Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity

Wall, Matthew B.; Pope, Rebecca; Freeman, Thomas; Kowalczyk, Olivia; Demetriou, Lysia; Mokrysz, Claire; Hindocha, Chandni; Lawn, Will; Bloomfield, Michael; Freeman, Abigail M.; Feilding, Amanda; Nutt, David; Curran, Valerie H.

doi:10.1177/0269881119841568

Cited by 68 publications

(73 citation statements)

References 61 publications

(97 reference statements)

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“…To our knowledge, our work provides the first demonstration of THC’s effects on mind wandering during a concurrent cognitive task. These finding are consistent with prior work on THC, including task-independent reports of mind wandering in structured interviews [ 86 , 87 ], failure to de-activate the default mode network during task performance [ 88 ] (but see [ 89 ]), and decreased error monitoring [ 42 , 43 , 90 ]. Similar to the effects of nicotine cravings [ 40 ] and alcohol [ 41 ], THC appears to increase mind wandering and other off-task mental states (e.g., “zoning out” or “mind blanking” [ 55 ]), and decrease awareness of task performance.…”

Section: Discussionsupporting

confidence: 89%

Δ9-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial

Adam

Doss

Pabon

et al. 2020

Neuropsychopharmacol.

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With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ 9 -tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded surprisingly little empirical support for an effect of THC or cannabis on working memory. We thus conducted a study with three main goals: (1) quantify the effect of THC on visual working memory in a well-powered sample, (2) test the potential role of cognitive effects (mind wandering and metacognition) in disrupting working memory, and (3) demonstrate how insufficient sample size and task duration reduce the likelihood of detecting a drug effect. We conducted two double-blind, randomized crossover experiments in which healthy adults ( N = 23, 23) performed a reliable and validated visual working memory task (the “Discrete Whole Report task”, 90 trials) after administration of THC (7.5 and/or 15 mg oral) or placebo. We also assessed self-reported “mind wandering” (Exp 1) and metacognitive accuracy about ongoing task performance (Exp 2). THC impaired working memory performance ( d = 0.65), increased mind wandering (Exp 1), and decreased metacognitive accuracy about task performance (Exp 2). Thus, our findings indicate that THC does impair visual working memory, and that this impairment may be related to both increased mind wandering and decreased monitoring of task performance. Finally, we used a down-sampling procedure to illustrate the effects of task length and sample size on power to detect the acute effect of THC on working memory.

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Section: Discussionsupporting

confidence: 89%

Δ9-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial

Adam

Doss

Pabon

et al. 2020

Neuropsychopharmacol.

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“…Decreases in DMN sFC during the acute effects of hallucinogens have been a replicable finding, occurring with psilocybin 30,34 , LSD 25,35 , DMT 33 , and ketamine 31,32 . Although it might be tempting to speculate that these effects reflect "ego dissolution" 30,40 , decreases in sFC within the DMN have also been observed with acute administration of drugs not typically associated with ego dissolution such as THC 62 , alcohol 63 , and amphetamine 64 . The small samples, short scan times, numerous reports based on single datasets, underreporting of comparable or larger effects on other brain networks, and inconsistency across studies between brain measures and ego dissolution undermine the strength of reverse inferential claims regarding the specificity of DMN effects to ego dissolution.…”

Section: Discussionmentioning

confidence: 99%

The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Doss

May

Johnson

et al. 2020

Sci Rep

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Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the first half of a 20-min scan (i.e., during peak effects). SA reduced brainwide dFC but increased brainwide eFC, though only the former effect survived multiple comparison corrections. Finally, using connectome-based classification, most models trained on dFC network interactions could accurately classify the first half of SA scans. In contrast, few models trained on within- or between-network sFC and eFC performed above chance. Notably, models trained on within-DMN sFC and eFC performed better than models trained on other network interactions. This pattern of SA effects on human brain function is strikingly similar to that of other hallucinogens, necessitating studies of direct comparisons.

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“…176,177 Human research has shown that THC intake resulted in decreases in the default mode network activation (a large scale of interacting brain regions known to have activity highly correlated with each other, especially during task disengagement 178 ), whereas a combination of THC and CBD attenuated the disruption in this network seen when THC is taken alone. 179 Patients with autism spectrum disorder were administered 600 mg of CBD and they also showed changes in functional connectivity as assessed by the fractional amplitude of low-frequency fluctuations. 180 While the direct underlying mechanism by which CBD regulates functional connectivity requires more research, there is a clear therapeutic effect on functional connectivity following CBD intake.…”

Section: Cerebrovasculaturementioning

confidence: 99%

Neuroprotection Following Concussion: The Potential Role for Cannabidiol

Singh

Neary

2020

Can. J. Neurol. Sci.

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ABSTRACT:Cannabidiol (CBD) has been generating increasing interest in medicine due to its therapeutic properties and an apparent lack of negative side effects. Research has suggested that high dosages of CBD can be taken acutely and chronically with little to no risk. This review focuses on the neuroprotective effects of a CBD, with an emphasis on its implications for recovering from a mild traumatic brain injury (TBI) or concussion. CBD has been shown to influence the endocannabinoid system, both by affecting cannabinoid receptors and other receptors involved in the endocannabinoid system such as vanilloid receptor 1, adenosine receptors, and 5-hydroxytryptamine via cannabinoid receptor-independent mechanisms. Concussions can result in many physiological consequences, potentially resulting in post-concussion syndrome. While impairments in cerebrovascular and cardiovascular physiology following concussion have been shown, there is unfortunately still no single treatment available to enhance recovery. CBD has been shown to influence the blood brain barrier, brain-derived neurotrophic factors, cognitive capacity, the cerebrovasculature, cardiovascular physiology, and neurogenesis, all of which have been shown to be altered by concussion. CBD can therefore potentially provide treatment to enhance neuroprotection by reducing inflammation, regulating cerebral blood flow, enhancing neurogenesis, and protecting the brain against reactive oxygen species. Double-blind randomized controlled trials are still required to validate the use of CBD as medication following mild TBIs, such as concussion.

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Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity

Cited by 68 publications

References 61 publications

Δ9-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial

Δ9-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial

The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Neuroprotection Following Concussion: The Potential Role for Cannabidiol

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