Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety‐related and substance abuse disorders

Abstract

Learning to associate cues or contexts with potential threats or rewards is adaptive and enhances survival. Both aversive and appetitive memories are therefore powerful drivers of behaviour, but the inappropriate expression of conditioned responding to fear-and drug-related stimuli can develop into anxiety-related and substance abuse disorders respectively. These disorders are associated with abnormally persistent emotional memories and inadequate treatment, often leading to symptom relapse. Studies show that cannabidiol, the main non-psychotomimetic phytocannabinoid found in Cannabis sativa, reduces anxiety via 5-HT 1A and (indirect) cannabinoid receptor activation in paradigms assessing innate responses to threat. There is also accumulating evidence from animal studies investigating the effects of cannabidiol on fear memory processing indicating that it reduces learned fear in paradigms that are translationally relevant to phobias and post-traumatic stress disorder. Cannabidiol does so by reducing fear expression acutely and by disrupting fear memory reconsolidation and enhancing fear extinction, both of which can result in a lasting reduction of learned fear. Recent studies have also begun to elucidate the effects of cannabidiol on drug memory expression using paradigms with translational relevance to addiction. The findings suggest that cannabidiol reduces the expression of drug memories acutely and by disrupting their reconsolidation. Here, we review the literature demonstrating the anxiolytic effects of cannabidiol before focusing on studies investigating its effects on various fear and drug memory processes. Understanding how cannabidiol regulates emotion and emotional memory processing may eventually lead to its use as a treatment for anxiety-related and substance abuse disorders. LINKED ARTICLESThis article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit

Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence

“…Cannabidiol (CBD) is a constituent of the Cannabis plant, which has potential therapeutic properties across many neuropsychiatric disorders. 8 Indeed, Epidiolex Ò (99% CBD; 0.1% D-9-tetrahydrocannabinol [THC]) has been approved in some places for the treatment of epilepsy 9 and clinical trials have established that CBD can be an effective treatment for pediatric epilepsy, 10,11 or epilepsy with a pediatric onset. 12,13 Interest in the broader therapeutic potential of CBD is exemplified by the burgeoning number of systematic reviews and meta-analyses published within the past few years that champion its use in a number of potential therapeutic indications.…”

“…3,25 The acute anxiolytic effects of CBD at low and intermediate doses are thought to involve 5-HT1A activation. 8,26 Whereas TRPV1 antagonism allows for the anxiolytic effects of higher CBD doses, the anxiogenic effects of higher CBD doses involves TRPV1 agonism. 8,26 TRPV1 activity seems to be unique to CBD and a few other minor cannabinoids, as THC does not interact with this receptor channel.…”

Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus

“…The therapeutic failure was ascribed, at least partially, to the specific mechanism of action of the drug, whose orthosteric inverse agonism on CB1 could lead to supra-physiological receptor alterations [8]. To this regard, the CBD could represent an innovative pharmacological approach: even though it is described as a CB1 ligand, the CBD was reported to have a low affinity for the CB1 orthosteric site [9], and this could be considered as one of the main factors influencing the lack of psychiatric symptoms following the administration in vivo [10]. Additionally, Laprairie and colleagues [11] suggested that the cannadidiol could act as a negative allosteric modulator rather than an orthosteric ligand.…”

Correlations Between Classroom Participation and Emotional Anxiety of English Learners

“…The English learning process is also a process for the cognition of new things. In this process, students are subject to the requirements such as the sense of accomplishment and competitiveness, so they will generate emotional anxiety during the English teaching activities, which is a kind of psychological behavior influenced by several aspects such as teaching environment, the mutual concern of learners, and the learning concepts, etc., and it is closely related to the effect of English teaching (Beuzen & Belzung, 1995) (Lee, Bertoglio, Guimarães et al, 2017).…”