A quantitative textual analysis of the subjective effects of ayahuasca in naïve users with and without depression PMC

Psychedelics have been used for healing purposes since prehistoric times in some cultures (Carod-Artal, 2015; Guerra-Doce, 2015). Despite psychedelics’ eventual prohibition by the UN Convention on Psychotropic Substances in 1971, usage has continued underground ever since. Millions of people around the world take psychedelics every year, most commonly in informal settings, but increasingly under the supervision of underground therapists (Sessa and Fischer, 2015) or in retreat or therapy centres in regions where psychedelics are less strictly regulated (Rucker and Young, 2021).

• Literature reports corroborate headaches as a known adverse effect of psilocybin.
• The ‘Future directions’ section (pg. 33) appears to be a little premature in offering solutions to the problem of BD interaction with psilocybin consumption, especially for qualitative research that, as the text itself states, should raise questions rather than provide answers.
• Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.
• Participants remarked on how their psilocybin experiences enabled emotion processing and development of new perspectives that supported positive changes in mood.
• Growing evidence suggests psilocybin can be an effective treatment for unipolar depression 25–28.

Greater relaxation and sleep

There are divergences relative to the findings of previous studies regarding the use of psychedelics and mental health. In fact, some studies have demonstrated the potential for psilocybin to treat or alleviate symptoms present in different clinical conditions. Several other limitations need to be considered when appraising this study.Self-nominating, non-probability sampling is subject to sampling and volunteerbiases that reduce sample representativeness. In essence, inherent differences mayexist between people who are reached by the recruitment and choose to volunteer toparticipate compared to those who are not. Differences could also occur among thosewho drop out early or who choose not to respond to specific questions. Although oursubanalysis among survey completers indicated a low chance of significant attritionbias, we cannot ascertain whether the rare case of skipping the EMT question mayhave been disproportionately more common among actual EMT seekers or non-seekers,therefore, biasing the rate of EMT seeking to either direction.

Predictors of EMT seeking

After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. A community in which pharmacology is discussed self-reported negative outcomes of psilocybin users: a quantitative textual analysis pmc in all its aspects; we welcome members regardless of background or education.

Persistent psychiatric symptoms after eating psilocybin mushrooms

Pearson’s Chi-square (χ2) or Fisher’s exact tests wereused to investigate associations between treatment-seeking status and gender(male/female), previous magic mushroom experience status (first time in the pastyear/experienced) and presence of mental health diagnosis (yes/no). Descriptivestatistics and graphs were created to explore the experiences and symptomprofiles of EMT seekers. In addition, two multiple correspondence analyses (MCA;see Supplementary Methods and Abdi and Valentin, 2007) were conductedto explore pattern of relationships between different self-reported symptoms andbetween different self-reported reasons for incidents. Negative outcomes were rated on an ordinal scale, and therefore could not be treated as continuous data. While an ordinal regression model could be applied for predicting responses to a single ordinally rated dependent variable, it is not possible to create any summary statistic of a multiple-item scale which would retain the ordinal nature of the data. Therefore, to create a regression model predicting overall prevalence of negative outcomes across all items, the items were first transformed into binary variables, indicating No/Yes presence of any severity of a negative outcome.

• The study observed that depression severity was significantly reduced in participants who were dosed with ayahuasca, as assessed through scores on the Montgomery-Asberg Depression Rating Scale—MADRS13 and Hamilton Depression Rating Scale—HAM-D14.
• If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.
• Crucially, respondents were asked to report on their experiences with the psychedelic they had found most useful in case they had self-treated with many.
• The study received approval from the UCSF Independent Review Board (IRB#20–31330).
• Previous studieson psilocybin had similarly shown younger age to predict more challengingexperiences (Carbonaro et al.,2016; Studerus etal., 2012).
• Crucially, although reported outcomes from naturalistic use seem mostly positive, psychedelics’ ability to bring up unprocessed trauma or grief may cause heightened psychological risks in clinical populations (Johnson et al., 2008; Watts et al., 2017).

Table. Summary of Included Studies.

