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- Mayo, Leah, et al.
(författare)
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Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial
- 2020
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Ingår i: Biological Psychiatry. - : ELSEVIER SCIENCE INC. - 0006-3223 .- 1873-2402. ; 87:6, s. 538-547
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Posttraumatic stress disorder, an area of large unmet medical needs, is characterized by persistence of fear memories and maladaptive stress responses. In rodents, elevation of the endocannabinoid anandamide due to inhibition of fatty acid amide hydrolase (FAAH) facilitates fear extinction and protects against the anxiogenic effects of stress. We recently reported that elevated anandamide levels in people homozygous for a loss-of-function FAAH mutation are associated with a similar phenotype, suggesting a translational validity of the preclinical findings. METHODS: In this double-blind, placebo-controlled experimental medicine study, healthy adults were randomized to an FAAH inhibitor (PF-04457845, 4 mg orally, once daily; n = 16) or placebo (n = 29) for 10 days. On days 9 and 10, participants completed a task battery assessing psychophysiological indices of fear learning, stress reactivity, and stress-induced affective responses. RESULTS: FAAH inhibition produced a 10-fold increase in baseline anandamide. This was associated with potentiated recall of fear extinction memory when tested 24 hours after extinction training. FAAH inhibition also attenuated autonomic stress reactivity, assessed via electrodermal activity, and protected against stress-induced negative affect, measured via facial electromyography. CONCLUSIONS: Our data provide preliminary human evidence that FAAH inhibition can improve the recall of fear extinction memories and attenuate the anxiogenic effects of stress, in a direct translation of rodent findings. The beneficial effects of FAAH inhibition on fear extinction, as well as stress- and affect-related behaviors, provide a strong rationale for developing this drug class as a treatment for posttraumatic stress disorder.
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| 2. |
- Wilhelmson, Katarina, 1958, et al.
(författare)
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Comprehensive Geriatric Assessment for Frail Older People in Swedish Acute Care Settings (CGA-Swed) : A Randomised Controlled Study
- 2020
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Ingår i: Geriatrics (Basel, Switzerland). - : MDPI AG. - 2308-3417 .- 0016-867X. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study is to evaluate the effects of the Comprehensive Geriatric Assessment (CGA) for frail older people in Swedish acute hospital settings - the CGA-Swed study. In this study protocol, we present the study design, the intervention and the outcome measures as well as the baseline characteristics of the study participants. The study is a randomised controlled trial with an intervention group receiving the CGA and a control group receiving medical assessment without the CGA. Follow-ups were conducted after 1, 6 and 12 months, with dependence in activities of daily living (ADL) as the primary outcome measure. The study group consisted of frail older people (75 years and older) in need of acute medical hospital care. The study design, randomisation and process evaluation carried out were intended to ensure the quality of the study. Baseline data show that the randomisation was successful and that the sample included frail older people with high dependence in ADL and with a high comorbidity. The CGA contributed to early recognition of frail older people's needs and ensured a care plan and follow-up. This study is expected to show positive effects on frail older people's dependence in ADL, life satisfaction and satisfaction with health and social care.
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