Tripping on nothing: placebo psychedelics and contextual factors

This placebo-only study (n=33) found that by creating a highly psychedelic-like setting (including actors), a majority of participants believed they felt some drug effects.

Abstract

“Rationale Is it possible to have a psychedelic experience from a placebo alone? Most psychedelic studies find few effects in the placebo control group, yet these effects may have been obscured by the study design, setting, or analysis decisions.

Objective We examined individual variation in placebo effects in a naturalistic environment resembling a typical psychedelic party.

Methods Thirty-three students completed a single-arm study ostensibly examining how a psychedelic drug affects creativity. The 4-h study took place in a group setting with music, paintings, coloured lights, and visual projections. Participants consumed a placebo that we described as a drug resembling psilocybin, which is found in psychedelic mushrooms. To boost expectations, confederates subtly acted out the stated effects of the drug and participants were led to believe that there was no placebo control group. The participants later completed the 5-Dimensional Altered States of Consciousness Rating Scale, which measures changes in conscious experience.

Results There was considerable individual variation in the placebo effects; many participants reported no changes while others showed effects with magnitudes typically associated with moderate or high doses of psilocybin. In addition, the majority (61%) of participants verbally reported some effect of the drug. Several stated that they saw the paintings on the walls “move” or “reshape” themselves, others felt “heavy… as if gravity [had] a stronger hold”, and one had a “come down” before another “wave” hit her.

Conclusion Understanding how context and expectations promote psychedelic-like effects, even without the drug, will help researchers to isolate drug effects and clinicians to maximise their therapeutic potential.”

Authors: Jay A. Olson, Léah Suissa-Rocheleau, Michael Lifshitz, Amir Raz & Samuel P. L. Veissière

Summary

Most psychedelic studies find few effects.

Introduction

Although the placebo effect is robust across various domains, psychedelic studies generally report few effects in the placebo control group. However, people sometimes report having a contact high, in which they experience drug-like effects without consuming a drug but merely by being around others who have.

Contact highs may occur when consuming psychedelic drugs in familiar environments conducive to the experience, such as parties with lights, music, and art, and a social setting that promotes the spreading of emotions and observational learning of drug effects.

The effects of psychedelic drugs are caused by three components: pharmacological factors, non-pharmacological (contextual) factors, and their interaction. Some studies have explored the interaction between the pharmacological and non-pharmacological factors by testing how different environments promote drug effects.

Psychedelic studies generally find few effects in their placebo control groups. The famous Good Friday experiment found that 40% of participants had a complete mystical experience, while none in the placebo group did.

We suspected that placebo psychedelic effects may be stronger than previously reported, as they may have been obscured by the lab setting, study design, or analysis decisions. Even strong effects may not be explored in detail, and participants who experience no effects may pull down reported averages.

Some studies with individual-level metrics do occasionally report strong effects from placebo psychedelics. The present feasibility study explored individual variation in responses to placebo psychedelics in a naturalistic context that may promote contact highs and placebo effects.

Participants

We recruited participants through social media advertisements and screened them to ensure that they were university students with no physical or mental health issues. 33 people showed up to participate (M = 21.7 years old, SD = 3.4; 18 men).

We ran two samples of participants, one with students from a different university, and one without. We removed the criterion for previous psychedelic drug use in the second sample.

Screening

The researcher explained that participants would consume a small dose of the psychedelic drug iprocin, which has effects similar to psilocybin.

Setting

We used a detailed procedure to make it appear that there was no placebo control group. Participants were met in the lobby of the Montreal Neurological Institute of McGill University and led through the hallways where numerous researchers held doors open.

The experiment room had a naturalistic atmosphere, resembling a party, with psychedelic paintings adorning the walls and a DJ playing ambient music. Discreet cameras recorded the experiment, and a psychiatrist was on site in case participants were anxious or had (placebo) emergencies.

Briefing

The experimenter stated that the study investigated the interaction between a drug and the environment on creativity. He explained that the drug, iprocin, would start to affect participants within 15 min, peak in 1 to 2 h, then quickly fade.

Participants did not seem to be sceptical about the study procedure, given that they were knowledgeable about drugs and the institution has done little psychedelic research since the 1960s. However, we had several factors working in our favour, including elaborate preparation and effort to conceal the true purpose.

Baseline measurements

After signing the consent form, participants completed questionnaires measuring personality, mood, and subjective experience. Their heart rate and blood pressure were read out as 10 units lower than they actually were.

