Psychedelic agents are substances—most of them naturally derived from plants—that change people’s mental states by temporarily altering their perception of reality. As a result, the substances can lastingly induce changes in thoughts and feelings.
Plant-derived hallucinogens such as psilocybin, mescaline, and ibogaine have been safely used, primarily in traditional cultures, since ancient times. Typically, they are consumed ritualistically in healing ceremonies and religious rites to facilitate communication with the gods, all under the guidance of experienced elders.
Since the 1970s, psychedelic substances have been illegal in the U.S. But starting the 1990s, at first quietly, then openly, medical interest in psychedelics has been resurgent. Renewed interest in the healing properties of such agents has led to the so-called “psychedelic renaissance,” in which many such substances are being studied for a wide range of conditions. A number of psychedelics are now under active clinical investigation for the treatment of disorders including PTSD , treatment-resistant depression , anorexia nervosa, cocaine and opioid addiction , obsessive-compulsive disorder, Alzheimer’s and other dementias, end-of-life terrors, and even stroke recovery.
The resurgence of interest can be attributed to the ability of the substances to induce lasting benefits with a remarkably short course of treatment—two or three doses. This time around, however, it is recognized that the presence of a trained and supportive therapist in a safe and comfortable environment is essential for obtaining the benefits of psychedelic agents. The U.S. Food and Drug Administration has indicated that, pending the outcome of ongoing clinical trials, it is willing to approve the use of psychedelic-assisted psychotherapy . Psychedelic-assisted psychotherapy promises a brightened outlook for an array of psychiatric afflictions and drug treatment delivered with compassion.
Key Takeaways
- Psychedelics affects mental, emotional, and physical wellbeing
- Understanding psychedelics is the first step toward managing it
- Evidence-based approaches can significantly improve outcomes
- Building daily habits is more effective than one-time interventions
How Psychedelics Work
Psychedelic-assisted psychotherapy (PAP) is proving to work for so many conditions, researchers believe, because the substances target the brain region central to so many brain operations and involved in so many disorders—the prefrontal cortex—and revamp its structure.
Drugs that induce the psychedelic experience share a molecular mechanism of action—they activate a specific serotonin receptor (5-HT2A) on a specific subset of neurons in the cerebral cortex, cells that are essential for integrating incoming information to create our experience of reality. They cause the neurons to fire in a very disorganized way , messing up all the inputs. They also vastly expand the formation of synapses, intensifying neural plasticity , which many consider key to their therapeutic action. Neural plasticity is the portal to possibility and change.
Significantly, as psychedelics stimulate hyperconnectivity between sensory brain regions, they relax connectivity in the so-called default mode network , the interconnected brain areas responsible for self-referential thought and the “me” aspect of self. The experience is felt as ego dissolution, a significant part of the psychedelic experience..
Psychedelics pharmacologically return the brain to what can be considered neural childhood . The effects mimic conditions during neurodevelopment, creating the optimal brain state for environmental input to have enduring effects. Experientially, this translates into a renewed, often very positive, sense of possibility.
Also, psychedelics increase disorder in the way brain cells operate, which has the effect of prioritizing incoming sensory input over existing beliefs, encouraging novel responses to incoming information. That may, for example, keep those who experience depression from becoming stuck in repetitive negative thought patterns.
Psychedelic drugs have the capacity to change people’s perception of reality . Patients find the experience powerful and full of meaning. Dissolution of the sense of ego makes people feel at one with the world, and the intensity of the experience makes it highly meaningful to people. The drugs act primarily on serotonin receptors. Not only is serotonin involved in processing sensory information, it also influences our emotional responses, such as fear , excitement, and empathy.
The Most Important Agents and Their Uses
Researchers and clinicians generally speak of “classic psychedelics" and non-classic agents. Classic psychedelics are derived from plants found in nature and include psilocybin, dimethyltryptamine (DMT), mescaline, and LSD, which is derived from naturally occurring ergotamine. All have a long history of safe use in many cultures, typically in religious ceremonies and in the presence of spiritual guides. Non-classic psychedelics include manipulated molecules such as MDMA and ketamine .
