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.

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.

Smoking As an Outcome Moderator In the Treatment of Alcohol Use Disorders.

AIMS: To clarify whether smoking interferes with successful treatment of alcohol use disorder (AUD). METHODS: The current systematic review investigates the potential moderating effect of smoking on behavioural and pharmacological treatment of AUD. In addition, this review summarizes the results of randomized controlled trials investigating the effect of smoking cessation treatments in subjects with AUD on drinking outcomes. RESULTS: Overall, the results show that 16 out of the 31 pharmacological and psychotherapeutic alcohol treatment studies showed that being a non-smoker or decreased tobacco consumption during AUD treatment is associated with beneficial drinking outcomes, including reduced drinking, later relapse and prolonged alcohol abstinence. As such, smoking predicts poorer drinking outcomes in alcohol treatments. In the stop-smoking studies in patients with AUD, reduced smoking had virtually no effect on drinking behaviours. The inverse association between smoking and drinking outcome observed here indicates that non-smokers may be more successful to attain alcohol abstinence than smokers do. However, this association does not imply per se that smoking triggers alcohol consumption, since it can also mean that alcohol consumption promotes smoking. CONCLUSIONS: It is concluded that (continued) tobacco smoking may have a negative moderating effect on the treatment outcome of AUD treatments. To optimize treatment outcome of AUD one may consider informing and counselling patients with AUD about the risks of smoking for treatment outcomes and offering support for smoking cessation.

The Added Value of Pharmacotherapy to Cognitive Behavior Therapy And Vice Versa in the Treatment of Alcohol Use Disorders: A Systematic Review.

AIM: To explore whether combined interventions i.e. psychotherapeutic plus psychosocial interventions are more effective than monotherapies in the treatment of alcohol use disorders. METHODS: Systematic review of the results of randomized controlled trials that compared combined therapies with monotherapies (either pharmacotherapy or psychotherapy). RESULTS: The search resulted in 28 eligible studies. Data from these RCTs showed that 10 out of 19 RCTs (53%) demonstrated an added value of combined therapy (psychotherapy + pharmacotherapy) compared to psychotherapy only, whereas only three out of nine RCTs (33%) comparing combined therapy with pharmacotherapy showed a possible added value for combined therapy. CONCLUSIONS: Pharmacotherapy is effective to treat AUD with or without psychotherapy and that psychotherapy can best be offered in combination with pharmacotherapy.

Slamsex in The Netherlands among men who have sex with men (MSM): use patterns, motives, and adverse effects.

BACKGROUND: This paper describes an online survey of men who have sex with men (MSM) and use drugs before or during sex ('chemsex') via injection ('slamming' or 'practising slamsex'). Approximately 15-30% of the MSM population in The Netherlands have practiced chemsex at some point, and 0.5-3.1% of them ever had 'slamsex'. This study investigates which substances are used in The Netherlands during slamsex, the motives for slamming and the health risks involved. METHOD: In total, 175 MSM from The Netherlands, who had used substances before or during sex via injection completed an ad hoc online questionnaire designed for this study. RESULTS: Mean age of respondents was 47.8years. During chemsex, almost every substance was used; the most common substances that were injected (slammed) were 3-methylmethcathinone (3-MMC), methamphetamine, ketamine, 4-methylethcathinone (4-MEC) and mephedrone (4-MMC). Reasons for slamming were mainly to experience a more intense rush and longer sex. Virtually none of the respondents used a condom during slamsex, but needles were almost never shared or used only once. Slammers reported health problems associated with injecting drugs (skin problems, collapsed veins and infections). Of most concern were the psychological symptoms reported by about three-quarters of respondents (e.g. insomnia, sadness, depressed mood, anxiety, suicidal tendencies). About half of respondents reported some degree of loss of control or concerns about their slamming behaviour. CONCLUSION: Results show that slamsex is associated with consciously chosen sexual risk behaviours and risk-avoidance slam behaviours. This study may contribute to the reinforcement of accessible, non-judgmental and well informed prevention and harm reduction activities to support MSM practising slamsex.

Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review.

