Psychoactive drugs are often discussed in the context of risk, yet science keeps asking a different question. What do psychedelics teach us about how people connect, feel, and heal, and how can we study those effects carefully in humans?

Dr. Harriet de Wit, director of the Human Behavioral Pharmacology Laboratory at the University of Chicago, has spent her career building tools to answer those questions.

She reflected on her work in a recent interview.

Two drugs sit at the center of the story, MDMA and LSD, because they shift internal states that standard lab tasks rarely capture.

Studying psychedelic connections

Dr. De Wit’s work spans basic psychopharmacology and clinical translation, and her research program has been funded by the NIH for more than 42 years.

“The challenge of translating behavioral observations across species has continued to be a central theme in my research for the past 45 years,” said Dr. de Wit.

She treats cross-species comparison as a tool to test which findings generalize and which do not.

Her path began with animal studies of drug taking, then moved into controlled trials with human volunteers. That shift opened the door to measuring self reported states that animals cannot convey.

She also insists on measuring both behavior and self reporting. That approach allows human studies to capture experiences, like empathy or awe, that nonverbal animals cannot report.

Psychedelics connect humans

A controlled laboratory study found that single doses of MDMA increased how connected people felt to a stranger during a guided conversation.

According to Dr. de Wit, demonstrating that MDMA enhances feelings of social connectedness during interpersonal interactions has profound implications for treating trauma-related disorders globally. 

In the same paradigm, methamphetamine produced a similar rise in ratings of closeness, but only MDMA’s closeness was linked to oxytocin levels in saliva.

Those data put numbers on an everyday observation that pharmacology can shift social experience. The finding also gives therapists a concrete target, the feeling of connection during real conversations, to measure in future trials.

The work used a double blind, with separate groups for MDMA and methamphetamine. Participants rated closeness at the end of the session and one week later, providing both immediate and short follow-up readouts.

The similar behavioral outcomes with different physiological patterns point to multiple routes to the same social endpoint. That matters because the mechanism will shape safety, dosing, and how a therapy session is structured.

LSD and MDMA microdosing

A randomized, double blind trial in healthy adults tested four low doses of LSD given every few days and found modest, short-lived subjective effects without lasting changes in mood or cognition.

Safety looked acceptable in that controlled setting, but the expected broad cognitive boost did not appear.

Across sessions, some acute effects weakened, suggesting that participants developed a tolerance for the low-dose LSD over time.

The high microdose reduced feelings of rejection during a social exclusion task during dosing days, yet those changes did not persist at follow up.

“Drugs such as MDMA and low doses of LSD produce unusual alterations in self reported internal states, such as feelings of empathy, awe, and oneness with the environment,” said Dr. de Wit.

Her research team now asks whether those altered states actually change future behavior, generosity, or values.

Craving can rise with abstinence

A translational human study in cigarette smokers documented incubation, the counterintuitive increase in cue triggered craving after longer abstinence periods.

Across groups, cue-induced craving was greater after 35 days than after 7 days, even as background withdrawal eased.

The result pushes back against the idea that craving simply fades with time away from a drug. Clinicians can plan check-ins for later windows when cue reactivity rebounds, which may help people stay off cigarettes.

The design verified abstinence day by day and tested responses to smoking cues in a controlled setting. That level of control strengthens confidence that timing itself can shape craving responses.

Why place matters in addiction

In a foundational human paper, volunteers developed a conditioned place preference for a room paired with amphetamine, and their preference tracked how much they liked the drug during conditioning.

The result validated a widely used animal assay in people and tied subjective liking to learned context.

Procedurally, the study used repeated conditioning sessions followed by a test day when people rated the rooms. That design allowed the team to connect learned preference to the specific feelings the drug produced during training.

Feeling connected with psychedelics

A phase 3 trial reported that MDMA assisted therapy reduced symptom severity and functional impairment in people with moderate to severe PTSD.

These clinical outcomes sit alongside lab-based evidence that MDMA can increase feelings of connection during real conversations.

Translation is never automatic, but it is not a shot in the dark. By pairing controlled human experiments with clinical trials, researchers can map which laboratory effects actually move the needle in care.

“I am concerned about the decline in respect for science, scholarship, and education,” said Harriet de Wit. A long running research program only exists when society is willing to invest in it.

The study is published in the journal Psychedelics.

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