IUPHAR-review: The integration of classic psychedelics into current substance use disorder treatment models.

Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical practice. We first describe contemporary evidence-based treatments for SUDs and highlight how classic psychedelic-assisted therapies might fit within each treatment. We suggest that classic psychedelic-assisted therapies can be integrated into most mainstream evidence-based SUD treatments that are currently used in clinical settings, indicating broad compatibility of classic psychedelics with contemporary SUD treatment paradigms.

Role of matrix metalloproteinase-9 in neurodevelopmental deficits and experience-dependent plasticity in Xenopus laevis.

Matrix metalloproteinase-9 (MMP-9) is a secreted endopeptidase targeting extracellular matrix proteins, creating permissive environments for neuronal development and plasticity. Developmental dysregulation of MMP-9 may also lead to neurodevelopmental disorders (ND). Here, we test the hypothesis that chronically elevated MMP-9 activity during early neurodevelopment is responsible for neural circuit hyperconnectivity observed in Xenopus tadpoles after early exposure to valproic acid (VPA), a known teratogen associated with ND in humans. In Xenopus tadpoles, VPA exposure results in excess local synaptic connectivity, disrupted social behavior and increased seizure susceptibility. We found that overexpressing MMP-9 in the brain copies effects of VPA on synaptic connectivity, and blocking MMP-9 activity pharmacologically or genetically reverses effects of VPA on physiology and behavior. We further show that during normal neurodevelopment MMP-9 levels are tightly regulated by neuronal activity and required for structural plasticity. These studies show a critical role for MMP-9 in both normal and abnormal development.

Classic psychedelics in the treatment of substance use disorder: Potential synergies with twelve-step programs.

Several pilot studies have provided evidence supporting the potential of classic psychedelics like psilocybin in the treatment of substance use disorders (SUDs). If larger trials confirm efficacy, classic psychedelic-assisted psychotherapy may eventually be integrated into existing addiction treatments such as cognitive behavioral therapy, contingency management, and medication-assisted therapies. Many individuals seeking treatment for SUDs also join twelve-step facilitation (TSF) programs like Alcoholics Anonymous (AA), which are among the most widely available and accessed treatments for alcohol use disorder worldwide. For such individuals, engaging in classic psychedelic-assisted psychotherapy could be seen as controversial, as members of AA/TSF programs have historically rejected medication-assisted treatments in favor of a pharmacotherapy-free approach. We argue that classic psychedelics and the subjective experiences they elicit may represent a special, more compatible case than conventional medications. In support of this claim, we describe Bill Wilson's (the founder of AA) little known experiences with psychedelics and on this basis, we argue that aspects of classic psychedelic treatments could complement AA/TSF programs. We provide a review of clinical trials evaluating psychedelics in the context of SUDs and discuss their potential large-scale impact should they be ultimately integrated into AA/TSF.

Optimism during pregnancy and obstetrical outcomes: A systematic review.

OBJECTIVE: To ascertain the strength of association between dispositional optimism, assessed with the Revised Life Orientation Test (LOT-R), and obstetrical outcomes, and to evaluate women's social characteristics that may lead to low dispositional optimism during pregnancy. STUDY DESIGN: The research was conducted using MEDLINE, EMBASE, Scopus, Web of Sciences, Cochrane Database, and ClinicalTrial.gov as electronic databases. The articles were identified with the use of a combination of the relevant heading term, key words, and word variants for: "optimism" or "happiness" and "pregnancy" or "obstetrical outcomes", from the inception of each database to June 2019. Review of articles also included the abstracts of all references retrieved from the search. Randomized, cohort, case-control, or case series were all accepted study designs. Only studies reporting obstetrical outcomes in women undergone LOT-R to assess dispositional optimism during pregnancy were included. Obstetrical outcomes included preterm birth, pre-eclampsia and small for gestational age fetuses. All analyses were carried out using the random effects model. Dichotomous variables were analyzed using the odds ratio (OR) with a 95 % confidence interval (95 % CI). No continuous variables were compared in the analysis. Significance level was set at P < 0.05. Heterogeneity was measured using I-squared (Higgins I2). RESULTS: Two prospective cohort studies, including 3,570 pregnancies undergone LOT-R - mostly during the second trimester - were included in the systematic review. Out of the 3,570 pregnancies included, 411 were in the lowest quartile of optimism, according to LOT-R score. Dispositional optimism showed a trend towards lower incidence of preterm birth (7.6 % vs 9.7 %; OR 0.76, CI 0.53-1.09); no difference between women at higher levels and women in the lowest quartile of optimism was found in preeclampsia and small for gestational age. Women at higher levels of dispositional optimism were significantly associated with: age ≥ 30 years; marriage or "marriage-like status"; lower rates of public assistance and smoking; white ethnicity; higher rates of higher education. CONCLUSION: There are limited data on optimism and obstetric outcomes. Higher levels of optimism, evaluated by the LOT-R tool in two studies, are associated with a non-significant decrease in preterm birth.

Stroke recurrence in pregnancy: Experience at a regional referral center.

BACKGROUND: Although stroke is more common with advancing age, especially in the elderly, women of reproductive age may still suffer from stroke, and from its deleterious consequences. Women of reproductive age who suffer a stroke may do so either due to a specific predisposition, or due to pregnancy-related hypertensive emergencies. OBJECTIVE: To assess the risk of stroke recurrence in pregnancy and the postpartum period in women who have suffered a stroke before pregnancy. STUDY DESIGN: This was a retrospective cohort study conducted at Thomas Jefferson University Hospital from January 2005 to December 2015. This is a tertiary referral center for high-risk obstetrics and one of the largest stroke referral centers for neurosurgery. All consecutive pregnant women that had a viable pregnancy (≥24 weeks of gestation) and a history of stroke prior to pregnancy were identified. The primary outcome of this study was stroke recurrence in pregnancy or the postpartum period defined as 6 weeks after delivery. RESULTS: Forty-eight pregnancies with a history of stroke before pregnancy were identified in 24 women. Thirty-one pregnancies (64.6%) had a history of an ischemic stroke, 11 (22.9%) had a history of transient ischemic attack, and 6 (12.5%) had a history of a hemorrhagic stroke. There was no stroke recurrence during pregnancy or the postpartum period for the three groups of stroke. In the ischemic stroke group, 8 (25.8%) had recurrence in the non-pregnant state compared to none in the TIA and the hemorrhagic stroke group. CONCLUSION: There was no stroke recurrence during pregnancy or the postpartum period for the three groups of stroke.