Cannabidiol Does Not Cause Significant Changes to Working Memory Performance in the N-Back Task.

Cannabis use can be traced back to several centuries before the Common Era, when it was used for industrial, medicinal and recreational purposes. More recently, over 100 different cannabinoid compounds have been identified, one of which is cannabidiol (CBD), a compound widely used for anti-inflammatory and anxiolytic treatment. The literature surrounding the cognitive effects of CBD is limited, with most studies focusing on the effects of other cannabinoids on cognition.

A Brief History and the Significance of the GABA Receptor.

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABA type B (GABA) receptors (GABARs) are the only metabotropic G protein-coupled receptors for GABA and can be found distributed not only in the central nervous system, but also in the periphery. This chapter introduces important, fundamental knowledge related to GABAR function and the various potential therapeutic applications of the development of novel GABAR-active compounds, as documented through extensive studies presented in subsequent chapters of this Current Topic in Behavioral Neurosciences volume on the role of the neurobiology of GABAR function.

Effects of Cannabinoid Exposure during Neurodevelopment on Future Effects of Drugs of Abuse: A Preclinical Perspective.

The endocannabinoid system plays a central role in the earliest stages of embryonic, postnatal and adolescent neurodevelopment. Aberrant activity of this system at key developmental phases has been shown to affect neural development. The aim of this review is to synthesise and analyse preclinical insights within rodent populations, focusing on the effects that perinatal (embryonic, gestational and early postnatal developmental stages) and adolescent (postnatal day 21-60) cannabinoid exposure impose across time on the subsequent activity of various drugs of abuse.

GABA Receptors and Cognitive Processing in Health and Disease.

GABA receptors are implicated in numerous central nervous system-based behaviours and mechanisms, including cognitive processing in preclinical animal models. Homeostatic changes in the expression and function of these receptors across brain structures have been found to affect cognitive processing. Numerous preclinical studies have focused on the role of GABA receptors in learning, memory and cognition per se with some interesting, although sometimes contradictory, findings.

Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances.

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission.

A Critical Review of the Role of the Cannabinoid Compounds Δ-Tetrahydrocannabinol (Δ-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment.

Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ-tetrahydrocannabinol (Δ-THC) has been approved to treat symptoms of spasticity. In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties.

The Gamma-Aminobutyric Acid B Receptor in Depression and Reward.

The metabotropic gamma-aminobutyric acid B (GABA) receptor was the first described obligate G protein-coupled receptor heterodimer and continues to set the stage for discoveries in G protein-coupled receptor signaling complexity. In this review, dedicated to the life and work of Athina Markou, we explore the role of GABA receptors in depression, reward, and the convergence of these domains in anhedonia, a shared symptom of major depressive disorder and withdrawal from drugs of abuse. GABA receptor expression and function are enhanced by antidepressants and reduced in animal models of depression.

Enhancing glutamatergic transmission during adolescence reverses early-life stress-induced deficits in the rewarding effects of cocaine in rats.

Adolescence marks a critical time when the brain is highly susceptible to pathological insult yet also uniquely amenable to therapeutic intervention. It is during adolescence that the onset of the majority of psychiatric disorders, including substance use disorder (SUDs), occurs. It has been well established that stress, particularly during early development, can contribute to the pathological changes which contribute to the development of SUDs.

Cannabinoid Regulation of Brain Reward Processing with an Emphasis on the Role of CB1 Receptors: A Step Back into the Future.

Over the last decades, the endocannabinoid system has been implicated in a large variety of functions, including a crucial modulation of brain-reward circuits and the regulation of motivational processes. Importantly, behavioral studies have shown that cannabinoid compounds activate brain reward mechanisms and circuits in a similar manner to other drugs of abuse, such as nicotine, alcohol, cocaine, and heroin, although the conditions under which cannabinoids exert their rewarding effects may be more limited. Furthermore, there is evidence on the involvement of the endocannabinoid system in the regulation of cue- and drug-induced relapsing phenomena in animal models.

Both GABA(B) receptor activation and blockade exacerbated anhedonic aspects of nicotine withdrawal in rats.

