Measuring white matter microstructure in 1,457 cannabis users and 1,441 controls: A systematic review of diffusion-weighted MRI studies.

Introduction: Cannabis is the most widely used regulated substance by youth and adults. Cannabis use has been associated with psychosocial problems, which have been partly ascribed to neurobiological changes. Emerging evidence to date from diffusion-MRI studies shows that cannabis users compared to controls show poorer integrity of white matter fibre tracts, which structurally connect distinct brain regions to facilitate neural communication. However, the most recent evidence from diffusion-MRI studies thus far has yet to be integrated. Therefore, it is unclear if white matter differences in cannabis users are evident consistently in selected locations, in specific diffusion-MRI metrics, and whether these differences in metrics are associated with cannabis exposure levels. Methods: We systematically reviewed the results from diffusion-MRI imaging studies that compared white matter differences between cannabis users and controls. We also examined the associations between cannabis exposure and other behavioral variables due to changes in white matter. Our review was pre-registered in PROSPERO (ID: 258250; https://www.crd.york.ac.uk/prospero/). Results: We identified 30 diffusion-MRI studies including 1,457 cannabis users and 1,441 controls aged 16-to-45 years. All but 6 studies reported group differences in white matter integrity. The most consistent differences between cannabis users and controls were lower fractional anisotropy within the arcuate/superior longitudinal fasciculus (7 studies), and lower fractional anisotropy of the corpus callosum (6 studies) as well as higher mean diffusivity and trace (4 studies). Differences in fractional anisotropy were associated with cannabis use onset (4 studies), especially in the corpus callosum (3 studies). Discussion: The mechanisms underscoring white matter differences are unclear, and they may include effects of cannabis use onset during youth, neurotoxic effects or neuro adaptations from regular exposure to tetrahydrocannabinol (THC), which exerts its effects by binding to brain receptors, or a neurobiological vulnerability predating the onset of cannabis use. Future multimodal neuroimaging studies, including recently developed advanced diffusion-MRI metrics, can be used to track cannabis users over time and to define with precision when and which region of the brain the white matter changes commence in youth cannabis users, and whether cessation of use recovers white matter differences. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: 258250.

Substance-Induced Psychoses: An Updated Literature Review.

Background: On the current psychopharmacological panorama, the variety of substances able to provoke an episode of acute psychosis is rapidly increasing. Such psychotic episodes are classified according to the major category of symptoms: positive, negative, or cognitive psychotic episodes. On one hand, the abuse of methamphetamines, cannabis, and cocaine plays a big role in increasing the incidence of episodes resembling a psychotic disorder. On the other hand, the progress in terms of pharmacodynamics knowledge has led to the synthesis of new drugs, such as cannabinoids and cathinone's, which have rapidly entered into the common pool of abusers' habits. Regarding these newly synthesized substances of abuse, further clinical studies are needed to understand their psychogenic properties. The topic of this review is complicated due to the frequent abuse of psychotomimetic drugs by patients affected by psychotic disorders, a fact that makes it extremely difficult to distinguish between an induced psychosis and a re-exacerbation of a previously diagnosed disorder. Methods: The present narrative review summarizes results from clinical studies, thus investigating the psychotogenic properties of abused substances and the psychotic symptoms they can give rise to. It also discusses the association between substance abuse and psychosis, especially with regards to the differential diagnosis between a primary vs. a substance-induced psychotic disorder. Findings: Our findings support the theory that psychosis due to substance abuse is commonly observed in clinical practice. The propensity to develop psychosis seems to be a function of the severity of use and addiction. Of note, from a phenomenological point of view, it is possible to identify some elements that may help clinicians involved in differential diagnoses between primary and substance-induced psychoses. There remains a striking paucity of information on the outcomes, treatments, and best practices of substance-induced psychotic episodes.

Sex differences in brain metabolites in anxiety and mood disorders.

Gender differences in mood and anxiety disorders are well-established. However, the neural basis of these differences is not clear yet, especially in terms of brain metabolism. Indeed, although several proton Magnetic Resonance Spectroscopy (¹H MRS) investigations reported different metabolic levels in both depression and anxiety disorders, which have been also linked to symptoms severity and response to treatment, the role of gender on these differences have not been explored yet. Therefore, this study aims at investigating the role of sex in neurometabolic alterations associated with both mood and anxiety disorders. A 3T single-voxel ¹H MRS acquisition of the dorsolateral prefrontal cortex was acquired from 14 Major Depressive Disorder, 10 Generalized Anxiety Disorder (GAD), 11 Panic Disorder (PD), patients and 16 healthy controls (HC). Among males, PD patients showed significantly lower GPC+PC (also observed in GAD+PD) and Glu levels compared to HC. Finally, a significant group x sex interaction effect was observed in the GPC+PC and Glu levels. We proved the presence of an association between sex and brain metabolites in anxiety spectrum.

Neurocognitive impact of ketamine treatment in major depressive disorder: A review on human and animal studies.

BACKGROUND: Most recent evidence support a rapid and sustained antidepressant effect of subanesthetic dose of intravenous ketamine in patients with major depressive disorder (MDD). However, clinical and animal studies investigating the effects of intravenous ketamine on specific functional domains disrupted by depression reported conflicting results. Therefore, the aim of this review is to provide an overview of the recent findings exploring the cognitive effects of ketamine in depression. METHODS: After a bibliographic search on PubMed, Medline and PsycInfo, we retrieved 11 original studies meeting our research criteria, 7 in humans with MDD or Treatment Resistant Disorder and 4 using rats models for depression. RESULTS: Overall the results showed that a) ketamine reduced activation and normalized connectivity measures of several brain regions related to depressive behaviors and reversed deficits in cognitive flexibility and coping response strategy in rats with depressive features, and b) ketamine leads to a no significant impairment on neurocognitive functions in most of the studies, with only three studies observing improvements in speed of processing, verbal learning, sustained attention and response control, verbal and working memory. LIMITATIONS: The methodological heterogeneity, in terms of neuropsychological tests used and cognitive domain explored, of the studies included. CONCLUSIONS: Most of the studies included showed no significant cognitive impairments in MDD patients after ketamine treatment. Furthermore, the results of the fMRI studies considered suggest that ketamine may have a normalizing effect on brain functions during attentional and emotional processing in MDD patients. However, further studies are needed to confirm these preliminary evidences.