Key Points Question How does smoked and vaporized cannabis acutely influence subjective drug effects, cognitive and psychomotor performance, and cardiovascular measures in healthy adults who infrequently use cannabis (>30 days since last use)? Findings In a crossover trial of 17 healthy adults, inhalation of smoked and vaporized cannabis containing 10 mg of Δ9-tetrahydrocannabinol (THC) produced discriminative drug effects and modest impairment of cognitive functioning, while inhalation of a 25-mg dose of THC was associated with pronounced drug effects, increased incidence of adverse effects, and significant impairment of cognitive and psychomotor ability. Vaporized cannabis produced greater pharmacodynamic effects and higher concentrations of THC in blood compared with equal doses of smoked cannabis. Meaning Significant, sometimes adverse, drug effects can occur at relatively low THC doses in infrequent cannabis users, and accordingly these data should be considered with regard to regulation of retail cannabis products and education for individuals initiating cannabis use.

Preclinical research and learning theory suggest that a longer duration of varenicline treatment prior to the target quit date (TQD) should reduce smoking rates before cessation and improve abstinence outcomes. A double-blind RCT tested this hypothesis among 60 smokers randomized to either Extended (4 weeks of pre-TQD varenicline) or standard run-in (3 weeks of placebo, 1 week of pre-TQD varenicline); everyone received 11 weeks of post-TQD varenicline and brief counseling. During the pre-quit run-in, the reduction in smoking rates was greater among the Extended group (42% vs. 24%, p<0.01) and this effect was greater among women (57% vs. 26%, p=0.001). Continuous abstinence during the final four weeks of treatment was enhanced among women in the Extended group (67% vs. 35%). While these data suggest that extending pre-quit varenicline reduces smoking during the pre-quit period and may further enhance cessation rates, confirmatory evidence is needed from larger clinical trials. Trial Registration: www.clinicaltrials.gov identifier: NCT00835900

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.

Purpose of Review This report provides an updated overview of pre-clinical and clinical research on the etiology and biological substrates of the cannabis withdrawal syndrome. Recent Findings Long-term cannabis use is associated with downregulation of type-1 cannabinoid receptors (CB1). Reduced CB1 receptor density is related to increased withdrawal during early abstinence, and the reduction in CB1 receptor density reverses with extended abstinence. Females have been shown to have increased rate and severity of a subset of cannabis withdrawal symptoms compared with men. Summary Recent studies have extended knowledge of the biological processes and individual difference variables that influence cannabis withdrawal. However, caveats include small sample sizes in clinical studies, participant samples that are predominantly male, and limited examinations of endocannabinoids, enzymes that degrade endocannabinoids, negative allosteric modulators, and other neurobiological systems that may directly impact cannabis withdrawal symptom expression.

Background: Prior controlled cannabis research has mostly focused on smoked cannabis and predominantly included frequent cannabis users. Oral cannabis products ("edibles") make up a large and growing segment of the retail cannabis market. This study sought to characterize the pharmacodynamic effects of oral cannabis among infrequent cannabis users.Methods: Seventeen healthy adults who had not used cannabis for at least 60 days completed four experimental sessions in which they consumed a cannabis-infused brownie that contained 0, 10, 25, or 50 mg THC. Subjective effects, vital signs, cognitive/psychomotor performance, and blood THC concentrations were assessed before and for 8 h after dosing.Results: Relative to placebo, the 10 mg THC dose produced discriminable subjective drug effects and elevated heart rate but did not alter cognitive/psychomotor performance. The 25 and 50 mg THC doses elicited pronounced subjective effects and markedly impaired cognitive and psychomotor functioning compared with placebo. For all active doses, pharmacodynamic effects did not manifest until 30 -60 min after ingestion, and peak effects occurred 1.5 -3 h postadministration. Blood THC levels were significantly correlated with some pharmacodynamic drug effects, but were substantially lower than what is typically observed after cannabis inhalation. Conclusion:Ingestion of oral cannabis dose-dependently altered subjective drug effects and impaired cognitive performance. Unlike inhaled forms of cannabis for which acute effects occur *

