Psilocybin for Treating Psychiatric Disorders: A Psychonaut Legend or a Promising Therapeutic Perspective?

Psychedelics extracted from plants have been used in religious, spiritual, and mystic practices for millennia. In 1957, Dr. Hofmann identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although there were limitations related to the scientific design of many studies, clinical observations performed during the 1950s and 1960s showed a potential therapeutic effect of psilocybin for patients affected by depressive symptoms, anxiety, and conversion disorder. Psilocybin was classed as a schedule I substance in 1970, but the fascination with psychedelics has remained almost unchanged over time, promoting a new scientific interest starting in the 1990s. Recent studies have provided further evidence supporting the suggestive hypothesis of the therapeutic use of psilocybin for treating various psychiatric disorders, including pathological anxiety, mood depressive disorder, and addiction.

Craving for heroin: difference between methadone maintenance therapy patients with and without ADHD.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder persisting in adulthood in 40-60% of cases. Clinical and neuroimaging studies suggest that patients affected by both drug addiction and ADHD show higher rates of craving for drug than patients without ADHD. We designed a pilot open-label study to investigate the effects of ADHD on craving for heroin in methadone maintenance therapy patients. METHOD: Patients were recruited from outpatient facilities in an addiction treatment unit in the municipality of Alba, Italy. They were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), the SCID-5 for Personality Disorders (SCID-5-PD), the Diagnostic Interview for Adult ADHD, second edition (DIVA 2.0), and the Clinical Opiate Withdrawal Scale (COWS). Categorical variables were examined using the chi-square test, and continuous variables, the t-test and Mann-Whitney's U test for normally and non-normally distributed data, respectively. Data distribution was evaluated using Shapiro-Wilk's test. Significance was set at p=0.05. Bonferroni correction was applied (0.0063) to avoid type I error. RESULTS: A total of 104 patients were included in the study: 14 affected by ADHD (13.5%) and 90 were not affected (86.5%). Patients with ADHD showed higher intensity of craving for heroin than patients without ADHD in the absence of withdrawal symptoms. CONCLUSION: Drug addiction and ADHD share various neurobiological mechanisms that mutually influence the evolution of both disorders. In particular, dopamine dysfunction within various brain circuits may influence impulsivity levels, motivation, inhibitory control, executive functions, and behavior and, consequently, the intensity of craving.

Craving for heroin: difference between methadone maintenance therapy patients with and without ADHD / Fissura por heroína: diferença entre pacientes em terapia de manutenção com metadona com e sem TDAH

Abstract Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder persisting in adulthood in 40-60% of cases. Clinical and neuroimaging studies suggest that patients affected by both drug addiction and ADHD show higher rates of craving for drug than patients without ADHD. We designed a pilot open-label study to investigate the effects of ADHD on craving for heroin in methadone maintenance therapy patients. Method Patients were recruited from outpatient facilities in an addiction treatment unit in the municipality of Alba, Italy. They were assessed using the Structured Clinical Interview for DSM-5 (SCID-5), the SCID-5 for Personality Disorders (SCID-5-PD), the Diagnostic Interview for Adult ADHD, second edition (DIVA 2.0), and the Clinical Opiate Withdrawal Scale (COWS). Categorical variables were examined using the chi-square test, and continuous variables, the t-test and Mann-Whitney's U test for normally and non-normally distributed data, respectively. Data distribution was evaluated using Shapiro-Wilk's test. Significance was set at p=0.05. Bonferroni correction was applied (0.0063) to avoid type I error. Results A total of 104 patients were included in the study: 14 affected by ADHD (13.5%) and 90 were not affected (86.5%). Patients with ADHD showed higher intensity of craving for heroin than patients without ADHD in the absence of withdrawal symptoms. Conclusion Drug addiction and ADHD share various neurobiological mechanisms that mutually influence the evolution of both disorders. In particular, dopamine dysfunction within various brain circuits may influence impulsivity levels, motivation, inhibitory control, executive functions, and behavior and, consequently, the intensity of craving.

