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The aim of this study was to test the hypothesis that past naturalistic use of classic psychedelics would be associated with decreased prevalence of substance use disorder, when controlling for known confounders. We calculated adjusted odds ratios by multivariate logistic regression, controlling for a range of sociodemographic variables, use of non-psychedelic illicit drugs and mental health related variables. Results: A total of 56, participants were included in this study. Past use of LSD and psilocybin were associated with increased odds of substance dependence or abuse compared to those who had never used psychedelics before, and this was more likely for those who had used LSD more recently. Past use of classic psychedelics was not associated with nicotine dependence. Future research should investigate why naturalistic use of different psychedelics is associated with different substance use disorder effects. Alcohol and drug addiction pose a major threat to public health 1. In , illicit drug dependence accounted for 20 million disability adjusted life years 2. In , alcohol and tobacco use cost the human population over a quarter billion disability adjusted life years and illicit drug use cost an additional tens of millions of disability adjusted life years 3 , 4. The public health burden of these diseases is likely to grow as the global prevalence of substance use disorders continues to rise 4. Substance use disorders SUD are complex conditions and treatment is not effective for many patients 5. Relapse rates for addictions are similar to those of chronic diseases like diabetes and asthma 6. In recent years there has been renewed interest in the use of classic psychedelics to aid in the treatment of SUD 9 , Classic psychedelics are serotonin 2A 5-HT 2A receptor agonists, such as lysergic acid diethylamide LSD , psilocybin and mescaline that induce hallucinogenic and mystical-type experiences and have anti-depressive, anxiolytic, and antiaddictive effects 10 — Though the exact anti-addictive mechanism of action is unknown, there is substantial evidence that drugs of abuse modulate serotonin transmission in the 5-HT raphe nuclei and their forebrain projections. As such, effective pharmacological manipulation of the 5-HT system may be the mechanism which is contributing to successful recovery from the repeating cycle of addiction by alleviating some of the neurochemical abnormalities associated with drugs of abuse The 5-HT 2A receptor agonism in frontal and limbic areas of the brain by classic psychedelics increase glutamatergic transmission and neuroplasticity 12 , so much so that research has shown that just one or two doses can have enduring positive outcomes for individuals with SUD Classic psychedelics both enable reorganization of disordered neural pathways in the default mode network and attenuate maladaptive signaling in the mesolimbic reward circuitry that plays a central role in addiction Persistent changes in substance use behavior seen after psychedelic experiences may be due to these neurological processes, but also seem to be mediated by psychological responses to the highly meaningful and mystical experience from psychedelics 9 , similar to brain changes seen after traumatic events Such profound mystical experiences are associated with sudden and lasting behavioral change, such as long-term abstinence from alcohol 7 , 15 — Still, the plasticity-inducing effects of 5-HT 2A receptor agonism make the psychedelic experience especially sensitive to context Contemporary research has found that set and setting is so important for realizing therapeutic effect because psychedelics put the user in a state of enhanced suggestibility 21 , In fact, in studies in which set and setting were neglected, therapeutic outcomes were less positive It is for this reason that researchers believe that many indigenous groups have participated in sacramental ritual use of psychedelics for religious and pedagogical purposes since ancient times 11 , Examples of such sacramental use include religious consumption of ayahuasca 12 , 23 and the religious sacrament performed by the Native American Church NAC in which peyote is consumed as part of an all-night communal prayer and song ceremony for the purpose of healing physical or spiritual imbalances that an individual or the community may be experiencing 15 , 24 — Similarly, ibogaine is often used in ceremonial contexts and in clinical research for addiction treatment 27 , Use in these contexts has been associated with remission of psychopathologies such as depression, anxiety, and SUD Current research continues to show the efficacy of treating various addictive disorders with psychedelic assisted psychotherapy in the clinical context 9 , 29 — In addition to the extraordinary effects of psychedelic assisted psychotherapy seen in clinical trials, large population-based studies of naturalistic i. One of the largest population studies on psychedelic use sought to evaluate the effect of naturalistic use of psychedelics on mental health. The results of this study showed that use of psychedelics was not only not an independent risk factor for mental health problems, but that psychedelic use was indeed associated with a lower rate of mental health problems Further epidemiological studies have suggested that naturalistic use of classic psychedelics is associated with positive mental health outcomes 11 , 34 — 37 , including smoking cessation 38 and decreased risk of opioid use disorder 39 , These studies of naturalistic use of psychedelics are particularly important for our understanding of psychedelics because of the central role played by set and setting in mediating therapeutic effects and because naturalistic psychedelic use happens outside of controlled settings. While past epidemiological studies have shown significant association between past use of classic psychedelics and specific substance use disorders, there are no known large population-based studies which look at the association between naturalistic use of classic psychedelics categorically across several compounds and the broad category of substance use disorders. Therefore, the goal of this study is to validate the effect of naturalistic use of classic psychedelics seen in substance use disorders across classic psychedelic compounds. Based on past research, we hypothesized that individuals exposed to any of these classic psychedelics would have lower rates of substance use disorder when controlling for demographic variables and for confounding by co-occurring mental illness. The NSDUH survey provides estimates of substance use and mental health indicators from a representative sample of the