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.
Brazilian Journal of Medical and Biological Research
April 1, 2006
Antônio Waldo Zuardi, J.a.s. Crippa, Jaime E. C. Hallak et al.
411 citations
A high dose of delta9-tetrahydrocannabinol, the main psychoactive component of cannabis, induces anxiety and psychotic-like symptoms in healthy volunteers, and these effects are significantly reduced by cannabidiol (CBD), a cannabis constituent without typical cannabis effects. Studies in animal models and healthy volunteers suggest an anxiolytic-like effect of CBD. Its antipsychotic-like properties have been investigated in animal models and supported by studies on healthy volunteers using binocular depth inversion and ketamine-induced psychotic symptoms. Open case reports and a preliminary controlled clinical trial indicate that CBD may be a safe, well-tolerated alternative treatment for schizophrenia. Future studies in other psychotic conditions are indicated.
Therapeutic Advances in Psychopharmacology
March 18, 2016
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
306 citations
A systematic review of clinical trials from 1990 to 2015 examined the therapeutic potential of ayahuasca, psilocybin, and LSD for mood and anxiety disorders and drug dependence. Six trials met inclusion criteria. The reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. However, all studies had small sample sizes, and half were open-label, proof-of-concept studies. The authors conclude these substances may be useful pharmacological tools, but randomized, double-blind, placebo-controlled studies with more patients are needed to replicate preliminary findings.
Frontiers in Pharmacology
May 11, 2017
Antônio Waldo Zuardi, Natália Pegoraro Rodrigues, Angélica L. Silva et al.
292 citations
Acute administration of 300 mg of cannabidiol (CBD) reduced subjective anxiety after a public speaking test in healthy adults, while 100 mg and 900 mg did not, confirming an inverted U-shaped dose-response curve similar to that seen in animal studies. Clonazepam (1 mg) also reduced anxiety but caused more sedation and smaller increases in blood pressure compared to CBD 300 mg. The public speaking test itself increased anxiety, heart rate, and blood pressure across all groups.
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.
Brazilian Journal of Psychiatry
March 1, 2010
Jaime E. C. Hallak, João Paulo Machado‐de‐Sousa, José Alexandre S. Crippa et al.
122 citations
A single dose of cannabidiol (CBD) does not improve selective attention in people with schizophrenia, and higher doses may worsen performance. In a study of 28 patients, those given 600 mg of CBD performed worse on the Stroop Color Word Test than those given 300 mg or placebo, while all groups showed some improvement from practice. No differences were found in electrodermal responses to sounds. The authors suggest that chronic CBD administration might still be beneficial, but acute treatment appears ineffective for cognitive symptoms.
Frontiers in Pharmacology
January 1, 2014
Raquel Levin, Fernanda Fiel Peres, Valéria de Almeida et al.
73 citations
Cannabinoid drugs affect sensorimotor gating deficits in spontaneously hypertensive rats (SHRs), a strain used as an animal model of schizophrenia. SHRs showed reduced prepulse inhibition (PPI) compared to Wistar rats, indicating impaired sensorimotor gating. The cannabinoid agonist WIN55212 (1 mg/kg) and cannabidiol (30 mg/kg) reversed this PPI deficit, while the CB1 antagonist rimonabant (0.75 mg/kg) worsened it. The anandamide uptake inhibitor AM404 had no effect. These findings suggest cannabinoid drugs may offer therapeutic strategies for schizophrenia-related sensorimotor gating impairments.
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.
European Neuropsychopharmacology
September 1, 2009
D. Almeida Prado, Joel Porfírio Pinto, José Alexandre S. Crippa et al.
9 citations
Ayahuasca, a traditional Amazonian brew, shows promise in psychiatry, with 66% of participants reporting significant improvement in depressive symptoms after treatment. This study involved 100 individuals seeking relief from mental health issues. Participants experienced enhanced emotional well-being and altered perspectives on life, suggesting a blend of psychological and philosophical enlightenment. The findings highlight ayahuasca's potential as a medicinal tool within the broader context of psychedelics and drug studies, offering new insights into the intersection of psychology, art, and anthropology in understanding human experience.
Experimental and Clinical Psychopharmacology
November 4, 2021
Tânia Cristina Libânio, R. Eufrásio, Suzy S Niigaki et al.
6 citations
Harmine, a component of the psychedelic brew ayahuasca, impairs memory in emotional contexts in rats, and even untreated rats housed with harmine-treated rats show memory deficits. In experiments using contextual and tone fear conditioning and a plus-maze discriminative avoidance task, harmine at 10 mg/kg impaired contextual fear conditioning, and all doses (5, 10, or 15 mg/kg) impaired discriminative avoidance. Untreated rats housed in cages with harmine-treated rats also showed memory deficits across all tasks, suggesting that social context and cohabitation can influence the drug's behavioral effects.