What Are Psychedelic Drugs & How Can They Help Treat Mental Illness?

Dr. Serenity
April 12, 2023

Exploring the Potential of Psychedelic Drugs for Treating Mental Illness

Psychedelic drugs have been known for their recreational uses, but scientists are now investigating their potential for treating mental illnesses. Itai Danovitch, MD, a professor and chair of the department of psychiatry, explains how these drugs offer new mechanisms to address mental illness and offer promising results when administered in measured doses under licensed medical professionals. However, it’s crucial to note that using these drugs recreationally or without a prescription can worsen symptoms instead of relieving them.

The Evolution of Psychedelic Drugs: From Ancient Cultures to Modern Medicine

Psychedelic drugs have a rich history that dates back centuries. Many of these mind-altering substances can be found in nature, while others are synthesized in labs to mimic natural hallucinogens. Despite being associated with recreational use, cultures throughout history have used psychedelics for medicinal and spiritual purposes.

One famous example is the English novelist and philosopher Aldous Huxley, who experimented with mescaline and LSD under the supervision of a psychiatrist to treat alcohol use disorder. In the mid-20th century, research studies suggested that psychedelics could be used to treat mental illnesses, including anxiety, depression, and addiction.

However, uncontrolled studies and changes in the law in the 1970s halted research on these drugs. The U.S. Congress passed the Controlled Substances Act in 1970, which classified LSD and other hallucinogens as having no accepted medical use and a high potential for abuse.

In recent years, there has been a renewed interest in the therapeutic potential of psychedelics. Mental illness affects a significant portion of the U.S. population, and researchers are looking for innovative ways to manage it. According to Itai Danovitch, MD, a professor of psychiatry and behavioral neurosciences, the current trend toward natural substances has contributed to the rediscovery of powerful agents that promote self-reflection and adaptive change. However, it’s important to note that the medicinal use of these drugs should only be administered under the supervision of licensed medical professionals.

Types of Psychedelic Drugs: A Look at Recreational Use and Medical Applications

Psychedelic drugs have long been used for recreational purposes, often through smoking, snorting, injecting, or drinking them. However, most research studies dispense psychedelics in pill form to ensure purity and consistent dosing, which are gold standards for clinical tests of treatments and drugs. Pill forms are also much safer than smoking or injecting psychedelic drugs.

Types of Psychedelic Medicines Currently Being Investigated

  • Psilocybin (4-Phosphoryloxy-N,N-Dimethyltryptamine)

Psilocybin, sometimes referred to as “magic mushrooms,” comes from certain mushrooms found in the United States, Mexico, and South America. It is considered the most researched psychedelic substance and is being explored as a treatment for depression, cancer-related distress, and different forms of addiction.

  • LSD (D-Lysergic Acid Diethylamide)

Colloquially known as “acid,” LSD is a clear or white material made from lysergic acid, which is found in a fungus that grows on grains like rye. Like psilocybin, LSD is being studied as a therapeutic agent for depression, cancer-related distress, and addiction.

  • MDMA (3,4-Methylenedioxymethamphetamine)

MDMA, often called “ecstasy” or “molly,” is a popular synthetic club drug that acts as a stimulant and hallucinogen. Researchers are looking at MDMA as a potentially game-changing treatment for post-traumatic stress disorder (PTSD).

  • Ketamine

Ketamine, known on the street as “special K,” has traditionally been administered intravenously as a surgical anesthetic in humans and animals. It has also been used in liquid, powder, or pill form as a date-rape drug that, when added to someone’s drink without their knowledge, can cause confusion, memory loss, and other symptoms that render that person more vulnerable to sexual assault. In 2019, a nasal spray form of ketamine called esketamine won U.S. Food and Drug Administration (FDA) approval as medication for treatment-resistant depression.

  • Peyote (Mescaline)

Mescaline occurs naturally in a small cactus called peyote, but it can also be synthetically made. It’s being investigated as a possible treatment for depression, anxiety, and related conditions.