Additionally, for each study, a funnel plot was created to evaluate publication bias. Study quality was assessed by the risk-of-bias tool for randomized trials (RoB2).14 Two of us (A.Y. and N.M.M.A.B) determined initial RoB2 scores for the included studies. An additional 2 of us (J.C. and J.E.T.) then independently assessed and verified initial scores. In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.

Treatment outcomes: Predictors

Future research can be improved with utilisation of prospective designs and additional predictive variables. The ‘Future directions’ section (pg. 33) appears to be a little premature in offering solutions to the problem of BD interaction with psilocybin consumption, especially for qualitative research that, as the text itself states, should raise questions rather than provide answers. Before outlining how psilocybin may be given to persons with BD in clinical trials, I believe you should specify what types of study could and should be conducted – not to mention the ethical aspects – to address this issue. A pattern of increased emotion processing, i.e., novel exploration of inner experiences (e.g., emotion, memories) in which participants described greater openness to emotional experience, was observed in several reported experiences during psilocybin use.

In addition, improvements in neuropsychological functioning have also been observed7. Growing evidence suggests psilocybin can be an effective treatment for unipolar depression 25–28. These findings led the Food and Drug Administration (FDA) to designate psilocybin as a “breakthrough therapy” for depression 29, 30. This designation demonstrates the FDA’s acknowledgment that the drug may outperform other available therapies, and thus expedites the Federal review of psilocybin. However, despite overlaps between unipolar depression and depression in the context of BD, modern clinical trials universally exclude individuals with any BD diagnosis or a family history of BD 19, 31. Little justification is typically provided for this and there is a dearth of published literature on the safety of psychedelic use in people with BD.

Figure 3. Association of Psilocybin With Dizziness, Blood Pressure, Paranoia, and Transient Thought Disorders.

Due to the dearth of published information regarding the knowledge and acceptance of psilocybin as a viable treatment option for patients, further research in psychedelic-assisted treatments may be warranted. We conducted a scoping review on psilocybin-assisted therapy for addiction, depression, anxiety and post-traumatic stress disorder. Psilocybin is a naturally-occurring tryptophan derivative found in species of mushroom with psycho-active properties. From 2022 records identified by database searching, 40 publications were included in the qualitative synthesis from which we identified 9 clinical trials with a total of 169 participants.

Trials used a peak-psychedelic model of therapy, emphasizing inward journey through the use of eyeshades, set musical scores and with medium to high doses of psilocybin. No serious adverse effects were reported; mild adverse effects included transient anxiety, nausea and post-treatment headaches. Overall, the 9 trials all demonstrated safety, tolerability and preliminary efficacy in the treatments of obsessive-compulsive disorder, substance use disorder, treatment-resistant unipolar depression, anxiety or depression in patients with life-threatening can… Contribution of polysubstance use to adverse psychedelic experiences have beenreported previously (Bienemannet al., 2020; VanAmsterdam et al., 2011). In both this study as well as in ourinvestigation on LSD-related EMT experiences (Kopra et al., 2022), majority ofrespondents consumed other substances prior to seeking EMT, most commonly cannabisand alcohol. In a previous survey study onpsilocybin-related challenging experiences, 53% reported having used cannabis and19% alcohol during or immediately before their experience (Carbonaro et al., 2016).

The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results. Two researchers conducted the interviews, which were carried out right after the end of the acute effects of ayahuasca. Interviews had an average duration of 13.7 min and started with an open-ended question (“Can you please freely describe your experience?”). When participants gave brief answers, or when further clarification was needed, they were probed with follow-up questions (e.g. “I saw a person” “Was that person known to you? Can you please provide more details?”).

Providing harm-reductioninformation likely plays a key role in preventing adverse effects. Moreresearch is needed to examine the detailed circumstances and predictors ofadverse reactions including rarer physiological reactions. Respondents reported on changes they had observed as a consequence of their self-treatment across 17 different aspects of well-being, psychiatric symptoms, social-emotional skills and health behaviours. Each item was rated on a 7-point scale, the two opposing values being −3 ‘strong negative consequences’ to +3 ‘strongly positive consequences’; 0 was considered ‘no change’, and respondents could also indicate not applicable (N/A).