scholarly journals Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis

2019 ◽  
Vol 25 (12) ◽  
pp. 3231-3240 ◽  
Author(s):  
Marco Colizzi ◽  
Nathalie Weltens ◽  
Philip McGuire ◽  
David Lythgoe ◽  
Steve Williams ◽  
...  
Keyword(s):  
Cannabis Use ◽  
Striatal Dopamine ◽  
Resonance Spectroscopy ◽  
Acute Administration ◽  
Double Blind ◽  
Glutamate Signaling ◽  
Caudate Head ◽  
Lower Baseline ◽  
Left Caudate ◽  
Psychotomimetic Effects

AbstractThe neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = −0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.

scholarly journals Does variation in trait schizotypy and frequency of cannabis use influence the acute subjective, cognitive and psychotomimetic effects of delta-9-tetrahydrocannabinol? A mega-analysis

2021 ◽  
pp. 026988112095960
Author(s):  
Abigail M Freeman ◽  
Claire Mokrysz ◽  
Chandni Hindocha ◽  
Will Lawn ◽  
Celia JA Morgan ◽  
...  
Keyword(s):  
Personality Traits ◽  
Memory Impairment ◽  
Linear Models ◽  
Cannabis Use ◽  
Acute Effects ◽  
Double Blind ◽  
Schizotypal Personality ◽  
Domain Specific ◽  
Individual Participant ◽  
Psychotomimetic Effects

Background: While the acute effects of cannabis are relatively benign for most users, some individuals experience significant adverse effects. This study aimed to identify whether variation in schizotypal personality traits and frequency of cannabis use influence the acute effects of delta-9-tetrahydrocannabinol (THC). Methods: Individual participant data from four double-blind, randomised, placebo-controlled, acute crossover studies involving 128 cannabis users were combined for a mega-analysis. Using multilevel linear models and moderation analyses, frequency of cannabis use and schizotypal personality traits were investigated as potential moderators of the subjective, cognitive and psychotomimetic effects of acute THC. Results: There was evidence of a moderating effect where increased frequency of cannabis use was associated with reduced intensity of subjective (changes in alertness and feeling stoned) and psychosis-like effects following THC when compared with placebo. Moderating effects of cannabis use frequency on acute memory impairment were weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC compared with placebo. Conclusions: Our results suggest that a pattern of domain-specific tolerance develops to the acute effects of THC. Tolerance to the alertness-reducing effects occurred more readily than tolerance to psychotomimetic effects. Only partial tolerance to feeling stoned was found, and there was weak evidence for tolerance to memory impairment. Trait schizotypy did not moderate THC’s effects on psychotomimetic symptoms.

scholarly journals Neurophysiological Effects of Whole Coffee Cherry Extract in Older Adults with Subjective Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 144
Author(s):  
Jennifer L. Robinson ◽  
Julio A. Yanes ◽  
Meredith A. Reid ◽  
Jerry E. Murphy ◽  
Jessica N. Busler ◽  
...  
Keyword(s):  
Decision Making ◽  
Reaction Time ◽  
Magnetic Resonance ◽  
Primary Objective ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Phytochemical Analysis ◽  
Acute Administration ◽  
Gamma Aminobutyric Acid ◽  
Double Blind

Bioactive plant-based compounds have shown promise as protective agents across multiple domains including improvements in neurological and psychological measures. Methodological challenges have limited our understanding of the neurophysiological changes associated with polyphenol-rich supplements such as whole coffee cherry extract (WCCE). In the current study, we (1) compared 100 mg of WCCE to a placebo using an acute, randomized, double-blind, within-subject, cross-over design, and we (2) conducted a phytochemical analysis of WCCE. The primary objective of the study was to determine the neurophysiological and behavioral changes that resulted from the acute administration of WCCE. We hypothesized that WCCE would increase brain-derived neurotrophic factor (BDNF) and glutamate levels while also increasing neurofunctional measures in cognitive brain regions. Furthermore, we expected there to be increased behavioral performance associated with WCCE, as measured by reaction time and accuracy. Participants underwent four neuroimaging scans (pre- and post-WCCE and placebo) to assess neurofunctional/metabolic outcomes using functional magnetic resonance imaging and magnetic resonance spectroscopy. The results suggest that polyphenol-rich WCCE is associated with decreased reaction time and may protect against cognitive errors on tasks of working memory and response inhibition. Behavioral findings were concomitant with neurofunctional changes in structures involved in decision-making and attention. Specifically, we found increased functional connectivity between the anterior cingulate and regions involved in sensory and decision-making networks. Additionally, we observed increased BDNF and an increased glutamate/gamma-aminobutyric acid (GABA) ratio following WCCE administration. These results suggest that WCCE is associated with acute neurophysiological changes supportive of faster reaction times and increased, sustained attention.

scholarly journals Cannabis Use among Older Persons with Arthritis, Cancer and Multiple Sclerosis: Are We Comparing Apples and Oranges?

