Tobacco-cannabis co-use among cancer patients and survivors: findings from 2 US cancer centers.

BACKGROUND: Cannabis use is prevalent among cancer patients and survivors and may provide some therapeutic benefits for this population. However, benefits may be attenuated when cannabis is co-used with tobacco, which is associated with more severe tobacco and cannabis use and adverse outcomes in noncancer populations. We compared cannabis use, primary mode of use, and therapeutic and/or nontherapeutic use among 3 groups of patients and survivors based on cigarette smoking status. METHODS: Survey data was collected from patients and survivors with cancer (n = 1732) at 2 US National Cancer Institute-designated cancer centers in states with varying cannabis regulatory policy. Prevalence of cannabis use (prior to diagnosis, after diagnosis, before treatment, after treatment), primary mode of use, and therapeutic and/or nontherapeutic use were assessed by cigarette smoking status (current, former, never) within and across centers using weighted bivariate analyses and multivariable logistic regression, controlling for demographic and clinical variables. RESULTS: Current cigarette use was associated with greater rates of cannabis use prior to diagnosis, after diagnosis, during treatment, and after treatment within each center (all P < .001) and in pooled analyses across centers (all P < .001). Primary mode of use, knowledge of cannabis products, and therapeutic and/or nontherapeutic use also statistically differed by tobacco status and study site. CONCLUSIONS: Results illustrate the importance of conducting assessments for both tobacco and cannabis use among cancer patients during and after cancer treatment, regardless of the cannabis regulatory environment. Given previous data indicating harms from co-use and continued tobacco use during cancer treatment, this issue introduces new priorities for cancer care delivery and research.

Prenatal tobacco and tobacco-cannabis co-exposure: Relationship with attention and memory in middle childhood.

We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9-12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (n = 133; n = 34 non-substance exposed, n = 37 exposed to tobacco only, n = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (p = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely.

The Cannabis Gray Market: A Case for Cannabis Regulatory Science Research.

The cannabis gray market poses significant public health concerns and remains a major threat to consumer and/or potential consumer uptake of regulated cannabis markets in jurisdictions with legal state-sponsored cannabis programs. In this perspective, we provide an overview of the cannabis gray market, and describe an integrated epidemiological and regulatory science framework to study the gray market. Using tobacco regulatory science as a guide, we introduce example cannabis regulatory science research activities as a means to improve the field's understanding of the cannabis gray market. Cannabis regulatory science is a developing field that can improve our understanding of the cannabis regulatory ecosystem and provide regulatory officials and policymakers alike with much needed data to inform regulatory decision-making and improve the success and uptake of state-sponsored cannabis programs.

Self-reported knowledge of tetrahydrocannabinol and cannabidiol concentration in cannabis products among cancer patients and survivors.

PURPOSE: Cannabis use may introduce risks and/or benefits among people living with cancer, depending on product type, composition, and nature of its use. Patient knowledge of tetrahydrocannabinol (THC) or cannabidiol (CBD) concentration could provide information for providers about cannabis use during and after treatment that may aide in risk and benefit assessments. This study aimed to examine knowledge of THC or CBD concentration among patients living with cancer who consume cannabis, and factors associated with knowledge of cannabinoid concentrations. METHODS: People living with cancer who consumed cannabis since their diagnosis (n = 343) completed an anonymous, mixed-mode survey. Questions assessed usual mode of delivery (MOD), knowledge of THC/CBD concentration, and how source of acquisition, current cannabis use, and source of instruction are associated with knowledge of THC/CBD concentration. Chi-square and separate binary logistic regression analyses were examined and weighted to reflect the Roswell Park patient population. RESULTS: Less than 20% of people living with cancer had knowledge of THC and CBD concentration for the cannabis products they consumed across all MOD (smoking- combustible products, vaping- vaporized products (e-cigarettes), edibles-eating or drinking it, and oral- taking by mouth (pills)). Source of acquisition (smoking-AOR:4.6, p < 0.01, vaping-AOR:5.8, p < 0.00, edibles-AOR:2.6, p < 0.04), current cannabis use (edibles-AOR:5.4, p < 0.01, vaping-AOR: 11.2, p < 0.00, and oral-AOR:9.3, p < 0.00), and source of instruction (vaping only AOR:4.2, p < 0.05) were found to be variables associated with higher knowledge of THC concentration. CONCLUSION: Self-reported knowledge of THC and CBD concentration statistically differed according to MOD, source of acquisition, source of instruction, and current cannabis use.

