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Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. Previous research has shown that cocaine-associated deaths occur more frequently in hot weather, which has not been described for other illicit drugs or combinations of drugs. The study objective was to evaluate the relation between temperature and risk of death related to cocaine, opioids and amphetamines in British Columbia, Canada. We extracted data on all deaths with cocaine, opioid or amphetamine toxicity recorded as an underlying or contributing cause from BC vital statistics for — We used a time-stratified case-crossover design to estimate the effect of temperature on the risk of death associated with acute drug toxicity during the warmer months May through September. We included deaths in the analyses. There were also elevated effects when toxicity from multiple drugs was recorded. Sensitivity analyses showed differences in the ORs by sex, by climatic region, and when the location of death was used instead of the location of residence. Increasing temperatures were associated with higher odds of death due to drug toxicity, especially for cocaine alone and combined with other drugs. Targeted interventions are necessary to prevent death associated with toxic drug use during hot weather. Psychoactive substances act on the brain to change mood, perception and behaviour, but differ in their mode of action and effects on the body. Some of these effects and their accompanying health risks can be exacerbated by environmental conditions. Both cocaine and amphetamines are psychostimulants that can increase dopamine levels in the brain. Strong prescription opioids such as morphine, oxycodone, hydromorphone and especially fentanyl and its derivatives carry a substantial risk of acute toxicity and fatal outcome if used inappropriately. There has been an ongoing crisis worldwide due to the entry of the synthetic opioids fentanyl and carfentanil into the illicit drug supply. Two ecologic studies in New York and 1 individual-level study in Quebec have reported that cocaine-associated deaths occur more frequently in hot weather. Similarly, a small body of evidence has associated colder weather with a higher risk of opioid toxicity. Although opioid toxicity has not been previously associated with warmer weather, we include it in this study for 2 reasons. First, deaths from illicit drug toxicity have been declared a public health emergency in the province of British Columbia since April Second, there is increasing use of drug mixtures, 14 including stimulant-opioid combinations that have different effects than either drug alone. The objective of this study was to evaluate the relation between temperature and death associated with cocaine, opioid and amphetamine toxicity in BC, when present in the vital statistics death record, either alone or in combination, using a time-stratified case-crossover design. The effect of temperature on death due to drug toxicity has not been widely studied. It is of growing importance as the global climate continues to warm and the global drug toxicity crisis continues to escalate, 18 especially since the COVID pandemic. We used a time-stratified case-crossover design to describe the effect of temperature on deaths associated with cocaine, opioid and amphetamine toxicity. The case-crossover design was developed to study the immediate determinants of acuteonset disease e. It can avoid confounding effects of factors that do not vary over the short term, such as sex, age, socioeconomic status, lifestyle, underlying comorbidities and seasonality. To evaluate the association between the outcome and the exposure, we compared the temperature for the date of death event date with the values for similar dates on which the death did not occur control dates. The control dates were selected with the time-stratified bidirectional referent approach, meaning that they were matched by day of week and calendar month to the death date for each individual. For example, a death that occurred on the second Tuesday in June would have its temperatures matched to those for the first, third, fourth and fifth when applicable Tuesdays in June. This approach results in 3—4 control dates for every event date. The bidirectional referent approach is less biased than selecting control dates from before the death only. British Columbia is the westernmost province in Canada, with a landmass covering km 2 and spanning 25 degrees of longitude and 11 degrees of latitude. The current population is about 5. In previous work, we have divided BC into 4 climatic regions to show how these regions modify temperature effects in the province. This study examines the relations between death from drug toxicity and temperature during the warmer months May through September of the year period from to The death records include the date of death, underlying and contributing causes, age, sex, 6-digit postal code of residence and 6-digit postal code of location of death from onward only. In most cases, the certificate of death is submitted by a clinician. However, any