U.S. physicians are reducing their reliance on opioid pain medications and turning to a different option for challenging pain: ketamine, an older surgical drug that has gained popularity as a psychedelic treatment.

In recent times, there has been a significant increase in the number of ketamine prescriptions, fueled by clinics and telehealth services that prioritize profit, and promote its usage for pain management, depression, anxiety, and other ailments. This widely available generic medication can be obtained inexpensively and is being prescribed by a variety of healthcare professionals, including physicians and some nurses, regardless of their level of training.

With insufficient evidence on its ability to alleviate pain, certain professionals express concern that the United States may be making similar errors that contributed to the opioid epidemic: excessive prescribing of a dubious medication that poses significant hazards for safety and potential misuse.

Dr. Padma Gulur, a pain specialist at Duke University, notes that there are limited choices for treating pain, leading to a tendency to resort to any potential solution. She is currently researching the use of ketamine for pain relief. However, she cautions against the widespread off-label use of ketamine without proper scientific evidence, citing a few published studies in medical journals that may have influenced this trend.

Gulur and her team monitored 300 patients who were given ketamine at Duke University. Over 33% of the patients experienced notable adverse effects, including hallucinations, disturbing thoughts, and changes in vision, which needed medical intervention.

According to Gulur, the use of ketamine did not lead to a decrease in opioid prescribing in the months after treatment, which is a typical desired outcome of therapy. Her study is currently being reviewed for publication in a medical journal.

Ketamine was originally authorized over 50 years ago as a potent anesthetic for individuals undergoing surgical procedures. When taken in smaller amounts, it can induce psychedelic and out-of-body experiences, leading to its use as a recreational drug in the 1990s. However, with its more recent use for pain management, patients are now experiencing these same effects.

Daniel Bass, a resident of Southgate, Kentucky, was horrified by the visual disruptions he experienced. His physicians recommended IV infusions of ketamine, lasting four to six hours, to alleviate pain caused by an uncommon bone and joint condition. Bass recalls feeling like a “guinea pig” while sitting in a plain hospital room with no distractions or information about the potential psychological impact of the drug.

However, he attributes the reduction of his pain to ketamine during the period in which he underwent bi-monthly infusions.

Bass stated that they are willing to undergo any experience, no matter how terrible, if it helps them become more productive.

The drug ketamine acts on a chemical in the brain known as glutamate, which is believed to contribute to both pain and depression. It is not certain if the psychedelic aspect of the drug is necessary for its therapeutic benefits, but some experts view it as crucial.

Dr. David Mahjoubi, owner of the Ketamine Healing Clinic in Los Angeles, explains that their goal is for patients to be able to disconnect from or feel detached from their physical or mental discomfort. According to Dr. Mahjoubi, if patients feel like they are simply sitting in a chair during the treatment, they are actually given even more relief.

Mahjoubi follows a common trend in the growing industry by providing IV ketamine treatment for alcohol addiction, chronic pain, anxiety, and post-traumatic stress disorder. The doses used for these conditions are lower than those used for surgery, but Mahjoubi prefers higher doses for pain compared to psychiatric issues.

Patients must use cash as insurance companies do not typically include non-surgical applications of ketamine, which have not been approved by the Food and Drug Administration. Mahjoubi specializes in anesthesiology, not psychiatry or addiction.

Individuals have the option to incur additional costs for ketamine nasal sprays and tablets, which can be utilized in between infusion treatments. These particular forms of the medication are not endorsed by the FDA and are produced by specialized pharmacies.

During the COVID-19 pandemic, online prescribing regulations were loosened, allowing telehealth services like MindBloom to enter the market of profitable businesses that send ketamine through the mail.

Experts in pain management who research ketamine suggest that there is limited proof for these variations.

Dr. Eric Schwenk of Thomas Jefferson University stated that there is limited literature available for nasal and oral formulations. There is a lack of strong evidence to provide guidance in this area.