Recreational vs. Medical Use

While psychedelics have long been used recreationally, there is growing interest in their potential medical applications. Researchers are exploring these drugs as treatments for depression, anxiety, PTSD, addiction, and cancer-related distress. Pill forms are preferred in clinical research for their purity and consistency, and are also safer than other methods of consumption. However, there are concerns about abuse potential, and laws around their use and distribution remain strict in many countries.

Understanding the Effects of Psychedelic Drugs on the Brain and Body

Psychedelic drugs, once associated with the counter-culture movement of the 1960s, are experiencing a renaissance of sorts, as scientists investigate their potential use in treating mental health conditions. While the use of these substances for recreational purposes is illegal, studies suggest that they may have the potential to help alleviate depression, anxiety, and PTSD, among other conditions.

How Do Psychedelic Drugs Work?

Psychedelics produce a temporary altered state of consciousness, but it is believed that these experiences can have lasting effects when it comes to treating mental health conditions. According to Matthew W. Johnson, PhD, a professor of psychedelics and consciousness research in the department of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine in Baltimore, “There is evidence that the brain becomes more flexible or ‘plastic’ after a psychedelic.” Kelley O’Donnell, MD, PhD, an assistant professor of psychiatry at the New York University (NYU) Grossman School of Medicine and a researcher at the NYU Langone Center for Psychedelic Medicine, adds that psychedelic drugs allow patients to access parts of themselves that are ordinarily inaccessible.

Psychedelic drugs work differently depending on the drug class to which they belong. Classic hallucinogens such as psilocybin, LSD, and peyote interfere with the brain chemical serotonin, which regulates mood, senses, sleep, hunger, sexual behavior, and other functions. Dissociative psychedelics, such as ketamine, affect the brain chemical glutamate, which regulates pain perception, emotion, learning, memory, and responses to the environment. MDMA, on the other hand, works by flooding the spaces between brain cells with serotonin, which explains its classification as an entactogen.

Potential Uses for Psychedelic Drugs

Research into psychedelic drugs is still in its early stages, but there is growing evidence that they may be effective in treating a range of mental health conditions. Psilocybin, for example, is being investigated as a treatment for depression, cancer-related distress, and different forms of addiction. LSD is also being studied as a therapeutic agent for depression, cancer-related distress, and addiction. Meanwhile, MDMA is being looked at as a potentially game-changing treatment for PTSD. In 2019, a nasal spray form of ketamine called esketamine won U.S. Food and Drug Administration (FDA) approval as medication for treatment-resistant depression.


Psychedelic drugs may have the potential to treat a range of mental health conditions, and researchers are exploring their therapeutic uses. The way these drugs work in the brain and body depends on the drug class to which they belong. While more research is needed to fully understand their effects, it is clear that psychedelic drugs are no longer relegated to the counterculture movement of the 1960s. Rather, they represent a promising area of research into novel treatments for mental health disorders.


Exploring the Potential of Psychedelics as Mental Health Treatments

Research on psychedelic medicine for mental illness is still in its early stages, but some studies have shown promising results. Here’s what the research says about psilocybin, LSD, ketamine, and MDMA as potential treatments for mental health conditions.


A study by Johnson and other researchers of 51 patients with life-threatening cancer diagnoses who also had depression or anxiety found that high-dose psilocybin improved symptoms and quality of life when given with psychological support. After six months, about 80 percent of participants continued to show clinically significant decreases in anxiety and depressed mood.

In a later small study, Johnson and his team reported that two doses of psilocybin, given with supportive psychotherapy, significantly reduced depressive symptoms among 15 adults with major depressive disorder (MDD) compared with 12 adults in a waitlist control group. More than half the study participants were in remission four weeks after treatment.

In April 2021, researchers compared the effects of psilocybin and a common antidepressant called Lexapro (escitalopram) among 59 people with depression. Thirty participants were randomly chosen to receive psilocybin, and 29 received escitalopram. Ultimately, the researchers found no significant difference in antidepressant effects between psilocybin and escitalopram, but they noted that longer and larger studies were needed to confirm these findings.