unattended deaths, deaths in public places, unexpected deaths and deaths among children must be investigated by the BC Coroners Service. In these cases, including drug toxicity deaths, the certificate of death is submitted by the coroner. Death data for this study were extracted from the vital statistics database, as described in more detail below. Temperature data for this study were extracted from the weather data archives of Environment and Climate Change Canada 33 and used as described below. These archives provide the geographic coordinates of each weather station, along with hourly measurements of air temperature and many other meteorological parameters. We identified deaths associated with cocaine, opioid or amphetamine toxicity from the vital statistics data, on the basis of their ICD codes. The same codes are used regardless of whether the drug was illicit or prescribed. All deaths from May to September in — with any T code for cocaine, opioid or amphetamine toxicity as a primary or secondary cause were included in the analyses. Many deaths associated with acute drug toxicity also had an F code for chronic drug use as an underlying or contributing cause. Deaths without a T code and with F codes for more than 1 of the 3 drugs were excluded from the comparative analyses. The complex topography of BC creates many microclimates, and there are clear differences in heat-related health risks across the province. We excluded deaths that were more than 50 km from the nearest station. The 2-day average of daily maximum temperatures was extracted for the death date and the matched control dates in the case-crossover study design. Time of death is not available in the vital statistics data, so we could not assess whether each death occurred before or after the hottest hours of the day. The 2-day average of maximum temperatures e. We ran all primary models with the continuous values and a binary variable indicating whether the 2-day average was equal to or greater than the 90th percentile value for the station over the year study period. The latter was done to reflect relatively hot weather, because absolute temperature distributions vary across different areas of the province. The location of residence and location of death are different for many decedents, and temperature at the location of death may provide a better assessment of exposure for drug toxicity deaths. However, information on the location of death was available only for vital statistic records from onward. We compared the effect of temperature at the location of residence with the effect of temperature at the location of death for the subset of cases for which both locations were available. Subgroup analyses were also conducted by sex and by climatic regions of the province i. Finally, we repeated analyses for deaths with only 1 chronic drug use F code and no acute toxicity T code present in the vital statistics record. Deaths with F codes for more than 1 drug were excluded. This was to better evaluate whether effects were associated with habitual drug use or acute toxicity. We used the R statistical computing environment version 3. The British Columbia Centre for Disease Control is a public health agency with the mandate to perform applied analytics to support policy and practice in British Columbia under the Public Health Act. During the May to September months of —, deaths in the BC vital statistics records were attributed to acute toxicity T code or chronic use F code of cocaine, opioids or amphetamines Table 1. Of these, 54 1. A further 20 0. Of the remaining deaths, had a code for acute drug toxicity T code , including The mean age at death was approximately 43 years, and Most decedents During the same period, deaths had chronic cocaine use F code indicated without indication of chronic opioid or amphetamine use or any acute toxicity. There were deaths that had only chronic opioid use and that had only chronic amphetamine use Table 2. There were small differences between the mean 2-day average of maximum temperatures on death dates and control dates across all 4 climatic regions Table 3. Summary information for all deaths included in the main analyses, with 1 or more cocaine, opioid or amphetamine toxicity T codes present in the vital statistics record. Summary of May to September temperatures for all weather stations in each climatic region, and death dates and control dates used in the case-crossover study design. The most elevated ORs were 1. The pattern of results was similar for the binary variable indicating whether the 2-day average of maximum temperature was over the 90th percentile. For example, the OR for cocaine toxicity only was 1. However, the OR for opioid toxicity alone was 1. Continuous temperatures were used in all further analyses. Daily maximum temperatures were measured at the weather station nearest to the residential location, within 50 km. There were deaths from to with postal codes for the residence and location of death. Models comparing the effect of temperatures assigned by residential location with the effect of temperatures assigned by the location