Transitioning to Remote Clinic Visits in a Smoking Cessation Trial During the COVID-19 Pandemic: Mixed Methods Evaluation.

BACKGROUND: The pandemic of SARS-CoV-2, which causes COVID-19, has caused disruptions in ongoing clinical trials and is expected to accelerate interest in conducting research studies remotely. OBJECTIVE: A quasi-experimental, mixed methods approach was used to examine the rates of visit completion as well as the opinions and experiences of participants enrolled in an ongoing clinical trial of smoking cessation who were required to change from in-person clinic visits to remote visits using video or telephone conferencing due to the COVID-19 pandemic. METHODS: For quantitative comparisons, we used a quasi-experimental design, comparing a cohort of participants followed during the pandemic (n=23, COVID-19 cohort) to a comparable cohort of participants followed over a similar time period in the calendar years 2018 and 2019 (n=51, pre-COVID-19 cohort) to examine the rates of completion of scheduled visits and biospecimen collection. For the qualitative component, interviews were conducted with participants who experienced the transition from in-person to remote visits. RESULTS: Participants in the COVID-19 cohort completed an average of 83.6% of remote clinic visits (95% CI 73.1%-91.2%), which was not significantly different than the in-person completion rate of 89.8% in the pre-COVID-19 cohort. Participants in the COVID-19 cohort returned an average of 93.2% (95% CI 83.5%-98.1%) of saliva specimens for remote clinic visits completed, which was not significantly different than the in-person saliva specimen completion rate of 100% in the pre-COVID-19 cohort. Two broad themes emerged from the qualitative data: (1) the benefits of remote visits and (2) the challenges of remote counseling compared to in-person counseling. Despite limited experience with telehealth prior to this transition, most participants expressed a willingness to engage in remote visits in the future. CONCLUSIONS: Even in the context of a rapid transition from in-person to remote visits necessitated by the COVID-19 pandemic, rates of visit completion and return of biospecimens remained high. Participants were generally accepting of the transition. Further research is needed to identify the optimal mix of in-person and remote visits beyond the pandemic context and to better understand how these changes may impact study outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262662; https://clinicaltrials.gov/ct2/show/study/NCT03262662.

Making lemonade from SARS coronavirus-2 lemons: Transitioning a smoking cessation trial to a virtual platform.

Clinical trials represent an essential component of improving treatment for substance use disorders (SUD). The SARS coronavirus-2 pandemic disrupted our ongoing clinical trial of smoking cessation and forced us to rapidly implement changes to assure participants access to ongoing counseling and monitoring via telephone calls and/or video chat sessions. Our experiences suggest that this pandemic will lead to changes for both future clinical trial participants and project staff. While challenges remain, it will be important to assessing the impact of these changes with regard to participant experiences and treatment outcomes.

Acute Pharmacokinetic Profile of Smoked and Vaporized Cannabis in Human Blood and Oral Fluid.

Currently, an unprecedented number of individuals can legally access cannabis. Vaporization is increasingly popular as a method to self-administer cannabis, partly due to perception of reduced harm compared with smoking. Few controlled laboratory studies of cannabis have used vaporization as a delivery method or evaluated the acute effects of cannabis among infrequent cannabis users. This study compared the concentrations of cannabinoids in whole blood and oral fluid after administration of smoked and vaporized cannabis in healthy adults who were infrequent users of cannabis. Seventeen healthy adults, with no past-month cannabis use, self-administered smoked or vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10 and 25 mg in six double-blind outpatient sessions. Whole blood and oral fluid specimens were obtained at baseline and for 8 h after cannabis administration. Cannabinoid concentrations were assessed with enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods. Sensitivity, specificity and agreement between ELISA and LC-MS-MS results were assessed. Subjective, cognitive performance and cardiovascular effects were assessed. The highest concentrations of cannabinoids in both whole blood and oral fluid were typically observed at the first time point (+10 min) after drug administration. In blood, THC, 11-OH-THC, THCCOOH and THCCOOH-glucuronide concentrations were dose-dependent for both methods of administration, but higher following vaporization compared with smoking. THC was detected longer in oral fluid compared to blood and THCCOOH detection in oral fluid was rare and highly erratic. For whole blood, greater detection sensitivity for ELISA testing was observed in vaporized conditions. Conversely, for oral fluid, greater sensitivity was observed in smoked sessions. Blood and/or oral fluid cannabinoid concentrations were weakly to moderately correlated with pharmacodynamic outcomes. Cannabis pharmacokinetics vary by method of inhalation and biological matrix being tested. Vaporization appears to be a more efficient method of delivery compared with smoking.