US civilian non-institutionalized population. The data included individuals 12 years of age and older. Each of the substances were also analyzed as individual substances and therefore each substance was represented with its own variable, except for peyote and mescaline which were collapsed into one variable since mescaline is the active compound in the peyote cactus. Lysergic acid diethylamide was the only classic psychedelic in the survey that included questions on recency of use. This variable was included to investigate whether there were differences in substance dependence or abuse among individuals based on how long ago they had last used LSD in comparison to individuals who had never used LSD before. The DSM-4 had two diagnoses: substance dependence and substance abuse. In the DSM-5, these diagnoses were collapsed into one diagnosis—substance use disorder mild to severe This variable was added as a secondary dependent variable because, unlike past year illicit drug or alcohol dependence or abuse, this variable included information on substance cravings. While the DSM-5 diagnosis of SUD largely focuses on substance dependence and abuse criteria, it also includes criteria on substance cravings. As such, nicotine dependence based on NDSS score was included as an additional dependent variable to investigate whether past exposure to classic psychedelics was differentially associated with nicotine dependence. This study investigated the presence of substance dependence or abuse among individuals who have and have not been exposed to classic psychedelics. Because SUD so often co-occurs with other mental illness, 43 , 44 a categorical variable on presence and severity of past year mental illness was included as a control variable. The Krebs and Johansen study 35 also included a control variable on lifetime exposure to an extremely stressful event. The NSDUH survey did not include any such variable and thus this control variable was not included in the study. Regression analysis was done to find the ratio of the odds of having past year illicit drug or alcohol dependence or abuse among individuals who used classic psychedelics in their lifetime compared to those that had never used before. The binary logistic regression was first run to get the unadjusted odds ratio, and then another logistic regression was run which included control variables. Another set of logistic regressions was run using nicotine dependence as the dependent variable, first by using the variable lifetime use of classic psychedelics as one binary variable and then by differentiating between the three categories of classic psychedelics. These regressions were also run first without and then with the control variables mentioned above. Lastly, a series of logistic regressions was run using recency of LSD use as the predictor variable in place of lifetime exposure to classic psychedelics. All data analysis was done using SPSS version All tests were two-sided. Lifetime exposure to at least one of the classic psychedelics was reported by 6, individuals Further summary data can be found in Table 1. Table 1. Summary demographic and mental health data of individuals who have and have not used any of the classic psychedelics included in this study. The unadjusted odds of past year drug or alcohol dependence or abuse among individuals exposed to LSD in their lifetimes was 5. When including control variables, however, we computed an aOR of 1. The results from these logistic regressions, including the attenuating affect of control variables are summarized in Table 2. Table 2. Results of logistic regression showing adjusted odds ratio for past year substance use disorder among users of any of the classic psychedelics in this study, as a class of substances and individually. When looking at nicotine dependence as the outcome variable, the odds ratio for individuals exposed to any psychedelic was 4. When including control variables, we found no significant association between nicotine dependence and exposure to psychedelics. These results are summarized in Table 3. Table 3. Odds ratios OR and adjusted odds ratios aOR of past year illicit drug or alcohol dependence or abuse and nicotine dependence among individuals exposed to classic psychedelics in comparison to individuals in the sample who have never used these psychedelics. When differentiating the effect on substance use disorder by recency of LSD use, participants who were exposed to LSD within the past 30 days had These same individuals had 4. Similarly, for individuals who had used LSD more than a month prior but in the past year, the odds of past year SUD were This group those who had used LSD within the past year but more than 30 days prior had 3. In the absence of control variables, individuals who had last used LSD more than a year prior had 4. This same group had 5. When including control variables in the analysis, individuals whose last use of LSD was more than a year prior had just 1. The adjusted odds ratio of drug or alcohol dependence for those who last used LSD more than a year prior was 0. No other associations were significant when controlling for other variables. These results are summarized in Table 4. Table 4. Odds ratios OR and adjusted odds ratios aOR of past year illicit drug or alcohol dependence or abuse and nicotine dependence among individuals based on recency of last LSD use. The purpose of this study was to investigate whether individuals who had used classic psychedelics in a naturalistic setting were less likely to have substance use disorder compared to those who had never used classic psychedelics. This study used a large sample of individuals who reported on their use of psychedelics, illicit drugs, alcohol, and nicotine, thereby illuminating several interesting facets of psychedelic use and its associated effects in a representative sample of the US population. Without adjusting for control variables, the part of the population that had used psychedelics in their lifetime were indeed significantly and dramatically more likely to have substance dependence or abuse in the past year. This makes sense when considering the growing prevalence of psychedelic use among users of other drugs 26 , 46 , Though prior psychedelic use was found to be associated with greater prevalence of substance dependence or abuse in the past year, adjusted analysis revealed a meaningful decrease in this effect. Furthermore, while lifetime exposure to classic psychedelics in general was associated with a slightly increased likelihood of past year substance dependence or abuse, differentiating between psychedelic substances in the regression analysis showed divergent effects between the different psychedelic compounds. Controlling