Abuse of drug substances and resultant overdose deaths are no longer very straightforward— viz. , attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance use ( i.e. , the use of combinations of substances). Further, the combinations are often of unknown purity, and even of unknown composition. Overdose deaths are at all-time highs. The depressing statistics are monitored and reported by several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies ( e.g ., DEA). The information is disseminated for free for review and use. But it is our observation that although numeric presentation is helpful and adequate for professionals, the non-expert and the visual learner often find a visual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and overdose using available maps of the data. The previous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated overdose deaths in the context of other abused drugs.
Raffa, R., Pergolizzi, J.J. and Cukier, H. (In Press) Polysubstance Use and Overdose Visualized via Maps: Opioids. Pharmacology & Pharmacy, 13, 107-118. https://doi.org/10.4236/pp.2022.134008
Compton, W.M., Valentino, R.J. and DuPont, R.L. (2021) Polysubstance Use in the U.S. Opioid Crisis. Molecular Psychiatry, 26, 41-50. https://doi.org/10.1038/s41380-020-00949-3
Tori, M.E., Larochelle, M.R. and Naimi, T.S. (2020) Alcohol or Benzodiazepine Co-Involvement with Opioid Overdose Deaths in the United States, 1999-2017. JAMA Network Open, 3, Article ID: e202361. https://doi.org/10.1001/jamanetworkopen.2020.2361
Kandel, D.B., Hu, M.C., Griesler, P. and Wall, M. (2017) Increases from 2002 to 2015 in Prescription Opioid Overdose Deaths in Combination with Other Substances. Drug and Alcohol Dependence, 178, 501-511. https://doi.org/10.1016/j.drugalcdep.2017.05.047
Xu, L., Chockalingam, A., Stewart, S., Shea, K., Matta, M.K., Narayanasamy, S., et al. (2020) Developing an Animal Model to Detect Drug-Drug Interactions Impacting Drug-Induced Respiratory Depression. Toxicology Reports, 7, 188-197. https://doi.org/10.1016/j.toxrep.2020.01.008
Jones, C.M. and McAninch, J.K. (2015) Emergency Department Visits and Overdose Deaths from Combined Use of Opioids and Benzodiazepines. American Journal of Preventive Medicine, 49, 493-501. https://doi.org/10.1016/j.amepre.2015.03.040
Boon, M., Van Dorp, E., Broens, S. and Overdyk, F. (2020) Combining Opioids and Benzodiazepines: Effects on Mortality and Severe Adverse Respiratory Events. Annals of Palliative Medicine, 9, 542-557. https://doi.org/10.21037/apm.2019.12.09
Uemura, K., Sorimachi, Y., Yashiki, M. and Yoshida, K. (2003) Two Fatal Cases Involving Concurrent Use of Methamphetamine and Morphine. Journal of Forensic Sciences, 48, 1179-1181. https://doi.org/10.1520/JFS2002293
Pennings, E.J., Leccese, A.P. and Wolff, F.A. (2002) Effects of Concurrent Use of Alcohol and Cocaine. Addiction, 97, 773-783. https://doi.org/10.1046/j.1360-0443.2002.00158.x
Jones, C.M., Paulozzi, L.J., Mack, K.A. and Centers for Disease Control and Prevention (2014) Alcohol Involvement in Opioid Pain Reliever and Benzodiazepine Drug Abuse-Related Emergency Department Visits and Drug-Related Deaths—United States, 2010. Morbidity and Mortality Weekly Report, 63, 881-885.
