Acute and chronic effects of Δ⁹-tetrahydrocannabinol (THC) on cerebral blood flow: A systematic review

Acute and chronic exposure to cannabis and its main psychoactive component, 9-tetrahydrocannabinol (THC), is associated with changes in brain function and cerebral blood flow (CBF). We therefore sought to systematically review the literature on the effects of THC on CBF following PRISMA guidelines. Studies assessing the acute and chronic effects of THC on CBF, perfusion and volume were searched in the PubMed database between January 1972 and June 2019. We included thirty-four studies, which altogether investigated 1259 humans and 28 animals. Acute and chronic THC exposure have contrasting and regionally specific effects on CBF. While acute THC causes an overall increase in CBF in the anterior cingulate cortex, frontal cortex and insula, in a dose-dependent manner, chronic cannabis use results in an overall reduction in CBF, especially in the prefrontal cortex, which may be reversed upon prolonged abstinence from the drug. Future studies should focus on standardised methodology and longitudinal assessment to strengthen our understanding of the region-specific effects of THC on CBF and its clinical and functional significance

What symptoms best predict severe distress in an online survey of UK health and social care staff facing COVID-19: development of the two-item Tipping Point Index

Objectives: COVID-19 has altered standard thresholds for identifying anxiety and depression. A brief questionnaire to determine when individuals are at a tipping point for severe anxiety or depression would greatly help decisions about when to seek assessment or treatment. Design: Data were collected as part of the Frontline-COVID Study, a cross-sectional national online survey with good coverage of health and social care settings. New questionnaire items reflecting when coping was actually breaking down were compared with standard measures of severe anxiety and depression. Data were collected between 27 May and 23 July 2020. Setting: The majority of participants worked in hospitals (53%), in nursing or care homes (15%), or in other community settings (30%). Participants: Of 1194 qualifying respondents, 1038 completed the six tipping point items. Respondents included nurses, midwives, doctors, care workers, healthcare assistants, allied healthcare professionals and other non-medical staff. Over 90% were white and female. Main outcome measures: Threshold for severe anxiety according to the Generalised Anxiety Disorder Scale-7 or moderately severe depression according to the Patient Health Questionnaire-9. Results: Answering yes to one of two simple questions (‘Over the last week have you been often feeling panicky or on the point of losing control of your emotions?’, ‘Over the last week have you felt complete hopelessness about the future?’) demonstrated very high sensitivity (0.95, 95% CI 0.92 to 0.97) and negative predictive value (0.97, 95% CI 0.95 to 0.98). Answering yes to both questions yielded high specificity (0.90, 95% CI 0.87 to 0.92) and positive predictive value (0.72, 95% CI 0.67 to 0.77). Results were replicated in two random subsamples and were consistent across different genders, ethnic backgrounds, and health or social care settings. Conclusions: Answering two simple yes/no questions can provide simple and immediate guidance to assist with decisions about whether to seek further assessment or treatment. Data availability statement: Anonymised data that support the findings of this study are available from TG upon reasonable request. The data have not been made publicly available due to their personal and sensitive nature

Trauma-informed care for adult survivors of developmental trauma with psychotic and dissociative symptoms: a systematic review of intervention studies

Developmental trauma is associated with an increased risk of psychosis and predicts poor prognosis. Despite this association, little is known about which treatments work best for survivors of developmental trauma with psychosis. We sought to do the first review, to our knowledge, to investigate treatments for people with psychotic and dissociative symptoms who have a history of developmental trauma. We searched MEDLINE, PsychINFO, and Google Scholar for studies reporting psychological and pharmacological treatments of psychotic or dissociative symptoms in adult survivors of developmental trauma. We identified 24 studies, most of which investigated various modalities of psychotherapy with two case reports of pharmacological treatments. There is preliminary evidence in favour of third wave cognitive therapies. However, because of low methodological quality and reporting in most of the studies found, it remains unknown which treatments are most effective in this clinical group. Nonetheless, our findings of potential treatment targets, including emotion regulation, acceptance, interpersonal skills, trauma re-processing, and the integration of dissociated ego states, could guide future work in this area. Methodologically rigorous studies are needed to enable clinicians and patients to collaboratively form evidence-based treatment plans. Our Review is registered with PROSPERO, number CRD42018104533

Chronic psychosocial stressors are associated with alterations in salience processing and corticostriatal connectivity

Psychosocial stressors including childhood adversity, migration, and living in an urban environment, have been associated with several psychiatric disorders, including psychotic disorders. The neural and psychological mechanisms mediating this relationship remain unclear. In parallel, alterations in corticostriatal connectivity and abnormalities in the processing of salience, are seen in psychotic disorders. Aberrant functioning of these mechanisms secondary to chronic stress exposure, could help explain how common environmental exposures are associated with a diverse range of symptoms. In the current study, we recruited two groups of adults, one with a high degree of exposure to chronic psychosocial stressors (the exposed group, n = 20), and one with minimal exposure (the unexposed group, n = 22). All participants underwent a resting state MRI scan, completed the Aberrant Salience Inventory, and performed a behavioural task - the Salience Attribution Test (SAT). The exposed group showed reduced explicit adaptive salience scores (cohen's d = 0.69, p = 0.03) and increased aberrant salience inventory scores (d = 0.65, p = 0.04). The exposed group also showed increased corticostriatal connectivity between the ventral striatum and brain regions previously implicated in salience processing. Corticostriatal connectivity in these regions negatively correlated with SAT explicit adaptive salience (r = -0.48, p = 0.001), and positively correlated with aberrant salience inventory scores (r = 0.42, p = 0.006). Furthermore, in a mediation analysis there was tentative evidence that differences in striato-cortical connectivity mediated the group differences in salience scores

The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers.

