The surprising new treatment for mental illness

In April 1943, Swiss chemist Albert Hofmann accidentally exposed himself to a drug he derived from ergot fungus and recorded its unexpected, mind-altering effects. The drug, lysergic acid diethylamide—or LSD—was soon heralded for its psychiatric potential. But how do LSD and other psychedelic drugs affect the body? And can they actually be medicinal?

Psychedelics are a class of drugs that alter mood, cognition, and perception, often triggering unusual states of consciousness like hallucinations. They all interact with the body's serotonin neurotransmitter system, which regulates many processes, including mood, sleep-wake cycles, appetite, and memory.

Lower rates of serotonin signaling are associated with impaired sleep and attention and diminished responses to positive information. Meanwhile, higher rates tend to track with more positive moods and greater emotional stability.

All psychedelic drugs increase the amount of serotonin signaling. However, they interact with the serotonin system in different ways and affect other neurotransmitter systems, all of which determines their unique effects and medical potential.

Hofmann's discovery inspired a wave of psychedelic research that largely stalled in the 1970s, due to concerns over breaches in research ethics, as well as conservative drug policies. However, it's picked back up in recent decades, and some psychedelics show promise in addressing even treatment-resistant conditions.

Take LSD and the mushroom-derived compound psilocybin: when they cross the blood-brain barrier, receptors recognize them as serotonin. Interestingly, they tend to suppress the areas that make up the brain's "default mode network" and initiate more connections with other brain regions.

The default mode network is important in self-referential thinking and mind wandering. It's thought that, by suppressing its activity, LSD and psilocybin may generate the distinctive psychedelic experience of ego dissolution, characterized by a radical shift in self-perception.

The default mode network is also associated with mental health disorders. By disrupting its activity, psilocybin and LSD might help normalize it. This may be why they can reduce the symptoms of conditions like depression—potentially doing so faster than traditional treatments.

Trials that pair LSD or psilocybin with talk therapy also show promise in treating disordered tobacco and alcohol use, perhaps by similarly altering people's self-perception. And they seem to activate receptors that facilitate social behavior, empathy, and gratitude, leading people to feel greater harmony with a larger community.

It's thought that this is why they can help alleviate the distress people living with advanced cancer diagnoses experience, as preliminary trials suggest. Overall, LSD and psilocybin seem to function similarly, but LSD is more potent and associated with longer-lasting psychedelic experiences.

MDMA, meanwhile, triggers the release of neurotransmitters, including dopamine, norepinephrine, and serotonin, and elevates levels of the hormone oxytocin. These changes generate effects like heightened heart rate and sensory perception, as well as feelings of euphoria, bonding, empathy, and safety.

Because of this, researchers have begun investigating MDMA as a possible therapy for post-traumatic stress disorder. MDMA releases oxytocin, sometimes referred to as the bonding hormone, which may help reinforce an environment of safety, trust, and connectedness. MDMA is also thought to modulate activity in the amygdala, which plays a central role in processing fear.

PTSD can be difficult to treat because of how painful it is to revisit traumatic experiences. However, it's thought that MDMA could help patients discuss trauma without debilitatingly negative emotions, and potentially aid in uncoupling traumatic memories from the threatening feelings they usually surface—a process known as fear extinction. More studies are needed to test this theory and determine MDMA's safety and effectiveness.

Psychedelics also show some promise in helping address chronic pain and cluster headaches. And unlike pain-relieving opioids, they aren't considered addictive.

However, they're not without risks. Some research suggests psychedelics can be stressful on the heart. And their extensive psychological effects make it hard to predict individual responses. Psychedelics can "unmask" pre-existing psychiatric disorders, like schizophrenia, which is why clinical trials usually Have thorough screening processes. And paranoia, psychosis, and hallucinations—which can persist even after the drug has been metabolized—are potential side effects.

Therapy sessions that employ psychedelics usually require preparation—like mindfulness and breathing techniques—and should take place in safe, supportive environments with emergency protocols in place.

We've learned a lot about psychedelics since Hofmann's fateful experiment. But there's much more to uncover—and not without challenges.

Psychoactive substances like psychedelics pose issues for blind clinical trials, since their effects can be pretty obvious to participants who shouldn't know they're receiving treatment.

To fully understand their therapeutic potential, we need many more scientifically, ethically rigorous trials that weed out bias, prioritize participant welfare, and grapple with complex results.

Who knows? The results could be mind bending.