Ketamine-Assisted Therapy for Substance Use Disorders: Breaking Through Treatment-Resistant Depression and Addiction

Ketamine-assisted therapy, or KAT, is a newly popular treatment for depression, anxiety, and PTSD. Because many patients with these diagnoses often struggle to find effective treatment, doctors and researchers continue to seek out new options. And today, many people are finding that ketamine-assisted therapy helps with recovery from substance use disorders.

Despite its historical stigma as a street drug, KAT is being researched as a therapy for a variety of conditions. And the data is promising. When used in appropriate clinical settings, it can serve as a valuable component of a comprehensive recovery plan.

What Is Ketamine and How Does It Work?

Ketamine is a dissociative anesthetic, and has long been used as a surgical analgesic. That is, anesthesiologists administer it to patients before surgery, usually in combination with other medications, to induce unconsciousness and provide pain relief.¹ However, ketamine’s dissociative qualities may have a more direct impact on mental health.

Dissociation is sometimes described as “a dreamlike state,” in which patients feel detached from present reality and even from their own identities. In its recreational use (or misuse), this is often the desired impact of ketamine. In a clinical setting, some physicians consider this a side effect. However, “it is possible that ketamine’s dissociative symptoms are essential to the neurobiological mechanism of action required to produce antidepressant effects.”² More research is needed on this subject.

Whether or not dissociation is a necessary component of the process, experts agree that ketamine is one of the most powerful antidepressants that we know of. In fact, according to one source, “no drug to date has been found to possess racemic ketamine’s rapid and robust antidepressant efficacy.”²

What Conditions Does Ketamine-Assisted Therapy Treat?

Experts believe ketamine is an appropriate treatment for a number of diagnoses. In addition to providing physical pain relief, it can also alleviate some symptoms of many mental health concerns, even those that resist other forms of treatment.

Ketamine for Treatment-Resistant Depression

Ketamine is widely recognized as an effective treatment for both acute and chronic symptoms of depression. It is sometimes used to treat suicidal ideation in emergency situations, because its effects are both immediate and long-lasting. One study, assessing its applications for suicidal patients, found that ketamine provides “​​persistent benefits” for suicidal patients in acute crisis. After only 3 days of treatment, 46% of patients in this study experienced full remission of suicidal thoughts.³

Ketamine can also be used for ongoing care. Evidence suggests that short-term or intermittent ketamine-assisted therapy for depression may have long-term benefits. One study found “significant improvement in depression, anxiety, and the severity of illness after 2 weeks and 1 month of the last dose of ketamine.”⁵ This data implies that engaging in KAT during rehab may have a lasting impact on patients’ mental health, even if you don’t continue treatments after leaving the program.

Ketamine therapy is an effective treatment for several forms of depression, including unipolar depression (also called major depression) and bipolar depression, which is one aspect of bipolar disorder.⁴ It is also “capable of significant and rapid symptom improvement” in the treatment of adults with treatment-resistant depression (TRD).⁵

Anxiety Disorders and Social Anxiety

Ketamine can reduce the symptoms of anxiety disorders, which often co-occur with depression. And experts believe it may have fewer negative side effects than other anxiety drugs.⁶

John Krystal, MD, chief psychiatrist at Yale Medicine, explains why ketamine can help with anxiety. “With most medications, like valium, the anti-anxiety effect you get only lasts when it is in your system. When the valium goes away, you can get rebound anxiety. When you take ketamine, it triggers reactions in your cortex that enable brain connections to regrow. It’s the reaction to ketamine, not the presence of ketamine in the body that constitutes its effects.” Because of its unique effects on the brain, ketamine can treat both depression and anxiety.⁷

Ketamine can also treat social anxiety.⁸ And in fact, much of the research into ketamine as an anxiety drug centers around this condition. Because social anxiety is associated with alcohol misuse, this may be helpful during recovery from co-occurring anxiety and substance use disorders.

And this condition isn’t only associated with alcohol use disorder. In addiction, there is “a high degree of comorbidity” between social anxiety and post-traumatic stress disorder (PTSD). If you have either or both of these conditions, KAT may be an appropriate treatment.⁹

Post-Traumatic Stress Disorder (PTSD)

Preliminary research suggests that ketamine-assisted therapy may be an effective treatment for post-traumatic stress disorder.¹¹ Specifically, a 2021 study found that “sublingual ketamine as an augmentation to somatic psychotherapy provided in a real-world clinic setting has the potential to meaningfully reduce PTSD and depression symptoms among a trauma-exposed population.”¹⁰

Although much more data is needed, these results are promising. Because substance use disorders and PTSD are so strongly associated with each other, KAT may prove to be an especially helpful treatment for patients in recovery from addiction.¹³

How KAT Supports Addiction Recovery

If you’re in recovery from substance misuse, any type of pharmaceutical treatment is potentially triggering, or even dangerous. Despite this, some prescriptions—including ketamine—can help alleviate your symptoms. And research supports the idea that ketamine is an effective treatment for substance use disorders (SUDs).¹⁴

According to the same study, “ketamine itself is a drug of potential abuse when used recreationally.” Despite this, “its lasting effects without repeated daily use have also shown promise for patients with SUDs.”¹⁵ This is especially true for patients with comorbid chronic pain, and those in recovery from opiate misuse. It’s also important to note the overlap between the latter two conditions; many people begin misusing opiates in response to preexisting chronic pain.