for the confounding effects of age, sex, education level, race, past year mental illness severity, marital status, family income level, how often the respondent likes to test self with risky behavior, and having ever used any of the aforementioned drugs resulted in considerably adjusted odds ratios. Interestingly, the older an individual was at the time of interview seems to have resulted in lower odds of having an SUD. While this effect was not significant across the board, this does follow a trend which shows that age likely served as a confounding variable. Similarly, sex seemed like an obvious confounder as females have significantly lower odds of SUD and are similarly a smaller percentage of psychedelic users as shown in Table 1. Controlling for race revealed that some races seemed to have a significantly greater aOR for SUD compared to the non-Hispanic white population, which justifies including it as a control variable. However, future research should be done on these differences because, for example, while the Native American population had greater odds of having SUD, there are also traditions like the Native American Church which use psychedelics in a ceremonial context for healing Past year mental illness and how often one likes to test oneself with risky behavior both showed clear, significant trends which also make it likely that these variables were confounders. In addition, marital status was a significant control variable, suggesting that it too was a confounding variable. As is expected, people who had used almost all other drugs which were included as a control variable had significantly greater odds of SUD, excluding users of PCP, inhaled anesthetics and amyl nitrite. People who had used inhaled anesthetics indeed had significantly lower odds of SUD which is a phenomenon worth investigating in future research as well. Lastly, the two socioeconomic status control variables, income and education level, did not seem to show any clear, significant trend. This perhaps suggests that the effect of psychedelic use on SUD is independent of socioeconomic status. This was a cross-sectional study and so the effect of time was necessarily taken out of the equation. Interestingly, there was a significant downward trend in unadjusted odds for SUD as time since last use of LSD passed, although no such trend was found for nicotine dependence or when adjusting for control variables. One notable chemical difference is that mescaline is a phenylalkylamine whereas LSD and psilocybin are indoleamines 48 , While it is well established that classic psychedelics share a common attribute of agonist activity at the serotonin 5HT 2A receptor 49 , 50 , there is also evidence that other receptor sites are involved in bringing about the psychopharmacological effects of classic psychedelics. One difference between phenylalkylamines and indoleamines that may be consequential in explaining the differences seen between the compounds studied in this work is that phenylalkylamines, like mescaline, are selective 5-HT 2 receptor agonists, whereas indoleamines are non-selective for 5-HT receptors While the research on this is still in its early stages, it seems that the non-addictive nature of classic psychedelics is at least partially associated with serotonin 5-HT 2C receptor agonism Another possible explanation for why mescaline use in our study was associated with decreased SUD while LSD and psilocybin use were not, could be that mescaline is typically used in a more supportive context than LSD or psilocybin 26 , While the influence of set and setting was not accounted for in this study due to survey limitations, set and setting could have contributed to the different SUD outcomes seen in the LSD or psilocybin users vs. Furthermore, LSD and psilocybin use is associated with use of other illicit substances 52 — While this is hardly evidence for different set and setting, the possibility that mescaline users are more likely to enjoy a therapeutic context for their mescaline use than most LSD and psilocybin users is worth investigating in future research, given the extensive evidence on contextual factors set and setting mediating the kinds of benefits realized by psychedelic users 18 , 19 , 21 , It is important to note that these two possible explanations for why decreased substance dependence or abuse was observed for mescaline only and not LSD or psilocybin are not mutually exclusive. Nonetheless, future research could compare the effects of LSD, psilocybin, and mescaline use for treating SUD, using a unified set and setting protocol. This could provide greater evidence for or against the hypothesis that pharmacological differences between classic psychedelics mediate therapeutic effects for treating SUD. Furthermore, the outcome measure for this cross-sectional study was the adjusted odds ratio. This measure is based on the prevalence of SUD among people who had used psychedelics and not the incidence of SUD among psychedelic users. There were several limitations in this study. Firstly, there was incomplete information on the outcome of substance use disorder and we therefore used two response variables—illicit drug or alcohol dependence or abuse and nicotine dependence. While illicit drug or alcohol dependence or abuse was a good variable for capturing dependence or abuse of a large variety of substances that people abuse or are dependent on, this variable did not include information on substance cravings which is a criterion that is included in the DSM-5 diagnosis of substance use disorder. While there was not a singular SUD outcome variable, significant and meaningful associations were found for both outcome variables. This study was a cross-sectional study and therefore, limited in that it was unable to show temporality or causality. Nonetheless, by using lifetime use of psychedelics as the primary exposure variable and past year drug or alcohol dependence or abuse and past year nicotine dependence as the outcome variables, much of the exposure likely preceded the outcomes. Furthermore, by using the recency of LSD use variable, a better picture emerged of how the outcome variables changed as time passed since last LSD use. Though no strong conclusions could be drawn from the inclusion of this variable, it does appear that there was a downward trend of SUD among people the more time had passed since their last LSD use which should be investigated further in future research. This study suggests that naturalistic use of different psychedelics may have different effects and should thus be investigated and compared in future research, while taking into account other possible mediating factors. Publicly available datasets were analyzed in this study. As such, JR performed the research, analysis, and writing of this manuscript under the supervision of her thesis advisors, SL-R and RG. SL-R and RG provided their expertise in psychiatry, reviewed and approved the statistical analysis, proceeding results, and contributed their oversight to the writing of the manuscript. In addition, SL-R advised on all matters related to addiction and substance use disorders. RG advised on all matters related to epidemiology and psychopharmacology, as well as his background in clinical use of psychedelics. All authors contributed to the article and approved the submitted version. The 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. 