2021 ◽  
Vol 11 (5) ◽  
pp. 532
Author(s):  
Brian Kaskie ◽  
Hyojung Kang ◽  
Divya Bhagianadh ◽  
Julie Bobitt
Keyword(s):  
Multiple Sclerosis ◽  
Older Persons ◽  
Behavioral Outcomes ◽  
Cannabis Use ◽  
Medical Cannabis ◽  
Opioid Use ◽  
Quality Of Sleep ◽  
Impact Processes ◽  
Lower Baseline

Although researchers have identified medications that relieve symptoms of multiple sclerosis (MS), none are entirely effective and some persons with multiple sclerosis (PwMS) use alternatives. Our study compared cannabis use among PwMS (N = 135) and persons diagnosed with arthritis (N = 582) or cancer (N = 622) who were age 60 and older, enrolled in the State of Illinois Medical Cannabis Program, and invited to complete a survey fielded between June and September, 2019. We used logistic regression to identify significant differences in self-reported effects of cannabis on psychological wellbeing, quality of life, and three behavioral outcomes, and we also considered effects of past year opioid use relative to these outcomes. We found that the majority of individuals from all groups used cannabis to address pain and improve quality of sleep. While PwMS reported lower baseline levels across all five outcomes, we found that the reported effects of cannabis were largely comparable across the groups. We also found that cannabis benefitted persons with sleep and digestive issues regardless of condition, whereas persons who used opioids in addition to cannabis were less likely to experience an improvement in any of the outcomes. This comparative evaluation suggests that cannabis’ effects are not specific to MS, arthritis, or cancer as much as they impact processes common among these distinct conditions. We also found evidence that cannabis may be a viable alternative to opioids for those with these conditions and experiencing pain.

scholarly journals In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yo-Han Joo ◽  
Yun-Kwan Kim ◽  
In-Gyu Choi ◽  
Hyeon-Jin Kim ◽  
Young-Don Son ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Glucose Metabolism ◽  
Cerebral Glucose Metabolism ◽  
Functional Coupling ◽  
Resonance Spectroscopy ◽  
Acute Administration ◽  
Multimodal Neuroimaging ◽  
Mk 801 ◽  
Genetic Ablation ◽  
Neuroimaging Study

Abstract Background Perturbed functional coupling between the metabotropic glutamate receptor-5 (mGluR5) and N-methyl-d-aspartate (NMDA) receptor-mediated excitatory glutamatergic neurotransmission may contribute to the pathophysiology of psychiatric disorders such as schizophrenia. We aimed to establish the functional interaction between mGluR5 and NMDA receptors in brain of mice with genetic ablation of the mGluR5. Methods We first measured the brain glutamate levels with magnetic resonance spectroscopy (MRS) in mGluR5 knockout (KO) and wild-type (WT) mice. Then, we assessed brain glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography before and after the acute administration of an NMDA antagonist, MK-801 (0.5 mg/kg), in the same mGluR5 KO and WT mice. Results Between-group comparisons showed no significant differences in [18F]FDG standardized uptake values (SUVs) in brain of mGluR5 KO and WT mice at baseline, but widespread reductions in mGluR5 KO mice compared to WT mice after MK-801 administration (p < 0.05). The baseline glutamate levels did not differ significantly between the two groups. However, there were significant negative correlations between baseline prefrontal glutamate levels and regional [18F]FDG SUVs in mGluR5 KO mice (p < 0.05), but no such correlations in WT mice. Fisher’s Z-transformation analysis revealed significant between-group differences in these correlations (p < 0.05). Conclusions This is the first multimodal neuroimaging study in mGluR5 KO mice and the first report on the association between cerebral glucose metabolism and glutamate levels in living rodents. The results indicate that mGluR5 KO mice respond to NMDA antagonism with reduced cerebral glucose metabolism, suggesting that mGluR5 transmission normally moderates the net effects of NMDA receptor antagonism on neuronal activity. The negative correlation between glutamate levels and glucose metabolism in mGluR5 KO mice at baseline may suggest an unmasking of an inhibitory component of the glutamatergic regulation of neuronal energy metabolism.

scholarly journals Effect of acute citalopram on self-referential emotional processing and social cognition in healthy volunteers

BJPsych Open ◽  
2020 ◽  
Vol 6 (6) ◽  
Author(s):  
Catherine Hobbs ◽  
Susannah E. Murphy ◽  
Lucy Wright ◽  
James Carson ◽  
Indra Van Assche ◽  
...  
Keyword(s):  
Social Cognition ◽  
Healthy Volunteers ◽  
Antidepressant Treatment ◽  
Affective Learning ◽  
The Self ◽  
Affective Processing ◽  
Antidepressant Effect ◽  
Acute Administration ◽  
Double Blind ◽  
Prosocial Behaviours