of death were similar Figure 2 and consistent with the primary results Figure 1. However, the OR for combined cocaine and opioid toxicity was significant in these models. Subset analyses by sex showed that risks were similar for both groups Figure 3. Subset analyses by climatic region showed that the ORs were most elevated for deaths due to cocaine and opioid toxicity in the mountain region. They were also elevated in the coastal and dry plateau regions. Effects were null in the north, and there were insufficient data to support robust stratified analyses for amphetamines Figure 4. Analyses were restricted to deaths from to , for which a location of death postal code was available. Daily maximum temperatures were measured at the weather station nearest the residential location top or the location of death bottom within 50 km. Daily maximum temperatures were measured at the weather station nearest the residential location, within 50 km. When the same models were applied for death records with chronic use F code of a single drug but no acute toxicity T code , the ORs were elevated for cocaine and amphetamines but not significant Figure 5. In all cases, the CIs for the F code analyses overlapped with those for the T code analyses. The OR for chronic cocaine use only was 1. The odds ratio for chronic opioid use only was 0. Finally, the OR for chronic amphetamine use was 1. Overall, increasing temperatures were most clearly associated with increased odds of death in the context of acute toxicity from cocaine alone or in combination with other drugs. Our results may also suggest an association with opioid toxicity, though models with continuous and binary temperatures produced somewhat inconsistent results Figure 1. Analyses on chronic drug use showed an elevated OR for cocaine use that overlapped with the OR for acute toxicity. These results suggest that chronic use and acute toxicity may contribute to temperature-related risks among those who use cocaine, which is plausible given that cocaine use affects acute and chronic cardiovascular outcomes. These findings are consistent with the small body of epidemiologic evidence on this topic. Marzuk and colleagues studied cases involving unintentional drug overdose from to in New York. They compared 3 mutually exclusive case groups cocaine, opioids and other drugs with 2 other groups homicides and deaths from motor vehicle crashes. There was no effect of hot days on deaths associated with opioid toxicity. We observed that concurrent toxicity due to cocaine, opioids and amphetamines was associated with the highest odds of death in hot weather. Studies in humans have found that stimulant—opioid combinations produce cardiovascular and subjective effects that differ from the effects produced by either drug alone. Opioids and stimulants have different effects. Opioids lead to respiratory depression, whereas cocaine and amphetamines lead to heat generation and reduced heat dissipation through different mechanisms. The province of BC is large, with a complex topography and different climatic regions. Temperatures are typically more moderate along the coast, more variable within the mountain ranges and cooler across the north Table 3. We observed the highest odds of death from cocaine toxicity in the mountain region, but the number of deaths in this group was small. However, there was a similar number of deaths from cocaine toxicity in the north, where the OR was not elevated at all. This marked difference between the groups may be due to lower temperatures in the north, or higher variability in the mountains, leading to more contrast between the case and control days in the case-crossover design Table 3. The results of this study must be interpreted in the context of the ongoing drug toxicity crisis and the changing climate in BC. The public health emergency related to drug toxicity was first declared in , but the numbers of cases and deaths have continued to rise, especially since the COVID pandemic. We have limited this study to deaths through because of the data delays, but the summer climate in BC has shifted notably in the past decade. Our study has some important limitations. Although many potential mechanisms could explain our observations, we cannot discount the possibility that our findings are confounded by heat-and cocaine-associated behaviours. Cocaine use may be more likely to occur on warmer rather than cooler days, or cocaine users may be more likely to engage in risky behaviour on hotter days. Both alternative hypotheses could explain, at least in part, the observed association. Individuals were matched to temperatures based on their residential 6-digit postal code in the vital statistics record, but they may have been exposed at other locations on the date of death or the control dates. Our subgroup analyses found small differences when residential and death locations were compared. The vital statistics data do not distinguish between toxicity due to illicit or prescribed drugs, and the temperature-related impacts may differ between groups. The vital statistics records do not include any