Association between altitude, prescription opioid misuse, and fatal overdoses

Abstract

Objective Prescription opioid misuse and fatal overdoses have increased significantly over the last two decades. Living at altitude has been linked to greater reward benefits of other drugs of abuse, and living at altitude may also exacerbate the respiratory depression linked to opioid use. Therefore, we examined the relationships between living at altitude, and prescription opioid misuse and fatal overdoses. Method State-level past year rates of prescription opioid misuse were retrieved from the Substance Abuse and Mental Health Services Administration. County-level overdose data were extracted from the Centers for Disease Control and Prevention. Multiple linear regression models were fit to determine the relationship between average state elevation and state rates of opioid misuse. Logistic regression models were fit to determine the relationship between county elevation and county-level fatal opioid overdose prevalence. Results After controlling for state opioid prescribing rates and other confounders, we identified a significant positive association between mean state altitude and state-level opioid misuse rates for women, but not men. We also found a significant positive association between county-level altitude and prevalence of fatal opioid overdose. Conclusions Living at altitude is thus demographically associated with increasing rates of misuse of prescription opioids, as well as of cocaine and methamphetamine. Animal studies suggest that the hypobaric hypoxia exposure involved with living at altitude may disrupt brain neurochemistry, to increase reward benefits of drugs of abuse. This increased misuse of both stimulants and opioids may increase likelihood of overdose at altitude, with overdoses by opioid use also potentially facilitated by altitude-related hypoxia.

Sex-Based Impact of Creatine Supplementation on Depressive Symptoms, Brain Serotonin and SSRI Efficacy in an Animal Model of Treatment-Resistant Depression

“…The hypobaric hypoxia experienced with living at altitude can cause deficits in blood oxygen levels and brain bioenergetic markers at as moderate an altitude as 4500 ft [23,25]. Living at altitude is linked to higher risk for MDD [4][5][6][7], and suicide [8][9][10][11][12][13][14] as well as for abuse of methamphetamine, cocaine and prescription opioids [72][73][74]. Both MDD and substance use disorders are linked to brain hypometabolic function and use of energetic compounds such as CRMH has been recommended as treatment for these metabolic disorders [33,34].…”

Mile high on heroin: Lessons on the opioid epidemic from the Mile High City

“…Nevertheless, epidemiological data indicate increased rates of opioid misuse and overdose at high altitudes, along with increased rates of cocaine and methamphetamine use, as well as suicides. [ 13 ] Since, respiratory arrest is the primary cause of death in opioid‐related overdose deaths, hypoxia can be a significant accelerator toward this deadly outcome. [ 13 ] Agents like naloxone have been incredibly helpful toward preventing these types of opioid‐related deaths, but medications like suboxone offer a tremendous advantage toward recovery from OUD.…”

“…[ 13 ] Since, respiratory arrest is the primary cause of death in opioid‐related overdose deaths, hypoxia can be a significant accelerator toward this deadly outcome. [ 13 ] Agents like naloxone have been incredibly helpful toward preventing these types of opioid‐related deaths, but medications like suboxone offer a tremendous advantage toward recovery from OUD. Suboxone is a combination of buprenorphine, a partial mu opioid receptor agonist, and naloxone, a mu opioid receptor antagonist, in a special formulation that combines the advantages of these opposing actions at the mu opioid receptor.…”