This is the final version of the article. Available from OUP via the DOI in this record.Background: Dopaminergic functioning is thought to play critical roles in both motivation and addiction. There is preliminary evidence that dopamine agonists reduce the motivation for cigarettes in smokers. However, the effects of pramipexole, a dopamine D3 receptor preferring agonist, have not been investigated. The aim of this study was to examine the effects of an acute dose of pramipexole on the motivation to earn cigarettes and nondrug rewards. Methods: Twenty dependent and 20 occasional smokers received 0.5 mg pramipexole using a double-blind, placebo-controlled crossover design. Motivation for cigarettes and consummatory nondrug rewards was measured using the DReaM-Choice task, in which participants earned, and later "consumed," cigarettes, music, and chocolate. Demand for cigarettes was measured using the Cigarette Purchase Task (CPT). Self-reported craving, withdrawal, and drug effects were also recorded. Results: Dependent smokers chose (p < .001) and button-pressed for (p < .001) cigarettes more, and chose chocolate less (p < .001), than occasional smokers. Pramipexole did not affect the number of choices for or amount of button-pressing for any reward including cigarettes, which was supported by a Bayesian analysis. The dependent smokers had greater demand for cigarettes than occasional smokers across all CPT outcomes (ps < .021), apart from elasticity. Pramipexole did not affect demand for cigarettes, and this was supported by Bayesian analyses. Pramipexole produced greater subjective "feel drug" and "dislike drug" effects than placebo. Conclusions: Dependent and occasional cigarette smokers differed in their motivation for cigarettes but not for the nondrug rewards. Pramipexole did not acutely alter motivation for cigarettes. These findings question the role of dopamine D3 receptors in cigarette-seeking behavior in dependent and occasional smokers. Implications: This study adds to the growing literature about cigarette versus nondrug reward processing in nicotine dependence and the role of dopamine in cigarette-seeking behavior. Our results suggest nicotine dependence is associated with a hypersensitivity to cigarette rewards but not a hyposensitivity to nondrug rewards. Furthermore, our results question the importance of dopamine D3 receptors in motivational processing of cigarettes in occasional and dependent smokers.This study was funded by BBSRC PhD funding

Cannabis dampens the effects of music in brain regions sensitive to reward and emotion

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here we investigate the effects of cannabis on listening to music - a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol (CBD), which may offset cannabis-related harms. Methods: Across three sessions, sixteen cannabis users inhaled cannabis with CBD, cannabis without CBD, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging (fMRI) within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (p<0.05). Results: Compared to placebo, cannabis without CBD dampened response to music in bilateral auditory cortex (right: p=0.005, left: p=0.008), right hippocampus/parahippocampal gyrus (p=0.025), right amygdala (p=0.025) and right ventral striatum (p=0.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (p=0.002) and increased functional connectivity with auditory cortex (right: p=0.000, left: p=0.000), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by CBD (right: p=0.003, left: p=0.030), and cannabis with CBD did not differ from placebo on any fMRI measures. Both types of cannabis increased ratings of wanting to listen to music (p<0.002) and enhanced sound perception (p<0.001). Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol

The neuropsychopharmacology of cannabis: a review of human imaging studies

The laws governing cannabis are evolving worldwide and associated with changing patterns of use. The main psychoactive drug in cannabis is Δ9-tetrahydrocannabinol (THC), a partial agonist at the endocannabinoid CB1 receptor. Acutely, cannabis and THC produce a range of effects on several neurocognitive and pharmacological systems. These include effects on executive, emotional, reward and memory processing via direct interactions with the endocannabinoid system and indirect effects on the glutamatergic, GABAergic and dopaminergic systems. Cannabidiol, a non-intoxicating cannabinoid found in some forms of cannabis, may offset some of these acute effects. Heavy repeated cannabis use, particularly during adolescence, has been associated with adverse effects on these systems, which increase the risk of mental illnesses including addiction and psychosis. Here, we provide a comprehensive state of the art review on the acute and chronic neuropsychopharmacology of cannabis by synthesizing the available neuroimaging research in humans. We describe the effects of drug exposure during development, implications for understanding psychosis and cannabis use disorder, and methodological considerations. Greater understanding of the precise mechanisms underlying the effects of cannabis may also give rise to new treatment targets