Biphasic effects of THC in memory and cognition

Calabrese, Edward J.; Rubio‐Casillas, Alberto

doi:10.1111/eci.12920

Cited by 89 publications

(57 citation statements)

References 118 publications

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“…However, recent pre-clinical studies have found that delta-9-THC can improve cognitive performances in rats (89) and mice (90). THC, in fact, appears to promote hippocampal neurogenesis to prevent neurodegenerative processes occurring in animal models of Alzheimer's disease, to protect from inflammation-induced cognitive damage, and to restore memory and cognitive function in old mice (91).…”

Section: Cannabimimeticmentioning

confidence: 99%

The Psychonauts’ World of Cognitive Enhancers

et al. 2020

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Background: There is growing availability of novel psychoactive substances (NPS), including cognitive enhancers (CEs) which can be used in the treatment of certain mental health disorders. While treating cognitive deficit symptoms in neuropsychiatric or neurodegenerative disorders using CEs might have significant benefits for patients, the increasing recreational use of these substances by healthy individuals raises many clinical, medico-legal, and ethical issues. Moreover, it has become very challenging for clinicians to keep up-to-date with CEs currently available as comprehensive official lists do not exist. Methods: Using a web crawler (NPSfinder ®), the present study aimed at assessing psychonaut fora/platforms to better understand the online situation regarding CEs. We compared NPSfinder ® entries with those from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and from the United Nations Office on Drugs and Crime (UNODC) NPS databases up to spring 2019. Any substance that was identified by NPSfinder ® was considered a CE if it was either described as having nootropic abilities by psychonauts or if it was listed among the known CEs by Froestl and colleagues. Results: A total of 142 unique CEs were identified by NPSfinder ®. They were divided into 10 categories, including plants/herbs/products (29%), prescribed drugs (17%), image and performance enhancing drugs (IPEDs) (15%), psychostimulants (15%), miscellaneous (8%), Phenethylamines (6%), GABAergic drugs (5%), cannabimimetic (4%), tryptamines derivatives (0.5%), and piperazine derivatives (0.5%). A total of 105 chemically different substances were uniquely identified by NPSfinder ®. Only one CE was uniquely identified by the EMCDDA; no CE was uniquely identified by the UNODC. Conclusions: These results show that NPSfinder ® is helpful as part of an Early Warning System, which could update clinicians with the growing numbers and types of nootropics in the increasingly difficult-to-follow internet world. Improving clinicians' knowledge of NPS could promote more effective prevention and harm reduction measures in clinical settings.

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Section: Cannabimimeticmentioning

confidence: 99%

The Psychonauts’ World of Cognitive Enhancers

et al. 2020

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“…The significant decline in plasma endocannabinoids 30 minutes after THC administration, attaining baseline levels 48 hours after the study, may be due to decline in THC levels or that of its metabolites, which cause direct adrenal stimulation or sedation induced by the drug. Thus, repeated THC treatment may induce a biphasic endocannabinoid response characterized by an early symphatico-adrenergic and glucocorticoid activation during high plasma levels of THC followed by a relaxation response associated with lower endocannabinoid plasma concentrations [25,26].…”

Section: The Circadian Rhythmmentioning

confidence: 99%

Changing the tone of clinical study design in the cannabis industry

Antony

McDonald

Noorbakhsh

et al. 2020

Translational Neuroscience

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AbstractCannabis (also known as marijuana) is the most frequently used psychoactive substance globally. Cannabis exerts therapeutic functions for many indications and has vast potential as a health and wellness product. Advances in our understanding of the composition and pharmacological properties of cannabis have revealed interactions between cannabis, an individuals’ circadian rhythms and their endocannabinoid signaling. Exogenously administered cannabinoids can bidirectionally entrain central and peripheral clocks that comprise circadian rhythms, and malfunctions in the endocannabinoid system are reported to impact neurological processes. Therefore, it is necessary to account for the circadian rhythm when designing clinical trials examining the pharmacological properties of cannabis-based products for health and wellness to limit its potential confounding impact on results. Consideration of the entrainment capabilities of the endocannabinoid system is warranted when designing clinical trials.

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“…However, it is also the main responsible for the recreational use of Cannabis and its psychotomimetic effect, restricting Cannabis therapeutic use. Besides, some THC effects are commonly biphasic and dose-dependent [133]: low doses have potential therapeutic value in cognitive and anxiety disorders while high doses cause harmful effects, and are related to the reported side effects resulting from direct activation of CB1 receptors [51,131]. This supraphysiological action can lead to a rapid down-regulation of these receptors [134,135], potentially resulting in tolerance and addiction [136,137].…”

Section: Discussionmentioning

confidence: 99%

Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies

et al. 2020

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Background: Posttraumatic stress disorder (PTSD) may stem from the formation of aberrant and enduring aversive memories. Some PTSD patients have recreationally used Cannabis, probably aiming at relieving their symptomatology. However, it is still largely unknown whether and how Cannabis or its psychotomimetic compound Δ 9-tetrahydrocannabinol (THC) attenuates the aversive/traumatic memory outcomes. Here, we seek to review and discuss the effects of THC on aversive memory extinction and anxiety in healthy humans and PTSD patients. Methods: Medline, PubMed, Cochrane Library, and Central Register for Controlled Trials databases were searched to identify peer-reviewed published studies and randomized controlled trials in humans published in English between 1974 and July 2020, including those using only THC and THC combined with cannabidiol (CBD). The effect size of the experimental intervention under investigation was calculated. Results: At low doses, THC can enhance the extinction rate and reduce anxiety responses. Both effects involve the activation of cannabinoid type-1 receptors in discrete components of the corticolimbic circuitry, which could couterbalance the low "endocannabinoid tonus" reported in PTSD patients. The advantage of associating CBD with THC to attenuate anxiety while minimizing the potential psychotic or anxiogenic effect produced by high doses of THC has been reported. The effects of THC either alone or combined with CBD on aversive memory reconsolidation, however, are still unknown. Conclusions: Current evidence from healthy humans and PTSD patients supports the THC value to suppress anxiety and aversive memory expression without producing significant adverse effects if used in low doses or when associated with CBD. Future studies are guaranteed to address open questions related to their dose ratios, administration routes, pharmacokinetic interactions, sex-dependent differences, and prolonged efficacy.

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Biphasic effects of THC in memory and cognition

Cited by 89 publications

References 118 publications

The Psychonauts’ World of Cognitive Enhancers

The Psychonauts’ World of Cognitive Enhancers

Changing the tone of clinical study design in the cannabis industry

Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies

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