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Background: Over the past 15 years, comparative assessments of psychoactive substance harms to both users and others have been compiled by addiction experts. None of these rankings however have included synthetic cannabinoids or non-opioid prescription analgesics NOAs, e. We present here an updated assessment by German addiction medicine experts, considering changing Western consumption trends—including those of NOAs. Methods: In an initial survey, German addiction medicine physicians evaluated both physical and psychosocial harms in 5 dimensions of 33 psychoactive substances including opioids and NOAs, to both users and others. In a second survey, 36 addiction medicine physicians estimated the relative weight of each health and social harm dimension to determine the overall harm rank of an individual substance. We compared our ranking with the most recent European assessment from Results: Illicit drugs such as methamphetamine, heroin, cocaine and also alcohol were judged particularly harmful, and new psychoactive drugs cathinones, synthetic cannabinoids were ranked among the most harmful substances. Cannabis was ranked in the midrange, on par with benzodiazepines and ketamine—somewhat more favorable compared to the last European survey. Prescribed drugs including opioids in contrast to the USA, Canada, and Australia were judged less harmful. NOAs were at the bottom end of the ranking. Conclusion: In Germany, alcohol and illicit drugs including new psychoactive substances continue to rank among the most harmful addictive substances in contrast to prescribed agents including opioid analgesics and NOAs. Current laws are incongruent with these harm rankings. Illicit drugs such as methamphetamine, heroin, and cocaine, and also alcohol were judged particularly harmful. Prescribed drugs including opioids in contrast to the USA, Canada and Australia and non-opioid analgesics including gabapentinoids were judged less harmful. Current laws are somewhat incongruent with these harm rankings. Abuse of addictive psychoactive substances is characterized by negative health and social consequences not only for the user, but also for non-users in the community or society 1 , 2. The DSM-5 has defined various specific substance-related dependence and addiction conditions 3 , and ICD coding reflects distinct mental and behavioral disorders related to alcohol, tobacco, opiates, cocaine, stimulants, hallucinogens, sedatives and hypnotics, cannabis and cannabinoids, and volatile solvents 4. Over the past 15 years, the relative health and social harms potential of various addictive substances has been determined in England 5 , the Netherlands 6 , Scotland 7 , France 8 , and most recently in Australia 9 by medical and non-medical addiction experts. These rankings do not necessarily display congruence with legislative and law enforcement priorities in terms of relative regulation and control of substances, with alcohol being a prime example of dissonance between overall harms and control efforts 5 — 9. Nutt et al. In , a group of 40 medical and non-medical addiction experts from 21 EU countries came to the same conclusion This survey included 20 substances In the interim, as in other Western countries, there have been shifting patterns of substance abuse trends as well as political framework conditions in Germany, especially. Given these developments, we sought to update the assessment of the health and social harms from substances that are commonly misused in Germany and elsewhere and also of substances less frequently abused in our country, but already emerging 11 , In this context, synthetic cannabinoids 14 were included into harms rankings for the first time. We also included index surveys of harms rankings for propofol, an intravenous anesthetic 19 , and some non-opioid analgesics NOA , i. We decided to include NOAs together with opioid analgesics into our ratings because gabapentin and pregabalin gabapentinoids have recently entered the focus of addiction medicine. In the last decade, several pharmacovigilance databases, population-based studies and case reports have warned of their potential abuse liabilities and putative contribution to fatal overdoses especially in combination with opioids 22 , Even though NSAIDs are commonly thought to be non-addictive, there are recent case reports 25 , 26 and epidemiologic 27 , 28 as well as clinical data 24 that are raising some safety concerns about this traditional view. Other NOAs have also shown potential abuse and dependence liability e. Therefore, we felt it prudent to include the aforementioned NOAs for the first time in a study of this kind, too. This cross-sectional questionnaire-study comprised two consecutive steps survey 1 and survey 2, see below , in which quantitative questionnaires were distributed in written form among German addiction medicine experts. These experts were recruited at German addiction congresses and conferences. Additionally, the questionnaires were sent via email to 40 heads of German drug addiction treatment centers who were asked to distribute them in their zone of influence among other addiction medicine experts. Only those questionnaires which had been filled out by physicians who i were specialists, i. The experts' identity was kept anonymous with the exception of information