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Background: In this review, we summarize current scientific knowledge on psychoactive cannabinoids synthesized from cannabidiol (CBD) and sold in the semi-legal market established in response to the passage of the US Agriculture Improvement Act of 2018, commonly known as the 2018 Farm Bill. The discussion focuses on recent developments that suggest this unregulated market may be fertile ground for a potential health crisis. Summary: Current research into CBD-derived cannabinoids is mainly limited to [Delta][sup.8]-tetrahydrocannabinol ([Delta][sup.8]-THC) products, with some recent publications beginning to explore O-acetyl-THC, a term describing the acetate ester of [Delta][sup.8]-THC or [Delta][sup.9]-THC, and its potential pulmonary toxicity. We advance the discussion on the CBD-derived cannabinoid market, shedding light on the introduction and associated dangers of novel cannabinoids, likely produced via fully synthetic routes using sidechain variants of CBD, with purportedly greater agonist activity at the human cannabinoid receptor 1 (as a source of euphorigenic activity) than [Delta][sup.9]-THC. We discuss the expanded incorporation of the acetate ester motif into other THC analogues. We also discuss the lack of regulatory oversight for the production of CBD-derived cannabinoids and the unlabeled presence of under-researched cannabinoids formed as reaction side products in the CBD-derived cannabinoid products being sold. Accordingly, we suggest approaches to monitoring the CBD-derived cannabinoid market and investigating the pharmacology of the cannabinoids being consumed. Finally, important epidemiological findings are discussed and future directions for research are suggested to call investigators to this critically understudied field. Key Messages: The CBD-derived cannabinoid market is growing internationally, and the market has diversified to include potent synthetic cannabinoids. The products sold on this unregulated market are under-researched despite growing availability and consumer interest. Ernest investigation of the pharmacology of these novel cannabinoids and the contents of CBD-derived cannabinoid products is critical for monitoring this potential source of another vaping-related epidemic. Keywords: Delta-8-tetrahydrocannabinol, Tetrahydrocannabiphorol, Hexahydroxycannabiphorol, Ketene, O-acetyl-trahydrocannabinol-O, Author(s): Charles N. Zawatsky; Sara Mills-Huffnagle; Corinne M. Augusto; Kent E. Vrana; Jennifer E. Nyland Introduction An unregulated market for novel psychoactive cannabinoids has proliferated in the wake of the [...]

Objectives: Use of Synthetic and designer products, including synthetic marijuana (SM), among adolescents poses a major risk to public health. Little is known about the motivating factors of synthetic substance use in adolescents. This study examined the motivations, predictors, perceived risks and benefits, and differences with SM versus natural marijuana among adolescents. Methods: Between April 2016 and May 2018, a convenience sample of adolescents receiving substance use treatment from a local counseling center completed an anonymous survey to assess the use of natural and synthetic marijuana use, the Strengths and Difficulties Questionnaire to assess levels of current psychiatric symptoms and the Community Assessment of Psychic Experiences-Positive Scale to assess symptoms of psychosis. Results: A total of 80 adolescents (age range of 14-18 years; 71% male; 53% Caucasian) completed the study. Of these, 39 (49%) reported natural marijuana use (natural marijuana users) and 41 (51%) reported both synthetic and natural marijuana use (dual users). The most commonly reported reasons for using SM were its low cost and reduced risk of detection. Participants who were familiar with SM and reported a desire to avoid detection on drug tests were likelier to use SM (all P <.05). Dual users reported more benefits and risks associated with SM use when compared to natural marijuana users (P ⩽.05). The use of SM also heightened the perceived medical risks of natural marijuana, including seizures and respiratory issues (P <.05), compared with natural marijuana users. While dual users self-reported more conduct (P =.009) and externalizing problems (P =.024) when compared to natural marijuana users, there were no group differences in psychotic symptoms, nor correlations with the frequency of synthetic or natural marijuana use and psychotic symptoms except that persecutory ideation correlated with the frequency of natural marijuana use during the past 12 months (rp = 0.28, P =.04). Conclusions: These results suggest that reports of cost savings, and lack of detection on urine drug screens are common reasons for SM use in adolescents despite being aware of the risks of using SM. Perceived benefits of using synthetics and other novel substances appear diverse, and merit further exploration as a better understanding of what motivates adolescents to use specific novel substances may guide prevention and treatment efforts. [ABSTRACT FROM AUTHOR]

Opioid addiction continues to be a crisis within the United States. Pharmacological treatments have been studied extensively and are considered superior treatment methods for opioid use disorder (OUD). Adjunctive therapy to pharmacological interventions, including peer recovery support services (PRSS), is also available for patients with OUD, but is less studied. PRSS are designed to provide individual coordination services for patients seeking recovery and treatment, administered by individuals who have lived through the substance use disorder and recovery process. An observational study looking at differences in demographics and treatment engagement between individuals with OUD who were and were not receiving PRSS was conducted. ANOVA and chi square analyses indicated no significant demographic differences between groups; however, additional ANOVA analyses demonstrated that patients receiving PRSS attended significantly more OUD medical appointments when compared to their non-PRSS counterparts, F(1, 275) = 8.72, p =.003. A negative binomial regression analysis indicated that receiving PRSS was associated with a greater number of OUD medical appointments attended, even after controlling for length of time in treatment. While these results suggest that PRSS may increase treatment engagement in patients with OUD, additional research that uses randomized designs is needed to examine the impact of PRSS on treatment engagement. [ABSTRACT FROM AUTHOR]

Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon‐like peptide‐1 (GLP‐1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP‐1 analogue, liraglutide (LIR), in reducing heroin addiction‐like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self‐administration, prevents escalation of heroin self‐administration and reduces drug‐induced reinstatement of heroin‐seeking behaviour in rats. A 1‐h pretreatment time, however, was too short to reduce cue‐induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR‐paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin‐naïve or heroin‐experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain. [ABSTRACT FROM AUTHOR]

Objective: Early work suggests the type of subjective experiences upon first opioid use may predict opioid use disorder (OUD) risk. This study developed and pilot-tested a brief survey to evaluate the "first response" to opioids., Design: A cross-sectional survey research study. The survey was administered to a subsample for the second time to assess test-retest reliability., Setting: Outpatient., Participants: Convenience sample of adults treated for OUD at an opioid treatment program., Main Outcome Measures: A seven-question First Response to Opioids Survey Tool (FROST), developed based on the existing questionnaires and stakeholder-advisor feedback, was evaluated., Results: Participants (N = 157) were 36.8 (standard deviation [SD] = 9.4) years old, with 79.6 percent identifying as Caucasian and 56.7 percent male. They reported opioid initiation at 20.6 (SD = 8.8) years old, with a prescription-based (78.3 percent), orally administered (66.2 percent), and illicitly procured (51.0 percent) opioids. Upon opioid initiation, positive-valence, euphoria-like subjective experiences of feeling "comfortable" (65.0 percent), "happy" (61.1 percent), "euphoria" (58.6 percent), and "energized" (44.6 percent) were common, and different (p < 0.05) from other types of subjective experiences. Among 64 individuals who answered a question about "drug-liking," 50 (78.1 percent) reported drug-liking. Among 31 respondents who completed the survey a second time, the test-retest consistency was 78.2 percent for subjective experience characteristics and 72 percent for drug-liking responses. Qualitative results corroborated quantitative findings., Conclusion: These results suggest that euphoria-type experiences and drug-liking upon opioid initiation are common among adults with OUD and FROST's promising psychometric properties. Future research should assess clinical utility of this brief survey, which could be applied at bedside and help identify those at risk for OUD, guide safer opioid prescribing, and reduce opioid-related harm.