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. Tenegra J, Leebold B. Substance abuse screening and treatment. Prim Care. Global burden of disease attributable to illicit drug use and dependence: findings from the global burden of disease study Global statistics on alcohol, tobacco and illicit drug use: status report. The global burden of disease attributable to alcohol and drug use in countries and territories, a systematic analysis for the global burden of disease study Lancet Psychiatry. Volkow N, Boyle M. Neuroscience of addiction: relevance to prevention and treatment. Am J Psychiatry. Principles of drug addiction treatment: a research based guide. Maryland: National Institute of Health Google Scholar. Bogenschutz M, Ross S. Therapeutic applications of classic hallucinogens. Curr Top Behav Neurosci. Krebs T, Johansen P. Lysergic acid diethylamide LSD for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol. Bogenschutz M, Johnson M. Classic hallucinogens in the treatment of addictions. Prog Neuropsychopharmacol Biol Psychiatry. DiVito A, Leger R. Psychedelics as an emerging novel intervention in the treatment of substance use disorder: a review. Mol Biol Rep. Classic psychedelics: an integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacol Ther. Dos Santos R, Hallak J. Therapeutic use of serotoninergic hallucinogens: a review of the evidence and of the biological and psychological mechanisms. Neurosci Biobehav Rev. Psychedelic drugs in biomedicine. Trends Pharmacol Sci. Contributions of serotonin in addiction vulnerability. Bogenschutz M, Pommy J. Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: from indirect evidence to testable hypotheses. Drug Test Anal. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychedelics and the essential importance of context. Gukasyan N, Nayak S. Psychedelics, placebo effects, and set and setting: insights from common factors theory of psychotherapy. Transcult Psychiatry. Nichols D. Pharmacol Rev. LSD enhances suggestibility in healthy volunteers. Psychedelics alter metaphysical beliefs. Sci Rep. Dupuis D. Psychedelics as tools for belief transmission. Front Psychol. Jones P. The native american church, peyote, and health: expanding consciousness for healing purposes. Contemp Justice Rev. Pharmacokinetic and pharmacodynamic aspects of peyote and mescaline: clinical and forensic repercussions. Curr Mol Pharmacol. Examination of recreational and spiritual peyote use among American Indian youth. J Stud Alcohol Drugs. Curr Neuropharmacol. Corkery J. Ibogaine as a treatment for substance misuse: potential benefits and practical dangers. Prog Brain Res. Psychedelics and psychedelic-assisted psychotherapy. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Ross S. Serotonergic hallucinogens and emerging targets for addiction pharmacotherapies. Psychiatr Clin North Am. Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder. Front Pharmacol. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Psychedelics and mental health: a population study. PLoS One. Population survey data informing the therapeutic potential of classic and novel phenethylamine, tryptamine, and lysergamide psychedelics. Front Psychiatry. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. An online survey of tobacco smoking cessation associated with naturalistic psychedelic use. Psychedelic use is associated with reduced daily opioid use among people who use illicit drugs in a Canadian setting. Int J Drug Policy. The association of psychedelic use and opioid use disorders among illicit users in the United States. Drug Alcohol Depend. Shiffman S, Sayette M. Validation of the nicotine dependence syndrome scale NDSS : a criterion-group design contrasting chippers and regular smokers. Treatment access barriers and disparities among individuals with co-occurring mental health and substance use disorders: an integrative literature review. J Subst Abuse Treat. Exploring the link between substance use and mental health status: what can we learn from the self-medication theory? J Health Care Poor Underserved. Green S. How many subjects does it take to do a regression analysis. Multivariate Behav Res. Palamar J, Le A. Am J Addict. Johnstad P. Who is the typical psychedelics user? Methodological challenges for research in psychedelics use and its consequences. Nordisk Alkohol Nark. Canal C, Murnane K. The serotonin 5-HT 2C receptor and the non-addictive nature of classic hallucinogens. Halberstadt A, Geyer M. Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Chemistry and structure-activity relationships of psychedelics. The epidemiology of mescaline use: pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects. Over 30 million psychedelic users in the United States. Does getting high hurt? Characterization of cases of LSD and psilocybin-containing mushroom exposures to national poison centers between and Adverse childhood events and lifetime alcohol dependence. Am J Public Health. Bell S, Britton A. An exploration of the dynamic longitudinal relationship between mental health and alcohol consumption: a prospective cohort study. BMC Medicine. Keywords : psychedelic agents, mescaline, addiction, substance use disorder, population study. 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 , 10 January The association between naturalistic use of psychedelics and co-occurring substance use disorders. Introduction Alcohol and drug addiction pose a major threat to public health 1. Variable selection 2. LSD recency Lysergic acid diethylamide was the only classic psychedelic in the survey that included questions on recency of use. Past year illicit drug or alcohol dependence or abuse The DSM-4 had two diagnoses: substance dependence and substance abuse. Nicotine dependence This variable was added as a secondary dependent variable because, unlike past year illicit drug or alcohol dependence or abuse, this variable included information on substance cravings. Control variables This study investigated the presence of substance dependence or abuse among individuals who have and have not been exposed to classic psychedelics. Data analysis Regression analysis was done to find the ratio of the odds of having past year illicit drug or alcohol dependence or abuse among individuals who used classic psychedelics in their lifetime compared to those that had never used before. Keywords : psychedelic agents, mescaline, addiction, substance use disorder, population study Citation: Rabinowitz J, Lev-Ran S and Gross R The association between naturalistic use of psychedelics and co-occurring substance use disorders. Edited by: Ben H.