Substance use disorders (SUDs) are one of the most prevalent psychiatric conditions and represent a significant public health concern. Substantial research has identified key processes related to reinforcement and cognition for the development and maintenance of SUDs, and these processes represent viable treatment targets for psychosocial and pharmacological interventions. Research on SUD treatments has suggested that most approaches are comparable in effectiveness. As a result, recent work has focused on delineating the underlying mechanisms of behavior change that drive SUD treatment outcome. Given the rapid fluctuations associated with the key neurocognitive processes associated with SUDs, high-temporal-resolution measures of human brain processing, namely event-related potentials (ERPs), are uniquely suited to expand our understanding of the underlying neural mechanisms of change during and after SUD treatment. The value of ERPs in the context of SUD treatment are discussed along with work demonstrating the predictive validity of ERPs as biomarkers of SUD treatment response. Example associations between multiple ERP components and psychosocial and/or pharmacological treatment outcome include the P3a and P3b (in response to neutral and substance-related cues), the attention-related negativities (e.g., N170, N200), the late positive potential, and the error-related negativity. Also addressed are limitations of the biomarker approach to underscore the need for research programs evaluating mechanisms of change. Finally, we emphasize the advantages of ERPs as indices of behavior change in SUD treatment and outline issues relevant for future directions in this context.

Recent approval of Epidiolex Ò (pharmaceutical cannabidiol/CBD) for the treatment of Lennox Gastaut syndrome (LGS) and Dravet syndrome highlights a therapeutic efficacy of CBD in the treatment of epilepsy. However, a large number of patients with epilepsy elect to use alternative artisanal CBD products due to cost or access constraints. Despite widespread availability and variety of these artisanal CBD products, studies evaluating their safety or efficacy are rare, making conclusions about clinical utility uncertain. The purpose of the present study was to evaluate cross-sectional and longitudinal associations of artisanal CBD product use with quality of life, mental health, healthcare utilization, and epilepsyspecific outcomes within a large, observational cohort of people with epilepsy. Participants who reported using artisanal CBD products at baseline (Artisanal CBD Users; n = 280) and participants who used no cannabis-based products (Controls; n = 138) completed web-based assessments evaluating psychiatric symptoms, healthcare utilization, and epilepsy-specific factors. Follow-up surveys were collected in a subset of participants (n = 190) following baseline assessment for longitudinal comparison. Crosssectionally, higher quality of life, lower psychiatric symptom severity, and improved sleep were observed among Artisanal CBD Users at baseline compared with Controls. Initiation of artisanal CBD product use was also related to improved health outcomes longitudinally. No group differences were observed for seizure control, but both groups included a high number of individuals with no past month seizures. Artisanal CBD Users reported significantly better epilepsy medication tolerability, use of fewer prescription medications overall, and reduced healthcare utilization compared with Controls. These findings are consistent with research indicating that practitioners recommending CBD in clinical care for epilepsy report integrating the use of CBD both as a means to improve patient quality of life as well as for seizure control.

The current project sought to examine the psychometric properties of a personality based measure (Substance Use Risk Profile Scale; SURPS: introversion-hopelessness, anxiety sensitivity, impulsivity, and sensation seeking) designed to differentially predict substance use preferences and patterns by matching primary personality-based motives for use to the specific effects of various psychoactive substances. Specifically, we sought to validate the SURPS in a clinical sample of substance users using cue reactivity methodology to assess current inclinations to consume a wide range of psychoactive substances. Using confirmatory factor analysis and correlational analyses, the SURPS demonstrated good psychometric properties and construct validity. Further, impulsivity and sensation-seeking were associated with use of multiple substances but could be differentiated by motives for use and susceptibility to the reinforcing effects of stimulants (i.e., impulsivity) and alcohol (i.e. sensation-seeking). In contrast, introversion-hopelessness and anxiety sensitivity demonstrated a pattern of use more focused on reducing negative affect, but were not differentiated based on specific patterns of use. Taken together, results suggests that among those receiving inpatient treatment for substance use disorders, the SURPS is a valid instrument for measuring four distinct personality dimensions that may be sensitive to motivational susceptibilities to specific patterns of alcohol and drug use.