about their age, gender, specialties, years of professional experience, years of work in tertiary care of SUD, and main focus of professional work acute care or rehabilitation hospital Table 1. The first survey was conducted from March to September and assessed the average harm of 33 substances in in 5 dimensions physical harm to users, psychological harm to users, social harm to users, physical and psychological harm to others, and social harm to others. As shown in Supplementary Figure 1 , these dimensions were defined by 16 criteria, which have been validated in several studies of this type 5 , 9 , 10 see Supplementary Materials—Methods Section. The questionnaire was returned by physicians and from those were evaluated since 21 experts did not meet the inclusion criteria. This information was needed to assess the validity of the ratings and to verify defined exclusion criteria, i. Consequently, the substances ayahuasca, khat, and kratom had to be excluded from the harm-evaluation Supplementary Figures 2 and 3. The second survey weighting of the dimensions to determine the overall harm in Figure 1 was conducted from September to May by cohort 2, which were recruited only from the emails to the aforementioned 40 heads of German drug addiction treatment centers. This follow-up survey was administered subsequently because the first survey was quite comprehensive, and combining the two surveys was deemed likely to overburden cohort 1 respondents, reducing the return quota. The second survey asked participants to estimate the relative weight as a proportion between 0 and 1 of each of the 5 dimensions used in the first survey for the constitution of overall harm of psychotropic substances. All of the 36 returned questionnaires were included. We used the mean relative weight given by the 36 experts to each dimension for calculating the overall harm of each substance Figure 1. Further details of the overall harm calculation of the remaining 30 substances and related data analyses including the comparison with the previous EU-ranking Figure 3 are presented in the Supplementary Materials. Figure 1. The relative contribution of the 5 dimensions Supplemental Figure 1 , Supplemental Table 1 had been weighted by cohort 2. Validation of rankings was performed first by evaluating the magnitude of variability between the overall harm rating and any of the five component dimensions. The specialist physicians had worked for a median of 15 years cohort 1 and Approximately three out of four participants worked in acute care hospitals, with the remainder working in rehabilitation clinics Table 1. Experts' ratings in the 5 separate dimensions are shown in the Supplementary Figures 4 — 8. Regarding overall harm, traditional drugs of abuse, i. The NPS, i. Ketamine, benzodiazepines, cannabis, psychotropic mushrooms, LSD, nicotine, and opioid analgesics were in the midrange. Methadone and buprenorphine both preferred in Germany for maintenance therapy of opioid dependence fell into the lower ranges, while methylphenidate in Germany the preferred medication for ADHD-treatment , and NOAs were at the lowest ranges of the harm-ranking. The assessments of the specialists from acute and rehabilitation hospitals were very similar as shown in Figure 2. Figure 2. This updated German survey assessed methadone, nicotine, cannabis and alcohol as less harmful than did the EU-raters in 10 , while psychotropic mushrooms, cathinones, ecstasy, GHB, methamphetamine, and crack were judged to be more harmful—see Figure 3. Figure 3. The lowest discrepancies between the average overall harm-rank and the 5 health and social dimension-ranks were found for the traditional illegal drugs crack and other cocaine , heroin, methamphetamine, and also for alcohol, which were also ranked at the top positions in terms of harms. The same applied to GHB and NPS ranking near the top, ketamine in the midrange, opioids at lower ranges, and most NOAs gabapentinoids, flupirtine, triptans at the lowest ranks. In the case of cannabis, the German literature currently reflects a general perception of relatively low physical harms and conversely a perception of elevated psychosocial harms to users, which dichotomy serves to corroborate the discrepancy here 29 — The discrepancy for nicotine and perhaps also for propofol to some extent may be owing in part to an unexpectedly low ranking of psychological harm to users which diverges from empiric evidence. This potential underestimation may therefore threaten the validity of the overall harm-ranks of these specific substances. When alternatively, we used the consensus-based weights of the EU-rating study 10 as a comparison sensitivity test, we found that the resulting ranking of overall harms Supplementary Figure 9 was very similar to our survey-derived weighted rankings shown in Figure 1 see Supplementary Table 2 for comparison. Our data corroborate the situation in many other countries 5 — 10 of discordance between expert harm rankings of popular drugs of abuse and their regulation by narcotic laws, as evidenced most strikingly by the assessment of alcohol—judged to be among the most harmful substances abused in our country. Similarly, the decreasing prevalence of nicotine use in Germany as tobacco smoking has been banned from many public areas such as hospitals, educational establishments, public