Dose-related effects of delta-9-THC on emotional responses to acute psychosocial stress

Childs, Emma; Lutz, Joseph A.; Wit, Harriet de

doi:10.1016/j.drugalcdep.2017.03.030

Cited by 88 publications

(58 citation statements)

References 55 publications

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“…Based on previous studies, it was unclear whether beneficial effects of FAAH inhibition would extend to the autonomic or neuroendocrine stress response. Exogenous CB 1 activation, e.g., by D 9 -tetrahydrocannabinol, can produce either anxiolytic or anxiogenic responses to an acute stressor, depending on dosage (60). Here, we found that FAAH inhibition attenuated autonomic and subjective responses to stress.…”

Section: Faah Inhibition In Healthy Humansmentioning

confidence: 55%

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Mayo

Asratian

Lindé

et al. 2020

Biological Psychiatry

150

105

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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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Section: Faah Inhibition In Healthy Humansmentioning

confidence: 55%

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Mayo

Asratian

Lindé

et al. 2020

Biological Psychiatry

150

105

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“…One potential explanation for this increased behavioral efficiency is that CB 1 R agonism attenuates the aversive emotional state associated with impending punishment. Systemic CB 1 R activation in humans has been associated with attenuated anxiety and stress, and produces anti-fear effects (Rabinak et al, 2013;Childs et al, 2017;Cuttler et al, 2018), and complementary data from rodent models demonstrate that CB 1 R agonist treatments have been associated with reduced aversive learning, impaired fear memory acquisition, enhanced fear extinction learning, reduced stress responsivity, and anxiolysis (Kangarlu-Haghighi et al, 2015;Simone et al, 2015;Nasehi et al, 2016;Fokos and Panagis, 2010;Gobira et al, 2013;Kangarlu-Haghighi et al, 2015;Kinden and Zhang, 2015;Schreiber et al, 2018;Uttl et al, 2018). Interestingly, the suppressive effects of cannabinoids on anxiety, fear, and stress appear to stem from CB 1 R activation in the basolateral amygdala (BLA), which is also involved in the integration of information regarding risk of punishment and reward value (Ganon-Elazar and Akirav, 2009;Orsini et al, 2015b;Morena et al, 2016).…”

Section: Direct Cb 1 R Activation Reduces Risky Choice Latencymentioning

confidence: 99%

Impact of Cannabinoid Type 1 Receptor Modulation on Risky Decision-Making

Freels

Liley

Gabriel

et al. 2020

Preprint

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Recent changes in policy regarding cannabis in the U.S. have been accompanied by an increase in the prevalence of cannabis use and a reduction in the perceived harms associated with consumption. However, little is understood regarding the effects of cannabinoids on cognitive processes. Given that deficient risk-taking is commonly observed in individuals suffering from substance use disorders (SUDs), we assessed the impact of manipulating cannabinoid type 1 receptors (CB 1 Rs; the primary target for ∆ 9 -tetrahydrocannabinol in the brain) on punishment-based risk-taking using the risky decision-making task (RDT) in male Long-Evans rats. The RDT measures preference for small, safe rewards over large, risky rewards associated with an escalating chance of foot shock. Systemic bidirectional CB 1 R manipulation with a CB 1 R agonist, CB 1 R antagonist, and FAAH inhibitor (which increases overall endocannabinoid tone) did not alter overt risk-taking in the RDT. Interestingly, direct CB 1 R agonism, but not indirect CB 1 R stimulation or CB 1 R blockade, resulted in reduction in latency to make risky choices while not altering safe choice latency. Our findings suggest that CB 1 R activation expedites engagement in punishment based risk-taking without affecting overall preference for risky vs. safe options. This indicates that risk preference and rate of deliberation for risk-taking are influenced by distinct neural substrates, an important consideration for development of precise treatments targeting the aberrant risk-taking typical of SUD symptomology.

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“…Low‐dose oral THC (7.5 mg) has been shown to produce subjective stress‐relieving effects, while higher doses (12.5 mg) may increase negative mood …”

Section: Traditional Anti‐anxiety Treatments Vs Cannabismentioning

confidence: 99%

“…40 Low-dose oral THC (7.5 mg) has been shown to produce subjective stress-relieving effects, while higher doses (12.5 mg) may increase negative mood. 41 While THC has shown variable effects on anxiety, CBD has consistently been shown to reduce anxiety. A preliminary double-blind, placebo-controlled cross-over study comparing a single dose of CBD (400 mg) to placebo was conducted in 10 treatmentnaive men with generalized social anxiety disorder.…”

Section: Tr Aditional Anti -Anxie T Y Tre Atments Vs C Annab Ismentioning

confidence: 99%

Denying renal transplantation to an adolescent medical cannabis user: An ethical case study

Ryan

Noeder

Burke

et al. 2019

Pediatric Transplantation

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Medical cannabis is now legal in over half of the United States. As more patients adopt this unconventional therapy, it is inevitable that potential transplant recipients will disclose their cannabis use during transplant evaluation. Transplant teams are tasked with the decision to utilize a pressure resource, often with little guidance from international and national professional organizations. Many healthcare providers remain uniformed or misinformed about the risks of cannabis use and organ transplantation. In order to illustrate the multifaceted and complex evaluation of transplant patients using medical cannabis, this article presents the case of a 20-year-old woman recommended for renal transplant who was originally denied active listing due to her medical cannabis use. A review of the literature explores the perceived and actual risks of cannabis use in the immunocompromised patient. Furthermore, a discussion of the ethics of medical cannabis use and organ transplantation is included with recommendations for multidisciplinary transplant teams.

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Dose-related effects of delta-9-THC on emotional responses to acute psychosocial stress

Abstract: Our findings suggest that a low dose of THC produces subjective stress-relieving effects in line with those commonly reported among cannabis users, but that higher doses may non-specifically increase negative mood.

Cited by 88 publications

References 55 publications

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Impact of Cannabinoid Type 1 Receptor Modulation on Risky Decision-Making

Denying renal transplantation to an adolescent medical cannabis user: An ethical case study

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