Psychological Medicine
December 29, 2016
Rebecca S. Crane, Judson A. Brewer, Christina Feldman et al.
861 citations
A framework defines essential characteristics of mindfulness-based programs (MBPs) like MBSR and MBCT, distinguishing them from other interventions. MBPs draw from contemplative traditions, science, medicine, psychology, and education; are grounded in a model addressing causes of human distress and pathways to relief; foster present-moment focus, decentering, and an approach orientation; cultivate qualities such as joy, compassion, wisdom, equanimity, and self-regulation; and involve sustained intensive meditation training, experiential inquiry, and exercises. The framework aims to support clarity for systematic research and maintain integrity as MBPs expand into healthcare, education, criminal justice, and workplaces.
Psychological Medicine
June 15, 2018
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
827 citations
A single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
Psychological Medicine
November 27, 2009
A. Chiesa, A. Serretti
752 citations
Mindfulness meditation (MM) practices are linked to specific neurobiological changes and clinical benefits across psychiatric disorders, physical illnesses, and healthy individuals. Electroencephalographic studies show increased alpha and theta activity during meditation. Neuroimaging reveals activation of the prefrontal cortex and anterior cingulate cortex, with long-term practice enhancing attention-related brain areas. Clinically, Mindfulness-Based Stress Reduction benefits many conditions and healthy subjects; Mindfulness-Based Cognitive Therapy reduces depression relapse in patients with three or more episodes; Zen meditation lowers blood pressure; and Vipassana meditation reduces substance abuse in prisoners. However, low-quality study designs make it unclear whether benefits stem from specific or non-specific effects.
Psychological Medicine
February 12, 2016
Taishiro Kishimoto, J. M. Chawla, K. Hagi et al.
363 citations
A single intravenous infusion of ketamine reduces depression significantly more than placebo in people with major depressive disorder or bipolar depression, with effects beginning within 40 minutes, peaking at one day, and lasting up to one week. Non-ketamine NMDAR antagonists were superior to placebo only on days 5–8. Ketamine also led to greater response and remission rates at multiple time points. Adverse effects were transient and clinically insignificant, and discontinuation rates did not differ from placebo. The review analyzed 14 randomized controlled trials involving 588 participants.
Psychological Medicine
February 5, 2016
Robin Carhart-Harris, Mendel Kaelen, Mark Bolstridge et al.
301 citations
A single intravenous dose of LSD (75 µg) in 20 healthy volunteers produced robust acute psychological effects, including heightened mood and elevated scores on a measure of psychosis-like symptoms. Two weeks later, participants showed increased optimism and trait openness compared to after placebo, with no changes in delusional thinking. The findings suggest that psychedelics can acutely induce psychosis-like symptoms yet improve psychological wellbeing in the mid to long term. The authors propose that acute mood changes stem from a more fundamental modulation of cognition, and that increased cognitive flexibility from serotonin 2A receptor stimulation promotes emotional lability during intoxication and leaves a lasting loosened cognition conducive to improved wellbeing.
Psychological Medicine
August 12, 2015
James W. Murrough, Laili Soleimani, Kaitlin E. DeWilde et al.
297 citations
A single infusion of ketamine, compared to midazolam as an active placebo, did not reduce suicidal ideation scores on the Beck Scale for Suicidal Ideation at 24 hours in patients with mood and anxiety disorders who were at elevated risk for suicidal behavior. A significant difference favoring ketamine emerged at 48 hours, but the effect was no longer significant by the end of 7 days. The intervention was well tolerated with no dropouts during the primary assessment period. The findings support the safety and tolerability of ketamine for suicidal ideation but larger studies are needed.
Psychological Medicine
July 23, 2009
R. Martín-Santos, Ana B. Fagundo, José Alexandre S. Crippa et al.
207 citations
A systematic review of neuroimaging studies published up to January 2009 assessed evidence for cannabis effects on brain structure and function. Among 41 included studies, functional imaging indicated that resting global and prefrontal blood flow are lower in cannabis users than in controls. Activation studies during cognitive tasks produced inconsistent results. Acute administration of THC or marijuana increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of eight structural imaging studies found differences between users and controls, providing minimal evidence of major effects of cannabis on brain structure.
