Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans

Chadwick, Verity; Rohleder, Cathrin; Koethe, Dagmar; Leweke, F. Markus

doi:10.1097/yco.0000000000000562

Cited by 52 publications

(35 citation statements)

References 49 publications

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“…Hitherto, available literature on the emotional effects of CBD in humans focuses mainly on anxiolytic properties. Results of published studies indicate that CBD does not affect anxiety per se, as it has no effect on baseline anxiety (18,19,35,36). Our results are consistent with these findings in the most general sense, although the used adjective mood rating scale does not retrieve anxiety, but depressiveness experience.…”

Section: Effects Of Cbd and Thc On Emotionsupporting

confidence: 90%

Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers

et al. 2020

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The two main phytocannabinoids—delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)—have been extensively studied, and it has been shown that THC can induce transient psychosis. At the same time, CBD appears to have no psychotomimetic potential. On the contrary, emerging evidence for CBD's antipsychotic properties suggests that it may attenuate effects induced by THC. Thus, we investigated and compared the effects of THC and CBD administration on emotion, cognition, and attention as well as the impact of CBD pre-treatment on THC effects in healthy volunteers. We performed a placebo-controlled, double-blind, experimental trial (GEI-TCP II; ClinicalTrials.gov identifier: NCT02487381) with 60 healthy volunteers randomly allocated to four parallel intervention groups, receiving either placebo, 800 mg CBD, 20 mg THC, or both cannabinoids. Subjects underwent neuropsychological tests assessing working memory (Letter Number Sequencing test), cognitive processing speed (Digit Symbol Coding task), attention (d2 Test of Attention), and emotional state (adjective mood rating scale [EWL]). Administration of CBD alone did not influence the emotional state, cognitive performance, and attention. At the same time, THC affected two of six emotional categories—more precisely, the performance-related activity and extraversion—, reduced the cognitive processing speed and impaired the performance on the d2 Test of Attention. Interestingly, pre-treatment with CBD did not attenuate the effects induced by THC. These findings show that the acute intake of CBD itself has no effect per se in healthy volunteers and that a single dose of CBD prior to THC administration was insufficient to mitigate the detrimental impact of THC in the given setting. This is in support of a complex interaction between CBD and THC whose effects are not counterbalanced by CBD under all circumstances.

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Section: Effects Of Cbd and Thc On Emotionsupporting

confidence: 90%

Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers

et al. 2020

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“…Of note, and contrasting its observed detrimental effects in BD subjects [55,56], some investigators also suggest a potential therapeutic role for cannabis derivative in BD [57]. The endocannabinoid system is known to exert neuro-modulatory effects on other neurotransmitter systems critical in controlling emotions [58]. Selective activation of the cannabinoid receptor 2 (CB2) and antagonism of cannabinoid receptor 1 (CB1) may alleviate the symptoms of BD and, according to Arjmand and colleagues [59], should be rigorously explored.…”

Section: Pharmacotherapies Of Comorbid Bd and Illicit Substance Usementioning

confidence: 99%

Bipolar Disorder and Comorbid Use of Illicit Substances

et al. 2021

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Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.

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“…Cumulative evidence suggests that the endocannabinoid system (ECS) is involved in the physiopathologic mechanism of depression[ 30 - 32 ]. ECS receptors include cannabinoid type 1 receptor (CB1R) and CB2R.…”

Section: Activation Of Endocannabinoid System and Brain Derived Neuromentioning

confidence: 99%

Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies

Luan

Zhao

Shi

et al. 2020

WJP

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This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies, including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway, anti-oxidative stress effects, enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway, increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway, and reducing the activity of the hypothalamic-pituitary-adrenocortical axis. We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning, shallow depth of stimulation, and difficulty in elucidating the neural circuit mechanism up- and down-stream of the stimulation target brain region.

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Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans

Cited by 52 publications

References 49 publications

Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers

Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers

Bipolar Disorder and Comorbid Use of Illicit Substances

Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies

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