Three Decades of Research on the Development of Ibogaine Treatment of Substance Use Disorders: A Scientometric Analysis.

Ibogaine is a natural psychoactive drug that has been investigated for its potential role in the treatment of substance use disorders since the mid-1960s. To evaluate the interest in ibogaine's use as a therapeutic agent, we performed a scientometric analysis covering the last three decades (1993-2002, 2003-2012, and 2013-2022). A complementary analysis was performed to select and describe published clinical trials and meta-analyses. A total of 1523 references were found. Linear growth of publications in the first and third decades were identified, and the average number of publications from 1993 to 2002 was lower than that in the other two decades. Researchers from five continents were identified. Globally, academic research centers in the United States and Canada were the most productive. Cocaine, tobacco, morphine, and alcohol prevailed as major keywords in the first two decades and opioids and psychedelics were included in the third decade. A few key authors were the most co-referenced. One preclinical meta-analysis and no meta-analysis in humans were found. Research trends for ibogaine are widespread, growing, and consonant with current attentiveness in drug abuse. Our findings support the pressing need for rigorous clinical research on ibogaine to evaluate its efficacy and safety.

Toxicity of Synthetic Cannabinoids in K2/Spice: A Systematic Review.

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as 'K2', 'K9' or 'Spice'. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings.

Bariatric surgery and its influence on alcohol consumption: Differences before and after surgery - A systematic review and meta-analysis.

BACKGROUND: Through new publications on the subject, the main goal of this article is to seek a change in the pattern of alcohol use before and after bariatric surgery. METHODS: We searched the National Library of Medicine, CINAHL, and PsycINFO databases. We included original articles regarding alcohol consumption before and after bariatric surgery to conduct the systematic review. RESULTS: Our systematic review, which included 18 articles, yielded mixed results. Meta-analysis of six articles did not reveal statistically significant differences in alcohol use behaviours before and one year after bariatric surgery. However, throughout the perspective of follow-up after bariatric surgery, nine out of the twelve articles showed improvement in the pattern of alcohol consumption when evaluated up to two years after the end of the surgical period, and four out of the five articles with monitoring beyond two years showed worsening in consumption, compared to pre-surgery alcohol use behaviours. CONCLUSIONS: Conclusions about the relationship between alcohol consumption and bariatric surgery are challenging primarily because of the variety of the methods used and the alcohol consumption measures. Despite that, our research pointed to an increased risk of alcohol use disorders two years after bariatric surgery.

Pharmacological Treatments for Cocaine Craving: What Is the Way Forward? A Systematic Review.

BACKGROUND: cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials. OBJECTIVES: we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes. RESULTS: Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes. LIMITATIONS: Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy. CONCLUSIONS: There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.

Poor sleep quality and lipid profile in a rural cohort (The Baependi Heart Study).

AIM: To test the association between cardiometabolic risk factors and subjective sleep quality assessed by the Pittsburgh sleep quality index (PSQI), independent of obstructive sleep apnea (OSA) and sleep duration. METHODS: A total of 573 participants from the Baependi Heart Study, a rural cohort from Brazil, completed sleep questionnaires and underwent polygraphy for OSA evaluation. Multivariable linear regression analysis tested the association between cardiovascular risk factors (outcome variables) and sleep quality measured by PSQI, adjusting for OSA and other potential confounders (age, sex, race, salary/wage, education, marital status, alcohol intake, obesity, smoking, hypertension, and sleep duration). RESULTS: The sample mean age was 43 ± 16 years, 66% were female, and mean body mass index (BMI) was 26 ± 5 kg/m2. Only 20% were classified as obese (BMI ≥30). Overall, 50% of participants reported poor sleep quality as defined by a PSQI score ≥5. A high PSQI score was significantly associated with higher very-low-density lipoprotein (VLDL) cholesterol levels (beta = 0.392, p = 0.012) and higher triglyceride levels (beta = 0.017, p = 0.006), even after adjustments, including the apnea-hypopnea index. Further adjustments accounting for marital status, alcohol intake, and medication use did not change these findings. No significant association was observed between PSQI scores and glucose or blood pressure. According to PSQI components, sleep disturbances (beta = 1.976, p = 0.027), sleep medication use (beta = 1.121, p = 0.019), and daytime dysfunction (beta = 1.290, p = 0.024) were significantly associated with higher VLDL serum levels. Only the daytime dysfunction domain of the PSQI components was significantly associated with higher triglyceride levels (beta = 0.066, p = 0.004). CONCLUSION: Poorer lipid profile was independently associated with poor sleep quality, assessed by the PSQI questionnaire, regardless of a normal sleep duration and accounting for OSA and socio-economic status.

Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women.

