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

From depression to addiction, psychedelic drugs offer new hope for people with mental health disorders.

Medically Reviewed
You probably know that psychedelic drugs, also called hallucinogens, affect a person’s mind by altering perceptions, moods, and thoughts.

In fact, the word “psychedelic,” derived from Greek, literally means “mind made visible.” And while these drugs are well-known for their recreational uses, scientists are now looking at their potential for treating mental illnesses.

“Psychedelic drugs offer new mechanisms to address mental illness, and some have shown promise where other treatments have been ineffective,” says Itai Danovitch, MD, a professor and the chair of the department of psychiatry and behavioral neurosciences at Cedars-Sinai Medical Center in Los Angeles. “This is a source of significant excitement.”

It’s important to note that Dr. Danovitch is referring to the medicinal use of psychedelic drugs administered in measured doses under the supervision of licensed medical professionals. Using the same drugs recreationally or without a prescription to manage mental health issues is not only illegal, but it's also dangerous, as it can lead to the opposite effect — worsening symptoms instead of relieving them.

History of Psychedelic Drugs

Psychedelic drugs are not new. Many are found in nature, such as in fungi, cacti, trees, seeds, and leaves. Others are created synthetically in laboratories from chemicals altered to mimic those of natural hallucinogens. And while research on the medical use of psychedelics is still in an early stage, these drugs have been used by different cultures to facilitate mystical or spiritual experiences and to treat mental illness since ancient times.

The 20th-century English novelist and philosopher Aldous Huxley famously experimented with two psychedelics, mescaline and LSD, under the supervision of the psychiatrist Humphry Osmond, who advocated that they be used under carefully controlled conditions as a treatment for alcohol use disorder.

Between the 1950s and 1970s, several research studies suggested that psychedelics showed promise as therapies for anxiety, depression, psychosomatic diseases, and addiction.

“However, these studies were not well controlled,” explains Dr. Danovitch. “And changes in the law essentially stopped most research for the decades that followed.”

In 1970, the U.S. Congress passed the Controlled Substances Act, which classified LSD along with several other hallucinogens as having a high potential for abuse and no accepted medical use. In 1986, LSD was banned throughout the country.

But in recent years, researchers have renewed their interest in psychedelics as they search for innovative ways to manage mental illness, which affects nearly one in five adults in the United States.

“There is a growing recognition that there is no health without mental health, that the body and mind are integrally connected,” says Danovitch. “Our culture’s current gravitation to natural substances probably also contributes to the current wave of openness to rediscovering agents that have long existed on the periphery of society and have powerful effects promoting self-reflection, empathic connectedness, and sometimes adaptive change.”

Types of Psychedelic Drugs

Psychedelic drugs are taken recreationally in ways including smoking, snorting, injecting, and drinking them. In contrast, most research studies dispense psychedelics in pill form to ensure their purity and to allow for consistent dosing, both gold standards for clinical tests of treatments and drugs. Pill forms are also much safer than smoking or injecting psychedelic drugs.

Well-known psychedelic medicines currently being investigated include psilocybin, LSD, MDMA, ketamine, and peyote.

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’s 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, says 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.

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.

How Do Psychedelic Drugs Work in the Brain and Body?

All psychedelics produce a temporary altered state of consciousness, but researchers believe these experiences may generate lasting effects when it comes to treating mental health, says Dr. Johnson.

“There is evidence that the brain becomes more flexible or ‘plastic’ after a psychedelic,” says Johnson.

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, puts it this way: Psychedelic drugs allow patients to access parts of themselves that are ordinarily inaccessible.

As Dr. O’Donnell explains, “The human brain is fundamentally a learning machine, and it derives its power from its ability to learn and recognize patterns and use those patterns to predict the future. It seems that psychedelics make that pattern much more flexible, so you have a window of opportunity to reopen a period of development, so even after the psychedelic experience, you can make choices and establish new patterns.”

How each psychedelic drug affects the brain and body depends on the drug class to which it belongs.

Classic hallucinogens, such as psilocybin, LSD, and peyote, interfere with the brain chemical serotonin, which regulates your 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 your environment.

MDMA is an entactogen, which works by flooding the spaces between brain cells with serotonin, Johnson explains.

What Research Says About Psychedelics as Mental Health Treatments

While the research on psychedelic medicine for mental illness is still considered new and emerging, some studies have shown compelling results.

Psilocybin

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 small later 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 (meaning a group that received no treatment). More than half the study participants were in remission four weeks after treatment.

In a study published 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 to receive 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

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.

And 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

Some of the most compelling results for MDMA as a treatment for mental illness have come from clinical trials involving people with 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.”

