Frontiers in Pharmacology
November 2, 2018
Adam D. G. Hampshire, Christopher Timmermann, Christopher Timmermann et al.
422 citations
Psychological well-being increased two weeks after a psychedelic experience and remained elevated at four weeks. Higher ratings of a 'mystical-type experience' positively influenced this change in well-being, while 'challenging experience' and 'visual effects' did not. Having 'clear intentions' for the experience fostered mystical-type experiences. A positive 'set' and recreational intentions reduced the likelihood of a challenging experience. The trait 'absorption' and higher drug doses amplified all aspects of the acute experience. Baseline traits had the strongest effect on well-being change, underscoring the importance of extra-pharmacological factors in shaping responses to psychedelics.
Frontiers in Pharmacology
March 31, 2022
Roberta Murphy, Roberta Murphy, Hannes Kettner et al.
229 citations
In a trial comparing psilocybin-assisted therapy to escitalopram for moderate-to-severe depression, a stronger therapeutic alliance with the therapist predicted greater emotional breakthrough and mystical-type experiences during psilocybin sessions, and these experiences in turn predicted larger reductions in depression symptoms six weeks after treatment. Emotional breakthrough during the first session strengthened the alliance before the second session, while a weaker alliance before the second session directly predicted higher depression scores at the endpoint, independent of the acute psychedelic experience. The findings suggest the therapeutic relationship plays a key role in shaping both the quality of the psychedelic experience and clinical outcomes.
Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
Scientific reports
November 23, 2021
Christopher Timmermann, Hannes Kettner, Chris Letheby et al.
208 citations
People who use psychedelic drugs often shift away from materialist views of reality and consciousness toward panpsychism and fatalism, with most changes lasting at least six months. In a large prospective online survey, these belief shifts correlated with greater past psychedelic use and improved mental health. Emotional synchrony with others during the experience mediated the changes, and baseline impressionability moderated them. An independent clinical trial confirmed the direction of belief change, suggesting psychedelics may causally influence metaphysical beliefs away from hard materialism, though contextual independence remains uncertain.
Psychopharmacology
August 8, 2022
Rosalind Watts, Hannes Kettner, Dana Geerts et al.
159 citations
A new scale, the Watts Connectedness Scale (WCS), measures a three-dimensional sense of connectedness to self, others, and the wider world. Analysis of data from 1,226 participants in online surveys and a randomized controlled trial of 52 people with major depressive disorder showed the scale has good internal consistency and construct validity. After psychedelic use, total connectedness scores increased significantly, and acute experiences of mystical experience, emotional breakthrough, and communitas correlated with these changes. In the trial, psilocybin-assisted therapy produced greater increases in WCS scores than daily escitalopram. The WCS may sensitively capture therapeutically relevant psychological changes.
International journal of environmental research and public health
December 16, 2019
Hannes Kettner, Sam Gandy, Eline C H M Haijen et al.
159 citations
People who use psychedelics report a stronger sense of connection to nature, and this increase lasts for at least two years. In a prospective online study, individuals planning to use a psychedelic completed questionnaires before and after their experience. Nature relatedness was significantly higher at 2 weeks, 4 weeks, and 2 years after the experience. The increase was linked to greater psychological well-being and depended on how strongly participants felt ego-dissolution and how much they perceived their natural surroundings during the acute psychedelic state. The findings suggest a causal, context-dependent effect of psychedelic use on nature relatedness, with implications for mental health treatments and planetary health.
Scientific Reports
January 21, 2021
Laura Kaertner, Michael B. Steinborn, Hannes Kettner et al.
152 citations
A prospective study of weekly psychedelic microdosing found that participants reported improved well-being, emotional stability, and reduced anxiety and depressive symptoms over four weeks. However, baseline positive expectancy scores predicted these improvements, suggesting a significant placebo response. The findings caution against overinterpreting the therapeutic value of microdosing.
Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
Frontiers in Psychiatry
August 7, 2020
Richard J. Zeifman, Anne Catherine Wagner, Ros Watts et al.
104 citations
In two prospective studies with convenience samples of people planning to use a psychedelic (total N=358), participants completed questionnaires before use and at 2 and 4 weeks afterward. Across both studies, significant decreases occurred in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may reduce experiential avoidance, depression severity, and suicidal ideation, and that reduced experiential avoidance may be a transdiagnostic mechanism in psychedelic therapy. Integrating psychedelics with therapies targeting experiential avoidance, such as acceptance and commitment therapy, may enhance outcomes.
Journal of Psychopharmacology
May 29, 2021
Pedro J. Teixeira, Matthew W. Johnson, Christopher Timmermann et al.
87 citations
Healthy behaviors like diet, exercise, and not smoking greatly reduce risks for cancer, diabetes, and cardiovascular disease, but lifestyle diseases remain a major burden. Psychedelic substances, particularly psilocybin, are being explored as tools to promote positive lifestyle change. Psilocybin has low toxicity, is non-addictive, and has shown favorable changes in patients with depression, anxiety, and substance misuse. The article describes proposed mechanisms of action and research linking psychedelics to health behavior change, suggesting that combining psychedelic experiences with methods like Cognitive Behaviour Therapy and Motivational Interviewing may help improve diet, exercise, nature exposure, and mindfulness.
