Recreational users of psychedelic drugs with low well-being are more likely than those with normal well-being to experience a positive mood change after taking LSD, psilocybin, or MDMA, according to new research published in the journal Drug Science, Policy and Law. The study examined how psychedelic use outcomes were related to personal, emotional, and environmental circumstances.

“There is a renewed interest in the use of psychedelics in the treatment of certain psychiatric conditions, like PTSD, anxiety, and depression. Importantly, it has been suggested that factors aside from the drug can influence the acute experience and mediate long-term effects. These factors include set (or, the internal state of the individual, like mood and well-being and certain personality traits), and setting (the environment in which the individual is taking the drug in),” explained study author Natasha L. Mason (@NL_Mason), a PhD candidate at Maastricht University.

“With this renewed interest in the (therapeutic) use of psychedelics, it is important to define optimal circumstances for administration of these substances. Specifically, as psychiatric populations often display clinical characteristics that are suggested to negatively impact the psychedelic experience, it is important to establish whether psychedelics are still a suitable therapeutic option, not leading to (more) negative, unwanted effects.”

“Currently, clinical trials include only a small number of highly selected/screened individuals, sometimes making it difficult to generalize to a broader psychiatric population. However, there is a wealth of information to be gained from recreational users, who report using the substance in various emotional and environmental circumstances, and for a number of different reasons,” Mason explained.

“Therefore, this study aimed to assess under which emotional (set) and environmental (setting) circumstances a large sample of psychedelic users consumed such substances, and the outcome of use in those with clinical characteristics.”

For their study, the researchers recruited 1,967 psychedelic users from online forums and had them complete an extensive questionnaire about their drug use, subjective well-being, personality, and other factors. The participants indicated the setting (at a party, at home, in a spiritual setting, etc) in which they usually used a particular psychedelic substance as well as which mood state they were usually in when they decided to use it. They also provided information about the emotional outcomes of their psychedelic use.

Most participants reported using psychedelic drugs when in a positive mood. The researchers also found that different substances were associated with different settings. More than 80% of participants said they usually took LSD or psilocybin at home, while more than half of participants said they used ayahuasca in a ceremonial or spiritual ritual setting. MDMA was usually used at a festival or party.

Based on the questionnaire, 1,324 participants were classified as having normal well-being while 643 participants were classified as having low well-being.

“The main take-away from our study was the finding that individuals with clinical characteristics (low well-being and higher scores in certain personality traits) report consuming psychedelics with positive outcomes. Interestingly, when comparing the ‘clinical’ group to the ‘healthy’ group, the clinical group was more likely to experience a positive mood change,” Mason told PsyPost.

“However, our findings also suggest that mood may not be the most important aspect of an individual’s ‘set’ when it comes to predicting their response to a psychedelic. Namely, we found that nearly 100% of individuals who took a psychedelic when in a negative mood reported a mood state change after use.”

“This is important because psychedelics are being investigated in individuals characterized with low mood (like depression), thus it suggests that they are still a therapeutic option, and importantly, when preparing an individual for a psychedelic experience, clinicians should focus on other set factors (for example, like preparedness and readiness for the experience, as has been suggested in other studies),” Mason explained.

The researchers also found that a personality trait was predictive of an individual’s response to psychedelic drugs.

“As scores in neuroticism increased, so did likelihood of experiencing unwanted side effects. Thus, as has been suggested in other studies, special attention should be given in preparing this population for a psychedelic experience. This would mean screening individuals on personality traits before entering clinical trials, and including longer preparation time for those that score high in this trait,” Mason said.

But the study — like all research — includes some limitations. “As this survey was advertised on forums focusing on psychedelics, the population that had unwanted experiences with psychedelics may not be involved with such forums, and thus were not reached,” Mason explained. The retrospective, self-report questionnaires may also be subject to poor or inaccurate memory recall.

“One obvious way to overcome these limitations would be to utilize an experimental, placebo-controlled study, where researchers give the drug to participants, and can ask these questions pre/post administration. However, this is easier said than done. These studies are very difficult to do, due to the legality and stigma surrounding these substances,” Mason said.

“Additionally, when they can run, these studies are very expensive, and currently include only a small number of highly screened individuals, which could make it difficult to generalize to a broader population. Thus we hope that questionnaire studies like this (in the ‘general’ population, with a large sample size) can provide data that scientists can reference when applying for approval and grants to carry out more controlled experimental trials.”

The study, “Reported effects of psychedelic use on those with low well-being given various emotional states and social contexts“, was authored by Natasha L. Mason, Patrick C. Dolder, and Kim P. C. Kuypers.