Psilocybin may also be an effective addition to current treatments for quitting smoking, according to a pilot study coauthored by Johnson.


LSD-assisted psychotherapy — meaning a combined intervention of therapy and medication — may lessen feelings of anxiety among people with life-threatening illnesses who are anxious about their illnesses, according to a small study with 12 participants. Follow-up research with participants one year after treatment found that those decreases in anxiety had lasted.

A review of six clinical trials with 536 participants linked a single dose of LSD administered within treatment programs for alcohol use disorder to a decrease of alcohol misuse.

Ketamine and Esketamine

Intranasal esketamine, administered together with standard antidepressant treatment, significantly reduced depressive symptoms and suicidal thoughts among patients with depression and high suicide risk, a small 2018 study found.

In another 2018 study, ketamine administered with ongoing antidepressant treatment was found to significantly reduce suicidal thoughts and behaviors within 24 hours compared with midazolam, a different anesthetic medication, among people with depression who were at risk of suicide.

In a March 2022 study, researchers found that among 537 people who received intravenous ketamine therapy in a clinical setting between 2016 and 2020, more than half of patients experienced improvement in their symptoms, and nearly 30 percent achieved remission. And 73 percent of people with suicidal thoughts and behaviors saw a decrease in these symptoms. The researchers noted that 8 percent of people experienced worsened depression after starting ketamine therapy, and 6 percent reported increased suicidal thoughts or behaviors.


MDMA, also known as “ecstasy,” is being studied as a potential treatment for PTSD. In a study with 90 participants, investigators found that 67 percent of people treated with MDMA-assisted therapy no longer met the diagnostic criteria for PTSD 18 weeks after starting treatment. The authors of the study concluded that “MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.”

Importance of Supportive Therapy in Psychedelic Medicine

The potential benefits of psychedelic medicine are promising, but it is crucial to note that the studies conducted involved careful administration of the drugs in a clinical setting under the supervision of medical professionals. The current research is based on small-scale, short-term studies that are often limited to specific patient groups, such as those with life-threatening illnesses. Therefore, the findings may not be applicable to all individuals who are being considered for psychedelic therapies.

In addition to the drug itself, supportive care in the form of psychotherapy is often a crucial component of psychedelic therapy. According to Dr. Danovitch, psychotherapy is necessary to facilitate change in clinical indications.

Psychedelic therapy typically involves four distinct phases:

  • The assessment phase, the mental health professional and patient collaborate to set therapy goals.
  • The preparation phase is aimed at getting patients physically and emotionally prepared for treatment.
  • The experience phase involves close monitoring of the patient as they take the medication.
  • The integration phase focuses on helping patients reflect and learn from their experience after the psychedelic treatment has ended.

According to O’Donnell, this type of supportive therapy, including preparing the patient for what to expect during the medication administration, is essential for successful treatment. It is vital to ensure that patients are well-informed and prepared for the experience to prevent any potentially traumatic outcomes. Psychedelic therapy is not a one-size-fits-all solution, and a therapeutic relationship with medical professionals is necessary to maximize the benefits of the treatment.


Side Effects of Psychedelics

Psychedelic therapy has shown promise in treating mental health disorders, but like any medication, it can come with potential side effects. Here are some of the most common side effects of psychedelics:

  • Altered sense of time: Many people report feeling like time is passing by slowly or that time has stopped altogether.
  • Anxiety or fear: Some people may experience anxiety or fear during the psychedelic experience.
  • Fast heart rate: Psychedelics can cause an increase in heart rate.
  • Increased blood pressure: Along with a fast heart rate, psychedelics can also cause an increase in blood pressure.
  • Mild headaches: Some people may experience mild headaches during or after their psychedelic therapy session.
  • Nausea: Psychedelics can cause nausea in some individuals.
  • Intensified sensory experiences: Seeing colors that are brighter than usual or experiencing other intensified sensory experiences are common during the psychedelic experience.