Frontiers in Psychiatry
June 29, 2021
Keri Mans, Hannes Kettner, David Erritzøe et al.
65 citations
Psychedelic substances like LSD and psilocybin have regained legitimacy in clinical research. In this naturalistic observational study of volunteers intending to take a psychedelic, well-being was assessed using fourteen measures at four time points: 1 week before and 2 weeks, 4 weeks, and 2 years after the experience (sample sizes 654, 315, 212, and 64, respectively). Changes clustered into three factors: 'Being well,' 'Staying well,' and 'Spirituality.' Repeated measures analysis showed improvements in Being Well and Staying Well in the weeks following the experience, and mixed model analyses indicated these improvements remained statistically significant up to 2 years, despite high attrition. Spirituality did not show significant change.
BJPsych Open
September 1, 2022
Tommaso Barba, Sarah Buehler, Hannes Kettner et al.
57 citations
Psilocybin, but not the antidepressant escitalopram, reduced rumination and thought suppression in people with major depressive disorder six weeks after treatment. In a randomized trial of 59 participants, only those given psilocybin showed significant decreases in both maladaptive coping strategies. Among treatment responders, thought suppression decreased exclusively in psilocybin responders, while rumination decreased in both psilocybin and escitalopram responders. Reductions in rumination and thought suppression correlated with ego dissolution and psychological insight during psilocybin sessions, suggesting distinct therapeutic mechanisms for the two treatments.
Contemporary Drug Problems
September 1, 2019
Hannes Kettner, Natasha L. Mason, Kim P. C. Kuypers
50 citations
Motives for using novel psychoactive substances (NPS) are largely similar to those for classical psychoactive substances (CPS), except for synthetic cannabinoids, whose main endorsed motive is getting intoxicated without regard to specific qualities. Across 12 substances, the most common motives are feeling euphoric (58.0%), enhancing an activity (52.3%), and broadening consciousness (48.1%). Coping-related reasons are more frequent among female participants, while males indicate a broader range of motives. These patterns can inform tailored educational campaigns and prevention strategies.
Hypertension
March 8, 2021
Otto Simonsson, Peter S. Hendricks, Robin Carhart‐Harris et al.
36 citations
Adults who had used a classic psychedelic at least once in their lifetime had 14% lower odds of hypertension in the past year, after adjusting for confounders. The association was strongest for tryptamine psychedelics (DMT, ayahuasca, psilocybin), which were linked to 20% lower odds of hypertension. No significant association was found for LSD or mescaline. The authors note these findings are correlational and call for randomized controlled trials to test causal effects.
European journal of psychotraumatology
January 1, 2024
Richard J Zeifman, Hannes Kettner, Stephen Ross et al.
34 citations
Therapeutic alliance—the quality of the relationship between therapist and client—predicts improvement in PTSD symptoms after MDMA-assisted psychotherapy. Among 22 adults with chronic PTSD who received MDMA during a clinical trial, stronger therapeutic alliance measured at sessions 4 and 9 (but not before the third session) was associated with lower clinician-assessed PTSD severity after treatment, even after accounting for initial symptom severity. Self-reported PTSD severity was also predicted by alliance at baseline, session 4, and session 9, though the baseline finding did not survive correction for multiple comparisons. These results provide initial evidence that common psychotherapeutic factors like alliance contribute to outcomes in MDMA-assisted therapy.
Scientific Reports
August 22, 2023
Hannes Kettner, Stephen Ross, Richard J. Zeifman et al.
31 citations
Co-using a low dose of MDMA with psilocybin or LSD is associated with less intense challenging experiences—such as grief and fear—and increased feelings of self-compassion, love, and gratitude, compared to using psilocybin or LSD alone. In a survey of 698 people planning to use these substances, the 27 who also took a low dose of MDMA reported these benefits without a reduction in mystical-type experiences or compassion. Medium-to-high MDMA doses did not show the same effects. The findings suggest MDMA may buffer against some difficult aspects of psychedelic experiences, but the study's small, non-experimental convenience sample limits certainty.
Scientific reports
January 29, 2025
Richard J Zeifman, Meg J Spriggs, Hannes Kettner et al.
26 citations
A preliminary test of the REBUS model found that a high dose of psilocybin (25 mg) reduced confidence in negative self-beliefs in 11 healthy individuals, both during the acute experience and four weeks later. Greater brain signal entropy and stronger subjective effects under psilocybin correlated with larger decreases in negative self-belief confidence. Decreases in negative self-belief confidence were linked to increases in well-being. The findings provide initial evidence that relaxing and revising negative self-beliefs may underlie psilocybin's positive psychological effects, with increased neuronal entropy as a possible mechanism. Replication in larger clinical samples is needed.
Scientific Reports
February 7, 2024
Tommaso Barba, Hannes Kettner, Caterina Radu et al.