Psychological Medicine
May 1, 2001
Sarajane Bhattachary, Jane H. Powell
138 citations
Recreational users of MDMA (ecstasy) show impaired verbal memory and verbal fluency compared to non-users, while visual memory and working memory remain unaffected. In a study comparing 80 participants divided into non-users, novice users, regular users, and currently abstinent users, all three MDMA-using groups performed significantly worse on tests of immediate and delayed prose recall and verbal fluency. The deficits were not explained by differences in general intelligence or cannabis use. Days since last use and total lifetime consumption of MDMA each independently contributed to the variance in recall scores, together accounting for nearly half the variance in delayed recall. The findings suggest that verbal memory impairments in MDMA users combine reversible acute effects that resolve over two to three weeks with longer-term changes linked to lifetime exposure.
Psychological Medicine
July 22, 2019
Fabrizio Schifano, Flavia Napoletano, Stefania Chiappini et al.
118 citations
A novel web-crawling tool called NPS.Finder® identified several thousand new psychoactive substances (NPS)—roughly four times more than European and international drug agencies report. Synthetic cannabinoids, new synthetic opioids, ketamine-like dissociatives, novel stimulants, novel psychedelics, and certain prescription and over-the-counter medicines were most commonly linked to psychopathological consequences. The rapid proliferation of recreational psychotropics poses a challenge for psychiatry because the pharmacodynamics and pharmacokinetics of many NPS remain poorly understood. Health and mental health professionals need up-to-date information on the range of NPS, their intake methods, sought-after effects, drug combinations, and associated medical and psychopathological risks.
Psychological Medicine
September 10, 2019
Thomas Pokorny, Patricia Duerler, Erich Seifritz et al.
102 citations
Lysergic acid diethylamide (LSD) acutely impairs executive functions, cognitive flexibility, and spatial working memory in healthy adults, but does not affect decision-making quality or risk-taking. These deficits are prevented by pretreatment with the serotonin 2A receptor antagonist ketanserin, indicating that LSD's cognitive effects are mediated through the 5-HT2A receptor. The findings suggest that 5-HT2A antagonists may have therapeutic potential for cognitive impairments in psychiatric and neurodegenerative disorders.
Psychological Medicine
March 18, 2020
Diego Quattrone, Laura Ferraro, Giada Tripoli et al.
89 citations
Daily use of high-potency cannabis is associated with more positive symptoms and fewer negative symptoms in first-episode psychosis patients. Among 901 patients and 1,235 controls across six European countries, those who used high-potency cannabis daily had the highest scores on positive symptoms, while negative symptoms were more common in patients who never used cannabis. Psychotic experiences in controls were linked to current cannabis use but not to lifetime use. Depressive symptoms showed no differences related to cannabis use in either group.
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
January 28, 2004
Karen L. Hanson, Mónica Luciana
71 citations
People who used MDMA (ecstasy) and met criteria for substance abuse or dependence showed greater cognitive deficits than those who used the drug recreationally. MDMA users overall performed worse on memory and executive function tasks compared to non-users. The findings suggest that clinically dysfunctional MDMA use, rather than occasional recreational use, is linked to cognitive impairment.
Psychological Medicine
May 24, 2013
James Stone, Helen L. Fisher, Barnaby Major et al.
69 citations
Cannabis use is linked to an earlier onset of psychosis and more severe manic symptoms and conceptual disorganization, but not to delusions, hallucinations, negative symptoms, or daily functioning. In a naturalistic cohort of 502 patients with first-episode psychosis assessed at entry to services and after one year, those who reduced or stopped cannabis use showed the greatest improvement in symptoms, while continued users remained more symptomatic than non-users. Effective interventions to reduce cannabis use could yield significant health benefits for this population.
Psychological Medicine
September 1, 2008
G. Bedi, J. Redman
68 citations
Heavy ecstasy use is associated with some lowering of higher-level cognitive functions, but not with substantial cognitive dysfunction. A study comparing 45 abstinent ecstasy polydrug users, 48 cannabis polydrug users, and 40 legal drug users found no clear differences between groups on tests of attention, memory, and executive function. Lifetime dose of ecstasy was inversely linked to verbal memory performance, and a combination of drug-use variables, including ecstasy, predicted attention and working memory, though each factor explained only 1–6% of the variance in scores.
Psychological Medicine
November 4, 2020
Simon B. Goldberg, Benjamin Shechet, Christopher R. Nicholas et al.
66 citations
Classical psychedelics such as psilocybin, ayahuasca, and LSD produce significant psychological effects lasting at least 24 hours after administration, according to a systematic review and meta-analysis of 34 experimental studies involving 549 participants. Large effects were observed for reducing targeted symptoms in psychiatric samples, improving negative and positive affect, social outcomes, and existential or spiritual well-being, with between-group effect sizes ranging from Hedges' g = 0.84 to 1.08. Effects may be larger in clinical samples. Evidence for changes in personality traits or mindfulness was weak. No post-acute adverse effects were found, but high risk of bias, heterogeneity, and possible publication bias underscore the need for larger, placebo-controlled trials.