A cognitive model-based approach to testing mechanistic explanations for neuropsychological decrements during tobacco abstinence.

RATIONALE: Cigarette smokers often experience cognitive decrements during abstinence from tobacco, and these decrements may have clinical relevance in the context of smoking cessation interventions. However, limitations of the behavioral summary statistics used to measure cognitive effects of abstinence, response times (RT) and accuracy rates, may restrict the field's ability to identify robust abstinence effects on task performance and test mechanistic hypotheses about the etiology of these cognitive changes. OBJECTIVES: The current study explored whether a measurement approach based on mathematical models of cognition, which make the cognitive mechanisms necessary to perform choice RT tasks explicit, would be able to address these limitations. METHODS: The linear ballistic accumulator model (LBA: Brown and Heathcote, Cogn Psychol 57(3):153-178, 2008) was fit to an existing data set from a study that evaluated the impact of overnight abstinence on flanker task performance. RESULTS: The model-based analysis provided evidence that smokers' rates of mind wandering increased during abstinence, and was able to index this effect while controlling for participants' strategy changes that were related to the specific experimental paradigm used. CONCLUSION: Mind wandering is a putative explanation for cognitive withdrawal symptoms during smoking cessation and may be indexed using the LBA. More broadly, the use of formal model-based analyses in future research on this topic has the potential to allow for strong and specific tests of mechanistic explanations for these symptoms.

Co-use of cannabis, tobacco, and alcohol during adolescence: policy and regulatory implications.

Legislative reforms have legalized use of cannabis for medical and recreational purposes. Efforts to evaluate the public health impact of these changes have predominantly focused on determining whether liberalizing cannabis policies has increased cannabis use patterns. Co-use of cannabis and other licit substances, namely tobacco and alcohol, is common during the developmental period of adolescence, which is generally characterized by an increase in risk-taking and novelty-seeking. However, limited research has sought to evaluate the potential implications of reforms to medical and recreational cannabis laws on concurrent and simultaneous use of cannabis, tobacco, and alcohol during adolescence. The current report reviews the extant literature detailing the prevalence and outcomes associated with concurrent and simultaneous cannabis-tobacco and cannabis-alcohol use, including recent work that has examined how concurrent and simultaneous use may be influenced by cannabis reform. This review details how the cannabis landscape and cannabis retail marketplace have evolved and briefly summarizes the corresponding policy and regulatory challenges that have emerged. The report concludes with a focused cannabis co-use research agenda that adopts different strategies including behavioural economic, self-administration, and survey research methods.

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

BACKGROUND: There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. METHODS: Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. RESULTS: Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. CONCLUSIONS: Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders.

Acute Effects of Smoked and Vaporized Cannabis in Healthy Adults Who Infrequently Use Cannabis: A Crossover Trial.

Importance: Vaporization is an increasingly popular method for cannabis administration, and policy changes have increased adult access to cannabis drastically. Controlled examinations of cannabis vaporization among adults with infrequent current cannabis use patterns (>30 days since last use) are needed. Objective: To evaluate the acute dose effects of smoked and vaporized cannabis using controlled administration methods. Design, Setting, and Participants: This within-participant, double-blind, crossover study was conducted from June 2016 to January 2017 at the Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, and included 17 healthy adults. Six smoked and vaporized outpatient experimental sessions (1-week washout between sessions) were completed in clusters (order counterbalanced across participants); dose order was randomized within each cluster. Interventions: Cannabis containing Δ9-tetrahydrocannabinol (THC) doses of 0 mg, 10 mg, and 25 mg was vaporized and smoked by each participant. Main Outcomes and Measures: Change from baseline scores for subjective drug effects, cognitive and psychomotor performance, vital signs, and blood THC concentration. Results: The sample included 17 healthy adults (mean [SD] age, 27.3 [5.7] years; 9 men and 8 women) with no cannabis use in the prior month (mean [SD] days since last cannabis use, 398 [437] days). Inhalation of cannabis containing 10 mg of THC produced discriminative drug effects (mean [SD] ratings on a 100-point visual analog scale, smoked: 46 [26]; vaporized: 69 [26]) and modest impairment of cognitive functioning. The 25-mg dose produced significant drug effects (mean [SD] ratings, smoked: 66 [29]; vaporized: 78 [24]), increased incidence of adverse effects, and pronounced impairment of cognitive and psychomotor ability (eg, significant decreased task performance compared with placebo in vaporized conditions). Vaporized cannabis resulted in qualitatively stronger drug effects for most pharmacodynamic outcomes and higher peak concentrations of THC in blood, compared with equal doses of smoked cannabis (25-mg dose: smoked, 10.2 ng/mL; vaporized, 14.4 ng/mL). Blood THC concentrations and heart rate peaked within 30 minutes after cannabis administration and returned to baseline within 3 to 4 hours. Several subjective drug effects and observed cognitive and psychomotor impairments persisted for up to 6 hours on average. Conclusions and Relevance: Vaporized and smoked cannabis produced dose-orderly drug effects, which were stronger when vaporized. These data can inform regulatory and clinical decisions surrounding the use of cannabis among adults with little or no prior cannabis exposure. Trial Registration: ClinicalTrials.gov Identifier: NCT03676166.

