Research investigating the potential for psychedelic drugs to treat various forms of disease—particularly psychiatric disorders—has proliferated in recent decades. Indeed, leading health systems such as Massachusetts General Hospital, UC San Francisco, UT Austin and Johns Hopkins Medicine have established research centers worth millions of dollars in recent years to pursue such studies in neuroscience and psychiatry. While psychedelic drugs have been used medicinally and recreationally by cultures across the world for millennia, modern uses in America and other developed countries have been limited in the past several decades as the drugs have been made illegal. While the burden of mental and behavioral disorders on society and our healthcare system continues to increase, research yields more promising findings for treating them—potentially indicating new opportunities for therapeutic uses and incorporation into clinical practice.
What are psychedelics?
Psychedelic drugs are used to alter states of consciousness. While the term is sometimes used synonymously with “classical hallucinogens,” there are actually three different categories of hallucinogenic drugs:
Psychedelics, which act on serotonin (a neurotransmitter that is involved in regulating mood, sleep and your digestive system)
Dissociatives, which act on glutamine (the most abundant amino acid in the body)
Deliriants, which act on acetylcholine (a neurotransmitter, to inhibit the parasympathetic nervous system)
Psychedelics can cause users to see images, hear sounds and feel sensations that seem real but do not exist, leading users to report mystical, spiritual or transpersonal experiences. They may be used in religious or recreational settings. These experiences are typically known as “trips,” and the onset and duration of effects vary widely among drug types. They might lead to short-term effects such as increased blood pressure, breathing rate or body temperature, feelings of paranoia or sleep problems. Though rare, long-term effects may include persistent psychosis and hallucinogen persisting perception disorder (typically observed more often in people with a history of mental illness). Only certain psychedelics (e.g., phencyclidine) are addictive and can lead to tolerance.
Psychedelics can be derived naturally from plants and fungi, or they can be manufactured in laboratories. Regardless of the source, most are currently illegal in the US. The most prominent forms include methylenedioxymethamphetamine (MDMA), psilocybin, ketamine, N, N-Dimethyltryptamine (DMT), D-lysergic acid diethylamide (LSD) and mescaline (additional details are presented in the following section).
How can psychedelics be used as a form of therapy?
Psychedelics are believed to reduce activity in the brain’s default mode network (DMN)—the habitual communication pathway between regions of the brain. Because the DMN is particularly overactive in certain mental health disorders, reducing its activity with psychedelics may help as a treatment to break habitual psychological patterns (and increase brain neuroplasticity and creativity). While it doesn’t directly correct neurochemical dysfunctions in the brain, psychedelic-assisted psychotherapy causes modifications in brain functioning and conscious experience. This, in turn, can lead to meaningful experiences that create emotional, cognitive and behavioral changes—and may lead to improvements in health.
Scientific research is actively studying the potential for psychedelics to treat various diseases, including:
Depression
Anxiety
Post-traumatic stress disorder (PTSD)
Addiction
Obsessive-compulsive disorder
Eating disorders (e.g., anorexia nervosa)
Research is still being conducted to determine how medications affect neural and physiological status before, during and after treatment and how different environmental conditions (such as light and music) affect status. Psychedelics are considered relatively safe. Indeed, LSD is regarded as one of the safest psychedelics—it’s also one of the most potent and restricted. Research suggests they can be used therapeutically, imposing minimal adverse side effects and without leading to addiction or tolerance.
Once studies yield results to show which conditions can be best treated with these drugs (and under which conditions), the goal will be to seek FDA approval to sell them to healthcare providers or patients for clinical use. The most prominent psychedelics currently being researched, and their application areas, are listed in the table below.
Psychedelics are distinct from other medical forms of treatment in that they require extensive psychological preparatory sessions, psychological support during the drug administration and integration sessions following the treatment. The integration sessions allow patients to solidify insights gained during their drug sessions and identify plans of action, leading to positive behavior change.
The legal history of psychedelics
Though research on the use of psychedelics to treat mental disorders began in the 1940s, concern over the adverse effects of non-medical use led to their being assigned as Schedule I under the United States Controlled Substances Act in 1970. (This class is the most restrictively regulated drug schedule and applies to drugs with no currently accepted medical use and a high potential for abuse.) This restriction has prevented their use for medical purposes since the 1970s. While it hasn’t overtly banned research, the restriction imposed significant barriers and delayed progress in research and the broader use of psychedelics in healthcare. However, in the 1990s, the research community renewed its interest in psychedelics, accelerating our understanding of their use in healthcare.
The only psychedelic listed above that is legal for use in psychotherapy at this time is esketamine, a nasal spray version of ketamine for which the FDA granted approval for severe depression in patients who don’t respond to other treatments in 2019. Because of the potential for abuse and misuse of the drug and the potential risk of adverse outcomes resulting from sedation and dissociation, esketamine is only available through a restricted distribution system, with supervision from a healthcare provider and with a Risk Evaluation and Mitigation Strategy in place. In 2017, the FDA also granted breakthrough therapy designation for MDMA-assisted therapy for PTSD. This will help optimize the completion of clinical trials (currently being evaluated) to yield data about its suspected effectiveness and inform the agency’s decision-making about legalizing its use.
Most recently, Oregon became the first state to legalize psychedelics widely. Ballot Measure 109, passed in November 2020, assigned the Oregon Health Authority to “license and regulate the manufacturing, transportation, delivery, sale and purchase of psilocybin products and the provision of psilocybin services” beginning in 2023. Oregon will become the only state where psychedelics may be legally administered for medicinal purposes (other than the current uses of ketamine across the US). Lobbyists are actively seeking to pass similar bills in other states.
Washington, New York, Colorado and California are all currently considering a variety of approaches to legalization. Several cities (e.g., Denver, Ann Arbor, Oakland and Santa Cruz) are also decriminalizing psychedelics. Additionally, other states are researching the potential medical benefits of psychedelics.
How does this impact your healthcare?
Refer to the Drug Enforcement Agency’s fact sheets to read more about the uses (including the illegal uses for recreational purposes) of these and other drugs.
To learn more and/or investigate opportunities to enroll in trials for any mental or behavioral disorders you may be experiencing, read more about the latest research into therapeutic applications from the Multidisciplinary Association for Psychedelic Studies or the specific research centers linked above.
Visit the Psychedelic Legalization & Decriminalization Tracker to learn more about how psychedelics are restricted in your state.
While these drugs have shown promising benefits for some conditions, none but the nasal spray form of ketamine (to treat depression) has been approved for use; therefore, they may not be used legally.
Resources
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Christina Badaracco, MPH, RD
Christina is a registered dietitian and author who aims to improve access to healthy and sustainable food and educate Americans about the connections between food and health. She loves to experiment with healthy recipes in the kitchen and share her creations to inspire others to cook.
Christina completed her dietetic internship at Massachusetts General Hospital and earned her Master of Public Health degree from the University of California, Berkeley. Previously, she graduated with a degree in Ecology and Evolutionary Biology from Princeton University, after conducting her thesis on sustainable agriculture and energy in Kenya. She has done clinical nutrition research at the National Institutes of Health, menu planning and nutrition education at the Oakland Unified School District and communications at the Environmental Protection Agency's Office of Water. She has also enjoyed contributing to children’s gardens, farmers markets and a number of organic farms.