Cardiovascular Risks of Simultaneous Use of Alcohol and Cocaine-A Systematic Review.

Background: The simultaneous use of cocaine and alcohol is highly prevalent and is associated with high numbers of emergency department admissions, primarily due to cardiovascular complications. Aims: To answer the question of whether the co-use of cocaine and alcohol increases the cardiovascular risk compared to the use of cocaine alone. Method: A systematic review of human studies comparing the cardiovascular risk of co-used cocaine and alcohol with the use of cocaine alone. Results: Despite a higher myocardial workload induced by the co-use of cocaine and alcohol and the potentiation of cocaine's cardiovascular effects by alcohol, the findings on the risk and severity of cardiovascular symptoms due to combined use are inconsistent. However, the co-use of cocaine and alcohol clearly leads to higher mortality. Interestingly, the presence of cocaethylene, a unique metabolite generated only via a pharmacokinetic interaction between alcohol and cocaine, carries an 18- to 25-fold increase over the absence of cocaethylene (cocaine-alone users) in the risk of sudden death and is associated with myocardial injury and cardiac arrest, probably due to the inhibition of cardiac ion channels by cocaethylene. Conclusion: Despite the inconsistency in some of the results, it is concluded that the co-use of cocaine and alcohol poses an additional risk of cardiovascular fatalities compared to the use of cocaine alone.

An International, Multidisciplinary Consensus Set of Patient-Centered Outcome Measures for Substance-Related and Addictive Disorders.

Background: In 1990, the United States' Institute of Medicine promoted the principles of outcomes monitoring in the alcohol and other drugs treatment field to improve the evidence synthesis and quality of research. While various national outcome measures have been developed and employed, no global consensus on standard measurement has been agreed for addiction. It is thus timely to build an international consensus. Convened by the International Consortium for Health Outcomes Measurement (ICHOM), an international, multi-disciplinary working group reviewed the existing literature and reached consensus for a globally applicable minimum set of outcome measures for people who seek treatment for addiction. Methods: To this end, 26 addiction experts from 11 countries and 5 continents, including people with lived experience (n = 5; 19%), convened over 16 months (December 2018-March 2020) to develop recommendations for a minimum set of outcome measures. A structured, consensus-building, modified Delphi process was employed. Evidence-based proposals for the minimum set of measures were generated and discussed across eight videoconferences and in a subsequent structured online consultation. The resulting set was reviewed by 123 professionals and 34 people with lived experience internationally. Results: The final consensus-based recommendation includes alcohol, substance, and tobacco use disorders, as well as gambling and gaming disorders in people aged 12 years and older. Recommended outcome domains are frequency and quantity of addictive disorders, symptom burden, health-related quality of life, global functioning, psychosocial functioning, and overall physical and mental health and wellbeing. Standard case-mix (moderator) variables and measurement time points are also recommended. Conclusions: Use of consistent and meaningful outcome measurement facilitates carer-patient relations, shared decision-making, service improvement, benchmarking, and evidence synthesis for the evaluation of addiction treatment services and the dissemination of best practices. The consensus set of recommended outcomes is freely available for adoption in healthcare settings globally.

Substitution therapy for patients with alcohol dependence: Mechanisms of action and efficacy.

New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, there has been little attention to substitution therapy for the treatment of AD. Here, we explain the mechanistic foundations of alcohol substitution maintenance therapy. Alcohol has many primary targets in the brain (and other organs) and the physical interaction of ethanol molecules with these specific ethanol-sensitive sites on a variety of ionotropic receptors (e.g. GABA-A, NMDA, and nicotinic acetylcholine (nACh) receptors) and ion channels provides the rationale for substitution. As such, a variety of compounds can interact with those ethanol-sensitive sites and can thus substitute for some of the effects of alcohol. For some of these compounds, alcohol discrimination studies have shown their substitution potential. Accordingly, potential substitution treatments include agonists acting at GABA receptors such as sodium oxybate, baclofen and benzodiazepines, NMDA receptor antagonists such as ketamine and memantine, or nAChRs agonists such as varenicline. All these compounds are already approved for other indications and we present clinical evidence for these drugs in the treatment of alcohol withdrawal syndrome (AWS) and in the long-term treatment of AD, and outline future steps for their acceptance as substitution treatment in AD. Finally, we discuss the substitution approach of managed alcohol programs for the most severely affected homeless populations. Results showed that sodium oxybate is probably the closest to a substitution therapy for AD and is already approved for the treatment of AWS and in the long-term treatment of AD in some countries. In conclusion, we argue that better AD treatment can be provided if substitution maintenance treatments for alcohol are implemented at a similar scale as for opioid and nicotine use disorder.

