Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

Fusar‐Poli, Paolo; Crippa, José Alexandre de Souza; Bhattacharyya, Sagnik; Borgwardt, Stefan; Allen, Paul; Martín‐Santos, Rocío; Seal, Marc L.; Surguladze, Simon; O'Carrol, Colin; Atakan, Zerrin; Zuardi, Antônio Waldo; McGuire, Philip

doi:10.1001/archgenpsychiatry.2008.519

Cited by 422 publications

(392 citation statements)

References 108 publications

(142 reference statements)

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“…Not surprisingly, and as witnessed in the aforementioned preclinical data, CBD has been shown to reduce anxiety in patients with social phobia and generalized social anxiety disorders [62][63][64]. CBD decreases autonomic arousal and subjective anxiety [65]; these anxiolytic effects were found to be linked to the modulation of limbic and paralimbic structures [57,62]. It remains to be determined if these properties translate in the attenuation of symptoms for other anxiety disorders than social phobia (e.g., post-traumatic stress disorder, panic disorder) [66].…”

Section: Cbd and Neurobiological Targets/effectsmentioning

confidence: 71%

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

et al. 2015

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Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ 9 -tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from Bmedical CBD^and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

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Section: Cbd and Neurobiological Targets/effectsmentioning

confidence: 71%

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

et al. 2015

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“…The fearful faces task activates the amygdala, and other medial temporal areas involved in [107] Varying in schizotypy and cannabis use, DBP Inhaled, 16 mg, acute Baseline VAS anxiety No significant effect of CBD HV = healthy volunteers; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; THC = Δ 9-tetrahydrocannabinol; STAI = Spielberger's state trait anxiety inventory; VAMS = visual analog mood scale; BP = blood pressure; SPST = simulated public speaking test; SCR = skin conductance response; SPECT = single-photon emission computed tomography; SSPS-N = negative self-evaluation subscale; HR = heart rate; VAS = visual analog scale, CBD = cannabidiol ↑ rCBF in the right posterior cingulate gyrus CBD = cannabidiol; HV = healthy controls; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; SPECT = single-photo emission computed tomography; rCBF = regional cerebral blood flow; fMRI = functional magnetic resonance imaging; HPC = hippocampus; HYP = hypothalamus; PHG = parahippocampal gyrus; STG = superior temporal gyrus; MTG = medial temporal gyrus; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex emotion processing, and heightened amygdala response activation has been reported in anxiety disorders, including GAD and PTSD [113,114]. CBD attenuated blood-oxygen-level dependent activation in the left amygdala, and the anterior and posterior cingulate cortex in response to intensely fearful faces, and also reduced amplitude in skin conductance fluctuation, which was highly correlated with amygdala activation [109]. Dynamic causal modeling analysis in this data set further showed CBD reduced forward functional connectivity between the amygdala and anterior cingulate cortex [110].…”

Section: Evidence From Neuroimaging Studiesmentioning

confidence: 93%

“…In a series of placebo-controlled studies involving 15 healthy volunteers, Fusar-Poli et al investigated the effects of CBD and THC on task-related blood-oxygen-level dependent functional magnetic resonance imaging activation, specifically the go/no-go and fearful faces tasks [109,110]. The go/no-go task measures response inhibition, and is associated with activation of medial prefrontal, dorsolateral prefrontal, and parietal areas [111].…”

Section: Evidence From Neuroimaging Studiesmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

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“…It releases the psychoactive cannabinoid compound called tetrahydrocannabinol, with Δ 9 -tetrahydrocannabinol (THC) being much more abundant and active than Δ 8 -tetrahydrocannabinol [9]. It contains several other cannabinoids, such as cannabidiol (CBD) and cannabinol (CBN), but these are not as abundant and their psychoactive effects not as well-expressed as that of THC [10,11]. Only through sufficient heating or dehydration the tetrahydrocannabinolic acid contained in marijuana can undergo decarboxylation and form the psychoactive THC [12,13].…”

Section: General Pharmacobiology Of Marijuanamentioning

confidence: 99%

Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility

Plessis

Agarwal

Syriac

2015

J Assist Reprod Genet

117

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Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus-pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system.

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Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

Cited by 422 publications

References 108 publications

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

Cannabidiol as a Potential Treatment for Anxiety Disorders

Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility

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