Adaptation of contingency management for stimulant use disorder during the COVID-19 pandemic.

The current coronavirus disease (COVID-19) pandemic has rapidly spread across the world. Individuals with stimulant use disorder are a vulnerable population, who are particularly at risk of negative outcomes during this pandemic due to several risk factors, including mental and physical comorbidities, weakened immune responses, high-risk behaviors, and barriers to healthcare access. Engaging patients with stimulant use disorder in regular treatment has become even more difficult during this pandemic, which has resulted in many cuts to addiction treatment programs. The most effective treatment options for stimulant use disorder are psychosocial interventions, which rely heavily on in-person interactions, posing an added challenge during physical distancing. In particular, contingency management (CM) is a behavioral therapy that utilizes tangible reinforcements to incentivize targeted behavior changes, and is an effective treatment intervention used for stimulant use disorder. This paper highlights the treatment challenges for individuals with stimulant use disorder and the importance of adapting CM programs during COVID-19. We present strategies for how CM can be adapted and its role expanded in a safe way during the COVID-19 pandemic to help prevent infection spread, stimulant use relapse, and worsened psychosocial consequences.

Social cognition and functional outcome in schizophrenia: The moderating role of cardiac vagal tone.

Individuals with schizophrenia face significant challenges in daily functioning, and although social cognition predicts how well patients respond to these challenges, associated physiological mechanisms remain unspecified. The present study draws from polyvagal theory and tested the hypothesis that respiratory sinus arrhythmia (RSA), an established indicator of the capacity to self-regulate and adapt to environmental demands, combines with social cognition to predict functional outcome. Using data from 41 schizophrenia patients and 36 healthy comparison subjects, we replicated group differences in RSA and social cognition and also demonstrated that RSA and social cognition interact to predict how effectively patients manage work and independent living activities. Specifically, RSA did not enhance functional outcomes when social cognition was already strong, but higher levels of RSA enabled effective role functioning when social-cognitive performance was impaired. Jointly, RSA and social cognition accounted for 40% of the variance in outcome success, compared with 21% when evaluating social cognition alone. As polyvagal theory suggests, physiological flexibility and self-regulatory capacity may compensate for poorer social-cognitive skills among schizophrenia patients.

Integrity of emotional and motivational states during the prodromal, first-episode, and chronic phases of schizophrenia.

Emotional and motivational dysfunction is fundamental to schizophrenia, and yet, the nature and scope of associated deficits are not well understood. This study assessed the integrity of emotional responding from the perspective of its underlying motivational systems during different phases of schizophrenia. Evaluative, somatic, and autonomic responses were measured during viewing of pictures categorized by emotional content, including threat, mutilation, contamination, illness, pollution, mild erotica, families, food, and nature. Participants were 13 patients at ultra high risk or prodromal for psychosis, 40 first-episode schizophrenia patients, 37 chronic schizophrenia patients, and 74 healthy comparison subjects. Irrespective of phase of illness, schizophrenia patients showed a robust and normal pattern of response across multiple systems, with differential engagement of the defensive and appetitive systems as a function of the motivational significance assigned to specific emotional contexts. Although the integrity of core motivational states also appeared to be intact in prodromal patients, a less consistent pattern of response was observed. As continuing efforts are made to identify emotional and motivational abnormalities in schizophrenia, identified deficits will likely be independent of a fundamental dysfunction in basic emotion and motivation response systems and involve integration with higher order processes.

Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviours.

The endocannabinoid system has been shown to regulate both the hypothalamic-pituitary-adrenal (HPA) axis and emotionality. The present experiment was designed to examine whether pharmacological modulation of the endocannabinoid system would affect the suppression of hippocampal cell proliferation and increase in defensive behaviours seen following exposure to predator odour (trimethylthiazoline; TMT) stress. Rats were administered either an endocannabinoid uptake inhibitor (AM404; 2 mg/kg) or a cannabinoid CB1 receptor antagonist (AM251; 5 mg/kg) 30 min prior to exposure to TMT. Exposure to TMT reduced cell proliferation in the dentate gyrus and increased the expression of defensive burying. Administration of AM404 significantly inhibited defensive burying, and attenuated the reduction in cell proliferation in response to TMT exposure. Administration of AM251 alone significantly increased cell proliferation; however, pretreatment with AM251 prevented neither the stress-induced suppression of cell proliferation nor the stress-induced increase in behavioural responses. These results support previous research demonstrating that augmentation of endocannabinoid signalling can suppress stress-responsive systems. They also suggest that endocannabinoids may play a complex role in the regulation of neurogenesis via cell proliferation in the hippocampus.