According to Epic Research’s analysis of over 125 million patient records, the demand for ketamine has caused prescriptions to increase by over 500% since 2017. Pain has consistently been the top reason for ketamine prescriptions, but there has been a rapid rise in its use for depression as well.

The increase in prescribing has resulted in a scarcity of commercially produced ketamine, causing a rise in the demand for compounded forms.

Ketamine has more support in its effectiveness against depression compared to pain. In 2019, the FDA granted approval for a ketamine-like compound created by Johnson & Johnson to treat severe depression. The medication, known as Spravato, is closely regulated by the FDA in terms of its use and administration by medical professionals.

The recommendations from pain associations highlight some indication for the utilization of ketamine in complex regional pain, a persistent ailment that typically impacts the limbs. However, the specialists discovered that there is insufficient or inadequate proof supporting ketamine’s effectiveness in numerous other conditions, such as back pain, migraines, fibromyalgia, and cancer pain.

Although the exact science behind ketamine remains unclear, the profit model is straightforward: Medical professionals can buy ketamine for under $100 per vial and then bill patients $500 to $1,500 for each infusion.

The current surge has been driven, to some extent, by venture capitalists. Another group of consulting firms provide assistance to doctors in establishing new clinics.

A recent post on Ketamine Startup’s blog outlines “Five compelling reasons to consider opening a ketamine clinic,” such as “Desire for independence as a business owner” and “Desire to have greater control over income.”

Clinics are experiencing more competition from telehealth options, such as MindBloom and Joyous. These services link individuals seeking medical attention with doctors who can prescribe ketamine from a distance and have it delivered by mail.

In May, the government was planning to reverse the COVID-related policy that permitted the online prescription of dangerous drugs like ketamine and opioids. However, due to criticism from telehealth companies and doctors, the Drug Enforcement Administration has decided to continue the lenient approach until 2024.

According to Dr. Samuel Wilkinson, a psychiatrist at Yale University who prescribes Spravato and ketamine for depression, the current situation can be described as a “wild west.” In the United States, doctors have significant flexibility in prescribing medications for uses that have not been approved, or are off-label.

He stated that there are both positives and negatives regarding that situation.

At high concentrations, ketamine can lead to harm in the bladder, a condition often observed in individuals who use the substance for recreational purposes. However, there is limited understanding of the potential neurological repercussions of prolonged use. Recent research on rats has suggested a connection between ketamine and changes in brain structure, as reported by FDA regulators.

The FDA issued a cautionary statement to medical professionals and individuals about compounded forms of ketamine, such as lozenges and pills. The agency stated that it does not oversee the ingredients in these products and cannot guarantee their safety. This warning comes after a previous advisory in the previous year regarding nasal spray forms of ketamine.

However, the majority of compounding pharmacies are small businesses that are regulated by state authorities rather than the FDA.

In April, the Massachusetts pharmacy board acknowledged the FDA’s warning to local pharmacies, but stated that state authorities would not intervene to prevent the ongoing compounding and dispensing of ketamine nasal spray.

The FDA does not have much control over doctors who promote ketamine, even if they make exaggerated or false statements.

Pharmaceutical companies must adhere to stringent FDA guidelines when advertising their medications, including the need to provide a balanced presentation of both potential risks and benefits. However, these regulations do not extend to physicians.

Despite the FDA’s attempts to control dangerous in-office procedures, such as untested stem cell infusions, the organization has had varying success in legal battles.

Currently, professionals predict that regulators are unlikely to take any further action beyond their recent cautionary statements regarding the use of ketamine for off-label purposes.

According to Dr. Caleb Alexander, a drug safety researcher at Johns Hopkins University, there is a sense of playing whack-a-mole and it is outside the scope of their regulatory authority. He believes that these clinics would create another challenge for them to handle and resolve.

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“Connect with Matthew Perrone on Twitter by following him at @AP_FDAwriter.”

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The Science and Education Media Group of the Howard Hughes Medical Institute provides support to the Associated Press Health and Science Department. The AP is solely responsible for all of its content.