transport, restaurants, pubs, and discos during the last 10 years or so may contribute to a lower-than-expected harm ranking. In addition it should be mentioned that nicotine use, despite its ability to produce considerable behavioral dependence is hardly associated with dramatic psychiatric effects, e. This study was the first to compare the harms of various NOAs with harms of well-characterized substances of abuse, and as expected identifies the harms of NOAs to be considerably lower than those of the traditional substances of abuse. The present study was also the first to include synthetic cannabinoids and propofol in an overall-harm ranking schema, which may be beneficial for the psychoeducation of users, for regulatory considerations, or for defining fields of political action for health promotion. NPS cathinones and synthetic cannabinoids have been assigned to the top harm-level group here. Policy-makers and clinicians would benefit from further data about the NPS-phenomenon, e. Compared with the EU-rating from 10 , cannabis, methadone and nicotine were assessed as less harmful, while crack, methamphetamine, GHB, cathinones, ecstasy, and psychotropic mushrooms were seen as more harmful Figure 3. Cannabis and hallucinogens i. It should be mentioned that psilocybin in Figure 1 listed as psychotropic mushrooms and LSD have both enjoyed re-emerging therapeutic potential in psychiatric diseases and appear to show low abuse potential in that context It is interesting to note that opioid analgesics were not within the top ranks of harmful drugs. The relatively low harm rankings of prescription opioids in our study stand in stark contrast to the high level of stigmatization of illicit opioids. These findings are congruent with the multi-decision analysis of nine experts 8 from the United Kingdom and 1 from the Netherlands suggesting that the overall harms of non-medically used prescription opioids are less than half that of injected street heroin Methadone was assessed as less harmful than standard opioid analgesics, which viewpoint might be biased by addiction medicine physicians' conception of methadone primarily as a standard opioid dependence maintenance treatment, which in this context has been repeatedly shown to reduce morbidity and mortality In the context of illicit use and abuse, methadone's harms e. This exposes a major limitation of drug harm-ranking studies based upon subjective assessments as they may not allow for clear differentiation between the harms of a drug with therapeutic indication in a medical context vs. These discrepancies in ranking of analgesics among other agents suggest that perhaps raters' experience in pain medicine should have been surveyed as well. It cannot be excluded that our ratings may be biased toward metropolitan rather than rural perception of substance use harms; clarifying this would require further study in larger samples. Also, a possible gender influence on drug harm perceptions was not explicitly investigated here 40 , As we had sent out the questionnaires without tracking all recipients, requesting forwarding to other German addiction medicine experts, we are unable to provide information about the exact number of experts who finally received our questionnaires. However, such modus operandi is not unusual for studies of this kind 5. Other limitations, similar to previous studies 5 — 10 include the fact that the present work cannot claim to meet strict requirements for representativeness. We aimed to reduce subjectivity biases by recruiting a large and homogeneous study group all physicians specializing in addiction medicine. However, no official statistic exists for how many specialists with more than 5 years of experience in tertiary care of SUD were working in Germany at the time of the study. We estimate that number to be somewhere between and physicians, thus our sample may yield a minority viewpoint. In Germany, addiction medicine experts usually are psychiatrists or general practitioners. Unlike the English 5 , EU 10 and Australian 9 studies, we used no consensus—feedbacks. Furthermore, prior consensus-based studies utilized smaller samples comprising addiction experts from different professions 5 , 9 , 10 , whose heterogeneity of experiences in the treatment of SUD more likely needed a consensus-based decision strategy than did our homogeneous group. Apart from the novel inclusion of NOAs, synthetic cannabinoids and propofol, there are a few strengths of the present study: i the utilization of one of the largest samples in this type of study; ii the considerable multidimensional addiction medicine experience of the participants, including that of rehabilitation clinic specialists Figure 2 , which in Germany focuses heavily upon psychosocial dimensions and outcomes; iii comparison with the previous EU-rating Figure 3 ; and iv the addition of comparisons of illicit and licit drug rankings to the current literature. It should be emphasized however that these relative overall rankings apply to population-level risks, and depending on the individual and situational context as well as on the intensity of the individual misuse, nearly every psychoactive substance can be used in a very dangerous and harmful way. This study provides an updated German addiction medicine expert ranking of the average overall harms as well as harms in specific health