Explaining the high mortality among opioid-cocaine co-users compared to opioid-only users. A systematic review.

RATIONALE: The opioid crisis in North America has recently seen a fourth wave, which is dominated by drug-related deaths due to the combined use of illicitly manufactured fentanyl [IMF] and stimulants such as cocaine and methamphetamine. OBJECTIVES: A systematic review addressing the question why drug users combine opioids and stimulants and why the combination results in such a high overdose mortality: from specific and dangerous pharmacokinetic or pharmacodynamic interactions or from accidental poisoning? RESULTS: Motives for the combined use include a more intensive high or rush when used at the same time, and some users have the unfounded and dangerous belief that co-use of stimulants will counteract opioid-induced respiratory depression. Overdose deaths due to combined (intravenous) use of opioids and stimulants are not likely to be caused by specific pharmacokinetic or pharmacodynamic interactions between the two drugs and it is unlikely that the main cause of overdose deaths is due to accidental poisoning. CONCLUSION: The unexpectedly high overdose rates in this population could not be attributed to accidental overdosing or pharmacokinetic/pharmacodynamic interactions. The most likely explanation for the high rate of drug-related deaths in opioid-cocaine co-users is careless overdosing with either cocaine, opioid(s) or both, probably facilitated by the high level of preexisting impulsivity in these co-users and a further acute increase in impulsivity following cocaine use. The primary corollary is that cocaine users should avoid IMF use in the same time window. In addition, IMF users should refrain from cocaine use to avoid impulsive IMF overdosing.

Psychedelic-assisted therapy for people with gambling disorder?

Gambling disorder is a severe mental health and behavioural problem with harmful consequences, including financial, relationship and mental health problems. The present paper initiates discussion on the use of psychedelics combined with psychotherapeutic support as a potential treatment option for people living with a gambling disorder. Recent studies have shown promising results using psychedelic-assisted therapy (PAT) to treat anxiety, depression, post-traumatic stress disorder, and various substance use disorders. Considering the similarities in the underlying psychosocial and neurobiological mechanisms of gambling disorder and other addictive disorders, the authors suggest that psychedelic-assisted therapy could be effective in treating gambling disorder. The paper also underscores the need for further research into the viability and effectiveness of psychedelic-assisted therapy for gambling disorder.

Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study.

Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy and safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, the current paper explored the experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with a single session of oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges with trust-building and expectation management; (2) navigating the experience; and (3) the need for a more comprehensive treatment. Subthemes of the first theme include a general distrust in mental healthcare, trust in study therapists, limited time for preparation, and managing expectations. The second theme included the following subthemes: trusting to surrender, profound and overwhelming experiences, and music as a guide. The third theme addressed a desire for multiple psilocybin sessions, and challenges with sensemaking. Patients' perspectives provided important insights into potential optimization of psilocybin treatment of TRD, including individualized preparation, investment in trust-building, offering additional psilocybin sessions, providing access to sustained (psycho)therapy with trusted therapists, and personalizing treatment approaches, which may also enhance real-world adaption of these treatments.

Patient Reported Outcome and Experience Measures (PROMs and PREMs) in substance use disorder treatment services: A scoping review.