The recreational use of nitrous oxide (N2O) has increased over the years. At the same time, more N2O intoxications are presented to hospitals. The incidental use of N2O is relatively harmless, but heavy, frequent and chronic use comes with considerable health risks. Most importantly, N2O can inactivate the co-factor cobalamin, which, in turn, leads to paresthesia's, partial paralysis and generalized demyelinating polyneuropathy. In some patients, these disorders are irreversible. Several metabolic cascades have been identified by which N2O can cause harmful effects. Because these effects mostly occur after prolonged use, it raises the question of whether N2O has addictive properties, explaining its prolonged and frequent use at high dose. Several lines of evidence for N2O's dependence liability can be found in the literature, but the underlying mechanism of action remains controversial. N2O interacts with the opioid system, but N2O also acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, by which it can cause dopamine disinhibition. In this narrative review, we provide a detailed description of animal and human evidence for N2O-induced abuse/dependence and for N2O-induced neurotoxicity.

Is Europe Facing an Emerging Opioid Crisis Comparable to the U.S.?

ABSTRACT: In the U.S., an opioid overdose crisis has emerged, attributable to over-prescription of opioid analgesics, driven by aggressive marketing by pharmaceutical companies, followed by surging heroin overdose deaths, and more recently, by the high mortality rates predominately because of illicitly manufactured fentanyl and analogs of fentanyl. In Europe, the use of prescription opioids for pain management has also increased in the last 2 decades, although it is debatable as to whether this could lead to a similar opioid overdose crisis. To address this issue, recent trends in opioid prescription rates, prevalence rates of fatal and nonfatal incidents, and addiction care treatment were used as proxies of opioid-related harm. The current overview, comparing opioid use and its negative consequences in Germany, France, the U.K., and the Netherlands, using the same indicators as in the U.S., demonstrates that there is no evidence of a current or emerging opioid crisis in these European countries. Scotland, however, is an alarming exception, with high rates of opioid-related harms. Considering that the use of prescription opioids has been declining rather than increasing in Europe, an opioid crisis is not anticipated there yet. Authorities should, however, remain vigilant.

Explaining the Differences in Opioid Overdose Deaths between Scotland and England/Wales: Implications for European Opioid Policies.

BACKGROUNDS: Between 2009 and 2018, the number of opioid-related deaths (ORDs) in Scotland showed a dramatic increase, whereas in England and Wales, a much lower increase in ORD was seen. This regional difference is remarkable, and the situation in Scotland is worrisome. Therefore, it is important to identify the drivers of ORD in Scotland. METHODS: A systematic literature review according to PRISMA guidelines was conducted to identify peer-reviewed studies about key drivers for the observed differences in ORDs between Scotland and England/Wales. In addition, non-peer-reviewed reports on nationwide statistical data were retrieved via Google and Google Scholar and analysed to quantify differences in ORD drivers between Scotland and England/Wales. RESULTS: The systematic review identified some important drivers of ORD, but none of these studies provided direct or indirect comparisons of ORD drivers in Scotland and England/Wales. However, the reports with nationwide statistical data showed important differences in ORD drivers between Scotland and England/Wales, including a higher prevalence of people using opioids in a problematic way (PUOP), more polydrug use in people using drugs in a problematic way (PUDP), a higher age of PUDP, and lower treatment coverage and efficacy of PUDP in Scotland compared to England/Wales, but no regional differences in injecting drug use, incarceration/prison release without treatment, and social deprivation in PUDP. CONCLUSION: It is concluded that the opioid crisis in Scotland is best explained by a combination of drivers, consisting of a higher population involvement in (problematic) opioid use (notably methadone), relatively more polydrug use (notably benzodiazepines and gabapentinoids), a steeper ageing of the PUOP population in the past 2 decades, and lower treatment coverage and efficacy in Scotland compared to England/Wales. The findings have important consequences for strategies to handle the opioid crisis in Scotland.

A Comparison of Excessive Drinking, Binge Drinking and Alcohol Dependence in Ethnic Minority Groups in the Netherlands: The HELIUS Study.

