Psychological medicine
June 1, 2024
Balázs Szigeti, Brandon Weiss, Fernando E Rosas et al.
74 citations
In a double-blind trial comparing escitalopram and COMP360 psilocybin for major depressive disorder, patients held higher expectations for psilocybin than for escitalopram. Higher pre-trial expectancy for escitalopram predicted better outcomes with escitalopram, but expectancy for psilocybin did not predict response to psilocybin. Pre-treatment trait suggestibility was linked to therapeutic response in the psilocybin arm but not the escitalopram arm. These findings suggest that psychedelic therapy may be less influenced by expectancy biases than previously thought, and that highly suggestible individuals may be especially responsive to psilocybin treatment.
Psychological medicine
March 1, 2023
Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes et al.
53 citations
In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy volunteers received 50 μg LSD or placebo. LSD produced psychedelic experiences, including altered consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, and increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated strongly with complex imagery, mystical experiences, and ego-dissolution. Suggestibility changes from LSD did not correlate with other effects. The results suggest the LSD state resembles psychosis and may offer a therapeutic tool, with mystical experiences linking the psychosis model and therapeutic potential. Meaning attribution appears important for the LSD psychosis model, and psychedelic-assisted therapy might benefit from suggestions that foster mystical experiences.
Psychological medicine
April 1, 2023
Eric L Garland, Spencer T Fix, Justin P Hudak et al.
51 citations
Long-term opioid therapy for chronic pain can lead to anhedonia, or reduced ability to experience pleasure from natural rewards. A behavioral intervention called Mindfulness-Oriented Recovery Enhancement (MORE) was tested in 63 veterans on long-term opioid therapy for chronic pain, who were randomly assigned to eight weeks of MORE or a supportive group therapy. MORE increased brain and physiological responses to natural reward cues and reduced subjective anhedonia more than the control. The reduction in anhedonia was linked to increased brain activity during savoring of rewards. MORE may be an effective treatment for anhedonia in chronic opioid users and those at risk for opioid use disorder.
Psychological medicine
October 1, 2023
Jonathan W Kanen, Qiang Luo, Mojtaba Rostami Kandroodi et al.
44 citations
LSD increases the rate at which people learn from both rewards and punishments during a probabilistic reversal learning task, suggesting a state of heightened learning plasticity. Healthy volunteers given intravenous LSD or placebo completed a task where they had to learn which of three stimuli was most often rewarded, with the reward contingencies later reversing. Computational modeling of reinforcement learning showed that LSD primarily enhanced the reward learning rate and also elevated the punishment learning rate, while decreasing stimulus stickiness (a measure of choice repetition), indicating increased exploration. These effects point to a potential mechanism by which LSD could help revise maladaptive associations in clinical treatment.
Psychological medicine
January 1, 2024
Brandon Weiss, Induni Ginige, Lu Shannon et al.
38 citations
In a trial comparing psilocybin therapy with the antidepressant escitalopram for moderate-to-severe major depressive disorder, both treatments led to personality changes in a direction consistent with improved mental health. Psilocybin was linked to decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness at six weeks, with some changes lasting six months. Escitalopram was linked to decreases in neuroticism, disagreeableness, and impulsivity, and increases in openness at six weeks, with neuroticism remaining decreased at six months. No significant differences between the two treatments were observed, except that patients' pre-trial positive expectations for escitalopram moderated personality changes after that treatment, but not after psilocybin.
Psychological medicine
October 1, 2022
Ashish K Sahib, Joana R Loureiro, Megha Vasavada et al.
36 citations
Ketamine infusion therapy can rapidly relieve depression, but its effects on whole-brain functional connections are not well understood. In patients with major depressive disorder (MDD), baseline resting-state functional connectivity (FC) differed from healthy controls in the somatomotor network and between association and default mode networks. After one and four ketamine infusions, these disrupted FC patterns trended toward those of controls. Serial ketamine treatment significantly decreased FC between the cerebellum and the salience network. Patients who remitted showed higher pre-treatment FC between the cerebellum and striatum that decreased after treatment, while non-remitters showed the opposite pattern. Ketamine induces neurofunctional plasticity in cortico-striatal-cerebellar loops involving the salience network, which may serve as a biomarker for treatment response.
Psychological medicine
December 1, 2023
Paul McCrone, Henry Fisher, Clare Knight et al.