Ketamine-assisted therapy promotes abstinence among people with heroin dependence, alcohol use disorders, and more. In fact, ketamine may be a helpful treatment for many different substance use disorders. “These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment.”¹⁶

Although ketamine is not “classified as a highly addictive drug,” its use may still be triggering for people in recovery. Because of this risk, it is absolutely essential that patients only use ketamine in a controlled environment.

What to Expect During a Session

Ketamine can be administered as either an IV treatment or a nasal spray. In 2019, the FDA approved the use of “Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant” for adults with treatment-resistant depression. The FDA has not yet approved ketamine for other mood disorders, but physicians can and often do prescribe it off-label to treat various conditions.

KAT should always be closely supervised by medical professionals in a protected environment. Because it is an anesthetic, ketamine induces a dreamlike state, in which it would be unsafe for a patient to go about their daily life. One patient, speaking to a New York Times reporter, “said the treatment made him ‘sleepy’ and provoked an ‘out of body’ experience. He described these sensations as ‘pleasant’—though he struggled with his balance and a sense of being ‘dazed’ for several hours following each session.”¹⁷

In some clinics, each patient undergoes treatment in a private room. In others, KAT is a group experience. Although it’s unlikely that patients will be physically able to interact during the treatment, simply sharing that time with other people can be an opportunity to bond.

Whether you’re treated alone or with a cohort, your session may begin or end with a talk therapy session. During that time, providers might ask you to set intentions for healing, process what you experienced during treatment, or—in a group setting—offer feedback to one another.

Research shows that ketamine-assisted therapy works best when combined with psychotherapy—not as a standalone treatment. Early studies found that patients who received structured therapy alongside ketamine had significantly higher rates of long-term abstinence from alcohol and heroin compared to standard treatment alone.

Current clinical trials continue exploring how different therapeutic approaches enhance ketamine's effectiveness for various substance use disorders. This research reinforces an important principle: Ketamine is most effective as a complement to behavioral therapy, not a replacement for it.¹⁶

The Benefits of Ketamine-Assisted Therapy for Recovery

KAT can be helpful for patients with a wide variety of physical and mental health symptoms. For example, ketamine can be used to treat chronic pain.¹⁸ There are “well-established associations” between chronic pain and substance use disorders.¹⁹ But managing this condition can be a huge challenge for people in recovery, because it’s hard to find pharmaceutical treatments that won’t trigger relapse. Depending on the exact treatment protocol, KAT can have either short- or long-term benefits for patients with these diagnoses.

In addition to treating mental health concerns like depression, anxiety, and PTSD, ketamine can also improve brain function. According to experts, “ketamine research has shown that the substance creates a high degree of neuroplasticity in rats. This may explain the so-called ‘cumulative effect’ in humans that produces transformative results from multiple sessions in a relatively short time frame, often just two weeks.”²⁰

The immediate effects of KAT may be especially appealing to people in the early stages of recovery. However, it’s important to remember that no single treatment—including ketamine therapy—will permanently make your symptoms disappear. While KAT can be an effective component of recovery, it should always be combined with other therapeutic modalities.

Safety Considerations and Limitations

Because of its potential for misuse, ketamine may be triggering for some patients with substance use disorders. And if you have a history of misusing ketamine itself, KAT is absolutely not an appropriate treatment during recovery.

This modality is not safe for patients with certain underlying conditions. According to Dr. McInnes, patients with “uncontrolled hypertension are not candidates” for ketamine therapy. KAT is also dangerous for patients with a hypersensitivity to ketamine, pregnant or breastfeeding patients, and anyone with schizophrenia.²¹

If you’re interested in engaging in KAT, make sure to check in with your team of healthcare providers. Because this therapy has a significant impact on the body and the mind, it’s important that you have support from experts in both physical and mental health.

Finding a Reputable KAT Program

In a few short years, the public interest in ketamine as mental health treatment has skyrocketed. As a result, considerable resources are being devoted to its research. Medical doctors, psychiatrists, and scientists are continuing to learn more about the potential applications of KAT.

This is an exciting time, but it’s important to proceed with caution. A growing body of research shows that ketamine can be hugely beneficial to patients with substance use disorders. However, it’s impossible to know what experts will learn in the future. If you decide to engage in KAT during recovery, make sure to look up the most recent available data before you begin treatment.

If conventional treatments haven't worked for you, ketamine-assisted therapy might offer the breakthrough you need. Explore rehabs that offer ketamine-assisted therapy in safe, supervised clinical settings designed to support your recovery journey.