Placebo

The participants took a pink placebo pill, which was filled with an inert powder. They were casually offered any pill cup from a tray, and the experimenter shined a flashlight in their mouth to ensure that they had swallowed it.

The participants had 30 min to mingle, and the confederates started to act out the effects of the drug in subtle ways. This made it appear as if the drug was having a physiological effect.

Filler creativity measures

We then collected data on creativity by asking participants to move to a new area of the room and complete creativity tasks.

Experience measurements

After 45 min of mingling, the participants completed the same mood and experience questionnaires as before, and the researcher increased their heart rate and blood pressure by 10 units. They were then asked about any effects they had noticed since the study began.

Debriefing

The participants were asked whether they had used any psychedelic drugs before, and whether they believed they had ingested a psychedelic drug or a placebo.

Measures

5-dimensional altered states of consciousness rating scale (5D-ASC)

The 5D-ASC measures changes in subjective experience and has 11 subscales: anxiety, spiritual experience, insightfulness, impaired control and cognition, disembodiment, experience of unity, blissful state, changed meaning of percepts, complex imagery, audio-visual synaesthesia, and elementary imagery.

Participants completed this measure before and after ingesting the pill. Two participants had unexpectedly high scores and were excluded from the entire scale.

Positive and negative affect schedule (PANAS)

The PANAS is a 20-item questionnaire that measures how much participants feel various emotions, such as “Enthusiastic” or “Distressed”. The internal consistency was good for positive affect but lower for negative affect.

Filler measures

The 44-item Big five inventory measures five broad personality traits and did not predict alterations in consciousness in our participants.

In the second sample, participants completed a creativity measure and a house tree person test. They were given 1 min to draw each item and another minute to add any details.

Alterations in consciousness

There was considerable individual variation in placebo effects, with some participants reporting greater changes in experience than those associated with ingesting moderate or high doses of psilocybin or moderate doses of LSD.

Verbal reports

One participant reported feeling light-headed, relaxed, and warm, and said she “definitely felt [she] was high on something”. She said she could make herself “sober” if she wanted to, but instead she was “trying to make [herself] feel it” to enjoy the experience.

I didn’t feel anything until we were doing the drawings, and then I had a sinking feeling in my head.

One participant reported perceptual changes, while others reported feeling energetic, uninhibited, warm, relaxed, mild, mellow, or dulled. Some participants reported minor headaches, zoning out more than usual, or feeling more inventive during the drawing task.

Previous drug use

Participants who had previously used psychedelic drugs reported similar effects to those who had not, with average 5D-ASC scores of 3.82 in experienced users and 3.59 in naive ones.

Mood

Participants’ positive and negative affect reduced throughout the study, with the “excited” and “nervous” items dropping the most on each subscale.

Scepticism

In the second sample, participants were asked whether they were certain they had taken a psychedelic, a placebo, or were uncertain. Overall, 35% were certain and 53% were uncertain.

Many participants were shocked when we revealed the study was a placebo. One participant asked if they had been watching paintings for 45 minutes.

Discussion

In this study, we explored the role of expectation in psychedelic experiences. Some participants reported effects stronger than those typically associated with moderate or high doses of psychedelic drugs, prompting the question of whether expectations and context remain important even when microdosing.

A balanced placebo design allows researchers to isolate how expectations interact with the drug to create psychedelic (or placebo) effects. This design is ideal for microdosing studies, in which it is more difficult to differentiate a placebo from the drug. To maximise placebo effects, we used an elaborate procedure that led participants to believe they would receive a psychedelic drug. However, using an active placebo that causes facial flushing would have likely promoted stronger effects.

Better understanding expectation and context may help explain the mystery of contact highs. The more confederates act out the effects of the drug, and the more the environment resembles naturalistic drug settings, the greater the contact highs will be.

A procedure similar to the one used in our study may be useful for placebo drug or alcohol studies looking to create credible experiments.

Understanding the optimal context for placebos and psychedelics may be useful for clinicians, as it may promote therapeutic outcomes. Some of the factors that promoted psychedelic-like effects in our participants could be translated into clinical contexts.

We cannot identify which factors promoted the effects of psychedelics without a separate control group. A control group could be an open-label placebo group or a different list of expected drug effects.

Some participants reported alterations in consciousness even before consuming the drug, but these changes were relatively small compared to after consuming the drug. Further research could include more behavioural or objective measures to assess whether these placebo effects are limited to subjective alterations in consciousness.

Our study highlights the importance of the placebo component of psychedelic drugs. Researchers should report individual effects found in their placebo (or very low dose) control groups and describe the setting in more detail to help explain differences in psychedelic effects across sites.