Supportive Therapy Is Essential, Too

Although the research on psychedelic medicine is promising, it’s important to note that these studies involved very careful administration of these drugs in a clinical setting under the supervision of doctors. Currently available research consists of very small, short-term studies, many of which are performed in specific groups of patients (such as people with life-threatening illnesses, for instance). This means that the findings from these studies may not be applicable to everyone being considered for psychedelic therapies.

In addition, many studies also included supportive care in the form of psychotherapy.

“For clinical indications, psychotherapy appears to be necessary to support and facilitate change,” says Danovitch.

He adds that therapy protocols typically involve the following phases:

  • Assessment phase During this phase, a mental health professional and the patient set goals for therapy.
  • Preparation phase This phase is intended to get patients physically and emotionally ready for treatment.
  • Experience phase During this phase, health professionals monitor patients carefully as they take the medication.
  • Integration phase This phase focuses on helping patients reflect and learn from the experience after treatment with the psychedelic has ended.

O’Donnell says this type of support, including preparing the patient for what will happen when taking the medication, is vital for successful treatment.

“If someone has no idea what they’re in for and someone gives them a psychedelic, that can be a really traumatic experience,” O’Donnell says. “A lot of people have the idea that it’s a one-and-done and your life is transformed forever, and that’s really not the case. That takes it out of the context of a therapeutic relationship, which is so important.”

Side Effects

Some of the most common side effects of psychedelics include:

  • Altered sense of time, such as feeling that time is passing by slowly
  • Anxiety or fear
  • Fast heart rate
  • Increased blood pressure
  • Mild headaches
  • Nausea
  • Intensified sensory experiences, such as seeing colors that are brighter than usual

Johnson adds, “A risk for anybody is a panic reaction during a ‘bad trip.’ But the potential for harms from this are mitigated through monitoring and a safe environment in medical trials.”

Some psychedelic medicines can be addictive. More research is needed to determine how addictive they might be when administered in clinical settings, as well as the best ways to reduce the risk of addiction.

Which Psychedelic Drugs Are FDA-Approved for Use?

Currently, Spravato (esketamine) is FDA-approved for treatment-resistant depression. It’s administered as a nasal spray by a health professional.

Though esketamine is a psychedelic medicine, the drug’s prescribing information lists hallucinogenic experiences as a side effect rather than a mechanism of action, or how the drug works.

“With the typical way esketamine is used, folks are told to ignore the psychedelic effects as a side effect, which is the opposite of true psychedelic therapy where one is encouraged to pay attention to the altered state of consciousness and try to learn from it,” says Johnson.
Some doctors prescribe ketamine — which is FDA-approved as a general anesthetic — “off-label” for depression. This means it’s not yet FDA-approved for depression, but some health professionals deem the medication appropriate for certain patients. Some physicians provide ketamine for depression at specialized clinics throughout the United States.

Additionally, the FDA has granted breakthrough therapy designations to psilocybin for MDD and MDMA for PTSD.

This designation accelerates their pathway to FDA approval. But these medicines aren’t legally available to the public yet and can only be used as part of a clinical trial.

Contraindications: Who Should Not Use Psychedelics?

People with a history of mania, severe heart disease, or psychotic disorders such as schizophrenia should not be considered for psychedelic therapy, Johnson says.

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 Future of Psychedelic Medicine for Mental Illness

The recent surge in psychedelics research will likely continue gaining steam.

“It’s receiving attention because of very large effects for very difficult to treat disorders — effects that often dwarf our best existing medications,” Johnson says. “That, combined with the fact that we are at peak levels of mental health trouble as a society and we’re pretty desperate for breakthrough changes. This shows good promise of being a game-changer,” he adds.

Still, Johnson and others say more extensive, rigorous studies need to be done before psychedelic drugs can be considered a mainstream therapy.

And although studies are showing positive results, there are still many unknowns, such as the ways these drugs will be administered if they become FDA-approved. “There are so many questions we have to study that we don’t know the answers to,” O’Donnell notes.

O’Donnell says she envisions specialized psychedelic clinics popping up in areas around the country where patients will receive guidance, support, and psychotherapy along with psychedelic treatment.

While the future of psychedelic therapy offers exciting possibilities, O’Donnell emphasizes that overcoming mental health disorders is a process that often takes time and hard work.

“Changing one’s life isn’t something that happens in an instant. It’s something we have to commit to and live out,” O’Donnell says. “Psychedelics give us an opportunity to settle into a new pattern, but we still have to choose that pattern and establish it consciously. There’s a real responsibility, and it can be a lifelong journey.”

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