Cannabinoid Regulation of Fear and Anxiety: an Update

Abstract

Purpose of Review Anxiety- and trauma-related disorders are prevalent and debilitating mental illnesses associated with a significant socioeconomic burden. Current treatment approaches often have inadequate therapeutic responses, leading to symptom relapse. Here we review recent preclinical and clinical findings on the potential of cannabinoids as novel therapeutics for regulating fear and anxiety. Recent Findings Evidence from preclinical studies has shown that the non-psychotropic phytocannabinoid cannabidiol and the endocannabinoid anandamide have acute anxiolytic effects and also regulate learned fear by dampening its expression, enhancing its extinction and disrupting its reconsolidation. The findings from the relevant clinical literature are still very preliminary but are nonetheless encouraging. Summary Based on this preclinical evidence, larger-scale placebo-controlled clinical studies are warranted to investigate the effects of cannabidiol in particular as an adjunct to psychological therapy or medication to determine its potential utility for treating anxiety-related disorders in the future.

Use of cannabidiol in anxiety and anxiety-related disorders

“…3 Taken together, these disorders have an estimated lifetime prevalence of approximately 29% for U.S. adults. 3,4 As such, they pose a substantial disease burden to patients and the health care system because of their association with decreased wellbeing, physical impairment, loss of productivity, and increased health care utilization costs. 3,4 At present, the primary pharmacologic treatment for anxiety and anxiety-related disorders involves the use of medications that modulate the activity of DA, NE, GABA, and 5-HT neurotransmitters.…”

“…[5][6][7] The endocannabinoid system (ECS) is a promising therapeutic target for anxiolytic-drug development owing to its purported role in modulating synaptic plasticity and neuronal activity involved in the anxiety response. 4,5,[8][9][10][11][12] Primary activity of signaling within the ECS is thought to be because of the action on 2 known cannabinoid receptors, CB1 and CB2. 4,5,[8][9][10][11][12] Cannabidiol (CBD), a chemical compound known as a phytocannabinoid, is derived from the plant Cannabis sativa and may have a role in the management of anxiety given its pharmacologic activity within the ECS.…”

“…4,5,[8][9][10][11][12] Primary activity of signaling within the ECS is thought to be because of the action on 2 known cannabinoid receptors, CB1 and CB2. 4,5,[8][9][10][11][12] Cannabidiol (CBD), a chemical compound known as a phytocannabinoid, is derived from the plant Cannabis sativa and may have a role in the management of anxiety given its pharmacologic activity within the ECS. 4,5,[8][9][10][11][12] Among the more than 400 chemicals produced by C sativa, delta-9-tetrahydrocannabinol (THC) and CBD are the major compounds.…”

“…4,5,[8][9][10][11][12] Cannabidiol (CBD), a chemical compound known as a phytocannabinoid, is derived from the plant Cannabis sativa and may have a role in the management of anxiety given its pharmacologic activity within the ECS. 4,5,[8][9][10][11][12] Among the more than 400 chemicals produced by C sativa, delta-9-tetrahydrocannabinol (THC) and CBD are the major compounds. 4,5,[8][9][10][11][12] THC is the most abundant psychoactive chemical and is primarily responsible for the wellknown hallucinogenic effects of C sativa.…”

“…4,5,[8][9][10][11][12] Among the more than 400 chemicals produced by C sativa, delta-9-tetrahydrocannabinol (THC) and CBD are the major compounds. 4,5,[8][9][10][11][12] THC is the most abundant psychoactive chemical and is primarily responsible for the wellknown hallucinogenic effects of C sativa. In contrast, CBD is not psychoactive.…”