BACKGROUND: Substance use disorders (SUD) pose significant challenges for healthcare systems, and there is a need to monitor the provision of effective, individualized care to persons accessing treatment. Patient-Reported Outcome Measures (PROMs) and Patient-Reported Experience Measures (PREMs) are increasingly used in healthcare services to measure treatment outcomes and quality of care as perceived by patients, and to guide service improvement. OBJECTIVES: This review aims to identify and characterize international developments regarding the use and systematic implementation of PROMs and PREMs in SUD treatment services. METHODS: A scoping review was conducted searching multiple databases to identify studies on the use and routine implementation of PROMs and PREMs in SUD treatment services. RESULTS: 23 articles were selected, all dating from 2016 onwards. There was large variation in the patient-reported measures that were used, how they were developed and how and when patient-reported data were collected. Treatment providers identified leadership support, the presence of an integrated electronic patient record, and regular feedback to be the most important facilitators of successful implementation of patient-reported measures into clinical practice, whilst treatment dropout and burden to staff and patients were the most important barriers to consider. CONCLUSIONS: PROMs and PREMs are increasingly used in SUD treatment services, but guidance is needed to support researchers and clinicians in selecting and implementing valid, meaningful, and comparable measures if we want to understand the effects of PROM and PREM data collection and feedback on treatment quality and results.

Combined use of cocaine and alcohol: A violent cocktail? A systematic review.

It is generally believed that the use of alcohol and cocaine alone and especially in combination elicits aggression and violent behaviour. Though there is overwhelming proof that heavy alcohol use is associated with violence, this is not the case for cocaine. Still, in the popular press and by spokesmen of the police, cocaine use is seen as a cause of violent incidents. In the current systematic review, available data from human studies on the relation between cocaine and violent behaviour is presented. In particular, we present scientific data on the acute induction of violence by cocaine alone, as well as, that by the combination of cocaine and alcohol known to be frequently used simultaneously. RESULTS: show that there is only weak scientific evidence for the acute induction of violent behaviour by cocaine, either when used alone or in combination with alcohol. Based on these data we were also able to refute misconceptions about the relation between cocaine and violence published in the popular press and governmental reports, because it appeared that there was hardly any empirical support for this widely shared opinion. Probably, contextual factors, including cocaine use disorder and personality disorder, may better explain the assumed association between cocaine and violence.

Legal Approaches to New Psychoactive Substances: First Empirical Findings.

BACKGROUND: Generic drug legislation, i.e., simultaneously banning groups of drugs, has been introduced worldwide to counteract the trade and use of emerging "new psychoactive substances" (NPSs) more effectively. SUMMARY: The potential and de facto positive and negative effects of generic drug legislation have been described using an analysis based on documented evaluations of the experiences in the UK and Germany, supplemented with data from other publicly available sources. In particular, the effects of generic drug legislation on availability, use, sales, and overall health harms of NPS, and switches from NPS to traditional (classical) drugs are addressed. The results show that the introduction of generic drug legislation in the UK and Germany has enabled stricter regulation of NPS but has also led to some major harms within the domain of public health. Depending on the population considered, the rate of NPS use remained stable, slightly declined, or increased following the banning of NPS. Once banned, NPSs were more often purchased on the black market, often together with other (more harmful) drugs. Moreover, NPS-related harms did not reduce following the ban, and in some cases even increased. Finally, when harmful NPS, like potent synthetic opioids and cannabinoids, become substantially used and endanger public health, legislators already have the legal means to ban the problem drug, thus overruling the need for a generic ban. KEY MESSAGES: Generic drug legislation may facilitate drug law enforcement, but it is not (very) effective in counteracting NPS use and it may increase NPS-related public health problems. It is concluded that, overall, the advantages of generic drug legislation are overshadowed by its serious disadvantages.

Predictors and motives of polydrug use in opioid users. A narrative review.