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Background and Aims: COVID has infected more than 77 million people worldwide and impacted the lives of many more, with a particularly devastating impact on vulnerable populations, including people with substance use disorders SUDs. Given the lack of multicentric epidemiologic studies, we conducted a rapid global survey within the International Society of Addiction Medicine ISAM network in order to understand the status of substance-use patterns during the current pandemic. Participants: Starting on April 4, during a 5-week period, the survey received responses from 77 countries. Measurements: To assess addiction medicine professionals' perceived changes in drug and alcohol supply, price, use pattern, and related complications during the COVID pandemic. With respect to changes in use patterns, an increase in alcohol Conclusions: The global report on changes in the availability, use patterns, and complications of alcohol and drugs during the COVID pandemic should be considered in making new policies and in developing mitigating measures and guidelines during the current pandemic and probable future ones in order to minimize risks to people with SUD. As of December 23, , the COVID pandemic has around 77 million cases of infection in more than countries with above 1,, overall deaths 1. Approximately 6 months after cases were first diagnosed, there remain few reliable treatments and no vaccines available, and an increasing number of countries are experiencing dangerous COVID transmission 2 , 3. Among vulnerable populations to infection and its complications are people with substance use disorders SUDs 4. Both comorbid medical conditions in SUDs such as cardiopulmonary diseases and related risk factors and drug—drug interactions between COVID medications and abused substances or SUD treatment medications , along with other factors, may lead to people with SUDs experiencing more complications when encountering COVID infections 4 — 6. People with SUDs are vulnerable given marginalization, stigmatization, and poor access to health and social services 7 , 8. Therefore, during the pandemic, gathering current information on the status of SUD is critical to support planning and mobilizing timely responses to minimize risks 4. Alterations in alcohol and drug supplies may change prices and availability and therefore use patterns. In the setting of COVIDrelated stressors, there may be decreases in drug and alcohol availability, increases in price and use patterns, and possible downstream effects on SUD presentations and treatment demands. Drug shortages, as the United Nation Office for Drug and Crime UNODC reports, could have negative health consequences regarding transitioning to consumption of harmful domestically produced substances along with more dangerous patterns of drug use including shifting to injections and using shared drug administration equipment, especially in the case of heroin 9. Concurrently, as legal liquor shops may remain closed during the lockdown in some countries, multiple problems may occur ranging from alcohol withdrawal to toxicity and death due to shifting to low-quality homemade liquor and accidental methanol ingestion 4 , For instance, as healthcare facilities become more difficult to access during lockdowns, people with SUDs may experience more difficulties relating to poor access to treatment centers. Socioeconomically disadvantaged backgrounds and diminished availability of public transportation may exacerbate such concerns 4 , 5 , 11 , especially for individuals receiving daily prescriptions of opioid substitution therapy 4. Professional authorities and health policymakers are expected to proactively address such emerging needs. However, the lack of reliable data complicates the generation and implementation of evidence-based policies. Although some activities and reports from different worldwide organizations have initially responded to the COVID pandemic, data provided have been limited and, in some occasions, as UNODC has reported, the information base for analyses has been restricted and feasibility of implementation unknown 1 12 — Thus, a vacancy exists for a comprehensive report describing the global situation with respect to drug use, drug supply, and related complications. In order to formulate a comprehensive health response, it is important to understand alcohol and drug markets' situation availability and price , use patterns and related complications, and how they may have changed during the pandemic. Designing a global in-depth epidemiologic study, apart from questions about its feasibility, is challenging during the pandemic. Therefore, the International Society of Addiction Medicine ISAM designed a comprehensive global survey and collected expert opinions on perceived changes in substance use situation and health system responses around the 1st week of April in what aims to be a longitudinal study Data related to the second section of the survey concerning substance use treatment and harm reduction services responses to the pandemic have been published recently We hypothesized that drug and alcohol use would increase, prices would increase, supply would decrease, and complications would increase and that results would differ by region given the differential spread of COVID and regional responses to the COVID pandemic. We hope that current data will help to address the urgent need for more accurate information about the status of drug and alcohol use in the current pandemic and provide information about appropriate modifications in health system services to respond to the emerging demands in the current pandemic and similar potential pandemics in the future. The complete study protocol has been previously published The ISAM mailing list and subsequent snowballing methodologies comprising addiction medicine professionals across the world were contacted on April 4, by email with an invitation to participate in the study by clicking on a link to the online survey. They also initially consented to be included as an author in the publications following the survey. Data collection was