Probing the Behavioral and Neurophysiological Effects of Acute Smoking Abstinence on Drug and Nondrug Reinforcement During a Cognitive Task.

INTRODUCTION: Smoking abstinence is theorized to increase smoking reinforcement and decrease nondrug reinforcement. A separate literature demonstrates the detrimental effects of abstinence on cognition. The present study integrates these two areas by examining the separate and combined effects of reinforcement and smoking abstinence on behavior and a neurophysiological index of response monitoring (ie, error-related negativity [ERN]) during a cognitive task. METHODS: After a screening visit, adult smokers attended two laboratory visits, once while smoking and once while abstinent. Participants completed a flanker task under cigarette-, money-, and no-reinforcement conditions. The initial 15 participants had an easier reaction time (RT) requirement; to ensure sufficient error rates for ERN computation, a harder RT deadline was employed for the remaining 21 participants. RESULTS: Smoking abstinence reduced speeded accuracy and ERN amplitude only among participants tested with the harder RT deadline. Cigarette and money reinforcement each increased speeded accuracy and ERN amplitude compared to no reinforcement. The effect of cigarette reinforcement tended to be greater during abstinence for speeded accuracy but not the ERN. The effect of money reinforcement was unaffected by abstinence. CONCLUSIONS: The impact of smoking abstinence on reinforcement may depend on task demands. However, the effects of cigarette and money reinforcement generalize well from operant paradigms to cognitive tasks, fostering integration between the two literatures. Results provided modest evidence of abstinence-induced increases in smoking reinforcement; the absence of abstinence-induced reductions in nondrug reinforcement is consistent with recent work in suggesting that such effects are limited to a subset of sensory reinforcers. IMPLICATIONS: This study draws attention to the need for greater integration of reinforcement and cognition to better understand the mechanisms that contribute to smoking relapse. Results emphasize thoughtful consideration of the nature of the nondrug reinforcer(s) included in the study of smoking abstinence in addition to the levels of cognitive demand impacted by acute smoking abstinence.

Selection criteria limit generalizability of smoking pharmacotherapy studies differentially across clinical trials and laboratory studies: A systematic review on varenicline.

BACKGROUND: The selection criteria used in clinical trials for smoking cessation and in laboratory studies that seek to understand mechanisms responsible for treatment outcomes may limit their generalizability to one another and to the general population. METHODS: We reviewed studies on varenicline versus placebo and compared eligibility criteria and participant characteristics of clinical trials (N=23) and laboratory studies (N=22) across study type and to nationally representative survey data on adult, daily USA smokers (2014 National Health Interview Survey; 2014 National Survey on Drug Use and Health). RESULTS: Relative to laboratory studies, clinical trials more commonly reported excluding smokers who were unmotivated to quit and for specific medical conditions (e.g., cardiovascular disease, COPD), although both study types frequently reported excluding for general medical or psychiatric reasons. Laboratory versus clinical samples smoked less, had lower nicotine dependence, were younger, and more homogeneous with respect to smoking level and nicotine dependence. Application of common eligibility criteria to national survey data resulted in considerable elimination of the daily-smoking population for both clinical trials (≥47%) and laboratory studies (≥39%). Relative to the target population, studies in this review recruited participants who smoked considerably more and had a later smoking onset age, and were under-representative of Caucasians. CONCLUSIONS: Results suggest that selection criteria of varenicline studies limit generalizability in meaningful ways, and differences in criteria across study type may undermine efforts at translational research. Recommendations for improvements in participant selection and reporting standards are discussed.

