis users.

Different drugs come with different motives: Examining motives for substance use among people who engage in polysubstance use undergoing methadone maintenance therapy (MMT).

BACKGROUND: Substance use motives (i.e., reasons for using a substance) are thought to be the most proximal variable leading to substance use. These motives have been described by various typologies, the most well known being the four-factor drinking motives model which separates motives into enhancement, social, coping, and conformity (Cooper, 1994). Although extensively studied in adult community samples, motives for use have less commonly been investigated among populations at a later stage of addiction, where polysubstance use is more common. Moreover, because the motives literature has largely focused on drinking motives, it is not clear whether existing findings can also be applied to other substances (Cooper et al., 2016). METHODS: Using Zero-inflated beta Bayesian linear mixed modeling, we investigated the stability of seven distinct substance use motives (enhancement, social, expansion, coping with anxiety, coping with depression, coping with withdrawal, and conformity) across six different drug categories (tobacco, alcohol, cannabis, opioids, stimulants, and tranquilisers) to determine the extent to which drug class can influence motive endorsement. One-hundred-and-thirty-eight methadone maintenance therapy (MMT) clients (F = 34.1%; M = 65.9%; age = 40.18 years) completed a novel short-form polysubstance motives questionnaire. RESULTS: External motives (i.e., conformity and social motives) were the most stable across drug categories, while all internal motives (i.e., enhancement, expansion, and all three coping motives) demonstrated varying levels of inter-drug variability. CONCLUSIONS: These findings have important implications for prevention and intervention strategies among people who engage in polysubstance use, highlighting the importance of both universal and substance-specific programming.

Evaluating cannabidiol (CBD) expectancy effects on acute stress and anxiety in healthy adults: a randomized crossover study.

RATIONALE: Cannabidiol (CBD) has been reported to attenuate stress and anxiety, but little is known about the extent to which such effects result from pharmacological versus expectancy factors. OBJECTIVES: We evaluated whether CBD expectancy alone could influence stress, anxiety, and mood, and the extent to which beliefs regarding CBD effects predicted these responses. METHODS: In this randomized crossover study, 43 health adults (23 women) attended two experimental laboratory sessions, where they self-administered CBD-free hempseed oil sublingually. During one session, they were (incorrectly) informed that the oil contained CBD and in the other session, that the oil was CBD-free. Following administration, participants engaged in the Maastricht Acute Stress Test (MAST). Heart rate variability (HRV) was assessed continuously, and subjective state was assessed at baseline, 90-min following oil administration, immediately following the MAST, and after a 10-min recovery period. RESULTS: The CBD expectancy condition was associated with increased sedation as well as with changes in HRV that were consistent with heightened anticipatory stress regulation. Overall, there were no systematic changes in subjective stress, or anxiety, according to expectancy condition. However, participants who endorsed strong a priori beliefs that CBD has anxiolytic properties reported significantly diminished anxiety in the CBD expectancy condition. CONCLUSIONS: CBD expectancy alone impacted several subjective and physiological responses. Additionally, expectancy-related factors were implicated in anxiolytic effects of CBD for those who believed it was helpful for such purposes, emphasizing the need to measure and control for CBD-related expectancies in clinical research that involves the administration of CBD.

The relative impact of acute nicotine and tobacco administration on craving, withdrawal, and cigarette self-administration in dependent and nondependent smokers.

Negative reinforcement mechanisms, wherein individuals smoke at regular intervals to ameliorate craving and withdrawal, are integral to persistent smoking. This is consistent with the behavior of dependent smokers but does not fully account for the behavior of intermittent smokers, who do not smoke enough to maintain steady nicotine levels. This study examined the independent and combined impacts of nicotine and tobacco consumption on cigarette craving, withdrawal, and subsequent smoking behavior in 18 nondependent light and intermittent smokers (LITS) and 23 daily, dependent smokers (DDS). Participants administered conventional nicotine-containing cigarettes (NC; 18.9 mg nicotine; 1.41 mg deliverable), reduced nicotine content cigarettes (RNC; 0.4 mg nicotine, 0.05 mg deliverable), nicotine inhalers (NI; 10 mg nicotine, 4 mg deliverable), or nicotine-free inhalers (NFI) across 4 sessions following overnight abstinence. Participants rated craving and withdrawal before and after product administration, then completed a cigarette self-administration task. For cigarette self-administration, neither smoking status nor product affected latency to initiate smoking; however, LITS were more likely to abstain from smoking and administered fewer puffs than DDS. Across participants, pharmacologically active products (NC, RNC, NI) were associated with fewer cigarette puffs than the NFI. For subjective measures, only cigarettes (NC, RNC) reduced craving in both LITS and DDS. NC, RNC, and NI reduced withdrawal in DDS, while withdrawal remained at floor levels across time points among LITS. While subjective ratings and smoking behavior were largely comparable across LITS and DDS, differing patterns of withdrawal symptoms suggest that dependent smoking is motivated by negative reinforcement while nondependent smoking is not. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Non-pharmacological Considerations in Human Research of Nicotine and Tobacco Effects: A Review.