concluded on May 8, The questionnaire consisted of 92 questions in two main sections: 1 situational assessment during the pandemic and 2 health response to the pandemic. This paper provides an analysis of data obtained from the situation assessment section of the survey concerning changes in drug use, supply, price, risky behaviors, as well as related measures, namely morbidities, mortalities, and overdose rates during the COVID pandemic period in different countries Questions on the situational assessment section of the survey are available in Supplementary Method 2. The questionnaire was distributed in English for all the respondents. All statistical analyses were conducted using RStudio v. Descriptive data are presented as means and percentages for each country's response, as well as the average of the global responses. The survey protocols and all materials, including the survey questionnaires, received approval from the University of Social Welfare and Rehabilitation Sciences', ethics committee in Tehran, Iran Code: IR. Overall, respondents from 77 countries participated. Data from the rest of the respondents were analyzed. The list of the countries that provided information for this survey is available as a supplement Supplementary Method 1. Figure 1 depicts a map of the respondents' global distribution. Figure 1. Global distribution of the respondents to the survey. The survey involves respondents from 77 countries around the world, ranging from 1 to 13 participants from each country, demonstrated as a color spectrum from orange to dark red. Respondents consisted of males The mean age of the respondents was Information related to the respondents' main disciplines and academic degrees is shown Table 1. Table 1. The demographic and professional information of survey respondents including their gender, age, academic degree, and primary discipline. Respondents provided information about drug use changes in their countries during the COVID pandemic. Perceived drug use changes by country are shown Figure 2 , Table 2. Details of drug use changes are reported in Supplementary Material. Figure 2. Changes in alcohol and drug use during the COVID pandemic reported by respondents from 77 countries globally. Countries' names are sorted in alphabetical order, and the number of respondents from each country is in parentheses following the country name. Each response is indicated as a single dot for no change or up and down triangles for increased and decreased answers, respectively, with a minor jitter for better visualization. Opioids: prescription opioids. Table 2. Summary of the survey responses in different sections related to situational assessment including respondents' information about changes in alcohol and drug use pattern, supply, price, morbidity and mortality, and overdose. Respondents provided information about perceived drug supply changes in their countries during the COVID pandemic. The drug categories included the following: alcoholic beverages, cannabis including marijuana and synthetic cannabinoids such as spice, K2, etc. Decreased supply patterns for all substances were noted. Details of drug supply changes are reported in the Supplementary Material. Figure 3. Changes in alcohol and drug supply during the COVID pandemic reported by respondents from 77 countries globally. Respondents were asked to report changes the supply of alcohol, amphetamines, cannabis, cocaine, and opiates through the following options: Increased supply, decreased supply, no change , and I do not know. The mean of all responses, regardless of their originated countries and without considering those who did not know the answer, alongside the average answers of all countries, regardless of the number of respondents in each country, are addressed in the last two rows below the countries' names. Respondents provided information regarding perceived drug price changes in their countries during the COVID pandemic. Details of drug price changes are reported in the Supplementary Material. Figure 4. Changes in alcohol and drug prices during the COVID pandemic reported by respondents from 77 countries globally. Respondents were asked to report changes in alcohol, amphetamines, cannabis, and opiates prices through the following options: Price increased, Price decreased, Price did not change , and I do not know. Countries' names are sorted in alphabetic order, and the number of respondents from each country is in parentheses following the country name. The information related to changes in drug price among different countries is shown in Figure 4 and Table 2. Respondents provided information about whether morbidity and mortality, including fatal and non-fatal overdose rates, in their countries had changed during the COVID pandemic. Details of changes in mortalities and overdose rates are reported in the Supplementary Material. Figure 5. Changes in mortality, morbidity, and overdose in people with SUD during the COVID pandemic reported by respondents from 77 countries around the world. Respondents were asked to report changes in morbidity or mortality rates in people with SUD and changes in fatal and non-fatal overdose episodes through the following options: Increased, Decreased, I do not know, I do not like to answer , and Not applicable. Countries' names are sorted in alphabetical order, and the number of each country's respondents is mentioned in front of the names. The mean of all responses, regardless of their originated countries and without considering those who did not know the answer, alongside the average answers of all countries, regardless of the number of respondents in each country, are addressed in the last two rows below the countries' names SUD, Substance Use Disorder. Respondents reported an increase in behavioral addictions during the pandemic Supplementary Figure 1. Figure 6. Changes in risky behaviors including shifting to injection, using shared drug use equipment, needle sharing, and risky sexual behaviors during the COVID pandemic period, reported by respondents from 77 countries globally. Respondents were asked to report changes in risky behaviors injection, shared drug use equipment, needle sharing, and risky sexual behaviors through the following options: Yes, No, I do not know, I do not like to answer , and Not applicable. Countries' names are sorted in alphabetical order, and the number of each countries' respondents is mentioned in front of the names. The numbers of respondents who reported Yes or No answers to each question are demonstrated inside the bars If nothing is written, it indicates that there was only one response within Yes and No answers. The percentages shown by the bars are also based on only Yes or No answers. The mean