Psilocybin is a naturally occurring compound in some species of mushrooms found in tropical regions and is undergoing clinical trials for the treatment of people with resistant depression . It is also in the early stages of testing for opioid addiction . Alzheimer's disease, post- traumatic stress disorder ( PTSD ), post-treatment Lyme disease syndrome (formerly known as chronic Lyme disease), anorexia nervosa, and alcohol use in people with major depression.
MDMA (3,4-methylenedioxymethamphetamine), also called Ecstasy or Molly, is a synthetic compound that has successfully undergone confirmatory Phase 3 clinical trials for the treatment of moderate to severe PTSD . The manufacturer is currently seeking new-drug approval from the FDA for MDMA-assisted psychotherapy.. MDMA is not a classic psychedelic, but it influences the release of serotonin and other neurotransmitters and alters perception. Studies indicate that MDMA reduces hyperactivity in the amygdala and increases connectivity between the amygdala and the hippocampus so that memories can be processed and safely stored without constantly intruding on the present. MDMA also releases the hormone oxytocin , boosting the sense of social connectedness. MDMA is also being tested for use as a treatment for depression, anxiety , and substance use.
LSD, or lysergic acid diethylamide, is derived from a fungus. It is currently under study as a treatment for alcoholism , anxiety disorders, Alzheimer’s disease, and other dementias.
Ketamine is not a classic psychedelic but a synthetic agent with a long history of safe use as an anesthetic agent in human and veterinary medicine. It produces dissociation and distortions of sights and sounds. Ketamine does not act on serotonergic 5-HT2A receptors. It is currently used in special clinics as a rapid-acting antidepressant .
The Future of Psychedelics
Psychedelic-assisted therapy is on the horizon. Because psychedelic agents present vivid new information and enable patients to approach memories and feelings they were unable to process before, patients need good guides for interpreting the contents of their minds and integrating the insights into their lives. Even before the drug is administered, patients need to be in a soothing environment to maximize the efficacy of psychedelic agents—one that conveys complete safety, minimizes anxiety, and delivers preparatory therapy that sets expectations for the possibility of real benefit. Patients typically receive a moderate to large dose of psychedelic drug in each of two or three sessions spaced over several weeks.
All current legal administration of psychedelic drugs is conducted under the direct supervision of specially certified therapists. Importantly, researchers contend that it is the psychotherapy that transforms MDMA, psilocybin, and other hallucinogens from a novelty into a medicine.
Psychedelic drugs such as psilocybin, LSD, MDMA, and other hallucinogens are controlled substances under federal law and, by statute, are deemed to have no medical use and high potential for abuse. Possession of such agents is, in short, criminal. However, several states (such as Oregon and Colorado ) and municipalities (Ann Arbor, Michigan; Denver, Colorado, for example) have approved ballot initiatives decriminalizing possession of certain hallucinogens.
Since the Millennium, however, psychedelic agents have been gathering the interest of researchers. Starting with Johns Hopkins, several American universities and research organizations have obtained approval from the Food and Drug Administration to study the medical use of hallucinogenic drugs , largely for the treatment of disorders that have resisted treatment. The drugs are administered in moderate to large doses in a specially soothing setting in the presence of a trained psychotherapist who also delivers psychotherapy.
Researchers argue that taking psychedelics is not a passive experience : The mindset of the patient matters. Taking the drug opens the mind; therapy helps people through the experience and guides them to do the necessary work of digesting the newly exposed information and, eventually, recalibrating their psychological reality. Therapy allows patients to explore and come to terms with challenging psychological material that is keeping them stuck. It also helps them reorganize their consciousness in the wake of the psychedelic experience.
To a considerable degree, the therapeutic value of the psychedelic experience hinges on the quality of the patient-therapist relationship . Therapists, who must receive special training and certification in the use of psychedelics, prepare patients for the experience by establishing a completely safe and trusting environment. They provide a reassuring presence even before the drug is administered, during the time it is active, and after the effects have worn off.
Frequently Asked Questions
What exactly is psychedelics?
Psychedelic agents are substances—most of them naturally derived from plants—that change people’s mental states by temporarily altering their perception of reality. As a result, the substances can lastingly induce changes in thoughts and feelings.
Is psychedelics a serious condition?
Psychedelics exists on a spectrum. While mild forms are a normal part of life, persistent or severe psychedelics can significantly impact daily functioning and quality of life. It's important to seek professional support if psychedelics is interfering with work, relationships, or wellbeing.
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