Non-Prescribed Substance Use during the First Month of Treatment by People Receiving Depot Buprenorphine for Opioid Use Disorder.

Background: Non-prescribed substance use (NPSU) during the treatment of opioid use disorder (OUD) is a recognized phenomenon. The use of non-prescribed substances is associated with discontinuing treatment and drop-out can occur within the early weeks of treatment, before benefit from treatment occurs. Recent developments in treatment include long-acting, slow-release depot buprenorphine injections. This article focuses on NPSU during the first month of treatment with depot buprenorphine, addressing the frequency with which it occurs, the substances used, and reasons for use. Methods: 70 semi-structured interviews (held at three time-points) were conducted with 26 patients initiating depot buprenorphine as part of a longitudinal qualitative study. Analysis prioritized content and framework analyses. Findings: 17/26 participants self-reported NPSU at various times during the first month of treatment. NPSU typically involved heroin, crack-cocaine and some use of benzodiazepines and/or cannabis. Participants' reasons for heroin use were connected to their subjective accounts of opioid withdrawal symptoms, the management of pain, and experimentation (to test the blockade effect of buprenorphine). Frequency of heroin use was typically episodic rather than sustained. Participants associated crack-cocaine use with stimulant-craving and social connections, and considered their use of this substance to be difficult to manage. Conclusions: Patients' initial engagement with treatment for OUD is rarely examined in qualitative research. This study highlights how NPSU amongst patients receiving new forms of such treatment continues to be a challenge. As such, shared decision-making (between providers and patients) regarding treatment goals and NPSU should be central to the delivery of depot buprenorphine treatment programmes.

Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies.

BACKGROUND: Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes. METHODS: We did a systematic review and meta-analysis in accordance with GATHER and PRISMA guidelines. We searched Embase, MEDLINE, CENTRAL, and PsycINFO from database inception to Aug 1, 2022; clinical trial registries and previous relevant Cochrane reviews were also reviewed. We included all RCTs and observational studies of adults (aged ≥18 years) with opioid dependence comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. Single-arm cohort studies and RCTs that collected data on buprenorphine retention alone were also reviewed. Data on study, participant, and treatment characteristics were extracted. Study authors were contacted to obtain additional data when required. Comparative estimates were pooled with use of random-effects meta-analyses. The proportion of individuals retained in treatment across multiple timepoints was pooled for each drug. This study is registered with PROSPERO (CRD42020205109). FINDINGS: We identified 32 eligible RCTs (N=5808 participants) and 69 observational studies (N=323 340) comparing buprenorphine and methadone, in addition to 51 RCTs (N=11 644) and 124 observational studies (N=700 035) that reported on treatment retention with buprenorphine. Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia. 1 040 827 participants were included in these primary studies; however, gender was only reported for 572 111 participants, of whom 377 991 (66·1%) were male and 194 120 (33·9%) were female. Mean age was 37·1 years (SD 6·0). At timepoints beyond 1 month, retention was better for methadone than for buprenorphine: for example, at 6 months, the pooled effect favoured methadone in RCTs (risk ratio 0·76 [95% CI 0·67-0·85]; I·=74·2%; 16 studies, N=3151) and in observational studies (0·77 [0·68-0·86]; I·=98·5%; 21 studies, N=155 111). Retention was generally higher in RCTs than observational studies. There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone. There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis and reported proportion of positive urine samples (over various time frames; standardised mean difference -0·20 [-0·29 to -0·11]; I·=0·0%; three studies, N=841), but no differences were found when using other measures. Some statistically significant differences were found between buprenorphine and methadone among secondary outcomes. There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone; and evidence of reduced hospitalisation and alcohol use in people receiving methadone. These differences in secondary outcomes were based on small numbers of studies (maximum five), and were often not consistent across study types or different measures of the same constructs (eg, cocaine use). INTERPRETATION: Evidence from trials and observational studies suggest that treatment retention is better for methadone than for sublingual buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and harmonisation of data collection and reporting to strengthen future syntheses. FUNDING: Australian National Health and Medical Research Council.

Urine Drug Test Results Among Adolescents and Young Adults in an Outpatient Office-Based Opioid Treatment Program.

