Behavioral sensitization to psychostimulants and opioids: What is known in rodents and what still needs to be explored in humans?

Repeated exposure to substances of abuse results in an increase in some behavioral responses. This phenomenon, called behavioral sensitization (BS), is well described in preclinical models. However, its existence in humans is still a matter of debate. After a review of preclinical evidence of BS and its mechanisms in animal models, we reviewed the evidence supporting the existence of BS in humans, despite the limited research available in this regard. We focused our review on opioids and psychostimulants, since they share the ability to promote addictive behaviors. Further, they induce BS despite their distinct sedative and stimulant properties. Moreover, we proposed future research perspectives in this review to address the remaining unsolved questions, especially regarding BS in humans using a harm reduction approach.

Feasibility of an Extensive Strategy for Adult Diagnosis of Attention Deficit Hyperactivity Disorder Among Patients Suffering From Substance Use Disorders.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is found in up to 20% adults with Substance Use Disorder (SUD). ADHD + SUD is associated with a more complex clinical presentation and poorer outcomes than each disorder alone. In the presence of SUD, adult ADHD is particularly difficult to diagnose as both disorders can mimic or hide the symptoms of each other. Our university hospital in Paris recently started an extensive outpatient diagnostic procedure for adult patients with SUD to ascertain or refute ADHD diagnosis and to provide therapeutic guidance. Here, we report the acceptability of the assessment procedure for patients and the preliminary description of the current and lifetime clinical profiles as a function of the final diagnosis "ADHD vs. no ADHD." Method: Adult SUD patients with suspected ADHD were included in the current pilot study after stating they had no objection that their de-identified data were used for research purposes, according to French ethical procedures. Patients were evaluated for ADHD, comorbid mental disorders, cognitive state and dimensional psychological variables. They were assessed by trained psychologists and psychiatrists using standardized tools over a day. ADHD diagnosis was mainly based on the Diagnostisch Interview Voor ADHD for DSM-5 (DIVA-5). Results: Out of 18 eligible patients, 17 were included in the cohort (1 excluded) and none was opposed to using their data. Thirteen (76%) participants were diagnosed with ADHD. All patients appointed for the ADHD diagnostic procedure came, respected schedules and finished the evaluation. All patients were impaired on cognitive functioning and were highly comorbid, but ADHD patients seems to suffer even more from those conditions, especially for cannabis and stimulant use disorders. Discussion: Preliminary results show high acceptability of the procedure by ADHD-SUD patients. This result could be explained by all the organization adapted to the psychopathology. Patients' baseline motivation to participate also represents an uncontrolled variable that could promote the ability to follow the procedure. Acceptance results of the protocol are promising and represent a starting point to identify the best procedures to design patient-centered pharmacological and non-pharmacological therapies.

Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers.

Background: Cannabidiol (CBD) is a cannabinoid of potential interest for the treatment of substance use disorders. Our aim was to review the outcome measures, surrogate endpoints, and biomarkers in published and ongoing randomized clinical trials. Methods: We conducted a search in PubMed, Web of Science, PMC, PsycINFO, EMBASE, CENTRAL Cochrane Library, "clinicalTrials.gov," "clinicaltrialsregister.eu," and "anzctr.org.au" for published and ongoing studies. Inclusion criteria were randomized clinical trials (RCTs) examining the use of CBD alone or in association with other cannabinoids, in all substance use disorders. The included studies were analyzed in detail and their qualities assessed by a standardized tool (CONSORT 2010). A short description of excluded studies, consisting in controlled short-term or single administration in non-treatment-seeking drug users, is provided. Findings: The screening retrieved 207 published studies, including only 3 RCTs in cannabis use disorder. Furthermore, 12 excluded studies in cannabis, tobacco, and opioid use disorders are described. Interpretation: Primary outcomes were validated withdrawal symptoms scales and drug use reduction in the three RCTs. In the short-term or crossover studies, the outcome measures were visual analog scales for subjective states; self-rated scales for withdrawal, craving, anxiety, or psychotomimetic symptoms; and laboratory tasks of drug-induced craving, effort expenditure, attentional bias for substance, impulsivity, or anxiety to serve as surrogate endpoints for treatment efficacy. Of note, ongoing studies are now adding peripheral biomarkers of the endocannabinoid system status to predict treatment response. Conclusion: The outcome measures and biomarkers assessed in the ongoing CBD trials for substance use disorders are improving.