Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.

El‐Alfy, Abir T.; Ivey, K. D.; Robinson, Keisha; Ahmed, Safwat A.; Radwan, Mohamed M.; Slade, Desmond; Khan, Ikhlas A.; ElSohly, Mahmoud A.; Ross, Samir A.

doi:10.1016/j.pbb.2010.03.004

Cited by 249 publications

(196 citation statements)

References 67 publications

(79 reference statements)

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“…Our behavioural the behavioural consequences of stress through enhancement of hippocampal neurogenesis [72] findings in the forced swimming test were confirmed by another study, published in the same year. CBD was tested at the doses of 20, 100 and 200 mg kg 21 [127], with the higher dose being effective. The drug had no effect, however, in the mouse tail suspension test.…”

Section: Cannabidiol and Depressionmentioning

confidence: 99%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

377

241

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Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D 9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca 2þ ) increase, etc.), on CBD behavioural effects.

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Section: Cannabidiol and Depressionmentioning

confidence: 99%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

377

241

View full text Add to dashboard Cite

show abstract

“…CBD improves performance in numerous animal models of cognitive impairments [30,[46][47][48]. It acts as an antidepressant in animal models of depression and decreases compulsive behaviors in rodents [35,49]. These actions are hypothesized to be linked to CB1-related mechanisms [50,51].…”

Section: Cbd and Neurobiological Targets/effectsmentioning

confidence: 99%

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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“…CBC dose-dependently decreases LPS-induced inflammation in paw edema assay with a noncannabinoid receptor mechanism of action (198). It inhibits nitric oxide production, IL-10, and IFN-␥ levels in LPS-activated macrophages (740), reduces inflammation-induced gut hypermotility in vivo in mice (384), and produces antidepressant-like activity in rodents (236). CBC is analgesic by stimulating the descending pathway of antinociception in the ventrolateral periaqueductal grey, through activation of TRPA1, inhibition of endocannabinoid inactivation, and subsequent elevation of local endocannabinoid levels, and potentiation of adenosine signaling (519).…”

mentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

377

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.

Cited by 249 publications

References 67 publications

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

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

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

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