Background Depression is characterised by negative views of the self. Antidepressant treatment may remediate negative self-schema through increasing processing of positive information about the self. Changes in affective processing during social interactions may increase expression of prosocial behaviours, improving interpersonal communications. Aims To examine whether acute administration of citalopram is associated with an increase in positive affective learning biases about the self and prosocial behaviour. Method Healthy volunteers (n = 41) were randomised to either an acute 20 mg dose of citalopram or matched placebo in a between-subjects double-blind design. Participants completed computer-based cognitive tasks designed to measure referential affective processing, social cognition and expression of prosocial behaviours. Results Participants administered citalopram made more cooperative choices than those administered placebo in a prisoner's dilemma task (β = 20%, 95% CI: 2%, 37%). Exploratory analyses indicated that participants administered citalopram showed a positive bias when learning social evaluations about a friend (β = 4.06, 95% CI: 0.88, 7.24), but not about the self or a stranger. Similarly, exploratory analyses found evidence of increased recall of positive words and reduced recall of negative words about others (β = 2.41, 95% CI: 0.89, 3.93), but not the self, in the citalopram group. Conclusions Participants administered citalopram showed greater prosocial behaviours, increased positive recall and increased positive learning of social evaluations towards others. The increase in positive affective bias and prosocial behaviours towards others may, at least partially, be a mechanism of antidepressant effect. However, we found no evidence that citalopram influenced self-referential processing.

scholarly journals Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial

2016 ◽  
Vol 159 ◽  
pp. 53-60 ◽  
Author(s):  
Frances R. Levin ◽  
John J. Mariani ◽  
Martina Pavlicova ◽  
Daniel Brooks ◽  
Andrew Glass ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Cannabis Use ◽  
Cannabis Use Disorder ◽  
Double Blind ◽  
Double Blind Placebo

Serotonin Dysfunction in Pathological Gamblers: Increased Prolactin Response to Oral m-CPP Versus Placebo

CNS Spectrums ◽  
2006 ◽  
Vol 11 (12) ◽  
pp. 956-965 ◽  
Author(s):  
Stefano Pallanti ◽  
Silvia Bernardi ◽  
Leonardo Quercioli ◽  
Concetta DeCaria ◽  
Eric Hollander
Keyword(s):  
Clinical Severity ◽  
Acute Administration ◽  
Double Blind ◽  
Pathological Gamblers ◽  
Healthy Control ◽  
Cortisol Responses ◽  
Gambling Severity ◽  
Prolactin Response ◽  
The Relationship

ABSTRACTObjectiveAcute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpi-perazine (m-CPP), that is used also as a street drug, has been reported to induce a “high” and craving response in various impulsive and sub-stance addiction disorders.IntroductionTo clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non substance addictions, we assessed behavioral (“high” and “craving”) and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed.MethodTwenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and “high” scales.ResultsPathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post–administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased “high” sensation after m-CPP administration compared with control.ConclusionThese results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of “high” might represent the path-way that leads to dyscontrolled behavior in patho-logical gamblers. Furthermore, the “high” feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behav-ioral and substance addictions.

scholarly journals Interaction of Cannabis Use Disorder and Striatal Connectivity in Antipsychotic Treatment Response

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Melanie Blair Thies ◽  
Pamela DeRosse ◽  
Deepak K Sarpal ◽  
Miklos Argyelan ◽  
Christina L Fales ◽  
...  
Keyword(s):  
Treatment Response ◽  
Reward Processing ◽  
Cannabis Use ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Cannabis Use Disorder ◽  
Schizophrenia Spectrum Disorders ◽  
Double Blind ◽  
History Of ◽  
The Relationship

Abstract Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between a history of cannabis use disorder (CUD) and a striatal connectivity index (SCI), a previously developed neural biomarker for AP treatment response in SSD. Patients were part of a 12-week randomized, double-blind controlled treatment study of AP drugs. A sample of 48 first-episode SSD patients with no more than 2 weeks of lifetime exposure to AP medications, underwent a resting-state fMRI scan pretreatment. Treatment response was defined a priori as a binary (response/nonresponse) variable, and a SCI was calculated in each patient. We examined whether there was an interaction between lifetime CUD history and the SCI in relation to treatment response. We found that CUD history moderated the relationship between SCI and treatment response, such that it had little predictive value in SSD patients with a CUD history. In sum, our findings highlight that biomarker development can be critically impacted by patient behaviors that influence neurobiology, such as a history of CUD.

scholarly journals Acute memory and psychotomimetic effects of cannabis and tobacco both ‘joint’ and individually: a placebo-controlled trial

2017 ◽  
Vol 47 (15) ◽  
pp. 2708-2719 ◽  
Author(s):  
C. Hindocha ◽  
T. P. Freeman ◽  
J. X. Xia ◽  
N. D. C. Shaban ◽  
H. V. Curran
Keyword(s):  
Verbal Memory ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Controlled Trial ◽  
Subjective Effects ◽  
Preliminary Evidence ◽  
Interactive Effects ◽  
Double Blind ◽  
Mixed Model Analysis ◽  
Psychotomimetic Effects

BackgroundCannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research.MethodThe individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions.ResultsCannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of ‘stoned’ and ‘dizzy’ induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure.ConclusionsRelative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences.

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