Resumo Introdução O transtorno de déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento que persiste na idade adulta em 40-60% dos casos. Estudos clínicos e de neuroimagem sugerem que pacientes afetados tanto por adição quanto por TDAH apresentam maiores índices de fissura (craving) por droga do que pacientes sem TDAH. Este estudo piloto aberto investigou os efeitos do TDAH sobre fissura por heroína em pacientes em terapia de manutenção com metadona. Método Os pacientes foram recrutados em serviços ambulatoriais em uma unidade de tratamento de adição na cidade de Alba, Itália. Eles foram avaliados usando os seguintes instrumentos: Structured Clinical Interview for DSM-5 (SCID-5), SCID-5 for Personality Disorders (SCID-5-PD), Diagnostic Interview for Adult TDAH, second edition (DIVA 2.0) e Clinical Opiate Withdrawal Scale (COWS). Variáveis categóricas foram examinadas utilizando o teste do qui-quadrado, e variáveis contínuas, o teste t e o teste U de Mann-Whitney para dados com distribuição normal e não normal, respectivamente. A distribuição dos dados foi avaliada usando o teste de Shapiro-Wilk. O nível de significância foi estabelecido em p=0,05. A correção de Bonferroni foi aplicada (0,0063) para evitar erro tipo I. Resultados Um total de 104 pacientes foram incluídos no estudo: 14 com TDAH (13,5%) e 90 sem (86,5%). Pacientes com TDAH mostraram maior intensidade de fissura por heroína do que pacientes sem TDAH na ausência de sintomas de abstinência. Conclusão Adição e TDAH compartilham mecanismos neurobiológicos que influenciam mutuamente a evolução dos dois transtornos. Em particular, a disfunção da dopamina em vários circuitos cerebrais pode influenciar os níveis de impulsividade, motivação, controle inibitório, funções executivas e comportamento, e, portanto, a intensidade da fissura.

Impulsivity in Alcohol-Dependent Patients with and without ADHD: The Role of Atomoxetine.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of hyperactivity, inattention, and impulsivity. As shown in the literature, this disorder is frequently associated with alcohol and drug abuse. Patients affected by ADHD show high levels of impulsivity and sensation seeking. These characteristics can significantly increase the risk of alcohol abuse, which is itself a clinical condition associated with high levels of impulsivity. Clinical studies suggest that atomoxetine is effective and safe in patients affected by both ADHD and alcohol dependence; however, information focused specifically on impulsivity is very limited. In an open-label study, we evaluated the difference in impulsivity level between alcohol-dependent patients with and without a diagnosis of ADHD. Furthermore, we hypothesized that, in patients with ADHD, atomoxetine could reduce the impulsivity trait.

Correlation between plasma homocysteine levels and craving in alcohol dependent stabilized patients.

BACKGROUND & AIMS: Homocysteine is a sulfur amino acid strictly related with alcohol consumption. In alcoholics, hyperhomocysteinemia can increase the risk of various alcohol-related disorders such as: brain atrophy, epileptic seizures during withdrawal, and mood disorders. OBJECTIVE: To evaluate the correlation among serum homocysteine concentrations, craving, hazardous and harmful patterns of alcohol consumption in patients stabilized for withdrawal symptoms. METHODS: Participants were adult outpatients accessed at the Addiction Treatment Unit. Alcoholism was assessed using the following tools: Mini-International Neuropsychiatric Interview Plus (MINI Plus), Alcohol Use Disorder Identification test (AUDIT), Visual Analogic Scale for craving (VAS). Furthermore, during the first visit a blood sample was taken from all patients to measure the plasma concentration of both homocysteine and Carboxy Deficient Transferrin (CDT). Differences between groups in socio-demographic and clinical characteristics were analyzed using the t-test and the Mann-Whitney's U test for normally and non-normally distributed data, respectively. Correlation between clinical scale scores and plasma concentration of homocysteine and CDT was evaluated using the Pearson's correlation coefficient and the Kendall's Tau-b bivariate correlation coefficient for normally and non-normally distributed data, respectively. RESULTS: Our study included 92 patients. No difference was found in socio-demographic characteristics between groups. The group with high homocysteine had higher prevalence of mood disorders (p < 0.001), plasma CDT percentage (p < 0.001), VAS score (p < 0.001) and AUDIT score (p < 0.001) than group with normal homocysteine. Plasma homocysteine showed a positive correlation with both VAS score (p < 0.001), and AUDIT score (p < 0.05). CONCLUSIONS: In our study, plasma homocysteine concentration is associated with craving, hazardous and harmful patterns of alcohol consumption. In particular, homocysteine is correlated with alcoholism in a bidirectional manner because its level appears to be related with alcohol degree, but simultaneously, hyperhomocysteinemia could enhance the alcohol consumption increasing the severity of craving in a circular self reinforcing mechanism.