percentages of all responses, regardless of their originated countries and without considering those who reported other than Yes and No answers, alongside the mean percentage answers of all countries, regardless of the number of respondents in each country, are addressed in the last two rows below the countries' names Risky Sex. Figure 7. Addiction medicine professionals were asked to report how seriously people with SUDs in their countries have been affected by the COVID pandemic using a range of between 1 and 1 representing Not affected , demonstrated with yellow at the beginning of the spectrum, and 10 representing Severely affected at the end of the spectrum, indicated with blue. Responses were collected beginning April 4, and through a 5-week period. They mostly believed that prices for alcohol and drugs have risen, and they have become less available during the pandemic. Most respondents reported increases in complications related to drug and alcohol use including increased morbidity and mortality in people with SUDs. Alterations in levels of alcohol consumption during pandemic are similar to those reported during prior social crises, like the — economic downturn Current reports from Australia indicate increases in purchases of alcoholic beverages during lockdown potentially due to the first mechanism However, India seems to be encountering a surge in numbers of individuals withdrawing from alcohol 5 , These independent reports from Australia and India are in line with our survey findings Figure 2. Initial reports from Australia and the United States indicate overall increases in alcohol sales, especially in online alcohol delivery subsectors 21 , although specific data from the industry on alcohol supply are largely lacking. However, there was no consensus among our survey respondents about changes in alcohol supply, as the responses that reported an increase, decrease, and no change were approximately equal. Approximately half of our survey respondents believed that there is no change in alcohol cost during the pandemic. This is while almost another half reported an increase in alcohol prices. We could not find any relevant reports indicating alcohol price alterations. Further data are needed as the pandemic progresses and hopefully resolves. There are currently concerns about morbidity and mortality spikes within people with AUDs and alcohol-associated liver disease during the pandemic The survey's results support the idea that these spikes can be seen among people with AUDs. Reports from Iran describe methanol poisoning of around 5, people with nearly deaths, which may be due to lack of education and illegal and uncontrolled alcohol sales because of alcohol bans in Iran 10 , 24 , However, to the best of our knowledge, there are yet no specific reports demonstrating the extent of alcohol overdose. The same pattern also applies to drug-related mortalities and morbidities. Survey results suggest increases in cannabis use in more than half of participating countries. The European Monitoring Centre for Drugs and Drug Addiction EMCDDA has investigated this matter through three large darknet markets 26 in the first 3 months of and reported overall increased market activity, mostly in relation to cannabis products 13 , This might show the initial effects of the pandemic on the European countries market, particularly before peaks in the number of people infected by COVID and subsequent widespread lockdowns. Opiates, amphetamines, and cocaine were generally reported to have a decrease or no change in patterns of usage in most countries. Although there are preliminary reports suggesting that opioid use is a risk factor for ICU admission in H1N1 infections and a possible risk factor for mortality following COVID infection, rumors about protective effects of opium use in Iran may have led to increased consumption 28 , In the US, an already severe opioid overdose crisis worsened since the COVID pandemic, with 30 out of 50 states reporting increases in overdoses between March and June of , with an increase in high potency synthetic opioids such as fentanyl in street supplies and decreased access to harm reduction and OUD treatment services cited as possible drivers of overdose increase 30 — While concerns have been also raised regarding probable effects of substances on COVID patients 4 , 33 , 34 , more research is needed on changes in drug use patterns and impacts on SUDs. Survey results also suggest increased use of prescription opioids, perhaps for similar reasons, and changes in services may be needed 35 , Canada, Australia, United Kingdom, and Scotland facilitated pharmacy-based methadone-dispensing programs as prescribing opioid-related medications increased This model may help to manage withdrawal syndromes during lockdown-related periods. In the United States, rapid changes in policies provided support to facilitate service delivery for people in opioid treatment programs, such as larger quantities of dispensed methadone and buprenorphine and relaxed regulations around virtual prescriber visits to initiate and continue medications for OUD in order to help patients access and maintain access to medications 35 , The EMCDDA has also noted that due to increases in the retail prices of cannabis and cocaine, the localized supply shortages may exist during the pandemic The UNODC has reported that across all regions globally, many countries have noted a general shortage of different drugs at the retail level, mostly due to reduction in imports or strict lockdown rules, resulting in fewer personal interactions for drug sales The UNODC has also noted a heterogeneous situation on bulk supply, both across drugs and across different countries Our results agree with multiple aspects of these reports of drug supplies. The UNODC reported that countries with strict rules on social distancing such as the Czech Republic, United Kingdom, Italy, and Iran have been facing increased street drug prices due to lack of availability Other reports from drug-producing countries suggest drug price decrements perhaps as a result of stockpiling of drugs Respondents mostly reported increases in behavioral addictions during the current pandemic, which may partly confirm the existing concerns on this matter 38 , Other small studies suggest increases in addictive behaviors 39 — Some forms of gambling may have decreased due to financial uncertainties, occupational problems, cessation of sporting events, closure of casinos, and other factors 40 , Discussing another addictive behavior, gaming has been represented to be a coping mechanism during the current stressful conditions Accordingly, gaming has increased among college students in India, who use gaming as an