34 citations
Psilocybin-assisted psychotherapy (PAP) may be a cost-effective treatment for severe depression, depending on the price of the drug and the level of therapist support. A decision model compared PAP with conventional medication, cognitive behavioural therapy (CBT), and their combination over six months. PAP produced the highest quality-adjusted life years (0.310) but also the highest expected healthcare cost (£6,132 to £7,652). PAP became cost-effective when therapist support costs were reduced by 50% and the psilocybin price dropped to £400–£800 per person. From a societal perspective, PAP's cost-effectiveness improved further. More long-term outcome data are needed.
Psychological medicine
November 20, 2024
B Yildirim, S S Sahin, A Gee et al.
19 citations
Psychedelic drugs are being studied for treating depression, but concerns about psychiatric side effects persist. A review of case reports found 17 cases of schizophrenia spectrum disorder and 17 of affective disorder (depression, mania, or both) after psychedelic use, excluding people with prior psychiatric illness or other drug use. These conditions could begin after a single use (5 of 17 schizophrenia cases; 6 of 17 affective disorder cases). Recovery was typical for affective disorder but not for schizophrenia spectrum disorder. Among 29 flashback cases, 12 had lasting psychiatric symptoms, mainly anxiety (5 cases) and depression (8 cases). Flashbacks resolved within a year in about half of cases but persisted for years in a few. Serious psychiatric disorders after psychedelic use are uncommon but documented.
Psychological medicine
June 1, 2023
Ben Alderson-Day, Peter Moseley, Kaja Mitrenga et al.
19 citations
Felt presence—the sense that someone else is nearby when no one is there—occurs across neurology, bereavement, psychosis, hypnagogic states, solo sports, and spiritual experiences, but systematic comparisons are rare. Three online surveys compared felt presence in people with psychosis or voice-hearing (75 participants), spiritualist believers (47 participants), and endurance/solo athletes (84 participants). Hierarchical linear regression showed that a general tendency toward hallucinations predicted felt presence frequency in all groups; paranoia and female gender were additional predictors in the psychosis sample. Qualitative analysis revealed shared features, especially immersive states, across contexts. The findings support a unitary model of felt presence, suggesting common underlying mechanisms.
Psychological medicine
September 1, 2022
Benjamin S C Wade, Joana Loureiro, Ashish Sahib et al.
18 citations
Before serial ketamine infusion, brain structure, function, and connectivity measures predicted how much depressive symptoms changed afterward. In 60 patients with depression, machine learning models using pretreatment MRI scans explained 19% of variance in core mood and anhedonia symptoms, 27% in a depression subscale, and 1% in rumination reflection. Greater connectivity in the right medial prefrontal cortex, anterior cingulate, and posterior insula, along with lower kurtosis of a white-matter tract, predicted larger symptom reductions. Connectivity of the left posterior cingulate, left insula, and right superior parietal lobule predicted changes in rumination. These findings suggest that anterior default mode network and posterior insula connectivity may serve as biomarkers for antidepressant response.
Psychological medicine
April 1, 2024
Otto Simonsson, Walter Osika, Cecilia U D Stenfors et al.
15 citations
People who used psychedelics during a two-month period reported a greater increase in days of mindfulness meditation per week than those who did not. Among psychedelic users, experiencing personal insight during the most intense psychedelic session was linked to larger increases in both mindfulness and loving-kindness or compassion meditation practice. Conversely, more frequent loving-kindness or compassion meditation at the start of the study was associated with less severe feelings of death or dying during the subsequent psychedelic experience. These findings suggest a bidirectional relationship: psychedelics may boost meditation engagement, while meditation may reduce challenging psychedelic experiences.
Psychological medicine
February 1, 2024
Pavo Orepic, Fosco Bernasconi, Melissa Faggella et al.
9 citations
A robotic procedure that creates sensorimotor conflicts and a feeling of another person's presence can induce auditory-verbal hallucination (AVH)-like sensations in healthy individuals. In two studies, participants showed increased false alarm rates on a voice detection task. Stronger sensorimotor conflicts led to more AVH-like sensations, supporting the self-monitoring deficit account. The otherness condition produced more false alarms when detecting other-voice stimuli than self-voice stimuli, consistent with the strong perceptual priors account. The findings integrate both theoretical models of AVH.
Psychological medicine
October 1, 2023
Imke Hanssen, Marloes Huijbers, Eline Regeer et al.