PURPOSE: Urine drug testing (UDT) is an important feature of outpatient treatment for opioid use disorder, but associations with patient characteristics among adolescent and young adult patients are unknown. This study assessed UDT results in office-based opioid treatment and characteristics associated with treatment compliance. METHODS: This was a retrospective study of adolescent and young adult patients enrolled in office-based opioid treatment between January 1, 2009, and December 31, 2020. UDT results were described as positive results or expected and unexpected results. Expected results were negative UDTs for opioids, marijuana (THC [tetrahydrocannabinol]), or cocaine/methamphetamine, or a positive UDT for buprenorphine. Unexpected results were positive UDTs for opioids, THC, or cocaine/methamphetamine, or a negative UDT for buprenorphine. Treatment compliance was defined as ≥75% of UDTs provided being expected results. Counts and percentages described UDT results. Regressions evaluated associations between patient characteristics (retention time, age, sex, race/ethnicity, insurance, and comorbid mental health diagnoses) with treatment compliance, and assessed change of positivity rates for UDTs over time. RESULTS: A total of 407 patients were included. Overall, 305 patients (74.9%) demonstrated treatment compliance. Rates of expected UDT results increased with longer retention time (p <.001), except for methamphetamine. Buprenorphine expected results ranged from 77.0% to 96.5%. Diagnosis of stimulant use disorder was associated with decreased compliance (p = .04), while diagnoses of depression, anxiety, nicotine use disorder, and post-traumatic stress disorder were associated with increased compliance (p ≤.04). DISCUSSION: Proportion of expected UDT results increased with retention time. Diagnosis of specific mental health conditions affected treatment compliance. Further research regarding long-term health outcomes is needed.

El auge y la caída del mito de la epinefrina en la mano / The Rise and Fall of the Epinephrine Myth in the Hand

La posibilidad de operar a los pacientes con afecciones de la mano bajo anestesia local con la lidocaína y la epinefrina usando la técnica WALANT provocó una revolución en la cirugía de la mano, que facilitó la vida de los pacientes y disminuyó los costos de los servicios hospitalarios. Es necesario que los cirujanos conozcan la técnica y la historia de esta técnica. El objetivo fue identificar los orígenes del auge y la caída del mito y del dogma de la prohibición de la adrenalina en los bloqueos anestésicos de los dedos. Se realizó un análisis crítico de los principales textos de los artículos y los libros sobre el uso de la epinefrina en la anestesia de los dedos. La creación del mito de prohibir el uso de la epinefrina en los bloqueos anestésicos de los dedos se produjo debido a la mala interpretación de los informes de los casos de necrosis ocurridos que, en realidad, no fueron causados por la epinefrina. Ese mito influyó en la aparición de un dogma. La historia del uso de la epinefrina en los bloqueos de los dedos anestésicos demuestra que las interpretaciones superficiales y erróneas de las complicaciones clínicas publicadas como informes de casos pueden generar mitos y dogmas. Solo la ciencia puede prevenir y destruir tales mitos y dogmas médicos(AU)

The possibility of operating patients with hand conditions under local anesthesia, with lidocaine and epinephrine, using WALANT technique caused a revolution in hand surgery, which made life easier for patients and lowered the costs of hospital services. Surgeons need to be aware of the possibilities and history of WALANT technique. The objective was to identify the origins of the rise and fall of the myth and dogma of the prohibition of adrenaline in anesthetic finger blocks. A critical analysis of the main texts of the articles and books on the use of epinephrine in finger anesthesia was carried out. The conception of the myth of banning the use of epinephrine in anesthetic finger blocks occurred due to misinterpretation of reports of necrosis occurring, which were not actually caused by epinephrine. That myth influenced the appearance of a dogma. The history of the use of epinephrine in anesthetic finger blocks demonstrates that superficial and misleading interpretations of clinical complications published as case reports can breed myth and dogma. Only science can prevent and destroy such medical myths and dogmas(AU)

Cannabidiol in the context of substance use disorder treatment: A systematic review.