24 citations
Psychedelics may improve sexual functioning and satisfaction days or weeks after use, according to two studies. In a large naturalistic study, people who used psychedelics reported greater pleasure, communication during sex, and satisfaction with their partner and appearance. A controlled clinical trial comparing psilocybin therapy with the SSRI escitalopram for depression found that those given psilocybin reported positive changes in sexual functioning after treatment, while those given escitalopram did not. This is the first quantitative investigation of psychedelics' post-acute effects on sexual functioning, suggesting a potential benefit and a need for further research.
Journal of Medical Internet Research
May 4, 2021
Sebastian Hübner, Eline Haijen, Mendel Kaelen et al.
23 citations
In web-based studies that track people before and after they use psychedelics, many participants stop responding, which can bias the results. Analyzing data from 654 initial participants, younger age, lower education, higher extraversion, and lower conscientiousness predicted dropping out before the four-week endpoint. Neither positive attitudes toward psychedelics nor intense challenging experiences during the drug session predicted dropout. These attrition patterns match those seen in other long-term studies, suggesting they are not unique to psychedelic research. The absence of dropout linked to psychedelic advocacy or negative drug experiences reduces concerns about certain biases in this type of data.
Scientific reports
July 17, 2024
Sara de la Salle, Hannes Kettner, Julien Thibault Lévesque et al.
21 citations
A prospective longitudinal survey of eight Canadians with cancer who received legal psilocybin-assisted psychotherapy under Section 56 exemptions found significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks after the session. Attitudes toward death, medical assistance in dying, and desire for hastened death remained unchanged. Most participants found the sessions highly meaningful, though one reported a substantial decrease in well-being. These preliminary data suggest that real-world psilocybin-assisted psychotherapy can produce psychiatric benefits similar to those in clinical trials, but limited enrollment and negative experiences indicate a need for formal real-world evaluation programs.
Journal of Psychopharmacology
January 1, 2023
Matthias Forstmann, Christina Sagioglou, Alexander Irvine et al.
18 citations
Among people who have used psychedelics, only past use of psilocybin—not LSD, mescaline, Salvia divinorum, ketamine, ibogaine, or DMT—reliably predicted a stronger sense of connection to nature (nature relatedness). The finding held even when people who had never used psychedelics were included in the analysis. For those who had used only psilocybin, more frequent use was linked to higher nature relatedness. This suggests that psilocybin may have a unique association with nature relatedness, possibly due to its pharmacology or the contexts in which it is used.
July 7, 2022
Richard J. Zeifman, Meg J. Spriggs, Hannes Kettner et al.
13 citations
preprint
The Relaxed Beliefs Under pSychedelics (REBUS) model suggests that psychedelics reduce the strength of deeply held beliefs. In a preliminary test of this idea, 11 healthy adults received a low (1 mg) and a high (25 mg) dose of psilocybin four weeks apart. Confidence in negative self-beliefs decreased after the high dose but not after the low dose. Greater brain signal entropy and stronger subjective effects during the high dose correlated with larger decreases in negative belief confidence, both during the session and four weeks later. Reduced confidence in negative beliefs was strongly linked to improved well-being at the four-week follow-up. These findings provide initial psychological support for the REBUS model, though replication in larger and clinical samples is needed.
Journal of affective disorders
February 1, 2025
Grant Jones, Matthew X Lowe, Sandeep Nayak et al.
12 citations
Psilocybin, the psychoactive compound in magic mushrooms, is linked to improved mental wellbeing on average, but few studies examine how effects differ by race. In a large online longitudinal study of 2,833 people planning naturalistic psilocybin use, race/ethnicity moderated changes in spiritual wellbeing, cognitive flexibility, and emotion regulation (expressive suppression) at 2–3 months post-experience, but not at 2–4 weeks. Participants of Color reported minor differences in context and subjective effects, such as being more likely to set an intention before use. Both groups showed comparable reductions in anxiety and depression, with no significant moderation by race.
PNAS nexus
April 1, 2025
Katie Zhou, David de Wied, Robin L Carhart-Harris et al.
9 citations
Delusional ideation decreased one month after a planned psychedelic experience, while magical thinking showed no change. Over 30% of participants reported hallucinogen persisting perception disorder (HPPD)-type effects at four weeks, though fewer than 1% found them distressing. Younger age, female gender, a history of psychiatric diagnosis, and baseline trait absorption predicted HPPD-like effects. Lifetime psychedelic use at baseline correlated positively with both magical thinking and delusional ideation, suggesting these traits may correlate with psychedelic use rather than being caused by it.
Frontiers in psychiatry
January 1, 2024
Matthew X Lowe, Hannes Kettner, Del R P Jolly et al.
9 citations
Ceremonial ayahuasca use is associated with significant improvements in mental health, well-being, and psychological functioning among Middle Eastern and North African (MENA) immigrants and refugees. In a longitudinal online survey of 15 primarily female participants, reductions in depression, anxiety, and shame were reported, along with increases in cognitive reappraisal and self-compassion. Most participants reported no lasting adverse effects and experienced positive behavioral changes persisting months after ingestion. The findings suggest naturalistic ayahuasca use might hold therapeutic potential for MENA populations exposed to trauma prior to and during migration, though data are preliminary.