Characterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure

D’Souza, Deepak Cyril; Ganesh, Suhas; Cortes-Briones, Jose; Campbell, Michael H.; Emmanuel, Maisha K.

doi:10.1017/s0033291719002721

Cited by 11 publications

(6 citation statements)

References 51 publications

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“…Since cannabis availability continues to expand, there is now growing concern about the possible negative effects of the main psychotomimetic component of cannabis, delta 9-tetrahydrocannabinol (THC), particularly during adolescence and other sensitive periods of brain development ( 4 ). Specifically, prolonged and heavy use of cannabis is a risk factor for cognitive impairments in psychiatric disorders later in life, especially in subsets of vulnerable adolescents ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence

et al. 2022

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IntroductionCannabis abuse during adolescence is a risk factor for cognitive impairments in psychiatric disorders later in life. To date, the possible causal relationship between cannabinoids, kynurenic acid (KYNA; i.e., a neuroactive metabolite of tryptophan degradation) and cognition has not been investigated in adolescence. Early exposure to delta 9-tetrahydrocannabinol (THC; i.e., the main psychotropic component of cannabis) causes enduring cognitive deficits, which critically involve impaired glutamatergic function in the prefrontal cortex (PFC). In addition, prenatal cannabis exposure results in enduring increases in PFC KYNA levels. Based on these findings, the effects of chronic THC exposure in rats, during another critical period of neurodevelopment particularly sensitive to perturbation by exogenous stimuli, such as adolescence, have been investigated.MethodsMale Wistar rats were chronically treated with vehicle or ascending intraperitoneal (i.p.) doses of THC starting on postnatal day (PND) 35 until PND 45. In adulthood (PND 75), cognitive assessment (Y-maze) and extracellular KYNA/glutamate levels were measured in the PFC by in vivo microdialysis, before and after a challenge with KYN (5 mg/kg i.p., the biological precursor of KYNA). By using the selective, brain-penetrable KAT II inhibitor PF-04859989, we then examined whether blockade of KYNA neosynthesis prevents the cognitive impairment.ResultsCompared to vehicle-treated controls, extracellular basal KYNA levels were higher in the PFC of adult rats chronically exposed to THC in adolescence (p < 0.01). No changes were observed in extracellular glutamate levels. Following a challenge with KYN, extracellular KYNA levels similarly increased in both groups (i.e., vehicle- and THC-treated; p < 0.001 and p < 0.01, respectively). Chronic adolescent THC exposure negatively affected short-term memory (reduced spontaneous alternation), in adult animals (p < 0.001), while PF-04859989 (30 mg/kg i.p.) restored the cognitive impairment (p < 0.05).DiscussionWe propose that the observed alterations in PFC KYNA signaling might be involved in the cognitive dysfunction induced by the exposure to THC during the adolescence. In the translational realm, these experiments raise the prospect of prevention of KYNA neosynthesis as a possible novel approach to counteract some of the detrimental long-term effects of adolescence cannabis use.

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Section: Introductionmentioning

confidence: 99%

Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence

et al. 2022

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“…Cannabis sativa is a recreational drug widely consumed in Europe, especially during the ages where SCZ onset usually occurs namely, late adolescence and early adulthood [13]. Chronic cannabis use alters cognitive, rewarding and affective processes [14][15][16] that are also critically altered in SCZ, by acting on the endocannabinoid system, and by modulating the activity of other neurotransmitters in the brain. The endocannabinoid system (ECS) consists of two major G protein-coupled receptors: the cannabinoid type 1 (CB 1 R) and type 2 (CB 2 R) receptors, two main endogenous ligands: anandamide (AEA) and 2-arachidonoylglycerol (2-AG) called endocannabinoids, and their synthetizing and degrading enzymes [17].…”

Section: Introductionmentioning

confidence: 99%

Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells from Schizophrenia Patients Studied by Synchrotron-Based FTIR Spectroscopy

et al. 2020

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Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component, but the presence of environmental stressors can be important for its onset and progression. Cannabis use can be a major risk factor for developing SCZ. However, despite the available data on the neurobiological underpinnings of SCZ, there is an important lack of studies in human neuronal tissue and living cells addressing the effects of cannabis in SCZ patients. In this study, we analysed the most relevant bio-macromolecular constituents in olfactory neuroepithelium (ON) cells of healthy controls non-cannabis users, healthy cannabis users, SCZ patients non-cannabis users, and SCZ patients cannabis users using Synchrotron Radiation-Fourier Transform Infrared (SR-FTIR) spectrometry and microscopy. Our results revealed that SCZ patients non-cannabis users, and healthy cannabis users exhibit similar alterations in the macromolecular profile of ON cells, including disruption in lipid composition, increased lipid membrane renewal rate and lipid peroxidation, altered proteins containing more β-sheet structures, and showed an increase in DNA and histone methylation. Notably, these alterations were not observed in SCZ patients who use cannabis regularly. These data suggest a differential effect of cannabis in healthy controls and in SCZ patients in terms of the macromolecular constituents of ON cells.

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“…That cognitive test performance in the CIPD group was not significantly different from the PsyNoCan group at the time of admission may be explained by a high quantity (median 730 joints) and duration (median 8 years) of cannabis use by the CIPD group (Table 1) in our sample compared to most earlier studies. Chronic heavy cannabis use may have added to the cognitive burden 28 imposed by the emergence of psychosis in our sample. Consistent with the explanation, a study that stratified cannabis using first episode patients by the quantity and frequency of cannabis use noted that heavy users have worse performance on cognitive tasks compared to non-users, whereas medium users didn’t show a significant difference 29 .…”

Section: Discussionmentioning

confidence: 98%

Presentation and Short-term Course of New Onset Cannabis Induced Psychotic Disorder in Males

D’Souza

Raj

Ganesh

et al. 2022

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Introduction: Cannabis use has been associated with several psychosis outcomes including acute and persistent psychosis termed Cannabis Induced Psychotic Disorder (CIPD). The clinical and cognitive profile, course of CIPD, and the extent to which it is different from psychosis unrelated to cannabis exposure (PsyNoCan) is not clear. Methods: The acute presentation and short-term (~4 weeks) course of hospitalized male patients with new onset CIPD were compared prospectively to PsyNoCan using measures of psychosis, depression, mania, memory and other cognitive processes at admission, and after 4 weeks of inpatient hospitalization. A subsample of CIPD patients were followed up after 4-6 months of discharge. Cognitive test performance was benchmarked for comparison in healthy controls and individuals with Cannabis Use Disorder. Results: Compared to PsyNoCan (n=53), CIPD (n=66) had a significantly lower severity of psychotic symptoms at admission but no differences in mood symptoms. After 4 weeks of hospitalization, the CIPD group had less psychosis. While both groups had significant cognitive deficits at baseline compared to healthy controls, cognitive test performance improved to a greater extent in CIPD. Amongst 16 CIPD cases with longitudinal follow-up data, 10 relapsed with psychosis within 6 months after resuming cannabis use. Conclusion: CIPD in males has a distinct presentation and short-term course, characterized by less severe psychosis, and greater resolution of psychopathology and cognitive deficits relative to PsyNoCan. Relapse of cannabis use may predict poorer long-term outcomes with greater psychotic relapses. The longer-term course, prognosis and biology of CIPD, and its presentation in females needs further study.

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Characterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure

Cited by 11 publications

References 51 publications

Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence

Alterations in rat prefrontal cortex kynurenic acid levels are involved in the enduring cognitive dysfunctions induced by tetrahydrocannabinol exposure during the adolescence

Effects of Cannabis Use on the Protein and Lipid Profile of Olfactory Neuroepithelium Cells from Schizophrenia Patients Studied by Synchrotron-Based FTIR Spectroscopy

Presentation and Short-term Course of New Onset Cannabis Induced Psychotic Disorder in Males

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