Human research of nicotine and tobacco effects demonstrates that non-pharmacological factors may systematically affect responses to administered substances and inert placebos. Failure to measure or manipulate these factors may compromise study reliability and validity. This is especially relevant for double-blind placebo-controlled research of nicotine, tobacco, and related substances. In this article, we review laboratory-based human research of the impact of non-pharmacological factors on responses to tobacco and nicotine administration. Results suggest that varying beliefs about drug content and effects, perceptions about drug use opportunities, and intentions to cease drug use systematically alter subjective, behavioral, and physiological responses to nicotine, tobacco, and placebo administration. These non-pharmacological factors should be considered when designing and interpreting the findings of human research of nicotine and tobacco effects, particularly when a double-blind placebo-controlled design is used. The clinical implications of these findings are discussed, and we propose methodological strategies to enhance the reliability and validity of future research. IMPLICATIONS: Growing research demonstrates that non-pharmacological factors systematically alter responses to acute nicotine, tobacco, and placebo administration. Indeed, varying beliefs about nicotine and/or tobacco administration and effects, differing perceptions about nicotine and/or tobacco use opportunities, and inconsistent motivation to quit smoking have been found to exert important influences on subjective, physiological, and behavioral responses. These variables are infrequently measured or manipulated in nicotine and tobacco research, which compromises the validity of study findings. Incorporating methodological strategies to better account for these non-pharmacological factors has the potential to improve the quality of addiction research and treatment.

The impacts of actual and perceived nicotine administration on insula functional connectivity with the anterior cingulate cortex and nucleus accumbens.

BACKGROUND: Changes in resting state functional connectivity between the insula and dorsal anterior cingulate cortex as well as between the insula and nucleus accumbens have been linked to nicotine withdrawal and/or administration. However, because many of nicotine's effects in humans appear to depend, at least in part, on the belief that nicotine has been administered, the relative contribution of nicotine's pharmacological actions to such effects requires clarification. AIMS: The purpose of this study was to examine the impacts of perceived and actual nicotine administration on neural responses. METHODS: Twenty-six smokers were randomly assigned to receive either a nicotine inhaler (4 mg deliverable) or a nicotine-free inhaler across two sessions. Inhaler content instructions (told nicotine vs told nicotine-free) differed across sessions. Resting state functional connectivity between sub-regions of the insula and the dorsal anterior cingulate cortex and nucleus accumbens was measured using magnetic resonance imaging before and after inhaler administration. RESULTS: Both actual and perceived nicotine administration independently altered resting state functional connectivity between the anterior insula and the dorsal anterior cingulate cortex, with actual administration being associated with decreased resting state functional connectivity, and perceived administration with increased resting state functional connectivity. Actual nicotine administration also contralaterally reduced resting state functional connectivity between the anterior insula and nucleus accumbens, while reductions in resting state functional connectivity between the mid-insula and right nucleus accumbens were observed when nicotine was administered unexpectedly. Changes in resting state functional connectivity associated with actual or perceived nicotine administration were unrelated to changes in subjective withdrawal and craving. Changes in withdrawal and craving were however independently associated with resting state functional connectivity between the nucleus accumbens and insula. CONCLUSIONS: Our findings highlight the importance of considering non-pharmacological factors when examining drug mechanisms of action.

Context matters: Characteristics of solitary versus social cannabis use.

INTRODUCTION AND AIMS: Given the increase in cannabis availability and use in North America, identification of risk factors for cannabis use and dependence is paramount. One factor that may be associated with various cannabis-related adverse outcomes is the context in which it is used. This secondary analysis study sought to examine the extent to which the social context of cannabis use is related to patterns of use and associated harms. DESIGN AND METHODS: One hundred and eighty-eight adult cannabis users were community-recruited in Halifax, Canada. Participants took part in a face-to-face structured interview where they provided information about the social context of their most recent cannabis-using occasion and about their patterns of, and motives for, cannabis use. RESULTS: Compared to individuals reporting their most recent cannabis-using occasion as social, solitary users (n = 55) were significantly more likely to screen positive for psychosis, endorse more symptoms of cannabis abuse/dependence, report using cannabis to cope, and use cannabis on more days within the previous 30 days. On the other hand, social users were significantly more likely to report using alcohol in addition to cannabis during their most recent cannabis-using occasion (all P < 0.05). DISCUSSION AND CONCLUSIONS: Results suggest that solitary cannabis use may be associated with specific motives for use and future adverse consequences. Findings from this study serve as a guide for future investigations which could ultimately inform public policy and the development of targeted harm-reduction strategies.