The impact of pre-cessation varenicline on behavioral economic indices of smoking reinforcement.

BACKGROUND: Varenicline was developed to aid smoking cessation by reducing smoking reinforcement. The present study tests this reinforcement-reduction hypothesis among smokers preparing to quit. METHOD: After a one-week baseline, treatment-seeking smokers were randomized to receive three weeks of varenicline or placebo (Weeks 2-4). During each of the four weeks of the study, smokers completed a hypothetical cigarette purchase task (CPT) via handheld devices in their natural environment. Behavioral economic measures of simulated smoking if cigarettes were free (demand intensity), sensitivity of consumption to increasing price (elasticity), and price at which purchases would drop to 0 (breakpoint) were estimated. RESULTS: The exponential demand equation fit the purchase task data well across subjects and time. As predicted, demand intensity decreased and sensitivity to price (elasticity) increased over time. However, changes in demand intensity did not differ by treatment group. Contrary to our hypothesis that varenicline would increase sensitivity to price, the placebo group tended to become more elastic in their purchases during Weeks 2 and 3; the groups did not differ in elasticity at Week 4. Breakpoint did not vary by group, time, or their interaction. CONCLUSION: Simulated smoking demand can be validly assessed in the natural environment of treatment-seeking smokers. Simulated demand indices of smoking reinforcement diminished as smokers approached their target quit date. However, there was no evidence that varenicline facilitated these changes over a three-week period, leaving open the mechanisms by which varenicline reduces smoking rate prior to cessation and improves long-term abstinence.

The effects of acute abstinence from smoking and performance-based rewards on performance monitoring.

RATIONALE: Abstinence from smoking disrupts performance in multiple cognitive domains, and such cognitive effects may serve to maintain smoking behavior. Rather than having specific effects on a narrow domain of processing, abstinence may disrupt more general cognitive control processes and/or motivation. OBJECTIVES: The present study tested the prediction that overnight abstinence from smoking would disrupt a general performance monitoring system indexed via the error-related negativity (ERN). A secondary aim was to determine the extent to which performance-based monetary rewards improved the ERN among smokers and whether the effect of the reward was diminished during abstinence. METHODS: The ERN was assessed during a flanker task among 25 heavy, non-treatment-seeking smokers both when smoking as usual and after overnight abstinence; reward and no-reward trial blocks occurred within each session. RESULTS: As predicted, mean ERN amplitude was reduced during abstinence. The ERN was enhanced by reward; this effect did not vary with smoking abstinence. CONCLUSION: This study provides novel data which suggest that acute abstinence from smoking disrupts a neurophysiological index of a general performance monitoring system that is involved in a range of cognitive functions. The ERN may be a useful complement to narrow-band cognitive studies of abstinence and interventions designed to target cognition in addiction. Because the ERN was concurrently sensitive to abstinence and performance-based incentives, it may be particularly useful for examining the interplay of cognition and motivation in smoking and smoking cessation.

The effects of varenicline on attention and inhibitory control among treatment-seeking smokers.

RATIONALE: Varenicline represents a new class of smoking cessation aids that has different mechanisms of action that are unique from bupropion or nicotine replacement therapies. An improved understanding of these mechanisms may lead to greater treatment success in quitting smoking. OBJECTIVES: We examined the effects of steady-state varenicline on attention and inhibitory control among adult treatment-seeking smokers. METHODS: Adult smokers enrolled in a randomized clinical trial received either 4 weeks of pre-quit varenicline (n = 31) or 3 weeks of placebo (n = 26) followed by 1 week of standard varenicline treatment. Participants in the present work completed cognitive assessments at a baseline session (prior to treatment) and again 3 weeks later (during active treatment). At both sessions, participants completed the stop signal task to assess both lapses in attention and inhibitory control. RESULTS: Analyses indicated that varenicline improved lapses in attention compared to placebo. There were no significant differences observed between groups at either session for inhibitory control. CONCLUSIONS: The present study demonstrated that varenicline improves lapses in attention among treatment-seeking smokers preparing to make a quit attempt. These findings suggest that the domain of attention may be a good candidate for larger studies of the role of improved cognition in understanding the mechanisms of varenicline treatment for smoking cessation.