INTRODUCTION: Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis plant. CBD has received significant medical attention in relation to its anticonvulsant, anxiolytic, and antipsychotic characteristics. An increasing number of studies focusing on the anti-addictive properties of CBD have recently been published. In this systematic review, we aim to offer a comprehensive overview of animal and human studies regarding the impact of CBD on substance use disorders (SUDs). METHODS: A systematic search was performed on the PubMed database in February 2021. We included all articles assessing the effects of CBD on substance use disorders. RESULTS: The current systematic review suggests that CBD might offer promising therapeutic potential for the treatment of SUD, based on available animal and human studies. Animal studies showed a positive impact of CBD in the context of alcohol, opioids, and methamphetamine use (e.g., diminishing of drug-seeking behaviors). The results for cocaine use were mixed among reviewed studies, and CBD was not found to have an effect in animal studies on cannabis use. No animal study was identified that focused on the impact of CBD on nicotine use. Human studies showed a positive impact of CBD in the context of nicotine, cannabis, and opioid use (e.g., frequency and quantity of consumption). In contrast, CBD was not found to have an effect in human studies on cocaine or alcohol use. No human study was identified that investigated the impact of CBD on methamphetamine use. CONCLUSIONS: CBD might offer promising therapeutic potential for the treatment of SUD, especially for nicotine, cannabis, and opioid use disorders, based on available human studies. The available research evidence is, however, sparse and more research on humans is needed.

Cocaine Allergy in Drug-Dependent Patients and Allergic People.

BACKGROUND: Adverse reactions to local anesthetics (LAs), especially esters, are not uncommon, but true allergy is rarely diagnosed. To our knowledge, currently there is no reliable method of determining IgE-mediated hypersensitivity to LAs and cocaine. OBJECTIVE: To assess the clinical value of allergy tests (prick, IgE, challenges, and arrays) in people suffering hypersensitivity reactions (asthma and anaphylaxis) during local anesthesia with cocaine derivatives and drug abusers with allergic symptoms after cocaine inhalation. METHODS: We selected cocaine-dependent patients and allergic patients who suffered severe reactions during local anesthesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity, and predictive value) of allergy tests using cocaine and coca leaf extracts in determining cocaine allergy was assessed, taking a positive challenge as the criterion standard. RESULTS: After prick tests, specific IgE, and challenge with cocaine extract, 41 of 211 patients (19.4%) were diagnosed as sensitized to cocaine. Prick tests and IgE to coca leaves (coca tea) had a good sensitivity (95.1% and 92.7%, respectively) and specificity (92.3 and 98.8%, respectively) for the diagnosis of cocaine allergy and LA-derived allergy. CONCLUSIONS: Cocaine may be an important allergen. Drug abusers and patients sensitized to local anesthesia and tobacco are at risk. Both prick tests and specific IgE against coca leaf extract detected sensitization to cocaine. The highest levels were related to severe clinical profiles.

Sex differences in guanfacine effects on stress-induced stroop performance in cocaine dependence.

AIMS: Chronic drug abuse leads to sex-specific changes in drug cue and stress physiologic and neuroendocrine reactivity as well as in neural responses to stress and cue-related challenges and in executive function such as inhibitory control, cognitive flexibility and self control. Importantly, these functions have been associated with high risk of relapse and treatment. Alpha-2 agonism may enhance inhibitory cognitive processes in the face of stress with sex-specific effects, however this has not been previously assessed in cocaine dependence. METHOD: Forty inpatient treatment-seeking cocaine dependent individuals (13F/27M) were randomly assigned to receive either placebo or up to 3mgs of Guanfacine. Three laboratory sessions were conducted following 3-4 weeks of abstinence, where patients were exposed to three 10-min personalized guided imagery conditions (stress, drug cue, combined stress/cue), one per day, on consecutive days in a random, counterbalanced order. The Stroop task was administered at baseline and immediately following imagery exposure. RESULTS: Guanfacine treated women improved their performance on the Stroop task following exposure to all 3 imagery conditions compared with placebo women (p=0.02). This improvement in cognitive inhibitory performance was not observed in the men. CONCLUSIONS: Enhancing the ability to cognitively regulate in the face of stress, drug cues and combined stress and drug cue reactivity may be key targets for medications development in cocaine dependent women.

Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity.

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca (Erythroxylum coca, Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme (Thymus vulgaris, Lamiaceae) and clove (Syzygium aromaticum, Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs. Phytochemicals in research papers published between 1996 and 2016 were retrieved from the point of view of well-known modes of anesthetic action, that is, the mechanistic interactions with Na⁺ channels, γ-aminobutyric acid type A receptors, N-methyl-d-aspartate receptors and lipid membranes. The searched phytochemicals include terpenoids, alkaloids and flavonoids because they have been frequently reported to possess local anesthetic, general anesthetic, antinociceptive, analgesic or sedative property. Clinical applicability of phytochemicals to local and general anesthesia is discussed by referring to animal in vivo experiments and human pre-clinical trials. This review will give structural suggestions for novel anesthetic agents of plant origin.