BACKGROUND: The Dutch multi-ethnic Healthy Life in an Urban Setting study recently showed that alcohol consumption was lower in ethnic minority groups than those of Dutch origin, but that binge drinking in drinkers of Turkish and Moroccan origin was relatively high. The aim of the current study is to examine factors that may contribute to the differences in drinking patterns and how they relate to the relationship between drinking patterns and alcohol dependence (AD) across ethnic groups. METHODS: The rate of last year alcohol use, alcohol use patterns and AD was assessed in 4,635 Dutch, 4,317 Moroccan, 4,036 Turkish, 2,459 Ghanaian, 4,426 African Surinamese and 3,357 South-Asian Surinamese participants (both men and women) born in Amsterdam, the Netherlands. RESULTS: Compared to the Dutch, the prevalence of (regular) drinking is substantially lower in all ethnic minority groups and regular drinkers among most ethnic minority groups have a lower adjusted risk to develop binge drinking and AD than the Dutch. For the prevalence of regular drinking, the ethnic differences are bigger than for the prevalence of current drinking. However, regular drinkers of Moroccan origin have a risk similar to the Dutch to develop binge drinking and AD; a finding that could not be explained by group differences in age, sex, religiosity, perceived discrimination, depression or guilt feelings about drinking. DISCUSSION: The prevalence data show that current drinking is lower and that regular drinking is much lower in ethnic minorities and - with the exception of those of Moroccan origin - ethnic minority regular drinkers also have a significant lower risk to develop binge drinking or AD than regular drinkers of Dutch origin. This implies that the magnitude of problematic alcohol use is substantially smaller in ethnic minorities than in the ethnic Dutch population of Amsterdam. Unfortunately, no explanation was found for the special risk situation of regular drinkers of Moroccan origin.

Contribution of Alcohol and Nicotine Dependence to the Prevalence of Depressed Mood in Different Ethnic Groups in The Netherlands: The HELIUS Study.

Objective: Ethnic minorities report different levels of drinking and smoking and higher rates of depression compared to native populations. In this study we aimed to investigate in six ethnic groups whether tobacco and alcohol use were associated with depressive symptoms, which are more prevalent in ethnic minorities.Methods: Cross-sectional data from the multi-ethnic Healthy Life in an Urban Setting (HELIUS) study sample (N = 22,471) was used, comprising 4,580 native Dutch participants which were compared with participants from five ethnic minority groups (3,259 South Asian Surinamese, 4,292 African Surinamese, 2,262 Ghanaian, 3,891 Turkish, and 4,187 Moroccan).Results: Alcohol misuse was positively associated with depressed mood in all ethnic groups except for the Dutch and the Ghanaians. Nicotine dependence was positively associated with depressed mood in all ethnic groups except for the Ghanaian group.Conclusions: Alcohol misuse and nicotine dependence were significantly associated with depressed mood in most but not all ethnic groups and especially in men. However, across all groups the contribution of alcohol misuse and nicotine dependence to depressed mood was small. Prospective multi-ethnic studies should confirm whether the relations are causal and elucidate their direction.

Acceptance of pharmaceutical cannabis substitution by cannabis using patients with schizophrenia.

BACKGROUND: Cannabis-smoking patients with a psychotic disorder have poorer disease outcomes than non-cannabis-smoking patients with poorest outcomes in patients smoking high-potency cannabis (HPC) containing high Δ9-tetrahydrocannabinol (THC) and low cannabidiol (CBD). Quitting cannabis smoking or substitution of HPC by cannabis variants containing less THC and/or more CBD may benefit these patients. The present study explores whether daily HPC-smoking patients with schizophrenia accept smoking such variants. METHODS: Twelve male patients were asked to smoke on six different occasions one joint: on two occasions, the cannabis they routinely smoke (HPC; not blind), and blind in random order; on two occasions, cannabis containing low THC and no CBD; and on two occasions, cannabis containing low THC and high CBD. RESULTS: Both substitute variants were appreciated, but patients preferred the HPC they usually smoked. The effect of the low THC/high CBD variant was reported by 32% to be too short and by 36% to be not strong enough, whereas this was reported by 5% and 64%, respectively, for the low THC cannabis variant. CONCLUSIONS: Based on these findings, a larger and longer study on the efficacy of cannabis substitution treatment in HPC-smoking patients with schizophrenia seems feasible and should be considered. TRIAL REGISTRATION: 2014-005540-17NL . Registered 22 October 2014, 2014-005540-17NL 20141215 CTA.xml.

