Mail-Order Medicine: The Ketamine Lozenge Boom

A Brief History of Ketamine

First synthesized in the 1960s at Wayne State University, ketamine immediately found use as a battlefield anesthetic. Since its discovery, ketamine's use has expanded. The drug remains a useful anesthetic for hypotensive patients, an abortive for acute refractory seizures, an off label option for chronic pain, and a recreational drug of abuse. Ketamine has also gained fame in psychiatry due to its potential to provide rapid antidepressant effects. In the early 2000s, small scale research began to support the use of ketamine as an antidepressant. Around 2010, off label IV ketamine clinics began to open up around the United States. In 2019, the FDA approved esketamine (Spravato), a nasal spray consisting of the S-enantiomer of ketamine, as an adjunct to oral antidepressants. In 2025 Spravato gained approval for use as a monotherapy. Both IV ketamine and Spravato are administered on-site at a healthcare facility under medical supervision.

The Rise of Online Ketamine Clinics

During the COVID-19 pandemic, ketamine’s use outside traditional clinical settings surged. Restrictions on in-person care fueled the rapid rise of telemedicine-based ketamine clinics, many of which began prescribing compounded sublingual lozenges shipped directly to patients. Some online practices began to advertise protocols through social media platforms that had little to no evidence supporting their safety and efficacy, such as Joyus Health, which began to prescribe "micro dosing" regimens of 30–60 mg of oral ketamine per day. Other practices prescribed up to 400 mg lozenges every three days.

Ketamine Bladder

As the use of ketamine lozenges continues to grow, it is important to recognize the lower urinary tract damage associated with long term ketamine use. This effect is extensively documented in those who abuse ketamine, and colloquially referred to as "ketamine bladder" or medically as "ketamine induced cystitis". Patients have described a progressive onset of urinary urgency, frequency, nocturia, dysuria, hematuria, and pelvic discomfort, particularly as the bladder fills. Some develop urge incontinence or ulcerative cystitis, and in more advanced cases, the bladder wall may become fibrotic, leading to a significant reduction in bladder capacity. Rarely, upper tract complications such as hydronephrosis may develop.

The underlying mechanism is thought to involve direct toxicity to the bladder epithelium, triggering inflammation, submucosal fibrosis, and neurogenic hypersensitivity—closely resembling but often more severe than interstitial cystitis. These symptoms may persist even after ketamine is discontinued, and in some cases, the damage may be irreversible.

On platforms such as r/TherapeuticKetamine, patients have described developing such symptoms after the use of oral lozenges, especially with frequent or high-dose administration. Given the low oral bioavailability of lozenges, the need for higher doses in comparison to other routes of administration may further exacerbate the issue. Taken together, the frequency of dosing, the poor oral bioavailability, growing reports of adverse effects, and lack of clinical evidence supporting the long term safety or efficacy raises serious questions about oral ketamine lozenges.

Conclusion

While ketamine undoubtedly fills a clinical need in psychiatric treatment, the rapid pop-culture adoption of ketamine as an antidepressant has led to a slew of telehealth companies advertising and prescribing oral ketamine directly to patients. When administered thoughtfully, ketamine has the potential to transform lives. Patients, however, must be aware of the lack of evidence supporting the safety and efficacy of oral ketamine protocols along with the potential for harm.