Psychedelics: Chemicals, Consciousness, and Creativity

This 2022 World Science Festival panel, moderated by physicist Brian Greene, brings together MAPS founder Rick Doblin, Johns Hopkins neuroscientist Gül Dölen, and musician and comedian Reggie Watts. Over roughly one hundred minutes they trace psychedelics from ancient ritual use through receptor biology to a police officer's therapy testimonial, covering why interest in these substances has returned to serious scientific attention.

A cross-cultural, cross-species pull

Watts frames psychedelic use as an extension of ordinary curiosity, a faster route to an altered state than meditation. Dölen notes humans already move through altered states daily (sleep, falling in love), and that some animals appear to seek psychedelic effects too. Doblin traces the practice to the Eleusinian Mysteries in ancient Greece, arguing psychedelics have long served meaning making functions in Western culture, not only in indigenous traditions, and describes centuries of suppression, from the Catholic Church ending the Eleusinian rites around 392 CE to the 1960s crackdown.

The tide turning: from stigma to phase 3 trials

Doblin describes the last decade's shift as an accumulation of safety and efficacy data strong enough to bring MDMA assisted therapy for PTSD into phase 3 clinical trials, the final stage before possible FDA approval, and notes the research was named among the Journal of Science's top breakthroughs of the year. He frames the moment cautiously, warning that overselling benefits and understating risks both fueled the 1960s backlash.

Personal accounts: fear, dissolution, and the "paradoxical state"

Greene describes a frightening night in an Amsterdam coffeeshop, losing his ordinary sense of time and space and asking his wife to tie him to the bed, which he connects to William James's idea that everyday consciousness is separated from other forms of awareness by only "the flimsiest of screens." Watts recalls his first LSD trip at fifteen or sixteen, resolving into laughter at "the silliness and the absurdity of life and consciousness," and a harder ketamine experience at a festival he attributes to an unfamiliar setting, not the drug itself. Doblin recalls his first LSD trip at seventeen as a frightening struggle to let go of control, and describes guiding an MDMA session for a sexual assault survivor whose perception of him shifted between the assailant and himself as she processed the trauma, offered as illustrative rather than clinical evidence.

Inside the brain: receptors, priors, and the default mode network

Dölen explains LSD binds to the serotonin 2A receptor and lodges there longer than serotonin itself, triggering a different cascade; the search for serotonin as a neurotransmitter was partly prompted by early attempts to explain LSD's outsized effects at minuscule doses. She pushes back on the idea that psychedelics simply "open a filter" to admit more raw information, citing lab findings that people on psychedelics tend to perceive a static photo of a waterfall as moving, since the prior that water flows outweighs the prior that paintings are static. Doblin connects this to the default mode network, tied to the everyday sense of self, which weakens under classic psychedelics, and prefers "ego dissolution" over "ego death," since an observing self typically remains.

A new theory: psychedelics and critical periods of plasticity

Dölen traces critical periods, brief windows of heightened brain plasticity, to Konrad Lorenz's studies of imprinting in geese, noting similar windows govern language, motor learning, and vision (uncorrected congenital cataracts can cause permanent blindness once the visual critical period closes). Her lab discovered a previously unknown critical period for social reward learning and found MDMA can reopen it in adult mice. Through what she calls reverse translation, her team is testing whether this explains MDMA assisted therapy in people: rapid in onset, durable (roughly two weeks in mice, which she speculates could translate to weeks or months in humans), and dependent on social context, since MDMA only reopens the window in mice housed with others. She stresses this remains a hypothesis, though she speculates it could extend to motor or language learning and beyond MDMA to other psychedelics.

Could psychedelics help heal social divides?

The panel plays a testimonial from a Winthrop, Massachusetts police lieutenant and psychotherapist who underwent MDMA assisted therapy in a research protocol and now advocates bringing similar therapy to officers facing PTSD and elevated suicide rates. Doblin ties policing's "us versus them" dynamic partly to the drug war and welcomes the idea. Dölen is more cautious: without deliberate work to build empathy across group lines, MDMA could reinforce in-group bonding instead, and her mouse data suggests people stay vulnerable and open for some time afterward, arguing against sending them into high-stakes situations too soon. Doblin closes by tying the discussion to neuroplasticity and context: psychedelics used within a supportive setting, not the compound alone, determine whether change lasts.

"If you put a bunch of priests in a room and give them psychedelics, they're going to see God. If you give a bunch of neuroscientists psychedelics, they're going to say, of course, it's the serotonin molecule," Dölen says.

Key takeaways

• ●The panel frames renewed interest as recovery from a long history of suppression, not only a rebound from the 1960s counterculture.
• ●MAPS reached phase 3 trials of MDMA assisted therapy for PTSD, the final stage before possible FDA approval.
• ●LSD binds unusually persistently to the serotonin 2A receptor; Dölen argues psychedelics work less by "opening a filter" and more by amplifying reliance on prior expectations.
• ●Doblin distinguishes "ego dissolution," tied to a weakened default mode network, from the more dramatic "ego death," since an observing self often persists.
• ●Dölen's lab found MDMA can reopen a critical period for social reward learning in mice, rapid and durable, a possible mechanism for MDMA assisted therapy.
• ●Set and setting are repeatedly described as more important to outcomes than the substance itself.
• ●A police lieutenant's testimonial and the panel's response both stress psychedelics are not a magic bullet for social divides.
• ●Every panelist frames psychedelics as tools whose effects depend on context, dose, and preparation, not guaranteed paths to healing.