Causal Factors of Increased Smoking in ADHD: A Systematic Review.

BACKGROUND: ADHD is a highly prevalent disorder and poses a risk for a variety of mental disorders and functional impairments into adulthood. One of the most striking comorbidities of ADHD is nicotine dependence. Youth diagnosed with ADHD are 2-3 times more likely to smoke than their peers without ADHD, initiate smoking earlier in life and progress more quickly and more frequently to regular use and dependence. Possible explanations for these increased risks are: (a) self-medication of ADHD symptoms with the stimulant nicotine; (b) ADHD symptoms like inattention and hyperactivity/impulsivity predispose for smoking initiation and impede smoking cessation; (c) peer pressure; and/or (d) common genetic or environmental determinants for ADHD and smoking. OBJECTIVE: Identify the most probable causes of the high prevalence of smoking and nicotine dependence in subjects with ADHD. METHODS: A systematic literature review was performed and the causality of the observed relations was ranked using the Bradford Hill criteria. FINDINGS: ADHD medication reduces early smoking initiation and alleviates smoking withdrawal. Nicotine patches, bupropion and (probably) varenicline ameliorate ADHD symptoms. Imitation of and interaction with peers and genetic and environmental determinants may contribute to the comorbidity, but seem to contribute less than self-medication. CONCLUSION: Smoking is probably best explained by a combination of imitation, peer pressure and typical traits of ADHD. In contrast, the positive relation between ADHD and nicotine dependence is currently best explained by the self-medication hypothesis. This hypothesis has a clear pharmacological rationale and is supported by ample evidence, but awaits confirmation from longitudinal naturalistic studies.

Recreational nitrous oxide use: Prevalence and risks.

Nitrous oxide (N2O; laughing gas) is clinically used as a safe anesthetic (dentistry, ambulance, childbirth) and appreciated for its anti-anxiety effect. Since five years, recreational use of N2O is rapidly increasing especially in the dance and festival scene. In the UK, N2O is the second most popular recreational drug after cannabis. In most countries, nitrous oxide is a legal drug that is widely available and cheap. Last month prevalence of use among clubbers and ravers ranges between 40 and almost 80 percent. Following one inhalation, mostly from a balloon, a euphoric, pleasant, joyful, empathogenic and sometimes hallucinogenic effect is rapidly induced (within 10 s) and disappears within some minutes. Recreational N2O use is generally moderate with most users taking less than 10 balloons of N2O per episode and about 80% of the users having less than 10 episodes per year. Side effects of N2O include transient dizziness, dissociation, disorientation, loss of balance, impaired memory and cognition, and weakness in the legs. When intoxicated accidents like tripping and falling may occur. Some fatal accidents have been reported due to due to asphyxia (hypoxia). Heavy or sustained use of N2O inactivates vitamin B12, resulting in a functional vitamin B12 deficiency and initially causing numbness in fingers, which may further progress to peripheral neuropathy and megaloblastic anemia. N2O use does not seem to result in dependence. Considering the generally modest use of N2O and its relative safety, it is not necessary to take legal measures. However, (potential) users should be informed about the risk of vitamin B12-deficiency related neurological and hematological effects associated with heavy use.

Ranking the harm of non-medically used prescription opioids in the UK.

A panel of nine experts applied multi-criteria decision analysis (MCDA) to determine the relative overall harm to users and harms to others of street heroin (injected and smoked) and eleven non-medically used prescription opioids. The experts assessed harm scores for each of the 13 opioids on each of 20 harm criteria, weighted the criteria and explored the resulting weighted harm scores for each opioid. Both forms of heroin scored very high: overall harm score of 99 for injected heroin and 72 for smoked heroin on a scale of 0-100. The main feature that distinguishes both forms of street heroin use is that their harm to others is more than five times that of the other eleven opioids. The overall harm score of fentanyl (including injection of fentanyl extracted from patches) and diamorphine (medically prescribed form of heroin) was 54 and 51, respectively, whereas that of orally used opioids ranged from 32 (pethidine) to 11 (codeine-containing pharmaceuticals). Injected street heroin, fentanyl and diamorphine emerged as most harmful to users, with the latter two very low in harm to others. Pethidine, methadone, morphine and oxycodone are also low in harm to others, while moderate in harm to users. We conclude that the overall harms of non-medically used prescription opioids are less than half that of injected street heroin. These data may give a basis for precautionary regulatory measures that should be considered if the rising trend in non-medical use of prescription opioids were to become evident in the UK.

Exploring the Attractiveness of New Psychoactive Substances (NPS) among Experienced Drug Users.

A growing number of New Psychoactive Substances (NPS) appear yearly on the European market (81 for the first time in 2013, adding to a total of over 350 NPS). Using semi-structured interviews with 25 Dutch experienced recreational drug users, the role of the Internet and friends in gathering and exchanging information about NPS was elaborated. Furthermore, we investigated how NPS were acquired and which aspects make NPS more or less attractive, including their legal status. It appeared that the Internet was an important source of information about NPS in general. Personal experiences with NPS were preferably shared face-to-face with friends, as for privacy reasons users were cautious to post their experiences on web sites and forums. NPS were usually obtained or bought from friends or-to a lesser extent-purchased via the Internet. The preference for a specific NPS depended on the desired effects (mostly stimulant or psychedelic), price (similar to MDMA or amphetamine), duration of effect (preferably around four hours), and setting (at home, at festivals, or in nightlife). Legal status was not relevant for the decision to use NPS. Most NPS are not superior to the already marketed drugs, and do not displace conventional illicit drugs.

Risk factors of γ-hydroxybutyrate overdosing.

The aim of this study was to identify in recreational drug users the factors which increase the risk of overdosing (OD) with γ-hydroxybutyrate (GHB). A purposive sample of 45 experienced GHB users was interviewed, equally divided into three groups (never OD, occasional OD, and repeat OD). The repeat OD group scored highest on many risk factors regarding GHB use, the occasional OD group scored intermediate, and the never OD group scored lowest. Participants, whether or not they had overdosed on GHB, most often perceived GHB use (e.g. using more GHB than usual, using GHB doses too closely together) as the main reason for GHB OD, and many participants who had overdosed on GHB reported that they had taken more GHB than usual at their most recent occasion of GHB OD. No significant differences in co-use of GHB with other substances were found between the three groups. Our findings indicate that using GHB in the company of groups of friends probably reduces, but does not eliminate, the risk of OD.

Risk assessment of GBL as a substitute for the illicit drug GHB in the Netherlands. A comparison of the risks of GBL versus GHB.

In the Netherlands, γ-hydroxybutyric acid (GHB) was recently banned, but γ-butyrolactone (GBL) was not. As such, GBL remained a legal alternative to GHB. This review compares the risks of GBL and GHB. Pure GBL is per unit of volume about threefold stronger and therefore threefold more potent than currently used GHB-preparations in the Netherlands. Like GHB, GBL use hardly leads to organ toxicity, although, as with GHB, frequent GBL use may lead to repeated comas that may result in residual impairments in cognitive function and memory. Little is known about the prevalence of GBL use in Europe, but the recent increase in improper trading in GBL confirms that users of GHB gradually switch to the use of GBL. This shift may result in an increase in the number GBL dependent users, because the dependence potential of GBL is as great as that of GHB. Severe withdrawal symptoms and a high relapse rate are seen following cessation of heavy GBL use. GBL-dependent users seem to be severe (dependent, problematic) GHB users who started using GBL, the legal GHB substitute. Subjects who are solely dependent to GBL are rarely reported. About 5-10% of the treatment seeking GHB dependent subjects also use GBL and this subpopulation forms a vulnerable group with multiple problems. Fatal accidents with GBL are rarely reported, but non-fatal GHB (or GBL) overdoses frequently occur for which supportive treatment is needed. It is recommended to monitor the recreational use of GBL, the rate of GBL dependence treatment, and the improper trading of GBL.

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.

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.