Faculty Bibliography

3,4-methylenedioxymethamphetamine (MDMA; commonly referred to as "ecstasy" or "molly") is a substituted amphetamine drug that is used recreationally for its acute psychoactive effects, including euphoria and increased energy, as well as prosocial effects such as increased empathy and feelings of closeness with others. Acute adverse effects can include hyperthermia, dehydration, bruxism, and diaphoresis. Post-intoxication phenomena may include insomnia, anhedonia, anxiety, depression, and memory impairment, which can persist for days following drug cessation. MDMA acts as a releasing agent for monoamine neurotransmitters, including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), by interfering with vesicular storage and transporter function, thus increasing extracellular levels of DA, NE, and 5-HT. Medical intervention in response to adverse events is complicated by the fact that illicitly-acquired MDMA is frequently adulterated, contaminated, or outright replaced with other psychoactive drugs such as synthetic cathinones ("bath salts") or methamphetamine, often unknown to the person using the drug. This review provides background on the legal status of MDMA and its use patterns, including proposals for its use as an adjunct in psychotherapy. It also discusses the pharmacological properties, mental and physical health effects, and interactions of MDMA with other drugs, with special focus on harm reduction strategies. This information will help healthcare providers assess adverse health effects related to MDMA/ecstasy use in order to facilitate appropriate treatment strategies and improve patient outcomes.

BACKGROUND:Ketamine's potential for treating depression has drawn increased clinical interest in recent years. However, despite growing therapeutic use, recreational use among individuals with depression remain underexplored. METHODS:We analyzed data from the 2015-2022 National Survey on Drug Use and Health focusing on adults in the US. Trends in past-year ketamine use, overall and by depression status, were estimated separately for 2015-2019 and 2021-2022 due to methodological changes in the survey. We also delineated correlates of ketamine use in each period, focusing on depression, sociodemographic characteristics, and other past-year drug use. RESULTS:Overall ketamine use prevalence increased from 2015 to 2019 (from 0.11 % to 0.20 %, an 81.8 % increase, p < 0.01) and from 2021 to 2022 (from 0.20 % to 0.28 %, a 40.0 % increase, p < 0.05). From 2015 to 2019, use increased among adults with and without depression (by 139.3 % [p < 0.05] and 66.7 % [p < 0.05], respectively), while from 2021 to 2022, an increase occurred only among those without depression (by 38.9 %, p < 0.05). Multivariable models revealed that depression was associated with increased odds of ketamine use in 2015-2019 (aOR = 1.80, 95 % CI: 1.12-2.89) but not in later years. New sociodemographic correlates emerged in 2021-2022, including adults aged 26-34 and those with a college degree being at higher odds for use. Various drugs (especially ecstasy/MDMA and gamma-hydroxybutyrate) were consistently associated with higher odds of use. CONCLUSION/CONCLUSIONS:We identified differential patterns and correlates of ketamine use over time. Shifts may be related to the evolving ketamine landscape and/or changing survey methodology. Monitoring of use patterns is crucial to inform prevention and harm reduction strategies.

INTRODUCTION/BACKGROUND:Cannabis use and cannabis use disorder (CUD) are associated with adverse psychosocial outcomes, but their impact on workplace absenteeism remains poorly understood. Moreover, few studies have examined the role of CUD severity. This study aims to address these gaps by examining the associations between cannabis use recency, frequency, CUD severity, and workplace absenteeism. METHODS:Cross-sectional data from a U.S. representative sample of full-time employed adults aged ≥18 from the 2021 to 2022 National Survey on Drug Use and Health (N=46,499) were analyzed. The associations between cannabis use recency, past-month cannabis use frequency, CUD severity, and workplace absenteeism (measured by self-reported number of missed days due to illness/injury and skipped work in the last 30 days) were evaluated using negative binomial regression, adjusting for sociodemographic characteristics and other substance use. Data were analyzed in 2023-2024. RESULTS:An estimated 15.9% of full-time employed adults used cannabis in the past month, with 6.5% meeting CUD criteria. Past-month cannabis use (compared to no lifetime use), more frequent past-month cannabis use (compared to no use in the past month), and each level of CUD (compared to no CUD) were associated with increased incidence of both missing work due to illness/injury and skipping work, with a dose-response relationship observed between CUD severity and skipping work (mild: adjusted incident rate ratio [aIRR]=1.60 [95% confidence interval [CI]=1.24, 2.08]; moderate: aIRR=1.98 [95% CI=1.50, 2.61]); severe (aIRR=2.87 [95% CI=2.12, 3.88]). CONCLUSIONS:Individuals with recent and frequent cannabis use and CUD are disproportionately prone to workplace absenteeism. Results support the enforcement of workplace drug prevention and treatment policies.

INTRODUCTION/BACKGROUND:Ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) is a drug commonly used by people who attend electronic dance music (EDM) events at nightclubs and dance festivals. Drug checking has gained popularity in recent years to test for adulterants, but epidemiology studies are needed to estimate potential shifts in prevalence of drug checking to further inform harm reduction efforts. METHODS:Adults entering randomly selected EDM events in New York City were surveyed in 2017 and 2022. Those reporting past-year ecstasy use were asked if they tested their ecstasy in the past year using a drug testing kit and whether they found out or suspected their ecstasy contained other drugs. We compared estimates between 2017 and 2022. RESULTS:In 2017, an estimated 23.1% had tested their ecstasy, and this estimate increased to 43.1% in 2022 (86.6% increase, p = 0.006). Among those who tested their ecstasy, in 2017, 31.2% always tested their drug, and this increased to 60.6% in 2022 (94.2% increase, p = 0.026). In 2017, 59.6% of those who tested their ecstasy reported finding out or suspecting their drug was adulterated, which decreased to 18.4% in 2022 (69.1% decrease, p < 0.001). Suspected methamphetamine adulteration in particular decreased, from 21.9% in 2017 to 3.6% in 2022 (83.6% decrease, p = 0.007). DISCUSSION AND CONCLUSIONS/CONCLUSIONS:The use of drug testing kits has increased among EDM event attendees who use ecstasy and, at the same time, among those who had tested their ecstasy, suspected adulteration has decreased. Continued interest in understanding ecstasy contents among this population suggests the need for formal drug checking services.