Blood homocysteine concentration and mood disorders with mixed features among patients with alcohol use disorder.

BACKGROUND: Blood homocysteine concentration (BHC) is higher in patients with alcohol use disorder (AUD). Previous studies have found a relationship between depressive symptoms severity and BHC in AUD patients and recently some authors have found high BHC among patients with bipolar disorder, both during manic and depressive episodes and in euthymic state. However, BHC in patients with mixed mood episode has not yet been investigated. The aim of this study was to evaluate the BHC of patients with AUD and mixed mood episode. METHODS: A sample of AUD outpatients was assessed by Mini-International Neuropsychiatric Interview (MINI Plus): those with a DSM-IV-TR mood disorder with mixed features were included in the MIXED group (n = 45), whereas those without mood episode were gathered in the NO MOOD group (n = 23). Two subgroups, MIXMANIA and MIXDEPRESSION, were formed according to the prevalence of manic or depressive symptoms, assessed by Young Mania Rating Scale (YMRS), and Hamilton Rating Scale for Depression (HDRS). The Alcohol Use Disorder Identification Test (AUDIT) was used to appraise the AUD. BHC was determined by High-Performance Liquid Chromatography. RESULTS: The MIXED group showed greater severity of both depressive (26.35 ± 9.96 vs. 4.77 ± 0.92; p < 0.001) and manic (22.35 ± 3.30 vs. 6.14 ± 1.12; p < 0.001) symptoms, and higher BHC (28.80 ± 11.47 vs. 10.83 ± 2.81; p < 0.001), than the NO MOOD group. BHC was strongly correlated to the HDRS, YMRS and AUDIT scores, just as HDRS was to YMRS, and AUDIT was to both HDRS and YMRS, in the MIXED group only (p < 0.001). The MIXDEPRESSION subgroup showed higher BHC than the MIXMANIA subgroup (Mdn = 42.96, IQR = 10.44 vs. Mdn = 19.77, IQR = 5.93; p < 0.001). A linear regression model conducted on the MIXED group found a significant predictive value for BHC of both HDRS (ß = 0.560, t = 2.43, p = 0.026) and AUDIT (ß = 0.348, t = 2.17, p = 0.044). CONCLUSIONS: Depressive symptoms seem to be mainly implicated in the BHC elevation among patients with both mixed features mood disorder and AUD.

JWH-122 Consumption Adverse Effects: A Case of Hallucinogen Persisting Perception Disorder Five-Year Follow-Up.

Synthetic cannabinoid receptor agonists are a heterogeneous group of psychotropic drugs functionally related to Δ9-tetrahydrocannabinol. These substances, marketed as cannabis substitutes, have been associated with numerous cases of severe intoxication and death across the world. In our article, we describe a case of hallucinogen persisting perception disorder developing in a natural cannabis user after consumption of JWH-122, a naphthoylindole largely used since 2010. Clinical symptomatology persisted for about four years and was alleviated through treatment with clonazepam. Considering that natural cannabis consumption can induce the development of a hallucinogen persisting perception disorder, it is not excluded that, in our patient, symptoms lasted a long time due to cannabis consumption. This article describes the clinical evolution from onset to resolution of all symptoms.

4,4'-DMAR: chemistry, pharmacology and toxicology of a new synthetic stimulant of abuse.

In recent years, the spread of new psychoactive substances has dramatically increased in term of availability of both number of compounds and chemical families. In November 2012, 4,4'-Dimethylaminorex (4,4'-DMAR), a novel synthetic stimulant, was first detected in the Netherlands. Between June 2013 and June 2014, thirty-one deaths associated with the consumption of this new drug have been registered across Europe. In this MiniReview, we have summarized the chemical, pharmacological and toxicological information about this new legal high.

Potential use of Magnolia officinalis bark polyphenols in the treatment of cannabis dependence.

In recent years, epidemiological data confirm that cannabis-related emergencies, cannabis-use disorders and dependence are significantly increased. Cannabis is generally considered a little dangerous substances of abuse, however, chronic consumption has been associated to the development of mental disorders, cognitive deficits, chronic bronchitis, emphysema, increased risk of myocardial infarction in the hour after use, increased mortality after myocardial infarction, liver inflammation and steatosis in patients affected by hepatitis C. In this article we described the pharmacological characteristics of Magnolia officinalis bark active principles suggesting a potential application in the treatment of both cannabis dependence and cannabis-related disorders.