Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol

2020 ◽  
pp. 1-8
Author(s):  
Marco Colizzi ◽  
Nathalie Weltens ◽  
David J Lythgoe ◽  
Steve CR Williams ◽  
Lukas Van Oudenhove ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Surrogate Marker ◽  
Anterior Cingulate ◽  
Differential Sensitivity ◽  
Acute Effects ◽  
Double Blind ◽  
Glial Function ◽  
Cortisol Levels ◽  
Psychotomimetic Effects ◽  
Hpa Axis Activity

Abstract Background Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested. Methods A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. Results The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo; M = −0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo; M = −275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. Conclusions The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.

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.

Melatonin enhances cortisol levels in aged but not young women

1995 ◽  
Vol 133 (6) ◽  
pp. 691-695 ◽  
Author(s):  
Angelo Cagnacci ◽  
Renza Soldani ◽  
Samuel SC Yen
Keyword(s):  
Hpa Axis ◽  
Young Women ◽  
Serum Cortisol ◽  
Serum Levels ◽  
Double Blind ◽  
Early Evening ◽  
Melatonin Administration ◽  
Animal Data ◽  
Early Follicular Phase ◽  
Cortisol Levels

Cagnacci A, Soldani R, Yen SSC. Melatonin enhances cortisol levels in aged but not young women. Eur J Endocrinol 1995;133:691–5. ISSN 0804–4643 In spite of animal data showing an effect of melatonin in the regulation of the hypothalamus–pituitary–adrenal (HPA) axis, no effect of melatonin on cortisol has been evidenced in young men. Gender and aging are believed to influence the regulation of the HPA axis, and may thus modulate the melatonin effect on cortisol. In this study we investigated whether an effect of melatonin on cortisol can be observed in women of different age. Six young women in early follicular phase (22–32 years; EFW) and eight aged women in postmenopause (54–62 years; PMW) were studied. At 08.00 h on two consecutive days each woman received, randomly and in double-blind fashion, a pill of placebo or melatonin (100 mg). Serum levels of melatonin and cortisol were evaluated at 20-min intervals for 48 h. In comparison to EFW, PMW showed an earlier onset of nocturnal melatonin (p < 0.05) and cortisol rise (p < 0.01) and higher cortisol levels at lunch (p < 0.05) and early evening (p < 0.01). Melatonin administration did not modify serum cortisol levels in EFW but elicited a marked increase of daytime cortisol levels in PMW (p < 0.02). The present data reveal that in aged PMW the cortisol levels are enhanced at selected circadian times and are stimulated by melatonin. Angelo Cagnacci, Istituto di Ginecologia e Ostetricia, Ospedale 5, Giovanni di Dio, via Ospedale 46, 09124 Cagliari, Italy

Racial discrimination and ethnic racial identity in adolescence as modulators of HPA axis activity

2020 ◽  
Vol 32 (5) ◽  
pp. 1669-1684
Author(s):  
Emma K. Adam ◽  
Emily F. Hittner ◽  
Sara E. Thomas ◽  
Sarah Collier Villaume ◽  
Ednah E. Nwafor
Keyword(s):  
Racial Identity ◽  
Racial Discrimination ◽  
Hpa Axis ◽  
Emotional Health ◽  
Past Research ◽  
Ongoing Research ◽  
Black And White ◽  
Stress Biology ◽  
Cortisol Levels ◽  
Hpa Axis Activity

AbstractWe review evidence of racial discrimination as a critical and understudied form of adversity that has the potential to impact stress biology, particularly hypothalamic–pituitary–adrenal (HPA) axis activity. We highlight ethnic racial identity (ERI) as a positive regulatory influence on HPA axis activity, as indexed by levels of salivary cortisol. In past research by our group, Black individuals with high adolescent discrimination had low adult cortisol levels (hypocortisolism). Here, we present new analyses showing that ERI, measured prospectively from ages 12 through 32 in 112 Black and white individuals, is related to better-regulated cortisol levels in adulthood, particularly for Black participants. We also describe ongoing research that explores whether the promotion of ERI during adolescence can reduce ethnic–racial disparities in stress biology and in emotional health and academic outcomes.