information on the toxic dose of drugs present at the time of death, meaning that we cannot evaluate the degree of intoxication, only the fact of intoxication. All these limitations are shared by similar studies on the topic. This study found that higher temperatures were associated with a higher risk of death when the code for acute cocaine toxicity was present in the vital statistics record, either alone or combined with other drugs. The risk was also elevated in other groups. Overall, targeted education and interventions may help to prevent deaths from drug toxicity during hot weather, especially as the drug supply becomes more toxic, the global climate continues to warm and extreme heat events become more frequent. People who use substances may not know that they are at higher risk. Simple interventions include training staff and volunteers who work with people who use substances, and displaying and distributing resources in areas where people gather, such as overdose prevention sites. The authors are grateful to the editors, statisticians and reviewers who have helped to strengthen this work. Competing interests: None declared. This article has been peer reviewed. Contributors: Sarah Henderson contributed to the conceptualization, methodology, formal analysis and supervision of the study and the drafting and review of the manuscript. Kathleen McLean and Jiayun Yao contributed to the formal analysis and data curation of the study, review of the manuscript and visualization. Yue Ding contributed to the formal analysis and data curation of the study, drafting the manuscript and visualization. Nikita Saha Turna and David McVea contributed to detailed literature review, interpretation of the data, and drafting and reviewing the manuscript. Tom Kosatsky contributed to conceptualization, methodology and supervision of the study, and the drafting and review of the manuscript. All authors gave final approval of the version to be published and agreed to be accountable for all aspects of the work. Funding: No funding was received for this work. The meteorological data were accessed through Environment and Climate Change Canada, and are publicly available online. Supplemental information: For reviewer comments and the original submission of this manuscript, please see www. As a library, NLM provides access to scientific literature. CMAJ Open. Published online Jun Sarah B. Henderson , PhD, Kathleen E. Corresponding author. Correspondence to: Sarah Henderson, ac. Associated Data Supplementary Materials Reviewer comments. Abstract Background: Previous research has shown that cocaine-associated deaths occur more frequently in hot weather, which has not been described for other illicit drugs or combinations of drugs. Methods: We extracted data on all deaths with cocaine, opioid or amphetamine toxicity recorded as an underlying or contributing cause from BC vital statistics for — Results: We included deaths in the analyses. Interpretation: Increasing temperatures were associated with higher odds of death due to drug toxicity, especially for cocaine alone and combined with other drugs. Methods We used a time-stratified case-crossover design to describe the effect of temperature on deaths associated with cocaine, opioid and amphetamine toxicity. Outcome: death associated with drug toxicity We identified deaths associated with cocaine, opioid or amphetamine toxicity from the vital statistics data, on the basis of their ICD codes. Exposure: temperature The complex topography of BC creates many microclimates, and there are clear differences in heat-related health risks across the province. Sensitivity and subgroup analyses The location of residence and location of death are different for many decedents, and temperature at the location of death may provide a better assessment of exposure for drug toxicity deaths. Ethics approval The British Columbia Centre for Disease Control is a public health agency with the mandate to perform applied analytics to support policy and practice in British Columbia under the Public Health Act. Results During the May to September months of —, deaths in the BC vital statistics records were attributed to acute toxicity T code or chronic use F code of cocaine, opioids or amphetamines Table 1. Code Description No. Open in a separate window. All deaths with a T code first row for each drug were included in the main analyses, and any deaths with an F code for only 1 of the drugs were used as a comparator. Table 2: Summary information for all deaths included in the main analyses, with 1 or more cocaine, opioid or amphetamine toxicity T codes present in the vital statistics record. Characteristic No. Table 3: Summary of May to September temperatures for all weather stations in each climatic region, and death dates and control dates used in the case-crossover study design. Figure Sensitivity and subgroup analyses There were deaths from to with postal codes for the residence and location of death. Interpretation Overall, increasing temperatures were most clearly associated with increased odds of death in the context of acute toxicity from cocaine alone or in combination with other drugs. Limitations Our study has some important limitations. Conclusion This study found that higher temperatures were associated with a higher risk of death when the code for acute cocaine toxicity was present in the vital statistics record, either alone or combined with other drugs. Supplementary Material Reviewer comments: Click here to view. Original submision: Click here to view. Acknowledgements The authors are grateful to the editors, statisticians and reviewers who have helped to strengthen this work. Footnotes Competing interests: None declared. References 1. Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine. Psychopharmacology Berl ; —5. Mechanism of cocaine-induced hyperthermia in humans. Ann Intern Med. Djurendic-Brenesel M, Pilija V. Chapter Opiate receptors and gender and relevance to heroin addiction. In: Preedy VR, editor. Cambridge MA : Academic Press; Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review. Association of elevated ambient temperature with death from cocaine overdose. Drug Alcohol Depend. Ambient temperature and mortality from unintentional cocaine overdose. Ambient temperature and risk of death from accidental drug overdose in New York City, — Changes in locomotor activity, core temperature, and heart rate in response to repeated cocaine administration. Physiol Behav. Fatal excited delirium following cocaine use: epidemiologic findings provide new evidence for mechanisms of cocaine toxicity. J Forensic Sci. Cocaine-induced agitated delirium with associated hyperthermia: a case report. J Emerg Med. Cocaine-induced agitated delirium: a case report and review. J Intensive Care Med. Increased risk of opioid overdose death following cold weather: a case—crossover study. Front Commun Lausanne ; 7 Fentanyl quantification using portable infrared absorption spectroscopy. A framework for community drug checking. Vib Spectrosc. The cardiovascular and subjective effects of intravenous cocaine and morphine combinations in humans. J Pharmacol Exp Ther. Psychopharmacology Berl ; — Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans. Tackling the overdose crisis: the role of safe supply. Int J Drug Policy. Nguyen T, Buxton JA. Pathways between COVID public health responses and increasing overdose risks: a rapid review and conceptual framework. Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol. Bateson TF, Schwartz J. Who is sensitive to the effects of particulate air pollution on mortality? A case-crossover analysis of effect modifiers. Case-crossover analyses of air pollution exposure data: referent selection strategies and their implications for bias. Case-crossover analysis of air pollution health effects: a systematic review of methodology and application. Environ Health Perspect. Does air pollution trigger suicide? A case-crossover analysis of suicide deaths over the life span. Eur J Epidemiol. Absolute temperature, temperature changes and stroke risk: a case-crossover study. Effects of cold temperature and snowfall on stroke mortality: a case-crossover analysis. Environ Int. The impact of temperature on mortality in Tianjin, China: a case-crossover design with a distributed lag nonlinear model. Int J Epidemiol. Comparison of the statistical efficiency of case—crossover and case—control designs: application to severe cutaneous adverse reactions. J Clin Epidemiol. Vulvovaginal candidiasis associated with acitretin. Snowfall, temperature, and the risk of death from myocardial infarction: a case-crossover study. Differences in heat-related mortality across four ecological regions with diverse urban, rural, and remote populations in British Columbia, Canada. Health Place. Historical data. ICDMortality Manual 2a — Establishing heat alert thresholds for the varied climatic regions of British Columbia, Canada. The effects of acute and chronic cocaine use on the heart. Kahlig KM, Galli A. Regulation of dopamine transporter function and plasma membrane expression by dopamine, amphetamine, and cocaine. Eur J Pharmacol. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. Amphetamine mechanisms and actions at the dopamine terminal revisited. J Neurosci. Qualitative review of serotonin syndrome, ecstasy MDMA and the use of other serotonergic substances: hierarchy of risk. Aust N Z J Psychiatry. Chapter Cocaine-induced breakdown of the blood—brain barrier and neurotoxicity. Int Rev Neurobiol. Snapshot of current data for paramedic-attended overdose calls across the province. Overdose response in BC communities. The Western North American heat dome increased climate change anxiety among British Columbians: results from a natural experiment. J Clim Chang Health. Analysis of community deaths during the catastrophic heat dome: early evidence to inform the public health response during subsequent events in greater Vancouver, Canada. Environ Epidemiol. Copy Download. Cocaine-related mental and behavioural disorders. Opioid-related mental and behavioural disorders. Poisoning by or adverse effect of psychostimulants. Psychostimulant-related mental and behavioural disorders.