Progress in Neuro-psychopharmacology and Biological Psychiatry
October 23, 2025
Danielle Bukovsky, Aron Amaev, Jianmeng Song et al.
A systematic review of 42 clinical studies involving 1,068 participants found that psilocybin, when administered in controlled settings, has a favorable safety profile. Common adverse events included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. Serious adverse events were reported infrequently, in only 2 of the 42 studies, and were limited to participants with underlying depressive disorders, such as suicidal behavior or hospitalization. All studies had a high risk of bias due to concerns regarding blinding. The review provides an outline of common and uncommon adverse events, serious adverse events, and considerations for future protocols.
Progress in Neuro-psychopharmacology and Biological Psychiatry
May 1, 2025
D. Behzad, S. Patel, R. Besa et al.
Inhaled cannabis routes (smoking, vaping) produce higher peak blood THC levels, while edible cannabis has a longer duration of action. Few differences between methods were found for cognitive performance, though two studies indicated worse attention after vaping versus edibles or smoking, and one study found worse memory with high-potency flower containing cannabidiol compared to concentrates. One study reported an inverse correlation between blood THC and cognition. Because THC levels are used to detect impairment, detection may be more challenging with edibles.
Progress in Neuro-psychopharmacology and Biological Psychiatry
December 1, 2023
Li Ren
Ketamine, an N-methyl-d-aspartate receptor antagonist, produces rapid antidepressant-like effects, unlike conventional antidepressants that take weeks. Its rapid action is thought to involve the glutamate system, synaptic plasticity, GABAergic and serotonergic systems, and astrocytes. However, serious side effects limit its clinical use. This review discusses the neural circuits and molecular mechanisms underlying ketamine's effects, aiming to clarify targets for rapidly acting antidepressants and guide new treatments for major depressive disorder.
Progress in Neuro-psychopharmacology and Biological Psychiatry
May 1, 2022
C. Wickens, Madison Wright, R. Mann et al.
In healthy young adults who use both alcohol and cannabis, the two drugs produce largely separate effects: cannabis primarily alters mood and subjective experience, while alcohol impairs cognitive and psychomotor performance. In a double-blind, placebo-controlled trial with 28 participants aged 19–29, those who received active cannabis (12.5% THC) showed greater increases in tension-anxiety, confusion, euphoria, and sedation compared to placebo, but minimal changes in cognition. Alcohol (target breath alcohol content 80 mg/dL) caused declines in verbal recall, digit-symbol substitution, and fine motor speed, with little effect on mood. Combining the two drugs produced additive effects, not synergistic.
Progress in Neuro-psychopharmacology and Biological Psychiatry
January 2, 2021
A. Pałucha-poniewiera, K. Podkowa, A. Rafało-ulińska
The mGlu2/3 receptor antagonist LY341495 produced a dose-dependent antidepressant-like effect in mice exposed to chronic unpredictable mild stress, after both a single dose and three daily doses. Combining a low, ineffective dose of LY341495 with a low, ineffective dose of ketamine reversed stress-induced behavioral deficits, suggesting the combination could lower ketamine's therapeutic dose. The combination activated the mTOR pathway and did not cause hyperactivity, memory impairment, or motor coordination problems that occur with a higher ketamine dose. The findings indicate mGlu2/3 receptor antagonists may safely reduce the effective dose of ketamine.
Progress in Neuro-psychopharmacology and Biological Psychiatry
September 2, 2020
K. Gicas, Alex Y T Cheng, W. Panenka et al.
In a sample of 437 adults recruited from single-room occupancy hotels in Vancouver's Downtown Eastside, early cannabis exposure (by age 15) was associated with a slightly increased risk of developing substance-induced psychosis, while later first use (after age 15) was linked to a higher risk of schizophrenia or schizoaffective disorder. No differences in neurocognitive function were found between groups, though brain structure differences appeared in the lateral orbitofrontal cortex and white matter tracts. The findings suggest that early cannabis exposure in this high-risk population may contribute to drug-associated psychoses, possibly through altered brain development.
Progress in Neuro-psychopharmacology and Biological Psychiatry
February 25, 2020
Muris Humo, Beyza Ayazgök, Léa J. Becker et al.
A single injection of ketamine (15 mg/kg) in mice with chronic neuropathic pain temporarily reduced mechanical hypersensitivity for less than 24 hours, but its antidepressant effect lasted at least 72 hours. Ketamine also normalized the expression of MKP-1 and phosphorylation of ERK in the anterior cingulate cortex, molecular changes that may underlie its therapeutic effects on pain-induced depression.
Progress in Neuro-psychopharmacology and Biological Psychiatry
March 1, 2019
J. Soler, B. Arias, J. Moya et al.
Both the ZNF804A gene and cannabis use are risk factors for psychosis, and this study examined their relationship with schizotypal personality traits in 385 healthy Spanish adults. People with the AA genotype of the rs1344706 variant scored higher on interpersonal schizotypy. An interaction between the AA genotype and lifetime cannabis use was found for cognitive-perceptual schizotypy, showing a dose-effect pattern: among AA carriers, schizotypy scores increased with more frequent cannabis use, from sporadic to intense use. These results suggest that cannabis use may modulate the effect of ZNF804A on psychosis proneness.
Progress in Neuro-psychopharmacology and Biological Psychiatry
August 16, 2016
S. Grieco, Yu-yan Cheng, H. Eldar-Finkelman et al.
An antidepressant dose of ketamine (10 mg/kg) increases expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect requiring ketamine-induced inhibition of glycogen synthase kinase-3 (GSK3). A specific GSK3 inhibitor also up-regulates hippocampal IGF2. Administering IGF2 siRNA reduces ketamine's antidepressant effect in the learned helplessness paradigm. Non-depressed resilient mice display higher IGF2 expression than susceptible depressed mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and may confer resilience to depression-like behavior.