BACKGROUND: The identification of variants in the nicotinic acetylcholine receptor (nAChR) subunit genes associated with smoking phenotypes are increasingly important for prevention and treatment of nicotine dependence. In the context of personalized medicine, the aims of this study were to evaluate whether cholinergic receptor nicotinic alpha 2 (CHRNA2), cholinergic receptor nicotinic alpha 3 (CHRNA3), cholinergic receptor nicotinic alpha 5 (CHRNA5) and cholinergic receptor nicotinic beta 3 (CHRNB3) polymorphisms were associated with nicotine dependence severity, and to investigate possible pharmacogenetics markers of smoking cessation treatment. METHODS: This study cohort enrolled 1049 smoking patients who received pharmacological treatment (varenicline, varenicline plus bupropion, bupropion plus/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores (Issa score) were analyzed for nicotine dependence. CHRNA2 (rs2472553), CHRNA3 (rs1051730), CHRNA5 (rs16969968 and rs2036527) and CHRNB3 (rs6474413) polymorphisms were genotyped by high resolution melting analysis. RESULTS: Females with GA and AA genotypes for CHRNA5 rs16969968 and rs2036527 polymorphisms had higher success rate in smoking cessation treatment: 44.0% and 56.3% (rs16969968), 41.5% and 56.5% (rs2036527), respectively, compared with carriers of the GG genotypes: 35.7% (rs16969968), 34.8% (rs2036527), (P = 0.03, n = 389; P = 0.01, n = 391). The GA or AA genotypes for the rs16969968 and rs2036527 were associated with higher odds ratio for success in women (OR = 1.63; 95% CI = 1.04 to 2.54; P = 0.03 and OR = 1.59, 95% CI = 1.02 to 2.48; P = 0.04; respectively). We did not find association of these polymorphisms with nicotine dependence related scores. Polymorphisms in the CHRNA2, CHRNA3 and CHRNB3 genes were not associated with the phenotypes studied. CONCLUSION: CHRNA5 rs16969968 and rs2036527 were associated with higher success rate in the smoking cessation treatment in women. These findings might contribute to advances in personalized medicine.

Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.

OBJECTIVE: The search for genetic vulnerability factors in cocaine dependence has focused on the role that neuroplasticity plays in addiction. However, like many other drugs, the ability of an individual to metabolize cocaine can also influence susceptibility to dependence. Butyrylcholinesterase (BChE) metabolizes cocaine, and genetic variants of the BChE gene (BCHE) alter its catalytic activity. Therefore, we hypothesize that cocaine users with polymorphisms in BCHE can show diverse addictive behaviors due to differences in effective plasma concentrations of cocaine. Those polymorphisms might also influence users to prefer one of the two main preparations (crack or powder cocaine), despite having equal access to both. The present work investigates polymorphisms in BCHE and if those genetic variants constitute risk factors for cocaine dependence and for crack cocaine use. METHODS: A total of 1,436 individuals (698 cocaine-dependent patients and 738 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in BCHE: rs1803274, rs4263329, and rs4680662. RESULTS: For rs4263329, a nominal difference was found between cases and controls. For rs1803274 (the functional SNP), a statistically significant difference was found between patients who used crack cocaine exclusively and those who used only powder cocaine (P = 0.027; OR = 4.36; 95% CI = 1.18-16.04). Allele frequencies and genotypes related to other markers did not differ between cases and controls or between the two cocaine subgroups. CONCLUSIONS: Our findings suggest that the AA genotype of rs1803274 is a risk factor for crack cocaine use, which is more addictive than powder cocaine use. Further studies are needed in order to confirm this preliminary result and clarify the role of BCHE and its variants in cocaine dependence.

Cocaína e crack: conceitos básicos

Texto que compõe a unidade 1 do módulo 4 "Cocaína e Crack" do Curso de Capacitação em Dependência Química, produzido pela UNA-SUS/UFMA. Aborda alguns conceitos básicos sobre a cocaína e o crack, as formas de uso, a farmacocinética e farmacodinâmica, os fatores de risco, a correlação da neurobiologia com a clínica do dependente de cocaína, bem como os déficits neurocognitivos associados ao uso de crack e da cocaína.

Cocaína e crack: tratamento

Texto que compõe a unidade 2 do módulo 4, "Cocaína e crack", do Curso de Capacitação em Dependência Química, produzido pela UNA-SUS/UFMA. Aborda os principais tipos de tratamento de dependentes de cocaína e crack, destacando as principais medidas a serem tomadas no processo de reconhecimento do problema e que propiciem a mudança no estilo de vida do dependente químico

Etiologia dos transtornos alimentares: aspectos biológicos, psicológicos e sócio-culturais / Etiology of eating disorders: biological, psychological and sociocultural determinants

Os transtornos alimentares possuem uma etiologia multifatorial, composta de predisposições genéticas, socioculturais e vulnerabilidades biológicas e psicológicas. Entre os fatores predisponentes, destacam-se a história de transtorno alimentar e (ou) transtorno do humor na família, os padröes de interaçäo presentes no ambiente familiar, o contexto sociocultural, caracterizado pela extrema valorizaçäo do corpo magro, disfunções no metabolismo das monoaminas centrais e traços de personalidade. A dieta é o comportamento precursor que geralmente antecede a instalaçäo de um transtorno alimentar. Contudo, a presença isolada da dieta näo é suficiente para desencadear o transtorno alimentar, tornando-se necessária uma interaçäo entre os fatores de risco e outros eventos precipitantes. Por último, o curso transitório ou crônico de um transtorno alimentar está relacionado à persistência de distorções cognitivas, à ocorrência de eventos vitais significativos e a alterações secundárias ao estado de desnutriçäo

IMAO e apetite / MAOI and appetite: correlations and clinical aspects

Os autores apresentam uma revisão sobre o uso dos inibidores da monoaminoxidase e sua influência no padrão alimentar. Aspectos fisiopatológicos e importância na prática clínica são abordados

IMAO e apetite: correlacao e aspectos clinicos

Os autores apresentam uma revisao sobre o uso dos inibidores da monoaminoxidase e sua influencia no padrao alimentar. Aspectos fisiopatologicos e importancia na pratica clinica sao abordados.