Neuropsychopharmacology
February 24, 2020
C. Abdallah, L. Averill, R. Gueorguieva et al.
181 citations
Ketamine produces rapid antidepressant effects within 24 hours, thought to involve mTORC1 activation. In a double-blind crossover trial, 20 depressed patients received either rapamycin (an mTORC1 inhibitor) or placebo before ketamine. Rapamycin did not block ketamine's 24-hour antidepressant effects. Over two weeks, rapamycin prolonged ketamine's benefits: response rates were 41% with rapamycin versus 13% with placebo, and remission rates were 29% versus 7%. These findings question whether systemic or local mTORC1 blockade matters and suggest rapamycin may extend ketamine's effects, potentially informing mechanisms of depression relapse.
JAMA Network Open
May 1, 2020
K. Beck, Guy Hindley, F. Borgan et al.
179 citations
Ketamine administration produces transient psychopathological effects in both healthy volunteers and patients with schizophrenia, with the nature and severity of these effects varying according to experimental factors such as dose, route of administration, and participant characteristics. The meta-analysis quantifies these outcomes, showing that ketamine reliably induces psychotic-like symptoms, dissociation, and cognitive impairments in healthy individuals, while its effects in patients with schizophrenia are more complex and may involve both symptom exacerbation and potential therapeutic benefits depending on the context.
World Journal of Biological Psychiatry
March 22, 2022
D. D’souza, M. Diforti, S. Ganesh et al.
Exposure to cannabis increases the risk for psychoses ranging from transient psychotic states to chronic recurrent psychosis. Greater dose and earlier age of exposure raise the risk. For some psychosis outcomes, evidence supports some causality criteria, but reverse causality and confounders cannot be ruled out. Cannabis is neither necessary nor sufficient to cause psychosis; it is likely one of multiple causal components. In those with established psychosis, cannabis negatively affects the illness course and expression. Emerging evidence suggests alterations in the endocannabinoid system in psychotic disorders. Delaying or eliminating cannabis exposure could potentially reduce psychosis rates, especially in high-risk individuals.
Psychological Medicine
October 16, 2019
D. D’souza, S. Ganesh, J. Cortes-Briones et al.
Heavy, chronic cannabis use that begins early and is not accompanied by other drugs is associated with more psychosis-relevant symptoms and poorer cognitive performance. Users averaged over 30,000 lifetime cannabis exposures and scored higher on the Schizotypal Personality Questionnaire (mean 24 vs. 13) and lower on a composite cognitive test (mean -0.23 vs. +0.28) compared to matched non-user controls. Moderate to large deficits appeared in attention, psychomotor speed, working memory, cognitive flexibility, visuo-spatial processing, and verbal memory. A subsample of users also showed worse outcomes than their non-using siblings.
Psychopharmacology
November 24, 2012
R. A. Sewell, Ashley Schnakenberg, Jacqueline Elander et al.
Intravenous THC, at doses from 0.015 to 0.05 mg/kg, produces time overestimation and underproduction in seconds-range tasks, indicating an increased internal clock speed. This effect is not dose related and is blunted in frequent cannabis smokers, who show no differences in time perception compared to infrequent or nonsmokers. Chronic cannabis use does not alter baseline time perception.