Potencial de la hoja de coca en la medicina actual / Potencial da folha da coca na medicina actual / Potential of coca leaf in current medicine

La hoja de coca es una droga vegetal con implicaciones medicinales y culturales diferentes a las de la cocaína, sustancia que se ha convertido en una droga de abuso. La hoja de coca posee un potencial terapéutico en el tratamiento de la astenia, de los dolores bucales o del tracto gastrointestinal, en la obesidad, especialmente si se encuentra asociada a diabetes tipo II, y en programas de entrenamiento para el ejercicio físico. Bajo valoración psiquiátrica podría ser útil en el tratamiento del síndrome ansioso depresivo y en la terapia de deshabituación de cocaína y alcohol. No se ha observado toxicidad aguda, adicción ni síndrome de abstinencia en consumidores habituales de hoja de coca. Se requieren más estudios clínicos que permitan establecer la posología más adecuada para cada una de las indicaciones (AU)

A folha de coca é um fármaco vegetal com implicaçóes medicinais e culturais diferentes das da cocaina, uma substancia que se tornou uma droga de abuso. A folha de coca tem potencial terapéutico no tratamento da astenia, dor oral ou do trato gastrointestinal, obesidade, especialmente se esta estiver associada a diabetes tipo II e também em programas de preparaçáo física, para aumento da resisténcia. Sob avaliaçáo psiquiátrica pode ser útil no tratamento da síndrome ansiosa depressiva, e também na terapia de desabituaçáo de cocaina e álcool. Nao se observou toxicidade aguda, dependencia ou sindroma de abstinencia em consumidores habituais de folha de coca. Sáo necessários mais estudos clínicos que permitam estabelecer a posologia mais adequada para cada uma das possiveis indicaçóes terapéuticas (AU)

Coca leaf is a herbal drug with medicinal and cultural implications different from those of cocaine, a substance that has become a drug of abuse. Coca leaf has a therapeutic potential in the treatment of asthenia, oral pain or gastrointestinal tract pain, obesity, especially if it is associated with type II diabetes, and in physical exercise training programs. Under psychiatric assessment may be useful in the treatment of anxiety-depressive syndrome and in the dishabituation therapy of cocaine and alcohol. No acute toxicity, addiction or withdrawal symptoms have been observed in regular coca leaf users. Further clinical studies are required to establish the most suitable dosage for each of the possible therapeutic indications (AU)

Topical treatment in pain medicine: from ancient remedies to modern usage.

Over several millennia, substances have been applied to the skin for treatment of pain. Some ingredients are in current use; others have been discontinued. Mechanisms of action include interactions with nociceptive neural networks and inflammatory processes. Substances must penetrate the stratum corneum barrier and vehicles that enhance penetration have been developed. Topical drugs with links to the past include menthol, capsaicin, some opioids, local anesthetic agents and NSAIDs. Mandragora is also described as an example of a herbal remedy that has been discontinued due to its toxicity. The future for topical drugs is promising, with the advent of new drugs tailored for specific pain mechanisms and the development of both penetration enhancers and sterile preparation methods.

Pain Symptoms Associated with Opioid Use among Vulnerable Persons with HIV: An exploratory study with implications for palliative care and opioid abuse prevention.

Current or former injection drug users with human immunodeficiency virus (HIV) are at high risk for pain, which adversely affects their quality of life and may increase their risk for illicit drug use or relapse. We explored associations between pain symptoms and substance use among injection-drug-using study participants with HIV who had histories of heroin use. Using generalized estimating equations and controlling for prior substance use, we found that pain in each six-month period was associated with the use of heroin and prescription opioids, but not the use of nonopioid drugs or alcohol. Routine clinical assessment and improved management of pain symptoms may be needed for persons with HIV and a history of injection drug use, particularly those with chronic pain, for whom there is increased risk for heroin use.

Local anaesthesia through the action of cocaine, the oral mucosa and the Vienna group.

Local anaesthesia through the action of cocaine was introduced in Europe by the Vienna group, which includeed Freud, Koller and Königstein. Before using the alkaloid in animal or human experimentation all these scientists tested it on their oral mucosa - so-called self-experimentation. Some of them with different pathologies (that is, in the case of Freud), eventually became addicted to the alkaloid. Here we attempt to describe the people forming the so-called 'Vienna group', their social milieu, their experiences and internal disputes within the setting of a revolutionary discovery of the times.

