This Week in the ASAM Weekly

Stuff happens as we move substance use along the spectrum between criminalization and commercialization. Canada found this out with cannabis, as legalization with restrictions was not initially associated with increased hospitalizations but commercialization definitely was and the most concerning elements were potency, frequency, and psychosis (JAMA Network Open). Popularity in research on LSD may have created a situation in which young adults with depression are increasingly more likely to try LSD, but it’s unclear if these are attempts at self-medication or something else (JAMA Psychiatry). 

Any substance that becomes more popular while also being viewed as less harmful is of particular concern for adolescent use. Given the complexities of this neurodevelopmental period, it can be tricky to decipher and then clearly message the long-term consequences (Translational Psychiatry). Maybe we should let the kids develop their own public health messaging about the harms of drug use (Yahoo).

Any movement toward decriminalization needs to be paired with low-barrier access to treatment, not low-barrier access to prison (NBC4). Given that homelessness is associated with a disproportionate share of overdose deaths, policies may also need to incorporate low-barrier supportive housing (Addiction). None of these policies, however, did or could have accurately predicted the rise and impact of xylazine (Annals of Internal Medicine). 

Which leads us to the Oregon experiment. Voters are unhappy, politicians are reactive, and experts continue to offer sage guidance; in order to be successful, decriminalization policies must account for the spectrum between access to fentanyl and access to treatment (KLCC).

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

with Co-Editors: Brandon Aden, MD, MPH, FASAM, Debra R. Newman, PA-C, MSPAS, MPH, Jack Woodside, MD, John A. Fromson, MD

Lead 

Xylazine Adulteration of the Heroin–Fentanyl Drug Supply

Annals of Internal Medicine

Since 2016, xylazine has appeared in the illicitly manufactured fentanyl supply and has increased in prevalence, due to its low cost, easy availability, and presumed synergistic psychoactive effect. It remains unclear whether a distinct xylazine withdrawal syndrome occurs. Xylazine may alter the findings and management of patients with fentanyl overdose and withdrawal. Inadequately treated opioid (and possibly xylazine) withdrawal contributes to the increase in self-directed discharges from treatment settings. Initiation of buprenorphine and perhaps methadone may be compounded by the concomitant use of xylazine. The presence of extensive wounds in people who use xylazine prevents them from accessing resources, including medically managed withdrawal treatment, leading to a cycle of continued and escalating use.

Research and Science

Changes in Cannabis-Attributable Hospitalizations Following Nonmedical Cannabis Legalization in Canada 🔓

JAMA Network Open

The study examines rates of cannabis-related hospital visits in Canada over time in relation to legal status and regulations, comparing pre-legalization, legalization with significant limitations on products and sales, and commercialization. Hospitalizations due to cannabis were trending up pre-legalization but did decrease slightly during the legalization with limits period, before increasing significantly during the commercialization period. Of note, the commercialization period coincided with the onset of the COVID-19 pandemic. The greatest increase in hospitalization during the commercialization period was for cannabis-induced psychosis (RR 1.4, CI 1.34-1.47). Commercialization allowed for sales of products with higher THC concentration, which may be related to this increase, though it is hard to tease out effects for the COVID-19 pandemic. 

Opioid-related overdose deaths among people experiencing homelessness, 2017 to 2021: A population-based analysis using coroner and health administrative data from Ontario, Canada 🔓

Addiction

This four-year population-based, time-trend analysis using coroner and health administrative databases from Ontario measured the change in proportion of opioid-related overdose deaths attributed to people experiencing homelessness (PEH). It also compared the opioid-related fatalities between individuals experiencing homelessness and not experiencing homelessness at time of death. PEH are over-represented among opioid-related overdose deaths and this burden is dramatically increasing, with one in six opioid-related deaths occurring among individuals experiencing homelessness at the time of death (and one in three among individuals experiencing homelessness within 1 year of death), contrasted to one in 150 Canadians estimated as experiencing homelessness annually.

Use of Lysergic Acid Diethylamide by Major Depression Status

JAMA Psychiatry

Using data from the NSDUH, this study compared trends in past-year LSD use from 2008 to 2019 between adults with and without past-year depression. Overall prevalence of past-year use increased significantly from 0.2% to 0.9%. Specifically, in adults without depression, the prevalence of past-year use increased from 0.2% in 2008 to 0.8% in 2019, while among those with past-year depression, the prevalence of past-year use increased from 0.5% in 2008 to 1.8% in 2019. Young adults with depression were most impacted. Given increases in major depression over the last decade, it is suggested that use of LSD may continue to increase as well, with the suggestion that LSD will increase in popularity as self-medication for depressive symptoms.

Learn More

Naloxone prescriptions among patients with a substance use disorder and a positive fentanyl urine drug screen presenting to the emergency department 🔓

Harm Reduction Journal

This study notes the rising number of overdose deaths from drugs such as sedatives and stimulants that unknowingly contain synthetic opioids such a fentanyl. The authors suggest that naloxone should be prescribed to all persons using illicit drugs, not just those using opioids. This study looked at all visits to an ED at an academic medical center in Georgia between 2019 and 2021 that included a diagnosis of SUD. Among patients with a discharge diagnosis of OUD, 16.3% received a naloxone prescription. With a non-opioid SUD diagnosis, 4.9% were prescribed naloxone, increasing to 8.4% if the UDS was also positive for fentanyl. Among all patients with a UDS positive for fentanyl, 3.5% were prescribed naloxone. The authors conclude that rates of naloxone prescription were low, particularly for patients with SUD for illicit substances other than opioids.

Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder

The American Journal of Drug and Alcohol Abuse

While extended-release naltrexone (XR-NTX) is effective treatment for opioid use disorder (OUD), it has the significant barrier of requiring an abstinence period prior to initiation. In the era of fentanyl, this may pose an even greater barrier. In this context, the authors conducted a trial using lofexidine, an alpha-2-adrenergic agonist, to help manage withdrawal symptoms with the goal of increasing initiation of XR-NTX. The study enrolled 20 participants, of which 10 (50%) initiated XR-NTX. Twelve patients reported some side effects, with dizziness being most common. The study supports use of lofexidine as a safe and feasible option to manage withdrawal symptoms during XR-NTX initiation, though additional larger controlled studies are needed. 

Consequences of adolescent drug use 🔓

Translational Psychiatry

Despite efforts to educate adolescents about the harms related to substance use, such as lasting changes on behavior and cognition, initiation remains high around the world. This review article considered some of the most recent literature surrounding adolescent substance use, highlighting alcohol, tobacco, and cannabis, in particular. The authors determined that future research could inform the predictors, mechanisms, and consequences of adolescent drug use. In addition, efforts to understand sex differences as well as the similarities and differences between substances in this population all have the potential to lead to effective treatment.