Archives of General Psychiatry
January 1, 2009
Paolo Fusar‐poli, José A. Crippa, Sagnik Bhattacharyya et al.
461 citations
In healthy men with minimal prior cannabis use, the two main psychoactive compounds in cannabis had opposite effects on anxiety and brain activity. Delta9-tetrahydrocannabinol (THC) increased anxiety, intoxication, sedation, and psychotic symptoms, while cannabidiol (CBD) showed a trend toward reducing anxiety. When participants viewed intensely fearful faces, THC increased skin conductance fluctuations (a measure of autonomic arousal), whereas CBD decreased them. CBD also dampened brain activation in the amygdala and anterior and posterior cingulate cortex, and this suppression correlated with reduced arousal. THC mainly altered activation in frontal and parietal areas. These distinct neural effects may explain why cannabis can both relieve and provoke anxiety.
Archives of General Psychiatry
April 1, 2009
Sagnik Bhattacharyya, Paolo Fusar‐poli, Stefan Borgwardt et al.
250 citations
Delta9-tetrahydrocannabinol (THC), a psychoactive constituent of cannabis, increased psychotic symptoms, anxiety, intoxication, and sedation in healthy men with minimal prior cannabis use, while cannabidiol had no significant effect on these measures. Verbal learning performance was not significantly affected by either drug. THC altered brain activation in the parahippocampal gyrus during encoding and in the ventrostriatum during retrieval, with the ventrostriatal change directly correlating with induced psychotic symptoms. These findings suggest THC modulates mediotemporal and ventrostriatal function, potentially underlying cannabis's effects on verbal learning and psychosis.
World psychiatry : official journal of the World Psychiatric Association (WPA)
June 1, 2022
Paolo Fusar‐poli, Andrés Estradé, Giovanni Stanghellini et al.
225 citations
Psychosis unfolds through distinct stages, each with its own core existential experiences. Early phases (premorbid and prodromal) involve loss of common sense, perplexity, lack of immersion in the world, heightened salience, a feeling that something important is about to happen, perturbation of the sense of self, and a need to hide inner turmoil. The first episode brings transitory relief from delusions, intense self-referentiality, permeated self-world boundaries, internal noise, and dissolution of self with social withdrawal. Later stages (relapsing and chronic) involve grieving losses, feeling split, and struggling to accept inner chaos, a new self, diagnosis, and uncertain future. Treatment experiences include both positive and negative aspects, with recovery understood as reconstructing personhood and re-establishing bonds toward meaningful goals.
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.
The International Journal of Neuropsychopharmacology
September 24, 2009
Paolo Fusar‐poli, Paul Allen, Sagnik Bhattacharyya et al.
165 citations
Cannabidiol (CBD), but not delta-9-tetrahydrocannabinol (THC), disrupts forward connectivity between the amygdala and the anterior cingulate cortex during the neural response to fearful faces. This disruption may represent a neurophysiological correlate of CBD's anxiolytic properties. The study used dynamic causal modelling and Bayesian model selection to analyze effective connectivity in 15 healthy subjects under a double-blind, randomized, placebo-controlled fMRI paradigm while they viewed faces eliciting different levels of anxiety.
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.
Eur Neuropsychopharmacol
November 7, 2025
Mikkel Højlund, Helin Y. Kafali, Begüm Kırmızı et al.
12 citations
A living systematic review with meta-analysis examined the efficacy, safety, and all-cause discontinuation of serotonergic psychedelics and MDMA for treating mental disorders. The review found that these substances show promise in reducing symptoms of conditions such as depression, anxiety, and post-traumatic stress disorder, with some evidence supporting their therapeutic potential. However, the authors note that the overall quality of evidence is limited by small sample sizes, short follow-up periods, and methodological concerns. Safety profiles varied, with most adverse events being mild to moderate, though serious adverse events were reported in some studies. The review emphasizes the need for larger, more rigorous trials to confirm these findings.
CNS Spectrums
December 1, 2024
Mauro Scala, Chiara Fabbri, Paolo Fusar‐poli et al.
8 citations
Psilocybin shows promise for treating mood and anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and substance use disorder, but significant evidence gaps remain. Current studies suggest psilocybin may alleviate depression, anxiety, obsessions, compulsions, and addictive behaviors, yet comparisons with standard antidepressants or anxiolytics are lacking, and optimal dosage, long-term efficacy, and safety are unclear due to trial limitations. Real-world implementation faces challenges including infrastructural requirements, personnel training, cultural stigma, and unresolved legal and ethical issues. Larger, more rigorous studies are needed to substantiate the evidence base before psilocybin can transition from research to clinical practice.
Neuropsychobiology
January 1, 2008
Paolo Fusar‐poli, Stefan Borgwardt
7 citations
Albert Hofmann, a Swiss chemist, first synthesized LSD in 1938 but set it aside. In 1943, he accidentally ingested a small amount and experienced an extremely stimulated imagination. Three days later, on April 19, 1943, he intentionally took 250 micrograms of LSD to verify the effects, then rode his bicycle home—a ride now known as Bicycle Day. LSD was initially hailed as a tool for psychoanalysis and understanding schizophrenia, but in the 1960s figures like Timothy Leary promoted it as a path to spiritual enlightenment.
Psychopathology
January 1, 2024
Milena Mancini, Cecilia Maria Esposito, Andrés Estradé et al.
6 citations
Abnormal self-experiences are common in major depression but are not included in current diagnostic manuals, which limits understanding and treatment. Through qualitative interviews analyzed with the Consensual Qualitative Research method, three categories of abnormal self-experience emerged: an inability to project oneself forward, not recognizing one's self, and losing control over one's self. The core of depressive experience appears to be an inability to recognize otherness as part of oneself, leading to specific symptoms of depersonalization that differ from those in schizophrenia. Narrative identity is central to the development and maintenance of depression.
European Journal of Neuroscience
November 1, 2025
Paolo La‐torraca‐vittori, Livio Tarchi, Elisa Arrigo et al.
1 citation
Lysergic acid diethylamide (LSD) reduces local brain activity and connectivity in sensory and association regions, with effects linked to specific neurotransmitter receptors. In 15 healthy adults, fMRI scans under LSD versus placebo showed decreased amplitude of low-frequency fluctuations (ALFF) in somatosensory, visual, default mode, and frontoparietal networks, and decreased regional homogeneity (ReHo) in sensory and subcortical areas. Test-retest reliability was high for ALFF and moderate for ReHo. LSD-induced changes correlated negatively with densities of D2 and 5-HT1A receptors, suggesting the drug engages neurochemical processes beyond its primary 5-HT2A target. These preliminary results indicate complex, dynamic mechanisms underlying LSD's neural effects.
Schizophr Res Cogn
June 11, 2026
Kristina Ballestad Gundersen, Tina Dam Kristensen, Alberte C.E. Jeppesen et al.
People at clinical high risk for psychosis and those with autism spectrum disorder both report unusual self-experiences, such as a diminished sense of self or altered bodily awareness, but the patterns differ between the two groups. The study compared these anomalous self-experiences and social cognition in both groups. It found that while both groups showed elevated levels of anomalous self-experiences compared to controls, the clinical high-risk group had more pronounced disturbances in self-awareness and agency, whereas the autism group showed greater impairments in social cognition, such as understanding others' mental states. These findings suggest that anomalous self-experiences may be a specific marker for psychosis risk, distinct from the social cognitive difficulties characteristic of autism.