Comparación entre la anestesia tópica con cocaína y lidocaína con adrenalina en la dacriocistorrinostomía con láser / Comparison between topical anaesthesia with cocaine versus lidocaine plus adrenaline for outpatient laser dacryocystorhinostomy

OBJETIVO: Comparar el uso de anestesia tópica de cocaína al 4% con la utilización de una mezcla de lidocaína al 2% y adrenalina al 1/100.000 para la dacriocistorrinostomía con láser (TCLDCR) y sedación consciente, sin infiltración local. MÉTODOS: En un estudio prospectivo, aleatorizado, a doble ciego, 46 pacientes fueron intervenidos tras la aplicación nasal de un apósito impregnado con cocaína al 4% y 46 pacientes fueron intervenidos tras emplear lidocaína al 2% y adrenalina 1/100.000 de idéntica forma. Se evaluó el bienestar intraoperatorio mediante la escala análogo visual, la presencia de alteraciones cardiovasculares (controlando la frecuencia cardiaca y la presión sanguínea) y la resolución de epífora con escala de Munk y control endoscópico. RESULTADOS: Los pacientes de ambos grupos estuvieron confortables durante la intervención, en el postoperatorio inmediato y a las 24 h tras la intervención. Los efectos secundarios cardiovasculares durante la cirugía fueron más frecuentes en el grupo de la cocaína. En el grupo 1, 16 pacientes tuvieron cifras tensionales elevadas frente a 2 del grupo 2, riesgo relativo (RR) 8. En el grupo 1, 12 enfermos presentaron frecuencia cardiaca por encima de 100 frente a uno del grupo 2, RR = 6. Un total de 12 pacientes del grupo 1 tuvieron un sangrado mayor de 5 ml (media 6,1 ml) frente a 2 del grupo 2 (media 2,1 ml) RR = 6. Las diferencias entre el grupo 1 y el 2, en cuanto a estas 3 complicaciones, fueron significativas (p = 1,1 × 10-9). En ningún grupo hubo casos de sangrado posquirúrgico que precisaran de taponamiento por más de 3 h. Los éxitos quirúrgicos fueron similares en ambos grupos 86,96 y 89,13% a los 6 meses de seguimiento. CONCLUSIONES: La combinación de lidocaína y adrenalina es efectiva para la dacriocistorrinostomía endoscópica con láser bajo anestesia tópica y sedación consciente. Esta combinación provee una adecuada anestesia y visualización del campo quirúrgico con menor sangrado e hipertensión arterial que la cocaína

OBJECTIVE: To evaluate the effectiveness of topical anaesthesia with cocaine versus lidocaine plus adrenaline for outpatient transcanalicular and endonasal dacryocystorhinostomy (TCLDCR) with diode laser under sedation. METHODS: A double blind randomised clinical trial was designed using topical anaesthesia for outpatient TCLDCR in the treatment of adult epiphora. A total of 92 patients were enrolled, and randomly allocated to be operated on under sedation and topical anaesthesia with cocaine 4% pledgets versus sedation and topical anaesthesia with lidocaine 2% plus 1/100.000 adrenaline pledgets. Main outcome measures were postoperative comfort, evaluated by a visual analogue scale, presence of secondary effects (blood pressure, heart rate), and resolution of epiphora, evaluated by Munk's scale and endoscopic control. RESULTS: Patients in both groups reported being comfortable during and immediately after TCLDCR. Visualization of the operative field was adequate, and surgery was successfully completed in all cases. Complications were more common in the cocaine group: Sixteen patients from the cocaine group had high blood pressures, versus 2 patients from the lidocaine group (RR = 8). Mean blood loss was 6.09 ml in cocaine group, versus 2.05 ml in lidocaine group (RR = 6). Both parameters were statistically significant (p = 1,1 × 10−9). There were no cases of postoperative epistaxis requiring nasal packing or hospital admission in any group. Success rate was similar in the 2 groups (86.96% group 1 and 89.13% group 2), after 6 months of follow-up. CONCLUSIONS: The combination of topical lidocaine and adrenaline is more effective for outpatient transcanalicular and endonasal dacryocystorhinostomy than topical cocaine. Patient comfort was adequate in both groups, but high blood pressure and blood loss more common after cocaine

O uso da folha de coca em comunidades tradicionais: perspectivas em saude, sociedade e cultura / The use of coca leaves in traditional communities: perspectives in health, society, and culture

Aborda as questões socioculturais que envolvem o uso da folha de coca nas regiões andina e amazônica. O estudo é de natureza teórica, sendo privilegiados artigos científicos e entrevistas com profissionais conceituados em revistas e jornais. Os resultados da pesquisa sugerem que a associação indiscriminada da coca à cocaína e, consequentemente, ao narcotráfico, parte de um preconceito construído historicamente que se sobrepõe às raízes históricas e culturais do uso milenar da planta. Cabe à psicologia, como ciência, romper o silêncio frente às questões indígenas e compreender a dinâmica dos processos socioculturais desses povos para se fazer atuar em espaços que exigem tratamentos diferenciados.

