Psychedelic Therapy for Depression

Psychedelic therapy for depression may be an effective treatment. Learn alongside Nicole LaMarco about this treatment option.
psychedelic therapy for depression
Author: Nicole LaMarco
By Nicole LaMarco
March 17, 2023

Psychedelic therapy for depression may be an effective treatment. Depression is a mood disorder that often causes symptoms of sadness and lack of interest which can disrupt daily life. Commonly treated with both medications and psychotherapy, finding the right combination for symptom relief can be challenging. Recently, a new treatment option has been exciting researchers – psychedelics. A wave of studies has indicated that psychedelics, like ketamine and psilocybin, may hold promise for treating depression. 

What is Depression? 

Depression is a mood disorder with the following symptoms: perpetual hopelessness, loss of interest, irritability, anxiety, trouble focusing, and unexplained physical symptoms, such as headaches. The symptoms can range from mild to severe. Intense depressive episodes can disrupt daily life and occasionally require hospitalization. However, even mild symptoms can result in losing interest in family, school, work, and hobbies.

Symptom type and severity can vary from person to person. Depression can present with distinct symptoms, known as specifiers, which help doctors to determine the type of major depression you are experiencing. Examples of types include anxious distress, catatonia, and seasonal pattern.   

Typically, depression treatments are a combination of medication and psychotherapy. Common medications may include selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), atypical antidepressants, and tricyclic antidepressants. One or more medications may be required, and determining which option works best for you can involve several weeks of trial and error. 

In addition, psychotherapy, which refers to discussing your condition and symptoms with a mental health professional, may be recommended. Examples of psychological therapy include cognitive behavioral therapy (CBT) or interpersonal therapy. Generally, psychotherapy will occur along with medication. 

Psychedelics and Mental Health Conditions 

Two psychedelics are currently receiving the most amount of research concerning depression. The first is ketamine, which is often grouped with psychedelics because it has hallucinogenic properties. Yet, ketamine is a dissociative anesthetic that doctors often use for anesthesia. The FDA has approved ketamine for medical aesthetic purposes only. Otherwise, it is a Schedule III non-narcotic. 

Research has found that ketamine may rapidly relieve depression symptoms, especially in those who do not respond to other forms of treatment. Doctors can currently prescribe ketamine for depression as an “off-label” treatment option, meaning that the FDA has not approved it for depression treatment. However, the FDA has approved a similar drug, esketamine, for depression management. 

Another psychedelic showing promise for depression treatment is psilocybin, better known as magic mushrooms. Psilocybin is a hallucinogenic compound. The Drug Enforcement Administration classifies it as a Schedule I substance, making it illegal. However, a couple of states, like Oregon and Colorado, have moved to legalize it in certain contexts. Breakthrough research has proven that it may be effective in treating anxiety, cluster headaches, and depression. 

How Can We Use Psychedelic Therapy for Depression? 

One way psychedelics can help treat depression is through their effect on serotonin. Serotonin is the neurotransmitter responsible for many bodily functions, including mood and behavior regulation. 

One theory is that low serotonin levels may cause depression, hence the treatment option of SSRIs, which inhibit the uptake of the neurotransmitter in the brain and, as a result, increase serotonin levels. Psilocybin stimulates serotonin receptors, similar to SSRIs, helping to raise the brain’s serotonin levels. 

Ketamine works differently, though researchers aren’t clear on how exactly. One characteristic of the drug is that it stimulates the brain’s NMDA glutamate receptor. This stimulation can trigger sedative, out-of-body, and pain-killing effects. 

But it also helps replenish glutamate receptors, increasing the ease of communication between these nerve cells. In those with depression, researchers believe that their glutamate receptors are weakened, decreasing communication between nerve cells. Another thought is that the various metabolites produced by ketamine help to lift mood. 

Aside from positively affecting brain synapse regrowth and reactivation, it’s important to note that both drugs produce dissociative effects, such as hallucinations, sensory distortions, unusual thoughts, euphoria, and an out-of-body feeling. 

In the case of both psychedelic substances, trials have shown positive benefits for those with depression. For example, one study found that psilocybin treatment produced significant and durable improvements in major depression symptoms after two doses two weeks apart, along with follow-up sessions. 

In another study, a single dose of 25mg of psilocybin reduced depression scores significantly. In a study of ketamine, participants had six intravenous injections of .5mg over two weeks. Researchers saw significant improvements in anxiety and depression after the first dose. In a similar study, six ketamine infusions showed positive antidepressant efficacy. 

Considerations of Psychedelic Administration 

It is important to note that during these studies, trained medical professionals gave the psychedelics in a medical facility. Furthermore, there was strict control over dosages and the time between doses. This included before and after care. The recreational use of psychedelics is not a treatment for depression. 

Finally, researchers paid close attention to the set and setting. The setting describes the environment in which they gave psychedelics. Patients often received the drug in a comfortable atmosphere. They reclined on a couch or chair, wore an eye mask, and listened to soothing music. 

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The set is equally as important. It refers to the mindset of the individual going into psychedelic therapy. Each patient underwent pre-nondrug sessions and post-nondrug sessions. The post-nondrug sessions often included psychotherapy to help the patient integrate their experience. 

Are There Any Downsides to Psychedelic Therapy for Depression? 

The small doses of psychedelic therapy are low enough not to cause substance addiction. However, in some studies, adverse experiences were associated with psychedelic use. Individuals may experience increased anxiety, uncomfortable sensations, extreme dissociation from reality, nausea, dizziness, hypertension, and loss of motor coordination. Generally, these are immediate side effects that don’t persist after the session. A trained medical professional can help during the session.  


Psychedelic therapy for depression has shown promise in various studies, especially treatment with ketamine and psilocybin. However, research is still limited, and scientists are not yet able to pinpoint how psychedelics improve depressive symptoms. Psychedelic therapy should only be completed in certified medical facilities under the care of trained medical professionals.  

The content provided is for educational and informational purposes only and should be a substitute for medical or other professional advice. Articles are based on personal opinions, research, and experiences of the author(s) and do not necessarily reflect the official policy or position of Psychedelic Support.

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Author: Nicole LaMarco
Nicole LaMarco
Nicole Lamarco is a freelance health writer with 18 years of experience. Her work has been featured in Shape, Psych Central, Healthgrades, Eat This Not That, Verywell Fit, and other health-related media. Check out her website Nicole LaMarco.

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