and social dimensions of various psychoactive substances, including analgesics. Alcohol was estimated to be among the most harmful addictive substances, along with heroin, cocaine, methamphetamine, GHB, and NPS i. The elevated risks of alcohol are somewhat discordant with the German narcotic law, similar to most countries. Cannabis and ketamine were ranked in midrange on par with benzodiazepines. Therapeutically used drugs such as non-opioid analgesics, methylphenidate, and opioids were estimated to be on the whole to be the least harmful at present. Such relative safety perception however is certainly subject to change should misuse and abuse patterns change over time The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. UB: conception and design. MSp: analysis of the data. UB and MSp: collection and interpretation of data. UB: drafting the article. All authors: revising it critically for important intellectual content. NS has received honoraria for several activities e. During the last 3 years he has participated in clinical trials financed by the pharmaceutical industry. TA has received honoraria e. TH has received honoraria for several activities e. He has received financial support for Investigator initiated trials from Medtronic GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We also thank the many physicians who kindly took the time to participate in this project. Mechanisms of action and persistent neuroplasticity by drugs of abuse. Pharmacol Rev. Morgen K. Counseling and Professional Identity in the 21st Century. Substance use Disorders and Addictions. Google Scholar. Diagnostic and Statistical Manual of Mental Disorders. Dilling H, Freyberger H. Bern: Huber Verlag Independent Scientific Committee on Drugs. Drug harms in the UK: a multicriteria decision analysis. Ranking the harm of alcohol, tobacco and illicit drugs for the individual and the population. Eur Addict Res. Quantifying the RR of harm to self and others from substance misuse: results from a survey of clinical experts across Scotland. BMJ Open. The Australian drug harms ranking study. J Psychopharmacol. 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Abuse liability of flupirtine revisited: implications of spontaneous reports of adverse drug reactions. J Clin Pharmacol. Abuse and misuse of pregabalin and gabapentin. Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol. Screening for physical and behavioral dependence on non-opioid analgesics in a German elderly hospital population. Addict Behav. Ibuprofen dependence: a case report. Identification of non-steroidal anti-inflammatory drug use disorder: a case report. Overuse and misperceptions of nonsteroidal anti-inflammatory drugs in the United States. Am J Med Sci. Adv Clin Exp Med. Use of an outpatient treatment center for cannabis abuse. Frequent non-medical cannabis use: health sequelae and effectiveness of detoxification treatment. Dtsch Med Wochenschr. Schneider D. Phenotypic effects of chronic and acute use of methiopropamine in a mouse model. Int J Legal Med. How deaths can help clinicians and policy-makers understand the risks of novel psychoactive substances. Br J Clin Pharmacol. Chi T, Gold JA. A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses. J Neurol Sci. The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents. Pain Rep. Estimation of the number of people with opioid addiction in Germany. Opioid prescription patterns in germany and the global opioid epidemic: systematic review of available evidence. Prescription opioid prescribing in Western Europe and the United States. Ranking the harm of non-medically used prescription opioids in the UK. Regul Toxicol Pharmacol. Bodnar RJ, Kest B. Sex differences in opioid analgesia, hyperalgesia, tolerance and withdrawal: central mechanisms of action and roles of gonadal hormones. Horm Behav. Gender differences and psychopathological features associated with addictive behaviors in adolescents. Front Psychiatry. Transparent prioritisation, budgeting and resource allocation with multi-criteria decision analysis and decision conferencing. Ann Operat Res. Rolles S, Measham F. Questioning the method and utility of ranking drug harms in drug policy. Int J Drug Policy. Balancing benefit and risk of medicines: a systematic review and classification of available methodologies. Pharmacoepidemiol Drug Saf. Substance related exogenous psychosis: a post-modern syndrome. CNS Spectr. Keywords: gabapentinoids, psychoropic drugs use, alcohol, illicit abused substance, new psychoactive drugs. Psychiatry The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Psychiatry , 26 October Key Points Illicit drugs such as methamphetamine, heroin, and cocaine, and also alcohol were judged particularly harmful. Introduction Abuse of addictive psychoactive substances is characterized by negative health and social consequences not only for the user, but also for non-users in the community or society 1 , 2. Methods This cross-sectional questionnaire-study comprised two consecutive steps survey 1 and survey 2, see below , in which quantitative questionnaires were distributed in written form among German addiction medicine experts. Table 1. Participants' characteristics. Table 2. Plausibility check of the overall harm ranks. D'Annunzio Chieti and Pescara, Italy.

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