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.
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.
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.
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.
Explore More About Psychedelics
For a comprehensive understanding of psychedelics, read our complete guide: