The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

D’Souza, Deepak Cyril; Perry, Edward; MacDougall, Lisa; Ammerman, Yola; Cooper, Thomas B.; Wu, Yu Te; Braley, Gabriel; Gueorguieva, Ralitza; Krystal, John H.

doi:10.1038/sj.npp.1300496

Cited by 903 publications

(754 citation statements)

References 132 publications

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“…The inhibition of synaptic transmission in the human cortex by cannabinoids shown in this study probably has a role in the impairment of perception and cognitive function occurring acutely after inhalation of cannabinoids (D'Souza et al, 2004;Ramaekers et al, 2006; for review, see Murray et al (2007)). We also demonstrated that the CB 1 receptor antagonist rimonabant disrupts DSI in the human cortex, a form of short-term synaptic plasticity.…”

Section: Discussionmentioning

confidence: 65%

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Kovacs

Knop

Urbanski

et al. 2011

Neuropsychopharmacol

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Activation of CB 1 receptors on axon terminals by exogenous cannabinoids (eg, D 9 -tetrahydrocannabinol) and by endogenous cannabinoids (endocannabinoids) released by postsynaptic neurons leads to presynaptic inhibition of neurotransmission. The aim of this study was to characterize the effect of cannabinoids on GABAergic synaptic transmission in the human neocortex. Brain slices were prepared from neocortical tissues surgically removed to eliminate epileptogenic foci. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in putative pyramidal neurons using patch-clamp techniques. To enhance the activity of cannabinoidsensitive presynaptic axons, muscarinic receptors were continuously stimulated by carbachol. The synthetic cannabinoid receptor agonist WIN55212-2 decreased the cumulative amplitude of sIPSCs. The CB 1 antagonist rimonabant prevented this effect, verifying the involvement of CB 1 receptors. WIN55212-2 decreased the frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin, but did not change their amplitude, indicating that the neurotransmission was inhibited presynaptically. Depolarization of postsynaptic pyramidal neurons induced a suppression of sIPSCs. As rimonabant prevented this suppression, it is very likely that it was due to endocannabinods acting on CB 1 receptors. This is the first demonstration that an exogenous cannabinoid inhibits synaptic transmission in the human neocortex and that endocannabinoids released by postsynaptic neurons suppress synaptic transmission in the human brain. Interferences of cannabinoid agonists and antagonists with synaptic transmission in the cortex may explain the cognitive and memory deficits elicited by these drugs.

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Section: Discussionmentioning

confidence: 65%

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Kovacs

Knop

Urbanski

et al. 2011

Neuropsychopharmacol

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“…Previous studies have identified environmental risk factors for schizophrenia, like urban place of birth (Pedersen and Mortensen, 2001) and neighborhood environment (van Os et al, 2000), which support the link between a stressful environment and the development of psychosis. Furthermore, cannabis abuse has been identified as a risk factor for schizophrenia (Arseneault et al, 2004), and activation of the hormonal stress response by cannabis could also participate to this phenomenon (D'Souza et al, 2004;D'Souza et al, 2005). Indeed, this sample may be at a higher risk of presenting all these environmental risk factors: for example, approximately 50% of these patients were currently using or abusing cannabis at the time of the study (unpublished data).…”

Section: Discussionmentioning

confidence: 97%

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

Pariante

Dazzan

Danese

et al. 2005

Neuropsychopharmacol

142

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Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamicpituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age-and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls ( þ 22%, po0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p ¼ 0.028), 17% larger in patients receiving atypicals (p ¼ 0.01), and 30% larger in patients receiving typicals (po0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( þ 11%, p ¼ 0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n ¼ 40, po0.001), 19% larger in depressed patients (n ¼ 13, p ¼ 0.022), 16% larger in bipolar patients (n ¼ 16, p ¼ 0.037), and 12% larger in those with other psychoses (n ¼ 9, p ¼ 0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

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“…Furthermore, perceptual anomalies are incorporated within a cognitive model of paranoid delusions, where paranoid beliefs arise from an attempt to explain anomalous and odd internal experiences (Freeman et al, 2002). Indeed, research has shown that perceptual anomalies increase the risk for the development of delusional ideas (Krabbendam et al, 2004) and anomalies of experience caused by illegal drug use have also been linked to delusional ideation (D'Souza et al, 2004). Our mediation model suggests that one route that people with sleep problems may experience paranoia is via perceptual anomalies.…”

Section: Perceptual Anomalies and Paranoiamentioning

confidence: 99%

Sleep quality and paranoia: The role of alexithymia, negative emotions and perceptual anomalies

Rehman

Gumley

Biello

2018

Psychiatry Research

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A B S T R A C TRecent evidence suggests that sleep problems are associated with psychotic like experiences including paranoia. However, the mechanisms underpinning this association are not well understood and thus studies modelling hypothesised mediating factors are required. Alexithymia, the inability to recognise and describe emotions within the self may be an important candidate. In two separate studies we sought to investigate factors mediating the relationship between sleep quality and paranoia using a cross-sectional design. Healthy volunteers without a mental health diagnosis were recruited (study 1, N = 401, study 2, N = 402). Participants completed a series of measures assessing paranoia, negative emotions, alexithymia and perceptual anomalies in an online survey. In study 1, regression and mediation analyses showed that the relationship between sleep quality and paranoia was partially mediated by alexithymia, perceptual anomalies and negative affect. In contrast, study 2 found that the relationship between sleep quality and paranoia was fully mediated by negative affect, alexithymia and perceptual anomalies. The link between sleep quality and paranoia is unclear and reasons for discrepant results are discussed. Novel findings in this study include the link between alexithymia and paranoia.

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The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

Cited by 903 publications

References 132 publications

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

Sleep quality and paranoia: The role of alexithymia, negative emotions and perceptual anomalies

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