PURPOSE OF REVIEW: To review the recent literature on predictors and personal motives of polydrug use in opioid users with a focus on combined use of opioids with stimulants, benzodiazepines and gabapentinoids. RECENT FINDINGS: In North America, methamphetamine is now the most prevalent co-drug in opioid users and is responsible for high mortality rates. In Europe, opioids are rather combined with either cocaine, benzodiazepines or gabapentionoids, but recent data are lacking.Main personal motives of opioid users to combine opioids with methamphetamine or cocaine is to boost the opioid high, inhibit the withdrawal effects of heroin and have a cheaper alternative to maintain the opioid high. Risk factors of polydrug use by opioid users included being male, younger age, homelessness, high-risk sexual behavior, needle sharing, incarceration, poor mental health and recent use of cocaine or prescription opioids. The motives for co-use of opioids and gabapentinoids also include seeking a better high, lower price and to self-medicate pain/physical symptoms, including those resulting from withdrawal. SUMMARY: When treating opioid users with polydrug drug use, special attention should be paid to dosing when in opioid agonist methadone/buprenorphine treatment and to the presence of physical pain. The validity of part of the personal motives seems questionable which deserves attention when counselling opioid users with polydrug use.

Phenomenology and therapeutic potential of patient experiences during oral esketamine treatment for treatment-resistant depression: an interpretative phenomenological study.

BACKGROUND: Ketamine and its enantiomers are widely researched and increasingly used to treat mental disorders, especially treatment-resistant depression. The phenomenology of ketamine-induced experiences and their relation to its psychotherapeutic potential have not yet been systematically investigated. AIMS: To describe the phenomenology of patient experiences during oral esketamine treatment for treatment-resistant depression (TRD) and to explore the potential therapeutic relevance of these experiences. METHODS: In-depth interviews were conducted with 17 patients after a 6-week, twice-weekly 'off label' generic oral esketamine (0.5-3.0mg/kg) treatment program. Interviews explored participants' perspectives, expectations, and experiences with oral esketamine treatment. Audio interviews were transcribed and analyzed using an Interpretative Phenomenological Analysis (IPA) framework. RESULTS: The effects of ketamine were highly variable, and psychological distress was common in most patients. Key themes included (a) perceptual effects (auditory, visual, proprioceptive), (b) detachment (from body, self, emotions, and the world), (c) stillness and openness, (d) mystical-type effects (transcendence, relativeness, spirituality), and (e) fear and anxiety. Key themes related to post-session reports included (a) feeling hungover and fatigued, and (b) lifting the blanket: neutralizing mood effects. CONCLUSION: Patients reported several esketamine effects with psychotherapeutic potential, such as increased openness, detachment, an interruption of negativity, and mystical-type experiences. These experiences deserve to be explored further to enhance treatment outcomes in patients with TRD. Given the frequency and severity of the perceived distress, we identify a need for additional support in all stages of esketamine treatment.

Anabolic Androgenic Steroid Use Patterns and Steroid Use Disorders in a Sample of Male Gym Visitors.

INTRODUCTION: The use of anabolic androgenic steroids (AAS) and other image- and performance-enhancing drugs is a growing public health concern. AAS use is associated with various physical and mental harms, including cardiovascular risks, cognitive deficiencies, and dependence. The aim of this study was to determine whether patterns of AAS use and other variables are associated with the presence of an AAS use disorder (AASUD). METHODS: An online survey was completed by 103 male AAS consumers visiting gyms. The association of different patterns of AAS consumption (cycling vs. continuous forms of AAS use), psychoactive substance use, mental health disorders, and sociodemographic variables with moderate-severe AASUD (fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ≥4 criteria) was investigated. The associations between duration of AAS use and the AAS dose with moderate-severe AASUD were investigated using logistic regression analysis with moderate-severe AASUD as the dependent variable. RESULTS: Moderate-severe AASUD was present in 25 (24.3%) of the participants. AAS consumers meeting criteria for moderate-severe AASUD, compared to those that did not, in the last 12 months reported a longer duration of AAS use (in weeks), a higher average AAS dose (mg/week), and a greater number of AAS side effects. Duration of AAS use and the AAS dose were the only independent predictors, with an increase of 3.4% in the probability of moderate-severe AASUD with every week increase of the duration of AAS use in the last year (p < 0.05) and an increase in moderate-severe AASUD of 0.1% with every 10 mg increase in the average AAS dose per week (p < 0.05), respectively. CONCLUSION: Our findings show that moderate-severe AASUD is relatively frequent among male AAS consumers and is positively associated with the duration and average dose of AAS use in the last 12 months.