scholarly journals Effects of childhood trauma on cortisol levels in suicide attempters and ideators

2018 ◽  
Author(s):  
Daryl Brian O'Connor ◽  
Jessica Green ◽  
Eamonn Ferguson ◽  
Ronan O' Carroll ◽  
Rory O' Connor
Keyword(s):  
Childhood Trauma ◽  
Hpa Axis ◽  
Psychological Intervention ◽  
Cortisol Reactivity ◽  
Suicide Attempters ◽  
Global Health Issue ◽  
History Of ◽  
Cortisol Levels ◽  
Laboratory Stress ◽  
Hpa Axis Activity

Objectives: Suicide is a global health issue. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, asmeasured by cortisol levels, has been identified as one potential risk factor for suicide. Recent evidence hasindicated that blunted cortisol reactivity to stress is associated with suicidal behavior. The current study investigatedwhether childhood trauma was associated with blunted cortisol reactivity to a laboratory stressor andresting cortisol levels in suicide attempters and ideators.Methods: 160 Participants were recruited and grouped according to history of previous suicidal attempt, suicidalideation or as control participants. Participants completed background questionnaires, including the ChildhoodTrauma Questionnaire, before completing a laboratory stress task. Cortisol levels were assessed at rest andduring the stress task.Results: The highest levels of childhood trauma were reported in those who had attempted suicide (78.7%),followed by those who thought about suicide (37.7%) and then those with no suicidal history (17.8%).Moreover, regression analyses showed that childhood trauma was a significant predictor of blunted cortisolreactivity to stress and resting cortisol levels, such that higher levels of trauma were associated with lowercortisol levels in those with a suicidal history. Family history of suicide did not interact with the effects ofchildhood trauma on cortisol levels.Conclusions: These results indicate that childhood trauma is associated with blunted HPA axis activity in vulnerablepopulations in adulthood. The challenge for researchers is to elucidate the precise causal mechanismslinking trauma, cortisol and suicide risk and to investigate whether the effects of childhood trauma on cortisollevels are amendable to psychological intervention.

scholarly journals Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance

2009 ◽  
Vol 194 (4) ◽  
pp. 342-349 ◽  
Author(s):  
Mario F. Juruena ◽  
Carmine M. Pariante ◽  
Andrew S. Papadopoulos ◽  
Lucia Poon ◽  
Stafford Lightman ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Severe Depression ◽  
Treatment Resistance ◽  
Receptor Activation ◽  
Depressive Illness ◽  
Patient Treatment ◽  
Lower Percentage ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Hpa Axis Activity

BackgroundPeople with severe depressive illness have raised levels of cortisol and reduced glucocorticoid receptor function.AimsTo obtain a physiological assessment of hypothalamic–pituitary–adrenal (HPA) axis feedback status in an in-patient sample with depression and to relate this to prospectively determined severe treatment resistance.MethodThe prednisolone suppression test was administered to 45 in-patients with depression assessed as resistant to two or more antidepressants and to 46 controls, prior to intensive multimodal in-patient treatment.ResultsThe patient group had higher cortisol levels than controls, although the percentage suppression of cortisol output after prednisolone in comparison with placebo did not differ. Nonresponse to in-patient treatment was predicted by a more dysfunctional HPA axis (higher cortisol levels postprednisolone and lower percentage suppression).ConclusionsIn patients with severe depression, HPA axis activity is reset at a higher level, although feedback remains intact. However, prospectively determined severe treatment resistance is associated with an impaired feedback response to combined glucocorticoid and mineralocorticoid receptor activation by prednisolone.

The Influence of HPA-Axis Activity on Aggression

2008 ◽  
Author(s):  
Robina Khan ◽  
Katja Bertsch ◽  
Ewald Naumann ◽  
Menno R. Kruk ◽  
Patrick Britz ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Hpa Axis Activity
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