(8) Tianeptine “Gas Station Heroin” Products: Public Health Concern or Niche Substance Use?

Background & Introduction: Tianeptine refers to a pharmaceutical prescribed in some European, Asian, and Latin American countries for depression and anxiety. Although tianeptine structurally resembles tricyclic antidepressants, it is a full agonist at mu opioid (MOR) receptors. This MOR activity is believed necessary for its therapeutic effects, though tianeptine’s abuse potential remains unclear. Tianeptine is rarely utilized medically in the US and is not FDA-approved. Recently there has been a proliferation of tianeptine products, sold as unregulated dietary supplements or “nootropics.” FDA considers these illicitly marketed, despite tianeptine not yet being scheduled federally. Tianeptine product use has been documented in the medical case report literature since 2017. Adverse events, numbering in the hundreds, have increased since 2000. Published US-based tianeptine-related case reports are >30, however, symptoms are severe and wide-ranging. These include agitation, psychosis, tachycardia, respiratory depression. Dependence and addiction are also reported, with naloxone and/or buprenorphine utilized by some physicians. Popular media has reported tianeptine consumers rapidly developing tolerance and withdrawal, with many referring to tianeptine as “gas station heroin.” As little is known about US adults who nonmedically use tianeptine, we aimed to characterize their attributes, treatment history, substance use motivations and patterns, and any problematic use related to tianeptine products.

Methods: We conducted a cross-sectional online survey between December 2023 and July 2024 focused on kratom and kava, which are also psychoactive products sold as “dietary supplements” within a grey market. As tianeptine use has been reported among people who use kratom and kava, we utilized this larger survey as an opportunity to include tianeptine-specific questions. Data were collected anonymously using Qualtrics. Participants were fully informed about the survey prior to voluntary participation. The Johns Hopkins University IRB approved this study. To be eligible, participants had to be >18 years of age and endorse lifetime use of one of the following: kratom, kava, akuamma seed, and/or tianeptine. Participants provided information pertaining to demographics, substance use, and to tianeptine use patterns using locally developed survey items used in prior kratom studies which were adapted for use here with respect to tianeptine. Data were stratified by lifetime tianeptine use; frequency and percentages for categorical variables were calculated while means and standard deviations were calculated for continuous variables. To compare those with and without lifetime tianeptine use, Fisher’s Exact Test or Chi-Square were used for categorical variables, and t-tests were used for continuous variables (i.e., age). Data were analyzed using SAS 9.4.

Results: Of the 369 respondents 5.96% (n=22) reported lifetime tianeptine use. There were no statistically significant differences for demographics. Those who reported lifetime tianeptine use were 35.6 years old on average; mean age of tianeptine use initiation was 31.0 years old with 68.2% having used tianeptine >100 times. This group was predominately White and male (81.8%), and college-educated (59.1%). Although those who used tianeptine did not differ from those who had never tried tianeptine with respect to having any medically diagnosed SUD, a larger proportion of tianeptine consumers believed they recently (27.3% vs.10.9%) or currently (40.9% vs. 20.2%) experienced an SUD (p=0002). Tianeptine consumers also had a greater proportion who had ever been prescribed methadone/buprenorphine (27.3% vs. 8.1%, p=0.009), and were in recovery (50.0% vs 23.9%, p=0.007) or interested in recovery (72.7% vs. 28.8%, p<.0001).

Alcohol, caffeine, nicotine, cannabis, and kratom were widely used sample-wide. Phenibut was used by 72.7% of tianeptine consumers (vs. 15.6%, p< 0.001). Additional between-group differences were found for opioids and uncommonly used drugs/supplements.

Mean tianeptine doses for respondents who had sustained use periods (n=18) was 5.9/day and 20.3/week. For past-year use (n=15), mean number of months of use was 5; for past-month use (n=11), mean number of days used was 10.7.

Reported effect onset was within minutes, although many said effects dissipated within minutes-hours. Most (68.2%) reported experiencing acute effects nearly each time they used. Acute effects included euphoria (63.6%), improved mood (63.6%), reduced social or general anxiety (36.4%-54.6%), analgesia (45.5%), sedation or energy (36.4%). This is consonant with participants’ primary reasons for using. One participant reported using tianeptine primarily as a long-term opioid substitute; two had used to attenuate non-opioid withdrawal.

One-third reported their tianeptine intake had moderately-significantly increased with 27.3% having quit. When asked about quit attempts, 41.0% reported never making one; of those who had attempted quitting, two reported >25 times attempts.

Tianeptine tolerance onset was considered somewhat-extremely “rapid” by 59.1%. None characterized it as “gradual.” One-third had experienced tianeptine-related adverse effects with 4 having sought medical care. Most (86.3%) believed it was possible to overdose on tianeptine. Applying DSM-5-derived SUD criteria to tianeptine for those with past-year use (n=15), 66.7% met diagnostic criteria; 2 were mild-moderate; 12 were severe.

Conceptualizations of tianeptine included: “potent” (72.7%), “habit-forming” (68.2%), “addictive” (68.2%), “problematic” (59.1%), “too expensive” (59.1%), “is an opioid” (50.0%), and “isn’t regulated” (50.0%). Only 27.3% endorsed “therapeutic,” “helpful,” or “benefit to my daily life.”

Conclusion & Discussion: Here, few used tianeptine, however, based on their responses, it is fair to characterize this group as comprised of individuals with diverse polysubstance use histories. Use of phenibut may be unique to those who use tianeptine as it is found in some products.

Although tianeptine use as an opioid substitute was reported by one participant, and no respondents reported taking tianeptine to attenuate opioid withdrawal, these motivations have been documented elsewhere. As reasons for use were diverse, and as most published case reports do not report patient use motivations, it is unclear what the primary drivers of tianeptine use are among the larger consumer population.

These findings, and the few published tianeptine-related published case reports, call into question whether these products will develop into a wide-spread public health concern or if tianeptine will remain a niche grey-market substance sought out by adults with complicated health histories and novelty-seeking. It is unclear that people who try tianeptine want to keep taking it: many respondents indicated that tianeptine was not beneficial, but was problematic and addictive. Clinicians should add tianeptine to assessments and publish case reports that include product information, patient use motivations, and the interventions utilized for treating tianeptine SUD.

References: Smith KE, Rogers JM, Strickland JC, Epstein DH. When an obscurity becomes trend: social-media descriptions of tianeptine use and associated atypical drug use. Am J Drug Alcohol Abuse. 2021;47(4):455-466. doi:10.1080/00952990.2021.1904408

Szczesniak L, Sullivan R. Microdose Induction of Buprenorphine in a Patient Using Tianeptine. J Addict Med. 2022;16(6):736-738. doi:10.1097/ADM.0000000000001003

Espiridion ED, Qutob M, Lozano P. A Case of “Neptune’s Fix Elixir”: The Dangerous Consequences of Unregulated Use of Tianeptine in Over-the-Counter Products. Cureus. Published online February 28, 2024. doi:10.7759/cureus.55120

Trowbridge P, Walley AY. Use of Buprenorphine-Naloxone in the Treatment of Tianeptine Use Disorder. J Addict Med. 2019;13(4):331-333. doi:10.1097/ADM.0000000000000490

Rawal VY, Gallardo M, Henderson K, Hall OT, Klisovic N, Sikic-Klisovic E. Severe tianeptine withdrawal symptoms managed with medications for opioid use disorder: a case report. J Addict Dis. Published online December 14, 2023:1-6. doi:10.1080/10550887.2023.2290139