A new study from scientists at McGill University has gone to extraordinary lengths to investigate how strong the placebo effect may be in psychedelic research. The experiment, led by a former magician turned psychiatry PhD candidate, created a fictional psychedelic drug and staged a fake party, to explore exactly how much of a psychedelic experience can be generated without administering a psychoactive drug.

The genesis of this new research grew out of an interesting observation. Most modern psychedelic science tends to report minimal effects in placebo control groups, yet in naturalistic settings many people frequently discuss the concept of "contact highs."

This is unsurprising from one perspective, given the extreme psychoactive effect of psychedelic drugs, most subjects in a control group during a clinical trial would quickly know if they had received an inactive placebo. To overcome this problem many psychedelic researchers incorporate active placebos in trials. This usually includes drugs such as niacin or ritalin, offering some kind of felt psychoactive sensation in the hope subjects don’t immediately conclude they have been given a non-psychedelic substance.

Still, despite the use of active placebos, the McGill University team suspected psychedelic placebo effects could be obscured by medical settings. The long-held anecdotal experience of a "contact high" suggests strong psychedelic-like sensations can be generated in people without consuming psychoactive drugs. But this effect has never been experimentally quantified.

To test exactly how significant the placebo effect may be in the context of psychedelic drugs, a unique experiment was designed. The researchers created a naturalistic party environment, and recruited a cohort of subjects who thought they were participating in a study investigating the effects of psychedelic drugs on creativity.

Lead author on the study Jay Olson, leveraged his former career as a magician to construct an elaborate scenario using a number of psychological and environmental tricks to amplify any potential psychedelic placebo effect.

A room was set up to resemble a party environment, with video projections, ambient music, cushions and snacks. The participants were told the environment was designed to test the effects of psychedelic drugs on creativity in a natural environment. However, to obscure the fact no actual drugs were being administered, the researchers amplified security procedures, giving the impression of serious scientific legitimacy.

The researchers created a fictional psychedelic drug called iprocin, to make sure any pre-existing notions around the effect of drugs such as LSD or psilocybin couldn't influence the subjects' responses.

“The experimenter explained that iprocin was a fast acting and legal drug similar to psychedelic mushrooms,” the researchers write in the study. “Its effects start quickly, within 15 min, peak in 1 to 2 h, then quickly fade. We told participants that they would stay in the room until the effects had worn off, but that these would unlikely persist beyond the 4-h study.”

Over the following four hours, researchers wearing white lab coats wandered in and out of the room, scribbling fictitious notes on clipboards, while undercover research assistants (called confederates) pretended to be participants in the experiment, expressing strong subjective psychedelic feelings to the test group.

“To make it appear as if the drug was having a physiological effect, one confederate with naturally large pupils told some participants individually, 'Your pupils are huge! Are mine like that?',” the researchers write. “The room contained no mirrors (nor did the bathroom) or phone cameras for participants to verify this statement, and the dark room with red lights naturally dilated their pupils.”

During a debriefing at the end of the experiment the unwitting subjects were asked a variety of questions about their experiences. Over 60 percent of the subjects reported feeling some kind of psychedelic drug effect.

The experiment was run twice, and on the second occasion the researchers broadened their post-test questions to include specifically asking subjects whether they thought they had taken a placebo or an active psychedelic. Only 35 percent of subjects were sure they were given a placebo. A striking 50 percent of those with previous experience using psychedelic drugs reported some kind of psychoactive effect from the placebo.

“The study reinforces the power of context in psychedelic settings,” explains Olson. “With the recent re-emergence of psychedelic therapy for disorders such as depression and anxiety, clinicians may be able to leverage these contextual factors to obtain similar therapeutic experiences from lower doses, which would further improve the safety of the drugs.”

The idea of “set and setting” fundamentally influencing the quality of a psychoactive drug experience has dominated psychedelic science since Timothy Leary coined the phrase in the early 1960s. Set, being the psychological mindset a person approaches an experience with and setting covering the physical and environmental conditions surrounding a person during the experience.

Leading psychedelic researcher Robin Carhart-Harris and his team at Imperial College London published an influential paper in 2018 suggesting set and setting (defined in the paper as "context") must be seriously considered in all modern psychedelic research. Olson and his McGill team, say their research affirms the importance of psychedelic clinical trials to report extra contextual information so other scientists can ascertain how much influence set and setting had on individual trial results.

“Given our results, we suggest that psychedelic researchers explore and report individual effects found in their placebo (or very low dose) control groups,” the new McGill study concludes. “We also suggest that researchers describe the setting in more detail – ideally with photographs – and mention the behavior of clinicians or experimenters. In particular, it would be helpful to describe the list of drug effects given to participants, which can influence their expectations and experiences.”

Samuel Veissière, a cognitive anthropologist at McGill who worked on the study, says this research highlights how significant placebo effects can be in psychedelic studies. Although this experiment obviously amplified the external influences, the results suggest even subtle social influences in psychedelic trials could be influencing the results.

“Placebo effects may have been under-estimated in psychedelic studies,” says Veissière. “The current trend towards ‘micro-dosing’ (consuming tiny amounts of psychedelic drugs to improve creativity), for example, may have a strong placebo component due to widespread cultural expectations that frame the response.”

The new research was published in the journal Psychopharmacology.

Source: McGill University