“Although there is a risk of panic reaction during a ‘bad trip,’ the potential for harms from this can be mitigated through monitoring and a safe environment in medical trials,” says Johnson.

Additionally, some psychedelic medicines have the potential to be addictive. Further research is needed to determine the degree of addiction potential when administered in clinical settings, as well as the best ways to reduce this risk.


Psychedelic Drugs and FDA Approval

The FDA has approved the use of Spravato (esketamine) nasal spray for treatment-resistant depression. However, the drug’s mechanism of action is not related to its hallucinogenic properties. Ketamine, which is FDA-approved as a general anesthetic, is also prescribed off-label for depression by some doctors.

  • Spravato

    • Spravato (esketamine) is FDA-approved for treatment-resistant depression.
    • Esketamine is administered as a nasal spray by a health professional.
    • Hallucinogenic experiences are listed as a side effect rather than a mechanism of action.
  • Ketamine

    • Ketamine is FDA-approved as a general anesthetic.
    • Some doctors prescribe ketamine “off-label” for depression.
    • Ketamine is appropriate for certain patients and provided at specialized clinics throughout the United States.
  • Breakthrough Therapy Designations

    • The FDA has granted breakthrough therapy designations to psilocybin for major depressive disorder (MDD) and MDMA for post-traumatic stress disorder (PTSD).
    • Breakthrough therapy designation accelerates the pathway to FDA approval.
    • Psilocybin and MDMA are not yet legally available to the public and can only be used as part of a clinical trial.


Psychedelic Therapy Contraindications: Who Should Not Use Psychedelics?

Psychedelic therapy may not be suitable for everyone. It’s important to take into consideration certain conditions that could make it unsafe or contraindicated.

Conditions to Consider:

  • History of mania: Individuals with a history of mania should not be considered for psychedelic therapy as it may exacerbate symptoms.
  • Severe heart disease: People with severe heart disease should avoid psychedelic therapy due to the risk of increased heart rate and blood pressure.
  • Psychotic disorders: Patients with psychotic disorders such as schizophrenia should not be considered for psychedelic therapy as it may exacerbate symptoms.

Clinical Monitoring and Supervision:

Individuals prescribed psychedelic therapies should always be clinically monitored and should never try to take the drugs on their own. “It is important to have supervision anytime someone consumes anything that dramatically alters perceptions of reality,” says Danovitch.


The Promise and Challenges of Psychedelic Medicine for Mental Illness

Introduction: The use of psychedelic drugs for mental illness treatment is gaining attention due to their potential to help individuals with treatment-resistant disorders. However, more rigorous studies are needed before they can be considered a mainstream therapy.

Key Points:

  1. The Potential of Psychedelic Medicine: The recent surge in psychedelic research is due to the large effects of these drugs on difficult-to-treat disorders, which often dwarf the effects of existing medications.
  2. Need for Rigorous Studies: While studies show positive results, more extensive, rigorous studies need to be conducted before psychedelic drugs can be considered a mainstream therapy.
  3. Unknowns and Challenges: Despite the positive results, there are still many unknowns such as the administration of these drugs if they become FDA-approved. Overcoming mental health disorders is a process that often takes time and hard work.
  4. Specialized Psychedelic Clinics: Experts envision specialized psychedelic clinics in areas around the country where patients receive guidance, support, and psychotherapy along with psychedelic treatment.
  5. Responsibility and Lifelong Journey: While psychedelics can offer a new pattern for patients, there is a real responsibility, and it can be a lifelong journey to establish and maintain it consciously.


The future of psychedelic therapy offers exciting possibilities, but more rigorous studies are needed to establish its efficacy and safety. In the meantime, specialized clinics can provide guidance, support, and psychotherapy for patients receiving psychedelic treatment.

Author Dr. Serenity

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