7 citations
Adding mindfulness-based cognitive therapy (MBCT) to treatment as usual (TAU) for bipolar disorder did not reduce depressive symptoms more than TAU alone at post-treatment or at 15 months follow-up. The 144 participants with bipolar I or II were randomly assigned to MBCT plus TAU or TAU only. At post-treatment, MBCT improved mindfulness skills more than TAU. At follow-up, TAU was more effective than MBCT plus TAU for reducing trait anxiety and improving mindfulness skills and positive mental health. Participants with higher baseline depression and functional impairment benefited more from MBCT plus TAU, suggesting MBCT may help those with moderate to severe depression and impairment.
Psychological medicine
August 8, 2025
Giulia Trotta, Edoardo Spinazzola, Hannah Degen et al.
4 citations
Childhood trauma, especially emotional and physical abuse, is strongly linked to paranoia, and cannabis use amplifies that effect. In a survey of 4,736 adults, those who experienced childhood trauma reported higher paranoia, and weekly cannabis use—measured in standard THC units—also predicted greater paranoia. Cannabis use partially mediated the link between trauma and paranoia, though trauma itself had a much larger direct effect. The findings suggest that assessing both trauma history and cannabis exposure in standard THC units could improve risk detection and guide interventions for people with childhood trauma.
Psychological medicine
August 26, 2025
Lydia Johnson-Ferguson, Michelle Loher, Laura Bechtiger et al.
2 citations
Frequent cannabis use in young adulthood predicts increases in psychotic-like experiences, internalizing symptoms, aggression, problematic substance use, and higher odds of not being in employment, education, or training, along with decreased general well-being from ages 20 to 24. These associations held whether cannabis exposure was measured by self-reported frequency or by hair THC concentrations, and effect sizes were small. Composite measures combining self-reports and hair data were no more informative than either source alone. The findings come from a community sample of 863 young adults, with 150 reporting weekly-to-daily use and 110 having detectable cannabis in hair at age 20.
Psychological medicine
May 8, 2026
Lou-Anne Chavigny, Véronique Desbeaumes Jodoin, Nicolas Garel et al.
A systematic review of 21 studies involving approximately 900–1,180 participants with treatment-resistant depression found that low-dose intravenous ketamine preserves and enhances certain cognitive functions. Improvements were frequently observed in processing speed and working memory, while attention remained stable or modestly improved. Results for verbal and visual memory varied across studies. Executive control, especially inhibitory performance on Stroop tasks, improved in several trials. No cognitive worsening was reported. Two studies directly examined cognition in relation to suicidal behaviors, suggesting that procognitive effects, particularly in executive control, may mediate ketamine's antisuicidal action. Standardized longitudinal studies are needed to clarify durability and clinical significance.
Psychological medicine
February 4, 2026
Katrina Mysko, Elise Quarterman Gear, Lyn Ellett
A systematic review and meta-analysis found a small negative association between trait mindfulness and psychotic-like experiences (PLEs) in nonclinical populations, meaning higher mindfulness levels are linked to fewer PLEs. However, mindfulness-based interventions showed no significant effect on reducing PLEs in these populations. The pooled correlation from eight studies was -0.25, and the summary effect from five intervention studies was not significant. The findings should be interpreted cautiously due to the small number of studies and high heterogeneity.
Psychological medicine
January 12, 2026
Lawrence Kin-Hei Chung, Thomas J Whitford, Anson Kai Chun Chau et al.
People with schizophrenia who hear voices experience inner speech—the silent, internal monologue—more frequently and with a different character than healthy individuals. Using repeated daily surveys on electronic devices, researchers found that voice-hearers reported more moments of inner speech and higher intensity of evaluative, other people's voices, condensed, and positive inner speech, though not dialogic inner speech. When voice-hearers experienced more intense dialogic, evaluative, other people's, or condensed inner speech, they also reported more severe auditory verbal hallucinations. Negative emotions strengthened the link between evaluative inner speech and hallucination severity. The findings suggest inner speech contributes to voice-hearing and that emotional state may be a target for therapy.
Psychological medicine
May 1, 2023
David Van den Berg, Eva Tolmeijer, Alyssa Jongeneel et al.
In people with psychosis who hear voices after experiencing trauma, trauma often shapes the content and emotional impact of those voices. Among 73 participants, independent links between trauma and voices—such as similar victimization types, emotional responses, or negative self-beliefs—were reported by 51-58% of participants and 8-41% of researchers. Dependent links, where the voice directly mirrored the trauma in content, identity, or relational dynamics, were found in 80% of participant reports and 66% of researcher ratings, with relational links being most common. Negative self-beliefs from trauma strongly predicted similar beliefs in voices. Trauma appears to be a powerful force shaping voice-hearing, suggesting that trauma-induced mechanisms may be important targets for intervention.