Nicotine dependence is maintained by the aversive, depression-like effects of nicotine withdrawal and the rewarding effects of acute nicotine. GABA(B) receptor antagonists exhibit antidepressant-like effects in rodents, whereas GABA(B) receptor agonists attenuate the rewarding effects of nicotine. Recent studies with GABA(B) receptor positive modulators showed that these compounds represent potentially improved medications for the treatment of nicotine dependence because of fewer side-effects than GABA(B) receptor agonists.

Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats.

Rationale: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA(B) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA(B) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior.

GABAB receptors in reward processes.

gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the brain which acts through different receptor subtypes. Metabotropic GABA(B) receptors are widely distributed throughout the brain. Alterations in GABA signaling through pharmacological activation or deactivation of the GABA(B) receptor regulate behavior and brain reward processes.

Behavioral pharmacology of cannabinoids with a focus on preclinical models for studying reinforcing and dependence-producing properties.

Cannabis preparations as recreational drugs are the most widely used illicit drugs in the world. Although cannabis derivatives produce clear subjective motivational responses in humans leading to drug-seeking behavior and in a specific proportion in repeated drug use, the reinforcing/rewarding attributes of these subjective effects are difficult to define in experimental animals. This led to the notion of cannabinoids being considered as "atypical" or "anomalous" drugs of abuse.

Positive modulation of GABA(B) receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats.

Acute administration of gamma-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABA(B) receptor-positive modulators may represent potentially improved therapeutic compounds because of their fewer side effects than receptor agonists. The present study investigated the effects of administration of the GABA(B) receptor-positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and N-[(1R,2R,4S)-bicyclo[2.

Enhancement of endocannabinoid neurotransmission through CB1 cannabinoid receptors counteracts the reinforcing and psychostimulant effects of cocaine.

Cannabinoids, in contrast to typical drugs of abuse, have been shown to exert complex effects on behavioural reinforcement and psychomotor function. We have shown that cannabinoid agonists lack reinforcing/rewarding properties in the intracranial self-stimulation (ICSS) paradigm and that the CB1 receptor (CB1R) agonist WIN55,212-2 attenuates the reward-facilitating actions of cocaine. We sought to determine the effects of the endocannabinoid neurotransmission enhancer AM-404 (1, 3, 10, 30 mg/kg) on the changes in ICSS threshold and locomotion elicited by cocaine and extend the study of the effects of WIN55,212-2 (0.

Lack of evidence for appetitive effects of Delta 9-tetrahydrocannabinol in the intracranial self-stimulation and conditioned place preference procedures in rodents.

Data on the ability of Delta 9-tetrahydrocannabinol (THC) to modify reward processes in experimental animals are inconsistent. This study examined the effects of Delta 9-THC on brain reward function using the rate-frequency curve shift paradigm of intracranial self-stimulation (ICSS) and the conditioned place preference (CPP) paradigm. In ICSS tests, rats were implanted with electrodes into the medial forebrain bundle.

Effects of endocannabinoid neurotransmission modulators on brain stimulation reward.

Rationale: The endogenous cannabinoid system is responsive to the neurobiological actions of Delta9-tetrahydrocannabinol (THC) and other cannabinoid ligands. While numerous studies have focused on the behavioral and pharmacological effects of THC and cannabinoid agonists in experimental animals, most recent work focuses on compounds that modulate endocannabinoid neurotransmission. However, the relevant studies concerning the ability of endocannabinoid modulators to modify reward processes in experimental animals remain rather scarce.

CB1 cannabinoid receptor agonists increase intracranial self-stimulation thresholds in the rat.

Rationale: Addictive drugs have a number of commonalities in animal behavioral models. They lower intracranial self-stimulation (ICSS) thresholds, support self-administration, and produce conditioned place preference (CPP). However, cannabinoids appear atypical as drugs of abuse, since there are controversial data in the literature concerning their reinforcing properties.

WIN 55,212-2 decreases the reinforcing actions of cocaine through CB1 cannabinoid receptor stimulation.

CB(1) cannabinoid receptor agonists show a different profile compared to other drugs of abuse on the basis of experimental data that reveal their reinforcing properties. Thus, there are controversial data in the literature concerning the ability of CB(1) receptor agonists to reinforce behavioral responses in experimental animals, i.e.