Li, Y., Delcher, C., Wei, Y.-J.J., Reisfield, G.M., Brown, J.D., Tighe, P., et al. (2020) Risk of Opioid Overdose Associated with Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population-Based Cohort Study. Clinical Pharmacology & Therapeutics, 108, 81-89. https://doi.org/10.1002/cpt.1807
Horsfall, J.T. and Sprague, J.E. (2017) The Pharmacology and Toxicology of the ‘Holy Trinity’. Basic Basic & Clinical Pharmacology & Toxicology, 120, 115-119. https://doi.org/10.1111/bcpt.12655
Ritchie, H. and Roser, M. (2018) Opioids, Cocaine, Cannabis and Illicit Drugs. https://ourworldindata.org/illicit-drug-use
Substance Abuse and Mental Health Services Administration (2019) Section 1 PE Tables - Results from the 2019 National Survey on Drug Use and Health: Detailed Tables. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, Rockville. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHNationalFindingsReport2018/NSDUHNationalFindingsReport2018.pdf
Faraone, S.V. (2018) the Pharmacology of Amphetamine and Methylphenidate: Relevance to the Neurobiology of Attention-Deficit/Hyperactivity Disorder and Other Psychiatric Comorbidities. Neuroscience & Biobehavioral Reviews, 87, 255-270. https://doi.org/10.1016/j.neubiorev.2018.02.001
Heal, D.J., Smith, S.L., Gosden, J. and Nutt, D.J. (2013) Amphetamine, Past and Present—A Pharmacological and Clinical Perspective. Journal of Psychopharmacology, 27, 479-496. https://doi.org/10.1177/0269881113482532
Hutson, P.H., Tarazi, F.I., Madhoo, M., Slawecki, C. and Patkar, A.A. (2014) Preclinical Pharmacology of Amphetamine: Implications for the Treatment of Neuropsychiatric Disorders. Pharmacology & Therapeutics, 143, 253-264. https://doi.org/10.1016/j.pharmthera.2014.03.005
Docherty, J.R. and Alsufyani, H.A. (2021) Pharmacology of Drugs Used as Stimulants. The Journal of Clinical Pharmacology, 61, S53-S69. https://doi.org/10.1002/jcph.1918
Cheng, M.H., Block, E., Hu, F., Cobanoglu, M.C., Sorkin, A. and Bahar, I. (2015) Insights into the Modulation of Dopamine Transporter Function by Amphetamine, Orphenadrine, and Cocaine Binding. Frontiers in Neurology, 6, Article No. 134. https://doi.org/10.3389/fneur.2015.00134
Taylor, A. and McLeod, G. (2020) Basic Pharmacology of Local Anaesthetics. BJA Education, 20, 34-41. https://doi.org/10.1016/j.bjae.2019.10.002
Tseng, W., Sutter, M.E. and Albertson, T.E. (2014) Stimulants and the Lung: Review of Literature. Clinical Reviews in Allergy & Immunology, 46, 82-100. https://doi.org/10.1007/s12016-013-8376-9
Trippenbach, T. and Kelly, G. (1994) Effects of Acute and Chronic Cocaine on Breathing and Chemosensitivity in Awake Rats. American Journal of Physiology, 266, R696-R701. https://doi.org/10.1152/ajpregu.1994.266.3.R696
Tseng, C.C., Derlet, R.W. and Albertson, T.E. (1992) Cocaine-Induced Respiratory Depression and Seizures Are Synergistic Mechanisms of Cocaine-Induced Death in Rats. Annals of Emergency Medicine, 21, 486-493. https://doi.org/10.1016/S0196-0644(05)82511-9
Tseng, C.C., Derlet, R.W., Stark, L.G. and Albertson, T.E. (1991) Cocaine-Induced Respiratory Depression in Urethane-Anesthetized Rats: A Possible Mechanism of Cocaine-Induced Death. Pharmacology Biochemistry and Behavior, 39, 625-633. https://doi.org/10.1016/0091-3057(91)90138-R
Richard, C.A., Harper, R.K., Schechtman, V.L., Ni, H. and Harper, R.M. (1993) Respiratory Patterning Following Cerebral Ventricular Administration of Cocaine. Pharmacology Biochemistry and Behavior, 45, 849-856. https://doi.org/10.1016/0091-3057(93)90131-C
Di Maio, V.J. and Garriott, J.C. (1978) Four Deaths Due to Intravenous Injection of Cocaine. Forensic Science International, 12, 119-125. https://doi.org/10.1016/0379-0738(78)90019-1
Erzouki, H.K., Allen, A.C., Newman, A.H., Goldberg, S.R. and Schindler, C.W. (1995) Effects of Cocaine, Cocaine Metabolites and Cocaine Pyrolysis Products on the Hindbrain Cardiac and Respiratory Centers of the Rabbit. Life Sciences, 57, 1861-1868. https://doi.org/10.1016/0024-3205(95)02166-G
Friedman, J.R. and Hansen, H. (2022) Evaluation of Increases in Drug Overdose Mortality Rates in the US by Race and Ethnicity Before and During the COVID-19 Pandemic. JAMA Psychiatry, 79, 379-381. https://doi.org/10.1001/jamapsychiatry.2022.0004
De Weerdt, S. (2019) Tracing the US Opioid Crisis to Its Roots. Nature, 573, S10-S12. https://doi.org/10.1038/d41586-019-02686-2
West, R. and Brown, J.D. (2013) Theory of Addiction. 2nd Edition, Wiley Blackwell, Hoboken, 1-263. https://doi.org/10.1002/9781118484890