Alterations in behavioral flexibility by cannabinoid CB1 receptor agonists and antagonists.

RATIONALE: Cannabinoid CB1 receptors are expressed in the prefrontal cortex, but their role in mediating executive functions such as behavioral flexibility is unclear. OBJECTIVE: The present study examined the effect of pharmacological activation or blockade of the cannabinoid CB1 receptors on behavioral flexibility using a strategy set-shifting task conducted on a cross maze. MATERIALS AND METHODS: In experiment 1, rats initially were trained to turn left or right while ignoring the visual cue to obtain a food; on the second test day, rats had to inhibit the previously learned rule and approach the cue to obtain the food. In experiment 2, the order of discrimination training was reversed. RESULTS: Administration of the cannabinoid CB1 receptor agonist HU-210 before the set-shift on day 2 elicited dose-dependent effects on performance. A 20-microg/kg dose of HU-210 increased perseverative errors, whereas the effects of a lower, 5-microg/kg dose caused differential effects depending on whether rats were required to shift from a response to a visual-cue discrimination strategy or vice versa. Conversely, administration of a 2-mg/kg, but not a 5-mg/kg dose of the CB1 receptor antagonist AM251 reduced perseverative errors. CONCLUSIONS: These data demonstrate a biphasic and dose-sensitive role for the cannabinoid system in behavioral flexibility, which in turn may have clinical implications for the role of the endocannabinoid system in psychiatric disorders where behavioral flexibility is compromised.

Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment.

This study examined the effects of long-term cannabinoid administration on the responsivity of 5-HT1A and 5-HT2A receptors, which have been implicated in depression. Animals received 12 d administration of the potent cannabinoid receptor agonist HU-210 (100 microg/kg), following which they were monitored on their behavioural, physiological and hormonal responses to a single challenge of a 5-HT1A and 5-HT2A receptor agonist, 8-OH-DPAT (0.3 mg/kg) and DOI (1 mg/kg) respectively. Chronic HU-210 treatment lead to a significant enhancement of DOI-induced wet-dog shakes, but a reduction of DOI-induced back muscle contractions. DOI-induced corticosterone release was unaffected by HU-210 treatment. The hyperthermic response to DOI appeared to be potentiated by long-term HU-210 treatment, as 50% of these subjects died from an apparent serotonin syndrome with core temperatures exceeding 43 degrees C. The 8-OH-DPAT-induced hypothermic response and elevation of corticosterone were both significantly attenuated by long- term HU-210 treatment. These data imply that chronic cannabinoid treatment may up-regulate 5-HT2A receptor activity while concurrently down-regulating 5-HT1A receptor activity, a finding similar to that sometimes observed in depression. This may partially explain the association between excessive cannabis consumption and the induction of affective disease.

Functional role of the endocannabinoid system and AMPA/kainate receptors in 5-HT2A receptor-mediated wet dog shakes.

These experiments sought to determine the influence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and the endocannabinoid system in the functional expression of the serotonin (5-HT) type 2A receptor-mediated wet dog shake response. Male Long-Evans rats were pretreated with either 1 mg/kg i.p. of the 5-HT(2A/2C) receptor antagonist ketanserin; 1, 10 or 30 mg/kg i.p. of the AMPA/kainate antagonist 6,7-dinitroquinnoxaline-2,3-dione (DNQX); 1, 5 or 10 mg/kg i.p. of the endocannabinoid uptake inhibitor AM404; or 1, 5 or 10 mg/kg i.p. of the cannabinoid CB(1) receptor antagonist AM 251 prior to injection of the 5-HT(2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 1 mg/kg i.p.). Results demonstrated that 10 mg/kg of AM404 significantly reduced the expression of DOI-induced wet dog shakes, but lower doses were ineffective. Administration of AM251 did not induce wet dog shakes behavior when administered alone, but significantly potentiated DOI-induced wet dog shaking behavior at a dose of 10 mg/kg. Pretreatment with DNQX significantly reduced the expression of DOI-induced wet dog shakes at all doses tested. These data suggest that AMPA/kainate receptors play a role in the mediation of 5-HT(2A) receptor activity, whereas the endocannabinoid system may act as a regulatory buffer system during periods of elevated activity, but not under basal conditions.