Psychological Medicine
October 2, 2017
André Schmidt, Felix Müller, Claudia Lenz et al.
62 citations
Activating the serotonin 2A receptor with LSD impairs the brain's ability to stop or inhibit responses, and this breakdown is linked to visual hallucinations. In a double-blind, placebo-controlled experiment with 18 healthy adults, LSD reduced brain activity in regions including the frontal and cingulate cortex, middle temporal gyrus, and cerebellum during a response-inhibition task. Parahippocampal activation related differently to performance under LSD versus placebo. Less activation in the left superior frontal gyrus during LSD exposure was associated with greater cognitive impairment and visual imagery. The findings suggest that 5-HT2A receptor activation disrupts hippocampal-prefrontal circuits, which may promote visual hallucinations.
Psychological Medicine
October 1, 2012
Zerrin Atakan, Sagnik Bhattacharyya, Paul Allen et al.
54 citations
A double-blind, placebo-controlled study of 21 healthy men with minimal cannabis experience found that oral administration of 10 mg THC induced transient psychotic symptoms in 11 participants but not in the other 10. Those who became transiently psychotic made more inhibition errors and showed opposite patterns of brain activation in the left parahippocampal gyrus, left and right middle temporal gyri, and right cerebellum compared to the non-psychotic group. The findings suggest that variability in sensitivity to THC's psychotogenic effects is linked to differential activation in ventral and medial temporal cortex and cerebellum.
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 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
July 19, 2023
Tehseen Noorani, Gillinder Bedi, Suresh Muthukumaraswamy
49 citations
When a medical research program overlaps with a social movement, new forms of sociality—termed 'chemosociality'—emerge from shared chemical exposure. In psychedelic-assisted therapy (PAT) clinical trials, this chemosociality creates 'dark loops': unrecorded social interactions that breach assumptions underlying causal inference used to establish treatment efficacy. These loops affect participant experiences but are not incorporated into trial data interpretation. Three researcher responses are proposed: chemosocial minimization (designing trials to reduce dark loops), chemosocial description (openly documenting them), and chemosocial valorization (actively leveraging them for positive outcomes). The hype surrounding psychedelic research continues to shape the phenomena under study, even as trials grow larger and more rigorous.
Psychological Medicine
August 29, 2019
Jelle Lamsma, Wiepke Cahn, Seena Fazel et al.
48 citations
In people with psychotic disorders, daily use of cannabis, stimulants, and depressants significantly increases the odds of violent behavior, as does nondaily use of stimulants and hallucinogens. Daily cannabis use was associated with 1.6 times higher odds of violence, daily stimulant use with 2.8 times higher odds, and daily depressant use with 2.2 times higher odds. Nondaily stimulant use raised odds by 1.6 times, and nondaily hallucinogen use by 1.5 times. Daily hallucinogen use, analyzed only in the UK sample, increased odds 3.3-fold. The findings suggest that any substance use, not just daily use, should be targeted to prevent violence in this population.
Psychological Medicine
March 3, 2016
Ravi Das, Amanda J. F. Tamman, Viktoriya L. Nikolova et al.
48 citations
Inhaling nitrous oxide shortly after a traumatic event speeds the decline of intrusive memories, reducing them by the next day compared to four days later with medical air. The gas appears to disrupt memory consolidation, but it increases intrusive memories in people who were highly dissociated at the time of the trauma. Sleep quality did not differ between groups. The findings suggest nitrous oxide may help prevent PTSD symptoms in some individuals, but caution is warranted for those with dissociation.
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
December 9, 2009
Jiřı́ Horáček, Martin Brunovský, Tomáš Novák et al.
42 citations
A single dose of ketamine (0.54 mg/kg infused over 30 minutes) rapidly alters brain electrical activity in healthy volunteers, producing a decrease in prefrontal theta cordance—a QEEG measure linked to cerebral blood flow—and an increase in central region theta cordance within 10 to 30 minutes. These changes resemble those seen after one week of treatment with standard antidepressants in people who respond to them, but occur much faster. The prefrontal theta cordance reduction correlated with ketamine and norketamine blood levels at 10 minutes. The findings suggest that theta cordance reduction could serve as a marker and predictor of ketamine's rapid antidepressant effect, a hypothesis warranting testing in depressed patients.