The article focuses on the sociocultural issues associated with the use of coca leaves in the Andes and Amazon regions. Approaching from a theoretical perspective, it explores scientific articles and magazine and newspaper interviews of distinguished professionals. The study's findings suggest that the tendency to indiscriminately link coca to cocaine, and consequently to drug-trafficking, stems from a historically constructed bias that eclipses the historical and cultural roots of the age-old use of this plant. It is up to psychology as a science to break the silence surrounding indigenous issues and come to understand the dynamics of these peoples' sociocultural processes so that it can figure in spaces where differentiated treatment is required.

The use of coca: prehistory, history, and ethnography.

The purpose of this article is to review the use of the natural mild stimulant coca, which is a story that originates with the prehistory of coca, evolves through its following historical uses, and leads up to the eventual development of cocaine. This discussion will begin with the botanical background of the coca plant, followed by a review of some of the prehistoric, historic and ethnographic evidence of coca use, which indicates the extensive antiquity and pervasiveness of coca use in South and Central America. The diverse roles that coca played among the Inca and other indigenous peoples led to the early adoption of coca in the West and, in turn, to the resultant discovery of cocaine and its assorted early applications, particularly for medicinal purposes.

Preclinical validation of a novel cocaine exposure therapy for relapse prevention.

BACKGROUND: Cocaine not only induces intense rewarding sensations but also craving for more cocaine, particularly during abstinence, an effect that contributes, together with other factors, to relapse. Here we sought to prevent this effect by extinguishing the conditioned interoceptive cues of cocaine that are thought to be acquired during repeated cocaine use. METHODS: Cocaine-induced craving was studied in rats using the well-validated model of drug-primed reinstatement of cocaine seeking. To extinguish the conditioned interoceptive effects of cocaine, rats received daily repeated cocaine priming in the absence of drug reinforcement. RESULTS: Cocaine-primed reinstatement of cocaine seeking dramatically decreased with repeated cocaine priming regardless of the testing dose and even following a history of extended access to cocaine self-administration. The extinction of cocaine-primed reinstatement of cocaine seeking was enduring, generalized to stress-another major trigger of drug craving and relapse-and was context-dependent. CONCLUSIONS: These findings clearly show that it is feasible to prevent the ability of cocaine and stress to induce cocaine seeking using an approach designed to extinguish the drug's conditioned interoceptive cues. Although this preclinical extinction approach has limitations that need to be overcome in future research (i.e., its context-dependency), it may nevertheless represent a promising basis for the development of a novel exposure therapy against cocaine relapse.

O namoro de Freud e a descoberta da anestesia tópica / Freud’s romantic attraction and the topic anesthesia

A descoberta por Kõller da anestesia tópica com a cocaína revolucionou a cirurgia no final do século XIX. No entanto, os pitorescos lances históricos que envolvem tal avanço médico, como a importante participação de Freud, o pai da Psicanálise, e a influência de seu namoro com Martha Bernays nessa descoberta, são muito pouco divulgados. O objetivo do artigo é exatamente abordar esses fatos.

The topical anesthesia with cocaine discovered by Kõller revolutionized surgery in the late nineteenth century. However, the picturesque historic anecdotes involving this medical advancement such as the important contribution of Freud, the father of Psychoanalysis, and the influence of his courtship with Martha Bernays in this discovery, is very little known. This article aims to address exactly these facts.

Breve historia del dolor y de la analgesia / Brief history of pain and analgesia

El dolor ha acompañado al ser humano desde el mismo momento en que éste apareció sobre la tierra. Desde entonces, y a lo largo de toda su historia, el hombre ha tratado no sólo de buscar la razón del mismo, sino también de encontrar remedios para su alivio(AU)

Pain has accompanied human beings since the moment this species appeared on Earth. From that moment on, and throughout his long history, mankind has tried not only to look for the causes of pain but also to find remedies to relieve pain(AU)