What Caregivers Need to Know About Emerging Psychedelic Treatments for Depression

In the past ten years, there’s been growing interest in using psychedelic drugs to treat depression. But since most psychedelics are still illegal at the federal level, there is still a lot we don’t know about how they work and which psychedelic treatments are most effective.

If you are caring for someone who is living with depression, you may be curious whether psychedelics can help your loved one. Here is an overview of what’s currently known about emerging psychedelic treatments for depression:

Which psychedelic treatments are being used for depression?

The Food and Drug Administration (FDA) is currently reviewing several psychedelics to determine their safety and efficacy. Most of the current research is focused on psilocybin, MDMA, and ketamine. 

Psilocybin is a naturally occurring psychedelic compound found in certain types of mushrooms. Research suggests that psilocybin may effectively treat major depression and certain types of anxiety. Psilocybin-assisted therapy is currently legal in Oregon and Colorado. However, since it has not been approved by the FDA, its therapeutic applications are unregulated. 

MDMA is a synthetic compound commonly known as ecstasy or molly. MDMA is only legal in the context of FDA-approved clinical trials. Most of the MDMA research to this point has focused on post-traumatic stress disorder (PTSD). However, preliminary research indicates that MDMA might also be effective at treating certain types of anxiety, and there is a growing interest in the use of MDMA to treat mood disorders. 

Ketamine is an anesthetic (substance that temporarily numbs or lessens pain) that has been used in surgical and trauma-care settings since the 1960s. While not technically a psychedelic, ketamine can produce psychedelic-like experiences at sub-anesthetic doses (lower amounts than what would be used for anesthesia). It has recently been marketed as a medication for depression. However, this treatment is considered “off-label,” as ketamine has not been approved by the FDA. 

The FDA has approved the use of a ketamine derivative called esketamine, which is given as a nasal spray. Research shows that esketamine can reduce the severity of depressive symptoms. However, questions remain about the long-term efficacy of this medication. Combining esketamine with regular antidepressant therapy may prolong the benefits.

Other psychedelics being studied as potential treatments for depression include LSD (commonly known as acid) and ayahuasca (an herbal brew derived from plants). However, since ketamine is the only psychedelic that is legally accessible in the U.S., the rest of this article will focus on ketamine treatment.

How is ketamine used to treat depression?

Ketamine can be administered in several different ways: nasally, orally, intravenously, or via injection. Esketamine is administered nasally and is the only ketamine treatment approved by the FDA. However, prescribers and clinics are increasingly offering other forms of ketamine therapy for depression.

The past several years have seen a rapid increase of ketamine clinics, both virtual and in-person. Patients complete a consultation with a psychiatrist or nurse practitioner, after which they receive a prescription for ketamine troches (medicated lozenges) or injections. Some clinics will even mail the medication to patients for self-administration. However, the American Society of Anesthesiologists cautions that ketamine should only be administered by trained healthcare professionals due to the risk of side effects or other adverse events. Experts also warn that the ketamine provided by mail-order or cash-only clinics is loosely regulated, so patients cannot be sure of the dose they receive.

In addition to stand-alone ketamine treatment, some clinics also provide ketamine-assisted psychotherapy (KAP). Patients are administered a dose of ketamine in their therapist’s office and wait for it to take effect (typically 15 to 45 minutes, depending on the method of administration). Patients then verbally process their experience in real time with the therapist. A 2022 research review indicates that KAP can produce long-term reductions in depressive symptoms.

How does ketamine work?

We don’t yet know the precise mechanisms by which ketamine works to treat depression. One theory is that ketamine promotes neuroplasticity, the brain’s ability to form new connections and pathways. Neuroplasticity can help those living with depressive disorders reshape negative thought patterns and integrate new ways of coping with painful emotions. 

Ketamine differs from traditional antidepressant medications in that it can rapidly reduce symptoms. While SSRIs (selective serotonin reuptake inhibitors) can take 4-6 weeks to take full effect, patients may experience relief from ketamine within a few days or even hours. This is particularly beneficial for patients who have functional impairments and/or suicidal ideation.

The course and duration of ketamine treatment vary from patient to patient and according to the method of administration. However, a typical course includes 4-8 weeks of regular treatment (1-2 times per week), followed by a “taper” phase of 1-5 treatments. Some patients may then schedule regular “booster” treatments to maintain progress, while others seek additional treatments only as needed.

What are the risks of ketamine?

Administered properly, ketamine can be a life-changing therapy for those living with depressive disorders, especially those who have not experienced relief from more traditional methods of treatment. However, as with any medication, there are potential risks and side effects associated with it. These include:

More common:

• Sedation (sleepiness or drowsiness)
• Dizziness
• Nausea
• Dissociation (disconnected or “out-of-body” feeling)
• Changes in vital signs such as heart rate and blood pressure
• Slowed breathing

Less common:

• Lower urinary tract and bladder symptoms
• Liver function impairment
• Anxiety
• Psychosis (especially for patients with a personal or family history)

Because the side effects of ketamine treatment can last up to 24 hours after administration, patients must arrange for transportation to and from the clinic and be supervised by an adult for the rest of the day.

Should you consider ketamine or psychedelic treatment for your loved one?

A healthcare provider experienced in ketamine therapy can help your loved one evaluate the risks and benefits. One thing to keep in mind is that ketamine is rarely the first line of treatment for depression. It’s typically only recommended after more traditional treatments have failed to provide adequate relief.

The bottom line on psychedelic treatments

Psychedelics show promise as a new line of treatment for depression. However, much of the research is in its infancy. Esketamine is the only psychedelic medication that is FDA-approved to treat depression. Other forms of ketamine are being used “off-label” as treatments for depression. As with any medication, there are advantages and disadvantages. An experienced provider can help your loved one decide whether or not to pursue ketamine therapy for depression.

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Author

Lindsay Schwartz is a psychotherapist in private practice in Acton, MA, where she specializes in the treatment of depressive and anxiety disorders. She has a background in school counseling and a special interest in mindfulness-based treatments. Lindsay earned her Bachelor’s degree in Psychology and English from Williams College, and her Master’s degree in Social Work from Simmons College. In her free time, Lindsay enjoys writing, reading, running, and spending time with her husband and 2 children.

Copy Editor

Nicole Tirone is a social worker turned adult learning expert with a passion for digital accessibility and plain language. She volunteers as an editor to help FFDA equip people with tools to support their loved ones. In her free time, Nicole enjoys podcasts, reading, painting, volunteering, and photography.