Cannabidiol as a Potential Treatment for Anxiety Disorders

Blessing, Esther; Steenkamp, Maria M.; Manzanares, Jorge; Marmar, Charles R.

doi:10.1007/s13311-015-0387-1

Cited by 537 publications

(390 citation statements)

References 120 publications

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“…Studies have also shown that cannabis may have therapeutic use for anxiety,12 sleep disorders, appetite stimulation in the context of chemotherapy, fibromyalgia, post-traumatic stress disorder, and some aspects of the motor symptoms of Parkinson’s disease, as well as for the management of agitation in dementia, bladder dysfunction, glaucoma, and Tourette’s syndrome 6. Other indications are often cited anecdotally but so far lack a firm evidence base.…”

Section: Evidence Of Efficacymentioning

confidence: 99%

The case for medical cannabis—an essay by M P Barnes

Barnes

2018

BMJ

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Section: Evidence Of Efficacymentioning

confidence: 99%

The case for medical cannabis—an essay by M P Barnes

Barnes

2018

BMJ

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“…In addition, CBD may modulate emotional memory processing and decrease symptoms associated with emotional memory disorders such as post-traumatic stress disorder (PTSD; Blessing et al, 2015,Betthauser et al, 2015.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

Norris

Loureiro

Kramar

et al. 2016

Neuropsychopharmacol

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Emerging evidence suggests that the largest phytochemical component of cannabis, cannabidiol (CBD), may possess pharmacotherapeutic properties in the treatment of neuropsychiatric disorders. CBD has been reported to functionally interact with both the mesolimbic dopamine (DA) and serotonergic (5-HT) receptor systems. However, the underlying mechanisms by which CBD may modulate emotional processing are not currently understood. Using a combination of in vivo electrophysiological recording and fear conditioning in rats, the present study aimed to characterize the behavioral, neuroanatomical, and pharmacological effects of CBD within the mesolimbic pathway, and its possible functional interactions with 5-HT and DAergic transmission. Using targeted microinfusions of CBD into the shell region of the mesolimbic nucleus accumbens (NASh), we report that intra-NASh CBD potently blocks the formation of conditioned freezing behaviors. These effects were challenged with DAergic, cannabinoid CB1 receptor, and serotonergic (5-HT 1A ) transmission blockade, but only 5-HT 1A blockade restored associative conditioned freezing behaviors. In vivo intra-ventral tegmental area (VTA) electrophysiological recordings revealed that behaviorally effective doses of intra-NASh CBD elicited a predominant decrease in spontaneous DAergic neuronal frequency and bursting activity. These neuronal effects were reversed by simultaneous blockade of 5-HT 1A receptor transmission. Finally, using a functional contralateral disconnection procedure, we demonstrated that the ability of intra-NASh CBD to block the formation of conditioned freezing behaviors was dependent on intra-VTA GABAergic transmission substrates. Our findings demonstrate a novel NAc → VTA circuit responsible for the behavioral and neuronal effects of CBD within the mesolimbic system via functional interactions with serotonergic 5-HT 1A receptor signaling.

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“…One drug showing broad therapeutic potential in various psychiatric diseases is cannabidiol (CBD), the main non-psychotropic constituent of the Cannabis sativa plant (Izzo et al, 2009; see chemical structure of CBD in Figure 1A). Studies in humans demonstrate the promise of CBD for treating anxiety (Blessing et al, 2015) and preclinical studies in rodents are elucidating the pharmacological mechanisms underlying its acute anxiolytic effects. These mechanisms include potentiation of serotonin (5-HT) transmission via 5-HT 1A receptor (5-HT 1A R) activation and elevation of endocannabinoid levels via inhibition of their metabolism and re-uptake, which indirectly facilitates cannabinoid receptor type1 (CB1R) activation (for a review see Campos et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders

et al. 2016

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Anxiety and trauma-related disorders are psychiatric diseases with a lifetime prevalence of up to 25%. Phobias and post-traumatic stress disorder (PTSD) are characterized by abnormal and persistent memories of fear-related contexts and cues. The effects of psychological treatments such as exposure therapy are often only temporary and medications can be ineffective and have adverse side effects. Growing evidence from human and animal studies indicates that cannabidiol, the main non-psychotomimetic phytocannabinoid present in Cannabis sativa, alleviates anxiety in paradigms assessing innate fear. More recently, the effects of cannabidiol on learned fear have been investigated in preclinical studies with translational relevance for phobias and PTSD. Here we review the findings from these studies, with an emphasis on cannabidiol regulation of contextual fear. The evidence indicates that cannabidiol reduces learned fear in different ways: (1) cannabidiol decreases fear expression acutely, (2) cannabidiol disrupts memory reconsolidation, leading to sustained fear attenuation upon memory retrieval, and (3) cannabidiol enhances extinction, the psychological process by which exposure therapy inhibits learned fear. We also present novel data on cannabidiol regulation of learned fear related to explicit cues, which indicates that auditory fear expression is also reduced acutely by cannabidiol. We conclude by outlining future directions for research to elucidate the neural circuit, psychological, cellular, and molecular mechanisms underlying the regulation of fear memory processing by cannabidiol. This line of investigation may lead to the development of cannabidiol as a novel therapeutic approach for treating anxiety and trauma-related disorders such as phobias and PTSD in the future.

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Cannabidiol as a Potential Treatment for Anxiety Disorders

Cited by 537 publications

References 120 publications

The case for medical cannabis—an essay by M P Barnes

The case for medical cannabis—an essay by M P Barnes

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders

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