BACKGROUND:The spread of illicitly manufactured fentanyl is driving steep increases in US overdose deaths. Fentanyl seizures are correlated with state-level opioid-related mortality; however, more granular seizure surveillance information has the potential to better inform overdose prevention and harm reduction efforts. METHODS:Using data on fentanyl pill and powder seizures from High Intensity Drug Trafficking Areas (HIDTA), we tested associations between seizure prevalence and overdose mortality, from 2013 to 2020. The primary exposure-seizure burden-was constructed by identifying counties having high (above the median) prevalence of pill, powder, or combined pill/powder seizure burden per 100,000 population. Poisson models accounted for county demographic, law enforcement and time trends. RESULTS:During the timeframe, there were 13,842 fentanyl seizures in 606 US counties. In adjusted models, counties with a high burden of pill or powder fentanyl seizures, or both (combined pills/powder) exhibited higher total overdose mortality than non-high burden counties (pills adjusted prevalence ratio [aPR]: 1.10 [95 % confidence interval [CI]: 1.08, 1.12]; powder aPR 1.12 [CI: 1.11, 1.13]; combined pills/powder aPR: 1.27 [CI: 1.25, 1.29]). A similar pattern of associations with fentanyl seizure burden was noted for overdose deaths involving synthetic opioids (pills [aPR]: 0.99 [CI: 0.96, 1.02]; powder aPR 1.29 [CI: 1.27, 1.30]; combined pills/powder aPR 1.55 [CI: 1.52, 1.58]). CONCLUSIONS:Law enforcement data on fentanyl seizures predicts drug overdose mortality at the county-level. Integrating these data with more traditional epidemiologic surveillance approaches has the potential to inform community overdose response efforts.

BACKGROUND:Rates of synthetic opioid-related deaths over time and across regions have been compared within the US, but other indicator data could help inform prevention and harm reduction as well. We compared regional trends in fentanyl seizures to examine potential shifts in illicit fentanyl availability. METHODS:Annual trends in fentanyl seizures were examined using data from High Intensity Drug Trafficking Areas for the US overall and by region from 2017 through 2023. Multiple measures included the number of seizures, the number of powder seizures, the number of pill seizures, the total weight of seizures, the number of pills seized, and the percentage of the number of pill seizures relative to the number of total seizures. RESULTS:The percentage of seizures in pill form in the US increased from 10.3 % in 2017 to 49.0 % in 2023 (adjusted annual percentage change [AAPC]=25.2, 95 % CI: 17.6, 33.2), with 115.6 million individual pills seized in 2023. Pill weight related to total seizure weight also increased from 0.4 % to 54.5 % (AAPC=112.6, 95 % CI: 78.6, 153.2). In 2023, the plurality of seizures was in the West, in seven out of eight of our measures, with 77.8 % of seizures in the West being in pill form. Although the Midwest had lower prevalence of seizures than the West, there were notable increases in the Midwest in the number of pill seizures (AAPC=142.2, 95 % CI: 91.9, 205.8) and number of pills seized (AAPC=421.0, 95 % CI: 272.7, 628.4). Total weight of fentanyl seized increased the most in the West (AAPC=84.6, 95 % CI: 72.3, 97.8). CONCLUSIONS:The number and size of fentanyl seizures is increasing in the US, with the majority of seizures, especially in pill form, in the West. Continued monitoring of regional shifts in the fentanyl supply can help inform targeted prevention and public health response.

BACKGROUND:Pentobarbital is a Schedule II/III short-acting barbiturate with limited medical use in humans. Veterinary professionals use pentobarbital to euthanize dogs, cats, and other companion animals. Pentobarbital is also utilized in capital punishment and small amounts are illegally shipped or diverted to assist in suicides. However, five kilograms of pentobarbital smuggled in from Mexico was recently seized by an organized crime drug enforcement task force (along with fentanyl, heroin, and cocaine), which may suggest a shift in illicit supply. We investigated potential indicators of illicit pentobarbital use or availability in the US to help determine whether this drug is becoming an emerging public health concern. METHODS:The National Drug Early Warning System requested information on pentobarbital from its sentinel surveillance sites and collaborators and conducted a search of current literature. RESULTS:In early 2024, multiple batches of counterfeit pills (e.g., pressed as "M30s" to represent oxycodone) confiscated near the Southwest border tested positive for pentobarbital plus combinations of fentanyl, fentanyl analogs, and xylazine. Other indicators suggest pentobarbital is being smuggled in powder form and possibly sold as another drug such as heroin. One national drug analysis program detected pentobarbital in 217 drug submissions from 2020 to 2023, and there were at least 12 fatal exposures linked to use from 2020 to 2022. CONCLUSION/CONCLUSIONS:Continued monitoring of illicit use and availability is needed as pentobarbital may continue to appear on the illicit market. Unknown exposure can occur if the drug is mixed into counterfeit pills or sold in powder form represented to be another drug.