antistress mechanism Increased gaming has been occurring globally during the pandemic 43 , as well as pornography viewing These and other concerns have led to guidance about Internet use during the pandemic ISAM conducted the first global survey in the field of addiction medicine and successfully sampled responses from 77 countries and experts globally. This timely and rapid survey was designed in a multistep fashion including literature review, expert communication, professional qualitative appraisal, and finally a pilot study 17 and was able to rapidly and reliably address urgent gaps in knowledge during the current pandemic. However, there are limitations such as heterogeneity the numbers of respondents from different countries and their disciplines and educational levels. The convenience sample also may impact response rates and other factors. The lack of validated measures is a limitation, as is the lack of options for open-ended responses that would provide a window on the mechanisms driving reported trends. Given the dynamic nature of pandemics and lack of multicentric epidemiological studies, the survey is a timely approach to provide a snapshot of global clinical addiction medicine concerns during these unprecedented times. The objective of the ISAM survey was to provide initial, rapid preliminary evidence about how COVID has affected different situational aspects experienced by people with SUDs globally in order to help reach a better understanding of the current status. Provision of this information to international organizations and regional policymakers should help authorities plan for addressing urgent needs and providing suitable services not only in the current pandemic but also in future similar situations. To properly respond to the emerging demands and situational shifts during the COVID pandemic in the addiction treatment services across the world, at a macro policy level , it is critical to recognize the importance of 1 the social safety net and measures used to reduce the social inequality widening gap when such epidemics deteriorate an already vulnerable system, 2 responsive and publicly well-resourced healthcare with adequate supply of appropriate medication, 3 civil liberties, which could help increased participation and a judicious response by law enforcement agencies, and 4 policies that have taken in justifying alcohol sales and cannabis dispensaries as essential services and legislation allowing pharmacists to provide maintenance medications such as benzodiazepines in order to guarantee safe supplies. At a meso organizational level , it is important that clinical experience and knowledge on localized drug supply, price, and associated morbidities and mortality is shared within the organization in order to respond adequately. This makes it vital that organizations have a responsive continuity plan that can change with the needs of the population throughout the acute stage of the pandemic. It is also important to establish, support, and sustain varied digital platforms to allow better access to treatment for drug and alcohol using populations and minimize morbidities and possibly mortality. Establishing joint advocacy groups of service users and providers is also critical. In this unique global survey, experts in addiction medicine provided information on changes in regional alcohol and drug availability, price, usage, and related complications. Reduced availability may have generated increases in prices. Changed drug use patterns may not only impact people with SUDs but also give rise to risky behaviors and related complications. Most issues may potentially be preventable if future lockdown regulations are accompanied by enhanced service provision for at-risk communities. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The studies involving human participants were reviewed and approved by the survey protocols and all materials, including the survey questionnaires, received approval from the University of Social Welfare and Rehabilitation Sciences' ethics committee in Tehran, Iran Code: IR. The participants provided their written informed consent to participate in this study. ME and PR analyzed the data and ran the statistical analyses. All authors discussed the results, implications, and commented on the final manuscript. The 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. 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. World Health Organization. WHO A novel coronavirus from patients with pneumonia in China, N Engl J Med. Am J Trop Med Hygiene. COVID and substance use disorders: recommendations to a comprehensive healthcare response. Autonomic Neurosci Basic Clin. Volkow ND. Ann Internal Med. Arch Clin Infecti Dis. O'Connell JJ. Dying in the shadows: the challenge of providing health care for homeless people. Stigma, discrimination and the health of illicit drug users. Drug Alcohol Depend. 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Avoiding a new epidemic during a pandemic: the importance of assessing the risk of substance use disorders in the COVID era. Psychiatry Res. Marinelli E. Eur Rev Med Pharmacol Sci. Rapid implementation of service delivery changes to mitigate COVID and maintain access to methadone among persons with and at high-risk for HIV in an opioid treatment program. AIDS Behav. Opioid use disorder and the COVID 19 pandemic: A call to sustain regulatory easements and further expand access to treatment. Subst Abus. J Addiction Med. COVID and addiction. Gambling before and during the COVID pandemic among European regular sports bettors: an empirical study using behavioral tracking data. Int J Mental Health Addiction. Ind J Public Health. J Behav Addictions. Comprehen Psychiatry. Keywords: COVID, addiction, substance use disorder, global survey, behavioral addiction, illicit drug market. 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 , 06 August Introduction As of December 23, , the COVID pandemic has around 77 million cases of infection in more than countries with above 1,, overall deaths 1. Methods Sample The complete study protocol has been previously published Questionnaire The questionnaire consisted of 92 questions in two main sections: 1 situational assessment during the pandemic and 2 health response to the pandemic. Statistical Analysis All statistical analyses were conducted using RStudio v. Ethics Approval The survey protocols and all materials, including the survey questionnaires, received approval from the University of Social Welfare and Rehabilitation Sciences', ethics committee in Tehran, Iran Code: IR. Results Respondents' Global Distribution Overall, respondents from 77 countries participated.

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